Effect of a selective restriction policy on antibiotic expenditure and use: an institutional model. Quality improvement of surgical prophylaxis in Dutch hospitals: evaluation of a multi-site intervention by time series analysis. Evaluation of an intervention designed to decrease the rate of nosocomial methicillin-resistant Staphylococcus aureus infection by encouraging decreased fluoroquinolone use. An antibiotic policy to prevent emergence of resistant bacilli. Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Outcomes of an intervention to improve hospital antibiotic prescribing: interrupted time series with segmented regression analysis. Reducing door-to-antibiotic time in community-acquired pneumonia: Controlled before-and-after evaluation and cost-effectiveness analysis. Hospital-wide restriction of clindamycin: effect on the incidence of Clostridium difficile-associated diarrhea and cost. A randomised controlled trial of a tailored multifaceted strategy to promote implementation of a clinical guideline on induced abortion care. Audit of antibiotic usage in medium-sized general hospital over an 11-year period. The impact of antibiotic policies. Effects of monitoring the usage of antibiotics: an interhospital comparison. Academic detailing to improve use of broad-spectrum antibiotics at an academic medical center. A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Impact of a multidisciplinary approach to the control of antibiotic prescription in a general hospital. A controlled trial of the cost benefit of computerized bayesian aminoglycoside administration. Clinical impact of rapid in vitro susceptibility testing and bacterial identification. Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital. Measuring the saving attributable to an antibiotic prescribing policy. Effectiveness of a vancomycin restriction policy in changing the prescribing patterns of house staff. The effect of antibiotic rotation on colonization with antibiotic-resistant bacilli in a neonatal intensive care unit. Successful control of Clostridium difficile infection in an elderly care unit through use of a restrictive antibiotic policy. Metronidazole cost containment: a two-stage intervention. Improved clinical outcomes with utilization of a community-acquired pneumonia guideline. Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use. Monitoring antimicrobial use and resistance: comparison with a national benchmark on reducing vancomycin use and vancomycin-resistant enterococci. Bloodstream infections: a trial of the impact of different methods of reporting positive blood culture results. Decreased mortality after implementation of a treatment guideline for community-acquired pneumonia. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Clinical impact of rapid identification and susceptibility testing of bacterial blood culture isolates. Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins. Antibiotic cost savings from formulary restrictions and physician monitoring in a medical-school-affiliated hospital. Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins. Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods. Integration of clinical and administrative strategies to reduce expenditures for antimicrobial agents. Improving compliance with hospital antibiotic guidelines: a time-series intervention analysis. Nursing home-acquired pneumonia: outcomes from a clinical process improvement program. Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial. Changing antibiotic prescribing by educational marketing. Antibiotic use, hospital admissions, and mortality before and after implementing guidelines for nursing home-acquired pneumonia. Effect of antibiotic order form guiding rational use of expensive drugs on cost containment. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Computer-assisted antimicrobial-use monitoring. Influencing drug use through prescribing restrictions. Reduction of incorrect antibiotic dosing through a structured educational order form. Improving the quality of care for patients with pneumonia in very small hospitals. Limited impact of a multicenter intervention to improve the quality and efficiency of pneumonia care. Use of clinical pharmacists to reduce cefamandole, cefoxitin, and ticarcillin costs. Use of antimicrobial drugs in adults before and after removal of a restriction policy. A multidisciplinary hospital-based antimicrobial use program: Impact on hospital pharmacy expenditures and drug use. A randomized trial to measure the optimal role of the pharmacist in promoting evidence-based antibiotic use in acute care hospitals. Improving empirical antibiotic treatment using TREAT, a computerized decision support system: cluster randomized trial. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Impact of regular attendance by infectious disease specialists on the management of hospitalised adults with community-acquired febrile syndromes. A team approach to hospital formulary replacement. Lack of effect of shorter turnaround time of microbiological procedures on clinical outcomes: a randomised controlled trial among hospitalised patients in the Netherlands. Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units. Pharmacy-implemented guidelines on switching from intravenous to oral antibiotics: an intervention study. Impact of a web-based antimicrobial approval system on broad-spectrum cephalosporin use at a teaching hospital. Antibiotic restriction does not alter endemic colonization with resistant gram-negative rods in a pediatric intensive care unit. Impact of an antibiotic policy on antibiotic use in a paediatric department. Individual based follow-up shows that antibiotics were chosen according to diagnoses and bacterial findings. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage. Curtailing unnecessary vancomycin usage in a hospital with high rates of methicillin resistant Staphylococcus aureus infections. Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection. Antibiotic optimization. An evaluation of patient safety and economic outcomes. Impact of a two-stage intervention program on cefazolin usage at a major teaching hospital. Limiting vancomycin use to combat vancomycin-resistant Enterococcus faecium. Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial. Changing surgical antimicrobial prophylaxis practices through education targeted at senior department leaders. Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days. An interrupted time series analysis of parenteral antibiotic use in Colombia. Aminoglycoside resistance in gram-negative bacilli during increased amikacin use. Comparison of experience in 14 United States hospitals with experience in the Minneapolis Veterans Administration Medical Center. Reduction of vancomycin-resistant enterococcal infections by limitation of broad-spectrum cephalosporin use in a trauma and burn intensive care unit. Improvement of intraoperative antibiotic prophylaxis in prolonged cardiac surgery by automated alerts in the operating room. Clinical and bacteriological survey after change in aminoglycoside treatment to control an epidemic of Enterobacter cloacae. A randomized, prospective evaluation of an interventional program to discontinue intravenous antibiotics at two tertiary care teaching institutions. Fluoroquinolone use and methicillin-resistant Staphylococcus aureus isolation rates in hospitalized patients: a quasi experimental study. Reduction in the incidence of methicillin-resistant Staphylococcus aureus and ceftazidime-resistant Klebsiella pneumoniae following changes in a hospital antibiotic formulary. Reducing vancomycin use utilizing a computer guideline: results of a randomized controlled trial. Control of nosocomial multiresistant Enterobacteriaceae using a temporary restrictive antibiotic agent policy.
Strictly enforced antibiotic formulary restriction in combination with formulation of agreed guidelines for antibiotic use in common infection problems such as septicemia, febrile neutropenia, urinary tract infection, biliary sepsis, liver abscess, peritonitis, nosocomial pneumonia, soft tissue infection and purulent meningitis, generated a combined savings of 307,748.5 bahts or 13.5 per cent cost reduction over a 6 month period, and improved quality of use, appropriate 54.8 vs 67.5 per cent, statistically significance (P less than 0.002). Although this saving was offset in part by increased spending of unrestricted antibiotics, such as Penicillin and Gentamicin, an overall cost saving remained. In the months during the restrictions, no significant changes occurred regarding patients response and mortality. However, after the onset of the controls, it was revealed that antibiotics were more appropriately used afterwards. This study has shown, most importantly, that savings were achieved with no negative effect on good patient care. Moreover, the antibiotic use control was operationally successful, most house-staff and attending physicians, not only antibiotic evaluating team, have accepted the program in a very positive way. Overall, this program successfully achieved its initial goal, cost saving without compromising good medical practice. We are now continuing our program and also trying to modify so that it will be useful to all departments in the hospital. Misuse of antibiotics in surgical prophylaxis is still quite common. The objectives of this study were to reduce the quantity and improve the quality of surgical prophylaxis and to reduce costs.
                Prospective multi-site study of elective procedures in 13 Dutch hospitals. The quality of prophylaxis was audited before and after an intervention consisting of performance feedback and implementation of national clinical practice guidelines. Process outcome parameters were antibiotic choice, duration, timing, antibiotic volume and costs. Segmented regression analysis was used to estimate the effect size of the intervention. Patient outcome was documented by the incidence of surgical site infections (SSI).
                Before the intervention, 1763 procedures were recorded and 2050 thereafter. Antimicrobial use decreased from 121 to 79 DDD (defined daily doses)/100 procedures and costs reduced by 25% per procedure. After the intervention, antibiotic choice was inappropriate in only 37.5% of the cases instead of in 93.5% expected cases had the intervention not occurred. Prolonged prophylaxis was observed in 31.4% instead of 46.8% expected cases and inappropriate timing in 39.4% instead of the expected 51.8%. Time series analysis showed that all improvements were statistically significant (P < 0.01) and that they could be fully attributed to the intervention. The overall SSI rates before and after intervention were 5.4% (95% CI: 4.3-6.5) and 4.6% (95% CI: 3.6-5.4), respectively.
                The intervention led to improved quality of surgical prophylaxis and to reduced antibiotic use and costs without impairment of patient outcome. Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens.
                Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate.
                An 87-bed Veterans Affairs teaching hospital with an extended-care facility.
                A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked.
                After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention (P=.04).
                Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate. Fear of infection in neonatal intensive care units (NICUs) often leads to early use of empiric broad-spectrum antibiotics, a strategy that selects for resistant bacteria. We investigated whether the emergence of resistant strains could be halted by modifying the empiric antibiotic regimens to remove the selective pressure that favours resistant bacteria.
                Two identical NICUs were assigned to different empiric antibiotic regimens. On unit A, penicillin G and tobramycin were used for early-onset septicaemia, flucloxacillin and tobramycin were used for late-onset septicaemia, and no broad-spectrum beta-lactam antibiotics, such as amoxicillin and cefotaxime were used. In unit B, intravenous amoxicillin with cefotaxime was the empiric therapy. After 6 months of the study the units exchanged regimens. Rectal and respiratory cultures were taken on a weekly basis.
                There were 436 admissions, divided equally between the two regimens (218 in each). Three neonates treated with the penicillin-tobramycin regimen became colonised with bacilli resistant to the empirical therapy used versus 41 neonates on the amoxicillin-cefotaxime regimen (p<.0001). The relative risk for colonisation with strains resistant to the empirical therapy per 1000 patient days at risk was 18 times higher for the amoxicillin-cefotaxime regimen compared with the penicillin-tobramycin regimen (95% CI 5.6-58.0). Enterobacter cloacae was the predominant bacillus in neonates on the amoxicillin-cefotaxime regimen, whereas Escherichia coli predominated in neonates on the penicillin-tobramycin regimen. These colonisation patterns were also seen when the units exchanged regimens.
                Policies regarding the empiric use of antibiotics do matter in the control of antimicrobial resistance. A regimen avoiding amoxicillin and cefotaxime restricts the resistance problem. To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients.
                Prospective, interrupted time-series analysis.
                University hospital in the south-eastern United States.
                Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003.
                A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation.
                The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention.
                There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units.
                A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability. Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality. To evaluate an intervention to reduce inappropriate use of key antibiotics with interrupted time series analysis.
                The intervention is a policy for appropriate use of Alert Antibiotics (carbapenems, glycopeptides, amphotericin, ciprofloxacin, linezolid, piperacillin-tazobactam and third-generation cephalosporins) implemented through concurrent, patient-specific feedback by clinical pharmacists. Statistical significance and effect size were calculated by segmented regression analysis of interrupted time series of drug use and cost for 2 years before and after the intervention started.
                Use of Alert Antibiotics increased before the intervention started but decreased steadily for 2 years thereafter. The changes in slope of the time series were 0.27 defined daily doses/100 bed-days per month (95% CI 0.19-0.34) and pound 1908 per month (95% CI pound 1238- pound 2578). The cost of development, dissemination and implementation of the intervention ( pound 20133) was well below the most conservative estimate of the reduction in cost ( pound 133296), which is the lower 95% CI of effect size assuming that cost would not have continued to increase without the intervention. However, if use had continued to increase, the difference between predicted and actual cost of Alert Antibiotics was pound 572448 (95% CI pound 435696- pound 709176) over the 24 months after the intervention started.
                Segmented regression analysis of pharmacy stock data is a simple, practical and robust method for measuring the impact of interventions to change prescribing. The Alert Antibiotic Monitoring intervention was associated with significant decreases in total use and cost in the 2 years after the programme was implemented. In our hospital, the value of the data far exceeded the cost of processing and analysis. Practice guidelines suggest that all patients hospitalised with community-acquired pneumonia (CAP) should receive antibiotics within 4 h of admission. An audit at our hospital during 1999-2000 showed that this target was achieved in less than two thirds of patients with severe CAP.
                An experienced multidisciplinary steering group designed a management pathway to improve the early delivery of appropriate antibiotics to patients with CAP. This was implemented using a multifaceted strategy. The effect of implementation was evaluated using a controlled before-and-after study design over two winter seasons (November-April 2001-2 and 2002-3). Cost-effectiveness analyses were performed from the hospital's perspective.
                The proportion of patients receiving appropriate antibiotics within 4 h of admission to hospital increased from 33% to 56% at the intervention site, and from 32% to 36% at the control site (absolute change adjusted for differences in severity of illness 17%, p = 0.035). The cost per additional patient receiving appropriate antibiotics within 4 h was 132 pound with no post-implementation evaluation, and 456 pound for a limited post-implementation evaluation. Simple modelling from the results of a large observational study suggests that the cost per death prevented could be 3003 pound with no post-implementation evaluation, or 16,632 pound with a limited post-implementation evaluation.
                The intervention markedly improved door-to-antibiotic time, albeit at considerable cost. It might still be a cost-effective strategy, however, to reduce mortality in CAP. Uncertainty about the cost effectiveness of such interventions is likely to be resolved only by a well-designed, cluster randomised trial. Widespread antibiotic use has been associated with increases in both bacterial resistance and nosocomial infection.
                To characterize the impact of hospital-wide clindamycin restriction on the incidence of Clostridium difficile-associated diarrhea and on antimicrobial prescribing practices.
                Prospective, observational cohort study.
                University-affiliated Veterans Affairs Medical Center.
                Hospitalized patients with symptomatic diarrhea.
                Clinical data on individual patients and data on antibiotic use were obtained from hospital pharmacy records. Hospital-wide use of antimicrobial agents was monitored. Isolates of C. difficile underwent antimicrobial susceptibility testing and molecular typing.
                An outbreak of C. difficile-associated diarrhea was caused by a clonal isolate of clindamycin-resistant C. difficile and was associated with increased use of clindamycin. Hospital-wide requirement of approval by an infectious disease consultant of clindamycin use led to an overall reduction in clindamycin use, a sustained reduction in the mean number of cases of C. difficile-associated diarrhea (11.5 cases/month compared with 3.33 cases/month; P < 0.001), and an increase in clindamycin susceptibility among C. difficile isolates (9% compared with 61%; P < 0.001). A parallel increase was noted in the use of and costs associated with other antibiotics with antianaerobic activity, including cefotetan, ticarcillin-clavulanate, and imipenem-cilastin. The hospital realized overall cost savings as a result of the decreased incidence of C. difficile-associated diarrhea.
                Hospital formulary restriction of clindamycin is an effective way to decrease the number of infections due to C. difficile. It can also lead to a return in clindamycin susceptibility among isolates and can effect cost savings to the hospital. To evaluate the effectiveness and efficiency of a tailored multifaceted strategy, delivered by a national clinical effectiveness programme, to implement a guideline on induced abortion.
                Cluster randomised controlled trial.
                All 26 hospital gynaecology units in Scotland providing induced abortion care.
                Following the identification of barriers to guideline implementation, intervention units received a package comprising audit and feedback, unit educational meetings, dissemination of structured case records and promotion of a patient information booklet. Control units received printed guideline summaries alone.
                Compliance with five key guideline recommendations (primary outcomes) and compliance with other recommendations, patient satisfaction and costs of the implementation strategy (secondary outcomes).
                No effect was observed for any key recommendation: appointment with a gynaecologist within five days of referral (odds ratio 0.89; 95% confidence interval 0.50 to 1.58); ascertainment of cervical cytology history (0.93; 0.36 to 2.40); antibiotic prophylaxis or screening for lower genital tract infection (1.70; 0.71 to 5.99); use of misoprostol as an alternative to gemeprost (1.00; 0.27 to 1.77); and offer of contraceptive supplies at discharge (1.11; 0.48 to 2.53). Median pre-intervention compliance was near optimal for antibiotic prophylaxis and misoprostol use. No intervention benefit was observed for any secondary outcome. The intervention costs an average of pound 2607 per gynaecology unit.
                The tailored multifaceted strategy was ineffective. This was possibly attributable to high pre-intervention compliance and the limited impact of the strategy on factors outside the perceived control of clinical staff. The objective of the present study was to evaluate trends in antibiotic expenditure over an 11-year period (1982-1992) in a 370-bed district general hospital in Northern Ireland and to examine the impact of two separate antibiotic policies on antibiotic usage. A further objective was to examine the attitudes of prescribers to the second policy. Drug utilization review was used to collect information on antibiotic expenditure and usage before and after introduction of separate antibiotic policies in 1985 (not intensively monitored) and 1989 (intensively monitored). A main questionnaire was used to determine the attitudes of prescribers. The first policy (1985) showed no benefits with regard to the number of antibiotic entities stocked (45 before, 45 after), number of dosage units issued (9.3% increase) or expenditure (33.3% increase). The 1989 policy led to significant reductions in the number of antibiotic entities stocked (28.9%), number of antibiotics issued (11.9%) and expenditure (6.1%). Expenditure began to spiral upwards when active monitoring of the second policy was suspended. The majority of prescribers (87.2%) who responded to the questionnaire (56.5% response rate) felt that the 1989 policy made a positive contribution to antibiotic usage in the hospital. Use of selected systemic antimicrobial agents at Boston City Hospital (BCH) has been monitored by requiring that choice of those agents be justified to a member of the Infectious Diseases Unit before the agent is dispensed for use in a patient. The amounts of various antimicrobial agents and classes of agents used at BCH in 1972 differed considerably from amounts used in other hospitals where restraint was not employed. Whether these differences in usage led to better care for the patient could not be determined from the data presented. These aspects must be studied in greater detail to determine the benefits, if any, that may be derived from such surveillance and control, especially in view of recent proposals for implementation of "peer review" in this as well as other areas. Antibiotic misuse is common and costly and may promote antibiotic resistance. We tested the efficacy of a targeted one-on-one educational program ("academic detailing") designed to improve the appropriateness of broad-spectrum antibiotic use.
                A randomized controlled trial was conducted in a large US teaching hospital. During an 18-week study period, 17 general medical, oncology, and cardiology services either received academic detailing or did not. The intervention was prompted by an order for either levofloxacin or ceftazidime that led to a computer-based review of data for that patient. Orders for the 2 target antibiotics deemed unnecessary by a priori criteria were included in the study. The primary outcome examined was the number of days that unnecessary levofloxacin or ceftazidime was administered in intervention and control groups.
                Before the trial, intervention and control services had similar prescribing patterns for the target antibiotics; the drugs were used for similar indications throughout the study period. During the intervention, there was a reduction of 37% in days of unnecessary levofloxacin or ceftazidime use per 2-week interval on services randomized to the educational intervention vs control services (P< .001). In multivariable analyses controlling for baseline prescribing and study interval, the rate of unnecessary use of the 2 target antibiotics was reduced by 41% on the intervention services compared with controls (95% confidence interval, 44%-78%; P< .001). Length of stay, intensive care unit transfers, readmission rates, and in-hospital death rates were similar in both groups (P> or =.10 for all).
                Targeted one-on-one education is a practical, effective, and safe method for reducing excessive broad-spectrum antibiotic use. Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings. We examined the impact of a rational antibiotic prescription programme based on a multidisciplinary consultative approach in a 600-bed hospital. The programme involved four measures: (1). drawing up of a local prescribing consensus with all prescribers; (2). a restricted prescriptions policy for the most expensive antibiotics; (3.assessment of the prescription of these antibiotics by regular audits; and (4). institutional training and information for prescribers. The impact of the programme was assessed by comparing actual prescriptions with the criteria of the local consensus, compliance with the restrictive prescription policy, changes in the average daily cost of antibiotic therapy per inpatient and changes in the local ecology of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae producing extended-spectrum beta-lactamases (EPESB) and ceftazidime-resistant Pseudomonas species (CRP). Using a participatory consensual approach, 182 reference recommendations were established (104 for adults, 78 for children), corresponding to 85% of the clinical settings encountered in the hospital. Six audits, conducted since June 1997, show that the rate of unjustified prescriptions first fell significantly (from 6 to 0%, P<0.001), then increased significantly (from 0 to 3%, P<0.05) before stabilizing at 3%. The cost of antimicrobials per inpatient day fell significantly (from US dollars 13.8 in 1997 to US dollars 11 in 2000, P<0.001). The prevalence of MRSA and CRP remained stable, while that of EPESB fell significantly (P<0.001). This multidisciplinary consultative approach thus reduced antibiotic costs, contributed to infection control, and improved the quality of antibiotic prescription. We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections. Patients were randomized to a control (dosing based on physician choice; n = 75) or experimental group (dosing based on the bayesian program; n = 72). Both groups used serum aminoglycoside concentration data when making dosing decisions. Improved response rates were seen in the experimental (60%; 42/68) compared with the control group (48%; 36/68). A higher, but not statistically significant, incidence of toxicity was found in the control (7/75; 9.7%) versus the experimental group (4/72; 5.1%). Mean length of total hospital stay was significantly longer for patients in the control group (20.3 days) compared with the experimental group (16.0 days) (p = 0.028). The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy. On the basis of a reduced length of stay, a potential cost savings of $1311 per patient can be achieved. During the past decade, a variety of instrument-assisted bacterial identification and antimicrobial susceptibility test systems have been developed which permit provision of test results in a matter of hours rather than days, as has been the case with traditional overnight procedures. These newer rapid techniques are much more expensive than older methods. It has been presumed but not proven that the clinical benefits of rapid testing to patients with infection offset the added cost. The intent of this study was to objectively define the clinical impact of rapid bacterial identification and antimicrobial susceptibility testing. A 1-year study was performed in which infected, hospitalized patients in a tertiary-care, teaching, medical center were randomly assigned to one of two groups: patients for whom identification and susceptibility testing was performed by using a semi-automated, rapid, same-day procedure and those for whom testing was accomplished by using traditional overnight techniques. The two groups were compared with respect to numerous demographic descriptors, and then patients were monitored prospectively through the end of their hospitalization with the aim of determining whether there existed objectively defineable differences in management and outcome between the two groups. The mean lengths of time to provision of susceptibility and identification test results in the rapid test group were 11.3 and 9.6 h, respectively. In the overnight test group, these values were 19.6 and 25.9 h, respectively (P < 0.0005). There were 273 evaluable patients in the first group and 300 in the second group. Other than the length of time required to provide susceptibility and identification test results, no significant differences were noted between the two groups with respect to > 100 demographic descriptors. With regard to measures of outcome, the mean lengths of hospitalization were also the same in both groups. Mortality rates were however, lower in the rapid test group (i.e., 8.8% versus 15.3%). Similarly, statistically significantly fewer laboratory studies, imaging procedures, days of intubation, and days in an intensive or intermediate-care area were observed with patients in the rapid test group. Rapid testing was also associated with significantly shortened lengths of elapsed time prior to alterations in antimicrobial therapy. Lastly, patient costs for hospitalization were significantly lower in the rapid test group. The results of this study indicate the rapid same-day bacterial identification and susceptibility testing in the microbiology laboratory can have a major impact on the care and outcome of hospitalized patients with infection. The impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD), over a five-year period between 1995 and 2000, were studied in the Preston Acute Hospitals Trust. In 1996 the policy was changed in the Preston Acute Hospitals Trust from cefotaxime to ceftriaxone for initial treatment of severe sepsis or pneumonia in medical patients. Over the next nine months the average number of patients with C. difficile toxin-positive stools per quarter increased from 16 to 39. The predicted use of ceftriaxone exceeded by 65% an estimate based on prior use of cefotaxime. A policy of restricted duration of ceftriaxone was introduced, and although this reduced usage by over 50%, CDAD continued at an average of 9.2 cases per month, despite withdrawal of oral cephalosporins in December 1998. In August 1999 levofloxacin was substituted for ceftriaxone in the policy. The incidence of CDAD fell progressively to five cases per month by 2000. It would appear that a short (typically three dose) course of third-generation cephalosporin poses a similar risk for CDAD as a more prolonged course. The six-month delay in the decline of CDAD after virtual withdrawal of cephalosporins may reflect a slowly diminishing environmental reservoir. An analytical framework is suggested for the economic evaluation of policies to improve the management of hospital infection. Consideration of the costs and benefits to be expected from improved policies implies the existence of an optimal infection rate which is higher than the minimum attainable. It follows that hospitals can and probably do spend too much on infection control in, at least, some areas. This optimal approach is not operational at present but its data requirements might be thought of as an agenda for future research. In the meantime, progress in infection control economics depends on a piecemeal approach. An example is given in the estimation of the cost savings attributable to an improved antibiotic prescribing policy at the Royal Liverpool Hospital. After noting a rise in vancomycin-resistant enterococci (VRE) infections, we initiated a program to decrease inappropriate vancomycin use that focused on improvement of house staff prescribing practices. The initial intervention in June, 1995, encouraging house staff to follow hospital guidelines for vancomycin use and eliciting support from service chiefs in this effort, had little impact. A more intensive educational intervention, beginning in January, 1996, involved concurrent review of all vancomycin orders and one-on-one discussion with the house staff regarding the rationale for the order by an infectious diseases clinical pharmacist. When usage was deemed inappropriate, the pharmacist asked that vancomycin be discontinued, but no automatic stop orders were issued. During the next two and one-half years, this second intervention proved effective at decreasing inappropriate use from 39% to 16.8% +/- 2.4% (p = 0.005). This change was primarily due to a decrease in appropriate vancomycin prophylaxis by cardiothoracic surgery. VRE infections decreased from 0.29/100 patients discharged prior to initiating the program to 0.13/100 patients discharged after the second intervention (p = 0.01). This educational program, although labor-intensive, preserved house staff decision-making skills related to antibiotic prescribing at the same time that it decreased inappropriate vancomycin use. This study was designed to test whether rotation of antibiotics can reduce colonization with resistant Gram-negative bacilli in a neonatal intensive care unit (NICU).
                A monthly rotation of gentamicin, piperacillin-tazobactam, and ceftazidime was compared with unrestricted antibiotic use in side-by-side NICU populations (rotation team vs control team). Pharyngeal and rectal samples were obtained 3 times a week and tested for Gram-negative bacilli resistant to each of the rotation antibiotics. Pulsed-field gel electrophoresis analysis determined the numbers of genetically discordant resistant organisms on each team. The association between colonization with a resistant bacillus (the primary outcome) and team assignment was tested.
                A total of 1062 infants were studied during a 1-year period. A total of 10.7% infants on the rotation team versus 7.7% on the control team were colonized with a resistant bacillus. No interteam differences were distinguishable when the numbers of genetically discordant resistant organisms were normalized to the total number of team admissions. The incidence of nosocomial infection and mortality also were similar across teams.
                These data indicate that rotation of parenteral antibiotics according to the applied protocol has no detectable effect in decreasing the reservoir of resistant Gram-negative bacilli in a tertiary-care NICU. Toxin-producing Clostridium difficile is the commonest bacterial cause of nosocomial diarrhoea and is a well recognized cause of hospital outbreaks in elderly care units. High C. difficile disease rates have been associated with the use of broad-spectrum antibiotics, especially cephalosporins. An outbreak of C. difficile infection in the elderly care unit at Gloucestershire Royal NHS Trust continued despite increased ward cleaning and strict implementation of infection control measures. A restrictive antibiotic policy that would maintain colonization resistance in the gastrointestinal tract was introduced throughout this unit. Patients admitted with suspected infection were prescribed intravenous (i.v.) benzylpenicillin 1.2-1.8 g every 6 h to cover streptococcal infections and i.v. trimethoprim 200 mg twice daily to cover urinary tract pathogens and Haemophilus influenzae. If the patient had septic shock a single iv dose of gentamicin was given (120-180 mg) to cover more resistant gram-negative bacilli. The following were monitored before and after the policy change. The number of cases of C. difficile toxin-positive diarrhoea; cefuroxime and total antibiotic use on the elderly care wards; patient mortality rates; and length of hospital stay: two hundred and fifty-two and 234 patients respectively with a discharge diagnosis of infection were admitted before and after the antibiotic policy change. Mortality rates and length of hospital stay were unchanged. Cefuroxime prescribing and total antibiotic prescribing costs fell by 5150 pounds sterling and 8622 pounds sterling respectively in the 7 month period after the change. Thirty-seven cases of C. difficile diarrhoea occurred in the period before and 16 in the period after the policy change. The incidence of C. difficile diarrhoea and of cefuroxime use has remained low since then. The use of narrow-spectrum antibiotics for hospital treatment of community-acquired infections in the elderly should be encouraged. Outbreaks of C. difficile diarrhoea should be managed with the combined approach of infection control and strict antibiotic policies. A two-stage intervention was undertaken to extend the dosing interval of metronidazole--from the typically prescribed q6h or q8h regimen to a q12h dosing interval. Following an 2-week informational period, all prescriptions for parenteral metronidazole specifying a dosage interval of 8 hours or less were modified to 12-hour dosage intervals, unless overridden by the prescriber. Prescriptions for the 6-month periods prior to and following the intervention were reviewed to assess its impact on prescribing patterns and cost containment. The incidence of regimens involving 12-hour intervals increased from 5 to 95% following the intervention. A 2-year general hospital/drug utilization health record screen found no drug substitution effect, nor any change in postoperative infection rate or death among metronidazole recipients. Overall, the two-stage intervention was a well-accepted and effective means of cost containment, resulting in an estimated yearly cost savings of $28,000. We previously reported decreased mortality following implementation of a community-acquired pneumonia guideline derived from specialty society recommendations. However, patients with respiratory failure and sepsis from pneumonia were not included, adjustment for comorbidities was limited, and no guideline compliance data were available. We also questioned whether decreased mortality continued after 1997.
                We utilized Utah data from the Centers for Medicare and Medicaid from 1993 to 2003 to determine if pneumonia guideline implementation was associated with 30-day all-cause mortality, length of hospital stay, and readmission rate. We adjusted outcomes by age, gender, Deyo comorbidity score, prior hospitalizations, and race. Guideline compliance was measured by initial default guideline antibiotic administration. We included patients > or = 66 years old with primary International Classification of Diseases, Ninth Revision, Clinical Modification codes 480.0-483.9, 485.0-486.9, 487.0, 507.0 or 518.81, and 038.x with secondary code pneumonia. We excluded patients with prior hospitalization within 10 days, patients with HIV infection or transplant recipients, and patients not treated by physicians closely affiliated with study hospitals.
                Mean (+/- SD) age of 17,728 pneumonia patients admitted to the hospital was 72.3 +/- 12.0 years, 55.2% were female, and 96.0% were white. Within Intermountain Healthcare hospitals, a 1-SD increase (10%) in guideline compliance (range, 61 to 100%) was associated with mortality odds ratio (OR) of 0.92 (95% confidence interval[CI], 0.87 to 0.98; p = 0.007). Mortality OR at 16 Intermountain Healthcare hospitals was 0.89 (95% CI, 0.82 to 0.97; p = 0.007) compared with 19 other Utah hospitals. This mortality difference corresponds to approximately 20 lives saved yearly. The readmission rate was also lower.
                Improved clinical outcomes were associated with pneumonia guideline utilization. To report the investigation and effective control of a nosocomial epidemic of Clostridium difficile-associated diarrhea.
                Concurrent surveillance for identification of new nosocomial cases, retrospective case-control analysis, and hospital formulary control of antibiotic use.
                University-affiliated Veterans Affairs Medical Center located in southwestern United States.
                Hospitalized patients who developed diarrhea submitted stool specimens for cytotoxin assay. Patients who were positive for cytotoxin were compared with control patients without infection.
                Isolates of C. difficile were typed by restriction endonuclease analysis. Antimicrobial agent use from hospital pharmacy records and selected patient data from chart review were correlated with frequency of specific laboratory abnormalities.
                For 13 months, the monthly incidence of C. difficile infection averaged more than five times that for the previous 21 months. Stool specimens from 34 patients (59%) contained a single strain (restriction enzyme analysis type J7). Clindamycin was statistically associated with the epidemic as shown by the following: clindamycin use at our center compared with national normal values, clindamycin use for years before compared with during the epidemic, monthly use of clindamycin compared with monthly frequency of infection, frequency of infection in patients receiving clindamycin compared with that in patients receiving other antimicrobial agents, and amount of clindamycin used by infected patients compared with that used by control patients. Restricting clindamycin use led to a prompt disease in infection rate and the type J7 organisms.
                A nosocomial epidemic of C. difficile diarrhea was controlled by analysis of antibiotic use patterns and by subsequent restriction of clindamycin. To determine if local monitoring data on vancomycin use directed quality improvement and decreased vancomycin use or vancomycin-resistant enterococci (VRE), we analyzed data from 50 intensive-care units (ICUs) at 20 U.S. hospitals reporting data on antimicrobial-resistant organisms and antimicrobial agent use. We compared local data with national benchmark data (aggregated from all study hospitals). After data were adjusted for changes in prevalence of methicillin-resistant Staphylococcus aureus, changes in specific prescriber practice at ICUs were associated with significant decreases in vancomycin use (mean decrease -48 defined daily doses per 1,000 patient days, p<0.001). These ICUs also reported significant decreases in VRE prevalence compared with those not using unit-specific changes in practice (mean decrease of 7.5% compared with mean increase of 5.7%, p<0.001). In this study, practice changes focused towards specific ICUs were associated with decreases in ICU vancomycin use and VRE prevalence. The impact of how positive blood culture results are reported on the evolution bloodstream infections (BSIs) has not been assessed.
                We randomly assigned patients with BSIs into 3 groups: group A (for which physicians received a conventional report), group B (for which physicians received a conventional report and a written alert on the chart with clinical advice), and group C (for which physicians received the above plus oral clinical advice). The adequacy of therapy before and after receipt of the different types of information was assessed.
                Overall, 297 episodes (109 in group A, 99 in group B, and 89 in group C) were studied. Patients who received inadequate treatment before receiving microbiological information had a longer mean (+/-SD) hospital stay (27.2+/-32.4 vs. 19.4+/-15.8 days; P=.017), a higher mean risk of Clostridium difficile-associated diarrhea (8.3% vs. 1.9%; P=.013), a higher mean overall mortality rate (30.8% vs. 19.4%; P=.025), and a higher mean risk of infection-related mortality (23.3% vs. 13.6%; P=.031). After receipt of microbiological reports, recommendations for changes in therapy were issued for patients in groups B (52.3%) and C (53.1%). For groups A, B, and C, the proportions of days on which adequate treatment was received were 66.3%, 92.1%, and 91.2% (P<.001); the mean numbers of defined daily doses of appropriate antibiotic therapy were 16.4, 22.2, and 20.7 (P=.003); the mean durations of hospital stay were 19.8, 23.6, and 24.1 days (P=.761); and the mortality rates during the late period were 12.9%, 15.6%, and 11% (P=.670), respectively. The mean costs of antimicrobials per episode in groups A, B, and C were 580.63, 537.98, and 434.53 (US707.85 dollars, US699.73 dollars, and US529.73 dollars, respectively).
                Written- or oral-alert reports with clinical advice should complement traditional microbiological reports for patients with BSIs. We developed a pneumonia guideline at Intermountain Health Care that included admission decision support and recommendations for antibiotic timing and selection, based on the 1993 American Thoracic Society guideline. We hypothesized that guideline implementation would decrease mortality.
                We included all immunocompetent patients > 65 years with community-acquired pneumonia from 1993 through 1997 in Utah; nursing home patients were excluded. We compared 30-day mortality rates among patients before and after the guideline was implemented, as well as among patients treated by physicians who did not participate in the guideline program.
                We observed 28,661 cases of pneumonia, including 7,719 (27%) that resulted in hospital admission. Thirty-day mortality was 13.4% (1,037 of 7,719) among admitted patients and 6.3% (1,801 of 28,661) overall. Mortality rates (both overall and among admitted patients) were similar among patients of physicians affiliated and not affiliated with Intermountain Health Care before the guideline was implemented. For episodes that resulted in hospital admission after guideline implementation, 30-day mortality was 11.0% among patients treated by Intermountain Health Care-affiliated physicians compared with 14.2% for other Utah physicians. Analysis that adjusted by logistic regression for age, sex, rural versus urban residences, and year confirmed that 30-day mortality was lower among admitted patients who were treated by Intermountain Health Care-affiliated physicians (odds ratio [OR]: 0.69; 95% confidence interval [CI]: 0.49 to 0.97; P = 0.04) and was somewhat lower among all pneumonia patients (OR: 0.81; 95% CI: 0.63 to 1.03; P = 0.08).
                Implementation of a pneumonia practice guideline in the Intermountain Health Care system was associated with a reduction in 30-day mortality among elderly patients with pneumonia. To evaluate the impact of an interventional multidisciplinary antibiotic management program on expenditures for antibiotics and on the incidence of nosocomial infections caused by Clostridium difficile and antibiotic-resistant pathogens during 7 years.
                Prospective study with comparison with preintervention trends.
                University-affiliated teaching hospital.
                All adult inpatients.
                A multidisciplinary antibiotic management program to minimize the inappropriate use of third-generation cephalosporins was implemented in 1991. Its impact was evaluated prospectively. The incidence of nosocomial C. difficile and resistant Enterobacteriaceae infections as well as the rate of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of National Nosocomial Infections Surveillance System hospitals of similar size.
                Following implementation of the program, there was a 22% decrease in the use of parenteral broad-spectrum antibiotics (P < .0001) despite a 15% increase in acuity of patient care during the following 7 years. Concomitantly, there was a significant (P = .002) decrease in nosocomial infections caused by C. difficile and a significant (P = .02) decrease in nosocomial infections caused by resistant Enterobacteriaceae. The program also appeared to have a favorable impact on VRE rates without a sustained impact on MRSA rates.
                These results suggest that an ongoing multidisciplinary antibiotic management program may have a sustained beneficial impact on both expenditures for antibiotics and the incidence of nosocomial infection by C. difficile and resistant bacterial pathogens. Two hundred twenty-six patients with bacteremia were prospectively enrolled in a randomized trial that was performed to determine the clinical impact of the receipt of in vitro microbiological data by the physician soon after organism detection as opposed to having the physicians wait until similar data were available by routine methods. Identification and antibiotic susceptibility patterns of 110 isolates were determined by direct inoculation of the Vitek AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.) with a sample from a positive blood culture vial. One hundred sixteen isolates were processed by routine methods. Microbiological results were available within an average of 8.8 h by the direct method versus an average of 48 h by the routine method. In both groups an infectious disease fellow used the information to make therapeutic recommendations to the responsible physician. When compared with that provided by the routine method, the information provided by the direct method was significantly more likely to result in an initiation of antibiotic therapy, a change to more effective therapy, or a change to less expensive therapy. Recommendations were significantly more likely to be followed in patients whose isolates were processed by the direct method versus the routine method. A projected savings of $158 per patient was estimated for the patients who were changed to less expensive therapy or in whom antibiotics were discontinued because results were available sooner. These cost savings, coupled with changes in therapy made for reasons of efficacy, support the usefulness of the earlier reporting of the identity and antibiotic susceptibility patterns of bacterial blood culture isolates. To describe the epidemiology, antimicrobial susceptibility, and control of widespread ceftazidime-resistant Klebsiella pneumoniae infections in a North American hospital and circumstances that led to delayed detection.
                A 2-year epidemiologic, microbiologic, and clinical cohort study.
                A 487-bed general hospital in New York City. PATIENTS AND CLINICAL ISOLATES: Patient records were reviewed retrospectively and prospectively. Isolates were obtained from the Clinical Microbiology Laboratory.
                Four hundred thirty-two isolates of ceftazidime-resistant Klebsiella pneumoniae were recovered during a 19-month study period. The peak incidence reached 17.3% of all Klebsiella isolates. One hundred fifty-five patients were colonized or infected, representing more than 70 per 1000 average daily census. Infections occurred in 39% of patients from whom ceftazidime-resistant Klebsiella was isolated. These included 14 bacteremias and 17 pulmonary infections among 52 infected patients. The outbreak coincided with increasing use of ceftazidime therapy for multiresistant Acinetobacter infections. Reduction in ceftazidime use and barrier precautions markedly reduced the incidence of colonization and infection. Ceftriaxone, ceftizoxime, cefotaxime, and cephamycins were inhibitory, but not bactericidal, against ceftazidime-resistant Klebsiella and appeared effective by routine disc diffusion tests. In contrast, imipenem provided consistent bactericidal activity. Preliminary studies indicated that the outbreak was caused by one or more plasmid-mediated beta lactamases.
                Nosocomial ceftazidime-resistant Klebsiella pneumoniae may be resistant to the bactericidal activity of all cephalosporins and cephamycins. Such isolates appear susceptible to cephalosporins other than ceftazidime by routine disc diffusion testing. Ineffective therapy, delayed detection of resistance, and epidemic spread are potential consequences. Imipenem provides consistent bactericidal activity. Ceftazidime restriction and barrier precautions for colonized and infected patients are effective control measures. Strictly enforced formulary restrictions for aminoglycosides, cephalosporins, and a vancomycin group generated combined savings of $2.61 (p less than 0.0046) per antibiotic day and $34,597 (p less than 0.0003) per month. Even after some cost increases (not significant) in new and other antibiotics, the program saved $1.33 (p less than 0.0175) per antibiotic day and $24,620 (p less than 0.0311) per month for all antibiotics. The pharmacy's 1985 average cost per antibiotic day and its monthly expenditures were $18.45 and $199,003, respectively. In the months following the formulary restrictions, no significant detrimental changes occurred in hospital length of stay or mortality. A retrospective analysis of 322 patients with bacteremia treated before and after the onset of the controls revealed that antibiotics were more appropriately used afterwards. Previous administration of third-generation cephalosporins predisposes to colonization and infections by multiresistant Enterobacter sp. The emergence of multiresistant bacteria infections in a neonatal unit during 1995, especially Enterobacter cloacae, stimulated this study.
                To evaluate the efficacy of measures to control colonization and nosocomial infection by multiresistant bacteria in a neonatal unit.
                A tertiary care university hospital.
                This study was conducted from October 1995 through December 1999 in 4 phases: a cross-sectional study, a longitudinal study with intervention measures, monthly cross-sectional studies, and determination of nosocomial infections caused by multiresistant bacteria (oxacillin-resistant Staphylococcus aureus and gram-negative bacteria resistant to either aminoglycosides or third-generation cephalosporins). Specimens for surveillance culture were obtained through umbilical and rectal swabs, and tracheal aspirates from intubated babies. The intervention measures were as follows: (1) appropriated training of the whole health care team, emphasizing measures to reduce cross-colonization, and the importance of rational usage of antibiotics and (2) suppression of usage of third-generation cephalosporins. Risk factors were analyzed through univariate and multivariate logistic regression.
                In the first phase, 32% (10/31) of the patients were colonized by multiresistant bacteria (29% by multiresistant E cloacae ). In the second phase, 342 patients were evaluated; 33% of them were colonized by E cloacae, and a multiresistant strain was isolated in 10.8% (37/342) of the babies. A logistic regression model indicated parenteral nutrition and antibiotic usage as risk factors for colonization by multiresistant E cloacae. In the third phase, for 6 months, only 2 patients were colonized by multiresistant E cloacae. In the fourth phase, the analysis of bacterial resistance profile indicated a reduction of nosocomial infections due to multiresistant bacteria from 18 cases in 1995 to 2 cases per year until 1999.
                These results have shown that the measures adopted were effective. Improving obstetric care in resource-limited countries is a major international health priority.
                To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods.
                Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate.
                Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04).
                Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings. A comprehensive program of clinical and administrative strategies to reduce expenditures for antimicrobial agents is described. Clinical intervention strategies include the use of antimicrobial order sheets, standardized dosage regimens, restriction policies for certain antimicrobial agents, and position statements on the use of restricted agents. A cornerstone of the program is the support for cost-reduction interventions offered by the pharmacy and therapeutics committee and its subcommittee on therapeutics; that support is demonstrated through endorsement and enforcement of pharmacy programs. Physicians are reminded of the cost-reduction programs through periodic articles in the pharmacy newsletter and an "antibiogram" card supplied by the division of epidemiology. The effectiveness of these interventions has been demonstrated by progressive decreases in expenditures for antimicrobial agents during 1987 and 1988. Antimicrobial agents also account for increasingly smaller percentages of the total drug budget. This combination of clinical and administrative strategies reduced expenditures for antimicrobial agents by more than $700,000 over two years without the use of clinical specialists or any apparent sacrifice in the quality of patient care. This study investigated the impact of a combined intervention strategy to improve antimicrobial prescribing at University Hospital Groningen. For the intervention, the antimicrobial treatment guidelines were updated and disseminated in paperback and electronic format. The credibility of the guidelines was improved by consultation with users. In a second phase, academic detailing (AD) was used to improve specific areas of low compliance with the guidelines. Materials and methods: Prescribing data were prospectively collected for 2869 patients receiving 7471 prescriptions for an antimicrobial for an infection covered by the guidelines between July 2001 and September 2003. After collection of baseline data, the guidelines were actively disseminated in February 2002. Next, after a 5 month interval, a second intervention, i.e. an AD approach, addressed suboptimal prescribing of ciprofloxacin and co-amoxiclav. Segmented regression analysis was used to analyse the interrupted time-series data.
                At baseline, compliance with the drug choice guidelines was 67%. The first intervention showed a significant change in the level of compliance of +15.5% (95% CI: 8%; 23%). AD did not lead to statistically significant additional changes in already high levels +12.5% (95% CI:-3%; 28%) of compliance. Post-intervention compliance was stable at 86%.
                Updating the guidelines in close collaboration with the specialists involved followed by active dissemination proved to be an efficient way to improve compliance with guideline recommendations. An 86% compliance level was achieved in this study without compulsory measures. A ceiling effect may have limited the added value of AD. At EHS Christ Hospital and Medical Center, an eight-step process improvement model was developed that incorporates continuous quality improvement concepts for monitoring, evaluating and improving patient care. Nursing home residents admitted with pneumonia were identified as the group having the most influence on mortality and costs associated with treatment of pneumonia at our hospital. A multidisciplinary team evaluated clinical resource use and patient care processes, and identified root causes of various influencing treatment. Clinical guidelines were created and outcomes were defined, resulting in significant improvement in the clinical management of these patients. Average length of stay decreased from 8.6 days in 1992 to 7.6 days in 1993, with a charge reduction of $1830 per patient. The methodologic framework of a process improvement program combines epidemiologic, clinical, and quality improvement sciences. This mix is essential in improving patient care and quantifying outcomes. Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement.
                Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation.
                In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group.
                The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe. A controlled cross-over study in 12 Victorian public hospitals was performed to examine the power of marketing techniques in influencing prescribing. The targeted prescribing behaviour was the use of antibiotic prophylaxis in surgery, and the criteria for judging the appropriateness of therapy were its duration and timing, as are detailed in the fourth edition of the booklet Antibiotic guidelines. The first intervention was mounted in 1985 in six hospitals (two metropolitan teaching hospitals, one suburban general hospital and three rural hospitals), and six matched hospitals acted as control hospitals. One year later, the intervention was mounted in the six hospitals that previously had been the control hospitals. The interventional campaign consisted of material that was similar to that which is used by the pharmaceutical industry, including an "academic" representative. Its effect was assessed by audits that were performed before and after the first interventional campaign and again, one year later, after the second interventional campaign. The proportion of antibiotic courses that were assessed as satisfactory in terms of duration increased significantly after the first campaign in the hospitals where the intervention was mounted. No significant changes in prescribing occurred in the control hospitals. In the hospitals which were control hospitals in 1985, and in which the intervention occurred in 1986, the proportion of antibiotic courses that were assessed as satisfactory also increased significantly after the interventional campaign. A fall-off in performance occurred during the 12 months after the campaign in the 1985-interventional hospitals. Calculated cost savings more than outweighed the costs of the campaign. We conclude that inappropriate prescribing behaviour in hospitals can be modified successfully by educational marketing techniques. To compare two strategies for implementing guidelines for nursing home-acquired pneumonia (NHAP) and to measure outcomes associated with treatment in accordance with the guidelines.
                Randomized controlled trial.
                Ten skilled nursing facilities (SNFs) from a single metropolitan area.
                Patients with an episode of pneumonia acquired more than 3 days after admission to SNF (N = 350): 226 preintervention episodes of pneumonia and 116 postintervention episodes.
                Multi-faceted education intervention including small-group consensus process limited to physicians and a similar intervention that included physicians and nurses within randomly selected SNFs.
                Antibiotic use at diagnosis compared with the guidelines, hospital admission, severity of pneumonia, and 30-day mortality.
                Data were complete for 344 episodes of NHAP. For the preintervention group (n = 226), 62.2% (79/127) of the episodes were treated with parenteral antibiotics (PA) when PA were recommended by the guidelines and 57.6% (57/99) of episodes were treated with oral antibiotics (OA) when OA were indicated by the guidelines. Postintervention, treatment with PA and OA according to the guidelines was not significantly different between the two groups of randomized SNFs. A multivariate analysis comparing PA use pre- and postintervention for all SNFs, adjusted for variation in the frequency and severity of pneumonia, found significantly more of the postintervention episodes were treated with PA in accordance with the guidelines (P < .02). A preintervention significant difference in 30-day mortality observed between episodes with indications for PA (37.8% (48/127)) and episodes with indications for OA (6.1% (6/99)) (P < .001) was not present postintervention (11.5% (6/52); (23.8% (15/64); P = .06). There was no significant difference in 30-day mortality preintervention and postintervention for episodes with guideline indications for OA (P = .35) or for PA (P = .05) (P = .16 for multivariate analysis). The difference in PA use was not associated with significant differences in hospital admissions for episodes on NHAP.
                The increase in the use of PA provides evidence that care within SNFs can be significantly changed using standard quality improvement techniques. Use of the guidelines did not significantly affect mortality. The addition of a practical severity of NHAP model or a change in reimbursement structure may enhance the guidelines' impact on hospitalization for NHAP. The financial benefits available with use of the guidelines will be limited unless the guidelines contribute to a reduction in rates of hospitalization. New injectable antimicrobial agents are generally costly and broad-spectrum. Overusage results in unnecessary economic loss and multi-drug resistant organisms. Effective strategies for decreasing costs without compromising patient care are required. This study aimed to evaluate the economic impact of a system using an antimicrobial order form to assist rational usage of expensive antimicrobial agents. The study was performed during 1988-1996 at a 900-bed, tertiary-care, medical school hospital in Bangkok. The target drugs were 3 costly, broad-spectrum antibacterial drugs, namely imipenem, vancomycin, and injectable ciprofloxacin. The restriction of these 3 drugs was started in 1992 and was extended to netilmicin and ceftazidime in 1995. A filled antimicrobial order form (AOF) was required by pharmacists before dispensing the drugs. The AOF guided the physicians to give explicit information about anatomic diagnosis, etiologic diagnosis, and suspected antimicrobial resistance patterns of the organisms. It also contained information about indications of the restricted drugs. The filled forms were audited daily during working days by the chairman of The Hospital Antibiotic Committee. Feedback was given to the prescribers by infectious disease specialists at least twice a week. The strategy was endorsed by the executive committee of the hospital. Impact of AOF without endorsement, audit and feedback, was evaluated in 1996. The expenditures of the drugs were adjusted to the average admitted patient-days per fiscal year of the study period. The system with endorsement was well accepted and could be maintained for 4 years. The adjusted expenditures per year of the 3 restricted antibiotics were 1.41-1.87 million baht less (22-29%) in 1992-1994 than the pre-intervention year 1991. The cost reduction of imipenem and injectable ciprofloxacin could also be maintained for 1995 but not vancomycin for which use increased. The costs of these 3 restricted drugs increased very sharply (69%) in 1996 when there was loss of endorsement and capacity to perform auditing and feed back by infectious disease specialists. The system did not work with ceftazidime which was commonly used for febrile neutropenia and nosocomial infections. To evaluate an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia (VAP).
                Prospective, randomized, controlled clinical trial.
                A medical ICU from a university-affiliated urban teaching hospital.
                Between April 2002 and July 2003, 290 patients completed the clinical trial.
                Patients were assigned to have the duration of antibiotic treatment for VAP determined by an antibiotic discontinuation policy (discontinuation group) or their treating physician teams (conventional group).
                Severity of illness using APACHE (acute physiology and chronic health evaluation) II score (22.8 +/- 9.0 vs 23.2 +/- 9.4, p = 0.683) [mean +/- SD] and the clinical pulmonary infection score (7.1 +/- 0.9 vs 7.2 +/- 0.9, p = 0.222) were similar for both patient groups. The duration of antibiotic treatment for VAP was statistically shorter among patients in the discontinuation group compared to patients in the conventional antibiotic management group (6.0 +/- 4.9 days vs 8.0 +/- 5.6 days, p = 0.001). The occurrence of a secondary episode of VAP was not statistically different between these two groups (17.3% vs 19.3%, p = 0.667). Hospital mortality (32.0% vs 37.1%, p = 0.357) and ICU length of stay (6.8 +/- 6.1 days vs 7.0 +/- 7.3 days, p = 0.798) were also statistically similar.
                The application of an antibiotic discontinuation policy for clinically suspected VAP was associated with a decrease in the overall duration of antibiotic treatment. These findings suggest that shorter courses of empiric antibiotic therapy for patients treated for clinically suspected VAP can be safely achieved. Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay.
                243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat.
                Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%).
                Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications. In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.
                To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.
                In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.
                At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%.
                Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications. The development and use of a hospital-pharmacy-based, computer-assisted antimicrobial monitoring program are described. In the pharmacy department of a teaching hospital in Spain, a manual system for collecting data on use of antimicrobial agents was replaced with a computer-assisted program that compiles data on culture and sensitivity results, the number of patients receiving antimicrobial or bacteriostatic agents (including combination therapy), and the specific agents used by hospital ward, clinical department, and physician. The antimicrobial report is reviewed daily by a pharmacist, and identified problems are discussed with the prescribing physician; about two hours per day is spent in this activity. Data for 1984 compiled by the computer program regarding the use of antimicrobial agents by group and by hospital ward and the relationship between cost and use of antimicrobial agents were evaluated. Based on the computer-generated data, guidelines for antibiotic use in surgical prophylaxis were proposed, and the pharmacy and therapeutics committee approved a new antibiotic policy that led to a reduction in the use of cephalosporins and to subsequent cost savings. Antimicrobial use at this hospital is similar to that reported at other institutions. In 1984 penicillins were the most commonly used agents, followed by aminoglycosides and cephalosporins. Antimicrobial agents accounted for 24.4% of all drug costs. This computer-assisted system of antimicrobial monitoring was used effectively to assess both individual patient therapy and overall antimicrobial use in a teaching hospital. The effect of several drug restriction policies on benzodiazepine and cephalosporin use was evaluated in a large federal hospital. Computerized drug-use data were examined for the 10-year period from 1972 through 1981. The five major types of drug restrictions implemented were the: (1) requirement that all diazepam prescriptions be countersigned by the chief of staff, (2) deletion of cephalothin sodium from the formulary, (3) required countersignature by a physician from the infectious disease service for all cefazolin sodium prescriptions, (4) requirement that justification accompany all cefazolin sodium prescriptions after the countersignature requirement was lifted, and (5) amendment of the countersignature requirement for diazepam with a series of designated exceptions. All of the restrictions resulted in a decrease in the number of dosage units dispensed; however, the required countersignature by the chief of staff and deletion from the formulary were the most effective in restricting drug use. The effect of the restriction policies appears to be related to the influence or power of the restriction enforcer and the perceived importance of the restriction, as well as the relative difficulty of drug acquisition by the prescriber. Formulary deletion, countersignature requirements, or restricted use to a service or physician are action plans that may alter the use rates of drugs. Antibiotics are often used inappropriately in hospitals. We created a structured antibiotic order form designed to guide physicians toward correct therapeutic decisions without restricting their clinical options. Educational messages and graphic reminders were incorporated into a new form required to order parenteral antibiotics at a teaching hospital. Pharmacokinetic considerations were emphasized. The forms were supplemented with brief literature reviews and appropriate references. Before introduction of the form, pharmacokinetically incorrect orders for clindamycin, cefazolin sodium, and metronidazole hydrochloride accounted for 90%, 60%, and 75% of patient-days of therapy for these drugs, respectively. Immediately after implementation of the form, nonrecommended dosing schedules dropped to under 6% of patient-days for all three antibiotics. Savings from these drugs alone accounted for over $76,000 annually. We conclude that in a period of increasing constraints on hospital budgets and proliferating restrictions on physicians' clinical choices, educational intervention at the time orders are written can provide a cost-effective and noncoercive means of improving some forms of acute-care clinical decision making. Despite the publication of guidelines for the management of pneumonia, significant variation in care continues to exist. While there have been several published reports of quality improvement projects for pneumonia, there are few data on the effectiveness of these efforts in small hospitals. The purpose of this study was to demonstrate that a project implemented by a quality improvement organization in small hospitals would lead to an improvement in care that could not be accounted for by secular trends in the management of pneumonia.
                Medicare-insured hospital admissions for pneumonia were reviewed from 20 small hospitals in Oklahoma (intervention group) at baseline and after feedback. Project intervention included onsite feedback presentations to the medical staff, samples of performance improvement materials, and comparative measures of performance of predefined quality indicators. A second group of 16 demographically similar hospitals (control group) was selected for review during the same 2 periods. These hospitals subsequently underwent an identical intervention with a follow-up assessment.
                Statistically significant improvements in process measures were demonstrated in the intervention hospitals, including performance of a sputum (P<.01) and blood (P<.001) cultures, antibiotic administration within 4 hours of hospital admission (P<.001), and administration of the first dose of antibiotic in the emergency department (P<.001). These measures in the control hospitals did not change significantly (P =.93, .08, .79, and .52, respectively) during the 2 periods.
                Improvements in processes of care achieved by the intervention hospitals resulted from activities initiated because of participation in a quality improvement organization-directed project. This study demonstrated the effectiveness of quality improvement activities in very small hospitals. To evaluate the impact of a multifactorial intervention to improve the quality, efficiency, and patient understanding of care for community-acquired pneumonia.
                Times series cohort study.
                Four academic health centers in the New York City metropolitan area.
                All consecutive adults hospitalized for pneumonia during a 5-month period before (n = 1,013) and after (n = 1,081) implementation of an inpatient quality improvement (QI) initiative.
                A multidisciplinary team of opinion leaders developed evidence-based treatment guidelines and critical pathways, conducted educational sessions with physicians, distributed pocket reminder cards, promoted standardized orders, and developed bilingual patient education materials.
                The average age was 71.4 years, and 44.1% of cases were low risk, 36.8% were moderate risk, and 19.2% were high risk. The preintervention and postintervention groups were well matched on age, sex, race, nursing home residence, pneumonia severity, initial presentation, and most major comorbidities. The intervention increased the use of guideline-recommended antimicrobial therapy from 78.1 to 83.4% (p = 0.003). There was also a borderline decrease in the proportion of patients being discharged prior to becoming clinically stable, from 27.0 to 23.5% (p = 0.06). However, there were no improvements in the other targeted indicators, including time to first dose of antibiotics, proportion receiving antibiotics within 8 h, timely switch to oral antibiotics, timely discharge, length of stay, or patient education outcomes.
                This real-world QI program was able to improve modestly on some quality indicators, but not effect resource use or patient knowledge of their disease. Changing physician and organizational behavior in academic health centers will require the development and implementation of more intensive, system-oriented strategies. The financial impact of using cefamandole and cefoxitin rather than cefazolin and of using ticarcillin rather than carbenicillin in one institution was assessed; the effectiveness of clinical pharmacists in reducing the costs associated with these drugs also was determined. During Phase 1 (July 1, 1980-March 31, 1981), the numbers of intravenous piggyback cefazolin, cephalothin, cefamandole, cefoxitin, carbenicillin, and ticarcillin doses prepared were recorded. Quarterly purchase data for each drug were determined from invoice records. During Phase 2 (April 1, 1981-September 30, 1981), eight clinical pharmacists reviewed all patient charts for cefamandole, cefoxitin, and ticarcillin orders. If the indication for these orders was missing or considered inappropriate, the pharmacist contacted the prescriber and recommended substituting appropriate doses of cefazolin for cefamandole and cefoxitin and of carbenicillin for ticarcillin. The number of doses prepared and quarterly purchase data were collected as in Phase 1. The projected savings resulting from clinical pharmacist input relating to these drugs was calculated. Based on Phase 1 data, the total theoretical expense resulting from cefamandole and cefoxitin use instead of cefazolin and from ticarcillin use in place of carbenicillin was projected to be $233,448 annually. Cefamandole and cefoxitin accounted for 59.8 and 39.7% of total cephalosporin use in Phases 1 and 2, respectively. Ticarcillin accounted for 77.1% of the total ticarcillin and carbenicillin doses in Phase 1, and 16.6% in Phase 2. A projected annual savings of $156,756 was achieved because of clinical pharmacist input at a cost of $16,000 for time devoted to the effort. Clinical pharmacists were effective in reducing the use of cefamandole, cefoxitin, and ticarcillin in situations where cefazolin or carbenicillin could be substituted. The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported. Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended. Data were obtained for nine restricted drugs and for three that were never restricted. Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin. For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103%. There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials. In the postrestriction period, ceftazidime and imipenem-cilastatin were used more often in patients who were less critically ill. Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed. Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods. The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent. The authors' hospital embarked on a three-component, multidisciplinary, hospital-based antimicrobial use program to cut costs and reduce inappropriate antimicrobial use. Initially, antimicrobial use patterns and costs were monitored for 12 months. For the next two years, an antimicrobial use program was implemented consisting of three strategies: automatic therapeutic interchanges; antimicrobial restriction policies; and parenteral to oral conversion. The program resulted in a reduction in the antimicrobial portion of the total pharmacy drug budget from 41.6% to 28.2%. Simultaneously, the average cost per dose per patient day dropped from $11.88 in 1991 to $10.16 in 1994. Overall, mean monthly acquisition cost savings rose from $6,810 in 1992 to $27,590 in 1994. This study demonstrates that a multidisciplinary antimicrobial use program in a Canadian hospital can effect dramatic cost savings and serve as a quality assurance activity of physician antimicrobial prescribing behaviour. There is a considerable gap between randomized clinical trials and implementing the results into practice. This is particularly relevant in the use of broad-spectrum antibiotics in hospitals. Hospital pharmacists can be effective vehicles for bridging this gap and promoting evidence-based medicine. To determine the most effective way of using the pharmacist in this role, a prospective cefotaxime intervention study was conducted with randomization incorporated into the design as well as patient-related therapeutic outcomes.
                A total of 323 patients who were prescribed cefotaxime were randomized into an intervention or nonintervention group where only the former was challenged by pharmacists for inappropriate cefotaxime usage relative to hospital guidelines. The primary outcome was the appropriateness of cefotaxime prescribing between groups. Logistic regression analysis was then used to identify factors that were associated with successful clinical response.
                Overall, 94% of orders in the intervention group met cefotaxime dosage criteria compared with 86% in the control group (p = .018). However, there was no impact with respect to promoting cefotaxime use for an appropriate indication (81% vs. 80%; p = .67). There was a trend for improved clinical outcomes in patients who received cefotaxime within hospital guidelines (OR = 1.73; p = .31).
                The pharmacist as a vehicle for promoting the appropriate use of broad-spectrum antibiotics in the acute care hospital setting can improve the dosing of such agents. However, several barriers to optimizing the impact of the pharmacist were implied by the data. Removing these barriers could increase the pharmacists' utility as an agent for improved patient care. Appropriate antibiotic treatment decreases mortality, while superfluous treatment is associated with antibiotic resistance. We built a computerized decision support system for antibiotic treatment (TREAT) targeting these outcomes.
                Prospective cohort study comparing TREAT's advice to physician's treatment followed by a cluster randomized trial comparing wards using TREAT (intervention) versus antibiotic monitoring without TREAT (control). We included patients suspected of harbouring bacterial infections in three hospitals (Israel, Germany and Italy). The primary outcome, appropriate antibiotic treatment, was assessed among patients with microbiologically documented infections (MDI). Length of hospital stay, adverse events, mortality (interventional trial) and antibiotic costs (both studies), including costs related to future antibiotic resistance, were compared among all included patients.
                Among 1203 patients included in the cohort study (350 with MDI), TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians (70% versus 57%, P < 0.001) using less broad-spectrum antibiotics at half physicians' antibiotic costs. The randomized trial included 2326 patients, 570 with MDI. The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [73% versus 64%, odds ratio (OR): 1.48, 95% confidence interval (CI): 0.95-2.29, intention to treat, adjusted for location and clustering]. For patients treated according to TREAT's advice in intervention wards, the difference with controls was highly significant (OR: 3.40, 95% CI: 2.25-5.14). Length of hospital stay, costs related to future resistance and total antibiotic costs were lower in intervention versus control wards.
                TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment. This study sought to assess the impact of restricting use of vancomycin and third-generation cephalosporins on vancomycin-resistant enterococci (VRE) prevalence. All clinical enterococcal isolates identified at a large academic medical center during a 10-year period were analyzed. Changes in VRE prevalence after sequential restrictions on use of vancomycin and third-generation cephalosporins were evaluated. The correlation between antibiotic use and VRE prevalence was also investigated. Vancomycin use initially decreased by 23.9% but returned to preintervention levels by the end of the study. Third-generation cephalosporin use decreased by 85.8%. However, VRE prevalence increased steadily from 17.4% to 29.6% during the 10-year period (P<.001). Clindamycin use was significantly correlated with VRE prevalence. Restricting the use of vancomycin and third-generations cephalosporins had little impact on VRE prevalence. The association between clindamycin use and the prevalence of VRE suggests that restriction of this and perhaps other antianaerobic agents might be an important component of future antimicrobial interventions. The impact of attendance by infectious disease specialists (IDS) on hospitalised adults with community-acquired infection was assessed by studying 402 consecutive febrile adults who were admitted randomly to either of two internal medicine wards over a 4-month period and given intravenous antibiotics. In ward 1, patients were attended by IDS, whereas those in ward 2 were attended by physicians from other specialties. In total, 160 patients were treated in ward 1 and 242 in ward 2 (median age 66 years; 49% male). The case-mix was comparable. Only 39% of ward 2 patients underwent minimal fever diagnostic tests compared to 82% in ward 1 (p < 0.001). Ward 1 and 2 patients received 188 and 315 antibiotic courses, respectively, of which 32% and 20% required approval from IDS (p 0.003). Patients in ward 1 were more likely to receive ceftriaxone (7.5% vs. 2%; p 0.002), erythromycin (7% vs. 1.5%; p 0.002) and cefuroxime (48% vs. 26%; p < 0.0001), but were less likely to receive amoxycillin-clavulanate (8% vs. 28%; p < 0.0001). The mean durations of therapy were 3.6 and 3.2 days (not significant), and therapy was deemed to be completely appropriate in 55.5% and 43% of cases, respectively (p 0.012). The crude mortality rates were 6.3% and 7.9%, respectively (not significant), while the medication costs were US dollars 27.4 and US dollars 26.4/patient/antibiotic day, respectively. Regular attendance by IDS resulted in significantly higher rates of accurate diagnosis and appropriate therapy. IDS prescribed more restricted (and expensive) agents, but preferred less expensive agents among unrestricted drugs, thereby offsetting the overall medication costs. A multidisciplinary antibiotic review team (MART) was implemented to improve patient care and reduce antimicrobial expenditures. MART consists of pharmacists and infectious disease (ID) physicians reviewing patients three times weekly. Antibiotic expenditures were reduced by recommending conversions to therapeutically equivalent antibiotics, conversion to an oral agent, and completion of treatment with home infusion therapy. In addition, MART proposed therapeutic interchanges from ceftriaxone to cefotaxime to the P and T committee. ID physician or pharmacist offered recommendations and initiated order changes if the attending physician agreed. Annualized savings was $74,371, with 40% of the recommendations resulting in an improved antimicrobial therapy. Shortening the turnaround time of microbiological procedures was associated with an improved clinical outcome in two studies performed in the USA. To study the clinical impact of a shortened turnaround time in a northwest European setting in which an automated system was used for bacterial identification and susceptibility testing, a single-blind, prospective, randomised controlled trial was conducted in a hospital in the Netherlands. All hospitalised patients with a bacterial infection confirmed by culture were randomly assigned to a control (conventional) group or an intervention (rapid) group. Overnight methods were used for identification and susceptibility testing in the control group, while the Vitek 2 system (bioMerieux, Marcy l'Etoile, France) was used in the rapid group. In each of three consecutive study periods, accelerating factors were added progressively to the laboratory workflow of the rapid group to increase same-day reporting, whereas methods remained identical in the conventional group. The turnaround time of the microbiological cycle using the Vitek 2 system as compared to conventional methods was studied and the clinical impact of a shortened turnaround time assessed in terms of mortality, morbidity, and cost. For the rapid groups, the turnaround time was significantly shorter for oral reporting of final susceptibility results in all three study periods and for reporting on paper in the third study period. There was no significant difference between groups in any of the clinical impact variables. Vitek 2 results were available for reporting significantly earlier as compared to conventional testing. For the overall patient group in our hospital setting, however, this had no clinical impact. To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews.
                Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group.
                25 of the 26 district general obstetric units in two former NHS regions.
                The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies.
                Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials.
                Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits.
                Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost pound860 each (at 1995 prices).
                There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence. A high proportion of medical in-patients in the UK receive intravenous (IV) antibiotic therapy. This may be inappropriate in non-severe infections, or unnecessarily prolonged.
                To assess the impact of guideline implementation on IV antibiotic prescribing in medical admissions to a general hospital.
                Observational intervention study.
                Data relating to infection and antibiotic therapy were collected for 4 weeks pre-intervention (group 1) and 4 weeks post intervention (group 2). Six months later, data were collected for a further 4 weeks following a second intervention (group 3). Interventions consisted of pharmacy-led implementation of guidelines incorporating criteria for IV therapy and switching to the oral route. The second intervention also included pharmacy-initiated feedback on prescribing. The main outcome measures were IV antibiotic duration, and appropriateness of the IV route and switching.
                Of 2365 admissions, 757 (32%) had 806 treated episodes. IV therapy was used in 40%, 46% and 36% (groups 1, 2 and 3, respectively) and was appropriate in 92% vs. 100% (group 1 vs. 2). In groups 2 and 3, oral switch timing was appropriate in 90% and 88%, vs. 17% in group 1 (p < 0.001). Between groups 1 and 2, median duration of IV therapy was reduced from 3 to 2 days (p = 0.01). More patients in group 2 received appropriate exclusively IV therapy (65% vs. 96%, p < 0.01). Duration of stay in IV-treated patients reduced from 13 to 10 days in groups 2 and 3 (p = 0.047). IV antibiotic expenditure reduced by 13% per patient admitted between groups 1 and 2.
                Pharmacy-led introduction of antibiotic guidelines appears to result in clinically appropriate reductions in IV therapy. To achieve sustained improvement in use of cefotaxime and ceftriaxone (CEFX) in a major teaching hospital, as measured against national antibiotic guidelines.
                Pre- and post-intervention survey of CEFX use in the Royal Melbourne Hospital, a tertiary hospital in Melbourne, Victoria.
                Web-based antimicrobial approval system linked to national antibiotic guidelines was developed by a multidisciplinary team and implemented in March 2001.
                Change in rate of CEFX use (defined daily doses [DDDs] per 1000 acute occupied bed days) over 8 months pre- and 15 months post-intervention; concordance of indication for CEFX with national antibiotic guidelines pre- and post-intervention.
                CEFX use decreased from a mean of 38.3 DDDs/1000 bed days pre-intervention to 15.9, 18.7 and 21.2 DDDs/1000 bed days at 1, 4 and 15 months post-intervention. Concordance with national antibiotic guidelines rose from 25% of courses pre-intervention to 51% within 5 months post-intervention (P < 0.002). Gentamicin use also increased, from a mean of 30.0 to 48.3 DDDs/1000 bed days (P = 0.0001).
                The web-based antimicrobial approval system achieved a sustained reduction in CEFX use over 15 months as well as increased prescribing concordance with antibiotic guidelines. It has potential for linking to electronic prescribing and for wider use for other drugs, as well as for research into the epidemiology of antibiotic use. To test whether a ceftazidime restriction policy in a pediatric intensive care unit (ICU) could decrease the endemic rate of colonization with ceftazidime-resistant gram-negative bacilli.
                Prospective, pre- vs. postintervention study.
                University hospital pediatric ICU.
                Consecutive children admitted to the pediatric ICU over a 19-mo period.
                After an observation period in which antibiotic use was not controlled, ceftazidime was prohibited unless the patient's microbiological results indicated that the drug was necessary for cure. Aminoglycoside use was not regulated. The size of the endemic reservoir of ceftazidime- and tobramycin-resistant organisms was determined by daily nasopharyngeal and rectal swab specimens obtained on all admissions to the ICU.
                Despite a 96% reduction in ceftazidime use, the incidence density (number of isolates/100 patient-days) of ceftazidime-resistant organisms increased through the course of the study, from 1.57 to 2.16. The incidence density of tobramycin-resistant organisms was unchanged. Ceftazidime restriction resulted in a small but nonsignificant decrease in the proportion of ceftazidime-resistant organisms acquired late (beyond 72 hrs) in the patients' ICU course (56.5% vs. 45.9%). However, there was a more substantial decrease in the proportion of ceftazidime-resistant organisms derived from species known to harbor derepressible amp C beta-lactamases (68.2% vs. 45.9%, p < .05).
                These data indicate that antibiotic restriction policies in an ICU fail to diminish the size of the endemic reservoir of antibiotic-resistant gram-negative rods, and suggest that such policies in the absence of broader efforts to limit antibiotic use will have little impact. Guidelines and clinical Cupertino for rational antibiotic use were implemented in a Norwegian paediatric department in 1994. From 1994 to 1998 the use of antibiotics and expenditures was reduced by 50%. There was an 80% decrease in the use of cloxacillin, a 74% decrease of aminoglycosides and a 59% decrease of cephalosporins. The use of penicillin V and G increased by 14% and ampicillins by 8%. Eight point prevalence studies showed that on average 23% (range 21-38%) of the patients were treated with antibiotics. Penicillins were used in 44% of courses, aminoglycosides in 35% of courses and cephalosporins in 9% of courses. Treatment was mostly adjusted to bacteriological findings. Compliance with guidelines was >90%. Guidelines for rational antibiotic policy and multidisciplinary co-operation lead to reduction in the use and expenses of antibiotics in a paediatric department. The rectal carriage of glycopeptide-resistant Enterococcus spp. (GRE) had been established at approximately 50% in a series of prevalence studies on a busy haematological malignancy unit. The aim of this study was to reduce the chance of patients acquiring GRE. A prospective three-phase sequential study was performed. In Phase 1, the acquisition rate of GRE detectable by rectal swab was measured without any intervention for a period of 4 months. For the following 8 months (Phase 2), the first-line treatment for febrile neutropenic episodes was changed from monotherapy with ceftazidime to piperacillin/tazobactam. In addition, an intense education programme was introduced to improve hygiene to reduce the risk of case-to-case spread. In the final 4 months (Phase 3), ceftazidime was again used as the first-line antimicrobial, while continuing the same level of training in relation to hygiene. The carriage of GRE was measured from rectal swabs done weekly. During the initial 4 months, at any time, 40-50% of patients in the unit were colonized with GRE, and 43 of 75 (57%) new patients initially negative for GRE acquired it within 6 weeks of their admission. In Phase 2, 25 patients out of 129 (19%) acquired GRE, with the acquisition rate falling progressively so that in the last 3 months, only one new patient acquired GRE (logrank comparison of probabilities for cohort 1 vs cohort 2b: P < 0.0001). A return to ceftazidime in Phase 3 was associated with a return of the risk of acquiring detectable GRE colonization, despite continued hygiene teaching and surveillance, with 21 out of 58 patients (36%) acquiring GRE (cohort 1 vs cohort 3: P = 0.08). Glycopeptide usage was not reduced during the period of the study. Clinical cases were seen only in Phases 1 and 3. Although the reduction in the risk of acquiring GRE may have been due in part to hygiene practices as well as to the change in antimicrobial usage, or may have occurred spontaneously for other reasons, the return of the problem with the reintroduction of ceftazidime strongly suggests that this antibiotic was responsible for encouraging the acquisition of detectable GRE. To implement and monitor the effectiveness of a strategy to curb unnecessary use of vancomycin and teicoplanin for inpatients in a teaching hospital/tertiary referral centre where 33% of S. aureus isolates (72% from ICU patients) were methicillin resistant.
                A sample of 182 vancomycin/teicoplanin inpatient prescriptions surveyed, revealed that only 31 (17%) conformed with Centre for Disease Control (CDC) guidelines. Following education (ward-rounds, bulletins) on appropriate CDC based guidelines for prescribing glycopeptides directed at relevant clinicians, 'Immediate Concurrent Feedback' (ICF) was gradually deployed throughout the hospital. This entailed review of respective inpatient records on the next working day. If the indication was deemed not to conform with our guidelines, the prescriber was issued a memo (copied to the supervising doctor). Each memo detailed the 'errant' incident, listed appropriate indications and explicitly advised desisting from such prescribing and suggested alternative therapy if necessary. Corresponding glycopeptide usage data for our hospital and others in Hong Kong were retrieved and analysed as were samples of records of our inpatients with staphylococcal septicaemia (pre and during ICF).
                Compared with baseline values, during 2 years of ICF, inpatient prescribing of vancomycin and teicoplanin deemed to conform increased to 71% (773/1086); difference 54% (P < 0.0001, 95% CIs 47-62%). Corresponding average monthly usage (DDDs/1000 admissions) decreased from 76 (pre-ICF) to 45; mean difference 31 (P < 0.0001, 95% CIs 24, 38). Mortality from staphylococcal bacteraemia remained unchanged. No comparable changes in glycopeptide usage ensued in comparator hospitals.
                ICF can be used safely to curb irrational overuse of vancomycin and teicoplanin in a hospital with high methicillin resistant S. aureus infection rates. Rapid diagnostic tests with a high sensitivity for lower respiratory tract infection (LRTI) could lead to improved patient care and reduce unnecessary antibiotic use and associated costs. Diagnostic yields, feasibility, and costs of real-time polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swab specimens in the routine diagnostic work-up for LRTI were determined.
                In a randomized controlled trial, nasopharyngeal and oropharyngeal swab specimens from patients admitted for antibiotic treatment of LRTI were evaluated by means of real-time PCR for respiratory viruses and atypical pathogens, as well as by conventional diagnostic procedures. Real-time PCR results for patients in the intervention group were reported to the treating physician; results for patients in the control group were not made available.
                A total of 107 patients (mean age [+/- standard deviation], 63.6+/-16.3 years) were included, of whom 55 were allocated to the intervention group. The pathogens detected most frequently were influenza virus (14 patients), Streptococcus pneumoniae (8), coronavirus (6), Staphylococcus aureus (5), and rhinoviruses (5). Real-time PCR increased the diagnostic yield from 23 cases (21% of patients) to 47 cases (43% of patients), compared with conventional diagnostic tests. The detection of viral pathogens by PCR was associated with the winter season, less infiltrates on chest radiographs, lower C-reactive protein levels, and shorter duration of symptoms. Use of real-time PCR results resulted in partial or total cessation of antibiotic treatment for 6 patients (11%; 95% confidence interval, 2-19), but overall antibiotic use was comparable in the intervention group and the control group (median duration of treatment, 10.0 vs. 9.0 days; P=not significant). Use of real-time PCR increased treatment and diagnostic costs with 318.17 per patient.
                Implementation of real-time PCR for the etiological diagnosis of LRTI increased the diagnostic yield considerably, but it did not reduce antibiotic use or costs. Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study.
                Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database.
                Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11).
                This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense. To reduce antimicrobial drug costs associated with the administration of cefazolin, a two-stage therapeutic intervention--employing persuasive (informational) and power (therapeutic interchange) strategies--was initiated at this 1,000-bed major Canadian teaching hospital. The target of the intervention was to extend the dosage interval of cefazolin to q8h. During a 12-week preimplementation period, 32% of orders specified 8-hour dosage intervals. This percentage increased to 58% after the 3-week, initial informational stage of the intervention. When therapeutic interchange was employed, the percentage of orders for extended intervals rose to an average of 97% over a 32-week postimplementation period. An estimated annual cost savings of $58,000 resulted from this intervention. Manpower requirements to implement and maintain this program were minimal and prescriber antagonism was not encountered. The implementation, monitoring, and impact of a program to restrict vancomycin use are described. A vancomycin restriction program was implemented in February 1995 at an acute care teaching hospital after guidelines for vancomycin use were established by a multidisciplinary group. Pharmacists reviewed each vancomycin order, suggested alternative treatments when vancomycin use did not comply with the guidelines, and set duration limits for all orders. Orders requiring greater clinical experience for review were referred to a pharmacist or a physician in the division of infectious diseases. The program was monitored by an infectious diseases pharmacist. Data collected after the program was established showed that the volume of vancomycin use decreased substantially. Problems in enforcing the restriction program included administration of vancomycin for surgical prophylaxis before the order reached the pharmacy, continuing use of vancomycin for initial empirical treatment of febrile neutropenic and immunocompromised patients, inadequate tracking of the evaluations, and deficiencies in the evaluations related to a need for continuing education of the pharmacists about the program. Use of vancomycin decreased after a pharmacy-enforced restriction program was implemented. Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.
                In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.
                Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.
                The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes. Prescribing antibiotics for perioperative prophylaxis in common surgical procedures presents an ideal target for educational intervention. In this situation, antibiotics are often used inappropriately, with consequent excess expense and risk of morbidity. We developed an educational intervention aimed at the choice and appropriate dosing of antibiotics for the prophylaxis of cesarean sections. Person-to-person educational messages targeted at authoritative senior department members were supplemented by brief reminders on a structured antibiotic order form. Time-series analyses were conducted on 34 months of antibiotic use data for 2,783 cesarean sections to estimate the trend of magnitude and significance of discontinuities associated with the start of the program. Prior to the intervention, 95% of sections receiving prophylaxis were given cefoxitin and 3% were given cefazolin. After the intervention, these proportions were reversed, with the shift in use occurring immediately after the intervention (p less than .001). Two years after the intervention, virtually all patients undergoing cesarean sections who receive antibiotic prophylaxis are given cefazolin. Savings from this change alone accounted for over $26,000 each year, or $47.36 per patient-day of prophylaxis. Substantial changes in prescribing practices for routine procedures can be accomplished through the implementation of a coordinated educational program that enlists influential senior staff members in a department in which policy-making is highly centralized, coupled with a structured educational ordering system. Lasting improvements in clinical practices may be brought about by means that are noncoercive, inexpensive and well-accepted by medical staff. Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days.
                Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling.
                One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02).
                The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy. A University-based hospital in Bogotá, Colombia, developed and implemented an educational intervention to complement a new structured antibiotic order form. This intervention was performed after assessing the appropriateness of the observed antibiotic prescribing practices using a quasi-experimental study. An application of interrupted time series intervention analysis was conducted in three antibiotic groups (aminoglycosides, cephradine/cephalothin, and ceftazidime/cefotaxime) and their hospital weekly rate of incorrect prescriptions before and after the intervention. A fourth time series was defined on prophylactic antibiotic use in elective surgery. Preintervention models were used in the postintervention series to test for pre-post series level differences. An abrupt constant change was significant in the first, third, and fourth time series indicating a 47, 7.3, and 20% reduction of incorrect prescriptions after the intervention. We conclude that a structured antibiotic order form, coupled with graphic and educational interventions can improve antibiotic use in a university hospital. Resistance to amikacin, gentamicin, and tobramycin was surveyed prospectively during controlled aminoglycoside usage in 14 hospitals. Following an initial baseline period (minimum, three months) during which gentamicin use predominated, gentamicin and tobramycin were placed on restrictive control, establishing amikacin as the aminoglycoside of general use (86 percent of total aminoglycoside usage). During an average of 35 months' restriction of gentamicin and tobramycin, significant reductions in gram-negative resistance to gentamicin (8.4 to 7.0 percent, p less than 0.001) and tobramycin (6.0 to 5.3 percent, p less than 0.01) were observed. The most significant decreases in resistance to gentamicin and tobramycin (p less than 0.001) were found for Pseudomonas aeruginosa, Klebsiella species, Serratia species, and Proteus species. Amikacin resistance among gram-negative bacilli was observed to increase marginally from 1.4 to 1.7 percent (p less than 0.05) during the surveillance period, primarily due to a significant increase in resistance among P. aeruginosa (3.0 to 3.9 percent, p = 0.05). These data were compared with data from a similar surveillance program at the 700-bed Minneapolis Veterans Administration Medical Center. Over a period of 54 months, both gentamicin and tobramycin resistance decreased significantly when amikacin was used (p less than 0.001), then increased with reintroduction of gentamicin (p less than 0.05), and decreased significantly with reintroduction of amikacin (p less than 0.001). Despite predominant amikacin use for a total of 38 months, amikacin resistance did not increase and actually decreased significantly (p less than 0.05) in the last 12 months. Both vancomycin and third-generation cephalosporin use are believed to contribute to a rise in vancomycin-resistant enterococci (VRE) infections. In 1998, the largest number of VRE infections in our hospital occurred in the trauma/burn intensive care unit (TBICU), accounting for nearly 20% of hospital infections. In an attempt to control the VRE infection rate, antibiotic protocols for prophylaxis, empiric, and definitive therapy were initiated during the final quarter of 1998 to minimize cephalosporin use by the introduction of piperacillin/tazobactam. Therefore, we undertook a study of the VRE infection rate for the TBICU in relation to vancomycin, piperacillin/tazobactam, piperacillin, third-generation cephalosporin, and total cephalosporin use before and after efforts to limit cephalosporins. These data were compared to those in the medical and surgical intensive care units. During 1998, seven VRE infections occurred in the TBICU. Following initiation of antibiotic protocols, one case of VRE infection occurred in the subsequent month and no cases in the 17 months since. The decrease in the VRE infection rate corresponded with a significant increase in the use of piperacillin/tazobactam and a reduction in third-generation and total cephalosporin use. In contrast, cephalosporin use in the medical and surgical intensive care units remains significantly higher than in the TBICU, and neither unit has had a reduction in their VRE infection rates. To assess the impact of an automated intraoperative alert to redose prophylactic antibiotics in prolonged cardiac operations.
                Randomized, controlled, evaluator-blinded trial.
                University-affiliated hospital.
                Patients undergoing cardiac surgery that lasted more than 4 hours after the preoperative administration of cefazolin, unless they were receiving therapeutic antibiotics at the time of surgery.
                Randomization to an audible and visual reminder on the operating room computer console at 225 minutes after the administration of preoperative antibiotics (reminder group, n = 137) or control (n = 136). After another 30 minutes, the circulating nurse was required to indicate whether a follow-up dose of antibiotics had been administered.
                Intraoperative redosing was significantly more frequent in the reminder group (93 of 137; 68%) than in the control group (55 of 136; 40%) (adjusted odds ratio, 3.31; 95% confidence interval, 1.97 to 5.56; P < .0001). The impact of the reminder was even greater when compared with the 6 months preceding the study period (129 of 480; 27%; P < .001), suggesting some spillover effect on the control group. Redosing was formally declined for 19 of the 44 patients in the reminder group without redosing. The rate of surgical-site infection in the reminder group (5 of 137; 4%) was similar to that in the control group (8 of 136; 6%; P = .42), but significantly lower than that in the pre-study period (48 of 480; 10%; P = .02).
                The use of an automatic reminder system in the operating room improved compliance with guidelines on perioperative antibiotic prophylaxis. The effect of a change in the first line antibiotic treatment in a neonatal unit was studied. A total of 238 neonates (G1), admitted between 1 January and 31 July 1989, and treated with gentamicin, were compared with 398 (G2) admitted between 1 August 1989 and 31 July 1990 who received amikacin, in the combination of ampicillin plus an aminoglycoside. This change was implemented in an attempt to prevent the spread of an epidemic strain of Enterobacter cloacae resistant to third generation cephalosporins and all aminoglycosides, except amikacin. The change in treatment had no effect on the incidence of nosocomial infections [19.7% (G1) vs. 16.3% (G2) RR = 1.21 (0.86-1.70)], but the proportion of patients with nosocomial infections caused by the E. cloacae decreased (6.3% vs. 2.0% RR 3.14 CI 1.35-7.28). Certain trends in the bacterial ecology emerged: E. aerogenes and Enterococci increased in G2. The proportion of gentamicin-resistant strains such as E. cloacae or Staphylococci decreased and there was no increase in aminoglycoside-resistant strains, except in Escherichia coli, in which resistance to amikacin rose from 0 to 3%. This study illustrates the influence of antimicrobial therapy on the species and the resistance of strains isolated in nosocomial infections. It also highlights the need for epidemiologic surveillance, and poses the question of how best to modify antibiotic policy. To evaluate a program to discontinue intravenous antibiotics at two teaching hospitals, 102 inpatients meeting eligibility criteria were randomly assigned to two groups. In one group, patients' physicians were contacted by pharmacists with recommendations to discontinue intravenous antibiotic therapy; in the other, patients were simply observed. Measured outcomes were antibiotic costs, length of stay, need to restart intravenous antibiotics, in-hospital mortality, and 30-day readmissions. The intervention significantly reduced mean antibiotic costs per patient ($19.82 vs $35.84, p = 0.03), but related labor costs exceeded this benefit. Readmissions were significantly more frequent in the intervention group than in the control group (29% vs 9.8% p = 0.02), but they were not infection related. No impact was demonstrated on the other measured outcomes. Institutions considering such programs or with one in place should conduct similar evaluations. We investigated the possible association between fluoroquinolone use and the rate of methicillin-resistant Staphylococcus aureus (MRSA) recovery from consecutive hospitalized patients.
                We conducted a nonrandomized, prospective, controlled interventional "fluoroquinolone-free" study at 4 large teaching hospitals in northwest France, catering to a total of 5,882,600 persons. During the intervention period (January through December 2001), fluoroquinolone use was prohibited at 1 of the 4 hospitals (Caen Hospital), unless no effective alternative was available. Three university hospitals were used as controls because they had similar preintervention rates of MRSA.
                During the intervention period (2001), the annual rate of fluoroquinolone use decreased from 54 to 5 defined daily doses per 1000 patients per day at Caen Hospital and remained stable in the control hospitals. At the end of the intervention, the rate of MRSA isolation was significantly lower at Caen Hospital than at the control hospitals (353 [32.3%] of 1093 S. aureus isolates were MRSA, compared with 2495 [36.8%] of 6787 isolates; odds ratio, 0.82; 95% confidence interval, 0.69-0.99; P=.036), as determined on the basis of a marginal model that took into account within-hospital clustering. In a before-after time series analysis, compared with forecasted rates, there was a significant downward trend in observed monthly rates of MRSA isolation at Caen Hospital at the end of the intervention.
                This quasi experimental study confirms the association between fluoroquinolone use and MRSA isolation among hospitalized patients. In 1995, changes in our hospital formulary were made to limit an outbreak of vancomycin-resistant enterococci and resulted in decreased usage of cephalosporins, imipenem, clindamycin, and vancomycin and increased usage of beta-lactam/beta-lactamase-inhibitor antibiotics. In this report, the effect of this formulary change on other resistant pathogens is described. Following the formulary change, there was a reduction in the monthly number (mean +/- SD) of patients with methicillin-resistant Staphylococcus aureus (from 21.9 +/- 8.1 to 17.2 +/- 7.2 patients/1,000 discharges; P = .03) and ceftazidime-resistant Klebsiella pneumoniae (from 8.6 +/- 4.3 to 5.7 +/- 4.0 patients/1,000 discharges; P = .02). However, there was an increase in the number of patients with cultures positive for cefotaxime-resistant Acinetobacter species (from 2.4 +/- 2.2 to 5.4 +/- 4.0 patients/1,000 discharges; P = .02). Altering an antibiotic formulary may be a possible mechanism to contain the spread of selected resistant pathogens. However, close surveillance is needed to detect the emergence of other resistant pathogens. Vancomycin-resistant enterococci represent an increasingly important cause of nosocomial infections. Minimizing vancomycin use represents a key strategy in preventing the spread of these infections.
                To determine whether a structured ordering intervention using computerized physician order entry that requires use of a guideline could reduce intravenous vancomycin use.
                Randomized controlled trial assessing frequency and duration of vancomycin therapy by physicians.
                Three hundred ninety-six physicians and 1,798 patients in a tertiary-care teaching hospital.
                Computer screen displaying, at the time of physician order entry, an adaptation of the Centers for Disease Control and Prevention guidelines for appropriate vancomycin use.
                The frequency of initiation and renewal of vancomycin therapy as well the duration of therapy prescribed on a per prescriber basis.
                Compared with the control group, intervention physicians wrote 32 percent fewer orders (11.3 versus 16.7 orders per physician; P = 0.04) and had 28 percent fewer patients for whom they either initiated or renewed an order for vancomycin (7.4 versus 10.3 orders per physician; P = 0.02). In addition, the duration of vancomycin therapy attributable to physicians in the intervention group was 36 percent lower than the duration of therapy prescribed by control physicians (26.5 versus 41.2 days; P = 0.05). Analysis of pharmacy data confirmed a decrease in the overall hospital use of intravenous vancomycin during the study period.
                Implementation of a computerized guideline using physician order entry decreased vancomycin use. Computerized guidelines represent a promising tool for changing prescribing practices. An observational study on the epidemiology of multiresistant Enterobacteriaceae was conducted in the neurology and neurosurgery wards of a university hospital to determine the impact of hospital hygiene measures and an additional temporary restrictive antibiotic agent policy on the sudden rise in incidence of these bacteria. The incidence and prevalence of patients with multiresistant Enterobacteriaceae were assessed, and patient isolates were typed phenotypically and by random amplified polymorphic DNA analysis. All hospital hygiene measures implemented were recorded, and the influence of the restrictive policy on antibiotic use was analyzed. This policy consisted of a prior authorization requirement and the withdrawal of all antibiotics with a possible selective pressure on multiresistant strains (gentamicin, tobramycin, quinolones, cotrimoxazole, broad-spectrum penicillins, and cephalosporins). This ban left only carbapenems and amikacin for treatment. Typing showed that 17 of the 61 (28%) patients involved were infected or colonized with a single multiresistant strain of Klebsiella oxytoca, for which an environmental source was identified. The isolates recovered from the other patients comprised eight different species, and subsequent genotyping yielded a great variety of strains. The increased incidence could not be controlled with hospital hygiene measures alone. Only after implementation of the restrictive antibiotic policy did the epidemic strain vanish and the endemic incidence of multiresistant Enterobacteriaceae decrease to <50% of the level before intervention. In the years since, the incidence has remained at this low level, and the antibiotic costs have decreased to a level lower than before intervention.