Prospective, randomized, double-blind comparison of metronidazole and tobramycin with clindamycin and tobramycin in the treatment of intra-abdominal sepsis. Comparison of imipenem/cilastatin with the combination of aztreonam and clindamycin in the treatment of intra-abdominal infections. Management of intra-abdominal infections. The case for intraoperative cultures and comprehensive broad-spectrum antibiotic coverage. The Canadian Intra-abdominal Infection Study Group. Comparison of intravenous/oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections. Treatment of acute bacterial peritonitis: a trial of imipenem/cilastatin against ampicillin-metronidazole-gentamicin. Imipenem (N-F-thienamycin) versus netilmicin plus clindamycin. A controlled and randomized comparison in intra-abdominal infections. The role of Pseudomonas species in patients treated with ampicillin and Sulbactam for gangrenous and perforated appendicitis. Treatment of intra-abdominal infections is appropriate with single-agent or combination antibiotic therapy. Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intraabdominal infections. A clinical comparison of cefepime and metronidazole versus gentamicin and clindamycin in the antibiotic management of surgically treated advanced appendicitis. Meropenem versus tobramycin with clindamycin in the antibiotic management of patients with advanced appendicitis. Comparison of cefotetan versus combination therapy in peritonitis and serious intra-abdominal sepsis. Comparison of cefoperazone plus sulbactam with clindamycin plus gentamicin as treatment for intra-abdominal infections. A comparison of imipenem/cilastatin with the combination of cefuroxime and metronidazole in the treatment of intra-abdominal infections. Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis. Piperacillin compared with cefuroxime plus metronidazole in diffuse peritonitis. Efficacy of two comparative antibiotic regimens in the treatment of serious intra-abdominal infections: results of a multicenter study. Piperacillin-tazobactam versus imipenem-cilastatin for treatment of intra-abdominal infections. Adjunctive antimicrobial therapy for complicated appendicitis: bacterial overkill by combination therapy. Imipenem versus tobramycin--antianaerobe antibiotic therapy in intra-abdominal infections. Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections. Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections. Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group. Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery. Meropenem monotherapy versus cefotaxime plus metronidazole combination treatment for serious intra-abdominal infections. Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group. Antibiotic treatment during surgery for diffuse peritonitis: a prospective randomized study comparing the effects of cefuroxime and of a cefuroxime and metronidazole combination. The efficacy and safety of isepamicin compared with amikacin in the treatment of intra-abdominal infections. Cefminox versus metronidazole plus gentamicin intra-abdominal infections: a prospective randomized controlled clinical trial. Piperacillin/tazobactam in comparison with clindamycin plus gentamicin in the treatment of intra-abdominal infections. Efficacy of a beta-lactamase inhibitor combination for serious intraabdominal infections. A randomized multicentre trial of pefloxacin plus metronidazole and gentamicin plus metronidazole in the treatment of severe intra-abdominal infections. Report from a Swedish Study Group. Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin. A randomized clinical study of cefoperazone and sulbactam versus gentamicin and clindamycin in the treatment of intra-abdominal infections.
In a prospective, double-blind study, clindamycin was compared with metronidazole, each combined with tobramycin and all by the intravenous route in the treatment of intra-abdominal sepsis. Twenty-three patients received clindamycin and 34 patients received 35 courses of metronidazole. Analysis of the clinical responses of patients indicates that the two antibiotic regiments are of equal efficacy in that there was no difference between them in terms of defervescence or duration of infection. Few adverse effects were noted, and all appeared to be of a minor nature. The clinical safety and efficacy of imipenem/cilastatin in the treatment of intra-abdominal infections was compared with the combination of aztreonam and clindamycin in a randomized prospective trial. The severity of illness was determined by means of the Apache II score and a fixed outcome reporting scheme was used. One hundred and four patients were entered into the study, of whom 80 were evaluable. Forty-two patients were treated with imipenem/cilastatin (500 + 500 mg qds) and 38 with aztreonam (600 tds) and clindamycin (1000 mg tds). The study groups were comparable for age and sex. The imipenem/cilastatin group differed from the aztreonam and clindamycin group in having significantly more patients with the diagnosis of acute appendicitis (P < 0.01) and a significantly lower mean Apache score (P < 0.05). The predominate microorganisms isolated in both groups were Escherichia coli and Bacteroides fragilis. Treatment with imipenem/cilastatin proved successful in 71% and failed in 24%, and initial success only was seen in 5%. The numbers in the group treated with aztreonam and clindamycin were 64%, 29% and 7% respectively. Severity of illness, as measured by Apache II score, had no influence on the study outcome. Imipenem/cilastatin as well as the combination of aztreonam and clindamycin were effective in the treatment of abdominal infections and no major adverse reactions were seen. To test the hypothesis that comprehensive broad-spectrum empirical antimicrobial therapy is superior to limited-spectrum empirical antimicrobial therapy in intra-abdominal infections.
                Prospective, randomized, double-blinded study.
                University-affiliated hospitals in Canada.
                Two hundred thirteen patients with intra-abdominal infections and planned operative or percutaneous drainage.
                Limited-spectrum empirical antimicrobial therapy consisted of cefoxitin sodium, 2 g, intravenously, every 6 hours (n = 109). Comprehensive broad-spectrum empirical antimicrobial therapy consisted of a combination of imipenem and cilastatin sodium, 500 mg, intravenously, every 6 hours (n = 104).
                Failure to cure the intra-abdominal infection (persistence of infection or death).
                Of initial isolates, 98% were sensitive to imipenem plus cilastin sodium compared with 72% for cefoxitin. No difference was found in the failure rate between treatment groups. Among various reasons for failure (including technical), 12 of 80 patients in the limited-spectrum empirical antimicrobial therapy group had resistant organisms at a second intervention compared with 1 of 74 in the comprehensive broad-spectrum empirical antimicrobial therapy group (P < .003, chi 2). One death in the limited-spectrum empirical antimicrobial therapy group was due to autopsy-proved disseminated Pseudomonas aeruginosa (blood, peritoneum, lung, and pleural fluid) that was resistant to cefoxitin, and the other was associated with peritonitis due to cefoxitin-resistant Enterobacter cloacae. One death in the comprehensive broad-spectrum empirical antimicrobial therapy group was associated with peritonitis from Clostridium perfringens that was sensitive to imipenem plus cilastin sodium, and the other was associated with peritonitis from Pseudomonas aeruginosa that was resistant to imipenem plus cilastin sodium.
                Treatment failure of intra-abdominal infection may be due, in part, to the presence of resistant pathogens at the site of infection. Therefore, routine culture of these sites seems worthwhile and empirical therapy should be as comprehensive as possible and should cover all potential pathogens. To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen.
                Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay.
                In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement.
                A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients.
                CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections. Imipenem/cilastatin at a dose of 0.5 g six hourly was compared to conventional combination therapy with ampicillin 0.5 g six hourly, metronidazole 0.5 g eight hourly and gentamicin 80 mg eight hourly (with dose adjustment by trough and peak serum levels) in the treatment of severe intra-abdominal infections. All antibiotics were given intravenously. Forty-five patients entered the trial. Of the 19 evaluable patients in the imipenem/cilastatin group, 16 were clinically cured with five microbiological successes and two failures. Of 24 evaluable patients in the combination group, 22 were clinically cured with one microbiological success and one failure. One patient in each group suffered an adverse effect. Patients in the I/C group tended to be older with more women and more severe infections. The origin of peritonitis was similar. I/C did not differ from combination therapy in efficacy or safety and was comparable in cost. However, I/C was easier to administer than combination therapy and there was no need for serum concentration monitoring. In a randomized study the clinical and bacteriologic effectiveness of imipenem was compared with the classical combination of netilmicin with clindamycin in patients who had surgery for an intraperitoneal infection, localized or generalized, with positive bacteriologic findings of the specimen taken at surgery. Excluded were all patients who received other antibiotics before surgery, or who died within 3 days after antibiotic therapy was started. Imipenem was given at a dose of 500 mg t.i.d., clindamycin 600 mg t.i.d., and netilmicin according to serum levels. The diagnoses ranged from postoperative peritonitis, gallbladder empyema, perforated gastroduodenal ulcer, small bowel perforation with and without obstruction, and perforated appendicitis to perforation of the colon. The bacteriologic work-up included examination of the primary specimen (aerobic and anaerobic), the urine, feces, and serologic testing for Candida albicans once or twice a week and after the course of antibiotic therapy. In addition, pH measurements of abscesses and drainage fluids were performed. Ninety-three patients entered the study. Forty-seven patients were treated with imipenem (test group), and 46 patients were treated with the combination therapy (control group). The two groups did not show significant differences in age, sex, diagnostic groups, risk factors, primary bacteriology, and duration of therapy (mean: 6.7 days). Thirty-eight patients (80.9%) treated with imipenem were cured, six patients (12.8%) were improved, and there were three (6.4%) failures. The respective numbers for the control group were 31 (67.4%), 10 (21.7%), and 5 (10.9%). The mean duration of hospitalization was 19 days for the test group and 24.5 days for the control group. There were four wound infections in the test group and 11 wound infections in the control group. Imipenem is at least as effective in the adjuvant therapy of intra-abdominal infections as the combination of netilmicin with clindamycin. A prospective, randomized, double-blinded comparison of Sulbactam and ampicillin and clindamycin and gentamicin is described. The combination of ampicillin and Sulbactam was not as effective in the management of perforated appendicitis and gangrenous appendicitis as was clindamycin and gentamicin. While both combinations of antibiotics had good anaerobic activity and failures were not associated with the recovery of Bacteroides fragilis group organisms, infectious complications were seen in patients from whom Pseudomonas were isolated. These pseudomonads were not nosocomially acquired and were found especially in patients with perforated appendicitis. We concluded that the combination of clindamycin and gentamicin, although less convenient to administer to the patient, remains the adjunctive antibiotic management of choice for perforated or gangrenous appendicitis. The epidemiologic factors of Pseudomonas species as a primary pathogen in peritonitis deserves further attention. In a prospective, randomized, single-blind trial, we studied 112 adults with intra-abdominal infections and compared antibiotic therapy with cefoxitin plus placebo to therapy with tobramycin plus clindamycin. Seventy-five percent of patients receiving tobramycin-clindamycin and 71% of those receiving cefoxitin-placebo had either shock, bacteremia, malnutrition, alcoholism, rapidly or ultimately fatal underlying disease, infection originating from the distal small bowel or colon, or had had failed therapy before treatment ("high-risk" group). One third of the patients in both groups grew bacteria in the initial culture resistant to the antibiotic regimen used. Ten patients receiving cefoxitin-placebo (17%) and 11 receiving tobramycin-clindamycin (21%) had recurrence of infection or died of infection (clinical failures). Nineteen failures occurred in high-risk patients (p less than 0.05) and 17 were in patients that had antibiotic-resistant bacteria in the initial culture (p less than 0.01). Adverse effects were rare and remitted after antibiotics were stopped. Our results suggest that both cefoxitin and tobramycin-clindamycin are appropriate antibiotic regimens to treat intra-abdominal infections. Clinical failure is more common in high-risk patients and when antibiotic-resistant organisms are isolated from initial cultures. Clinafloxacin is a novel quinolone with wide activity against the plethora of microorganisms encountered in intraabdominal infections. This trial was performed to examine its clinical efficacy.
                Clinafloxacin is representative of a new class of quinolones with considerable antimicrobial activity resulting from their mechanisms of action and pharmacodynamics. There is, however, concern about specific potential toxicities, including photosensitivity.
                This prospective, randomized, double-blind trial was conducted to compare clinafloxacin with imipenem/cilastatin as adjuncts in the management of complicated intraabdominal infections.
                Five hundred twenty-nine patients were included in the intent-to-treat population, with 312 meeting all criteria for the valid population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was the most common (approximately 50%). One hundred twenty-three of the 150 valid patients treated with clinafloxacin (82%) had successful outcomes, as did 130 of the 162 (80%) treated with imipenem. For the intent-to-treat groups, 219 of 259 patients treated with clinafloxacin (85%) had successful outcomes, as did 219 of 270 patients treated with imipenem/cilastatin (81%). Treatment failure occurred in 39 patients who underwent drainage. There were substantially more gram-negative organisms recovered from the patients with treatment failure who were initially treated with imipenem/cilastatin.
                The results of this study clearly demonstrate the safety and efficacy of clinafloxacin in the treatment of a range of intraabdominal infections, and in patients with a broad range of physiologic disturbances. Many antibiotics and antibiotic combinations are used for the treatment of peritonitis because of advanced (gangrenous or perforated) appendicitis. An aminoglycoside combined with an antianaerobe antibiotic is one standard treatment, but there is concern about the potential nephrotoxicity of the aminoglycoside and the necessity for monitoring aminoglycoside blood levels. Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life, has excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to the aminoglycosides, but it has less potential for inducing renal injury. A double-blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5 milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB (G/C), administered up to 14 days, in 96 surgically treated patients with gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six gangrenous and 40 perforated) in the G/C group. The mean number of days of postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six of which were probably a result of enterococci. No deaths occurred. Our study results show that the efficacy of cefepime plus metronidazole is equivalent to that of clindamycin plus gentamicin. Meropenem (MP), a new carbapenem antibiotic, has excellent antimicrobial activity against the enteric flora commonly encountered in acute appendicitis. Although similar to imipenem, it may have clinical advantages.
                We compared patients with advanced appendicitis (gangrenous or perforated) treated with 1,000 mg MP every eight hours with those given the combination of tobramycin 5 mg/kg/day at eight hour intervals and clindamycin 900 mg every eight hours. Both treatments were given intravenously. Patients were randomized to either group of the double-blind study.
                Of 129 evaluable cases, 63 received MP and 66 received both tobramycin and clindamycin (T/C). The two groups were similar in age, sex, and severity of disease. The mean number of days of postoperative fever (MP = 3.1 +/- 1.7 SD compared to T/C = 4.4 +/- 2.2 SD, p < or = 0.01), days of antibiotic therapy (MP = 6.1 +/- 1.6 SD compared to T/C = 7.3 +/- 2.2 SD, p = 0.01), and therefore hospital stay (MP = 8.0 +/- 3.5 SD compared to T/C = 9.4 +/- 2.6 SD, p < 0.01) were significantly better for patients treated with MP. No difference was found between the numbers of failures in each group (MP = 5 compared to T/C = 6).
                This study demonstrates a small but significant reduction (approximately one day) in post-operative fever, duration of antibiotic treatment, and hospital stay for patients treated with MP compared to those treated with T/C. nan This study compared the safety and efficacy of cefoperazone plus sulbactam with that of clindamycin plus gentamicin in the treatment of intra-abdominal infection. Seventy-six patients were included in the analysis of an open, randomized, comparative, single-site trial. Forty-seven patients received cefoperazone-sulbactam, and 29 patients received clindamycin plus gentamicin. Thirty-three patients (70%) who received cefoperazone-sulbactam and 15 patients (52%) who received clindamycin plus gentamicin were cured of infection, did not suffer a relapse within one month after the end of treatment, and did not receive any other antibiotics during the follow-up period (P = 0.17). In patients treated with cefoperazone-sulbactam there were four cases of superinfection, one patient had a prolonged prothrombin time, six patients had a poor response, two patients received antibiotics during follow-up, and one patient died during follow-up because of cancer. Treatment with clindamycin plus gentamicin was associated with five cases of superinfection, four patients had a poor response, four patients had a drug reaction, and one patient required antibiotics in the follow-up period. Serum levels of cefoperazone-sulbactam measured at one and three hours after dosing were consistent with earlier findings in normal volunteers. Two hundred and one pathogens were isolated, and 17 of 122 aerobic isolates (14%) were resistant to cefoperazone-sulbactam, and 17 of 122 (14%) were resistant to both clindamycin and gentamicin. Eleven of 79 (14%) anaerobic isolates were resistant to cefoperazone, none was resistant to cefoperazone-sulbactam, and 10 of 79 (13%) were resistant to clindamycin. The results of this study show that cefoperazone-sulbactam is an effective and safe alternative to clindamycin plus gentamicin in the treatment of intra-abdominal infections. 515 patients with intra-abdominal infection participated in an open randomized comparative multicenter trial in order to compare the efficacy, safety, and tolerance of imipenem/cilastatin with cefuroxime/metronidazole. 258 patients (mean age 56 years) received imipenem/cilastatin 1.5-2.0 g/day, and 257 patients (mean age 54 years) received cefuroxime 3.0-4.5 g/day plus metronidazole 1.0-1.5 g/day for at least 3 days. 130/161 evaluable patients (80.8%) receiving imipenem/cilastatin and 124/145 evaluable patients (85.5%) receiving cefuroxime/metronidazole were clinically cured. The microbiological response was favorable in 86.9% in the imipenem/cilastatin group and in 90.8% in the cefuroxime/metronidazole group. The two treatment groups were similar with respect to median time to defervescence which was 4 days. The median duration of treatment was 6 days and the median time to discharge from hospital was 9 days in both groups. Drug-related adverse reactions were observed in 14 patients receiving iminpenem/cilastatin and in 8 patients receiving cefuroxime/metronidazole. 19 patients in the imipenen/cilastatin group and 12 patients in the cefuroxime/metronidazole group died. No correlation was found between the deaths and the study drugs. The present study shows that intra-abdominal infections can be treated successfully with imipenem/cilastatin as well as with cefuroxime/metronidazole. Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved a better clinical efficacy than imipenem-cilastatin, due to reduced development of microbiological resistance. Tolerance was comparable, with the exception of diarrhea, which was more frequent with piperacillin-tazobactam. Eighty-five patients were randomly allocated to receive either piperacillin (n = 38) or cefuroxime plus metronidazole (n = 45) after surgical treatment of diffuse peritonitis; 78 were evaluable. A mean of 1.5 (piperacillin group) and 1.7 (cefuroxime/metronidazole group) pathogens/patient were identified. Twenty-seven patients (71%) were successfully treated in the piperacillin group compared with 29 (64%) in the cefuroxime/metronidazole group. These data suggest that piperacillin was neither better nor worse than cefuroxime/metronidazole in diffuse, secondary peritonitis. A multicenter, open-label randomized trial was conducted to evaluate the efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) compared with combination therapy with clindamycin and an aminoglycoside (C+A) for treatment of 117 patients with serious intra-abdominal infections. Fifty-three patients (45%) received I-C and 64 patients (55%) received C+A. The overall clinical success rate was 96.2% for the I-C patients and 92.2% for the C+A patients. Clinical failure rates were 3.8% and 7.8%, respectively (P = NS). Eradication or suppression of pathogens was observed in 81.8% and 82.2% of patients, respectively. Uniform bacteriologic response was observed among all infection subgroups. Fourteen of 145 patients experienced adverse symptoms, including six of 66 (9.1%) monotherapy patients and eight of 79 (10.1%) combination-therapy patients (P = NS). The results of this study demonstrate that I-C monotherapy was as effective as C+A combination therapy for the treatment of serious intra-abdominal infections, regardless of the site or severity of infection or the clinical status of the patient. Both regimens also were found to be comparable in tolerability. In order to compare the clinical and microbiological efficacies and safety of piperacillin plus tazobactam with those of imipenem plus cilastatin, 134 patients with intra-abdominal infections (73 patients with appendicitis) participated in an open randomized comparative multicenter trial. A total of 40 men and 29 women (mean age, 53 years; age range, 18 to 92 years) were enrolled in the piperacillin-tazobactam group and 40 men and 25 women (mean age, 54 years; age range, 16 to 91 years) were enrolled in the imipenem-cilastatin group. The patients received either piperacillin (4 g) and tazobactam (500 mg) every 8 h or imipenem and cilastatin (500 mg each) every 8 h. Both regimens were given by intravenous infusion. A total of 113 patients were clinically evaluable. Of 55 patients who received piperacillin-tazobactam, 50 were clinically cured, while 40 of 58 patients in the imipenem-cilastatin group were clinically cured. The differences were significant (Wilcoxon test; P = 0.005). There were 4 failures or relapses in the piperacillin-tazobactam group and 18 failures or relapses in the imipenem-cilastatin group. The microorganisms isolated were eradicated in similar proportions in the two patient groups. Adverse reactions, mainly gastrointestinal disturbances and nausea, were noted in 13 patients who received piperacillin-tazobactam and in 14 patients who received imipenem-cilastatin. Results of the present study show that piperacillin-tazobactam is effective and safe for the treatment of intra-abdominal infections. Although single antimicrobials with broad-spectrum aerobic and anaerobic coverage are effective in patients with appendicitis, many general surgeons continue to use multiple agents. A prospective, double-blind, randomized trial was designed to detect any clinical correlate of in vitro susceptibility advantage of multiple antimicrobials as adjunctive therapy for 114 patients undergoing operation for complicated appendicitis. There was clinical resolution of intraabdominal infections with no occurrence of postoperative infectious complications in 90% (36 of 40) of the cefotetan group and 86% (31 of 36) of the clindamycin/amikacin group (p = 0.11). The number of patients who had changes in antibiotic therapy due to postoperative complications was higher in the clindamycin/amikacin group: five (12.5%), compared to one (2.8%) in the cefotetan group (p = 0.07). Although Bacteroides fragilis group organisms resistant to cefotetan were identified, none was responsible for the postoperative infections. Adverse drug events in 28% of the cefotetan group and 26% of the clindamycin/amikacin group consisted primarily of transient elevations of liver function tests. Monotherapy with a second-generation, broad-spectrum cephalosporin, such as cefotetan, given twice a day is an economical and effective adjunctive regimen in patients with complicated appendicitis for which operation is the definitive treatment. Aminoglycosides and other, more potent antimicrobials should be reserved for resistant organisms or nosocomial infections. The authors compared broad-spectrum monotherapy with imipenem to an aminoglycoside-based antibiotic regimen for the management of intra-abdominal infections. One hundred and four patients who had intra-abdominal infection were randomly allocated to receive imipenem (52) or tobramycin plus clindamycin or metronidazole (52). Patients treated with imipenem had fewer febrile episodes and occurrences of breakthrough bacteremia, less antibiotic resistance and need for drug change; their hospital stay was shorter. The death rate from sepsis was 4% in patients who received imipenem and 13% in those who received the combined regimen (p = 0.08). Treatment was successful in 79% of patients on imipenem versus 67% of those receiving an aminoglycoside. Patient stratification by the APACHE II system and probability of death calculation using delayed-type hypersensitivity scores predicted a similar death rate for the two treatment groups. Imipenem appears to be a safe and efficacious alternative broad-spectrum antibiotic for treating patients who are seriously ill with intra-abdominal infection. This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs. In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8 h, or imipenem/cilastatin, 500 mg/500 mg q 8 h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections. 118 patients with complicated intra-abdominal infections participated in an open randomized comparative multicenter trial in order to compare the clinical and microbiological efficacy and safety of biapenem with imipenem/cilastatin (Tienam). 31 men and 27 women (mean age 52.3 years) were enrolled in the biapenem group, and 43 men and 17 women (mean age 52.3 years) in the imipenem/cilastatin group. The patients received either biapenem 500 mg every 8 h or imipenem/cilastatin 500 mg/500 mg every 6 h by intravenous infusion for up to 13 days (mean 6.5 days). 28/43 evaluable patients (65.1%) receiving biapenem and 27/40 evaluable patients (67.5%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 28/43 evaluable patients (65.1%) receiving biapenem and in 27/40 evaluable patients (67.5%) receiving imipenem/cilastatin. No significant differences in clinical or microbiological efficacy between the two treatment groups were found. The present study shows that biapenem may be useful in the treatment of intra-abdominal infections. In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated. In an open, randomised, multicentre trial, the efficacy and tolerability of empirical meropenem monotherapy (1 g intravenously every 8 hours) and cefotaxime (2 g every 8 hours) plus metronidazole (0.5 g intravenously every 8 hours) for 5 to 10 days was compared in 94 patients with serious intra-abdominal infection who required surgery. Eighty-three patients had an evaluable clinical response. Significantly more patients in the meropenem group had a satisfactory clinical response at the end of treatment (41/43 [95.3%] vs 30/40 [75.0%]; p = 0.008). The bacteriological response was also higher in the meropenem group (31/33 vs 26/32). In the bacteriologically evaluable population, a satisfactory clinical response was observed in 31/33 of those who received meropenem compared to 24/32 of the cefotaxime/metronidazole recipients (p = 0.03). Empirical meropenem monotherapy should prove a useful alternative to the currently standard combination treatment for serious intraabdominal infections. In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP. In a prospective randomized open study of patients operated upon for diffuse peritonitis, the effects of two different antibiotic regimens were evaluated. Cefuroxime given as a single drug (Group I; n = 59) was compared with a combination of cefuroxime and metronidazole (Group II; n = 63). Bacteriological cultures, both aerobic and anaerobic, were obtained peroperatively and in the event of any complication. The antibiotic sensitivities of isolated bacteria, and the serum and tissue concentrations of cefuroxime were determined. Postoperative infectious complications occurred in 22 per cent of Group I patients (cefuroxime), and in 17.5 per cent of Group II (cefuroxime plus metronidazole). The mortality rates were 5 per cent for Group I and 8 per cent for Group II. Tissue concentrations of cefuroxime were well above the MIC (minimal inhibiting concentration) values for most of the bacteria isolated. From a few patients in Group I, however, cultures were obtained with isolates sensitive to metronidazole but resistant to cefuroxime. Our findings suggest that, in the antibiotic treatment of patients operated for diffuse peritonitis, an agent which is primarily effective against aerobic bacteria (but not entirely without effect on anaerobes) is as effective as combination therapy covering both aerobic and anaerobic bacteria. This multicentre, randomised, open-label, parallel group study compared the efficacy and safety of isepamicin (15 mg/kg once daily) and amikacin (7.5 mg/kg twice daily) when given intravenously in combination with metronidazole to 267 hospitalised adults with intra-abdominal infections. Clinical cure or improvement was achieved in 96.3% (130/135) evaluable patients (efficacy population) in the isepamicin group and 94.3% (66/70) patients in the amikacin group. Bacteriological elimination occurred in 93.3% (126/135) evaluable isepamicin patients and 95.7% (67/170) amikacin patients. there was not statistically significant differences between the groups. Adverse events were reported by 9% of patients in the isepamicin group (16/178) and 10% of patients in the amikacin group (9/89). Events considered to be related to treatment occurred in 6% of patients in both groups. The most frequent adverse events were diarrhoea, nausea and vomiting. Renal problems caused three patients (2 isepamicin, 1 amikacin) to withdraw from the study. Ototoxicity (detected by audiometric testing) occurred in one patient (treated with isepamicin). In conclusion, isepamicin at a dose of 15 mg/kg once daily was shown to be as effective as amikacin (7.5 mg/kg twice daily) in the treatment of intra-abdominal infections in hospitalised adults also treated with metronidazole. Both treatments were well tolerated. The aim of this prospective study was to compare the safety and efficacy of a new cephamycin, cefminox 2 g/12 h, to those of the usual regimen combining metronidazole 500 mg/8 h and gentamicin 80 mg/8 h (M+G).
                160 patients with clinically proven intra-abdominal infection were prospectively included in an open parallel randomized comparative multicenter trial. Antibiotics were started preoperatively and discontinued after clinical and laboratory evidence of resolution of the infection. Serum and peritoneal fluid levels and serum bactericidal activities were also studied.
                150 patients were clinically evaluable. There was one failure in the cefminox group and three in the M+G group (not significant, RR: 1.07, 95% CI: 1-1.15). No differences were found in the number of wound infections, length of stay or duration of antibiotic therapy. Adverse effects were reported in 11 cases, all of them mild to moderate. Escherichia coli and Bacteroides fragilis were the most frequently found microorganisms.
                Cefminox is as effective and as safe as M+G in the treatment of intra-abdominal infections. Concerned about the inactivation of piperacillin by beta-lactamase and the risk of aminoglycoside-induced nephrotoxicity and clindamycin-induced enterocolitis, we conducted the following phase III clinical trial.
                Between November 1991 and March 1993, 77 surgical patients with intraabdominal infections were enrolled and randomly assigned in a 3:2 ratio to receive either piperacillin/tazobactam or clindamycin plus gentamicin to compare safety, tolerance and efficacy between both two treatment groups.
                There were 76 clinically and 50 bacteriologically evaluable patients with 80 isolated pathogens. The demographic data were comparable in both groups. There was no statistically significant difference of clinical response at any time-point of treatment, with 97.8% favorable clinical response rate in piperacillin tazobactam group and 96.6% in clindamycin plus gentamicin group at endpoint. The bacteriological eradication rates were similar, with 97.7% in piperacillin/tazobactam group and 94.4% in clindamycin plus gentamicin group at pathogen level, and 96.7% in piperacillin/tazobactam group and 95.0% in clindamycin plus gentamicin group at patient level. By susceptibility tests, only 3 (4%) isolated pathogens were resistant to piperacillin/tazobactam, which was much superior to the use of piperacillin, clindamycin or gentamicin alone in antimicrobial activity. The piperacillin tazobactam-related adverse experiences included 1 (2.1%) urticaria and 2 (4.3%) diarrhea. However, there were no significant differences in the adverse experiences between these two groups.
                This study has demonstrated that piperacillin/tazobactam is comparable with clindamycin plus gentamicin in efficacy, safety and tolerance in the treatment of surgical patients with intra-abdominal infections. The combination of piperacillin/tazobactam could potentially be the treatment of choice in adjunt to surgical management in intra-abdominal infection. A double-blind trial was conducted in 385 patients with suspected bacterial intra-abdominal infections to compare the efficacy and safety of ampicillin-sulbactam with cefoxitin. Patients were randomized to receive either 3 g ampicillin-sulbactam (2 g ampicillin-1 g sulbactam), or 2 g cefoxitin, every 6 hours. To be evaluable, patients had to demonstrate positive culture evidence of peritoneal infection at the time of operation. A total of 197 patients were evaluable for clinical efficacy. The two treatment groups were comparable in demographic features and in the presence of risk factors for infection. Clinical success (absence of infection and of adverse drug reaction) was observed in 86% of patients in the ampicillin-sulbactam group and 78% in the cefoxitin group. Eradication of infection occurred in 88% of the ampicillin-sulbactam group and 79% of the cefoxitin group. There were no differences in the nature or frequency of side effects observed in the two groups. Ampicillin-sulbactam demonstrated no difference in safety or efficacy when compared with cefoxitin in the treatment of serious intra-abdominal infections of bacterial origin. In order to compare the efficacy and safety of pefloxacin plus metronidazole with those of gentamicin plus metronidazole, 271 patients with severe intraabdominal infection were enrolled in an open, randomized comparative trial. Seventy males and 66 females (mean age 54 years; range 18-90) were enrolled in the pefloxacin/metronidazole group and 74 males and 61 females (mean age 52 years; range 18-90) in the gentamicin/metronidazole group. After verification of the intra-abdominal infection by laparotomy, drainage or puncture and microbiological cultures, patients received iv either pefloxacin 400 mg, bd, after an 800-mg loading dose, or gentamicin 1.4 mg/kg body weight every 8-24 h depending on the renal function. Metronidazole was given to both groups as a 500 mg intravenous infusion tid. Eighty-seven patients were excluded from the efficacy analysis, principally because of unproven infection, previous antimicrobial therapy or treatment duration less than three days. Ninety-four of 104 patients receiving pefloxacin/metronidazole (90.4%) were cured or improved and there were two failures and eight relapses. In the gentamicin/metronidazole group, 64 of 80 patients (80.0%) were cured or improved while there were three failures, nine relapses, and two deaths. The bacteria originally isolated were eradicated in similar proportions of the patients in the two groups. Eleven of 136 patients receiving pefloxacin/metronidazole (8.1%) and seven of 135 patients given gentamicin/metronidazole (5.2%) had adverse reactions. This study shows that pefloxacin can be considered as effective and safe as gentamicin for the treatment of severe intraabdominal infections. A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring. This report summarizes the experience of investigators in four medical centres who compared the combination of cefoperazone/sulbactam against gentamicin/clindamycin in the treatment of intra-abdominal infections. One hundred and fifty-two patients were enrolled in the study and all were evaluable for safety and tolerance, 110 were evaluable for efficacy. Of the 76 patients (49 male, 27 female) treated with cefoperazone/sulbactam 66 (86.8%) were cured, five (6.6%) improved and five (6.6%) failed to respond to treatment. Of 34 patients treated with gentamicin/clindamycin, 21 (61.8%) were cured, four (11.8%) improved and nine (26.4%) failed. Cure rates for patients receiving cefoperazone/sulbactam were significantly higher than those of patients receiving gentamicin/clindamycin (P less than 0.006). Failures in both groups were attributable in part to pseudomonal and enterococcal infection and abscess formation. The addition of sulbactam to cefoperazone rendered cefoperazone-resistant organisms susceptible to cefoperazone in 11 of the 76 cases (14.4%) and thus permitted treatment with this agent. The present study confirms the safety and clinical efficacy of cefoperazone/sulbactam and suggests that this combination is a viable alternative to an aminoglycoside plus clindamycin for intra-abdominal infections.
No specific recommendations can be made for the first line treatment of secondary peritonitis in adults with antibiotics, as all regimens showed equivocal efficacy. Other factors such as local guidelines and preferences, ease of administration, costs and availability must therefore be taken into consideration in deciding the antibiotic regimen of choice. Future trials should attempt to stratify patients and perform intention-to-treat analysis to allow better external validity.