Cefazolin and netilmycin versus vancomycin and ceftazidime in the treatment of CAPD peritonitis. Treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis with intraperitoneal urokinase: a double-blind clinical trial. Is initial (24 hours) lavage necessary in treatment of CAPD peritonitis? A comparison between oral ciprofloxacin and intraperitoneal vancomycin and netilmicin in CAPD peritonitis. A comparison between oral ciprofloxacin and intra-peritoneal vancomycin and gentamicin in the treatment of CAPD peritonitis. Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial. Cefepime versus vancomycin plus netilmicin therapy for continuous ambulatory peritoneal dialysis-associated peritonitis. A prospective, randomized study of the comparative safety and efficacy of intraperitoneal imipenem versus vancomycin and netilmicin in the treatment of peritonitis on CAPD. Netilmycin and vancomycin in the treatment of peritonitis in CAPD patients. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in peritoneal dialysis patients. Intravenous or intraperitoneal vancomycin for the treatment of continuous ambulatory peritoneal dialysis associated gram-positive peritonitis? Cefazolin plus netilmicin versus cefazolin plus ceftazidime for treating CAPD peritonitis: effect on residual renal function. CAPD peritonitis: a prospective randomized trial of oral versus intraperitoneal treatment with cephradine. A randomized prospective comparison of oral versus intraperitoneal ciprofloxacin as the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. A randomized prospective trial of three different regimens of treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis. A randomised prospective comparison of oral ofloxacin and intraperitoneal vancomycin plus aztreonam in the treatment of bacterial peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD). Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients? The value of low-dose intraperitoneal immunoglobulin administration in the treatment of peritoneal dialysis-related peritonitis. A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD. Intraperitoneal vancomycin/oral pefloxacin versus intraperitoneal vancomycin/gentamicin in the treatment of continuous ambulatory peritoneal dialysis peritonitis. Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS). Role of intraperitoneal urokinase in acute peritonitis and prevention of catheter loss in peritoneal dialysis patients. Intraperitoneal ciprofloxacin and rifampicin versus cephradine as initial treatment of (C)APD-related peritonitis: a prospective randomized multicenter comparison (CIPPER trial). A comparison between intraperitoneal ciprofloxacin and intraperitoneal vancomycin and gentamicin in the treatment of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Intraperitoneal teicoplanin in the treatment of peritonitis associated with continuous ambulatory peritoneal dialysis. Tenckhoff catheter replacement or intraperitoneal urokinase: a randomised trial in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. A prospective randomized comparison of single versus multidose gentamicin in the treatment of CAPD peritonitis. Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy. A prospective, randomized trial of two antibiotic regimens in the treatment of peritonitis in CAPD patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis.
In spite of several recommendations, choosing the initial antibiotic to treat continuous ambulatory peritoneal dialysis (CAPD) peritonitis remains difficult. In our prospective randomized study we attempted to evaluate the efficacy and safety of less toxic combinations of cephalosporins with vancomycin or netilmycin. From November 1993 to September 1996 we treated 52 episodes of peritonitis in 34 patients. Peritonitis was diagnosed according to the valid criteria. Patients were treated for 14 - 28 days with a combination of either cefazolin plus netilmycin or vancomycin plus ceftazidime. The most frequent bacteria causing peritonitis in the two groups were comparable. The efficacy of the cefazolin/netilmycin combination was 91.6% (22/24) without yeasts and 84.0% (21/25) in the vancomycin/ceftazidime combination. There were no statistically significant differences between the two otherwise efficient combinations of antibiotics. No side effects were observed. We believe that the frequent use of vancomycin could be avoided thus reducing the risks of resistance and ototoxicity. Resistant peritonitis in continuous ambulatory peritoneal dialysis (CAPD) is an indication for catheter removal, followed by interim haemodialysis and subsequent catheter replacement. This involves two surgical procedures using general anaesthetic and the availability of adequate hospital haemodialysis facilities. Urokinase is an alternative therapy but evidence of its effect is anecdotal and it has not been studied in a double-blind manner. Patients with resistant peritonitis (either no resolution of peritonitis within 4 days of appropriate antibiotic therapy or a third episode of peritonitis within 6 months) were randomized to receive intraperitoneal urokinase or placebo (saline) followed by 14 days of antibiotics in this double-blind prospective study. Treatment success was resolution of peritonitis within 4 days of giving urokinase/placebo (persistent infection) and no recurrence with the same organism for 6 months (recurrent infection). Twelve patients received urokinase and 12 placebo. Treatment was successful in 8/12 in the urokinase group and 1/12 in the placebo group (Fisher's exact test; P = 0.0047). Urokinase was successful in 8/12 patients with resistant peritonitis and significantly better than placebo. Urokinase is an effective and simple treatment that may avoid the need for catheter removal and interim haemodialysis in patients with resistant CAPD peritonitis. A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial 24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits--1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock. This report describes a prospective, randomized comparison of oral ciprofloxacin and intraperitoneal vancomycin/netilmicin in the treatment of 50 consecutive episodes of CAPD peritonitis in 35 patients. Successful cure of peritonitis was achieved in 76% of subjects taking oral ciprofloxacin and 72% of those given intraperitoneal antibiotics. Satisfactory concentrations of ciprofloxacin in dialysate were achieved in all patients. Failure of ciprofloxacin was due to persistence of an isolate of intermediate sensitivity (1), to persistence with acquisition of resistance (1), and to relapse/reinfection in the remaining four cases (with resistant or moderately sensitive strains in three cases). Ciprofloxacin was well tolerated in the majority of cases. A significant rise in serum creatinine was noted in almost all patients taking oral ciprofloxacin. The advantages of oral drug administration indicate that oral ciprofloxacin is the preferred first-line treatment of CAPD-associated peritonitis. Fifty-one patients were included in a prospective, randomized comparison of oral ciprofloxacin and intraperitoneal vancomycin/gentamicin in the treatment of CAPD peritonitis. Staphylococcal species accounted for 40% of the isolates with an equal incidence of Staphylococcus aureus and coagulase negative staphylococci. Although, overall, there was no significant difference between the regimens in outcome, ciprofloxacin was significantly less effective when peritonitis was due to coagulase negative staphylococci. Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis.
                We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate.
                We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90).
                We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis. Cefepime is a cephalosporin with a broad spectrum of activity against most gram-positive and gram-negative pathogens. In this study, we attempted to compare the safety and efficacy of cefepime monotherapy against the potentially more toxic combination of vancomycin and netilmicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated bacterial peritonitis. Eighty-one consecutive CAPD patients who presented with peritonitis from January 1, 1998, to June 30, 2000, were recruited for study. Patients were randomized to be administered either intraperitoneal (IP) cefepime, 1 g once daily (group A), or intravenous vancomycin and netilmicin at conventional doses (group B) for 10 days. Bacterial growth was obtained in 52 episodes (66%), and pathogens identified included gram-positive organisms (30 episodes; 38%), gram-negative organisms (14 episodes; 18%), mixed organisms (2 episodes; 2.5%), and fungus (6 episodes; 8%). Eight patients were excluded after randomization for various reasons (6 patients, fungal peritonitis; 2 patients, wrong diagnoses). Because of the relatively low peritonitis rate after the use of a disconnect system, the sample size of this study was relatively small, giving a power of 0.45. There were no significant differences in primary response rates and cure rates (no relapse >28 days after completion of antibiotic therapy) between both groups of patients (group A versus group B, 82% [32 of 39 patients] versus 85% [29 of 34 patients] and 72% [28 of 39 patients] versus 76% [26 of 34 patients], respectively; P = not significant). No significant side effect was encountered in either group. Total peritonitis-related hospitalizations were 84 patient-days (1, 7, 8, 11, 20, and 37 patient-days) and 115 patient-days (3, 6, 9, 14, 21, 21, and 41 patient-days), whereas total costs per patient cure were estimated to be US $1,039 and US $1,371 in groups A and B, respectively. We conclude that once-daily 1-g IP cefepime monotherapy is a simple, safe, and cost-effective alternative to vancomycin and netilmicin therapy in the treatment of CAPD-associated bacterial peritonitis. nan This study was undertaken to evaluate: 1. The efficacy of netilmycin and vancomycin as combined first line antimicrobial regime, compared to cefuroxime, in the treatment of peritonitis. 2. To measure the levels of netilmycin and vancomycin in the serum and dialysate. 3. To report on the use of this combination over a one year period and compare it with that of cefuroxime used during the previous one year. To determine if intraperitoneal administration of vancomycin (a slowly absorbed antibiotic) improves the management of dialysis-associated peritonitis over that obtained by using cefazolin, an equally potent, rapidly absorbed antibiotic.
                A university operated teaching hospital, with patient treatment initiated at home.
                One hundred thirty-one patients trained to perform peritoneal dialysis (CAPD and CCPD) and followed at the University of Iowa Hospitals and Clinics Home Dialysis Treatment Center.
                Patients were prospectively allocated into groups adding either vancomycin 25 mgm/L, or cefazolin 50 mgm/L to their dialysate when signs or symptoms of peritonitis developed. Treatment results were analysed using chi-square testing.
                Compared to cefazolin, initial peritonitis therapy with vancomycin improved the peritonitis resolution rate [67% vs 81%; p = 0.008], reduced the incidence of hospital admissions [68% vs 48%; p = 0.001], and decreased the risk of superinfection [4% vs 0%; p = 0.039].
                Vancomycin appeared to be superior to cefazolin in the treatment of peritoneal dialysis associated peritonitis. The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors' and nurses' observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis. A clinical and pharmacokinetic study was carried out to determine whether an intraperitoneal (IP) loading dose of vancomycin was as effective as an intravenous (IV) load in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated gram-positive peritonitis. Each patient continued a 14-day treatment on IP maintenance doses. All cases of peritonitis (10 in each group) were eradicated. Side effects occurred in 3 patients following IV vancomycin and in none following IP vancomycin. Serum and peritoneal vancomycin concentrations equilibrated fully and rapidly with each route. It is concluded that an IP loading dose of vancomycin, followed by IP maintenance doses, is as effective as and produces fewer side effects than an IV loading dose in the treatment of CAPD peritonitis. BACKGROUND. The International Society for Peritoneal Dialysis (ISPD) treatment guidelines for continuous ambulatory peritoneal dialysis (CAPD) peritonitis 2000 recommended the use of cefazolin plus ceftazidime as the initial empirical therapy in patients with residual renal function (RRF). However, this treatment regimen has not been compared with the conventional regimen of cefazolin plus netilmicin in prospective, randomized controlled trials.
                Stable CAPD patients who developed clinical evidence of peritonitis were randomized to receive intraperitoneal (i.p.) cefazolin plus netilmicin or cefazolin plus ceftazidime once daily in the long dwell for 14 days. For patients with RRF (>1 mL/minute) before entry into the study (N= 50), RRF and 24-hour urine volume were measured at days 1, 14, and 42 after commencement of i.p. antibiotic treatment.
                One hundred and two patients were recruited into the study. The primary cure rates of i.p. cefazolin plus netilmicin and cefazolin plus ceftazidime were 66.7% and 64.7%, respectively. The overall cure rate for the 2 treatment regimens was 82.3% for both. Seven patients (14%) from each treatment group required removal of the dialysis catheters due to treatment failure. Relapse of peritonitis occurred in 2 patients (4%) in both treatment groups. Thirty-six patients with RRF at baseline achieved primary cure of their peritonitis by the assigned antibiotics. In this subgroup of patients, their RRF and daily urine volume showed significant reduction at day 14 and returned to near baseline values at day 42. The degree of reduction in RRF and urine volume did not differ significantly between the patients treated with cefazolin plus netilmicin and cefazolin plus ceftazidime.
                Intraperitoneal cefazolin plus netilmicin and cefazolin plus ceftazidime have similar efficacy as empirical treatment for CAPD peritonitis. In CAPD patients with RRF, significant but reversible reduction in RRF and 24-hour urine volume could occur after an episode of peritonitis, despite successful treatment by i.p. antibiotics. The effect of i.p. cefazolin plus netilmicin, or i.p. cefazolin plus ceftazidime on RRF in CAPD patients with peritonitis does not appear to be different. Our findings do not support the routine use of cefazolin and ceftazidime as the empirical treatment for CAPD peritonitis. In a prospective randomized clinical trial 84 peritonitis episodes were treated with cephradine, either orally or intraperitoneally. No difference in treatment outcome between both groups could be demonstrated. In episodes caused by susceptible micro-organisms a good response was seen in 82% in the oral and 82% in the intraperitoneal groups. These clinical findings were supported by the demonstration of adequate cephradine concentrations in serum and dialysate after oral as well as after intraperitoneal administration. Altogether cephradine was given orally or intraperitoneally in 88 episodes of peritonitis as drug of first choice. In 52 a complete cure was obtained, in 36 another antibiotic was subsequently needed as soon as bacterial susceptibility was known. No patient deteriorated appreciably during the delay between the start of cephradine and the switch to another antibiotic. Of the 36 episodes 14, caused by methicillin-resistant Staphylococcus epidermidis, responded well initially to cephradine but relapsed later. Change to another antibiotic effected a complete recovery in all 14 cases. Of the remaining 22 episodes, 14 were cured by the other antibiotic, in eight the catheter had to be removed. Aminoglycosides could be avoided except for ten of the episodes. During peritonitis CAPD was continued, in 71% of the cases on an outpatient basis. Mortality due to peritonitis was absent. We conclude that oral cephradine can be used as drug of first choice in the initial treatment of CAPD peritonitis, because a good initial response was obtained in 66 (52 + 14) i.e. 75% of 88 episodes. However, complete cure by cephradine alone was achieved in only 60%.(ABSTRACT TRUNCATED AT 250 WORDS) The present study compared oral versus intraperitoneal (ip) ciprofloxacin (ciproxin) as primary treatment of bacterial peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) in a randomized, prospective trial. A total of 54 episodes in 46 patients were recruited for study. After excluding nonbacterial episodes and those not treated according to protocol, 48 episodes evenly divided between the two treatment arms were eligible for analysis. The primary cure rate was 41.7% and 66.7%, respectively, in the oral and ip treatment group. Half of those who failed or relapsed were due to infection with resistant, mostly gram-positive bacteria, which accounted for 79% of culture-positive episodes. Of the gram-positive isolates 42.3% were either resistant or intermediately susceptible to ciproxin compared to 16.7% of gram-negative isolates. The high level of bacterial resistance to ciproxin and treatment failure rate were related to the previous exposure to fluoroquinolones. Inadequate trough peritoneal drug levels also accounted for the failures in the ip but not the oral treatment group. We conclude that oral ciproxin is ineffective as a primary treatment of CAPD peritonitis in patients previously exposed to fluoroquinolones and that when administered ip, a dose of 50 mg/L instead of 25 mg/L of ciproxin should be used as maintenance in order to achieve adequate trough peritoneal drug levels. A randomized prospective study was undertaken in patients on continuous ambulatory peritoneal dialysis (CAPD) to evaluate the efficacy of three different antibiotic regimens for the treatment of peritonitis. There were 39 episodes in each treatment group. Patients were treated with intraperitoneal (IP) cephalothin (250 mg/L) and tobramycin (8 mg/L) in group 1, oral ofloxacin (400 mg loading followed by 300 mg daily) in group 2, and a combination of ofloxacin (400 mg followed by 300 mg daily) and rifampicin (300 mg daily). Treatment duration was 10 days. The average culture-positive rate was 75%. The overall cure rate was 80.6% with IP antibiotics, 78.4% with oral ofloxacin, and 81.1% with ofloxacin and rifampicin. After the exclusion of tunnel infections and episodes of peritonitis due to Pseudomonas and resistant organisms, the corresponding figures were 100%, 90.6%, and 93.7%, respectively. Side effects were minimal with IP treatment and with oral ofloxacin, but severe nausea and vomiting occurred in some cases with the combination of ofloxacin and rifampicin. It was concluded that oral ofloxacin is an acceptable first-line therapy for peritonitis in CAPD patients. Forty six patients who developed 48 episodes of peritonitis while on CAPD were randomised to receive either oral ofloxacin or intraperitoneal (i.p.) vancomycin/aztreonam. Three patients were excluded from analysis: 2 were transferred to other hospitals and 1 was later found to have candida peritonitis. Of the remainder, 22 episodes were treated with oral ofloxacin and 23 with i.p. vancomycin/aztreonam. The primary cure rate in the oral ofloxacin and i.p. vancomycin/aztreonam group was 77.3% and 87.5% respectively. There were 3 primary failures and 2 relapses in the former and 1 failure and 2 relapses in the latter group. Two of the 4 primary failures were peritonitis episodes secondary to infection with pseudomonas species. The total number of days of hospital stay was 48 and 58 respectively in the two groups. Analysis of the cost of treatment revealed that i.p. vancomycin/aztreonam was 30 times more expensive than oral ofloxacin. Despite a slightly higher cure rate with i.p. vancomycin/aztreonam, oral ofloxacin is a more cost-effective primary treatment of bacterial peritonitis in patients on CAPD especially in countries with a limited health budget. This prospective randomized study is an evaluation of efficacy of cefazolin and ofloxacin in 23 end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD) who experienced 38 episodes of peritonitis (P). Cefazolin was administered intraperitoneally: 1000 mg as loading dose and 250 mg every exchange as maintenance dose for ten days. Ofloxacin was given orally: first 300 mg, followed by ten daily doses of 200 mg. Microbes most frequently isolated from peritoneal effluent were Staphylococci (coagulase-negative in 55.3%, aureus in 7.9%), Acinetobacter (in 5.3%), Klebsiella (in 5.5%), and Micrococcus (in 5.3%). Used as monotherapy, we found the efficacy of both cefazolin and ofloxacin inadequate for treatment of P in CAPD patients (cefazolin 65%, ofloxacin 67%) (NS). Peritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The value of immunomodulatory therapeutic approaches and, especially, methods aimed at augmenting opsonization in the treatment of peritoneal dialysis (PD)-related peritonitis is unclear. In this study, the effect of intraperitoneal (IP) immunoglobulin (Ig) usage, as an approach for strengthening opsonization, was evaluated in CAPD peritonitis.
                The study included 24 patients with CAPD peritonitis. The patients were divided into two groups, A and B, each consisting of 12 patients. There were no significant differences between the groups in terms of age, gender, CAPD duration, and peritonitis rate. Empiric antibiotic treatment was a 2-week IP ampicillin+sulbactam/netilmycin combination. Group B was additionally given low-dose IP IgG (2 mL = 320 mg) with every exchange. The dialysate leucocyte counts were obtained in both groups until the number was <100 cells/microL to monitor the response to peritonitis treatment.
                In group A, the number of exchanges done until the dialysate leucocyte counts decreased to <100/mL was 13.9 +/- 1.4 and for group B 6.6 +/- 0.4 (p<0.001). The reduction in neutrophils was significantly faster in group B compared to group A (p<0.001). The number of exchanges until abdominal pain completely disappeared was 12.5 +/- 1.7 in group A and 5.6 +/- 0.7 in group B (p<0.001).
                The results of this study show that low-dose, continuous IP IgG administration in the treatment of PD-related peritonitis is safe and effective in shortening the treatment time. To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).
                A randomized multicenter prospective open-label comparative clinical study.
                University and Hospital Authority hospitals in Hong Kong.
                All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial.
                A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones.
                Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones. Sixty patients were enrolled in a prospective, randomized study to evaluate the efficacy of two different regimens for the empirical treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. At presentation, Group I received intraperitoneal vancomycin (1 g) and oral pefloxacin (400 mg b.i.d.), and Group II intraperitoneal vancomycin (1 g) and gentamicin (80 mg loading dose, followed by 15 mg/2 L). Treatment duration was 14 days. Despite randomization, Group I had significantly more patients with primary Candida peritonitis. When fungal peritonitis was excluded from analysis, there were no significant differences in the treatment success rate (Group I, 73.3% vs Group II, 80.0%, p = NS), number of relapses (Group I, 0 vs Group II, 1), and Tenckhoff catheter removal rates (Group I, 26.6% vs Group II, 16.6%, p = NS) between the two groups. The patients treated with pefloxacin had an increased incidence of nausea and vomiting. In selected situations oral pefloxacin may be a suitable substitute for intraperitoneal gentamicin as out-patient therapy for CAPD peritonitis. Intermittent intraperitoneal antibiotic administration appears as a practical and economical therapeutic concept in continuous peritoneal dialysis (CPD)-related peritonitis, but the equivalence of this principle with standard continuous treatment awaits confirmation by prospective, randomized clinical trials. This study evaluates the efficacy, safety, and clinical acceptance of an initial combination treatment including a glycopeptide (vancomycin or teicoplanin) and ceftazidime, each applied either intermittently or continuously, in a cohort of pediatric patients with CPD-related peritonitis. Patients randomized for continuous treatment received an intraperitoneal loading dose of glycopeptide and ceftazidime followed by maintenance doses added to each dialysate bag. In the intermittent treatment groups, the glycopeptide was administered in two loading doses 7 d apart, and ceftazidime during one dialysis cycle per day. Initial treatment response was evaluated after 60 h by the change in a Disease Severity Score and by the clinical decision to continue initial treatment. Of 152 patients observed for a total of 234 patient years, 90 patients developed 195 episodes of peritonitis (including 27 relapses within 4 wk after end of treatment). Dialysate cultures were positive in 83% of the episodes. In gram-positive peritonitis (79% of culture-positive cases), the primary success (overall 95%) and relapse rates (21%) were not different between continuous and intermittent, or between vancomycin and teicoplanin treatment. Oversensitivity reactions occurred in three and ototoxicity in one vancomycin-treated patient, whereas no such side effects were observed with teicoplanin. Residual renal function declined during peritonitis episodes regardless of treatment modality. In gram-negative peritonitis (18% of cases), intermittent ceftazidime treatment was less successful than continuous treatment according to clinical judgment (3 of 11 versus 10 of 14, P < 0.05), but not when rated by Disease Severity Score (8 of 11 versus 12 of 14). In conclusion, intermittent and continuous intraperitoneal treatment of CPD-related peritonitis with glycopeptides and ceftazidime is equally efficacious and safe when measured by objective clinical criteria. This contrasts with a strong tendency of clinicians to move from intermittent to continuous treatment in severe peritonitis. Some studies have demonstrated the efficacy and safety of intraperitoneal (i.p.) urokinase in the resolution of recurrent or relapsing peritonitis, while others have not. Most studies were small, and they varied in methodology. Furthermore, the role of i.p. urokinase in shortening the duration of peritonitis or in preventing recurrence after initial peritonitis has not been examined. In addition, no previous studies have examined the role of i.p. urokinase in preventing, after first infection, catheter loss due to unresolving (resistant) peritonitis. Over a period of 3 years, we prospectively randomized into two groups all peritoneal dialysis (PD) patients who developed a first episode of peritonitis. Group I (n = 40) received i.p. urokinase on the first day of diagnosis (5000 IU intraluminally in the peritoneal catheter and left for 4 hours before next exchange). Group II (n = 40) received no urokinase. The duration of peritonitis was assessed by daily PD fluid white blood cell (WBC) count. Indications for catheter removal were: persistent peritonitis after four days from initiation of antibiotic therapy, or peritonitis with multiple organisms, suggesting bowel perforation. No statistically significant difference was seen between the two groups in regard to primary cause of end-stage renal disease (ESRD), age, sex, race, weight, type of dialysis [continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), continuous cycling peritoneal dialysis (CCPD)], or duration of dialysis prior to first peritonitis. No statistically significant difference was seen between the two groups in the duration of peritonitis or in the severity of symptoms and signs of peritonitis. Neither was any difference seen in the peritonitis recurrence or relapse rate (10% in the urokinase group vs 7.5% in the control group). Nine patients lost their catheters (3 in the urokinase group: 1 Pseudomonas aeruginosa and 2 Candida tropicalis; 6 in the control group: 1 Klebsiella pneumonia, 1 enterococcus, 2 Pseudomonas aeruginosa, and 2 Candida tropicalis). The difference in the rate of catheter loss between the two groups was not statistically significant; it appeared to relate to the type of organism rather than to the response to urokinase. In conclusion, i.p. urokinase plays no significant role in shortening the course of peritonitis or in preventing recurrence or loss of the PD catheter. Loss of PD catheters in patients having their first peritonitis appears to be related primarily to the type of organism causing the infection. The initial treatment of peritonitis has evolved from single-agent to combination regimens. The initial response rates improved with these newer regimens but relapsing peritonitis continues to occur. For biofilm-embedded or intracellularly sequestrated bacteria, a combination of intracellularly- and biofilm-active agents such as ciprofloxacin and rifampicin might be beneficial. Many Dutch centers continue to use cephradine as initial treatment, claiming clinically adequate responses with this regimen. We compared the impact of these two regimens on outcome in patients who developed a new episode of peritonitis.
                Prospective randomized open trial.
                Multicenter study including 14 Dutch dialysis units.
                From October 1996 to October 1999, 367 patients from 14 centers were randomized to be treated with ciprofloxacin + rifampicin (CR; each 50 mg/L) or cephradine (C; 250 mg/L) in case of peritonitis. Of these 367 patients, 98 developed peritonitis, 44 of whom were treated with CR and 54 with C.
                Clinical response, divided into early (during the 2 weeks of therapy) and late (including the following 4 weeks) response. Success was defined as disappearance of all signs and symptoms by days 4-6, through day 42. Bacteriological response was either success (eradication) or failure (persistence, superinfection, or eradication with relapse/reinfection).
                The groups were comparable for age, sex, duration of continuous ambulatory/automated peritoneal dialysis, and occurrence of diabetes. Bacteriological cultures in both groups revealed predominantly gram-positive micro-organisms. Initial and late clinical successes were obtained in 27/54 and 20/54 episodes (50% and 37%) in the C group, and 33/44 and 28/44 episodes (75% and 63.6%) in the CR group (p = 0.021 and p = 0.019). Bacteriological success occurred in 29.6% in the C group, and in 59.1% in the CR group (p= 0.026), with failure in 46.3% and 18.2%, respectively. Peritonitis episodes were bacteriologically not evaluable in 24.1% of episodes in the C group and 22.7% of episodes in the CR group, due mostly to no growth in the initial culture.
                The CIPPER Trial showed ciprofloxacin + rifampicin to be superior to cephradine as empiric treatment of peritonitis. In a prospective, randomized, controlled trial in 40 patients, intraperitoneal ciprofloxacin was shown to be as effective as the currently recommended regimen of intraperitoneal vancomycin and gentamicin for the treatment of CAPD peritonitis. There was one treatment failure in the ciprofloxacin arm and four in the comparative arm. A single drug regimen is preferred by patients. The intraperitoneal route of administration of ciprofloxacin therapy has advantages over the oral route. The efficacy of teicoplanin in the treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was evaluated in a randomised comparison with vancomycin. The dosage regimen used was 50 mg of vancomycin or teicoplanin per 2 1 bag of dialysate for 48 h followed by 25 mg per bag for a further five days. Twelve episodes of peritonitis were studied. There was no significant difference in the bacteriological or clinical cure rates of either antibiotic. A randomised trial, comparing Tenckhoff catheter replacement as a one-stage procedure and i.p. urokinase, was undertaken in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. In addition to appropriate i.p. antibiotic treatment, 17 patients received i.p. urokinase (5000 i.u.) on the second and fourth days of antibiotic treatment, and 14 patients underwent CAPD catheter replacement. An additional six patients also underwent catheter replacement following the recurrence of peritonitis after urokinase treatment. The subsequent recurrence rate of peritonitis following CAPD catheter replacement (5%) was significantly less than after urokinase (41%) (p less than 0.001). Fourteen patients remained free of peritonitis for at least three months after catheter replacement, and five patients were peritonitis-free following urokinase for this period. There is an increasing trend towards the use of aminoglycosides in a once-daily dose administration for the treatment of severe infections in nonrenal failure patients. The use of once-daily dose aminoglycoside therapy may be associated with a reduction in toxicity. We performed a prospective randomized study comparing once-daily versus multiple-dose gentamicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Seventy-three patients with 100 new episodes of peritonitis were enrolled in the study. At presentation of peritonitis, the patients were alternately assigned to receive either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4 times per day. All patients also received intraperitoneal vancomycin at a dose of 1 g per week. There were no significant differences in the treatment success (88% vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily dose and multiple-dose groups. The mean trough serum gentamicin level was higher in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72 vs 1.50 +/- 1.40 mg/L). In conclusion, gentamicin administered in a once-daily dose is as effective as multiple-dose administration in the treatment of CAPD peritonitis. The lower gentamicin level with once-daily dose administration may be associated with a reduction in aminoglycoside toxicity. The use of intraperitoneal (IP) vancomycin as initial, single agent therapy for gram positive and "no organism" continuous ambulatory peritoneal dialysis (CAPD) peritonitis is described, comparing continuous and intermittent administration schedules. "Continuous" therapy consisted of an IP 1-g loading dose of vancomycin followed by 30 mg/L dialysate effluent. "Intermittent" therapy consisted of 2 IP doses of 30 mg vancomycin/kg body weight--the initial dose delivered at diagnosis and the second dose 1 week later. All patients presenting with peritonitis (n = 90) were randomized to receive either continuous or intermittent vancomycin therapy. Patients in whom gram negative organisms and fungi were identified by microscopy and culture were transferred to therapy with a more appropriate antibiotic (n = 39). In the remainder (n = 51), CAPD peritonitis was treated solely with vancomycin (continuous, n = 21; intermittent, n = 30). Clinical resolution was seen in all patients, requiring a mean of 3.2 days for macroscopic clearing of dialysate effluent. Recurrence of peritonitis within 1 month of cessation of therapy was unusual and did not vary between treatment protocols (4/21 v 3/30; P = NS). There were no differences in observed side effects. Thus, IP vancomycin proved to be a useful single agent therapy for gram positive and no organism CAPD peritonitis. Therapy with two IP doses was effective and as safe as continuous IP vancomycin therapy, and therefore should replace other vancomycin administration schedules in the treatment of CAPD peritonitis. A multicentre, comparative, randomized study was performed to compare the efficacy and tolerability of two antibiotic regimens in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. After informed consent had been obtained, 68 patients were randomized prospectively to receive either teicoplanin plus tobramycin or cephalothin plus tobramycin. Patients were followed throughout the study and for up to 4 weeks after the end of treatment, when clinical and microbiological parameters were assessed again. The incidence of clinical failure was 4.6 times higher in the cephalothin plus tobramycin group than in the teicoplanin plus tobramycin group (7/28 versus 2/37; P < 0.05). There was no significant difference in bacterial eradication between the two groups. Local and systemic tolerability were good for both regimens. The study shows that teicoplanin plus tobramycin is more effective than cephalothin plus tobramycin and might become a 'first-line' treatment for peritonitis in CAPD patients. Intraperitoneal (IP) urokinase is a fibrinolytic agent that has been used in the adjunctive treatment of continuous ambulatory peritoneal dialysis (CAPD) and resistant and relapsing peritonitis. However, its efficacy and role in treating resistant CAPD bacterial peritonitis remain unclear and results from previous prospective studies have been conflicting. We prospectively randomized 88 CAPD patients with bacterial peritonitis resistant to initial empirical IP antibiotics into two groups: IP urokinase 60,000 IU and a placebo group. Patients were treated concomitantly with susceptible antibiotics according to culture results. Peritoneal dialysate grew pseudomonas aeruginosa in 13 patients (14.8%), non-pseudomonas bacteria in 63 patients (71.6%) and negative cultures in 12 patients (13.6%). For the clinical outcomes, there were no significant differences in the primary response rates (61.4 vs. 50%), relapse rates (9.1 vs. 13.6%), Tenckhoff catheter removal rates (22.7 vs. 29.5%) and mortality rates (6.8 and 6.8%) between the urokinase group and the controls (p=ns). Subgroup analysis of culture negative patients (n=12) also demonstrated no sgnificant benefit for urokinase treatment. No significant adverse effects were encountered with the IP urokinase instillation. Total median peritonitis-related length of hospitalization for the urokinase group and controls were 7 and 11 days, respectively (p=0.32). We concluded that IP urokinse plays no significant role as an adjuvant therapy in the treatment of bacterial CAPD peritonitis resistant to initial IP antibiotic therapy.
Based on one study, IP administration of antibiotics is superior to IV dosing for treating PD peritonitis. Intermittent and continuous dosing of antibiotics are equally efficacious. There is no role shown for routine peritoneal lavage or use of urokinase. No interventions were found to be associated with significant harm.