A prospective, randomized trial of two antibiotic regimens in the treatment of peritonitis in CAPD patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. Preventing Staphylococcus aureus infection during chronic peritoneal dialysis. A randomized prospective comparison of oral versus intraperitoneal ciprofloxacin as the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD. CAPD peritonitis: a prospective randomized trial of oral versus intraperitoneal treatment with cephradine. Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial. Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS). Prophylactic antibiotics in the insertion of Tenckhoff catheters. Antibiotic treatment during surgery for diffuse peritonitis: a prospective randomized study comparing the effects of cefuroxime and of a cefuroxime and metronidazole combination.
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. In the interest of studying the prevention of chronic peritoneal dialysis infections, serial studies of the bacterial epidemiology in peritonitis and of antibiotic prophylaxis, respectively, were carried out. For 18 months, prospective evaluation of catheter exist site cultures, performed at the time patients developed acute peritonitis, showed that Staphylococcus aureus peritonitis was associated with concordant S. aureus at the exist site in 85% of cases, significantly more frequent than that for other organisms (P less than 0.02). Furthermore, active inflammation along with concordant culture results at the exit site characterized more than 60% of S. aureus peritonitis cases, also significantly more than that for other organisms (P less than 0.01). Over the ensuing 2 yr, patients beginning chronic peritoneal dialysis with a new percutaneously placed catheter were prospectively entered into a randomized, controlled trial of long-term antibiotic prophylaxis with trimethoprim-sulfamethoxasole. Patients receiving prophylaxis tended to have fewer episodes of peritonitis; however, the lower rate of peritonitis reached statistical significance only comparing patients who were S. aureus carriers at entry into the study to patients who were not S. aureus carriers. In particular, the prophylaxis trial seemed to reduce the specific incidence of S. aureus peritonitis overall, with S. aureus appearing in only 2 of 28 total peritonitis episodes among treated patients as compared with 11 of 37 total episodes among non-treated patients (P less than 0.01). Further analysis of the time to first peritonitis suggests that the effect of prophylaxis was most prominent during the first 3 months of therapy (P less than 0.02) rather than later in the course of treatment.(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. 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. 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) 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. 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. We assessed the efficacy of preoperative antibiotic prophylaxis in a prospective trial for patients undergoing insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis (CAPD). The prophylactic regimen was a single dose of cefazolin (500 mg) and gentamicin (80 mg) given intravenously half an hour before surgery. There was no significant difference in the number of exit site infections (8 in the antibiotic group vs. 8 in the controls) and the number of episodes of peritonitis (5 in the antibiotic group vs. 2 in the controls). Our study showed that prophylactic preoperative antibiotics did not reduce the number of exit site infections and peritonitis after the insertion of Tenckhoff catheters. 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.
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.