Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis. Treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis with intraperitoneal urokinase: a double-blind clinical trial. Role of intraperitoneal urokinase in acute peritonitis and prevention of catheter loss in peritoneal dialysis patients. [Infection prevention in elective large intestine surgery. Results of a prospective randomized comparative study]. Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy. Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS). A prospective randomized control study of oral nystatin prophylaxis for Candida peritonitis complicating continuous ambulatory peritoneal dialysis. 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 (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. 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. 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. In a prospective randomized trial clinical results of orthograde bowel lavage alone (group I) versus combined bowel lavage and parenteral antibiotic prophylaxis with 4 gm Cefoxitin (group II) in two separate dosages (perioperative short-term-prophylaxis) are compared with regard to the reduction of septic complications after colorectal surgery. Septic wound complications were 11/27 = 41% in group I and 2/30 = 7% in group II. The rate of anastomotic leakages was significantly different in the two groups (5/27 in group I, 0 in group II). The monetary costs for given antibiotics and the duration of hospitalization were less in group II. Orthograde bowel lavage alone proved to be of no effect in reducing the rate of septic complications when used without antibiotic perioperative short-term-prophylaxis and therefore cannot be recommended to be used solely. 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. 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. A prospective randomized study of the prevention of candida peritonitis (CP) in continuous ambulatory peritoneal dialysis patients using oral nystatin given concomitantly with antibiotic therapy was carried out for 2 years. Patients were randomized into two groups. Nystatin tablets 500,000 units four times a day were given to group 1 but not group 2 patients whenever antibiotics were prescribed. There were 199 patients at risk (mean follow-up, 18.0 months) in group 1 and 198 patients at risk (mean follow-up, 16.6 months) in group 2. The peritonitis and antibiotic prescription rates were comparable between the two groups. There were four episodes of CP in four patients in group 1 and 12 episodes in 11 patients in group 2. The probability of CP-free survival at 2 years was higher in group 1 compared with group 2 (0.974 v 0.915; P < 0.05). However, only three (75%) CP episodes in group 1 and six (50%) in group 2 were considered "antibiotics related." The incidence of antibiotics-related CP was 1.39 and 3.19 per 100 peritonitis episodes and 0.66 and 1.43 per 100 antibiotic prescriptions in groups 1 and 2, respectively (P = NS). We conclude that oral nystatin prophylaxis with each antibiotic prescription reduced the rate of CP in patients on continuous ambulatory peritoneal dialysis irrespective of its apparent temporal relationship to antibiotic prescription. 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.
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.