netilmicin and 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.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefazolin; Ceftazidime; Drug Therapy, Combination; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Treatment Outcome

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.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Treatment Outcome; Vancomycin

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.

Topics: Cefazolin; Ceftazidime; Drug Therapy, Combination; Humans; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Treatment Failure; Vancomycin

Single daily dosage of netilmicin is generally accepted in systemic infections, due to biphasic bactericidal activity and prolonged postantibiotic effect of aminoglycosides. Since little is known about the efficacy of single daily intraperitoneal application of netilmicin in the treatment of CAPD-associated peritonitis, we conducted this prospective study. Seven patients with CAPD-associated peritonitis were treated with a single daily dose of netilmicin (loading dose 1.5 mg/kg, followed by 40 mg/21 bag/day). Serum and intraperitoneal levels as well as bactericidal activity of netilmicin against Acinetobacter baumanii, E. coli and Pseudomonas aeruginosa were measured for 48 hours. Serum and peritoneal levels widely varied among the patients due to different interindividual plasma clearance of netilmicin. The intraperitoneal antibacterial action of netilmicin was decreased, more over, substantial differences in the bactericidal activity were found among the patients. However, with high initial netilmicin levels sufficient bactericidal activity was found for Acinetobacter and E. coli, but not for Pseudomonas aeruginosa. Hence, a single daily dosage of netilmicin can be a suitable treatment of CAPD-associated peritonitis, only if the dose is adapted according to the first serum and peritoneal levels. In infections with Pseudomonas aeruginosa higher peritoneal levels of netilmicin and the combination with other antibiotics will be needed for a sufficient peritoneal bactericidal activity.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Vancomycin

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Topics: Adult; Aged; Bacteremia; Bacterial Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Netilmicin; Peritonitis; Pneumonia; Prospective Studies

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.

Topics: Acute Disease; Bacterial Infections; Humans; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritoneal Lavage; Peritonitis; Recurrence; Vancomycin

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.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Ciprofloxacin; Female; Humans; Injections, Intraperitoneal; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Vancomycin

This multicentre trial compared the clinical efficacy of amoxycillin/clavulanate used as a single-agent therapy with that of the three-agent combination usually prescribed in the post-operative period for appendicular peritonitis in children. Only bacteriologically documented peritoneal infections were included. Sixty-four patients were randomly distributed between two groups: Group A (29 cases) treated with amoxycillin/clavulanate, first administered iv (100 mg/kg/day) followed by conversion to the oral route (50 mg/kg/day) once the patient had been afebrile for 48 h; Group B (35 cases) first treated by the iv route with benzylpenicillin (100,000 IU/kg/day) plus netilmicin (5 mg/kg/day) plus metronidazole (30 mg/kg/day) followed by conversion to the oral route for metronidazole (30 mg/kg/day). In both groups, the total duration of parenteral and oral treatment was not less than five days. A total of 180 bacterial strains were recovered from peritoneal fluid samples obtained during surgery; 86% of these were sensitive to amoxycillin/clavulanate. Clinical efficacy, assessed on the basis of time until return to normal temperature and gut transit and duration of hospitalization, was identical in both groups, with follow-up monitoring on day 30 showing recovery in all cases. Cure was obtained without any problems of infection in 25/29 patients in group A and in 34/35 patients in group B (non-significant difference). Tolerance was excellent and identical in the two groups with the exception of three cases of thrombophlebitis which occurred in group B. The results of this study suggest that amoxycillin/clavulanate may be useful as single-agent therapy as a first-line curative treatment for appendicular peritonitis in children.

Topics: Amoxicillin; Appendicitis; Child; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Infant; Male; Metronidazole; Netilmicin; Penicillin G; Peritonitis; Postoperative Period; Randomized Controlled Trials as Topic

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.

Topics: Adolescent; Adult; Aged; Clindamycin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Imipenem; Length of Stay; Male; Middle Aged; Netilmicin; Peritonitis; Postoperative Complications; Random Allocation; Reoperation; Surgical Wound Infection; Thienamycins

The efficacy of netilmicin combined with tinidazole (N + T) or clindamycin (N + C) in the treatment of severe abdominal infections was evaluated in a prospective randomized study with 20 patients in the N + T group and 21 patients in the N + C group. Normally the maintaining dose for netilmicin was 2.25 mg/kg every 12 h, for tinidazole 400 mg every 12 h and for clindamycin 300-600 mg every 6-8 h. The mean duration time of treatment was 8 days in the N + T group and 10 days in the N + C group respectively. In the N + T group 18 patients were cured and in the N + C group 17 patients. Among aerobic bacteria Escherichia coli was most frequently isolated and among anaerobes Bacteroides sp. All aerobic bacteria with 2 exceptions were susceptible to netilmicin and all anaerobic bacteria but 2 to tinidazole or clindamycin. Adequate serum levels were obtained for each antibiotic during therapy. In this study with a small number of patients the combination of netilmicin and tinidazole was as effective as netilmicin and clindamycin.

Topics: Adolescent; Adult; Aged; Bacteria; Clindamycin; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Nitroimidazoles; Peritonitis; Surgical Wound Infection; Tinidazole

The clinical behavior and optimal treatment of relapsing and recurrent peritonitis episodes in patients undergoing long-term peritoneal dialysis are poorly understood.. Retrospective study over 14 years.. University dialysis unit; 157 relapsing episodes (same organism or culture-negative episode occurring within 4 weeks of completion of therapy for a prior episode), 125 recurrent episodes (different organism, occurs within 4 weeks of completion of therapy for a prior episode), and 764 control episodes (first peritonitis episode without relapse or recurrence).. Exit-site infection, empirical antibiotics.. Primary response (resolution of abdominal pain, clearing of dialysate, and peritoneal dialysis effluent neutrophil count < 100 cells/mL after 10 days of antibiotic therapy), complete cure (resolution by using antibiotics without relapse/recurrence), catheter removal (for any cause while on antibiotic therapy), and mortality.. Compared with the control group, more relapsing episodes were caused by Pseudomonas species (16.6% versus 9.4%) and were culture negative (29.9% versus 16.4%); recurrent infections commonly were caused by Enterococcus species (3.2% versus 1.2%) or other Gram-negative organisms (27.2% versus 11.1%) or had mixed bacterial growth (17.6% versus 12.7%). There were significant differences in primary response, complete cure, and mortality rates among groups (P < 0.001 for all comparisons). Compared with the control and relapsing groups, post hoc analysis showed that the recurrent group had a significantly lower primary response rate (86.4%, 88.5%, and 71.2%, respectively), lower complete cure rate (72.3%, 62.4%, and 42.4%, respectively), and higher mortality rate (7.7%, 7.0%, and 20.8%, respectively).. Retrospective analysis.. Relapsing and recurrent peritonitis episodes are caused by different spectra of bacteria and probably represent 2 distinct clinical entities. Recurrent peritonitis episodes had a worse prognosis than relapsing ones.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefazolin; Ceftazidime; Female; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Logistic Models; Male; Middle Aged; Netilmicin; Peritoneal Dialysis; Peritonitis; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Vancomycin

Peritonitis due to Pseudomonas species is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. The clinical course of peritonitis due to Pseudomonas complicating CAPD remains unclear.. All of the Pseudomonas species episodes of peritonitis in our dialysis unit were studied from 1995 to 1999. During this period, there were 859 episodes of peritonitis recorded, 113 of which were caused by the Pseudomonas species. Nine episodes were excluded because they were mixed growth. The remaining 104 episodes in 68 patients were reviewed.. The underlying renal diagnosis and prevalence of comorbid conditions of the 68 patients were similar to those found in our entire dialysis population. There was a history of antibiotic therapy within 30 days of the onset of peritonitis due to the Pseudomonas species in 69 episodes (66.3%). In 47 episodes (45.2%) there was a concomitant exit site infection. The overall primary response rate was 60.6% and the complete cure rate was 22.1%. The presence of exit site infection was associated with a lower primary response rate (22 in 47 vs. 41 in 57 episodes, P < 0.01) and a lower complete cure rate (5 in 47 vs. 18 in 57 episodes, P < 0.02). The episodes that had received recent antibiotic therapy had a significantly lower complete cure rate than the de novo cases (8 in 69 vs. 15 in 35 episodes, P < 0.001). Episodes receiving third-generation cephalosporin as part of the initial antibiotic regimen had a significantly higher primary response rate than the ones that initially received aminoglycoside (54 in 81 episodes vs. 8 in 22 episodes, P < 0.05), but their complete cure rates were similar. Twenty-four cases failed to respond to antibiotics and the Tenckhoff catheter was removed. The chance of returning to CAPD was higher when the Tenckhoff catheter was removed on day 10 than on day 15 (9 in 14 cases vs. 5 in 10 cases), although the result was not statistically significant. The Tenckhoff catheter was removed and replaced at another site simultaneously in another 14 cases after the effluent cleared up. None of these patients had a relapse of peritonitis within three months.. Recent antibiotic therapy is the major risk factor for peritonitis due to the Pseudomonas species. Exit site infection and recent antibiotic therapy are associated with poor therapeutic response to antibiotics. When the therapeutic response is suboptimal, early Tenckhoff catheter removal may help preserve the peritoneum for further peritoneal dialysis. Elective Tenckhoff catheter exchange after clearing up the peritoneal dialysis effluent may also reduce the likelihood of relapse. It is desirable to use third-generation cephalosporin in the initial antibiotic regimen for peritonitis treatment in localities with a high incidence of peritonitis due to the Pseudomonas species.

Topics: Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Equipment Contamination; Female; Gentamicins; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Pseudomonas Infections; Retrospective Studies; Secondary Prevention; Vancomycin

Topics: Adult; Aged; Dialysis Solutions; Drug Administration Schedule; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

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.

Topics: Adult; Aged; Cefuroxime; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Pilot Projects; Random Allocation; Staphylococcal Infections; Vancomycin

Pharmacokinetic profiles in small animals substantially differ from those observed in man. We hence devised a man adapted animal model to critically assess the impact of such differences on antimicrobial efficacy. We approximated in mice the human pharmacokinetic profiles of netilmicin, ticarcillin and ceftazidime. The CD50 (curative dose for 50% of lethally intra-peritoneally infected animals) against Pseudomonas aeruginosa was comparatively determined for murine versus man-adapted pharmacokinetic profiles. With netilmicin the man-adapted profile was significantly less efficacious than the murine profile. In contrast, a significant superiority of the man-adapted profile was found with the beta-lactam drugs. We conclude that determinations of antimicrobial activity in small animals may yield misleading results in respect to man. Depending on the drug in question, murine pharmacokinetics may lead to overestimation or underestimation of antimicrobial activity. Our findings are of particular importance for the interpretation of studies in small animals comparing different antimicrobial compounds or different dosage regimens.

Topics: Animals; Ceftazidime; Disease Models, Animal; Drug Administration Schedule; Female; Half-Life; Injections, Subcutaneous; Mice; Mice, Inbred ICR; Netilmicin; Peritonitis; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Sepsis; Specific Pathogen-Free Organisms; Ticarcillin

Topics: Ciprofloxacin; Drug Therapy, Combination; Female; Humans; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Pseudomonas Infections

Cefotetan is a semi-synthetic cephamycin antibiotic. It has combined activity against aerobes and anaerobes which makes it of particular use in the treatment and prevention of intra-abdominal infections in the surgical patient. In the course of 3 years we have evaluated the therapeutic use of cefotetan in 107 patients. Early in the evaluation of this antibiotic we used cefotetan in combination with aminoglycosides in 35 severely ill patients with intra-abdominal infections. These patients were generally in poor condition. Good results were obtained in this high risk group. A further 72 patients received cefotetan monotherapy, usually at a dose of 2 g twice daily. The majority of these patients presented with intra-abdominal infections. Overall a successful clinical response of 94% was obtained with antibiotic therapy. In conclusion the results obtained support the therapeutic use of cefotetan in the treatment of moderate to severe intra-abdominal infection.

Topics: Adult; Bacterial Infections; Cefotetan; Female; Humans; Male; Netilmicin; Peritonitis; Prognosis

Antibiotics play an important role in helping the host fight infection; however, the direct cellular effect of antibiotics on polymorphonuclear cells remains undefined. Adherence, chemotaxis, phagocytosis, and superoxide anion production are important steps in the cascade of events initiated by the polymorphonucleocyte in bacterial killing. Previous studies have shown inhibition as well as stimulation of neutrophil antibacterial therapy by antibiotics. Peritoneal and blood polymorphonuclear neutrophils (PMN) respond differently to peritonitis and to external agents. The purpose of this study was to investigate the effects of in vivo clindamycin and netilmicin on infected rabbit peritoneal and blood polymorphonuclear adhesiveness, phagocytosis, chemotaxis, and superoxide anion production. Peritoneal and blood PMNs were obtained from rabbits which had undergone appendiceal devascularization 18 hr earlier: antibiotics were administered intramuscularly 1 hr prior to appendectomy and every 8 hr postoperatively for 5 days; these PMNs were compared to infected rabbits which did not receive antibiotics. Clindamycin and netilmicin in vivo cause significant inhibition of phagocytosis, peritoneal adhesiveness, and, when used in combination, blood adhesiveness and peritoneal superoxide anion production. No effects were seen on chemotaxis. Based on this data we conclude that antibiotics, while vitally important in fighting infections, may in and of themselves be agents of immunosuppression at the cellular level.

Topics: Animals; Cell Adhesion; Chemotaxis, Leukocyte; Clindamycin; Drug Therapy, Combination; Netilmicin; Neutrophils; Peritonitis; Phagocytosis; Rabbits; Superoxides

The efficacy and systemic absorption of netilmicin following intraperitoneal instillation were studied during ten episodes of clinical peritonitis in chronic renal failure patients managed by CAPD. Episodes were unselected for sensitivity of microorganism in vitro to netilmicin. Five subjects studied as inpatients had sequential dialysate and frequent plasma samples assayed for netilimicin up to 110 hours of therapy. Five patients who managed their peritonitis at home had dialysate and plasma netilmicin levels estimated at two and six days. In a dose of 10 mg/l, netilmicin was curative in the majority of patients (70%). Toxic blood levels were not found. Experience with netilmicin compared favourably with that observed in eight consecutive episodes of outpatient peritonitis managed with intraperitoneal cefamandole, the first line treatment for CAPD peritonitis in our unit (75% cure). No side effects were recorded with either agent. We conclude that netilmicin can be used effectively in the majority of microbiologically undifferentiated episodes of CAPD peritonitis, including in the home setting.

Topics: Absorption; Humans; Kidney Failure, Chronic; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis

Topics: Adult; Bacteria; Bacterial Infections; Cefotetan; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Netilmicin; Peritonitis

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Female; Gentamicins; Humans; Metabolic Clearance Rate; Mice; Netilmicin; Peritonitis; Pseudomonas Infections; Ticarcillin

The purpose of this study was to determine the effect of an immunostimulative polymer, Copovithane (Cpv), plus antibiotics (netilmicin and clindamycin) in a murine model of fecal peritonitis. Cpv augments humoral immunity with little effect on T cells and is nontoxic. Cpv 100 mg/kg iv administered at the onset of sepsis increased median survival time (MST) by 40-55% over untreated controls. Four experiments were performed. Cpv in combination with antibiotics when given at the time of onset of sepsis was significantly more effective than antibiotics alone (MST 235 vs 105 hr, P less than 0.05 at 144, 168, 192, 216 hr). In the second and third experiments Cpv alone and with antibiotics was administered 15 hr after the onset of sepsis. Cpv significantly augmented survival over controls in the second experiment (MST 87 vs 60 hr, P less than 0.025 at 96 hr). Cpv plus antibiotics was significantly better than antibiotics alone in the third experiment (MST 111 vs 64 hr, P less than 0.05 at 72 hr, P less than 0.005 at 120 hr). In the final experiment, Cpv did not inhibit growth of 20 bacterial species in agar and liquid media. Cpv significantly enhances survival in murine fecal peritonitis even when administered after the onset of sepsis; furthermore Cpv plus antibiotics in established peritonitis produces longer survival than antibiotics alone. Synthetic immunomodulators such as Cpv could eventually play a significant role in the management of peritoneal infection in humans.

Topics: Animals; Bacteria; Carbamates; Clindamycin; Drug Therapy, Combination; Gentamicins; Immunization; Immunotherapy; Male; Mice; Mice, Inbred CBA; Netilmicin; Peritonitis; Polymers; Povidone

The first line treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in our hospital was recently altered from a combination of gentamicin and clindamycin, given as continuous peritoneal lavage, to one of vancomycin and netilmicin given in peritoneal dialysis fluid with prolonged dwell time (4-6 h). The change was prompted by the emergence of multiply resistant Staphylococcus epidermidis among CAPD patients and nursing staff. In 9 of 19 episodes of peritonitis treated with gentamicin/clindamycin, the infecting organism could still be isolated from peritoneal fluid 5-15 days after commencement of therapy. All of 35 culture verified episodes treated with vancomycin/netilmicin were cleared bacteriologically within 3 days (P less than 0.0005). The vancomycin and netilmicin serum levels achieved were 6.5-37.0 mg/l and 1.0-8.1 mg/l, respectively. Apart from an asthmatic reaction, possibly triggered by vancomycin, no side effects were seen. However, audiometry was not performed regularly and the possible effect of netilmicin on the residual renal function was not systematically investigated.

Topics: Adult; Bacteria; Drug Combinations; Drug Resistance, Microbial; Female; Gentamicins; Humans; Netilmicin; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Vancomycin

Clinical aspects of Continuous Ambulatory Peritoneal Dialysis (CAPD) were studied in the first fifty patients started on CAPD at our hospital. CAPD was found to achieve good control of the uremic symptoms and of the biochemical values studied. Hypertension became less pronounced. The costs were found to be low. Twenty-four diabetic subjects were studied in detail. Intraperitoneal administration of insulin resulted in good metabolic control of the diabetes. The two catheters used for peritoneal access were compared. Because of problems related to the removal of the Toronto Western Hospital catheter it was concluded that the Tenckhoff catheter was to be preferred. Peritonitis was found to be the worst complication. Coagulase negative staphylococci accounted for 57% of the cases. During the study an increasing percentage of infections were caused by bacteria with multiple resistance to antibiotics. Netilmicin, a new aminoglycoside, was evaluated for the treatment of CAPD-related peritonitis. 84% of the cases responded. One of the nineteen patients treated sustained reversible vestibular toxicity. No other side effects were noted. In two patients right-sided hydrothorax was found to be a complication of peritoneal dialysis. In one case it was demonstrated that defects in the right diaphragm was the cause of the complication. In the other CAPD was continued despite the complication.

Topics: Anti-Bacterial Agents; Catheters, Indwelling; Diabetic Nephropathies; Humans; Hydrothorax; Netilmicin; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Staphylococcal Infections; Sweden; Time Factors; Uremia

In the present study, we used netilmicin for the postoperative complications and obtained the following results. 1. Netilmicin was used in totally 29 cases; 23 with localized peritonitis, 4 with generalized peritonetis and 2 with wound infection. Excellent effects were obtained in 2 cases, effective results in 24 cases and ineffective results in 3 cases. The effective rate was 89.7%. 2. Adverse reactions or abnormal clinical laboratory test results which might be attributable to the use of netilmicin were not noticed.

Topics: Adult; Aged; Child; Drug Evaluation; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Peritonitis; Postoperative Complications; Surgical Wound Infection