netilmicin and Kidney-Failure--Chronic

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

The effect of piperacillin administration on the dispositions of netilmicin and tobramycin was assessed in 12 chronic hemodialysis patients. Six subjects each received netilmicin (2 mg/kg) or tobramycin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Subjects also received a single dose of piperacillin (4 g) on a separate occasion. The serum concentration-versus-time profiles of netilmicin and tobramycin were biexponential. The terminal elimination half-life (t1/2 beta) of tobramycin was markedly reduced (59.62 +/- 25.18 [mean +/- standard deviation] versus 24.71 +/- 5.41 h) and total body clearance (CLP) was significantly increased in the presence of piperacillin (3.45 +/- 1.61 versus 7.16 +/- 1.64 ml/min). In contrast, the t1/2 beta (41.80 +/- 13.24 versus 40.07 +/- 10.37 h) and CLP (5.11 +/- 2.15 versus 5.55 +/- 2.32 ml/min) of netilmicin were not significantly altered when netilmicin was administered in combination with piperacillin. No change in the central or steady-state volume of distribution of netilmicin or tobramycin was observed. The disposition of piperacillin in hemodialysis patients was not altered in the presence of either aminoglycoside antibiotic. Although no adjustment in netilmicin dosing is required, tobramycin should be administered more frequently when given concomitantly with piperacillin to hemodialysis patients to avoid prolonged periods of subtherapeutic concentrations.

Topics: Adult; Drug Interactions; Female; Humans; Kidney Failure, Chronic; Male; Netilmicin; Piperacillin; Renal Dialysis; Tobramycin

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

In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments. Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin. For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method. In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency. The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923. Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs.

Topics: Adult; Aged; Cefotaxime; Ceftazidime; Digitoxin; Digoxin; Hemofiltration; Humans; Imipenem; Kidney Failure, Chronic; Metronidazole; Middle Aged; Netilmicin; Pharmaceutical Preparations; Phenobarbital; Phenytoin; Theophylline; Tobramycin; Vancomycin

The pharmacokinetics of netilmicin was studied in 26 patients with varying degrees of renal impairment (11 were dialysis patients) in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum level curves of netilmicin follows a two-compartment open kinetic model. Several relationships between pharmacokinetic parameters and renal function indicators are defined. A clinical useful correlation indicates that the half-life is approximately 3 times the serum creatinine concentration, and may be used for adjusting the netilmicin dosage in the treatment of patients with impaired renal function. During hemodialysis the serum half-life decreases approximately 10-fold compared with the interdialysis periods. The percentage of dose extracted by hemodialysis during a single 4 h session is 56.1 +/- 6.65%. The dialysis clearance is 87.28 +/- 28.8 ml/min.

Topics: Adult; Aged; Female; Fluorescence Polarization; Fluorescent Antibody Technique; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Netilmicin; Renal Dialysis

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

The serum concentration time profile of netilmicin and tobramycin before, during, and after hemodialysis was assessed in 5 noninfected adult chronic hemodialysis patients. The pharmacokinetic profile was biexponential for both agents in the pre-hemodialysis period. The total body clearance of netilmicin was significantly greater than that of tobramycin (5.32 +/- 0.75 ml/min vs 3.66 +/- 1.00 ml/min; p less than 0.05). The hemodialysis clearances of netilmicin and tobramycin were similar (60.8 +/- 16.6 ml/min and 54.7 +/- 18.8 ml/min, respectively). Netilmicin and tobramycin serum concentrations increased significantly 10 minutes after cessation of hemodialysis and maximally rebounded to 38.3 +/- 16.2% and 18.3 +/- 3.0% at 1.7 +/- 0.3 hours and 1.9 +/- 0.7 hours, respectively. This phenomenon may be a primary contributor to the marked variability observed in the clinical pharmacokinetics of these agents in hemodialysis patients. These data suggest that clinical serum concentrations should not be drawn until two hours after hemodialysis.

Topics: Adult; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Netilmicin; Renal Dialysis; Time Factors; Tobramycin

Seventy-seven elective or emergency surgical patients were treated with a prophylactic course of netilmicin. Netilmicin (150 mg intramuscularly) was given 1 hour prior to operation and continued 12 hourly until the patient was free of risk of post-operative infection. There was no microbiological or clinical evidence of post-operative infection in general surgical or orthopaedic patients. Netilmicin seems to be less nephrotoxic than other aminoglycosides. Netilmicin serum levels were within expected values. Netilmicin was found to be an effective and well-tolerated antibiotic, and prophylactic treatment shortened the mean patient bed-stay and hence costs incurred.

Topics: Adult; Aged; Female; Gentamicins; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Netilmicin; Postoperative Complications; Wound Infection