netilmicin and Kidney-Diseases

The effectiveness and safety of once-daily versus several-times-daily aminoglycosides were studied in a meta-analysis. MEDLINE for 1988 to 1995 was searched, and additional studies were identified from review articles and references in retrieved articles. Studies selected for meta-analysis were randomized controlled clinical trials in nonneutropenic adult patients comparing the clinical effectiveness or nephrotoxicity or ototoxicity of once-daily with several-times-daily aminoglycosides. Differences between groups were expressed as odds ratios. The results were combined by the procedure of Mantel and Haenszel, and 95% confidence intervals and exact confidence intervals were computed. An odds ratio smaller than 1 would indicate a lesser likelihood of a given endpoint in the once-daily group, and an odds ratio greater than 1 would indicate a greater likelihood. Eighteen studies involving 2317 patients were included in the meta-analysis. Summary odds ratios were 1.47 for effectiveness (95% CI = 1.13-1.94), 0.56 for ototoxicity (95% CI = 0.26-1.16), and 0.60 for nephrotoxicity (95% CI = 0.40-0.86). A meta-analysis showed that treatment with single daily doses of aminoglycosides seems to be more effective, less nephrotoxic, and as ototoxic as multiple doses daily.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Controlled Clinical Trials as Topic; Drug Administration Schedule; Ear Diseases; Gentamicins; Humans; Infections; Kidney Diseases; Middle Aged; Netilmicin

Animal studies report equal or greater clinical efficacy with once daily versus multiple daily aminoglycoside dosing; however, results are inconsistent. Extrapolation of these animal data to human data is difficult, since marked variability exists in terms of pharmacokinetic disposition of aminoglycosides. Human data suggest that once daily aminoglycoside dosing regimens are as effective as multiple dosing regimens. However, studies need to be performed assessing the efficacy of once daily aminoglycoside dosing for infectious sites other than intra-abdominal and the urinary tract. In addition, the results of these studies should not be extrapolated to those with renal dysfunction, the immunocompromised, or in patients with aminoglycoside treatment durations of greater than 8 days, as the efficacy of once daily dosing in these patient populations has not been proven. Animal studies assessing nephrotoxicity suggest that multiple daily aminoglycoside dosing results in more frequent or more severe nephrotoxicity compared to once daily dosing. Nine human studies have been published comparing the nephrotoxicity of once daily versus multiple daily aminoglycoside dosing. The majority of investigators have studied nonimmunocompromised patients with urinary tract infections. Netilmicin has been the most frequently used aminoglycoside, although other agents such as gentamicin, amikacin, and sisomicin have been studied. The most common netilmicin dosage regimen has ranged from approximately 4 to 6 mg/kg administered once daily. Eight of the nine trials performed have documented no significant differences in serial serum creatinine concentrations between once daily and multiple daily aminoglycoside dosing regimens, by the end of the study period. In conclusion, preliminary data suggest that once daily aminoglycoside dosing in nonimmunocompromised patients is equally efficacious and nephrotoxic compared to multiple daily dosing regimens.

Topics: Animals; Anti-Bacterial Agents; Drug Administration Schedule; Humans; Kidney; Kidney Diseases; Netilmicin

This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.

Topics: Amikacin; Aminoglycosides; Cost-Benefit Analysis; Ear Diseases; Gentamicins; Humans; Kidney Diseases; Netilmicin; Tobramycin

Sisomicin is a naturally occurring aminoglycoside antibiotic produced by Micromonospora inyoensis, while dibekacin and netilmicin are both semisynthetic aminoglycosides. Dibekacin is 3',4'-dideoxykanamycin B and netilmicin is 1-N-ethyl sisomicin. In both cases, these modifications render the agents insusceptible to some of the enzymes found in resistant strains of bacteria which inactivate the parent compounds. Antibacterial activity: All 3 drugs show bactericidal activity against a wide range of Gram-negative bacteria (including E. coli, Enterobacter, Klebsiella and Proteus spp. and Ps. aeruginosa) and also against staphylococci; however, in common with other amino-glycosides, streptococci are usually resistant (except when beta-lactam antibiotics are used in combination) and anaerobic organisms are not sensitive. Sisomicin is closely related structurally to gentamicin Cla, but in vitro studies have shown it to have superior activity to gentamicin against Ps. aeruginosa, closely paralleling the activity of tobramycin, while still possessing the high activity of gentamicin against Serratia and other Gram-negative rods. However, sisomicin is inactivated by virtually all bacterial enzymes which inactivate gentamicin and tobramycin. Nevertheless, it retains useful activity against a number of gentamicin-resistant strains of Ps. aeruginosa which are resistant by non-enzymatic (possibly permeability barrier) mechanisms; in this respect it closely resembles tobramycin. Dibekacin closely resembles tobramycin structurally and in vitro it seems to have a very similar antibacterial spectrum, including activity against some strains of Ps. aeruginosa resistant to gentamicin. Netilmicin has a generally broader antibacterial spectrum than gentamicin, tobramycin, sisomicin or debekacin and is resistant to inactivation by phosphorylating and adenylylating enzymes; however, it is inactivated by all acetylases, apart from acetylase 3-I. Its spectrum is therefore not as wide as that of amikacin against 'gentamicin-resistant' strains. Nonetheless, it is intrinsically more active than amikacin, weight-for-weight, against sensitive strains, apart possibly from Ps. aeruginosa. In fact, its activity against species of the Enterobacteriaceae and staphylococci sensitive to gentamicin is of the same order as the latter and possibly better for Klebsiella-Enterobacter species. All 3 agents show marked antibacterial synergy with a variety of beta-lactam antibiotics against a range of

Topics: Aging; Animals; Bacterial Infections; Dibekacin; Drug Interactions; Drug Resistance, Microbial; Drug Synergism; Gentamicins; Humans; Kanamycin; Kidney Diseases; Netilmicin; Sisomicin

For a decade gentamicin has been used extensively because of its antimicrobial efficacy and the relatively low prevalence of clinical toxicity. Recently the more frequent appearance of resistant organisms, reports of increased nephrotoxicity and ototoxicity, and the development of newer aminoglycoside antibiotics have raised doubts about the continued use of this agent. This paper reassesses the role of gentamicin. It is clear that an appreciation of the pharmacokinetics and the clinical use of gentamicin as well as an understanding of the patterns of toxicity in animals and humans can lead to more efficient treatment with this antimicrobial agent. Despite ample competition from a number of newer aminoglycoside antibiotics, gentamicin will probably continue to be used widely in the near future.

Topics: Amikacin; Animals; Bacterial Infections; Drug Synergism; Ear Diseases; Gentamicins; Humans; Kidney; Kidney Diseases; Netilmicin; Penicillin Resistance; Penicillins; Respiratory Tract Infections; Sisomicin; Tobramycin; Urinary Tract Infections

The effect of aminoglycosides on renal function was evaluated in 30 full-term infants who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (9 infants, group B), or netilmicin (10 infants, group C). Renal function was assessed before, during, and 48 h after discontinuation of therapy by measuring the plasma creatinine concentration (PCr), the fractional excretion of sodium (FENa), potassium, magnesium, phosphate (FEP), uric acid, and the urinary excretion of calcium (UCA/UCr ratio) immediately before (trough) and after (peak) the infusion of the aminoglycosides. The results were compared with 10 control newborns who did not receive antibiotics. Significant alterations in renal function were observed only during therapy with gentamicin (group B). These consisted of a sustained elevation of FENa and UCa/UCr ratio throughout therapy, a latent increase in FEP on the 7th day (P < 0.05), and lack of the normal postnatal decline of PCr in 3 of 9 infants (P < 0.01). These abnormalities persisted up to 2 days after discontinuation of therapy. Therapeutic doses of gentamicin may result in significant electrolyte disturbances in sick full-term infants.

Topics: Amikacin; Anti-Bacterial Agents; Gentamicins; Humans; Infant, Newborn; Kidney Diseases; Kidney Function Tests; Netilmicin; Time Factors; Water-Electrolyte Imbalance

A prospective, randomized multicentre study was conducted in order to evaluate the potentially superior tolerability profile of teicoplanin plus netilmicin compared with vancomycin plus netilmicin in patients in ICUs. We considered that these glycopeptides have been shown to have comparable efficacy and that comparative tolerability is of paramount importance, particularly in severely ill patients. A total of 56 patients were enrolled into the study (36 males and 20 females). Twenty-four patients were included in the teicoplanin plus netilmicin group (15 males, 9 females: mean age 56.8 years). The mean simplified acute physiological score (SAPS) was 9.4 (range 4-20). Thirty-two patients were randomized to receive vancomycin plus netilmicin (21 males, 11 females; mean age 56.4 years). The mean SAPS was 9.3 (range 2-16). Septicaemia was the most common infection (14 cases in each group). Most infections were caused by Staphylococcus aureus or coagulase-negative staphylococci. The mean daily doses were: for teicoplanin, 457 mg (6.7 mg/kg); for vancomycin, 1678 mg (24.4 mg/kg); and for netilmicin 263.3 mg (3.9 mg/kg) in the teicoplanin group and 248 mg (3.8 mg/kg) in the vancomycin group. The trough levels of teicoplanin in the serum remained mostly between 7 and 10 mg/l, while more fluctuation was seen in patients receiving vancomycin. The mean trough levels of netilmicin in the serum were 1.2 (SD 0.9) mg/l in the teicoplanin group, compared with 1.7 (SD 1.4) mg/l in the vancomycin group (NS: p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Critical Care; Cross Infection; Drug Monitoring; Drug Therapy, Combination; Female; Gram-Positive Bacterial Infections; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Teicoplanin; Vancomycin

Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg once daily i.v. or netilmicin 5.5 mg/kg once daily i.v. (with dosage reduction in case of renal dysfunction). Exclusion criteria were neutropenia or severe renal failure. Median first serum trough and peak concentrations were 0.4/9.5 mg/L and 0.4/12.2 mg/L, for gentamicin and netilmicin respectively. A good clinical response was observed in 50/54 (92.6%) evaluable patients treated with gentamicin and in 48/52 (92.3%) netilmicin-treated patients. Nephrotoxicity (a rise of serum creatinine > or = 45 mumol/L) developed in 5/72 (6.9%) gentamicin patients treated > or = 48 hours and in 10/69 (14.5%) netilmicin patients (difference 7.5%, 95% CI -3.9% to +16.2%). High-tone audiometry was performed when possible; no significant differences were found between the regimens with regard to hearing loss or prodromal signs of ototoxicity. We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.

Topics: Aged; Bacterial Infections; Creatinine; Female; Gentamicins; Hearing Disorders; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Risk Factors

We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Hearing Loss, Bilateral; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Tobramycin

The pharmacologic parameters and toxicity of netilmicin (6 mg/kg/day) given once daily (qd) or thrice daily (tid) for the treatment of urinary tract infections were studied in a randomized prospective study of 60 cancer patients. The overall efficacy was 96%. Nephrotoxicity, assessed by the measure of urinary excretion of phospholipids, was lower for the patients receiving the qd regimen than for those receiving the tid regimen. Elevation of serum creatinine (20% over baseline) occurred in one patient receiving the qd regimen and in three receiving the tid regimen. Cochleotoxicity, assessed by pure-tone audiometry (250 to 18,000 Hz) occurred in one patient receiving the qd regimen and none receiving the tid regimen. Concentrations in sera were measured on days 1 and 5. No significant accumulation was observed in either group. Median serum bactericidal titers, expressed as reciprocal values (percentage of the sera with a titer greater than or equal to 8), were measured against 25 test organisms in samples collected 6 h after the administration of netilmicin and were, for the qd group, 16 (82%) against members of the family Enterobacteriaceae and less than 2 (8%) against Pseudomonas aeruginosa, and for the tid group, 4 (57%) against members of the Enterobacteriaceae and less than 2 (0%) against P. aeruginosa. The rate of killing in serum was rapid (2 to 3 log in 2 h against P. aeruginosa; 3 to 5 log in 2 h against members of the Enterobacteriaceae) and correlated with the sampling time and hence the concentration in serum of netilmicin. The duration of the postantibiotic effect in serum depended also on the strain and the sampling time of the serum.

Topics: Adult; Aged; Aged, 80 and over; Bacteria; Blood Bactericidal Activity; Cochlea; Female; Hearing Disorders; Humans; Kidney Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Netilmicin; Urinary Tract Infections

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.

Topics: Audiometry; Bacterial Infections; Creatinine; Edetic Acid; Electronystagmography; Gentamicins; Hearing Disorders; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Diseases; Middle Aged; Netilmicin; Randomized Controlled Trials as Topic; Vestibular Diseases; Vestibular Function Tests

Topics: Aged; Alanine Transaminase; Ceftazidime; Creatinine; Drug Combinations; Female; Furosemide; Humans; Kidney Diseases; Kidney Tubules; Male; Multicenter Studies as Topic; Netilmicin; Piperacillin; Random Allocation; Time Factors

The aim of the study was the evaluation of the clinical efficacy and the kidney tolerance of ceftazidime in comparison with netilmicin in pediatric patients. Forty subjects, ranging from six months to ten years of age were randomly allocated in two groups and treated either with ceftazidime (80-100 mg/kg/day) or netilmicin (6 mg/kg/day). A control group of twenty subjects was selected in order to establish the normal values of beta 2-microglobulin and urinary enzymes excretion. beta 2-microglobulin, enzymuria, cylindruria and urinary osmolability were estimated, as well as hematological parameters. Ceftazidime was as efficacious as netilmicin in the clinical outcome and in addition it did not cause any pathological change in early markers of tubular damage.

Topics: beta 2-Microglobulin; Ceftazidime; Child; Child, Preschool; Humans; Infant; Kidney Diseases; Liver Function Tests; Netilmicin; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Evaluation; Gentamicins; Humans; Kidney; Kidney Diseases; Netilmicin; Tobramycin

Fifty-three patients with documented or suspected mixed flora infections were randomly assigned to receive either netilmicin or tobramycin in combination with clindamycin. Data from 36 patients with 43 documented infections yielding 102 clinical isolates were evaluated for efficacy. In the 18 patients receiving netilmicin-clindamycin, 90% of the infections responded favorably and 96% of the pathogens were eliminated. In the 18 patients receiving tobramycin-clindamycin, 81% of the infections resolved and 88.5% of the pathogens were eliminated. Forty-nine patients were included in the safety analysis. The incidence of nephrotoxicity was similar in both groups (netilmicin, 20%; tobramycin, 21%). Auditory toxicity occurred less frequently in the netilmicin-clindamycin group (4.5%) than in the tobramycin-clindamycin group (21.7%). These results demonstrate that both the netilmicin-clindamycin and the tobramycin-clindamycin combinations are comparable in efficacy and in potential for causing nephrotoxicity. In this study, however, netilmicin was considerably less ototoxic than tobramycin.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clindamycin; Drug Combinations; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Random Allocation; Recurrence; Tobramycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Ear Diseases; Female; Gentamicins; Humans; Kidney Diseases; Netilmicin

Netilmicin or tobramycin was administered to 197 patients in a prospective randomized double-blind trial. Of these patients, 140 recipients of nine or more doses of netilmicin or tobramycin could be evaluated for nephrotoxicity. Fifty-five patients were able to cooperate in the administration of serial audiograms. Nephrotoxicity of similar severity developed in 7 of 73 (9.6%) recipients of tobramycin and in 7 of 67 (10.4%) recipients of netilmicin (P greater than 0.05). Mild or slight auditory toxicity developed in 5 of 28 (17.8%) recipients of tobramycin and in 2 of 27 (7.4%) recipients of netilmicin (P greater than 0.05).

Topics: Adult; Aged; Auditory Threshold; Clinical Trials as Topic; Creatinine; Double-Blind Method; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Random Allocation; Tobramycin

Netilmicin and gentamicin were compared in a multicenter clinical trial in 12 study locations. The two aminoglycosides were randomly assigned to hospitalized adult patients with systemic infections, and were administered by i.m. injection or slow i.v. infusion in divided doses generally calculated to deliver either 4-6.5 mg/kg per day of netilmicin, or 3-5 mg/kg per day of gentamicin. Lower dosages were given to patients with impaired renal function. Data from 210 patients receiving netilmicin and 212 receiving gentamicin were analyzed for efficacy. Favorable bacteriologic responses occurred in 95.5% (255/267) of the netilmicin-treated sites and in 90.1% (247/274) of the gentamicin-treated sites (p = 0.05). Netilmicin eliminated or reduced 95.6% (283/296) of all pathogens isolated from all infection sites compared with 89.5% (289/323) for gentamicin (p = 0.012). Favorable clinical responses were observed in 94.2% (275/292) of the netilmicin-treated patients and 89.5% (289/323) of the gentamicin-treated patients. Data from 377 netilmicin-treated patients and 378 gentamicin-treated patients were analyzed for safety. Evidence of nephrotoxicity probably related to treatment was observed in 8 of the netilmicin-treated patients and 14 of the gentamicin-treated patients. Audiometrically documented hearing loss probably related to treatment was observed in one gentamicin-treated patient. In one netilmicin-treated patient there were transient auditory and vestibular effects. Local tolerance to parenteral administration of the two drugs was excellent.

Topics: Adolescent; Adult; Bacterial Infections; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Male; Netilmicin; Vestibular Function Tests

The efficacy and tolerance of netilmicin was studied in 28 elderly male patients with varying degrees of renal function impairment who suffered from complicated urinary tract infections. Doses of netilmicin, equivalent to 2 mg/kg divided by milligrams of creatinine per 100 ml, were administered every 12 h. A 62% cure rate, defined as negative urine culture at 1-week follow-up, was obtained. Treatment failure correlated with impaired renal function. Nephrotoxic reaction, defined as any significant increase in serum creatinine during treatment, was found in 6 of 28 patients (21%). The increase in serum creatinine was transient in all except one of these patients. Apart from the finding of a significant correlation between nephrotoxic reaction to netilmicin and postoperative urinary tract infection, no clinical or therapeutic features correlated with nephrotoxicity; trough concentrations correlated with serum creatinine.

Topics: Aged; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Time Factors; Urinary Tract Infections

Aminoglycosides are commonly used antibiotics with excellent renal parenchymal penetration. Their clinical effectiveness is counter balanced with the risk of renal toxicity, which develops in a dose-dependent fashion. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome (BLS), or distal renal tubular acidosis.(1-4) Although tubulopathy associated with amikacin and gentamicin was reported in adults and rarely children, to the best of our knowledge, netilmicin-associated BLS neither in adults nor in children has been reported in the literature. We here report a 30-week, 770 g male preterm infant who developed BLS just after netilmicin treatment for neonatal sepsis and recovered 6 weeks after the drug cessation.

Topics: Adult; Anti-Bacterial Agents; Bartter Syndrome; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Netilmicin; Pregnancy; Sepsis

A once-daily dosing regimen for aminoglycosides is less expensive, at least as effective and possibly less toxic than multiple-daily dosing regimens. Once-daily dosing might also allow the frequency of measuring the serum concentrations of these antibiotics to be reduced since two of the major objectives of monitoring, high peak and low trough concentrations, are more likely to be achieved with this regimen. A novel strategy for monitoring serum concentrations which relies on a single sample obtained 8 h after a dose, as opposed to both trough and peak samples, is evaluated here. Serum kinetics of netilmicin were studied prospectively in 51 adult patients with initial serum creatinine concentrations of < 130 mumol/L who were treated with a median daily dosage of 400 mg. Concentrations measured 8 h after administration were within the target range of 1.5-6 mg/L in 113 of 134 dosing intervals studied. Concentrations above and below this range correlated significantly with higher and lower 24-h trough concentrations and areas under the curve respectively. There was also a significant correlation between 8-h netilmicin concentrations and nephrotoxicity (P < 0.05); a relative increase of > or = 25% in the serum creatinine concentration or an absolute increase of > 25 mumol/L was detected in 0 of 7 patients with an 8-h concentration of < 1.5 mg/L, in 3 of 33 patients (9.1%) with an 8-h concentration of 1.5-6 mg/L and in 4 of 11 patients (36%) with an 8-h concentration of > 6 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Creatinine; Drug Administration Schedule; Drug Monitoring; Humans; Kidney Diseases; Netilmicin; Prospective Studies

The pharmacokinetics of netilmicin in plasma and blister fluid were compared in 10 healthy volunteers with normal renal function and 10 voluntary patients with varying degrees of renal impairment. Netilmicin kinetics in plasma were characterized by an open two-compartment kinetic model. For the study of the kinetics of the antibiotic in blister fluid a specific kinetic distribution model was employed. In the healthy volunteers the plasma kinetics of netilmicin showed a behaviour similar to that of other aminoglycoside antibiotics, although a high blister/plasma partition coefficient was obtained, with a mean value of 4.27 +/- 1.65. The transfer of netilmicin in blister fluid governed by the constants K1b/Vb and Kbl had mean values of 0.19 +/- 0.09 h-1 l-1 and 0.25 +/- 0.10 h-1, respectively. In the patients with renal impairment plasma and blister fluid antibiotic levels showed a progressive accumulation. In these patients the affinity of netilmicin for blister fluid was significantly altered. The blister/plasma partition coefficient in this group of patients had a mean value of 2.65 +/- 1.33; the decrease being statistically significant (p = 0.023) with respect to the value obtained in the healthy volunteers. Similarly, the exit constant of netilmicin from blister fluid (Kb1) showed a statistically significant increase (p = 0.035) in the patients with renal impairment. The findings point to a loss of affinity of netilmicin for blister fluid as a result of renal impairment. Linear and logarithmic relationships were established between some pharmacokinetic parameters and creatinine clearance. Dosage schedules are proposed for netilmicin in patients with renal impairment.

Topics: Adult; Aged; Blister; Exudates and Transudates; Female; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin

Enzymuria is a well known parameter of evaluation of drugs nephrotoxicity, particularly of antibiotics. Alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT) and N-acetyl-bêta-D-glucosaminidase activities were measured in native urine. This study included 19 patients treated by an association of netilmicin-vancomycin. Enzymuria was measured on 24 hours urines at J0 then every two days during treatment. Enzymuria increased 24 or 48 hours after the beginning of the treatment. The Principal Components Analysis (PCA) of the results of enzymuria, seric urea and creatininemia shows the presence of two groups of responses. The first principal component exhibits two populations: the patients with pathological seric urea and pathological seric creatinine and the others. The PCA does not allow this discrimination using only the results of enzymuria; in contrast, with these results, the patients may be classified by the PCA on the basis of treatment duration. The enzymuria allows the clear identification of nephrotoxic drugs but does not allow the prediction of renal injury or of its aggravation.

Topics: Acetylglucosaminidase; Adolescent; Adult; Aminopeptidases; Bacterial Infections; CD13 Antigens; Child; Child, Preschool; Creatinine; Drug Therapy, Combination; gamma-Glutamyltransferase; Hexosaminidases; Humans; Kidney; Kidney Diseases; Middle Aged; Netilmicin; Urea; Vancomycin

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Gentamicins; Gram-Negative Bacteria; Humans; Kidney Diseases; Kidney Function Tests; Middle Aged; Netilmicin; Retrospective Studies; Tobramycin

Habekacin is a new aminoglycoside antibiotic. In this study we want to know the effect of increasing dose of habekacin on renal function and on renal morphology. We decide to compare the renal alterations induced by habekacin to these provoked by gentamicin, netilmicin and amikacin. Female Wistar rats received intraperitonally a single injection daily of 10, 30, 50, 150 mg/kg of habekacin for seven days. Wistar rats received also 50 mg/kg gentamicin, 50 mg/kg netilmicin and 150 mg/kg amikacin. No mortality was observed in groups treated with 10, 30, 50 mg/kg habekacin but 50 per cent of rats died with 150 mg/kg habekacin. Habekacin--30 mg/kg seven days--induced a decrease of cortical enzymatic activities, an increase of the number of lysosomes, a great accumulation of myeloid bodies, an alteration of lysosomal membranes Habekacin--50 mg/kg seven days and 150 mg/kg--induced a decrease of creatinine clearance and ultrastructural alterations of renal tubular cells. Comparative studies with other aminoglycosides showed that amikacin--150 mg/kg was the lesser nephrotoxic drug. With a same dose of 50 mg/kg, gentamicin appeared lesser nephrotoxic than habekacin and habekacin seemed to induce a same degree of renal modifications than netilmicin. With the dose of 150 mg/kg habekacin this drug was higher nephrotoxic than 50 mg/kg gentamicin. In conclusion, if it could be necessary to use habekacin and to prefer this aminoglycoside to gentamicin from an antibacterial activity point of view it is necessary to keep in mind that this drug is potentially nephrotoxic and that the dosage had to be strictly respected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Female; Gentamicins; Kanamycin; Kidney Cortex; Kidney Diseases; Netilmicin; Rats; Rats, Inbred Strains

Basic glutathione transferase released from the proximal tubular epithelium in the kidney was monitored in the urine of 69 recipients of renal allografts. The enzyme was isolated from human liver and the urinary analysis performed with radioimmunoassay. Patients receiving cyclosporine A without toxicity or rejection did not excrete this enzyme in their urine; whereas the urine of patients with cyclosporine A-induced nephrotoxicity contained significant amounts of the transferase (P less than 0.001). Patients with allograft rejection also showed increased urinary concentrations of the basic glutathione transferase, but had significantly lower values than patients with cyclosporine induced nephrotoxicity (P less than 0.001). During aminoglycoside and co-trimoxazole treatment, the urinary concentration of this transferase also increased. Patients with renal infarction showed a sudden increase in urinary transferase to very high levels. The results indicate that quantitative analysis of the basic glutathione transferase in urine is useful for monitoring renal tubular lesions present in various complications following transplantation, such as cyclosporine and antibiotic induced nephrotoxicity and renal infarction.

Topics: Adolescent; Adult; Aged; Child; Clinical Enzyme Tests; Cyclosporins; Drug Combinations; Drug Therapy, Combination; Female; Glutathione Transferase; Graft Rejection; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Netilmicin; Postoperative Complications; Radioimmunoassay; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Left-sided endocarditis caused by Pseudomonas aeruginosa is frequently associated with failure of medical therapy in man. The efficacy of ciprofloxacin and netilmicin + azlocillin has been studied in 79 rabbits with aortic valve endocarditis caused by a serum-resistant strain of P. aeruginosa. Infected animals received either: no therapy; ciprofloxacin (80 mg/kg/day); or netilmicin (6.5 mg/kg/day) + azlocillin (400 mg/kg/day). Ciprofloxacin significantly lowered vegetation titers of P. aeruginosa at days 6 and 10 of therapy compared with netilmicin + azlocillin (P less than 0.001). Similarly, ciprofloxacin was significantly more effective in sterilizing vegetations (P less than 0.005), curing P. aeruginosa endocarditis (P less than 0.001), and preventing bacteriological relapse after discontinuing antibiotic therapy (P less than 0.005). Both antibiotic regimens were equally effective in sterilizing renal abscesses. Resistance to azlocillin was occasionally observed in vivo among P. aeruginosa isolates within cardiac vegetations during the second week of therapy, but not to ciprofloxacin or netilmicin.

Topics: Abscess; Animals; Anti-Infective Agents; Aortic Valve; Azlocillin; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Kidney Diseases; Microbial Sensitivity Tests; Netilmicin; Penicillin Resistance; Pseudomonas Infections; Quinolines; Rabbits

Respiratory tract infections in intensive care units have a high fatality rate, perhaps as a result of the poor diffusion into bronchial secretions of aminoglucosides given by a systemic route. Endotracheal administration of aminoglycosides has been advocated but the optimal dosage remains to be determined. To investigate this problem we studied 13 patients free of renal failure and 6 patients with renal failure. Netilmicin was given by continuous endotracheal infusion in a daily dosage of 3 to 30 mg/kg. A good correlation was found between infused doses and serum concentrations; very high bronchial secretion concentrations were consistently found. There is a significant risk of accumulation in patients with renal failure. The characteristics of the respiratory tract secretions had no influence on the passage of netilmicin into the bloodstream. The dosages we advocate on the basis of our results are 8 mg/kg/day in patients free of renal failure and 4 mg/kg/day in patients with renal failure; serum netilmicin concentrations should not exceed 1 microgram/ml.

Topics: Adult; Aged; Aged, 80 and over; Bronchi; Female; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Respiratory Tract Infections; Trachea

Topics: Adolescent; Adult; Aged; Drug Evaluation; Female; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Urinary Tract Infections

Gentamicin, tobramycin, and netilmicin were given to rats in daily doses of either 5 or 20 mg/kg for 30 days to determine the renal accumulation kinetics of the compounds and to correlate steady-state renal parenchymal concentrations with nephrotoxicity. Four rats from each group were sacrificed daily and renal parenchymal tissue concentrations were determined microbiologically. Nephrotoxicity was assessed by changes in creatinine values in serum, renal creatinine clearances, and pathological scores. There was no indication of aminoglycoside-induced nephrotoxicity in any tests performed. The following steady-state levels resulted: 36, 148, and 176 micrograms/g after 5 mg/kg per day and 148, 260, and 510 micrograms/g after 20 mg/kg per day for tobramycin, gentamicin, and netilmicin, respectively. We conclude that aminoglycoside parenchymal accumulation in rats follows this order: tobramycin less than gentamicin less than netilmicin. Therefore, differences in the relative toxicities of gentamicin, tobramycin, and netilmicin do not correlate with the renal parenchymal accumulation of these agents and may be more dependent on intrinsic toxicity to the renal proximal tubule than to the concentration of the aminoglycoside in the kidney.

Topics: Animals; Gentamicins; Kidney; Kidney Diseases; Kinetics; Male; Netilmicin; Rats; Rats, Inbred Strains; Time Factors; Tobramycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Ear Diseases; Humans; Kidney Diseases; Netilmicin

Hydroxygentamicin, an aminoglycoside antibiotic, was administered subcutaneously to cats in doses up to 160 mg base/kg daily for 10 to 13 weeks. Gentamicin and a vehicle solution were tested as positive and negative control, respectively; in one test netilmicin was also included for comparative purposes. Several parameters, including serum urea nitrogen, serum creatinine, organ/body weight ratios, serum and tissue concentrations of the antibiotics, and renal pathology, were determined to ascertain the nephrotoxic potential of the three aminoglycosides. In addition, observations for the onset of ataxia and impairment of righting reflex were made during the course of the studies to compare the vestibular ototoxic effects of the three antibiotics. Although serum urea nitrogen and serum creatinine values increased markedly in those cats which eventually died or were sacrificed moribund, these parameters in survivors were slightly but not significantly higher than controls. Serum concentrations of the drugs were proportional to the doses administered, but renal concentrations were approximately two and five times as high for netilmicin and gentamicin, respectively, as they were for equivalent doses of hydroxygentamicin. The morphological changes observed in the kidney of cats given 60 mg base/kg of hydroxygentamicin were slightly less than those seen in cats administered 10 mg base/kg of gentamicin; similarly, kidney changes in cats given netilmicin were observed approximately twice as frequently as they were in those receiving equivalent doses of hydroxygentamicin. The nephrotoxic effects of aminoglycoside antibiotics were directly related to renal drug concentration and not to serum concentration, which was a function of dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Urea Nitrogen; Cats; Creatinine; Female; Gentamicins; Hearing Disorders; Kidney Diseases; Male; Netilmicin; Vestibular Function Tests

The nephrotoxicity of hydroxygentamicin and amikacin was examined in young adult Fischer 344 rats. Serum creatinine (SCr) and urea nitrogen (BUN) levels were not significantly affected following sc injection of 80 or 160 mg/kg/day of hydroxygentamicin for 15 days. However, 250 mg/kg of amikacin produced significant increases in both parameters and in kidney/body weight ratios. The ratios were also significantly increased after 80 or 160 mg/kg of hydroxygentamicin, but kidneys of rats receiving amikacin were considerably heavier than those of rats treated with hydroxygentamicin. The antibacterial potency of 250 mg/kg of amikacin is comparable to that of 100 mg/kg of hydroxygentamicin. Additional studies, directly comparing hydroxygentamicin, a mutational biosynthetic, with gentamicin or netilmicin, all at 40, 80, and 160 mg base/kg, and incorporating renal function parameters as well as SCr, BUN, organ weight, tissue concentration, and kidney histopathology, revealed a characteristic pattern typical of aminoglycoside nephrotoxicity in mature adult male rats. In most parameters, values in rats given hydroxygentamicin or netilmicin were normal and comparable to those in controls, but kidney/body weight ratios were significantly increased at high doses. However, kidneys of rats medicated with gentamicin at comparable doses were considerably heavier than those of hydroxygentamicin-treated rats. Significant nephrotoxicity also was seen in rats given low doses of gentamicin or netilmicin. Eosinophilic granulation and vacuolization of renal proximal tubular epithelium, interstitial inflammation, and tubular dilation were observed microscopically with all three drugs in the following descending order of severity: gentamicin greater than netilmicin greater than hydroxygentamicin. The effects on proximal tubular epithelial cells following treatment with amikacin, netilmicin, or hydroxygentamicin correlated reasonably well with renal drug concentrations, but drug concentrations of gentamicin, which produced the most extensive kidney injury, were lower than those of the other three aminoglycosides. Elevated SCr or BUN were indicative of the presence of nephrosis, but early stages of tubular epithelial degeneration were not predicted by increases in BUN or SCr. Although minimal or mild nephrosis was seldom predicted by polyuria, proteinuria, or changes in osmolality, effects observed in renal function parameters usually correlated well with renal histopathology. Howeve

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Urea Nitrogen; Body Weight; Creatinine; Gentamicins; Kidney Diseases; Kidney Function Tests; Male; Netilmicin; Organ Size; Rats; Rats, Inbred F344

The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.

Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Proteins; Dibekacin; Gentamicins; Kidney Diseases; Kidney Tubules; Male; Netilmicin; Protein Binding; Rabbits

To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg/kg/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.

Topics: Absorption; Aminoglycosides; Animals; Anti-Bacterial Agents; Gentamicins; Kanamycin; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Netilmicin; Proteins; Rats; Rats, Inbred Strains

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Gentamicins; Kidney Cortex; Kidney Diseases; Lipidoses; Liver; Netilmicin; Phospholipids; Rats; Rats, Inbred Strains; Time Factors

Little attention has been given to whether an effective concentration of an antibiotic is obtained in the urine of a patient without azotemia who has one poorly functioning kidney and a contralateral normal kidney. This study was undertaken to measure the concentration of various antibiotics in the urine from both kidneys of 20 patients with unilateral renal disease and a radiologically and functionally normal contralateral kidney. Prior to ureteric catheterization each patient received a single parenteral dose of an antibiotic. The peak urinary drug concentration from the damaged kidney per unit of its creatinine clearance exceeded that for the normal kidney for 11/13 patients treated with an aminoglycoside and 6/7 given a cephalosporin. The most severely damaged kidney had a creatinine clearance of 0.6 ml/min. This patient received sisomicin and the peak urinary concentration was only 1.8 micrograms/ml. If a damaged kidney has a creatinine clearance less than 10-15 ml/min it would seem more appropriate to use a cephalosporin rather than an aminoglycoside antibiotic.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cefazolin; Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Netilmicin; Sisomicin; Tobramycin

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Kidney Diseases; Kidney Function Tests; Netilmicin; Salmonidae; Time Factors; Tobramycin; Trout

The electrophoretic mobility of phosphatidyl inositol liposomes at pH 7.4, 25 degrees C, was reduced by aminoglycoside antibiotics, neamine and several polyamines in general accordance with the number of amino-groups on each molecule. There was good agreement between the relative position of the tested compounds on the mobility-concentration graph and available information about their relative mammalian toxicities in vivo. The slope of the graph for netilmicin was distinctively flat; a comparatively flat dose-response curve for netilmicin has been reported also from in vivo studies of nephrotoxicity. Investigation of a homologous series of alpha,omega straight chain diaminoalkanes revealed that hydrophobicity did not contribute significantly to the observed interaction in this system. L-Lysine showed the weakest effect amongst all compounds tested, supporting the view that the overall positive charge on the molecule was the major determinant of the observed effect. Further structure-activity work is required to confirm whether this 'in vitro' test is predictive of the toxicity of aminoglycoside antibiotics in man.

Topics: Aminoglycosides; Anti-Bacterial Agents; Electrophoresis; Kidney Diseases; Liposomes; Netilmicin; Polyamines; Structure-Activity Relationship

Topics: Animals; Blood Urea Nitrogen; Creatinine; Dogs; Furosemide; Gentamicins; Glucuronidase; Hexosaminidases; Kidney Diseases; Male; Muramidase; Netilmicin

Topics: Adult; Child; Creatinine; Double-Blind Method; Enzymes; Female; Gentamicins; Humans; Kidney Diseases; Middle Aged; Netilmicin; Urinary Tract Infections

29 patients with serious renal or urinary tract infections were treated with netilmicin (initial dose 1.5 mg/kg twice daily). All but two patients were bacteriologically cured and responded well clinically. 13 patients with initial renal impairment were analysed separately. Whereas the patients with initial normal renal function did not show any increase of serum creatinine levels during and after treatment, the patients with renal impairment showed a significant increase of serum creatinine during the course of treatment, but no clinical signs of renal function deterioration. During the follow-up period (18 months), serum creatinine values in all cases but one returned to the pretreatment levels. Thus, the investigation revealed that netilmicin had a good clinical and bacteriological effect without signs of persistent renal damage.

Topics: Adult; Aged; Creatinine; Female; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Pyelonephritis; Renal Dialysis; Sepsis; Urinary Tract Infections

Topics: Animals; Anti-Bacterial Agents; Blood Urea Nitrogen; Body Weight; Creatinine; Gentamicins; Kidney; Kidney Diseases; Kidney Tubules; Netilmicin; Rats; Tobramycin; Water-Electrolyte Balance

Pharmacokinetics, nephrotoxicity, and therapeutic efficacy of (2S-cis)-4-O-[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]-2-deoxy-6-O-[3-deoxy-4-C-methyl-3-(methyl-amino)-beta-L-arabinopyranosyl]-N1-ethyl-D-streptamine sulfate (netilmicin) and tobramycin were investigated in rats. The excretion rates of tubular cells and of the urinary enzyme malic dehydrogenase served as parameter of nephrotoxicity. Both compounds were, similar to other aminoglycosides, tubulotoxic within the range of dosages used for human therapy. Netilmicin, however, produced less renal damage than did tobramycin in all dosages applied. Pharmacokinetic studies revealed lower renal concentrations of netilmicin after repetitive administration. Experimental chemotherapy of the chronic E. coli pyelonephritis in rats with both aminoglycosides resulted in a significant reduction of the renal bacterial counts. In spite of approximately identical serum concentration curves and in vitro activity, especially the low dosage of netilmicin led to more favourable therapeutic results than equal doses of tobramycin. These animal experiments suggest higher renal tolerance and efficacy of netilmicin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Female; Gentamicins; Kidney Diseases; Kinetics; Netilmicin; Rats; Time Factors; Tobramycin

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 mug/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.

Topics: Adult; Aged; Female; Gentamicins; Half-Life; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Renal Dialysis

Topics: Adult; Aged; Drug Resistance, Microbial; Enterobacteriaceae Infections; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Urinary Tract Infections