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PubMed1977

Renal pharmacology of netilmicin.

Netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was studied for its effects on kidney function and mechanisms by which it is handled by the kidneys. Measurements of glomerular filtration rate (GFR) and urinalysis in chronic rat studies indicated that the nephrotoxicity of netilmicin was remarkably less than that of gentamicin. Gentamicin caused a dose-related reduction in GFR in association with glucosuria and elevated fractional excretion of K(+). By contrast, high doses of netilmicin produced only slight reduction in GFR with increased fractional excretion of K(+) but without glucosuria. In separate experiments, rats were shown to excrete 71 to 90% of netilmicin or gentamicin in 24 h after daily intramuscular administration of doses of 20 or 40 mg/kg for 4 days. In acute experiments on anesthetized dogs, GFR and renal plasma flow were unaffected at serum levels of 11.0 +/- 0.6 mug/ml maintained by constant infusion of netilmicin for 5 h. The renal clearance of netilmicin was significantly correlated with GFR. The urinary output of netilmicin was 80.0 +/- 4.2% of the infusion rate and was independent of urine flow over the range of 0.04 to 0.33 ml/kg per min. Preferential accumulation of netilmicin occurred in the renal cortex; the cortex-serum and medulla-serum ratios were 9.9 +/- 1.2 and 4.2 +/- 0.6, respectively. In addition, the extraction ratio of netilmicin, which was lower than that of inulin, suggested that netilmicin reabsorption occurs in the proximal tubule and results in cortical accumulation. It is concluded that netilmicin, like gentamicin, is excreted by the dog kidney by glomerular filtration plus limited reabsorption. However, the new drug is characterized by low intrinsic nephrotoxicity in rats.

Animals↗

PubMed1981

Compatibility of netilmicin sulfate injection with commonly used intravenous injections and additives.

The compatibility and stability of netilmicin sulfate in a concentration of 3 mg/ml in 37 intravenous injections and in 5% dextrose and 0.9% sodium chloride injection with 26 commonly used additives were studied. Compatibility between an intravenous administration set and selected admixtures were also evaluated. The admixtures were stored at 4 and 25 degrees C for seven days. After mixing and on days 1, 3, and 7, all admixtures were evaluated for netilmicin potency, pH, color, osmolarity, and clarity. A microbiological assay was used to measure netilmicin potency. No changes in netilmicin potency, pH, osmolarity, color, or clarity were observed in any of the 37 netilmicin sulfate admixtures. Similarly, no changes in pH, osmolarity, or clarity were seen in the admixtures of netilmicin sulfate with a second additive. Netilmicin activity was retained for seven days in 22 of the 26 admixtures with a second additive. Netilmicin sulfate in admixtures with multivitamin injection or vitamin B complex (Upjohn) was stable for only one day; with diphenhydramine hydrochloride or neostigmine methylsulfate, for only three days. No incompatibilities between the intravenous infusion set and admixtures of netilmicin sulfate were apparent. Netilmicin sulfate injection is compatible and stable for at least seven days stored at 4 and 25 degrees C when mixed in 37 intravenous injections, and when mixed individually with 22 additives in 5% dextrose and 0.9% sodium chloride injection.

Colorimetry↗

PubMed1976

In vitro study of netilmicin compared with other aminoglycosides.

Netilmicin (Sch 20569) is an ethyl derivative of gentamicin C(1a) that is active against most Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus isolates. Among 342 clinical isolates tested, all staphylococci; 92% of Escherichia coli, 93% of Klebsiella pneumoniae, and 92% of Enterobacter were inhibited by 0.8 mug or less of netilmicin per ml, but only 78% of P. aeruginosa were inhibited by 3.1 mug or less per ml. Most clinical isolates of enterococci, Serratia marcescens, and Providencia were not inhibited by 3.1 mug of netilmicin per ml. Like other aminoglycosides, the netilmicin in vitro activity was markedly influenced by the growth medium used, with activity decreased by sodium, calcium, and magnesium. Netilmicin was more active at alkaline pH. Addition of magnesium to Pseudomonas or Serratia pretreated with netilmicin produced inhibition of killing. Netilmicin was more active than gentamicin, sisomicin, tobramycin, or amikacin against E. coli and K. pneumoniae. Netilmicin inhibited growth of all gentamicin-resistant isolates of Klebsiella and Citrobacter tested, but only 73% of E. coli; Pseudomonas and Providencia were resistant to netilmicin. Most Serratia (95%) and indole-positive Proteus (83%) isolates were resistant to netilmicin but were inhibited by amikacin.

Amikacin↗

PubMedDate not supplied

Netilmicin sulfate: a comparative evaluation of antimicrobial activity, pharmacokinetics, adverse reactions and clinical efficacy.

Netilmicin, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside antibiotic that was recently marketed in the United States. Its role in therapeutics is not yet established. The pharmacokinetic profile of netilmicin is very similar to that of gentamicin. Its antimicrobial spectrum and clinical efficacy is similar to that of gentamicin, tobramycin and amikacin. It is less active in vitro against Pseudomonas aeruginosa that gentamicin and tobramycin, but in clinical trials the efficacy of netilmicin against the organism has been similar to other aminoglycosides. Netilmicin is active against some gentamicin and tobramycin-resistant strains of gram-negative bacilli, particularly those harboring adenylating and phosphorylation enzymes. Most of these strains are sensitive to amikacin as well, and amikacin is also active against most netilmicin-resistant strains of these bacteria. Therefore, amikacin remains the aminoglycoside of choice against gentamicin tobramycin and netilmicin-resistant gram-negative bacilli. In comparison to other currently available aminoglycosides, a lower frequency of nephrotoxicity and ototoxicity has been observed in laboratory animals given netilmicin. This has not been unequivocally demonstrated in humans. The frequency of nephrotoxicity in humans has been similar to that of other aminoglycosides. The frequency of ototoxicity associated with netilmicin in humans has been low but not significantly less than in other aminoglycosides, except in one trial. If further studies document a significantly lower frequency of ototoxicity with netilmicin, it may become the aminoglycoside of choice for patients with significant risk factors for ototoxicity, such as advanced age, renal impairment, concomitant ototoxic drug therapy and prolonged aminoglycoside administration.

Animals↗

PubMed2002

Release of netilmicin and vancomycin from cancellous bone.

First, we studied the effect of the following variables used for netilmicin- and vancomycin-impregnation of cancellous bone: a) antibiotic concentration of the impregnation fluid, b) time used for impregnation, c) pH of the impregnation fluid, d) the degree of bone morselizing and e) antibiotic combination. An increase in the antibiotic concentration of the impregnation fluid increased the amount of antibiotics released from bone. In addition, the amount of vancomycin eluted was also dependent on the time used for impregnation. The fraction of the total amount of netilmicin and vancomycin released after 24 h was 80% and 30%, respectively. More netilmicin and vancomycin were eluted from bone impregnated with antibiotics at pH 7 than the amount eluted from bone impregnated at pH 3. More netilmicin was eluted from fine morselized bone than from coarse morselized bone. By combining netilmicin and vancomycin in the impregnation fluid, the release of vancomycin was reduced. Secondly, we analyzed if the release of antibiotics from bone was complete: 99.9% of the total amount of netilmicin adsorbed to the bone was released by elution during 6 weeks. Finally, after implantation of netilmicin-impregnated bone in rabbit femur condyle, we measured netilmicin and vancomycin in serum: peak serum values of netilmicin were 4.2 (3.7-4.7) mg/L 2-3 h postoperatively.

Animals↗

PubMed2005

Once-daily netilmicin for neutropenic pyrexia in paediatric oncology.

AIM: To establish the safety and efficacy of single daily intravenous netilmicin 6 mg/kg with piperacillin 100 mg/kg every 8 h for empirical, first-line management of children with neutropenic pyrexia following cytotoxic chemotherapy. METHODS: Observational study of children admitted to a regional oncology unit from October 1999-April 2002. Primary outcome measure was temperature 72 h after commencing antibiotic therapy; secondary measures were mortality, nephrotoxicity, symptomatic ototoxicity and serum netilmicin levels. RESULTS: 280 episodes for 128 patients (median age 7.1 y) were documented, and 248 episodes were evaluated and compared with a previous cohort of 100 episodes for which the only difference was administration of netilmicin three times daily. Twenty-seven per cent of single-dose netilmicin episodes remained febrile at 72 h compared to 32% in the comparator group (difference -4.7%; 95 % CI: -6.8% to 16.2%; p = 0.41). No patients died and we were unable to find evidence of nephrotoxicity or ototoxicity. Eighty-nine per cent of "peak" serum netilmicin levels measured 30 min after infusion were 10 mg/l or greater, and 94% and 86% measured 12-16 h after the first and third dose, respectively, were 1 mg/l or less. Peak serum netilmicin level measurements and 12-16-h measurements after the first dose were abandoned after the first 180 episodes. CONCLUSIONS: Netilmicin can safely be given as a single daily dose to children with febrile neutropenia who do not have biochemical evidence of nephrotoxicity. Monitoring peak serum levels of netilmicin is unnecessary. Levels taken 12-16 h after the third dose are adequate to monitor therapy if used in conjunction with a therapeutic guideline detailing the response to abnormal serum creatinine and netilmicin levels.

Adolescent↗

PubMed1991

Effect and pharmacokinetics of netilmicin given as bolus intramuscular administration: an open comparative trial versus amikacin and fosfomycin in elderly patients affected by urinary tract infections.

A randomized comparative open clinical trial was performed on 96 hospitalized patients of both sexes, most of whom (84.4%) over 60 years of age, affected by simple and complicated urinary tract infections. Patients were divided in three unequal sized groups and treated with a single administration of netilmicin (5 mg/kg intramuscularly), of amikacin (15 mg/kg i.m.) or of fosfomycin (3 g per os). Patients were evaluated clinically and microbiologically before the beginning of the therapy, 1, 7, 15, 30 days thereafter and at monthly intervals, up to the 18th month, after the drug administration. The pharmacokinetic study was performed in six elderly patients of both sexes, apparently in good general health, except for their urinary tract infections. Symptoms of urinary tract infection disappeared in 50 out of 53 (94.3%) patients treated with netilmicin 14.48 +/- 9.6 hours after the drug administration, in 22 out of 23 (95.6%) of those treated with amikacin after 31.9 +/- 14.3 hours and in 16 (84.2%) out of 19 of symptomatic patients treated with fosfomycin after 37.5 +/- 10.6 hours. The disappearance of symptoms in netilmicin-treated patients is significantly (p less than 0.01) faster than in the other two groups. Twenty-four hours after the administration, netilmicin and amikacin produced sterilization of the cultures in more than 95% of cases, fosfomycin in 90%. Of those patients in which sterilization of cultures was achieved about 70%, in the netilmicin group, and 50% in the other two treatment groups had sterile urine cultures after one month. At the end of the study, 18 months later, more than 60% of the patients treated with netilmicin, the infection had not recurred in comparison with 39.1% and 50% in the amikacin and fosfomycin groups respectively. If only the patients with uncomplicated infections were considered, 88.9% and 83.3% had sterile cultures after 1 and 18 months respectively in the netilmicin group. The corresponding figures in other two groups were: 66.7% for both time intervals in the case of amikacin and 60% both for 1 and 18 months in the case of fosfomycin. The pharmacokinetic results indicate that netilmicin is rapidly absorbed and distributed from the injection site, possesses a beta half-life of about two hours and is mainly excreted by the kidneys. The single dose administration produces very high urinary concentrations of the drug in the first 24 hours and concentrations above 4 micrograms/ml, the 90% minimum inhibitory concentration cut-off point for netilmicin sensitive strains, for four days(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1990

Effect of E. coli pyelonephritis on the intracortical accumulation kinetics of gentamicin and netilmicin in rats.

The role of serum levels on the intrarenal accumulation kinetics of gentamicin and netilmicin in normal and infected kidneys was evaluated in a short-term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin and netilmicin achieving individual steady-state serum levels ranging from 0.5 to 120 micrograms/ml. The model of pyelonephritis used resulted in severe left pyelonephritis and mild right pyelonephritis. Only the right infected kidneys were studied. Gentamicin and netilmicin cortical concentrations were analysed as a function of serum levels by linear (least-squares regression analysis) and non-linear regression. For the non-linear regression analysis, the Michaelis-Menten kinetic was the best fitting curve. Steady-state elevation of serum concentrations of gentamicin and netilmicin was associated with a non-linear increase of cortical concentrations in normal kidneys, suggesting a saturable process. By contrast, in the mildly-infected right kidneys, the steady-state elevation of serum concentrations of gentamicin was associated with a linear increase of cortical concentrations while the accumulation kinetic of netilmicin showed a saturable process. At lower serum levels (therapeutic range, from 0.5 to 15 micrograms/ml) both gentamicin and netilmicin showed a first order kinetics of accumulation and netilmicin accumulated less than gentamicin in normal kidneys (p = 0.0004). By contrast, the uptake of netilmicin was higher in the right infected kidneys, as compared to the uptake of netilmicin in the normal kidneys, (p = 0.00005), and as compared to gentamicin in the respective kidneys. We conclude that renal infection modifies the intrarenal accumulation of aminoglycosides.

Animals↗

PubMed1982

[Clinical trial of netilmicin in infections of respiratory organs and studies on its penetration into pleural fluid II. (author's transl)].

To 10 cases with respiratory infections, 200 mg, twice daily, of netilmicin was administered without other antibiotics and the following results were obtained. 1) Netilmicin was administered to 2 cases of pneumonia and 8 cases of bronchitis for 7 to 30 days, and 4 remarkably effective and 6 effective cases were observed, that is, netilmicin was effective in all cases. 2) Abnormal laboratory test values were found in 2 cases; 1 case showed slightly elevated creatinine value, and 1 case showed slightly increase GTP value, and these values were normalized rapidly without any treatment after discontinuation of netilmicin administration. Netilmicin 100 mg was intramuscularly injected to 15 patients with pleural effusion to see the time-course distribution of the drug to serum and to pleural fluid by determining the concentration of netilmicin. 1) Netilmicin concentrations in serum reached the peak at 30 minutes after the intramuscular injection and it gradually decreased, while in the pleural fluid, it reached the peak at 3 hours after the injection, and the peak value in the pleural fluid in average was 2.63 +/- 1.98 micrograms/ml, and it was still detectable at 24 hours after the injection. 2) The ratio of netilmicin concentrations in the serum and pleural fluid at the peak was 31.7 +/- 23.4%, and distribution of netilmicin into the pleural fluid was considered to be high enough.

Adult↗

PubMed1981

Multicenter comparative evaluation of netilmicin and gentamicin in adult patients. Efficacy and safety.

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.

Adolescent↗

PubMed1996

Pharmacokinetics and bactericidal activity of a single daily dose of netilmicin in the treatment of CAPD-associated peritonitis.

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.

Acinetobacter↗

PubMed1978

Kinetics of netilmicin and gentamicin.

The kinetic parameters of netilmicin were studied in normal human subjects. In the intravenous study a steady-state was obtained in 4 subjects by the constant infusion of 2 mg/kg of netilmicin during the first hour followed by 0.5 mg/kg/hr for each of three successive hours. Creatinine clearance was greater than the simultaneous serum and renal clearance of netilmicin. In the intramuscular study 6 subjects received a single injection of 1 mg/kg of netilmicin followed by the same dose of gentamicin 1 wk later. A mean peak serum levels of 3.9 microgram/ml was found for both antibiotics, but the mean serum half-life of netilmicin was shorter than that of gentamicin. Doubling the intramuscular dose of netilmicin approximately doubled the peak serum level. In both studies 75% to 90% of the netilmicin was recovered in the urine within the first 24 hr. Netilmicin appears to be primarily excreted by glomerular filtration. The apparent volume of distribution was similar to that reported for other related aminoglycosides. Netilmicin and gentamicin have similar kinetic parameters. There were wide individual differences among normal subjects with both drugs.

Female↗

PubMed1991

Distribution kinetics of netilmicin in human blister fluid: effect of renal impairment.

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.

Adult↗

PubMed1985

Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats.

Netilmicin, a semisynthetic aminoglycoside antibiotic, is less ototoxic in a variety of species than other aminoglycosides currently in therapeutic use. In this study, mixed-breed cats (four/group) were given daily sc injections of netilmicin (20, 40, and 80 mg/kg), gentamicin (20 and 40 mg/kg), or tobramycin (20, 40, and 80 mg/kg) for up to 30 weeks or until ototoxicity was observed. The animals were examined throughout the study for effects on cochlear and vestibular function. Hematologic, serum chemical, and drug-serum (24-hr postdose) assays were performed at approximate monthly intervals during the dosing period. The cochleae, kidneys, and liver were examined microscopically. The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin (40 and 80 mg/kg) or gentamicin. No vestibular dysfunction was observed in any of the netilmicin 20-mg/kg-dosed cats, in two cats each of the tobramycin 20-mg/kg and netilmicin 40-mg/kg groups, and in one netilmicin 80-mg/kg-dosed animal. Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with gentamicin at 20 and 40 mg/kg and tobramycin at 40 and 80 mg/kg. Less than 50% of the tissues from cats of the tobramycin 20-mg/kg and netilmicin 40- and 80-mg/kg-dosed groups had similar degenerative cochlear changes. No cochlear damage was noted in any of the cats given netilmicin at 20 mg/kg. Results of the clinical laboratory determinations were generally unremarkable. Proximal tubular degeneration was the principal finding observed in the kidneys of the animals. Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin.

Animals↗

PubMed1990

Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass.

The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery.

Adolescent↗

PubMed1983

Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin.

254 patients with serious gram-negative bacillary infections were enrolled into a multicentre, randomised, blind clinical trial and treated with tobramycin-ticarcillin or netilmicin-ticarcillin. The two treatment groups were similar as to sex, age, and weight. The mean daily dose of netilmicin (237 mg) was higher than that of tobramycin (211 mg), p less than 0.01, but the mean duration of therapy was longer with tobramycin (9.4 days versus 8.7 days), p less than 0.01. The netilmicin cohort also had more serious underlying diseases, p less than 0.028. Clinical (tobramycin, 93% and netilmicin, 91%) and bacteriological responses (tobramycin, 87% and netilmicin, 89%) were similar. 84 tobramycin and 73 netilmicin patients had serial audiograms. Eighth nerve deficits developed in 10 (12%) tobramycin and two (3%) netilmicin patients, p = 0.037. Drug-related renal dysfunction developed in 5 (4%) of 114 tobramycin patients whose renal function was monitored and in 1 (1%) of 116 netilmicin patients, p = 0.12.

Anti-Bacterial Agents↗

PubMed1999

Improved efficacy with nonsimultaneous administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus in in vitro and in vivo models.

The effect of combined administration of netilmicin and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) was investigated by using in vitro and in vivo models. Thirty one isolates of MRSA were tested for sensitivity to netilmicin, minocycline, and combination of both by the chequer board method. We used then a dynamic in vitro system, which simulates in vivo serum kinetics, to assess the effect of various combination regimens of these antibiotics against an MRSA isolate with a fractional inhibitory concentration index of 0.25. The following dose regimens were compared: netilmicin given alone; minocycline given alone; both antibiotics given simultaneously; netilmicin followed by minocycline at 2 h; or minocycline followed by netilmicin at 2 h. Netilmicin showed a stronger activity than minocycline. On the other hand, their combination was synergistic against 19% of isolates and additive against 77% of isolates. Against one isolate only, it was indifferent, and no antagonism was observed. In the auto-simulation system, the combination of antibiotics was generally more effective than single drugs, with the regimen netilmicin followed by minocycline at 2 h showing the highest antibacterial effect. In the mouse model of pulmonary infection, the bacterial counts and histopathological findings of the lungs improved by treatment with this regimen. This regimen led also to a significantly high survival rate of mice with systemic infection compared to the other treatment regimens. Therefore, it was concluded that administration of netilmicin followed by minocycline at 2 h may be an effective combination against MRSA infection.

Animals↗

PubMed1986

Bactericidal activity of netilmicin compared with gentamicin and streptomycin, alone and in combination with penicillin, against penicillin tolerant viridans streptococci and enterococci.

Netilmicin was compared with gentamicin and streptomycin for in-vitro activity against 30 strains of penicillin-tolerant streptococci including 16 strains of enterococci. Both netilmicin and gentamicin tested alone at 4 mg/l caused 99.9% kill of more than half of the 13 strains of viridans streptococci tested, whereas streptomycin, 4 mg/l, had no bactericidal effect against these strains. Netilmicin, gentamicin and streptomycin tested alone at 8.0 mg/l against 10 strains of Streptococcus faecalis resulted in 99.9% kill of six, one and zero strains respectively. Combinations of penicillin with 2 mg/l of either netilmicin or gentamicin resulted in bactericidal synergy against 12 of 13 strains of viridans streptococci and all 10 strains of S. faecalis after 18 to 24 h incubation. Parallel experiments showed that higher concentration of penicillin were required to obtain 99.9% kill of 10 streptococcal strains when 4 mg/l streptomycin was compared with 2 mg/l of the other aminoglycosides. Killing curves showed similar bactericidal synergy for netilmicin-penicillin and gentamicin-penicillin combinations against most streptococci tested after 24 h incubation but there was sometimes a greater bactericidal effect noted with netilmicin after only 6 h incubation of the broth or after 48 h incubation. The results of this in-vitro study suggest that netilmicin is at least as effective as gentamicin as a bactericidal synergic agent with penicillin against penicillin-tolerant viridans streptococci and S. faecalis strains isolated from patients with endocarditis. Neither gentamicin or netilmicin were effective as bactericidal synergic agents with penicillin against 4 of 6 strains of S. faecium tested.

Drug Synergism↗