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PubMed1985

Comparison of netilmicin with cefoperazone for the treatment of severe or complicated urinary tract infections.

A randomised trial was undertaken to compare the efficacy and safety of netilmicin and cefoperazone for the treatment of severe or complicated urinary tract infections. Thirty-two patients completed the study. Fifteen of 16 patients treated with netilmicin and nine of 16 treated with cefoperazone were cured. This difference was statistically significant (p = 0.037). No serious side effects or toxicity occurred with either drug, although five patients developed diarrhea after treatment with cefoperazone.

Acute Disease↗
PubMed1985

Intensive treatment of pseudomonas chest infection in cystic fibrosis: a comparison of tobramycin and ticarcillin, and netilmicin and ticarcillin.

Seventeen cystic fibrosis patients aged 3.1 years to 19.8 years had 30 courses of intensive treatment for relapse of their pseudomonas chest infection. The combination of netilmicin and ticarcillin was compared with tobramycin and ticarcillin in an open study. A significant subjective and objective improvement occurred in all patients. Pseudomonas was cleared temporarily from the sputum in 11 out of the 30 courses of treatment (37%). There was no significant difference between the netilmicin and tobramycin groups, nor evidence of sustained renal or ototoxicity. Intensive therapy of pseudomonas chest infection in cystic fibrosis patients is described in detail.

Adolescent↗
PubMed1987

Experimental pneumococcus infection in mice: correlation of bactericidal activity in vitro with the effect in vivo for gentamicin, netilmicin and tobramycin.

An experimental model in mice, incorporating the intraperitoneal inoculation of a Streptococcus pneumoniae type 3, was used to evaluate the effect in vivo after single-dose administration of the three aminoglycosides, gentamicin, tobramycin and netilmicin, and to correlate this effect with their in vitro activity against the pathogen, in particular the bactericidal rate. The minimal inhibitory concentrations (MIC's), which were equal to the minimal bactericidal concentrations (MBC's), were 12.5 micrograms/ml for netilmicin, and 25 micrograms/ml for the two other aminoglycosides, respectively. All three antibiotics showed excellent bactericidal activities even at concentrations 1/4 times the MIC's, but the bactericidal rate was clearly lower for tobramycin than for the two other aminoglycosides. The effect in vivo measured as the 50% effective dose (ED50) closely reflected the relative bactericidal activities of the drugs. Of the pharmacokinetic parameters investigated on dosages equal to the ED50's for the three drugs, the best to correlate with the bactericidal rates in vitro were the peak serum concentrations.

Animals↗
PubMed1980

Comparison of netilmicin and gentamicin pharmacokinetics in humans.

In a crossover study, single doses of netilmicin and gentamicin were administered intramuscularly, each at 1.0 and 2.5 mg/kg. The serum concentrations, analyzed by a two-compartment open model with a first-order absorption, indicated that the pharmacokinetics of the drugs are essentially the same. Both drugs were rapidly absorbed and distributed after administration. No significant differences were observed between the two drugs in disposition half-life, rate of distribution and elimination, area under the serum concentration-time curve, urinary excretion, total body clearance, and renal clearance. After 1.0 mg/kg, the maximum serum concentration of netilmicin (5.18 microgram/ml) was only slightly lower than that for gentamicin (5.76 microgram/ml), but no difference was found after the 2.5-mg/kg dose.

Adolescent↗
PubMed1981

Pharmacokinetics of netilmicin in children with and without cystic fibrosis.

The pharmacokinetics of intravenous netilmicin was studied in cystic fibrosis (CF) and non-CF patients who were closely matched according to age. The serum concentrations showed a moderately higher variance within the CF group. The serum half-life in CF patients was 1.37 h compared with 2.29 h in the non-CF subjects (P less than 0.05). The apparent distribution coefficients were 0.306 and 0.356 liters/kg in the CF and non-CF groups, respectively. The mean body clearance was 6.6 liters/h per 1.73 m2 in the CF group compared with 5.3 liters/h per m2 in the non-CF controls, but the difference was not significant. The mean renal clearance in CF patients was 4.7 liters/h per 1.73 m2. From a pharmacokinetic point of view, the dosage of netilmicin required may be the same in CF as in non-CF patients.

Child↗
PubMed1982

Assay of netilmicin, using enzyme immunoassay for gentamicin.

A homogenous enzyme immunoassay for the quantitative determination of netilmicin in serum was developed. The procedure utilizes a commercially available assay for gentamicin (EMIT; Syva Co., Palo Alto, Calif.). The method was adapted to a microcentrifugal analyzer, and log-logit regression analysis was performed with a computer. The results of samples assayed by this method correlate well with microbioassay (r2 = 0.985) and radioimmunoassay (r2 = 0.986). This method is not only precise and accurate, but also very rapid and economical and compares favorably to other available methods of netilmicin assay.

Gentamicins↗
PubMed1987

Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance.

An in vitro pharmacokinetic model was used to study the comparative antibacterial activities of multiple-dose regimens of enoxacin and netilmicin. Strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were exposed to changing drug concentrations, mimicking human two-compartment pharmacokinetics. Oral administration was simulated for the quinolone, and intravenous administration was simulated for the aminoglycoside. Similar ratios of peak concentration to MIC resulted in similar changes in bacterial concentrations over time with both compounds. Following the initial dose, a rapid bactericidal effect occurred, with a greater than 99% reduction of the bacterial counts within 4 h at peak concentrations more than three times the MIC. However, bacterial regrowth occurred within 24 h unless the peak concentration/MIC ratio exceeded 8:1 (P less than 0.01). For the regrowing bacteria, MICs were four- to eightfold higher, and little or no bactericidal effect occurred following the second and subsequent doses. These data demonstrate the equally potent bactericidal activity of orally administered enoxacin and intravenously administered netilmicin. Selection of resistant subpopulations was similar with each drug. The peak concentration/MIC ratio may be an important parameter in the clinical use of quinolone and aminoglycoside antibiotics.

Administration, Oral↗
PubMed1983

Infection with netilmicin resistant Serratia marcescens in a special care baby unit.

An outbreak of colonisation and infection with a netilmicin resistant strain of Serratia marcescens occurred in a special care baby unit. S marcescens was isolated from a total of 13 babies; significant infection occurred in five, of whom two died. Epidemiological investigation failed to detect a common source but gastrointestinal colonisation of babies formed a prolonged and possibly important reservoir for infection. Containment proved difficult until the unit was closed to new admissions, and even then spread to a temporary unit ensued. O Serotyping and bacteriophage typing disclosed a single epidemic strain. This produced an aminoglycoside acetylating enzyme (AAC(6')) conferring resistance to netilmicin and tobramycin and moderate resistance to amikacin. Use of gentamicin resulted in the isolation of serratia with increased resistance to all aminoglycosides, and, similarly, increased resistance to third generation cephalosporins emerged with their use.

Acetyltransferases↗
PubMed2005

Gentamicin induced ototoxicity during treatment of enterococcal endocarditis: resolution with substitution by netilmicin.

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.

Aged↗
PubMed1980

In vitro activity of netilmicin, gentamicin, tobramycin and amikacin against glucose fermenting and nonfermenting bacteria.

The in vitro activity of netilmicin was compared to gentamicin, tobramycin and amikacin against 461 strains of glucose fermenting and nonfermenting bacteria. The minimum inhibitory concentrations of netilmicin, gentamicin and tobramycin against the majority of Enterobacteriaceae, Staphylococcus and Streptococcus were quite similar. Gentamicin, however, was approximately fourfold more active against strains of S. marcescens. Amikacin was the most effect antibiotic against strains of fermenting and nonfermenting bacilli resistant to at least one aminoglycoside. Many gentamicin-resistant species of nonfermenting bacilli, however, remain highly resistant to all four aminoglycosides tested.

Amikacin↗
PubMed1982

Interactions of antimicrobial drugs and combined phagocytic/serum bactericidal activity of defibrinated human blood against Serratia marcescens. II. Aminoglycosides: amikacin, gentamicin, and netilmicin.

Minimal bactericidal concentrations of the aminoglycoside antibiotics amikacin, gentamicin, and netilmicin killed intraphagolysosomal test bacteria of selected assay strains of Serratia marcescens, though not as efficiently as rifampin. The system employed consisted of 55 vol% of fresh defibrinated human blood treated with 2 mg/ml of phenylbutazone which permitted ingestion of bacteria, but selectively inhibited microbicidal activity of the peripheral blood leukocytes. Extraphagocytic bacteria were killed with the aid of group A (phage tail) bacteriocins of S. marcescens. Inhibitory and subinhibitory concentrations of amikacin, gentamicin, and netilmicin combined with 55 vol% of defibrinated blood, respectively, yielded additive effects against all test strains of S. marcescens utilized and against Escherichia coli control strain ATCC 25922.

Amikacin↗
PubMed1985

Ro 17-2301: in vitro comparison with aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin.

The in vitro activity of the novel monobactam antibiotic, Ro 17-2301 has been compared with those of aztreonam, imipenem, ceftazidime, cefotaxime and netilmicin. A total of 438 clinical isolates of aerobic gram-negative rods were employed and an agar dilution method was used for measurement of MIC. Ro 17-2301 was highly active against a wide variety of Enterobacteriaceae species (MIC range less than or equal to 0.03-8, MIC50 less than or equal to 0.03, MIC90 0.06 mg/l). The activity of aztreonam parallelled that of Ro 17-2301 although the latter seemed to have more uniformly high activity against Klebsiella sp. The other agents showed generally high activity against Enterobacteriaceae except netilmicin against Providencia stuartii (MIC50 4, MIC90 greater than or equal to 16 mg/l). Activity against Pseudomonas aeruginosa. was more variable. Ro 17-2301 and aztreonam were moderately active (MIC50 2, MIC90 8 and 16 mg/l, respectively). Imipenem was the most active agent against Acinetobacter, whereas Ro 17-2301 was moderately active. In conclusion, Ro 17-2301 shows impressive activity against Enterobacteriaceae and moderate activity against Acinetobacter and P. aeruginosa. Ro 17-2301 may well prove to be a useful agent in the treatment of gram-negative infections.

Acinetobacter↗
PubMed1992

Netilmicin plus ceftriaxone versus amikacin plus ceftriaxone in the treatment of infections in granulocytopenic patients.

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Adult↗
PubMed1994

Teicoplanin plus pefloxacine versus teicoplanin plus netilmicin in empiric therapy of febrile patients with cancer and neutropenia. A randomized study of two once daily regimens in patients with previously inserted catheters.

In a comparative randomized trial, teicoplanin 5 mg/kg plus either netilmicin 5 mg/kg or pefloxacine 10 mg/kg was administered in a once daily empiric therapy to 40 cancer patients with fever and neutropenia after cytotoxic chemotherapy. Both regimens were analyzed with respect to the localisation of the underlying disease, catheter presence and agents isolated from blood culture. The cure and improvement rate were 80% (teicoplanin plus netilmicin) and 85% (teicoplanin plus pefloxacin), with no statistically significant difference between the groups. Teicoplanin with either an aminoglycoside or a quinolone administered once daily seems to be a suitable approach in empiric therapy for fever in neutropenia and may prevent catheter insertion in cancer patients.

Adult↗
PubMedDate not supplied

Comparison of the bactericidal action of amikacin, netilmicin and tobramycin in free and liposomal formulation against Pseudomonas aeruginosa.

The rates at which free, cationic and anionic liposomal forms of amikacin, netilmicin and tobramycin kill Pseudomonas aeruginosa were studied in vitro. Control inocula with no antibiotic yielded 6.76, 9.53 and 9.74 log CFU/ml at 0, 6 and 24 h, respectively. Empty anionic or cationic liposomes had no effect on bacterial growth. The killing rates of free antibiotics against the bacterial strain were not enhanced by the addition of either empty anionic or cationic liposomes. After 6 and 24 h of exposure at 1, 2 and 4 times the minimum inhibitory concentrations, free amikacin, netilmicin and tobramycin demonstrated a more rapid bactericidal effect than encapsulated anionic or cationic liposomes. The killing rates of liposomal aminoglycosides were lower than those of free aminoglycosides at identical concentrations, suggesting that only fractions of the encapsulated drugs were released from liposomes.

Amikacin↗
PubMed1979

Comparison of multiple-dose regimens of netilmicin in patients with urinary tract infections.

A clinical trial involving forty hospitalized patients with urinary tract infections was conducted to compare the effectiveness and tolerance of four dosage regimens of netilmicin: 1, 2, 3, and 4 mg/kg administered twice daily for 7 or 8 days. Each of the dosages was effective and the first three were equally well tolerated. At 4 mg/kg there was one case of renal dysfunction possibly related to netilmicin therapy. Serum concentrations of the drug measured 1 hour after injection were dose-related, as were those measured 1 hour before administration; no appreciable accumulation occurred with any of the regimens.

Adult↗
PubMedDate not supplied

Comparative cochlear toxicities of streptomycin, gentamicin, amikacin and netilmicin in guinea-pigs.

All the aminoglycoside antibiotics now in clinical use are ototoxic. This study was designed to compare the toxic effects of four aminoglycoside antibiotics, streptomycin, gentamicin, amikacin and netilmicin, administered to guinea-pigs systemically (at respective doses of 125 mg/kg, 50 mg/kg, 150 mg/kg or 37.5 mg/kg, twice daily for 1 week) or topically via the transtympanic route (0.25 ml/kg in 4% saline, twice daily for 1 week). Chosen doses were 10-20 times higher than the recommended human dosage. Cochlear damage was observed in all animals that were given systemic and local aminoglycosides. The severity of the cochlear damage was in the order gentamicin, amikacin, streptomycin, netilmicin, with gentamicin being the most toxic. No statistically significant difference between the severity of cochlear damage resulting from the systemic and topical applications was detected.

Administration, Topical↗