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PubMed1989

Evaluation of the combination effects of ampicillin or vancomycin combined with streptomycin, gentamicin, tobramycin or netilmicin against enterococci.

Seven strains of Streptococcus faecalis, of which two possessed high-level resistance to streptomycin (MIC greater than or equal to 2000 mcg/ml), and two strains of Streptococcus faecium were evaluated with respect to killing-effect and duration of post-antibiotic effect (PAE) of ampicillin and vancomycin in combination with streptomycin, gentamicin, tobramycin and netilmicin. No synergistic combination effects were seen with the two strains highly-resistant to streptomycin or with the two Streptococcus faecium strains to netilmicin and tobramycin. When these strains were excluded, no significant difference in average killing could be detected between the four aminoglycosides. The mean prolongation in recovery period of susceptible strains was significantly longer with combinations of ampicillin and netilmicin or streptomycin as compared with either gentamicin or tobramycin. A similar relationship was seen for combinations of vancomycin with the four aminoglycosides.

Ampicillin↗
PubMed1979

Netilmicin treatment of complicated urinary tract infection in patients with renal function impairment.

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.

Aged↗
PubMed1980

Tentative interpretive criteria for the diffusion susceptibility test using 30-microgram netilmicin disks.

The disk diffusion inhibitory zone diameters for 10-microgram and 30-microgram netilmicin disks were correlated with minimum inhibitory concentrations against 471 clinical strains tested in cation-supplemented Mueller-Hinton broth. Regression line and error-rate bounded analysis favored the use of 30-microgram netilmicin disks utilizing zone size breakpoints of greater than or equal to 17 mm to indicate susceptibility (less than or equal to 8 microgram/ml) and less than or equal to 13 mm to indicate resistance (greater than 32 microgram/ml). Significant minor interpretive errors may be expected when testing populations of Pseudomonas that have netilmicin minimum inhibitory concentrations near the intermediate range (16 microgram/ml).

Anti-Bacterial Agents↗
PubMed1981

In vitro studies with Win 42122-2: comparison with gentamicin, netilmicin, and amikacin.

The in vitro activity of Win 42122-2 against gram-negative clinical isolates was compared in serial twofold broth dilution tests with gentamicin, netilmicin, and amikacin. Against 173 gentamicin-susceptible Enterobacteriaceae, the activity of Win 42122-2 was generally twofold less than those of gentamicin or netilmicin and similar to that of amikacin. Against 60 gentamicin-susceptible nonfermentative gram-negative bacilli, including P. aeruginosa, the activity of Win 42122-2 was four- to eightfold less than that of gentamicin or netilmicin and two- to fourfold less than that of amikacin. Minimal bacterial concentrations for Win 42122-2 were usually similar to minimal inhibitory concentrations. Win 42122-2 was not highly active against gentamicin-resistant bacteria. Win 42122-2 was as active as gentamicin against Mycobacterium tuberculosis but was less active than gentamicin or amikacin against atypical mycobacteria. Win 42122-2 interacted synergistically with penicillin G against enterococci, including strains highly resistant to streptomycin.

Amikacin↗
PubMed1982

Homogeneous enzyme immunoassay for netilmicin.

A newly developed homogeneous enzyme immunoassay for the determination of netilmicin in serum was evaluated and compared with a radioenzymatic assay. A total of 102 serum samples from patients treated with netilmicin were measured by both methods. This comparison showed an excellent correlation (r = 0.993). The enzyme immunoassay has proved to be precise, accurate, and specific. Because of its rapidity and the ease of performance, this method is a useful alternative to current assays for monitoring serum netilmicin concentrations.

Gentamicins↗
PubMed1985

Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans.

The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has been described in the literature. Thirty-three healthy male volunteers received a continuous intravenous infusion of isotonic saline with inulin, followed 1 h later by inulin plus gentamicin, dibekacin, tobramycin, netilmicin, or amikacin (1 mg/kg per h) or amikacin (4 mg/kg per h) over a period of 2 h. Brain-stem-evoked response audiometry was performed both before and at the end of each infusion. The latency of wave V remained constant whichever antibiotic was considered. The glomerular filtration rate did not vary significantly during the infusion of each drug. The percent fractional excretion was 79 +/- 6, 81 +/- 22, 85 +/- 5, and 99 +/- 9 for gentamicin, dibekacin, tobramycin, and netilmicin, respectively, and 83 +/- 4 and 124 +/- 13 for amikacin at concentrations of 1 and 4 mg/kg per h, respectively. Net balance and renal clearance were similar for the five aminoglycosides when administered at a rate of 1 mg/kg per h. With gentamicin only, fractional excretion was correlated with the urinary flow rate. We can conclude that (i) gentamicin, generally considered the most nephrotoxic agent, had the highest degree of net reabsorption; (ii) netilmicin exhibited a net zero tubular balance; (iii) amikacin had different patterns of tubular disposition according to the dose, i.e., reabsorption at 1 mg/kg per h and secretion at 4 mg/kg per h, raising the hypothesis of a saturable process of reabsorption; and (iv) these differences in tubular reabsorption could account at least in part for the known different nephrotoxic potentials of these five aminoglycosides in humans.

Adult↗
PubMed1991

Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection.

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.

Adult↗
PubMed1994

Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.

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

Adult↗
PubMed1987

Netilmicin: new approach to treating gonorrhoea.

Resistance and side effects to antibiotics or other chemotherapeutic agents are the main limiting factors in the treatment of gonorrhoea. As no such side effects have been reported with a new aminoglycoside, netilmicin, the therapeutic efficiency of this substance was evaluated in 1200 patients (690 women, 510 men) with uncomplicated gonorrhoea, who each received a single dose of 300 mg netilmicin by intramuscular injection. Efficacy of treatment was assessed by smear microscopy and culture, which gave results in all 1200 patients. No serious side effects were reported. These results indicate that netilmicin is an extraordinarily safe and efficient agent for treating uncomplicated gonorrhoea.

Female↗
PubMed1978

In vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against Pseudomonas aeruginosa.

The in vitro activity of carbenicillin, ticarcillin, sisomicin and netilmicin alone and in combination against 35 strains of Pseudomonas aeruginosa was investigated. Ticarcillin was more active than carbenicillin and sisomicin was more active than netilmicin. There was enhanced killing of many strains of P. aeruginosa by the combination of carbenicillin or ticarcillin with sisomicin or netilmicin.

Carbenicillin↗
PubMed1992

Exposure effects of netilmicin on Enterobacter cloacae clinical isolates.

The effects of netilmicin exposure on two aminoglycoside (AMG)-resistant and two AMG-susceptible Enterobacter cloacae isolates were studied. It was found that 1 h incubation of bacterial suspensions with netilmicin at 16 mg/l reduces the amounts of lipopolysaccharides present on the bacterial surface. Also, netilmicin pretreatment increased both the susceptibility to normal human serum and the adhesion to human epithelial cells of all four E. cloacae strains examined.

Bacterial Adhesion↗
PubMed1985

Low ototoxicity and its mechanism of netilmicin.

The ototoxicity and nephrotoxicity of netilmicin were compared with those of dibekacin, kanamycin and amikacin using rabbits. Groups of 5 rabbits each were given doses of 50 or 100 mg/kg of either one of the four drugs for 30 days, and 10 days after the last injection, all animals were prepared for histopathological studies. Results show the least ototoxicity of netilmicin in comparison to the other three antibiotics. It has been concluded that the low ototoxicity of netilmicin is due not to its lack of accumulation in the perilymph but to its low toxicity to the hair cells.

Amikacin↗
PubMed1981

Safety and efficacy of netilmicin in neonates with serious systemic infections.

Twenty-five hospitalized neonates, each with two or more serious symptomatic infections, were given netilmicin by intramuscular injection. The antibiotic was administered usually at 1.5 or 3.0 mg/kg twice a day (q 12 hr) for 7 to 13 days. At the end of therapy the signs and symptoms of infection were completely resolved in twenty-four of the twenty-five patients and markedly improved in the remaining one. Thirty-five causative organisms were isolated from 30 of the 59 infection sites; after netilmicin therapy 31 causative organisms were completely eliminated and 4 were markedly reduced in number. One of the babies had a slight increase in serum creatinine level, possibly related to therapy, and a mild transient rash which was doubtfully related to netilmicin. None of the other neonates had adverse reactions.

Bacterial Infections↗
PubMed1983

Netilmicin (Netromycin, Schering-Plough).

Netilmicin sulfate, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside recently released for use in Canada and not yet released in the U.S. Its place in therapeutics, compared with gentamicin (G), tobramycin (T), and amikacin (A), is not yet established. Preliminary work in animals has suggested a lower incidence of nephrotoxicity and ototoxicity than with other aminoglycosides, and in vitro work has suggested some activity against G/T-resistant organisms. However, netilmicin appears to be virtually identical to G,T, and A in antimicrobial spectrum (except for its poorer activity against P. aeruginosa), human toxicity, and clinical use. For G/T-resistant organisms, amikacin is still the aminoglycoside of choice. In summary, netilmicin has not been demonstrated to have significant advantages over other aminoglycosides (G,T,A), and it is more expensive; thus, its potential value is limited.

Animals↗
PubMed1985

Serum bactericidal activity of ceftazidime increased by netilmicin.

Cephalosporins are often used in combination with aminoglycoside antibiotics in the treatment of gram-negative infections. Although ceftazidime possesses activity against gram-negative bacteria, especially against Pseudomonas, combined use with aminoglycosides is useful. In this study, 12 healthy volunteers (6 men, 6 women; mean age 21.5 yr) received a single dose of ceftazidime 1 g iv and one week later ceftazidime 1 g iv with netilmicin 100 mg iv. Both antibiotics were infused over five minutes. Concentrations of ceftazidime were determined by high performance liquid chromatography. Serum bactericidal activity (SBA) was evaluated against seven microorganisms isolated from clinical specimens. The mean peak serum level of ceftazidime was 113.4 micrograms/ml. At eight hours, we observed a concentration of 2.6 micrograms/ml. The total clearance was 126 ml/min, while the renal clearance was 100 ml/min. Ceftazidime exhibited a half-life of 1.9 hours. Up to ten hours, the SBA of ceftazidime against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, and Salmonella typhi was greater than 1:8 in more than 90 percent of samples. At one hour, ceftazidime exhibited a SBA of 1:4 for Staphylococcus aureus, and 1:16 for Pseudomonas aeruginosa. With the addition of netilmicin, median SBA against Staph. aureus and P. aeruginosa were 1:32 and 1:64, respectively, at one hour. Netilmicin enhanced the SBA of ceftazidime. The combination was not effective against Streptococcus faecalis.

Adult↗
PubMed2001

Pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) in neonates.

The pharmacokinetics of once-a-day netilmicin (4.5 mg/kg) was studied in 16 neonates, divided for analysis into three groups according to gestational age: group 1 >36 weeks (n=7); group II between 34-36 weeks (n=4); and group III <34 weeks (n=5). The serum netilmicin (mean +/- SD) 4h and 24h after the first dose were 4.7 +/- 0.8 and 0.8 +/- 0.5 mg/L; 4.9 +/- 0.8 and 1.9 +/-0.2 mg/L; 4.9 +/- 0.5 and 1.7 +/- 0.5 mg/L in groups I, II and III respectively. After the second dose, concentrations at 2, 4, 8, 16 and 24 h were 7.2 +/- 1.0, 5.0 +/- 0.8, 3.0 +/- 0.6, 1.7 +/- 0.4 and 0.9 +/- 0.2 mg/L (group I); 8.6 +/- 0.2, 6.1 +/- 0.5, 4.2 +/- 0.7, 2.6 +/- 0.1 and 1.4 +/- 0.4 mg (group II); 9.0 +/- 1.2, 6.3 +/- 0.9, 4.1 +/- 0.7, 2.6 +/- 0.5 and 1.7 +/- 0.3 mg/L (group III). There was a large degree of inter-patient variability in serum concentrations and serum half-life (t1/2), volume of distribution (VD), area-under-the-curve (AUC), relative serum clearance (Clp) such that these parameters could not be correlated to age or weight. Absolute serum clearance (L/h) was correlated with gestational age (r = 0.672, P <0.01). There was no statistically significant evidence of accumulation between the first and second doses for any patient group. One baby from each group II and group III had concentration >2 mg/L 24h after the first dose and one baby from group III had concentration >2 mg/L 24h after the second dose. There are no established correlations between serum netilmicin concentrations and efficacy or toxicity in neonates and keeping 24 h trough concentration below 2 mg/L with a once-a-day dose of 4.5 mg/L would have to be validated in terms of its clinical efficacy and potential toxicity in a neonatal population.

Drug Administration Schedule↗
PubMedDate not supplied

[Antimicrobial activity of ciprofloxacin and netilmicin compared to various antibiotics in Lome, Togo].

We report the antimicrobial activity of ciprofloxacin and netilmicin on 577 strains such as S. aureus, Pseudomonas, E. coli, Salmonella, Proteus, Klebsiella and Enterobacter. Isolation and identification were performed by standard methods. Disk diffusion tests were performed to evalute the susceptibility. The percentage resistance to ciprofloxacin for bacteria was: E. coli = 15%, Enterobacter = 13%, Proteus = 10%, Pseudomonas = 9%, S. aureus and Klebsiella = 4%. The percentage resistance to netilmicin for bacteria was: Pseudomonas = 29%, Proteus = 26%, S. aureus = 21%, Enterobacter = 16%, Klebsiella = 14% and E. coli = 5%. The antimicrobial activity of ciprofloxacin and netilmicin was higher than that of others antibiotics.

Anti-Infective Agents↗
PubMed2001

[Netilmicin in the complex therapy of pneumonia in newborns].

Clinical efficacy of netilmicin was evaluated at 22 newborns (body weight from 1000 to 3600 g, delivery on pregnancy period from 28 to 41 weeks) with pneumonia caused by artificial pulmonary ventilation. Pneumonia was moderate at 13 patients and severe at 9 patients. Microorganisms isolated from tracheobronchial aspirates were mainly (in 19 cases of 22) susceptible to netilmicin. The usage of netilmicin in combination with cephalosporins was effective at the main part of the newborns and resulted with the full recovery of 11 newborns (all the patients with moderate pneumonia), in 9 cases improvement was registered (including 7 newborns with severe pneumonia). Newborns with severe pneumonia had a slow pathogens elimination.

Gentamicins↗