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Netilmicin in the treatment of Pseudomonas bacteremia.

The effectiveness of netilmicin was evaluated retrospectively in 40 patients with culture-documented bacteremia due to Pseudomonas aeruginosa. Netilmicin was the only antibiotic active in vitro against P aeruginosa that was administered to these patients. In 18 patients, Pseudomonas bacteremia developed in association with a Pseudomonas infection of the urinary tract; in 22 patients, Pseudomonas bacteremia developed from nonurinary or unknown sources. A clinical resolution or improvement was observed in 92% of the evaluable patients, and P aeruginosa was eliminated from the blood of 90% of the patients. The drug had nephrotoxic effects in two patients, but in no patient was there subjective or audiometric evidence of ototoxic effects. Three patients died during therapy. Based on these data, netilmicin is effective, and is associated with a low incidence of toxic effects, in the treatment of patients with Pseudomonas bacteremia.

Female↗

[Critical remarks on gonorrhea therapy: netilmicin].

Several failures of gonorrhea treatment due to neisseria producing penicillinase (PPNG), resistance against other antibiotics, side effects like allergies, gastrointestinal problems, and other factors are the reasons for continuing trials with new drugs in the treatment of gonorrhea. With regard to modern aminoglycosides, the development of early resistance has not been observed so far. Especially with Netilmicin, no such disadvantages have been reported in the literature. Therefore a single dose schedule was introduced with Netilmicin given to 600 patients suffering from uncomplicated gonorrhea in order to evaluate the efficacy and safety of the drug. 300 mg Netilmicin were administered intramuscularly in a one shot therapy. With all patients, the diagnosis had been confirmed by culture. The efficacy of therapy was controlled by a second culture, which proved to be negative in all 600 cases. Gonorrhea was also clinically cured in all patients.

Female↗

A prospective randomised controlled trial of mezlocillin versus netilmicin in biliary surgery.

A prospective randomised controlled trial of mezlocillin versus netilmicin in 133 patients undergoing biliary surgery at a district hospital is reported. Sixty-four patients received mezlocillin and 69 received netilmicin. The two groups of patients were comparable with regard to age, sex, underlying pathology and operative procedures performed. The incidence of infected bile at operation was 14.2% and both antibiotics were equally effective in reducing postoperative bacteraemia (0.75%) and wound infection (4.5%) to acceptable levels. It is concluded that netilmicin is a more cost-effective antibiotic in biliary surgery than mezlocillin.

Aged↗

Intraocular penetration of netilmicin.

The intraocular penetration of the aminoglycoside netilmicin following intramuscular and subconjunctival injection was studied in 102 patients undergoing elective cataract surgery. Those who received either a single 1.5-mg/kg intramuscular injection or two 1.5-mg/kg injections 6 hours apart subsequently had therapeutic serum levels but aqueous levels of less than 2.4 micrograms/mL. Those who received a subconjunctival injection of either 12.5 or 25 mg of netilmicin subsequently had aqueous levels of up to 36 or 85.6 micrograms/mL; therapeutic levels in the anterior chamber persisted for 7 to 9 hours, with higher levels following the 25-mg injection. Despite wide variation in the aqueous levels following subconjunctival injection the ocular penetration of netilmicin was comparable to that reported for other aminoglycosides. No major complications were associated with the use of this antibiotic by either route.

Aqueous Humor↗

Netilmicin and tobramycin. Comparison of nephrotoxicity in dogs.

We compared the effects of netilmicin and tobramycin on renal function and histology in dogs. Separate groups, each containing 5 dogs, received control injections, or either netilmicin or tobramycin at doses of 25, 50, or 75 mg per kg of body weight per day for 14 days. Renal function decreased markedly only in the group receiving the 75-mg tobramycin dosage; the serum creatinine levels rose from 1.0 +/- 0.1 to 3.6 +/- 0.9 mg per 100 ml (P less than 0.05) and the endogenous creatinine clearance fell from 42.5 +/- 9.4 to 7.8 +/- 2.2 ml per min (P less than 0.05). Dogs in this group developed glycosuria, proteinuria, and polyuria, and three died before the end of the study, probably from neuromuscular toxicity. Peak drug levels were stable when renal function was normal, but increased when renal failure occurred. Light microscopic changes occurred in all groups receiving either drug, but were most severe in the high-dose tobramycin group. Ultrastructural changes were similar in all groups and identical to changes produced by gentamicin. These results show that, on a weight basis, netilmicin is less nephrotoxic than tobramycin in dogs.

Animals↗

A comparison of netilmicin and gentamicin in the treatment of pelvic infections.

Seventy-five women admitted with the symptom complex suggestive of pelvic inflammatory disease( PID) were started on a penicillin-aminoglycoside antibiotic regimen. An aminoglycoside, gentamicin or netilmicin (Schering-Plough), was chosen randomly and given parenterally. Forty-two patients received netilmicin and 33 received gentamicin for 5 days. Therapeutic response to the 2 antibiotic regimens was similar. Aminoglycosides have been associated with both nephrotoxicity and ototoxicity. Blood chemistries were studied in all patients. The only manifested toxicity was in 2 patients treated with gentamicin. Endometrial-endocervical cultures were obtained before and after therapy. The microbacteria isolated by standard culture techniques before therapy revealed Neisseria gonorrhoeae in 69% and 51% of the netilmicin and gentamicin groups, respectively; anaerobic organisms were cultured in about 75% of each group.

Acute Disease↗

[Penetration of netilmicin into respiratory secretions].

Aminoglycosides are often used in the treatment of severe Gram-negative infections, particularly those involving the respiratory tract. The purpose of this study was to evaluate the penetration of netilmicin into bronchial secretions. In 8 tracheostomized patients samples of bronchial secretions were taken at intervals through the tracheostomy cannula after intramuscular injection of netilmicin 2 mg/kg bodyweight. Concentrations of the drug were measured in bronchial secretions and in blood samples taken simultaneously, using the agar diffusion method (Grove and Randall procedure). The results showed significant penetration of netilmicin, with a mean bronchial peak reaching 3.4 micrograms/ml 1 h after the injection. Elimination was slow, with a mean residual level of 2 micrograms/ml at 6 hours. The bronchial to serum levels ratio was high (greater than 30% at 1 hour). Individual variations in both serum and bronchial levels were noted; they were unrelated to the underlying pathology. However, changes in bronchial concentrations correlated with changes in serum concentrations, which suggests passive diffusion across the blood-bronchoalveolar barrier. The fluctuations in bronchial levels and the usually low bronchial concentrations of aminoglycosides previously reported are discussed in relation to the methods used.

Adult↗

[Antibiotic activity and synergism of ceftazidime and netilmicin against gram-negative pathogenic bacteria].

The in vitro activity of ceftazidime and netilmicin against gram-negative bacteria often causing hospital infections was evaluated and furthermore synergistic effects of these antibiotics were studied. Ceftazidime was as active as netilmicin against Enterobacteriaceae, e.g. Enterobacter, Klebsiella, Morganella inhibiting 90% of these strains at concentrations from 0.5 to 4 micrograms/ml. Ceftazidime was the most effective agent against Pseudomonas aeruginosa, being even more active than cefsulodin, with a mean minimal inhibitory concentration (MIC) of 4.57 micrograms/ml (median 2.0 micrograms/ml), also inhibiting cefoperazone- and cefsulodin-resistant Pseudomonas. There was at most a two-fold difference in either MIC or minimal bactericidal concentration (MBC). In all genera tested an increase of the inoculum size from 10(4) to 5 X 10(6) colony forming units had minimal effects upon the MIC or MBC of ceftazidime and there was no decrease of the MIC in the presence of clavulanic acid or sulbactam. When ceftazidime and netilmicin were combined synergism was observed against all strains tested.

Anti-Bacterial Agents↗

A comparative study of netilmicin-cefoxitin and gentamicin-cefoxitin in surgical patients with serious systemic infection.

A double-blind, randomized study of gentamicin and netilmicin, each in combination with cefoxitin, was done to compare their respective efficacy and toxicity in patients with serious systemic infection. Thirty-seven surgical patients were evaluated for efficacy and 46 patients were evaluated for toxicity. The most frequently cultured organisms were Escherichia coli (15), Klebsiella sp (9), Proteus sp (6), and Bacteroides sp (4). For 23 patients treated with gentamicin-cefoxitin (G-C), the clinical response was favorable in 20/21 (95.2%) evaluable cases, and elimination or marked reduction of 33/34 (97.1%) organisms was achieved. For 14 patients treated with netilmicin-cefoxitin (N-C), the clinical response was favorable in 13/13 (100%) evaluable cases, and 19/20 (95%) organisms were eliminated or markedly reduced. Nephrotoxicity was defined as an increase in serum creatinine to greater than 25% over baseline with an absolute rise of at least 0.5 mg/100 ml to a value greater than or equal to 1.3 mg/100 ml. Based on these criteria, nephrotoxicity was seen in 2/27 (7.4%) patients treated with G-C and in 3/19 (15.8%) patients treated with N-C. Ototoxicity was defined as a greater than 20 dB loss at any frequency. Based on these criteria, ototoxicity was seen in 5/27 (18.5%) patients treated with G-C and 2/19 (10.5%) patients treated with N-C. The data show no significant difference in toxicity and suggest that netilmicin and gentamicin are both highly effective in combination with cefoxitin in patients who have serious infections after surgery.

Adolescent↗

[Intraocular penetration of netilmicin].

The penetration of netilmicin, a semisynthetic aminoglycosid into the primary human aqueous humor was determined. The antibacterial spectrum of netilmicin is adequate to gentamicin. The efficacy also covers gentamicin resistant strains. After intramuscular injection of 5 mg/kg body weight aqueous levels higher than the minimum inhibitory concentration (MIC) of staphylococcus aureus, Escherichia coli, Klebsiella, Enterobacter, Citrobacter and Proteus morganii were obtained. In the therapy of bacterial endophthalmitis the synergistic effect of netilmicin with beta-Lactam antibiotics in the form of a combined therapy should be made use of. For perioperative prophylaxis the newer aminoglycosids are not indicated because there is the danger of a development of resistant strains.

Aged↗

Netilmicin therapy of patients with leukaemia or malignant lymphoma.

Seventy-four febrile patients with leukaemia or malignant lymphoma, of whom 42 had severe granulocytopenia, were treated with netilmicin in combination with other antibiotics, usually ampicillin and methicillin. Of 36 patients with proven bacterial infection, 72% responded to treatment with complete resolution or improvement. Moderate and reversible renal affection occurred in 10 patients of whom 8 concomitantly were treated with other potentially nephrotoxic drugs. Five of the 10 patients had unintendedly high valley concentrations of netilmicin. Ototoxicity was not documented. It is concluded that netilmicin is an effective and tolerable aminoglycoside.

Bacterial Infections↗

Netilmicin: new aminoglycoside effective against bacterial endophthalmitis.

Bacterial endophthalmitis is difficult to treat because antibiotics administered systemically, subconjuctivally or topically cannot be delivered in bactericidal amounts to the infected tissues. Netilmicin, a new aminoglycoside, is active against Pseudomonas aeruginosa, Staphylococcus and most Enterobacteriaceae, including Escherichia coll, Klebsiella and Enterobacter, that have been resistant to other aminoglycosides. In rabbits an intravitreal injection of 250 mu g/0.1 ml rapidly provided a bactericidal concentration (greater than 10 mu g/ml) in the vitreous, and this level was maintained for 100 hours. This dose was not toxic to ocular tissues, unlike higher doses (1000 to 2000 mu g). Intravenous, subconjunctival and topical administration yielded only low concentrations of the drug in the vitreous, although subconjunctival injection yield significant concentrations in the aqueous for 4 hours. Experimentally induced Staphylococcus aureus endophthalmitis was quickly eradicated by a single intravitreal dose of netilmicin without detectable sequelae in 9 to 10 eyes studied. A solution of netilmicin infused during vitrectomy and lensectomy prevented infection.

Administration, Topical↗

The ototoxic potential of netilmicin compared with amikacin. An animal study in guinea pigs.

The potential ototoxicity of netilmicin and amikacin was compared in guinea pigs. When the toxicity in animals is determined two parameters should be discussed: Dose related comparison of ototoxicity and a comparison related to the antibacterial potency. None of the netilmicin test groups (50-100 mg/kg body weight) showed a higher percentage of degenerated hair cells than the control group. Even the individual animals showed a sensory cell damage within the control animal range. With the antibacterial potency taken into account, a dose three times higher was given to the animals treated with amikacin than to those treated with netilmicin. The amikacin group of animals showed a high percentage of degenerated hair cells under these conditions.

Amikacin↗

[Clinical effects of netilmicin].

In the present study, we used netilmicin for the postoperative complications and obtained the following results. 1. Netilmicin was used in totally 29 cases; 23 with localized peritonitis, 4 with generalized peritonetis and 2 with wound infection. Excellent effects were obtained in 2 cases, effective results in 24 cases and ineffective results in 3 cases. The effective rate was 89.7%. 2. Adverse reactions or abnormal clinical laboratory test results which might be attributable to the use of netilmicin were not noticed.

Adult↗

[Clinical evaluations of netilmicin in urinary tract infections].

Netilmicin was administered to 1 case of simple acute pyelonephritis and 21 cases of complicated urinary tract infections, 22 cases in total, and the effects were evaluated clinically. Total clinical effects of netilmicin evaluated by the UTI standard for evaluation of drug effects showed 61.9% of clinical effectiveness in 21 cases, and the results are satisfactory because 11 cases out of 21 cases were catheterized. The result was examined bacteriologically; the frequency of detection of particular strains among 23 strains clinically isolated from complicated urinary tract infections was that 10 strains of P. aeruginosa (43.5%), 3 of S. marcescens (13.0%), and 3 of E. coli (13.0%), and the ratios of bacteriologically disappeared strains were 70%, 33.3% and 66.7%, respectively, and the overall disappearance ratio was 73.9%. The MIC's determined for 17 strains and disappearance of the bacteria were examined; when MIC was less than 6.25 mcg/ml, 10 strains out of 12 disappeared, that is, 83% of disappearance was obtained. When MIC was larger than 100 mcg/ml, 2 strains out of 5 disappeared, that is, 40% of disappearance was obtained. Disappeared 2 strains of bacteria were isolated from patients who were not catheterized. Neither subjective symptoms nor abnormal laboratory findings related to the drug were observed. It may be said from these findings that netilmicin is an effective drug for urinary tract infections.

Aged↗

Pharmacokinetics of amikacin, netilmicin and tobramycin in children with chronic renal failure.

The single-dose pharmacokinetics of amikacin, netilmicin and tobramycin administered intramuscularly at doses of 7.5 mg/kg amikacin, 2.5 mg/kg netilmicin or 3 mg/kg tobramycin were studied in 30 children with chronic renal failure. Serum amikacin, netilmicin and tobramycin levels were measured by a radioimmunoassay method. The correlation between serum creatinine levels and the half-life of the antibiotics was found to be statistically significant. There were interpatient differences in serum aminoglycoside levels among those with the same serum creatinine levels. Thus, monitoring of serum creatinine and aminoglycoside levels is recommended, especially for those with renal failure, in order to maintain an optimal dosage between toxic and noneffective serum aminoglycoside levels.

Adolescent↗

Clinical efficacy and toxicity of netilmicin in the treatment of gram-negative infections.

Netilmicin, a new semisynthetic aminoglycoside antibiotic, was used to treat 41 infections in 38 patients. The outcome of four infections could not be evaluated: two patients received inadequate therapy and two did not have gram-negative infections. Clinical improvement occurred in 36 (97%) of the 37 gram-negative infections, and bacteriologic cure occurred in 30 (86%) of the 35 evaluable infections. Therapeutic serum concentrations of netilmicin were readily achieved by both intramuscular and intravenous routes. Reversible ototoxic effects occurred in 1 (3%) of 35 courses of therapy evaluated, reversible nephrotoxic effects occurred in 5 (14%) of 36 courses and mild reversible alterations in liver function occurred in 3 (19%) of 34 courses. Netilmicin appears to be effective and safe in the treatment of aerobic gram-negative infections.

Adolescent↗

In vitro activity of netilmicin against clinical isolates of methicillin resistant and susceptible Staphylococcus aureus.

BACKGROUND: The emergence of methicillin-resistant Staphylococcus aureus and its multidrug-resistant property has led to the search for an effective antibiotic to combat staphylococcal sepsis. At present, vancomycin remains the most effective antibiotic. This study evaluated the in vitro efficacy of netilmicin (an aminoglycoside) and compared its activity with 4 other antibiotics, viz. vancomycin, amikacin, tobramycin and ofloxacin. METHODS: The minimum inhibitory concentration of the antibiotics was determined by the agar dilution method. Thirty strains each of methicillin-resistant and -susceptible S. aureus isolated from pus and blood cultures were included. RESULTS: The susceptibility to netilmicin was found to be 100% and was the same as that observed for vancomycin. CONCLUSION: All the methicillin-resistant S. aureus strains tested showed 100% susceptibility to netilmicin, suggesting its use in patients with such infections as an alternative to vancomycin. However, this finding needs to be verified in the clinical setting.

Amikacin↗