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PubMed1982

The use of netilmicin in a district general hospital.

Twenty patients with a variety of serious or difficult infections and 5 additional orthopaedic patients with clinical evidence of post-operative wound infection were treated with netilmicin. The results indicate that twice daily dosage with 150 mg intramuscularly, either alone or in combination with other antibiotic therapy, was highly effective. Overall, 25 (96%) infections responded clinically and 19 (73%) were improved bacteriologically. There was no evidence of ototoxicity: a number of patients had impaired renal function which developed during therapy, but all returned to normal or pre-treatment levels by the time that treatment was completed, despite the fact that 15 patients were receiving diuretics. It is suggested in view of its effectiveness, more predictable serum levels after standard dosage and apparent lack of toxicity, that netilmicin should be considered as the first choice aminoglycoside antibiotic instead of gentamicin.

Adult↗
PubMed2000

Determination of tissue spaces of the isolated hindlimb of the rat using netilmicin as an extracellular space indicator.

The kinetic behaviour of drugs in extracellular space is of interest as it influences the drug's access to, and permanence in, those areas of the body upon which drugs exert pharmacological or toxicological actions. A series of experiments was carried out to characterize the vascular, interstitial and cellular spaces of the isolated hindlimb of the rat. Certain specific experimental conditions were met: body weight was under 230 g to avoid fat tissue in the preparations; a perfusion flow rate of 3 mL min(-1); and 3% of bovine albumin in the perfusate supplied at 25 degrees C to the tissues. The isolation of the hindlimb followed the method described by Ruderman with some modifications to restrict the perfusion to the right hindlimb. Tritiated water, netilmicin and methylene blue were injected separately and efferent fluid samples were collected for 15 min after solute injection. Analysis of the efferent curves was performed to calculate the statistical moments (AUC, area under concentration-time curve; MTT, mean transit time; VTT, variance of mean transit times) and solute distribution volumes, which were subsequently used to estimate the tissue spaces of the isolated hindlimb. The results revealed that methyl blue and netilmicin can be respectively used as alternatives to radiolabelled indicators of the vascular and extracellular spaces of tissues included in the rat isolated hindlimb.

Animals↗
PubMed2005

Comparative study of the disposition of levofloxacin, netilmicin and cefepime in the isolated rat lung.

An experimental model of artificially perfused and mechanically ventilated lung has been applied to compare the kinetic behaviour of levofloxacin, cefepime and netilmicin in this body tissue. The study has been performed to explore the usefulness of the isolated lung technique in the pharmacokinetic field, particularly to study the disposition of antibiotics in pulmonary tissue. The lung was perfused with Krebs-Henseleit medium containing 3% bovine albumin at a flow rate of 5 mL min(-1). It was ventilated at 60 respirations/min with a 2-mL tidal volume of air previously humidified and warmed to 37 degrees C. The concentrations of the above antibiotics were determined by HPLC techniques and the outflow curves were analysed by stochastic, as well as by model-dependent, methods. The results show pharmacokinetic differences among these antibiotics, which are in accordance with previously reported data, levofloxacin being the drug with the highest distribution coefficient in this tissue (1.25 +/- 0.14 vs 0.39 +/- 0.07 and 0.41 +/- 0.06 mL g(-1) for netilmicin and cefepime, respectively). Accordingly, the isolated lung of the rat, under the experimental conditions used here, constitutes an alternative model to be incorporated to pharmacokinetic studies with a great potential use for those drugs that show a pharmacological or toxicological action depending on the kinetic profile in the lung tissue.

Animals↗
PubMed1993

Nonparametric meta-analysis of published data on kidney-function dependence of pharmacokinetic parameters for the aminoglycoside netilmicin.

The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values.

Creatinine↗
PubMedDate not supplied

[Evaluation of Emit netilmicin and amikacin assays on Dimension RXL HM (Dade Behring) open channels].

The aim of this study was to evaluate and to validate an enzyme immunoassay in homogeneous phase for netilmicin and amikacin, adapted on the Dimension RXL HM (Dade Behring) machine. The results were compared with those obtained with automated polarization of fluorescence immunoassay using TDx FLx (Abbott). The protocol of the study and the analytical criteria were inspired by the protocol Valtec version 2002 recommended by the French Society of Clinical Biology (SFBC). The validation of this technique as adapted to the Dimension RXL HM has allowed its use for routine dosage adjustment of amikacin and netilmicin. The practicability is however the weak point of the adaptation of these techniques, even limiting as for their implementation.

Amikacin↗
PubMedDate not supplied

[Antibiotic prophylaxis with netilmicin in patients undergoing cystoscopic study].

Thirty adults of either sex, in several cases affected by severe urinary pathology, underwent check cystoscopy. An intramuscular injection of netilmicin 200 mg was administered one hour before the diagnostic procedure as antibiotic prophylaxis. Treated patients were controlled up to three months after cystoscopy, in order to verify the presence of urinary infections. Data obtained proved the efficacy of netilmicin in preventing postcystoscopy urinary infections in 87% of the cases. Safety was very good in all patients.

Adult↗
PubMed1990

Simulation of human pharmacokinetic profiles in mice, and impact on antimicrobial efficacy of netilmicin, ticarcillin and ceftazidime in the peritonitis-septicemia model.

Pharmacokinetic profiles in small animals substantially differ from those observed in man. We hence devised a man adapted animal model to critically assess the impact of such differences on antimicrobial efficacy. We approximated in mice the human pharmacokinetic profiles of netilmicin, ticarcillin and ceftazidime. The CD50 (curative dose for 50% of lethally intra-peritoneally infected animals) against Pseudomonas aeruginosa was comparatively determined for murine versus man-adapted pharmacokinetic profiles. With netilmicin the man-adapted profile was significantly less efficacious than the murine profile. In contrast, a significant superiority of the man-adapted profile was found with the beta-lactam drugs. We conclude that determinations of antimicrobial activity in small animals may yield misleading results in respect to man. Depending on the drug in question, murine pharmacokinetics may lead to overestimation or underestimation of antimicrobial activity. Our findings are of particular importance for the interpretation of studies in small animals comparing different antimicrobial compounds or different dosage regimens.

Animals↗
PubMed1989

Antimicrobial activity of dactimicin in vitro compared with that of dibekacin, netilmicin, sisomicin and micronomicin.

Antimicrobial activity of dactimicin, a pseudo-disaccharide aminoglycoside antibiotic, was compared with those of dibekacin, netilmicin, sisomicin and micronomicin using clinical isolates of four Gram-positive and sixteen Gram-negative bacteria. Dactimicin was more active than the reference amino-glycosides against Serratia marcescens, especially gentamicin-resistant Serratia sp., Proteus vulgaris, P. rettgeri and Klebsiella oxytoca, but less active against Pseudomonas aeruginosa and P. mirabilis. Dactimicin was equally active as the references excepting netilmicin against Gram-positive bacteria and some Gram-negative bacteria including Escherichia coli, K. pneumoniae, Morganella morganii, Haemophilus influenzae, Citrobacter freundii, Enterobacter aerogens, E. cloacae, Acinetobacter calcoaceticus and Campylobacter jejunii. Dactimicin was active against resistant strains possessing various aminoglycoside-modifying enzymes including AAC(3)-1, by which dactimicin was acetylated.

Aminoglycosides↗
PubMedDate not supplied

[Adjusting the dosage of netilmicin from two measurements. Program validation].

The aim of this study is to give to clinicians a well validated usefull tool allowing an increase of safety in the monitoring of netilmicin. During the first administration of the drug, two plasmatic concentrations are measured, and input in a preprogrammed hand-held calculator. A posology and a rythm of administration are returned by the calculator. After six days of this dosage regiment, the peak and the valley concentrations are compared with those previously given by the computer as values at equilibrium. No significant difference can be observed. There is no change in plasmatic creatinine level from the first to the sixth day of treatment. So, a preprogrammed hand-held computer can be convenient and safe to monitor netilmicin.

Adolescent↗
PubMed1986

[Piperacillin combined with netilmicin and cloxacillin. Usefulness in the treatment of febrile episodes in neutropenic children].

No preventive treatment other than intestinal decontamination with oral colimycin was given. Antibiotic therapy with piperacillin 200-300 mg/kg, netilmicin 6-7.5 mg/kg and cloxacillin 50-100 mg/kg was initiated within 6 to 12 hours of clinical onset, using a central catheter. Twenty-nine children with bone marrow aplasia and less than 1000 leucocytes/mm3 were treated: 20 had acute lymphoblastic leukaemia or lymphoma (first episode 13, relapse 7, including 3 undergoing bone marrow transplantation), 6 had acute myeloblastic leukaemia (first episode 4, relapse during transplantation 2), and there was 1 case each of idiopathic bone marrow aplasia, metastatic sympathico-blastoma and lymphohistiocytosis. Mean age was 9 years (range: 2-19 years). The combined antibiotic therapy was continued until recovery from aplasia in case of success and discontinued after 48 hours in case of failure. Bacteriological examinations were negative in 19 patients and positive in 10; 13 strains were isolated, mostly staphylococci and streptococci. Apyrexia was obtained in 24 patients, 11 of whom had a rise of temperature with negative bacteriology about 10 days later. There were 4 initial failures and one unassessable result. An atopic patient developed a skin rash on the 3rd day of treatment. There was no death, no superinfection and non clinical or biochemical side-effect. It is concluded that the piperacillin-netilmicin -cloxacillin combination, which gave a high success rate and was well tolerated, can be recommended in neutropenic children with febrile episodes.

Adolescent↗
PubMed1988

[Use of ceftazidime combined with netilmicin in the treatment of febrile episodes occurring after bone marrow transplantation in children].

Thirteen episodes of fever in bone marrow transplantation recipients (23 months to 11 years old children) were treated by ceftazidime (100-200 mg/kg/j) and netilmicin (7 mg/kg/j). Vancomycin was added at the 24th hour in 10 cases of persistent fever. 6 presumed agents of infection were isolated before antibiotic treatment: blood cultures (streptococci 2, staphylococcus 1, proteus 1), fecal sample (E. coli 1), urine (E. coli 1). Modifications of aerobic fecal flora were studied under this treatment. E. coli, staphylococci and enterococci were the mainly strains isolated. There were no third generation cephalosporins resistant Gram-negative bacteria. High level resistance to aminoglycosides was observed in enterococcal strains, isolated during and after treatment. Ceftazidime-netilmicin (+/- vancomycin) was an effective and safe combination for the management of febrile neutropenic episodes.

Bacteria↗
PubMed1988

Pharmacokinetics of netilmicin during hemodialysis: comparison of four artificial kidneys.

The pharmacokinetics of netilmicin was studied in 11 patients with terminal renal impairment (Clcr less than 5 ml/min) during the course of a 4-h hemodialysis session, using four different kinds of dialyzer: Biospal 2400, Biospal 3000, Allegro HF, and Andante HF. All patients received a single dose of 2 mg netilmicin/kg body wt at the beginning of the dialysis session. The type of dialyzer influences the serum half-life, the dialysis clearance and the percentage of drug extracted during dialysis. A linear relationship was established between the drug fraction extracted by dialysis and the dialysis clearance of the antibiotic. During the hemodialysis sessions, the serum half-life of netilmicin decreased approximately 10-fold compared with the interdialysis periods.

Adult↗
PubMed1986

Epidemiology of resistance to netilmicin and other aminoglycosides.

The authors carried out a study to evaluate the epidemiology and resistance of netilmicin, gentamicin, tobramycin and amikacin during the 1984-1985 period. Clinical specimens of different origin, drawn both from hospitalized and outpatients were used in the study. The strains were tested for their sensitivity to aminoglycosides. In particular the degree of resistance in both fermentative and non-fermentative gram-negative strains was determined. As previously pointed out in other works, netilmicin showed good antimicrobial activity in respect to other aminoglycosides.

Amikacin↗
PubMed1986

Netilmicin in gram-negative sepsis: comparative abilities of a dosage nomogram and clinical microbiologists to predict the preferred individual dose.

The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres. The dose was based upon the attainment of recommended serum concentrations. Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), and the preferred dose from 100 to 750 mg/24 h. The dose generated by a nomogram for netilmicin was compared in retrospect with the initial dose assigned to each patient by the clinical microbiologist concerned. With respect to the preferred dose, the nomogram underdosed, on the average, by 40 mg/24 h, and the microbiologists, by 30 mg/24 h. The correlation with the preferred dose was stronger for the nomogram dose (r = 0.66; p less than 0.001, 37 df) than for the microbiologists' dose (r = 0.47; p less than 0.005, 37 df) but there was no significant difference between the two in the frequency with which they predicted the preferred dose to within 50 mg/24 h (nomogram 19/39; microbiologists 16/39). The prescription of a fixed dose of 450 mg/day to all patients would have had a similar success rate (15/39). The performance of the nomogram was better in patients with serum creatinine concentrations of greater than or equal to 100 microM (r = 0.82; p less than 0.001, 13 df; 10/15 within 50 mg/24 h of preferred dose) than in those with creatinine concentrations less than 100 microM (r = 0.55; p less than 0.01, 22 df; 9/24 within 50 mg/24 h of preferred dose).

Adolescent↗
PubMed1985

Clinical evaluation of netilmicin in the field of internal medicine.

An open clinical trial was carried out to evaluate therapeutic efficacy and safety of netilmicin. Forty hospitalized adult patients suffering from complicated urinary tract infections (UTI) (19), lower respiratory tract infections (20), septicemia (3) and soft tissue infection (1) due to in vitro susceptible microorganisms were admitted to the study. Twenty-nine of these patients had severe underlying diseases interfering with host defenses. Twenty-nine out of the 40 patients (73%) were cured and 6 (15%) had a favorable clinical response giving an overall satisfactory clinical response of 88%. Eradication of causative microorganisms was obtained in 29 (73%) patients, and three substitutions during or at the end of treatment were observed. Netilmicin was well tolerated: neither clinical abnormalities of otovestibular function nor hepatic or hematological alterations were found, while only two patients developed a mild and transient increase of BUN and creatinine serum levels.

Adult↗
PubMed1985

[3H]netilmicin binding constants and phospholipid composition of renal plasma membranes of normal and diabetic rats.

We examined the hypothesis that the decreased renal accumulation of aminoglycosides in rats with streptozotocin-induced diabetes mellitus is due to decreased membrane binding of drug consequent to reduced membrane content of the putative aminoglycoside receptor, phosphatidylinositol. Renal brush border membrane (BBM) and basolateral membrane (BLM) vesicles were prepared from normal and diabetic Sprague-Dawley rats by differential centrifugation and Percoll gradient techniques which yielded relatively pure membrane fractions as assessed by measurements of marker enzymes and by electron microscopy. Binding of [3H]netilmicin to plasma membranes was performed using a fast filtration technique. Scatchard analysis of the binding data indicated that netilmicin bound to a single class of receptors on BBM and BLM from normal rats with an affinity constant of 33 +/- 2 X 10(3)M-1 and 23 +/- 2 X 10(3)M-1, respectively. The maximal binding capacity of BLM (70 +/- 4 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (38 +/- 1 nmol/mg of protein). The affinity constants and maximal binding capacities of BBM and BLM from diabetic rats were not significantly different from those of normal rats. Moreover, 2 days of gentamicin injections at 100 mg/kg/day for 2 days had no appreciable effect on these binding parameters in either group. In control rats the total phospholipid content of BLM (785 +/- 19 nmol/mg of protein) was significantly greater (P less than .01) than that of BBM (592 +/- 19 nmol/mg of protein) and reflected significantly greater quantities of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗