SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
An International Standard for Netilmicin has been established on the basis of a collaborative assay. There were five participating laboratories in five countries. The activity of the contents of each ampoule of the International Standard for Netilmicin is defined as 4810 IU of netilmicin.
The objective of this study was to examine the influence of the rate at which the tissue is perfused on the disposition of levofloxacin and netilmicin in the pulmonary tissue, using an experimental model of the isolated rat lung. Analysis of the results was performed using two pharmacokinetic approaches. By stochastic analysis of outflow curves the corresponding statistical moments and derived distribution coefficient were calculated. Model-dependent analysis based on a three-compartment dispersion model was also applied to the outflow concentration data. A statistically significant decrease in the distribution coefficient was observed for both antibiotics when the flow rate was decreased. For levofloxacin this parameter takes values of 2.14 and 1.25 mL/g for 10 and 5 mL/min flow rates, respectively. In the case of netilmicin these values were 0.81 and 0.39 mL/g for the higher and lower flow rates, respectively. Model parameters related to the distribution process were also modified as a consequence of the flow rate decrease. Tissue flow rate seems to be a determinant factor on the distribution of levofloxacin and netilmicin in the isolated rat lung.
OBJECTIVES: The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy. METHODS: A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide). RESULTS: Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases). CONCLUSION: The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.
A study of the disposition of netilmicin in the isolated rat kidney was carried out in order to establish the influence of the infusion rate on the drug profile in this tissue. A dose of 800 microg administered as a bolus injection or at infusion times of 5, 7.5 and 10 min, respectively, was injected through the afferent cannula into the isolated kidney. Analysis of outflow curves was carried out using different kinetic approaches. Comparison of statistical moments and derived parameters pointed to changes in the distribution process with the infusion rate. In contrast, elimination remained constant, since the extraction coefficient and relative area under the curve values did not change with the infusion rate, although the MTT (mean transit time) and distribution volume decreased for the longest infusion times. The UDF (unit disposition function) profiles were not superimposed for the different infusion rates and combined with the results of the kinetic analysis revealed that the behaviour of netilmicin in the isolated kidney depends on infusion rate. The apparent partition coefficients in renal cortex and medulla showed higher values for the slower perfusion rates. Yet, a progressive decrease in the absolute amount of netilmicin was predicted in the tubular epithelium compartment whereas the residence time tended to increase. The latter phenomenon could account for the higher aminoglycoside nephrotoxicity reported when these drugs are administered over longer infusion times.
The purposes of this study were to test the pharmacokinetics and renal and otologic tolerances of a once-daily regimen of netilmicin and teicoplanin administered intramuscularly, alone or in combination (4.5 and 6 mg/kg, respectively), for 7 days in 30 healthy male volunteers. Teicoplanin induced only a mild increase in enzymuria. Nephrotoxicity was moderate and reversible with netilmicin; there was increased enzymuria and alteration in diluting ability, without significant changes in urinary beta 2-microglobulin levels, concentrating ability, and glomerular filtration rate. Ototoxicity was not detected in any of the subjects. Our results suggest that (1) teicoplanin and netilmicin given once daily induced only slight, reversible tubular damage, without any sign of ototoxicity; (2) their combination was not more toxic; and (3) clinical studies can be envisaged to evaluate the efficacy and tolerance of once-daily regimens in long-term treatment.
PURPOSE: The purpose of this study was to evaluate both efficacy and safety of a new ophthalmic steroid-antibiotic fixed combination containing dexamethasone and netilmicin in the postsurgical management of cataract surgery. METHODS: In total, 223 patients were randomly treated with dexamethasone 1 mg/ml plus netilmicin 3 mg/ml (n=148), or dexamethasone 1 mg/ml plus tobramycin 3 mg/ml (n=75, TOBRADEX) four times in a day for 7+/-1 days starting immediately after surgery. Efficacy (anterior chamber (AC) inflammation, conjunctival hyperaemia, corneal and lid oedema, ocular infection, pain, photophobia and tearing) and safety (burning, stinging, blurred vision, intraocular pressure, and visual acuity) were analysed in the operated eye after 1 and 7+/-1 days. A follow-up visit was performed at day 14+/-2. The extent of AC inflammation, measured by slit-lamp according to a standard scoring system, was used as primary efficacy parameter. RESULTS: At the primary end point (day 7) both fixed combinations were equally effective in reducing postoperative inflammation. The safety profile of the dexamethasone/netilmicin combination was excellent with no evidence of poor local tolerance or adverse reaction. CONCLUSIONS: A new fixed combination of dexamethasone and netilmicin was effective and safe in controlling ocular inflammation after cataract surgery.
Cefepime is a cephalosporin with a broad spectrum of activity against most gram-positive and gram-negative pathogens. In this study, we attempted to compare the safety and efficacy of cefepime monotherapy against the potentially more toxic combination of vancomycin and netilmicin in the treatment of continuous ambulatory peritoneal dialysis (CAPD)-associated bacterial peritonitis. Eighty-one consecutive CAPD patients who presented with peritonitis from January 1, 1998, to June 30, 2000, were recruited for study. Patients were randomized to be administered either intraperitoneal (IP) cefepime, 1 g once daily (group A), or intravenous vancomycin and netilmicin at conventional doses (group B) for 10 days. Bacterial growth was obtained in 52 episodes (66%), and pathogens identified included gram-positive organisms (30 episodes; 38%), gram-negative organisms (14 episodes; 18%), mixed organisms (2 episodes; 2.5%), and fungus (6 episodes; 8%). Eight patients were excluded after randomization for various reasons (6 patients, fungal peritonitis; 2 patients, wrong diagnoses). Because of the relatively low peritonitis rate after the use of a disconnect system, the sample size of this study was relatively small, giving a power of 0.45. There were no significant differences in primary response rates and cure rates (no relapse >28 days after completion of antibiotic therapy) between both groups of patients (group A versus group B, 82% [32 of 39 patients] versus 85% [29 of 34 patients] and 72% [28 of 39 patients] versus 76% [26 of 34 patients], respectively; P = not significant). No significant side effect was encountered in either group. Total peritonitis-related hospitalizations were 84 patient-days (1, 7, 8, 11, 20, and 37 patient-days) and 115 patient-days (3, 6, 9, 14, 21, 21, and 41 patient-days), whereas total costs per patient cure were estimated to be US $1,039 and US $1,371 in groups A and B, respectively. We conclude that once-daily 1-g IP cefepime monotherapy is a simple, safe, and cost-effective alternative to vancomycin and netilmicin therapy in the treatment of CAPD-associated bacterial peritonitis.
The purpose of this study was to compare the cytotoxic effects of the fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin. Human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0 mg/mL) for 4 or 24 hours. Cell proliferation and viability were assessed with the MTT assay, neutral red uptake, and bromo deoxy uridine incorporation. In both cell lines, ofloxacin inhibited cell proliferation and viability. These effects were time and dose dependent. Concentrations of ofloxacin ranging from 0.4 to 2.4 mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability. In contrast, netilmicin induced no toxic effect. The differences between ofloxacin and netilmicin were highly statistically significant (p < 0.001). This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is compromised.
Twenty-eight patients, 24 men and 4 women, aged between 17 and 72 years old, and suffering from chronic osteomyelitis (19), mastoiditis (5), or serious wound infections (4) were treated for an average of 35 days with netilmicin at doses of 2.4 to 6.9 mg/kg/day. The total dose of netilmicin given to each patient ranged from 3700 to 23 220 mg. Although the renal function was initially normal in all patients and stayed normal throughout therapy in all patients with no underlying disease, netilmicin nephrotoxicity was detected in two diabetic patients (7.6%). Vestibular toxicity developed in two (7.6%) but no change in audiograms was noted. Long-term therapy was associated with a significant increase (P less than 0.001) in half-life, from 1.5 to 1.9 h, and AUC 7.9 to 13.1 mg/l/h.
Pericardial fluid, serum and atrial appendage concentrations of netilmicin and gentamicin were determined in 80 patients who received one or two pre-operative doses of either netilmicin 200 mg im or gentamicin 120 mg im. Mean atrial appendage concentrations of netilmicin and gentamicin after a single dose were 4.8 and 2.1 mg/kg; mean serum concentrations were 6.9 and 3.9 mg/l, and mean pericardial fluid concentrations 3.8 and 2.6 mg/l, respectively. After two doses apparent sequestration of the antibiotic in pericardial fluid was observed. A review of the cases of prosthetic valve endocarditis during the last decade suggests that aminoglycoside/isoxazolyl penicillin combinations provide good anti-staphylococcal prophylaxis. A change in the pattern of infections has been observed. The incidence of staphylococcal infection has fallen; early infections may be of fungal aetiology and late infections show a similar distribution of infecting organisms to that seen in native valve endocarditis.
The first line treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in our hospital was recently altered from a combination of gentamicin and clindamycin, given as continuous peritoneal lavage, to one of vancomycin and netilmicin given in peritoneal dialysis fluid with prolonged dwell time (4-6 h). The change was prompted by the emergence of multiply resistant Staphylococcus epidermidis among CAPD patients and nursing staff. In 9 of 19 episodes of peritonitis treated with gentamicin/clindamycin, the infecting organism could still be isolated from peritoneal fluid 5-15 days after commencement of therapy. All of 35 culture verified episodes treated with vancomycin/netilmicin were cleared bacteriologically within 3 days (P less than 0.0005). The vancomycin and netilmicin serum levels achieved were 6.5-37.0 mg/l and 1.0-8.1 mg/l, respectively. Apart from an asthmatic reaction, possibly triggered by vancomycin, no side effects were seen. However, audiometry was not performed regularly and the possible effect of netilmicin on the residual renal function was not systematically investigated.
The safety and efficacy of a single daily dose of netilmicin plus metronidazole after appendicectomy for gangrenous and perforated appendicitis was compared with the traditional thrice daily dosage. Twenty patients were enrolled in each group. The antibiotics were given intramuscularly for seven days after operation. Eradication of infection was observed in all patients and the postoperative wound sepsis was the same for each group. A significantly higher peak serum netilmicin level was achieved in the group receiving a single daily dose but nephrotoxicity was not observed. We concluded that the single daily dose of netilmicin was well tolerated and was as efficacious in this small series as the thrice daily regimen. The single-dose regimen has the advantage of simplicity and potentially increased bactericidal activity.
Twenty one patients with serious Staphylococcus aureus infection and bacteraemia were randomized prospectively to receive either teicoplanin and netilmicin or flucloxacillin and netilmicin. After at least 48 h of treatment serum samples were collected for the determination of trough and peak antibiotic concentrations, the serum killing level and the serum bactericidal rate. With the help of a severity-of-disease scoring system (APACHE II) the clinical efficacy of antimicrobial therapy was assessed. Eighteen patients were evaluable. The clinical results and the results of the serum assays suggest that treatment with teicoplanin or flucloxacillin, combined with netilmicin, is a safe approach in patients with bacteraemia caused by S. aureus.
In a randomized study the clinical and bacteriologic effectiveness of imipenem was compared with the classical combination of netilmicin with clindamycin in patients who had surgery for an intraperitoneal infection, localized or generalized, with positive bacteriologic findings of the specimen taken at surgery. Excluded were all patients who received other antibiotics before surgery, or who died within 3 days after antibiotic therapy was started. Imipenem was given at a dose of 500 mg t.i.d., clindamycin 600 mg t.i.d., and netilmicin according to serum levels. The diagnoses ranged from postoperative peritonitis, gallbladder empyema, perforated gastroduodenal ulcer, small bowel perforation with and without obstruction, and perforated appendicitis to perforation of the colon. The bacteriologic work-up included examination of the primary specimen (aerobic and anaerobic), the urine, feces, and serologic testing for Candida albicans once or twice a week and after the course of antibiotic therapy. In addition, pH measurements of abscesses and drainage fluids were performed. Ninety-three patients entered the study. Forty-seven patients were treated with imipenem (test group), and 46 patients were treated with the combination therapy (control group). The two groups did not show significant differences in age, sex, diagnostic groups, risk factors, primary bacteriology, and duration of therapy (mean: 6.7 days). Thirty-eight patients (80.9%) treated with imipenem were cured, six patients (12.8%) were improved, and there were three (6.4%) failures. The respective numbers for the control group were 31 (67.4%), 10 (21.7%), and 5 (10.9%). The mean duration of hospitalization was 19 days for the test group and 24.5 days for the control group. There were four wound infections in the test group and 11 wound infections in the control group. Imipenem is at least as effective in the adjuvant therapy of intra-abdominal infections as the combination of netilmicin with clindamycin.
PURPOSE: To determine the concentration of netilmicin in tears after eye drop administration. METHODS: A clinical study was carried out on 32 healthy volunteers. Subjects were divided into four groups and underwent tear collection at 5, 10, 20, and 60-minutes after drug administration, respectively. Tear samples were collected through capillary suction from the inferior conjunctival "cul-de-sac" and analyzed by high-pressure liquid chromatography (HPLC). RESULTS: Netilmicin concentration in tears decreased after a first order kinetics, a best-fit curve was drawn and the minimum inhibitory concentration (MIC90) intersection for the most common ocular pathogens was calculated. CONCLUSIONS: The extrapolation of the curve shows that the concentration of netilmicin on the ocular surface can be effective against microorganisms more than 120 minutes after eye drop instillation.
Thirty-two neonates were treated with netilmicin 3 mg/kg every 12 h by IV infusion for 30 min for suspected infections, colonization, or proven infections. Pharmacokinetic studies were performed in order to define the situations in which monitoring of plasma levels would be appropriate. Mean plasma levels were within the therapeutic range and did not differ in fullterms and preterms. In the 4 children who had 2 successive pharmacokinetic studies, plasma levels were increased between H1 and H5 at the second evaluation due to netilmicin accumulation. Plasma half-life was longer in proven infections and seemed to decrease in preterms with increased gestational age. These results suggest that the dosage schedule should be left inchanged, but that administration time should be reduced from 30 to 20 min and that peak and trough plasma levels should be measured only in proven infections, in very premature babies (gestational age less than 33 wk), and during netilmicin treatment longer than 5 d.
The cochleo- and vestibulotoxicity of dibekacin and netilmicin were compared in a guinea pig model. Both aminoglycosides were administered subcutaneously for 21 days at the dose level of 150 mg/kg/day. Control animals were injected with saline. Dibekacin-treated animals showed a significant (P less than 0.05) increase in the thresholds of the Preyer pinna reflex and the VIIIth nerve compound action potential in response to sound click stimulation. Moreover, a deterioration of the electrophysiologic auditory response and an almost complete suppression of the post-rotatory nystagmus were detected. In contrast, netilmicin did not induce any significant change in auditory and vestibular functions as compared to the control group. Our results demonstrated that netilmicin was devoid of ototoxicity in the guinea pig, while dibekacin provoked mild cochlear and severe vestibulotoxicity.
The stability of ampicillin, piperacillin and cefotaxime, alone or in combination with either netilmicin or amikacin, was tested by microbiological methods at 29 degrees C (ampicillin, also at 22 degrees C) in an L-amino acid solution specially prepared for newborn infants. In the case of ampicillin, the mean concentration had dropped to 84% of the initial value after 24 hours. This fall is acceptable. Piperacillin and cefotaxime were stable. Admixture of netilmicin or amikacin did not affect the activity of ampicillin, piperacillin and cefotaxime. The concentrations of netilmicin and amikacin were stable for 24 hours. Combination with ampicillin, piperacillin or cefotaxime did not affect the activity of either aminoglycoside. The antibiotics investigated could therefore be used in our TPN infusion system.