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PubMed1993

Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis.

We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter-induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a beta-lactam-sensitive strain of Streptococcus sanguis or a beta-lactam-resistant strain of Streptococcus mitis. Treatment with the antibiotics alone (CRO, 10 mg/kg of body weight every 8 h; NET, 18 mg/kg every 24 h) or in combinations which had proved synergistic in in vitro time-kill curves was commenced 48 h postinfection and continued for 72 h. The results show that the combination was markedly effective against S. sanguis and moderately effective against S. mitis, while, with the protocol used here, the agents alone were not. The results suggest that CRO-NET should be an effective combination for treating streptococcal endocarditis in humans and may permit a shorter duration of treatment and once-a-day dosing to be used.

Animals↗
PubMed1993

Simulated human serum profiles of one daily dose of ceftriaxone plus netilmicin in treatment of experimental streptococcal endocarditis.

We performed experiments in rats aimed at determining whether a combination of ceftriaxone (CRO) and netilmicin (NET), by using once-daily administration in rats, which simulated profiles of drug in human serum, was more effective than either agent alone in the treatment of endocarditis caused by viridans group streptococci. A programmable infusion pump system enabled the production of profiles of CRO in serum that simulate those found in humans after the intravenous administration of 2 g. The subcutaneous administration of 18 mg of NET per kg of body weight produced levels in the sera of rats comparable to those after the intravenous administration of a dose of 5 mg of NET per kg in humans. Rats with catheter-induced aortic vegetations were infected intravenously with two test strains, a CRO-susceptible Streptococcus sanguis strain (MICs of CRO and NET, 0.064 and 8 mg/liter, respectively) and a relatively CRO-resistant Streptococcus mitis strain (MICs of CRO and NET, 2 and 8 mg/liter, respectively). Against both strains, the combination of CRO and NET was synergistic in vitro as determined by time-kill curves. Treatment of rats was started 48 h postinfection and lasted for 3 days. CRO alone was effective against the susceptible strain (P < 0.001 compared with control animals) but was not effective against the resistant organism. A significantly enhanced antibacterial activity of the CRO-NET combination in reducing the valvular bacterial counts was observed with both test strains (P < 0.001). The synergistic effect was obtained with a single daily injection of NET which provided detectable levels in serum for only 8 h, suggesting that in vivo synergism in the treatment of infections caused by viridans group streptococci can be obtained without 24 h of aminoglycoside coverage. These experimental data might provide a rationale for clinical trials of a once-a-day dosing regimen in the treatment of streptococcal but nonenterococcal endocarditis.

Animals↗
PubMed1983

Quality control parameters for susceptibility tests with 30-micrograms netilmicin disks.

A nine-laboratory cooperative study was performed to evaluate quality control parameters for susceptibility tests with 30-micrograms netilmicin disks. The applicability of currently recommended zone-size limits was confirmed. However, alternative statistical methods suggested that tighter control limits might be more appropriate but would require better standardization of reagents, especially Mueller-Hinton agars.

Agar↗
PubMed1984

Modification of interpretive breakpoints for netilmicin disk susceptibility tests with Pseudomonas aeruginosa.

Regression analysis of data correlating 30-micrograms netilmicin disk zone diameters with microdilution MICs, obtained by testing close-interval dilution steps, was performed with 77 selected strains of Pseudomonas aeruginosa, each tested in three independent laboratories. A zone of greater than or equal to 15 mm correlated with an MIC of less than or equal to 12 micrograms/ml (susceptible), and a zone of less than or equal to 12 mm correlated with an MIC of greater than 16 micrograms/ml (resistant). Additional disk tests were performed with 256 strains having known resistance mechanisms and 280 susceptible strains: the majority were appropriately categorized by these interpretive zone standards. The previously recommended standards of greater than or equal to 17 mm (MIC, less than or equal to 8.0 micrograms/ml) for the susceptible category inappropriately placed a significant number of truly susceptible P. aeruginosa strains in the intermediate category.

Drug Resistance, Microbial↗
PubMed1983

Clinical pharmacology of netilmicin in the newborn.

The plasma peak, trough, and peak-trough concentrations of netilmicin given to preterm and term infants were measured after different regimens to determine which dosage would provide satisfactory peak and trough concentrations. In infants aged less than 7 days, dosage regimens of 3.0 or 2.5 mg/kg every 12 hours gave satisfactory peak levels (range 5.2-12.0 micrograms/ml) but troughs were above the desirable maximum level of 3 micrograms/ml in more than half the preterm infants. Subsequently a dosage regimen of 3.0 mg/kg immediately followed by 2.0 mg/kg every 12 hours resulted in trough levels that exceeded 3 micrograms/ml in only 2 of 25 preterm determinations and never in term infants, yet gave satisfactory peak levels (range 4.5-7.4 micrograms/ml). In preterm infants aged 4 to 7 weeks a dosage of 3 mg/kg every 8 hours gave satisfactory peak and trough levels.

Body Weight↗
PubMed2001

Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin, astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the rabbit.

Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles. However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated. We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular block was assessed by mechanical response with single twitch stimulation. Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated. The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.

Aminoglycosides↗
PubMed1990

Fosfomycin trometamol versus netilmicin in children's lower urinary tract infections.

Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36-48 h after a single oral dose of 1-2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever (less than 38 degrees C), erythrocyte sedimentation rate (less than 25 mm/l h) and C-reactive protein (less than 20 micrograms/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and children.

Adolescent↗
PubMed1998

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

Adolescent↗
PubMed2001

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Adolescent↗
PubMed1990

Safety, pharmacokinetics and efficacy of once-a-day netilmicin and amikacin versus their conventional schedules in patients suffering from pelvic inflammatory disease.

The safety, pharmacokinetics and efficacy of one daily injection (qd) of amikacin (AK) and netilmicin (NT) was compared with the recommended schedules (cs), i.e. twice-daily or thrice-daily, respectively. Women (17-43 years, n = 78) suffering from pelvic inflammatory disease were randomly assigned to qd or cs of either AK (14 mg/kg per day) or NT (6.6 mg/kg per day). Biometric parameters were similar in the 4 groups and all patients received ampicillin (4 g/day) and tinidazole (0.8 g/day). The Repeated Measures Analysis of Variance was used to distinguish the effects of the schedules and of the drugs choice on critical parameters. Efficacy was similar in the 4 groups and not influenced by the schedule of administration. No significant differences in nephro- and oto-toxicity were observed as assessed by serum creatinine and losses of hearing at low frequencies, but early phospholipiduria and auditory losses at high frequencies were significantly reduced with the qd administration compared to cs and by AK compared to NT. These data suggest that the qd schedule of AK and of NT is as efficacious as their cs schedules, and causes less renal and auditory alterations.

Amikacin↗
PubMed1999

[Neuromuscular blocking properties of arbekacin, astromicin, isepamicin and netilmicin in the rabbit].

The neuromuscular blocking properties of aminoglycoside group of antibiotics arbekacin sulfate (ABK), astromicin sulfate (ASTM), isepamicin sulfate (ISP), netilmicin sulfate (NTL) and d-tubocurarine were studied in 30 rabbits anesthetized with pentobarbital. The left gastrocnemius tendon was cut and secured to a force-displacement transducer. The left tibial nerve was directly stimulated by electrodes with supramaximal square waves of 0.1 msec duration at a frequency of 0.1 Hz. The resultant force of twitch tension was recorded. The intravenous administration of ABK 60-100 mg/kg, ASTM 160-320 mg/kg, ISP 320-480 mg/kg or NTL 20-40 mg/kg resulted in dose-dependent decreases in twitch tensions. The ED50 values of 4 antibiotics were NTL = 30.2 mg/kg (4.2 x 10(-2) mmol/kg) < ABK = 78.3 mg/kg (1.4 x 10(-1) mmol/kg) < ASTM = 215.2 mg/kg (3.6 x 10(-1) mmol/kg) < ISP = 359.7 mg/kg (6.3 x 10(-1) mmol/kg), respectively. These antibiotics-induced blockades were antagonized by calcium or by neostigmine. Although the relative neuromuscular blocking potencies of 4 antibiotics equipotent to d-tubocurarine on the basis of therapeutic doses in man were below 0.6 mg, it may be concluded that the potential clinical hazard lies in the sequence of administration of the aminoglycoside group of antibiotics.

Aminoglycosides↗
PubMedDate not supplied

Outcome of peritonitis treated with intraperitoneal (i.p.) weekly vancomycin and i.p. daily netilmicin.

The treatment of peritoneal dialysis related peritonitis has been streamlined by the recommendations of an ad hoc committee, which has advocated avoidance of vancomycin as an empirical therapy because of the prevailing problems of vancomycin resistant enterococci (VRE). This report relates to the continued use of vancomycin combined with netilmicin in our programme as empiric therapy for CAPD peritonitis and reports on favorable results of over 80% cure rate using this regimen. The need for change to vancomycin avoiding regimes has to be related to the knowledge of local prevalence of VRE and staphylococcal sensitivity patterns.

Anti-Bacterial Agents↗
PubMed1991

Influence of aztreonam-netilmicin association on outer membrane proteins of P. aeruginosa strains.

P. aeruginosa is highly resistant to a wide range of antimicrobial agents. This intrinsic resistance mainly depends on the rate of permeation across the outer membrane (o.m.). In order to promote antibiotic uptake across the hydrophilic channel of the o.m. porins, a permeator can be used with a hydrophilic antibiotic. In the present study we assess the o.m. electrophoretic profile of three P. aeruginosa strains cultured with and without antibiotic Aztreonam and Netilmicin (A:N) using the MIC concentration in the association (3:1). The observed increase in the band can be referred to the F porin when the strains are treated with Aztreonam.

Aztreonam↗
PubMed1991

[Pharmacokinetics of netilmicin in patients after abdominal surgery].

The pharmacokinetics of netilmicin (NTL) was examined in normal volunteers and patients after abdominal surgery who received a single administration of 100 mg, intramuscularly (i.m.) or intravenously (d.i.v.) over 30 or 60 minutes. In postoperative patients, the serum half life after i.m. or d.i.v. was increased, and absorption after i.m. was delayed compared to those in normal volunteers. No large differences between normal volunteers and postoperative patients were found in peak serum levels. The clearance of NTL from circulation was so rapid that the serum level decreased to below 1.0 micrograms/ml at 8 hours after administration. Renal functions were monitored after abdominal surgery in 116 patients who received NTL at a dose of 200 mg daily for 3-13 days by i.m. or d.i.v. Slight increases in serum creatinine were observed in only 2 patients after i.m., but not after d.i.v. From these results, intravenous infusion over 30 or 60 minutes of NTL seemed safe and effective for the prevention of postoperative infections after abdominal surgery.

Abdomen↗
PubMed1990

[Therapeutic effects of a combination treatment with cefmetazole and netilmicin against infections complicated with hematological disorders].

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Adult↗
PubMed1989

[Netilmicin in single daily doses for the bacterial bronchopulmonary complications in patients with advanced bronchogenic carcinoma].

In 40 patients with bacterial bronchopulmonary complications during polychemotherapy for advanced bronchogenic carcinoma, once-daily netilmicin (4.5 mg/kg every 24 h) brought about complete resolution of the infective process in 90% of the cases and eradication of the responsible pathogen in 82%. This result must be considered good in view of the patients' precarious condition due to their advanced neoplastic disease.

Adult↗
PubMed1989

[Bactericidal activity of daptomycin and vancomycin alone or in combination with tobramycin, netilmicin or ampicillin against enterococcus].

The in vitro bactericidal activity of daptomycin and vancomycin alone or in combination was studied against enterococci in a microtiter checkerboard assay and by kill-kinetic experiments. Daptomycin was more active than vancomycin and was bactericidal. Better Fractional Bactericidal Concentration indices were observed with combinations of vancomycin with aminoglycosides, but in kill-kinetic studies, the combinations of 4 MICs of daptomycin with 4 mg/l of tobramycin or netilmicin produced the more lethal effect; these combinations were even more lethal than ampicillin and aminoglycosides in the same conditions. While vancomycin and ampicillin were antagonistic, synergistic FBC indices were observed with daptomycin and ampicillin in combination, but at 4 MICs of each antibiotic, the combination was less bactericidal than ampicillin alone. The bactericidal effect obtained with daptomycin in combination with aminoglycosides suggest that further evaluation of these combinations in enterococcal endocarditis could have a clinical interest if this bactericidal effect was confirmed by in vivo studies.

Ampicillin↗