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PubMed1997

Comparison of postantibiotic effects of imipenem and netilmicin alone and in combination against Pseudomonas aeruginosa.

Imipenem (CAS 64221-86-9) as well as netilmicin (CAS 56391-57-2) at suprainhibitory concentrations induced the postantibiotic effects against three P. aeruginosa strains. Imipenem (2 x or 4 x minimal inhibitory concentration (MIC)) showed postantibiotic effects in the range of 0.3-1.6 h and 0.9-4.0 h. Netilmicin at the same concentrations produced postantibiotic effects of 3.0-3.8 h and 3.5-4.5 h. Postantibiotic effects manifested by imipenem (2 x or 4 x MIC) + netilmicin (2 x MIC) combination were somewhat longer (in the range of 4.6-4.9 h and 5.8-7.4 h) than the mathematical sum of postantibiotic effects induced by drugs alone (in the range of 4.1-4.7 h and 4.7-7.0 h).

Carbapenems↗
PubMed1976

Sisomicin versus netilmicin: in vitro susceptibility testing.

Antimicrobial susceptibility to sisomicin and netilmicin (Sch 20569) was determined on 164 clinical isolates using a broth microdilution method. Sisomicin was active against 86.1%, and netilmicin against 96.4%, of the isolates. In addition, netilmicin was active against 93.7% of the strains that were resistant to gentamicin, kanamycin, tobramycin, and sisomicin.

Aminoglycosides↗
PubMed1977

Antibacterial activity of netilmicin, a new aminoglycoside antibiotic, compared with that of gentamicin.

The antibacterial activity of netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was compared with that of gentamicin against a variety of gram-negative bacteria, staphylococci, and streptococci. Both antibiotics had similar activity against most organisms, but netilmicin had appreciably greater activity against gram-negative organisms that were resistant to gentamicin because these species synthesized aminoglycoside 3-N-acetyltransferase I or aminoglycoside 2''-O-nucleotidyltransferase. Netilmicin was also more active than gentamicin against gentamicin-resistant strains of Staphylococcus aureus that produced two enzymes-aminoglycoside-2''-O-phosphotransferase and aminoglycoside-6'-N-acetyltransferase.

Anti-Bacterial Agents↗
PubMed1977

Synergy of penicillin-netilmicin combinations against enterococci including strains highly resistant to streptomycin or kanamycin.

The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of </=7 mug/ml for either netilmicin or sisomicin. Studies on the kinetics of killing produced by these combinations showed the rate and extent of killing to be directly dependent upon the organism's relative susceptibility to the aminoglycoside alone and the aminoglycoside concentration in the combination. Results also indicated that the interaction between penicillin and netilmicin was true synergy; i.e., rapid and complete killing was produced by combinations containing each drug at concentrations insufficient to produce any killing alone, and the killing observed could not be produced by either drug alone at a concentration equivalent to the total drug concentration in the combination. The potential clinical application of this synergistic interaction should be investigated further, especially in view of recent reports showing netilmicin to be considerably less toxic than gentamicin in experimental animals.

Anti-Bacterial Agents↗
PubMed1977

Activity of netilmicin compared with those of gentamicin and tobramycin against enterobacteria and Pseudomonas aeruginosa.

The inhibitory activity of netilmicin against 500 isolates of gram-negative bacteria was compared with those of gentamicin and tobramycin. Netilmicin was considerably less active than tobramycin and slightly less inhibitory than gentamicin for Pseudomonas aeruginosa but was at least as active against Escherichia coli and Klebsiella pneumoniae as were the other two antibiotics. A few Klebsiella and Serratia isolates resistant to gentamicin and tobramycin were inhibited by netilmicin. All three antibiotics were strongly bactericidal for E. coli, K. pneumoniae and P. aeruginosa but had less lethal activity against the otherwise susceptible Serratia isolates tested. Some necessary precautions in reading minimal inhibitory concentrations on agar media are stressed, and some possible advantages of a 4-h bactericidal test, using a constant antibiotic concentration, are defined.

Anti-Bacterial Agents↗
PubMed1978

Pharmacology and efficacy of netilmicin.

Twenty-six patients, 20 to 77 years of age, were treated with netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min intravenous infusion. The mean serum half-lives in patients with creatinine clearances of >/=90 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of </=1.4 mg/100 ml and creatinine clearances of >/=60 ml/min, mean serum levels were 9.0 and 1.2 mug/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 mug/ml, respectively, 1 and 8 h post-intramuscular injection. Twenty-five patients had acute pyelonephritis; 7 of the 25 had bacteremia. The infecting bacteria were Escherichia coli (15), Proteus mirabilis (5), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (1), Enterobacter hafniae (1), and both Proteus rettgeri and Proteus morganii (1). All were inhibited by 6.3 mug of netilmicin per ml, except for the P. rettgeri, which required 25 mug/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous renal insufficiency. Three patients, one with abnormal renal function, developed ototoxicity detected only with audiograms. These studies suggest that netilmicin is effective in serious gram-negative bacillary infections, but is nephrotoxic and ototoxic in humans.

Adult↗
PubMed1978

In vitro activity of netilmicin (SCH 20569) against bacterial isolates from ill children.

A new aminoglycoside antibiotic, netilmicin, was tested against 306 clinical isolates from ill children and compared with sisomicin and gentamicin. Activity against Enterobacteriaceae was similar to that of gentamicin but less than that of sisomicin. Two gentamicin-resistant strains of Enterobacteriaceae (Klebsiella, MIC 6.25 microgram/ml, Escherichia coli, MIC 12.5 microgram/ml) were susceptible to netilimicin (MIC 3.12 microgram/ml). Netilmicin was ineffective against almost all strains of Pseudomonas but active against the majority of strains of Staphylococcus, Neisseria meningitidis and Haemophilus influenzae tested. Disc diffusion sensitivity results correlated in general with the agar dilution test. Netilmicin had little activity against Pseudomonas but may be useful in the treatment of infections due to gentamicin-resistant Enterobacteriaceae.

Aminoglycosides↗
PubMed1985

Gentamicin, tobramycin, amikacin, and netilmicin levels in tears following intravenous administration.

Peak and trough tear and serum concentrations were determined in 27 human volunteers undergoing intravenous (IV) gentamicin sulfate, tobramycin sulfate, amikacin sulfate, and netilmicin sulfate therapy. Although effective serum concentrations were achieved, tear levels were subtherapeutic. The mean peak tear concentrations were 0.4 microgram/mL, 0.5 microgram/mL, 1.7 micrograms/mL, and 0.3 microgram/mL for gentamicin, tobramycin, amikacin, and netilmicin, respectively. These levels did not approach the minimum inhibitory concentrations for Pseudomonas and raise some concern regarding the risk-benefit ratio of IV antibiotics for bacterial keratitis.

Adult↗
PubMed1983

Penetration of netilmicin into heart valves, subcutaneous and muscular tissue of patients undergoing heart surgery.

In 57 patients undergoing heart surgery concentrations of netilmicin in plasma, heart valves, muscle, and subcutaneous tissue were determined after a 5 min intravenous bolus injection of 1.5 mg/kg body weight. Within 8 h netilmicin serum concentration declined from 3 micrograms/ml to 1 microgram/ml. In heart valves the concentrations during heart surgery were high enough to inhibit most staphylococci, Klebisiella, Enterobacter and Escherichia coli strains. No different serum and tissue concentrations in patients with and without extracorporal circulation could be found.

Adipose Tissue↗
PubMed1990

The impact of different dosing regimens of the aminoglycosides netilmicin and amikacin on vestibulotoxicity in the guinea pig.

The purpose of this study was to assess whether vestibulotoxicity caused by aminoglycoside antibiotics is influenced by the treatment schedule used: i.e., a single high dose given once daily (o.d.) vs multiple divided doses (tres in die, t.i.d.). Two groups of guinea pigs (5 animals/group) were injected intramuscularly for 21 days with either netilmicin or amikacin 150 mg/kg o.d., whereas other groups received each drug at 50 mg/kg t.i.d. at 8-h intervals. Amikacin was also given at 225 mg/kg o.d. and 75 mg/kg t.i.d. Vestibular functions were assessed by measuring vestibulo-ocular reflexes. Acoustic function was also evaluated by measuring Preyer's pinna reflex. Sensory epithelia of the inner ears were evaluated histologically under a scanning electron microscope. Netilmicin failed to affect either the vestibular or the acoustic apparatus in the animal groups receiving the two dosing regimens. Amikacin in a dose of 150 mg/kg per day induced an acoustic deficit which was more severe in the t.i.d. group. The higher dose of amikacin provoked significant lesions of acoustic and vestibular function, irrespective of the dosing regimen used. These data suggest that the o.d. dosing regimen of the aminoglycoside antibiotics might provide effective treatment for infectious diseases without enhancing the risk for vestibular and acoustic side effects.

Acoustic Stimulation↗
PubMed1983

Short course netilmicin prophylaxis in renal stone surgery.

Following surgery for the removal of intrarenal calculi 30% of patients will develop severe wound complications. This study assesses the role of a short course of netilmicin given over the operative period, in 20 consecutive patients. Preoperative studies demonstrated that whilst 20% of patients had bacterial growth in the urine, culture of the removed calculus demonstrated that 50% of the stones exhibited a significant bacterial growth. Of the 20 patients, only one developed a wound complication. Following the preoperative dose, satisfactory netilmicin levels were obtained and no patient had levels greater than 1 microgram ml-1 by 7 h. Despite some degree of renal impairment, serum urea and creatinine values were unaffected.

Adult↗
PubMed1979

Auditory function in guinea pigs treated with netilmicin and other aminoglycoside antibiotics.

The following aminoglycoside antibiotics netilmicin, sisomicin, gentamicin, and kanamycin were submitted to a comparative study of their ototoxicity using both reflexological (Preyer's pinnareflex) and electrophysiological (near and far field) methods. The daily s.c. administration of sisomicin, gentamicin, and kanamycin for 21 days provoked a dose-related impairment of the cochlear function, detected with all the employed techniques. On the other hand, a very low ototoxic effect of netilmicin was demonstrated with electrophysiological but not with the reflexological evaluation. The reliability of the methods used in these experiments is also compared.

Action Potentials↗
PubMed1987

Netilmicin disk susceptibility tests: effect of cations on the MIC correlates.

When testing Pseudomonas aeruginosa against netilmicin, MICs were markedly affected by the concentration of cations added to the test medium. A susceptible disk test result (zone greater than or equal to 15 mm) corresponded to MIC less than or equal to 4.0 micrograms/ml in unsupplemented broth, less than or equal to 12 micrograms/ml in broth with half the usual amount of cations and less than or equal to 32 micrograms/ml in broth with the recommended concentration of cations. Tests with 30 micrograms netilmicin disks best predicted susceptibility as determined by MICs in broth without added cations. When the MICs were determined in cation supplemented broth, the number of interpretive discrepancies increased to an unacceptably high level.

Cations↗
PubMedDate not supplied

Interpretive criteria for susceptibility testing of coagulase-negative staphylococci with special reference to netilmicin.

Antibiotic susceptibility of 171 isolates of coagulase-negative staphylococci from 66 preterm infants at a neonatal intensive care unit was tested by the microbroth dilution method. Results were interpreted according to DIN as well as according to NCCLS. Because of the bimodal distribution of MIC values within the CNS population tested, results of susceptibility interpretation according to DIN were identical to NCCLS with the exception of netilmicin (NCCLS: 89% susceptibility; DIN: 16% susceptibility). Since netilmicin is frequently used for treatment of infections caused by coagulase-negative staphylococci, this difference may be of clinical significance.

Cross Infection↗
PubMed2004

Piperacillin-tazobactam and netilmicin as a safe and efficacious empirical treatment of febrile neutropenic children.

GOALS OF WORK: We evaluated piperacillin-tazobactam in association with netilmicin (TN) in the early empirical treatment of neutropenic children, as data are limited in number. PATIENTS AND METHOD: In 1996, an observational study was initiated to assess the efficacy and safety of this association, with a glycopeptide (TNG) if needed. The impact on the bacterial ecology of our unit was also observed. Children were treated for hematological malignancy or solid tumor between September 1996 and December 1998 and presented a febrile neutropenia. RESULTS: There were 148 evaluable febrile neutropenic episodes in 104 patients. Median age was 7 years, 55% of the episodes were fever of unknown origin, 22% were clinically documented and 23% microbiologically documented (27 bacteriemia). A glycopeptide was added in 67 episodes. The initial unmodified treatment was successful in 114 episodes (77%): 75/81 episodes in the TN group and 39/67 in the TNG group. For successful episodes, median treatment duration was 6 days. There were 22 febrile recurrences. These patients, as well as initial failures, always responded to a second-line treatment. One child was considered a failure because he developed a skin rash probably due to piperacillin-tazobactam and required another beta-lactamase. CONCLUSION: This study suggests that piperacillin-tazobactam in association with netilmicin presents a satisfactory efficacy and a good tolerance as empirical therapy for febrile neutropenic children. It allowed us to maintain the bacterial ecology of our unit.

Adolescent↗
PubMed1990

Ceftriaxone vs. azlocillin and netilmicin in the treatment of febrile neutropenic children.

Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children.

Adolescent↗
PubMed1988

A multicentre study to compare piperacillin with the combination of netilmicin and metronidazole for prophylaxis in elective colorectal surgery undertaken in district general hospitals.

We have conducted a multicentre randomized study to compare piperacillin with the combination of netilmicin and metronidazole in patients undergoing elective colorectal surgery. There was no significant difference in the incidence of operation-related infection, chest or urinary tract infection. Major life-threatening sepsis occurred in 6% and the overall incidence of operation-related infection was 24%. Organisms which normally inhabit the bowel lumen were cultured from most of the postoperative infections; however, Staphylococcus aureus was isolated as a causative organism in nine patients in the piperacillin group compared with none in the netilmicin and metronidazole group. We are concerned at the high incidence of infection in both groups, and we believe that other factors in addition to prophylactic antibiotics need to be evaluated if the incidence of infection is to be reduced further.

Adult↗
PubMed2005

Capillary electrophoresis assay of netilmicin sulphate.

An effective method based on capillary electrophoresis (CE) for the determination of netilmicin sulphate in commercial ophthalmic formulations was developed and validated. The use of a polymer-coated capillary and a non-absorbing running buffer permitted the elution of netilmicin in cationic mode at pH 3.0 and with direct UV detection at lambda=195 nm. Since pre-treatment of the samples is not required, this procedure may be straightforwardly applied to the other aminoglycosides provided that their extinction coefficient is not too low.

Electrophoresis, Capillary↗