netilmicin and Bacterial-Infections

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.. 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).. 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).. 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.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Postoperative Complications; Retrospective Studies; Treatment Outcome; Urinary Tract Infections

Conventionally, aminoglycosides have been administered in two or three daily doses. Numerous in-vitro and animal experiments and several clinical trials favour a once-daily dosage regimen of aminoglycosides, which provides a more rapid concentration-dependent bacterial killing and is probably less toxic than two or three dosage regimens. In this article the pharmacological and microbiological background for once-daily aminoglycoside administration is reviewed, and some controlled trials are discussed. Recommendations for clinical practice are given.

Topics: Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Gentamicins; Guidelines as Topic; Humans; Meta-Analysis as Topic; Netilmicin; Randomized Controlled Trials as Topic

Netilmicin is a semisynthetic aminoglycoside derived from sisomicin. It is active against most Gram-negative and some Gram-positive bacteria, including many gentamicin-resistant strains. Netilmicin has proved to be effective in Gram-negative infections of the urinary tract, skin and skin structure, and lower respiratory tract, as well as in intra-abdominal infections, septicaemia and other miscellaneous infections. In some trials, the more easily implemented once daily administration of netilmicin has been as effective as multiple dosing regimens. However, further investigation is required to confirm that efficacy and safety are not compromised with once daily administration. Comparative studies have generally revealed similar clinical and bacteriological efficacies between netilmicin and gentamicin, amikacin or tobramycin. As with other aminoglycosides, the principal adverse effects of netilmicin are nephrotoxicity and ototoxicity. Although animal studies strongly suggest that these are less common with netilmicin than with related drugs, there appears to be no difference in their incidence in clinical use; in clinical trials the incidence of nephrotoxicity and ototoxicity has been low, with the symptoms in many cases being minor and reversible. Netilmicin is, therefore, an effective antibacterial drug for the parenteral treatment of severe infections, offering theoretical advantages in safety which may indicate its use for patients believed to be at risk of adverse effects.

Topics: Animals; Bacteria; Bacterial Infections; Humans; Netilmicin

This article presents an overview of the aminoglycoside antibiotics used in clinical practice. Facts concerning the discovery and properties of the aminoglycosides are followed by information about spectrums of activity and mechanisms of action and resistance. Individual compounds are compared and proposals on the possibilities for their clinical use, both as single drugs and in combination with beta-lactam antibiotics, are made. The importance placed on measuring the serum concentrations of aminoglycoside antibiotics should serve as a remainder that this procedure is important, on one hand, to increase clinical efficacy and, on the other, to reduce the side effects of these antibiotics. Finally, the aminoglycosides are compared briefly with other antibacterial compounds, some of which are very new. There is no doubt that in the future the aminoglycosides will continue to occupy an important place in the treatment of severe infections, although newly developed agents appear to be effective complements.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Humans; Kanamycin; Kinetics; Neomycin; Netilmicin; Pneumonia; Sepsis; Sisomicin; Streptomycin; Tobramycin

The discovery that aminosugars found in nature kill common bacteria initiated use of a new class of antibiotics that have played a key role in the management of several major medical problems over the past 40 years. The rapid bactericidal effect of the aminoglycosides on aerobic Gram-negative bacilli has expanded their use to approximately 6% of all our general hospital patients. These agents have many desirable properties, but also have the potential for producing ototoxicity and nephrotoxicity that imposes pharmacological limitations on their optimum use. The experience of earlier investigations demonstrated the need for quantitative measurements and individual patient dosing which has reduced the risk of toxicity many fold. Using sensitive measurements, toxic manifestations can be classified as detectable by laboratory means only, some that have clinical expression and rarely a lasting handicap. Semisynthetic modification of kanamycin (amikacin) and sissomicin (netilmicin) protects these compounds against inactivation by most bacterial enzymes and preserves their effectiveness. Netilmicin seems to have less potential for causing toxicity, especially ototoxicity that is irreversible, and offers the possibility of further gains through pharmacological flexibility without crippling toxicity.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Utilization; Humans; Kanamycin; Male; Netilmicin; Otitis

Sisomicin is a naturally occurring aminoglycoside antibiotic produced by Micromonospora inyoensis, while dibekacin and netilmicin are both semisynthetic aminoglycosides. Dibekacin is 3',4'-dideoxykanamycin B and netilmicin is 1-N-ethyl sisomicin. In both cases, these modifications render the agents insusceptible to some of the enzymes found in resistant strains of bacteria which inactivate the parent compounds. Antibacterial activity: All 3 drugs show bactericidal activity against a wide range of Gram-negative bacteria (including E. coli, Enterobacter, Klebsiella and Proteus spp. and Ps. aeruginosa) and also against staphylococci; however, in common with other amino-glycosides, streptococci are usually resistant (except when beta-lactam antibiotics are used in combination) and anaerobic organisms are not sensitive. Sisomicin is closely related structurally to gentamicin Cla, but in vitro studies have shown it to have superior activity to gentamicin against Ps. aeruginosa, closely paralleling the activity of tobramycin, while still possessing the high activity of gentamicin against Serratia and other Gram-negative rods. However, sisomicin is inactivated by virtually all bacterial enzymes which inactivate gentamicin and tobramycin. Nevertheless, it retains useful activity against a number of gentamicin-resistant strains of Ps. aeruginosa which are resistant by non-enzymatic (possibly permeability barrier) mechanisms; in this respect it closely resembles tobramycin. Dibekacin closely resembles tobramycin structurally and in vitro it seems to have a very similar antibacterial spectrum, including activity against some strains of Ps. aeruginosa resistant to gentamicin. Netilmicin has a generally broader antibacterial spectrum than gentamicin, tobramycin, sisomicin or debekacin and is resistant to inactivation by phosphorylating and adenylylating enzymes; however, it is inactivated by all acetylases, apart from acetylase 3-I. Its spectrum is therefore not as wide as that of amikacin against 'gentamicin-resistant' strains. Nonetheless, it is intrinsically more active than amikacin, weight-for-weight, against sensitive strains, apart possibly from Ps. aeruginosa. In fact, its activity against species of the Enterobacteriaceae and staphylococci sensitive to gentamicin is of the same order as the latter and possibly better for Klebsiella-Enterobacter species. All 3 agents show marked antibacterial synergy with a variety of beta-lactam antibiotics against a range of

Topics: Aging; Animals; Bacterial Infections; Dibekacin; Drug Interactions; Drug Resistance, Microbial; Drug Synergism; Gentamicins; Humans; Kanamycin; Kidney Diseases; Netilmicin; Sisomicin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Gentamicins; Humans; Netilmicin; Penicillins

The data on the toxicity of netilmicin in laboratory animals as well as preliminary data in man are reviewed. Netilmicin is less toxic to the VIIIth nerve than is gentamicin in all species tested. The data suggest that it probably is less ototoxic than tobramycin, although confirmatory studies should be performed. Netilmicin is also nephrotoxic than gentamicin in all species tested. It is less nephrotoxic than tobramycin in the rat and dog. Comparisons in the rat suggest that netilmicin has a flat dose--response curve that resembles the curve produced by streptomycin. In animals, netilmicin produces more neuromuscular blockade than gentamicin; however, neuromuscular blockade with aminoglycosides in man is rare and thus far no episodes have been associated with netilmicin during clinical investigation. Initial clinical studies in man indicate that netilmicin is efficacious and well tolerated. Presently available data suggest that netilmicin offers distinct advantages over older aminoglycosides. Final conclusions must await prospective randomized double-blind trials in man.

Topics: Abnormalities, Drug-Induced; Amikacin; Animals; Anti-Bacterial Agents; Bacterial Infections; Cochlea; Gentamicins; Glomerular Filtration Rate; Hair Cells, Auditory; Hearing; Humans; Kidney; Netilmicin; Reproduction

For a decade gentamicin has been used extensively because of its antimicrobial efficacy and the relatively low prevalence of clinical toxicity. Recently the more frequent appearance of resistant organisms, reports of increased nephrotoxicity and ototoxicity, and the development of newer aminoglycoside antibiotics have raised doubts about the continued use of this agent. This paper reassesses the role of gentamicin. It is clear that an appreciation of the pharmacokinetics and the clinical use of gentamicin as well as an understanding of the patterns of toxicity in animals and humans can lead to more efficient treatment with this antimicrobial agent. Despite ample competition from a number of newer aminoglycoside antibiotics, gentamicin will probably continue to be used widely in the near future.

Topics: Amikacin; Animals; Bacterial Infections; Drug Synergism; Ear Diseases; Gentamicins; Humans; Kidney; Kidney Diseases; Netilmicin; Penicillin Resistance; Penicillins; Respiratory Tract Infections; Sisomicin; Tobramycin; Urinary Tract Infections

We compared the effectiveness of a single dose and a three-day course of antibiotic prophylaxis in preventing bacterial infections in high-risk neonates. The study was a prospective, randomized controlled trial conducted in a 20-bed tertiary referral neonatal intensive care unit (NICU). A series of 130 neonates admitted consecutively to the NICU, fulfilling risk factors for infection, were assigned at random to receive intravenous antibiotic prophylaxis with ampicillin and netilmicin either in two daily doses for 72 h (three-day-administration group, 67 infants) or in a single bolus injection on admission (bolus group, 63 infants). Hospital-acquired infection, the main outcome measure, was defined as infection that developed at least 48 h after admission, and vertical infection (maternally transmitted) was considered to be present when clinical symptoms and abnormal laboratory findings became evident within 48 h of birth. Infections were considered as suspected when clinical and laboratory findings of infection were present, without positive cultures, and as confirmed when positive cultures were also present. No significant differences were found between the two groups of neonates studied in mean birth weight, gestational age or postnatal age on admission. The incidence of vertical infection was similar in the two groups (16/67, 23.9% vs. 14/63, 22.2%). Of the 130 newborns studied, 29 (22.3%) acquired at least one nosocomial infection during their NICU stay; total hospital-acquired infections, calculated as the incidence density of infection (the number of infective episodes divided by the number of days in the NICU), were less frequent among newborns who received the three-day course than the bolus (relative risk 0.69). This difference, although not statistically significant, depended on the different incidence density of confirmed nosocomial infections rather than on suspected infections (relative risk 0.59; 95% confidence interval 0.32-1.09; P=0.1). There were no significant differences between the two groups in overall mortality. A single bolus administration on admission is therefore likely to be as effective as a three-day course of antibiotic prophylaxis in preventing bacterial infection in high-risk infants admitted to an NICU.

Topics: Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Cross Infection; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infection Control; Infusions, Intravenous; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Italy; Male; Netilmicin; Treatment Outcome

A randomized comparative investigation was carried out in two equal groups of patients with pyo-inflammatory diseases of lower extremities (the total number 50 patients) in order to study effectiveness and tolerance to Netilmycin (1st group) and Gentamycin (2nd group) given in combination with Cefasolin. Clinical symptoms were estimated immediately after operation, in 3, 6 and 10-12 days after it. Bacteriological investigations were fulfilled immediately after operation, in 72 h and in 6-10 days after the beginning of antibacterial therapy. Clinical and biochemical investigations of blood were fulfilled before and in 10 days after the beginning of the treatment. Effectiveness of the treatment in the first group was 100%, in the second group--80%. In the second group the antibiotics were changed in 20% of cases and the average duration of hospitalization among the patients of this group was reliably longer that in the first group. The eradication rating of Netilmycin was higher than that of Gentamycin (25 strains from 25 and 20 from 25 respectively). Gentamycin had a pronounced nephrotoxic effect (elevation of the level of creatinin and urea of blood in dynamics by 21% and 32%), as compared with Netilmycin (9% and 3%). Total expenses to antibiotic therapy in the first group made up 97,650 rub, and in the second group 106,245 rub. Netilmycin in combination with Cefasolin was more effective for acute pyo-inflammatory diseases of lower extremities than a combination of Gentamycin with Cefasolin, it more rapidly resulted in reduction of clinical signs of inflammation, was better endured and more economical.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cefazolin; Cost-Benefit Analysis; Female; Gentamicins; Humans; Inflammation; Lower Extremity; Male; Middle Aged; Netilmicin; Suppuration; Treatment Outcome

To compare the efficacy and safety of two aminoglycoside antibiotics, etimicin and netilmicin, in the treatment of bacterial infections.. A randomized, open label, controlled clinical trial was conducted for the treatment of 65 patients hospitalized with respiratory tract infections, urinary tract infections, and skin and tissue infections. Thirty-four patients received etimicin and thirty-one patients received netilmicin at a dose of 100 mg every 12 hours by intravenous infusion. The duration of treatment was 7-10 days in both groups.. 47 patients were enrolled in the etimicin group; 35 patients were assessable for safety and 34 patients were assessable for efficacy, 46 patients were enrolled in the netilmicin group; 32 patients were assessable for safety and 31 patients were assessable for efficacy. The results show that overall efficacy was 85.3% for the etimicin group and 83.9% for the netilmicin group, whereas bacterial clearance rates were 87.5% for the etimicin group and 89.7% for the netilmicin group. The incidence of adverse reactions was 8.6% (3/35) and 9.4% (3/32), respectively.. Etimicin and netilmicin were effective and safe for the treatment of respiratory tract infection, urinary tract infection, and skin and tissue infections. The results show there was no statistically significant difference between the two groups (P > 0.05).

Topics: Adolescent; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Female; Humans; Male; Middle Aged; Netilmicin; Respiratory Tract Infections; Skin Diseases, Bacterial; Urinary Tract Infections

To reduce drug acquisition costs, the clinical and bacteriological efficacy of low-dose ceftazidime i.v. (1 g tid) was compared with cefotaxime i.v. (2 g tid). Both regimens were combined with netilmicin i.v. (2 mg/kg bodyweight tid), in an open, randomized, multicentre trial in febrile neutropenic patients. The addition of antibiotics for gram-positive coverage was part of the protocol; alteration in the antibiotics for gram-negative cover or premature discontinuation of the study antibiotics were judged as failure. One hundred and eighty six patients were randomized by nine German centres, the patients matched for age, underlying diseases and duration of neutropenia (median duration 14 days) in both treatment arms. Infections were documented microbiologically in 29% of the patients, clinically in 16% and suspected (fever of unknown origin) in 102/186 patients (55%). The 82 pathogens isolated were predominantly gram-positive bacteria. In an intent-to-treat analysis, the overall response rate without modification at the final evaluation was 58% in the ceftazidime group and 34% in the cefotaxime group (P < 0.01). The success rates with modification were 84% and 64%, respectively. The failure rate in a highly immunosuppressed subgroup of the patients (bone marrow transplant recipients) was higher for cefotaxime (53%) than for the ceftazidime arm (14%) (P < 0.001). Response rates were significantly higher in the ceftazidime group for patients with microbiologically documented and possible infections. No major bacterial superinfections occurred in the low-dose treatment arm. The tolerability was good for both regimens. Low-dose ceftazidime combined with netilmicin proved to be superior to recommended doses of cefotaxime/netilmicin in febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Neutropenia; Superinfection; Treatment Outcome

The aim of this study was to compare the clinical and microbiological efficacy of netilmicin plus imipenem-cilastatin (Net + Imi) vs netilmicin plus ceftazidime (Net + Cef) as empiric antimicrobial therapy in bone marrow transplant (BMT) febrile neutropenic patients (pts). Sixty-six pts undergoing BMT for hematological malignancies and solid tumors were randomized to receive Net + Imi or Net + Cef as first-line antibiotic therapy. A lasting return of temperature to normal and complete disappearance of either clinical or cultural signs of infection without any modification of therapy was considered as improvement; the persistence of fever after 72 hours, the addition of a third antibiotic or a protocol change was considered as failure. Sixty-nine episodes were randomized during the course of the trial; bacteriological evidence of infection was obtained in 17 (25%) febrile episodes. Overall outcome based on clinical responses was as follows: 80% of pts on Net + Imi responded compared to 73% of those on Net + Cef. For microbiologically documented infections response rates were 70% in Net + Imi group and 43% in the Net + Cef group (p = ns). Neither septic death nor toxicity were observed. Both empiric regimens were shown to be effective; Net + Imi appeared to be more effective in microbiologically documented infections but there was no statistical significance. In conclusion, both Net + Imi and Net + Cef are active and safe as empirical treatment of febrile episodes in neutropenic BMT pts.

Topics: Adolescent; Adult; Bacteria; Bacterial Infections; Bone Marrow Transplantation; Ceftazidime; Cephalosporins; Child; Cilastatin; Drug Synergism; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Imipenem; Male; Middle Aged; Netilmicin; Neutropenia; Postoperative Complications; Protease Inhibitors; Thienamycins; Treatment Outcome

Little has been reported on serum levels attained using once-daily aminoglycoside regimens and their relation to dosage administered and renal function. Consecutive patients with serious infections were randomized to receive gentamicin 4 mg/kg q 24h i.v. (n = 69), gentamicin 1.33 mg/kg q 8h i.v. (n = 46) or netilmicin 5.5 mg/kg q 24h i.v. (n = 59) (with dose reduction in case of renal dysfunction). In the three groups, median first serum trough levels were 0.4, 1.0 and 0.4 mg/l, respectively, and median first serum peak levels were 9.5, 4.7 and 12.2 mg/l (p < 0.01 once-daily vs. thrice-daily regimens). Dose adjustment because of first trough concentrations of > 2 mg/l and/or peak concentrations of < 6 mg/l was required in 6%, 78% and 12% of patients, respectively. Second trough and peak concentrations were significantly higher in the thrice-daily gentamicin group; serum levels remained constant in the other two groups. The six patients in the once-daily groups who developed elevated trough levels later in therapy were characterized in most cases by a decline in renal function.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Gentamicins; Humans; Kidney Function Tests; Male; Middle Aged; Netilmicin; Prospective Studies

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of > or = 20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a > 25 mumol/L or > 25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4 mg/L). Half-lives of netilmicin determined between 1 and 8 h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P < 0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined between 8 and 24 h in the od group (mean of 5.7 h, P < 0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Drug Administration Schedule; Female; Gentamicins; Hearing; Humans; Kidney; Male; Middle Aged; Netilmicin; Prospective Studies

Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg once daily i.v. or netilmicin 5.5 mg/kg once daily i.v. (with dosage reduction in case of renal dysfunction). Exclusion criteria were neutropenia or severe renal failure. Median first serum trough and peak concentrations were 0.4/9.5 mg/L and 0.4/12.2 mg/L, for gentamicin and netilmicin respectively. A good clinical response was observed in 50/54 (92.6%) evaluable patients treated with gentamicin and in 48/52 (92.3%) netilmicin-treated patients. Nephrotoxicity (a rise of serum creatinine > or = 45 mumol/L) developed in 5/72 (6.9%) gentamicin patients treated > or = 48 hours and in 10/69 (14.5%) netilmicin patients (difference 7.5%, 95% CI -3.9% to +16.2%). High-tone audiometry was performed when possible; no significant differences were found between the regimens with regard to hearing loss or prodromal signs of ototoxicity. We conclude that with once-daily dosing no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.

Topics: Aged; Bacterial Infections; Creatinine; Female; Gentamicins; Hearing Disorders; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Risk Factors

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Topics: Adult; Aged; Bacteremia; Bacterial Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Netilmicin; Peritonitis; Pneumonia; Prospective Studies

Detection of hearing impairment in early childhood is difficult. We serially recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of ototoxicity in term, healthy newborns and compared the results to a second group of term babies treated for perinatally acquired bacterial infection with ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation, in the group of 45 healthy children born at term, well reproducible emissions were observed in all but two children. In each of these two, initially well reproducible TEOAEs were detected in one ear only. At the time of the second recording (mean at day 8.5) excellent emissions were seen in all ears of all children. Similarly, in the second group receiving ampicillin plus either cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE-reproducibility was equal or even increased at the time of the second evaluation in all 17 patients. In the following group of 59 patients, all receiving ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time of follow-up examinations. In all patients, a reduced general condition tended to be associated with less reproducible TEOAEs. We conclude that at conventional doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and that in early childhood serial TEOAE-recording may be useful for evaluation of inner ear function.

Topics: Ampicillin; Anti-Bacterial Agents; Auditory Perception; Bacterial Infections; Cefotaxime; Cochlea; Evoked Potentials, Auditory; Female; Follow-Up Studies; Humans; Infant, Newborn; Male; Netilmicin; Reflex, Acoustic; Reproducibility of Results; Tobramycin

We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Hearing Loss, Bilateral; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Netilmicin; Prospective Studies; Tobramycin

A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including either initial 24 hours lavage before resumption of routine CAPD schedule (prior standard approach) or continued prolonged exchanges as in routine CAPD schedule. Median time to solved infection (normalization of white cell count in dialysis effluent) was identical (3 days) in the two groups. Treatment success rate was found to be 72% in the group with initial lavage and 89% in the group with prolonged exchanges. The difference in treatment success (17%) in favour of continued CAPD schedule was not found significant (95% confidence limits--1% to 35%). The results suggest lavage to be of no clinical benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock.

Topics: Acute Disease; Bacterial Infections; Humans; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritoneal Lavage; Peritonitis; Recurrence; Vancomycin

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.

Topics: Audiometry; Bacterial Infections; Creatinine; Edetic Acid; Electronystagmography; Gentamicins; Hearing Disorders; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Diseases; Middle Aged; Netilmicin; Randomized Controlled Trials as Topic; Vestibular Diseases; Vestibular Function Tests

We examined the efficacy of ciprofloxacin as an empirical treatment for fever in 97 neutropenic patients in a randomized study of ciprofloxacin and benzylpenicillin versus netilmicin and piperacillin. Benzylpenicillin was included because of evidence of in-vitro resistance to ciprofloxacin in some streptococci. Clinical response rate was similar in the two groups (46% resolution for ciprofloxacin/benzylpenicillin and 52% for netilmicin/piperacillin). Microbiological assessment revealed more pathogens eradicated by ciprofloxacin and benzylpenicillin (66%) and fewer persisting (3%) than in patients receiving netilmicin and piperacillin (52% and 13% respectively). Staphylococcus epidermidis was the commonest pathogen, accounting for 38% of all isolates and 30% of all treatment failures. There were no treatment failures or superinfections due to streptococci. More therapy-related adverse reactions were seen in patients on netilmicin and piperacillin (28%) compared with those on ciprofloxacin and benzylpenicillin (10%). The combination of ciprofloxacin and benzylpenicillin is as effective as a standard regimen of netilmicin and piperacillin, with fewer adverse effects, and is highly attractive as empirical therapy for the febrile, neutropenic host. The inclusion of benzylpenicillin prevents streptococcal-associated treatment failure.

Topics: Adult; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Fever; Humans; Injections, Intravenous; Middle Aged; Netilmicin; Neutropenia; Penicillin G; Piperacillin; Prospective Studies; Randomized Controlled Trials as Topic

One hundred and ninety-seven patients with intraabdominal infections were enrolled in a prospective randomized multicenter study of netilmicin administered once daily (n = 98) versus thrice daily (n = 99) in combination with tinidazole administered once daily. Randomization was achieved for the infection site, clinical severity score, daily and total netilmicin dose, and duration of treatment. The mean maximum peak and trough levels of netilmicin in serum were 21.1 and 1.3 mg/l respectively for once daily treated patients, and 10.0 and 2.3 mg/l for thrice daily treated patients (p less than 0.05 for both parameters). The clinical response did not differ between patients treated once daily and those treated thrice daily. Overall rates for clinical cure, improvement and failure of therapy were 77%, 17% and 6% respectively. No significant differences were found between once daily and thrice daily regimens in the occurrence of auditory, vestibular and renal toxicity, overall rates being 5%, 1% and 10% respectively. Impairment of renal function was significantly related to higher maximum netilmicin serum trough levels during therapy, a higher clinical severity score and advanced age. It is concluded that netilmicin given once daily is as effective and safe as the multiple dose regimen. However, monitoring of aminoglycoside serum through levels is still advisable, especially in the old and severely ill patient.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Drug Administration Schedule; Female; Humans; Kidney; Male; Middle Aged; Multicenter Studies as Topic; Netilmicin; Prospective Studies; Randomized Controlled Trials as Topic

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.

Topics: Adolescent; Agranulocytosis; Azlocillin; Bacteria; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Netilmicin; Neutropenia; Randomized Controlled Trials as Topic

Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside.. We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin.. Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses.. Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Prospective Studies; Randomized Controlled Trials as Topic

A prospective, randomized study was carried out in order to assess the efficacy and safety of the mezlocillin-netilmicin combination in the prophylaxis of first permanent transvenous cardiac pacemaker implantation. Five hundred and fifty-two consecutive patients were randomly administered either 2 g mezlocillin and 200 mg netilmicin both as an i.v. bolus before implantation or 2g mezlocillin before and then 6 and 12 hours after surgery and 200 mg netilmicin before and then 12 hours after implantation. No adverse events were seen. Neither pocket nor electrode infections were observed in the 457 subjects still alive (mean follow-up: 29.2 months) or in patients who died after 1 year of follow-up (mean follow-up: 20.1 months) or before this time (mean follow-up: 4.7 months). The serum and pocket concentrations of mezlocillin and netilmicin at the end of surgery were found to be adequate to cover microorganisms that most often cause infections, including methicillin-resistant staphylococci.

Topics: Bacterial Infections; Drug Therapy, Combination; Humans; Injections, Intravenous; Mezlocillin; Netilmicin; Pacemaker, Artificial; Postoperative Complications; Premedication; Prospective Studies; Risk Factors

The Authors report the results obtained in 35 patients of either sex suffering from various systemic infections and treated with netilmicin. Netilmicin has been intramuscularly administered in once daily dose of 4.5 mg/kg (mean daily dose 294.3 mg) for a mean duration of 17.8 days. The clinical resolution of the infections has been achieved in 97.1% (34 patients) of the study population; only one patient showed failure. Thirty-three of the 35 baseline causative pathogens have been eradicated. The local and systemic tolerability was good. The serum pharmacokinetics showed bactericidal levels of netilmicin and no serum accumulation.

Topics: Adult; Aged; Bacterial Infections; Drug Administration Schedule; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin

A randomized study of treatment with ciprofloxacin combined with benzylpenicillin (CB) versus a standard regimen of netilmicin combined with piperacillin (NP) as first-line empiric therapy was conducted in febrile neutropenic patients. Ninety-six patients were evaluable for determination of efficacy: 50 patients received CB and 46 patients received NP. There was no significant difference between the two groups in terms of age or primary diagnosis. Overall clinical response rate at the end of therapy was 66 percent for CB and 65 percent for NP. Microbiologic assessment revealed more pathogens eradicated by CB (64 percent) and fewer persisting (4 percent) than in the NP group (52 percent eradicated, 13 percent persisting). Only 10 percent of patients in the CB group had treatment-related adverse reactions as opposed to 28 percent of the NP-treated patients; these were predominantly renal impairment and were likely to have been due to the aminoglycoside. Staphylococcus epidermidis was the most commonly isolated pathogen, accounting for 38 percent of all isolates and 30 percent of all patients in whom treatment failed. Although streptococci accounted for 18 percent of the isolated pathogens, no treatment failures or superinfections were due to these organisms. This indicates an advantage of combining ciprofloxacin with benzylpenicillin. We conclude that the CB regimen is as effective as the NP treatment and is associated with fewer side effects.

Topics: Adult; Agranulocytosis; Bacteria; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Fever; Humans; Infusions, Intravenous; Middle Aged; Netilmicin; Neutropenia; Penicillin G; Piperacillin; Random Allocation

To assess the efficacy of ciprofloxacin in neutropenic patients, we conducted a randomized prospective trial comparing the combination of ciprofloxacin and netilmicin against piperacillin plus netilmicin as an empiric treatment of fever in cancer patients with neutropenia. Of 214 evaluable episodes, 115 and 99 were randomly assigned to the ciprofloxacin and the piperacillin arms, respectively. The overall response rates were very similar (59 and 62% for the ciprofloxacin and piperacillin arms, respectively). The response for the gram-positive bacteremias was almost identical (around 40%); this low response was due in part to an outbreak of infection by a multiply resistant strain of Staphylococcus epidermidis (for which the ciprofloxacin MIC was greater than or equal to 128 micrograms/ml) which occurred during the second half of the trial. Among gram-negative bacteremias, 9 of 11 infections (82%) responded to the ciprofloxacin combination compared with 3 of 7 (43%) that responded to the piperacillin combination (P = 0.23). The incidences of persistent, profound neutropenia were comparable in both treatments, but the susceptibility of the gram-negative organism to ciprofloxacin and netilmicin was significantly higher than was susceptibility to the other combination. Ciprofloxacin was well tolerated, and patients were able to convert from intravenous to oral therapy in 64 of 115 episodes.

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Intravenous; Injections, Intravenous; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Piperacillin; Prospective Studies; Random Allocation

In a randomized trial ceftazidime plus piperacillin or azlocillin, and netilmicin plus piperacillin or azlocillin were used as initial empirical therapy in 202 febrile neutropenic episodes. Netilmicin plus azlocillin was the most effective combination with a clinical response rate of 81% in clinically and microbiologically documented infections compared with 63% for ceftazidime plus piperacillin. All of the episodes of Gram-negative bacteraemia treated with azlocillin responded compared with 43% of those treated with piperacillin. Gram-positive organisms accounted for 52% of all bacteriologically documented infections and 40% of the febrile episodes were treated with vancomycin for presumptive or documented Gram-positive infection. Patients treated with netilmicin had significantly more nephrotoxicity than those given the double beta-lactam combinations (14.8% vs 3.5%; P less than 0.05). However, this difference was not shown in those patients who did not receive concurrent vancomycin or amphotericin. The double beta-lactam combinations were associated with more hypokalaemia (58.2% vs. 37.7%; P less than 0.05) and more colonization with yeasts (24% vs. 10.4%; P less than 0.05) but there was no evidence that their use was associated with prolongation of neutropenia. These results indicate that ceftazidime plus a ureidopenicillin would be adequate empirical therapy in situations where the concomitant use of nephrotoxic agents precludes the use of aminoglycoside containing combinations.

Topics: Adult; Anti-Bacterial Agents; Azlocillin; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fever; Humans; Male; Microbial Sensitivity Tests; Netilmicin; Neutropenia; Penicillin G; Piperacillin; Random Allocation

This multicentric, randomized, double-blind trial compared the efficacy and safety of netilmicin, 4.5 mg/kg od and 1.5 mg/kg tid, in patients with intra-abdominal infections. Of 114 patients enrolled, 57 patients (mean age 40.3 years) in the od group and 55 (mean age 36.8 years) in the tid group were evaluated for efficacy; 58 and 56 patients in corresponding groups were evaluated for safety. Among those evaluated for efficacy were 12 od-treated and 11 tid-treated patients with documented septicaemia, and 32 and 30 patients of respective groups with polymicrobial infections. Initially, 86 and 81 netilmicin-susceptible causative microorganisms were isolated in corresponding groups. Of these pathogens, 55% in the od group and 62% in the tid group were Escherichia coli. Daily dosage of netilmicin ranged from 3.70 to 4.71 mg/kg (mean 4.50) for the od group and from 3.06 to 4.76 mg/kg (mean 4.46) for the tid group. Duration of netilmicin therapy ranged from six to 13 days (mean 8.7 days) for od-treated patients and from seven to 16 days (mean 8.8 days) for tid-treated patients. Concomitant metronidazole was administered to 41 patients of the od group and 34 of the tid group; one patient in the tid group received clindamycin. Clinical and bacteriological responses were assessed, and peak and trough serum netilmicin levels were measured periodically, during therapy. Laboratory tests, including determinations of serum creatinine and blood urea nitrogen values, were performed throughout the trial. A clinical cure was achieved in 57/57 od-treated patients and 54/55 tid-treated patients; treatment failed in one tid-treated patient (1/55). In od and tid groups, 86/86 and 80/81 netilmicin-susceptible pathogens initially isolated were considered to be eliminated, respectively; one isolate (Esch. coli) persisted in the tid group. Mean peak serum netilmicin concentration in the od group was approximately two-fold greater than that in the tid group; mean trough serum netilmicin concentrations were similar for the two groups. Adverse reactions were limited to mild pain at the site of netilmicin administration in several patients in each treatment group. Netilmicin od and tid (alone or in combination with metronidazole) were similarly efficacious in the treatment of patients with appendicitis and other intra-abdominal infections caused by netilmicin-susceptible pathogens. Both dosage regimens of netilmicin were safe and well tolerated.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Appendicitis; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Netilmicin; Random Allocation

Twenty-two patients undergoing major head and neck surgery were included in a randomized trial to value the efficacy and side effects of parenteral short-term antibiotic prophylaxis of post-operative infections. Two different antibiotic regimens were compared: group A, ceftazidime i.v. (2 g) in three doses (half an hour before surgery, 8 and 16 hours, from the first dose); group B, netilmicin (100 mg) plus clindamycin (600 mg i.v.), following the same chronological schedule. Overall infection rate was 18% (4/22): all post-operative infections occurred in group A patients, including one case of wound infection and 3 mixed infections (wound infection associated with lung infection), with a significant reduction of post-operative infection rate in group B patients (p = 0.045; Fisher's exact test).

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Ceftazidime; Clindamycin; Drug Evaluation; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Netilmicin; Postoperative Complications; Premedication

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.

Topics: Adult; Aged; Bacterial Infections; Colon; Drug Therapy, Combination; Female; Humans; Male; Metronidazole; Middle Aged; Netilmicin; Piperacillin; Postoperative Complications; Premedication; Rectum; Surgical Wound Infection

Ceftazidime in doses of 100 mg/kg/day was used, combined with netilmicin 6 mg/kg/day, as first-line treatment in two successive studies conducted on febrile neutropenic children (neutrophils less than 500/mm3). Study n. 1, performed at the Infantile Haematology unit of Saint Louis hospital, Paris, included 75 children. Study n. 2 was a multicentre study involving 88 children from 11 medical centres. The children's age in both studies ranged from 2 months to 16 1/2 years (mean 7 years). The percentage of bacteriologically documented febrile episodes was 45 per cent (34/75 and 39/88), and the most frequent infections were those caused by Gram-positive cocci (56 and 58 per cent respectively of the cases). Vancomycin 40 mg/kg/day was introduced if fever was still present 48 hours after the beginning of the antibiotic therapy. Effective treatments were continued until the neutropenia was corrected. These children were being treated for acute leukaemia, lymphoma, solid tumours or bone marrow aplasia. In study n. 1 apyrexia was obtained in 85 per cent of the cases with the ceftazidime-netilmicin combination and in 91 per cent of the cases after addition of vancomycin. The initial therapy was effective in all patients with a documented infection. There were tow super-infections with septicaemia: one due to Streptococcus D, the other to Staph. epidermidis. In study n. 2 73 per cent of the patients were apyretic after the first combination and 85 per cent after vancomycin was introduced. In proven infections the ceftazidime-netilmicin combination was effective in 30 cases and in another 6 cases after addition of vancomycin. Three patients remained febrile until they came out of aplasia. In all cases the bacterial cultures were sterilized by the ceftazidime-netilmicin combination. There was no superinfection. The mean duration of antibiotic therapy was 21 days in study n. 1 and 14 days in study n. 2. The drugs were perfectly tolerated both clinically and biochemically. No death occurred in the two studies. Thus, owing to its broad spectrum, effectiveness and safety ceftazidime is a very useful antibiotic when combined with netilmicin as first-line treatment of febrile neutropenic children.

Topics: Adolescent; Agranulocytosis; Bacterial Infections; Ceftazidime; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Humans; Infant; Multicenter Studies as Topic; Netilmicin; Neutropenia

In a prospective randomised study 60 patients with gynaecological or intra-abdominal infections were given either 2g iv every 12 hours of cefotetan or a combination of netilmicin (150mg iv every 12 hours) and clindamycin (600mg iv every 8 hours). The clinical condition of nearly half the patients (26 of 60) was characterized as serious and surgical manipulation and drainage were performed in 57 of the 60 patients. The clinical response was similar in both groups with 21 of 29 patients in the cefotetan group and 29 of 33 patients in the netilmicin plus clindamycin group. Side effects were few and mild in nature with no significant differences between the two groups. This work is continuing but the results to date suggest that cefotetan monotherapy is a safe and effective alternative to a combination of netilmicin and clindamycin in the treatment of gynaecological and intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Cefotetan; Clindamycin; Drug Evaluation; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Genital Diseases, Female; Humans; Male; Middle Aged; Netilmicin; Prospective Studies; Random Allocation

In an open prospective study performed in 2 neonatal units, infants with suspected neonatal sepsis (SNS) of unknown microbial cause were randomly allocated to receive treatment with either cefotaxime (CTX) or netilmicin plus penicillin (N + P). 236 patients were entered into the trial, of whom 222 were evaluable. The number of 'definitely' and 'probably' infected babies was similar in both groups. There was no difference in clinical outcome between patients in the 2 treatment groups and no side effects were recorded for either of the antibiotic regimens. Antibiotic sensitivity testing of bacterial isolates from peripheral sites showed almost universal sensitivity of potential pathogens to both antibiotic regimens at the start of treatment in all infants. Thereafter, organisms resistant to CTX were isolated from patients in both treatment groups, possibly reflecting the antibiotic sensitivity profile of the colonising bacteria in both neonatal units. The results of this study indicate that either CTX or N + P are suitable, in our units, for the 'blind' treatment of early SNS. In units where listerial infections are prevalent, specific cover should be added to CTX. For SNS developing after admission, the choice of antibiotics will depend upon the background antibiotic sensitivity profile of the colonising bacteria.

Topics: Bacterial Infections; Birth Weight; Cefotaxime; Drug Therapy, Combination; Escherichia coli; Humans; Infant, Newborn; Injections, Intravenous; Netilmicin; Penicillins; Prospective Studies; Pseudomonas; Random Allocation; Streptococcus agalactiae

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; beta-Lactamase Inhibitors; Child; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Netilmicin; Neutropenia; Penicillins; Retrospective Studies; Sepsis; Ticarcillin; Tobramycin

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.

Topics: Adolescent; Adult; Bacterial Infections; Cefotaxime; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Netilmicin; Random Allocation; Sepsis; Staphylococcal Infections

We initially used ciprofloxacin to treat immunocompromised patients whose fever had failed to respond or had recurred in spite of multiple broad-spectrum antibiotics. Results in this group encouraged us to proceed with a randomized trial of ciprofloxacin plus benzylpenicillin versus our standard empirical regimen of netilmicin and piperacillin for the treatment of fever in immunocompromised patients. Although the numbers of patients in this study are at present too small for comparison to be made, the favourable results seen in the refractory treatment group appear to be borne out so far in those receiving ciprofloxacin as first-line therapy.

Topics: Adolescent; Adult; Bacterial Infections; Ciprofloxacin; Drug Therapy, Combination; Humans; Immune Tolerance; Infusions, Intravenous; Middle Aged; Netilmicin; Opportunistic Infections; Penicillin G; Piperacillin; Random Allocation

Netilmicin is active in vitro against a wide variety of gram-negative bacteria, including certain gentamicin-resistant isolates, and Staphylococcus aureus. This study presents the results of a prospective, randomized, double-blinded protocol designed to determine the relative efficacy and toxicity of netilmicin and gentamicin in the therapy of gram-negative infections. The demographic make-up of both treatment groups was similar. Cure rates were 96.7 percent with netilmicin and 94.4 percent with gentamicin. Possible transient nephrotoxicity developed in nine patients receiving netilmicin and in eight patients receiving gentamicin.

Topics: Adult; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Gentamicins; Gram-Negative Bacteria; Humans; Netilmicin; Random Allocation; Respiratory Tract Infections; Urinary Tract Infections

Thirty children (age 3 months to 10 years) with complicated and uncomplicated lower urinary tract infections were treated with a single intramuscular injection of netilmicin 4.5 mg/kg. The diagnosis of lower urinary tract infection was based on the absence of fever and the presence of normal values for erythrocyte sedimentation rate, C-reactive protein concentration and urinary excretion of N-acetyl-beta-D-glucosaminidase. Follow-up urine cultures in all children demonstrated a cure rate of 97% and reinfection and relapse rates each of 7% respectively. The subgroup (12 children) with radiological abnormalities of urinary tract showed a cure rate of 92%, and reinfection and relapse rates of 9% respectively. The rates of cure, reinfection and relapse in the complicated and uncomplicated urinary tract infections were not statistically different (p greater than 0.05). A pharmacokinetic study (performed in 5 children) demonstrated that netilmicin urinary concentrations were over the MIC's of the infecting organisms up to 96 hours after the single-dose injection. Netilmicin was well tolerated and no side effects appeared during treatment. Single-dose netilmicin therapy is an effective and safe regimen for complicated and uncomplicated urinary tract infections in children. The response to single-dose netilmicin therapy seems to be related to its prolonged urinary elimination.

Topics: Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Female; Gentamicins; Humans; Infant; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Netilmicin; Urinary Tract Infections

Fifty patients with acute non-lymphocytic leukaemia were treated by random allocation with either ceftazidime alone or a combination of piperacillin, netilmicin and cefotaxime for 65 febrile neutropenic episodes. Nineteen of 33 patient episodes (58%) responded to ceftazidime alone compared with 21 of 32 episodes (66%) treated with the combination. There was one infective death in a patient given the combination; rates of documented superinfection were low. The treatment groups appeared identical in terms of patient demography, underlying disease and other risk factors, though patients with a clinical site of infection responded more slowly than those without. Bacteraemia per se did not appear to influence outcome. Bactericidal serum concentrations greater than or equal to 8 X the minimum bactericidal concentration were predictive of a rapid response (within 4 days) to antibiotics. Furthermore, serum from patients treated with ceftazidime maintained adequate cidal activity against Pseudomonas aeruginosa for longer than that obtained from patients treated with the three-drug combination. Ceftazidime was shown to be a safe and effective alternative to the three-drug combination for the initial management of febrile neutropenic episodes in leukaemic patients.

Topics: Adolescent; Adult; Bacterial Infections; Cefotaxime; Ceftazidime; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Netilmicin; Neutropenia; Penicillin Resistance; Piperacillin; Random Allocation; Sepsis

Fifty-three patients with documented or suspected mixed flora infections were randomly assigned to receive either netilmicin or tobramycin in combination with clindamycin. Data from 36 patients with 43 documented infections yielding 102 clinical isolates were evaluated for efficacy. In the 18 patients receiving netilmicin-clindamycin, 90% of the infections responded favorably and 96% of the pathogens were eliminated. In the 18 patients receiving tobramycin-clindamycin, 81% of the infections resolved and 88.5% of the pathogens were eliminated. Forty-nine patients were included in the safety analysis. The incidence of nephrotoxicity was similar in both groups (netilmicin, 20%; tobramycin, 21%). Auditory toxicity occurred less frequently in the netilmicin-clindamycin group (4.5%) than in the tobramycin-clindamycin group (21.7%). These results demonstrate that both the netilmicin-clindamycin and the tobramycin-clindamycin combinations are comparable in efficacy and in potential for causing nephrotoxicity. In this study, however, netilmicin was considerably less ototoxic than tobramycin.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clindamycin; Drug Combinations; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Male; Middle Aged; Netilmicin; Random Allocation; Recurrence; Tobramycin

In two prospective, randomized studies conducted in West Germany and involving 80 patients, netilmicin-ticarcillin was compared to tobramycin-ticarcillin in the treatment of serious systemic infections. Both regimens were essentially identical with respect to the clinical and bacteriological results they produced. The netilmicin group developed significantly less nephrotoxicity than the tobramycin group (0% versus 15%, P = 0.03). Ototoxicity also occurred less frequently in the netilmicin-treated patients (3% versus 10%, P = 0.4). In a large collaborative study involving 15 centres, 254 patients were enrolled. Clinical and bacteriological responses were excellent, with netilmicin and tobramycin equally effective, but the incidences of nephrotoxicity and ototoxicity were lower in patients treated with netilmicin than those receiving tobramycin.

Topics: Acute Kidney Injury; Aged; Bacterial Infections; Clinical Trials as Topic; Ear Diseases; Female; Gentamicins; Gram-Negative Bacteria; Humans; Male; Netilmicin; Random Allocation; Tobramycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Ear Diseases; Female; Gentamicins; Humans; Kidney Diseases; Netilmicin

From the results from over 150 clinical trials of netilmicin 3376 completed patient treatment courses have been reviewed to assess its efficacy and safety. Fourteen-hundred and twenty-three patients with 2273 infections caused by 2322 pathogens were evaluable for treatment efficacy. Favourable clinical responses were observed in 90% of the infections treated. Eighty-three per cent of the causative pathogens were eliminated from the infection sites. Netilmicin's safety was evaluated in all patients. Nephrotoxicity considered to be probably netilmicin-related occurred in 1.7% of the patients, and was possibly related in an additional 5.2%. Auditory toxicity was probably netilmicin-related in 1.6% and possibly related in 1.9% of the patients. Vestibular toxicity, probably or possibly drug-related, was observed in 0.62% of the patients. Extensive clinical trials with netilmicin have confirmed its excellent efficacy and safety profile.

Topics: Adult; Bacterial Infections; Clinical Trials as Topic; Female; Gentamicins; Humans; Kidney; Male; Middle Aged; Netilmicin; Vestibulocochlear Nerve

Topics: Bacterial Infections; Clinical Trials as Topic; Diarrhea, Infantile; Female; Follow-Up Studies; Gentamicins; Humans; Infant, Newborn; Male; Netilmicin; Pneumonia; Sepsis; Urinary Tract Infections

The effectiveness and safety of two antibiotic regimens, netilmicin-ticarcillin (NT) and tobramycin-ticarcillin (TT), were compared in a prospective, randomized, blind-evaluator study involving 60 elderly patients with serious systemic infections. Fifty-three patients were evaluated for treatment effectiveness; 25 (93%) of 27 patients in the NT group and 24 (92%) of 26 patients in the TT group had complete clinical resolution or improvement of their infections. There were two clinical failures in each group. Bacteriological responses were comparable in both treatment groups, with 87% (58/67) of the pathogens eliminated from patients in the NT group and 83% (59/71) eliminated from the patients in the TT group. The elimination rate for Pseudomonas aeruginosa, the organism most frequently isolated, was 88% (14/16) in the NT group and 77% (10/13) in the TT group. The differences between response rates of the treatment groups were not statistically significant. Auditory toxicity, detected by pure tone audiometry, was observed in two of the 24 patients treated with TT and in none of the patients treated with NT. Dizziness or vertigo, possibly resulting from aminoglycoside administration, occurred in one of the 29 patients given NT and in four of the 31 patients given TT. Nephrotoxicity, detected by serial serum creatinine determinations, developed in none of the patients in the NT group and in five of the 31 patients in the TT group, the difference being statistically significant (P = 0.05). The results of this study indicate that NT and TT are comparable in efficacy and that NT is less likely than TT to cause nephrotoxicity or disturbances in eighth cranial nerve function.

Topics: Aged; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Gentamicins; Hearing Tests; Humans; Kidney Function Tests; Liver Function Tests; Male; Netilmicin; Penicillins; Random Allocation; Ticarcillin; Tobramycin

254 patients with serious gram-negative bacillary infections were enrolled into a multicentre, randomised, blind clinical trial and treated with tobramycin-ticarcillin or netilmicin-ticarcillin. The two treatment groups were similar as to sex, age, and weight. The mean daily dose of netilmicin (237 mg) was higher than that of tobramycin (211 mg), p less than 0.01, but the mean duration of therapy was longer with tobramycin (9.4 days versus 8.7 days), p less than 0.01. The netilmicin cohort also had more serious underlying diseases, p less than 0.028. Clinical (tobramycin, 93% and netilmicin, 91%) and bacteriological responses (tobramycin, 87% and netilmicin, 89%) were similar. 84 tobramycin and 73 netilmicin patients had serial audiograms. Eighth nerve deficits developed in 10 (12%) tobramycin and two (3%) netilmicin patients, p = 0.037. Drug-related renal dysfunction developed in 5 (4%) of 114 tobramycin patients whose renal function was monitored and in 1 (1%) of 116 netilmicin patients, p = 0.12.

Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Ear; Female; Gentamicins; Humans; Kidney; Male; Netilmicin; Pseudomonas aeruginosa; Random Allocation; Tobramycin; Vestibulocochlear Nerve

A prospective, randomized trial comparing treatment of 61 febrile episodes with cefotaxime (CTX) versus a combination of ampicillin, methicillin, and netilmicin (AMN) was carried out in 58 patients with leukaemia or malignant lymphoma, of whom 28 had a granulocyte count of less than or equal to 500 X 10(6)/l. The overall response frequency was 63% for CTX against 49% for the AMN combination, the latter figure being lower than generally reported in the literature. The difference was not statistically significant. In 21 episodes pathogens were isolated, 16 of them from the blood. All isolated bacteria but one, a strain of Bacteroides fragilis, were fully sensitive to at least one of the three antibiotics in the combination, and all but one, a strain of Listeria monocytogenes, were fully sensitive to CTX. These results indicate that CTX seems to be a promising alternative as monotherapy for empiric treatment of febrile episodes in patients with haematologic malignancies. Further investigations will, however, be required before completely rational choices between mono and combination therapy of febrile episodes in immunosuppressed patients can be made.

Topics: Adolescent; Adult; Aged; Ampicillin; Bacterial Infections; Cefotaxime; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Lymphoma; Male; Methicillin; Middle Aged; Netilmicin; Penicillins; Prospective Studies; Random Allocation

Thirty children with serious gram-negative infections were treated with either netilmicin, 2 mg/kg, or tobramycin, 1 mg/kg, every eight hours for a minimum of 72 hours. Because of the administration of different doses, a "blind" investigator evaluated treatment response while another investigator adjusted the doses on the basis of each patient's drug serum levels and bacteriological response. Comparisons between the two study groups showed both treatments to be equally effective. All 15 patients treated with netilmicin and 14 of the 15 patients treated with tobramycin experienced complete resolution of clinical signs and symptoms and elimination of pathogens. One child in the tobramycin group was considered a treatment failure because of a persistent urinary tract infection. There were no adverse effects attributable to either drug.

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Netilmicin; Respiratory Tract Infections; Tobramycin; Urinary Tract Infections

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.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bacteroides Infections; Cefoxitin; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Gentamicins; Hearing; Humans; Male; Middle Aged; Netilmicin; Random Allocation; Surgical Wound Infection; Vestibular Function Tests

429 patients undergoing surgery for head and neck tumors were involved in 4 consecutive, randomized clinical trials of antimicrobial prophylaxis: placebo versus ampicillin plus cloxacillin (2 g of each daily for 6 days), ticarcillin (5 g X 12, 8-hourly) versus carbenicillin (10 g X 12, 8-hourly) short carbenicillin prophylaxis (1 day) versus prolonged carbenicillin prophylaxis (4 days) and clindamycin (900 mg, 4 daily doses) versus clindamycin plus netilmicin (90 mg, 4 daily doses). Aerobic gram-negative strains were the microorganisms most frequently isolated either from colonized or infected wounds. The first controlled study showed a significant decrease in the rate of postoperative bacterial infections in the treated group as compared to the placebo-treated group (p less than 0.05). In all the subsequent treatment groups, postoperative infection rates ranged from 6 to 16%. Short prophylaxis was as effective as prolonged prophylaxis. A regimen directed mainly against anaerobes (clindamycin) did not seem of less value than broad spectrum regimens covering most aerobic gram-negative bacilli.

Topics: Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Head and Neck Neoplasms; Humans; Netilmicin; Penicillins; Premedication; Surgical Wound Infection

A total of 804 pediatric patients (572 neonates and 232 infants and children) with suspected or documented serious infections were enrolled in a multicenter open study of netilmicin, a new semisynthetic aminoglycoside. All patients were evaluable for safety; 161 (20%) had bacteriologically documented infections and were thus evaluable for efficacy. Clinical success was seen in 94.4% (169/179) and bacteriological success in 91.1% (163/179) of sites; clinical success was seen in 94% (205/218) and bacteriological success was seen in 90.3% (196/217) of organisms. No significant adverse renal function changes were seen, and only one instance of an eighth nerve problem, probably related to netilmicin therapy, was encountered.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Gentamicins; Humans; Infant; Infant, Newborn; Infusions, Parenteral; Injections, Intramuscular; Male; Netilmicin

Data from 24 prospective, controlled clinical studies of the aminoglycosides gentamicin, tobramycin, amikacin, and netilmicin are reviewed. According to these findings, netilmicin is the safest and most effective of the four types (P less than 0.01, both comparisons), and gentamicin is more effective than tobramycin (P less than 0.05) and less ototoxic than amikacin (P less than 0.05).

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Gentamicins; Humans; Netilmicin; Prospective Studies; Tobramycin

The efficacy and tolerance of netilmicin administered in a simplified dosage schedule (150 mg BID) were evaluated in an open study of 20 patients with acute systemic infections. Duration of therapy ranged from 6 to 11 days. All isolated causative organisms were eradicated; 85% (17/20) of the patients experienced complete clinical resolution, and the remaining 15% (3/20) experienced definite improvement. No patients developed nephrotoxicity of ototoxicity. The results of this study demonstrate that netilmicin is both effective in the treatment of serious systemic infections and well tolerated when administered at 150 mg twice daily.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clinical Trials as Topic; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin

Netilmicin and gentamicin were compared in a multicenter clinical trial in 12 study locations. The two aminoglycosides were randomly assigned to hospitalized adult patients with systemic infections, and were administered by i.m. injection or slow i.v. infusion in divided doses generally calculated to deliver either 4-6.5 mg/kg per day of netilmicin, or 3-5 mg/kg per day of gentamicin. Lower dosages were given to patients with impaired renal function. Data from 210 patients receiving netilmicin and 212 receiving gentamicin were analyzed for efficacy. Favorable bacteriologic responses occurred in 95.5% (255/267) of the netilmicin-treated sites and in 90.1% (247/274) of the gentamicin-treated sites (p = 0.05). Netilmicin eliminated or reduced 95.6% (283/296) of all pathogens isolated from all infection sites compared with 89.5% (289/323) for gentamicin (p = 0.012). Favorable clinical responses were observed in 94.2% (275/292) of the netilmicin-treated patients and 89.5% (289/323) of the gentamicin-treated patients. Data from 377 netilmicin-treated patients and 378 gentamicin-treated patients were analyzed for safety. Evidence of nephrotoxicity probably related to treatment was observed in 8 of the netilmicin-treated patients and 14 of the gentamicin-treated patients. Audiometrically documented hearing loss probably related to treatment was observed in one gentamicin-treated patient. In one netilmicin-treated patient there were transient auditory and vestibular effects. Local tolerance to parenteral administration of the two drugs was excellent.

Topics: Adolescent; Adult; Bacterial Infections; Female; Gentamicins; Hearing Disorders; Humans; Kidney Diseases; Male; Netilmicin; Vestibular Function Tests

Eighty patients were treated with either amikacin or netilmicin in a prospective randomized study of serious gram-negative bacillary infections, including 11 due to gentamicin-resistant pathogens. Thirty-six treated with netilmicin and 35 treated with amikacin were evaluable for efficacy or toxicity, or both. The overall groups differed significantly only in age. There were no significant differences in efficacy of the two drugs. There were no statistically significant differences at the 95% level between the netilmicin group and the amikacin group with respect to nephrotoxic reactions (38 versus 28%, respectively) or ototoxic reactions (9 versus 25%, respectively). Further comparative trials of netilmicin and other aminoglycosides appear warranted before it is widely used.

Topics: Adult; Aged; Amikacin; Bacterial Infections; Clinical Trials as Topic; Drug Resistance, Microbial; Female; Gentamicins; Humans; Kanamycin; Lung Diseases; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

The toxicity of netilmicin was compared with that of amikacin in a randomized, prospective trial in 90 adults with a variety of serious gram-negative infections. There was no instance of antibiotic-related nephrotoxicity in the group given amikacin and only one instance in the group given netilmicin. Cochlear toxicity, as measured by a change in audiogram, occurred in 4/14 (28.5%) of the amikacin recipients and 3/19 (15.8%) of the netilmicin recipients. Vestibular toxicity, as determined by a change in ice-water calorics, was noted in 3/16 (19%) of the amikacin-treated patients and 0/15 of the netilmicin-treated individuals. Despite the trend toward lesser ototoxicity with netilmicin, the differences between the drugs were not statistically significant. There was, however, a significant association between male sex and the development of ototoxicity. Although many patients could not be evaluated for efficacy, there did not appear to be any difference in the therapeutic activity of the two drugs.

Topics: Aged; Amikacin; Audiometry, Pure-Tone; Bacterial Infections; Caloric Tests; Clinical Trials as Topic; Creatinine; Female; Gentamicins; Hearing; Humans; Kanamycin; Kidney; Male; Middle Aged; Netilmicin; Random Allocation; Sex Factors; Vestibule, Labyrinth; Vestibulocochlear Nerve

Netilmicin is a new semisynthetic aminoglycoside which was developed by Schering Corporation, USA, for the treatment of serious gram-negative and staphylococcal infections. Nephrotoxicity and ototoxicity in animal studies have indicated that netilmicin is both quantitatively and qualitatively safer than other aminoglycosides. Also, netilmicin has a broader spectrum of activity than either gentamicin or tobramycin. 37 clinical studies were conducted by 29 investigators in 10 countries. 840 courses of treatment in 960 infection sites were analyzed for effectiveness. Of the 724 courses in which a clinical determination could be made, 91% had either complete resolution or improvement. Bacteriologic responses were available for 782 infecting organisms and showed an 82% elimination rate. The pharmacokinetic profile of netilmicin permits twice daily administration in most patients with systemic infections and in all patients with urinary tract infections. The clinical safety of netilmicin was measured in 890 evaluable treatment courses, and only 0.4% auditory reactions, 0.6% vestibular reactions, and 0.9% renal reactions were considered to be probably netilmicin related, when netilmicin was given as recommended.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Drug Resistance, Microbial; Female; Gentamicins; Hearing Loss; Humans; Infant; Infant, Newborn; Kidney; Male; Middle Aged; Netilmicin; Respiratory Tract Infections; Skin Diseases, Infectious; Urinary Tract Infections

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Monitoring; Gentamicins; Humans; Injections; Netilmicin; Tobramycin

Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to that of netilmicin except for a methyl group at the C-6' position. In the present study, the in vitro antibacterial activity of vertilmicin was studied, and its susceptibility to modifications by the recombinant aminoglycoside bifunctional modifying enzyme AAC(6')-APH(2'') was compared with those of verdamicin and netilmicin. A total of 1,185 clinical isolates collected from hospitals in Beijing between 2000 and 2001 were subjected to the in vitro antibacterial activity evaluations, including MIC, minimum bactericidal concentration (MBC), and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin-resistant strains, respectively. For most of the non-gentamicin-resistant bacteria (except for the isolates of Pseudomonas spp.), the MIC(90)s of vertilmicin were in the range of 0.5 to 8 microg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC(50)s and/or MIC(90)s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC(90)s, 16 microg/ml, for the gram-positive gentamicin-resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis. Meanwhile, vertilmicin was a potent bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for Escherichia coli, Klebsiella pneumoniae, and S. aureus and 1 to 4 for S. epidermidis. The time-kill curve determination further demonstrated that this effect was rapid and concentration dependent. In evaluations of susceptibility to modifications by the recombinant AAC(6')-APH(2'') with maximum rate of metabolism/K(m) measurements, vertilmicin exhibited susceptibilities to both acetylation and phosphorylation lower than those of netilmicin and verdamicin.

Topics: Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Base Sequence; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Gentamicins; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Phosphotransferases (Alcohol Group Acceptor); Recombinant Proteins

The aim of the study was to evaluate the aminoglycoside resistance of Gram-negative bacilli isolated from patients. To the examination 35 strains of Enterobacteriaceae and 18 of non-fermentative bacteria were included. Resistance to aminoglycosides (gentamicin (G), netilmicin (Nt), tobramycin (T), amikacin (A), kanamycin (K), neomycin (N)) was established by disk diffusion method. Interpretation of enzymatic mechanisms was performed by Livermore. The most common enzymes AAC(6')I were found in Enterobacteriaceae group (mostly in E. cloaceae and P. mirabilis) and AAC(3') and in non-fermentative bacteria: AAC(6')I in P. aeruginosa and APH(3')VI and AAC(3')I in A. baumanii. The most frequent phenotype was resistance to six antibiotics (G, Nt, T, A, K, N) Resistance rates were high for gentamicin (>70 %) in both groups and amikacin (88,89 %) in non-fermentatives.

Topics: Acetyltransferases; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Gentamicins; Gram-Negative Bacteria; Humans; Kanamycin; Microbial Sensitivity Tests; Neomycin; Netilmicin; Phenotype; Pseudomonas aeruginosa; Tobramycin

Two protocols are used by French neonatologists for the treatment of suspected maternofetal infection (SMFI). Three groups of premature and term neonates were included to study the impact of antibiotics on fecal flora: 10 infants with SMFI treated with amoxicillin and netilmicin (group BI), 10 infants with SMFI treated with amoxicillin, cefotoxime and netilmicin (group TRI) and 10 infants without antibiotic therapy as controls (group C). Group BI samples were colonized with Klebsiella oxytoca and Escherichia coli resistant to amoxicillin and by Eneterococcus faecium and coagulase-negative staphylococci. In group TRI biodiversity of the intestinal flora was low, with rapid growth of staphyloccoci and occurrence of Candida spp. These modifications of the intestinal flora should encourage us to use antibiotic treatment as targeted as possible.

Topics: Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Colony Count, Microbial; Drug Resistance, Bacterial; Enterococcus faecium; Escherichia coli; Feces; Humans; Infant, Newborn; Infant, Premature; Infectious Disease Transmission, Vertical; Klebsiella oxytoca; Netilmicin; Staphylococcus

Aim of our study was making easier choice of right antibiotic to treatment newborns with sepsis after receiving results of bacteriological test. We analysed antibiograms that were results of first bacteriological test of blood samples taken from 59 neonates, who were admitted in first week of life to the Neonatal Pathology Clinic in Zabrze. On the ground of our analysis we propose applying netilmicin and cephalotin in every case of neonate with symptoms suggesting the sepsis. These two antibiotics have the best effects in treatment the sepsis.

Topics: Bacterial Infections; Cephalosporins; Cephalothin; Drug Resistance, Microbial; Gentamicins; Humans; Infant, Newborn; Netilmicin

Topics: Animals; Bacteria; Bacterial Infections; Drug Resistance, Microbial; Humans; Netilmicin

Neonatal bacterial infections are potentially lethal. The infant must be started on an antibiotic regimen to cover the organisms most frequently implicated. Since the introduction of gentamicin therapy for neonatal infections, attention has focused on aminoglycoside pharmacokinetics in these very young patients.. The pharmacokinetics parameters of netilmicin during its first administration were analysed in 22 newborn infants with a gestational age over 34 weeks, aged 1 to 3 days, in whom a maternofetal infection was suspected. Netilmicin was given intravenously at a dose of 6 mg/kg/day in two daily injections for 35 minutes. Blood concentrations of netilmicin were measured from samples taken 5, 15, 30, 60 minutes and 2 1/2, 5 1/5 and 11 1/2 hours after injection. The patients were also given cefotaxime plus ampicillin.. The kinetics were bicompartimental: prematurity, proven infections and other perinatal factors influenced the pharmacologic parameters and it was not possible to define a predictive formula for antibiotic administration.. The blood levels of netilmicin must be monitored even in infants who were not born prematurely. Because of the large distribution volume and the long half-life, we propose a dose of 6-7.5 mg/kg given once daily.

Topics: Bacterial Infections; Female; Gestational Age; Humans; Infant, Newborn; Maternal-Fetal Exchange; Netilmicin; Perfusion; Pregnancy

Topics: Adult; Aged; Bacterial Infections; Central Nervous System Diseases; Cerebral Hemorrhage; Female; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Middle Aged; Netilmicin; Subarachnoid Hemorrhage

The object of this work is to study in neutropenic mice the in vivo postantibiotic effect (PAE) of isepamicin, a new aminoglycoside, gentamicin and netilmicin on Staphylococcus aureus and Escherichia coli and in vivo killing kinetics using two different schedules (A and B) of isepamicin and gentamicin administration against S. aureus: (A) at time zero and every hour up to the 7th or 9th hour and (B) two doses only, at time zero and at the end of the PAE. The PAE of the three aminoglycosides was long (3-5 h), showing that of isepamicin to be the largest, especially on S. aureus. Both A and B treatment models show the same effectiveness for the two tested drugs. These results support the idea that the major significance of the PAE is in its application to dosing regimens.

Topics: Animals; Bacterial Infections; Disease Models, Animal; Escherichia coli; Female; Gentamicins; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Netilmicin; Neutropenia; Staphylococcus aureus; Thigh; Time Factors

The purpose of the study was to evaluate the effect of a mouthrinse regimen comprising both chemical plaque control and mechanical plaque removal. 20 adult patients with acute myeloid leukaemia were assigned to one of the following 2 regimens: (1) (group 1) mouthrinse twice daily with a 0.1% chlorhexidine solution; or (2) (group 2) the same regimen, but preceded by mechanical removal of plaque and calculus on day 1. All patients were followed for 28 days from the initiation of remission-induction therapy. In group 2, the plaque scores remained lower than those of group 1 throughout the study, although only 3 patients remained completely free of plaque after 28 days. Gingival inflammation as judged by bleeding scores remained unchanged in group 1, whereas in group 2, the degree of inflammation was reduced from 52% (median value) on day 1 to 31% (median value) on day 28. The bleeding scores were also lower in group 2 (31%) than in group 1 (60%) on day 28. No differences were found between the 2 groups with respect to the occurrence of other oral infections. It is concluded that chemical plaque control with chlorhexidine should be preceded by mechanical removal of plaque and calculus, when used in patients with acute myeloid leukaemia and thrombocytopenia.

Topics: Aclarubicin; Acute Disease; Adolescent; Aged; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Chlorhexidine; Cytarabine; Dental Calculus; Dental Plaque; Dental Scaling; Female; Gingival Hemorrhage; Gingivitis; Humans; Leukemia, Myeloid; Leukopenia; Male; Middle Aged; Mouthwashes; Netilmicin; Piperacillin; Premedication; Thrombocytopenia

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Retrospective Studies

Pharmacokinetics and tissue penetration of netilmicin were studied after the use of a single dose (6 mg/kg) given for antibioprophylaxis in colo-rectal surgery. Thirteen patients, scheduled for elective surgery, were given 6 mg/kg IV netilmicin over 30 min, together with 1000 mg IV ornidazole. Netilmicin peak serum concentration (10 min after end of infusion) was 24.4 +/- 3.4 mg/l and trough level (24 h) was 0.9 +/- 0.5 mg/l. Plasma elimination half-life was 409 +/- 70 min, le volume apparent volume of distribution was 38 +/- 101 and total body clearance was 0.07 +/- 0.02 ml/min. Adequate netilmicin levels (5 greater than or equal to CMI 90 of involved pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus) were obtained in 100 per cent of patients in abdominal wall and epiploid fat, at time of opening, and in colonic wall at time of anastomosis. Adequate levels were obtained at time of closure in abdominal wall and epiploid fat in 92 to 100 per cent of patients. In situation of allergy to beta-lactam antibiotics, the use of netilmicin in combination with ornidazole may be recommended.

Topics: Aged; Bacterial Infections; Colonic Diseases; Female; Fluorescence Polarization; Humans; Male; Middle Aged; Netilmicin; Preoperative Care; Rectal Diseases; Surgical Wound Infection

A method is described to predict the efficacy of antibiotics at changing concentrations in vitro or in an experimental thigh infection in granulocytopenic mice from the activity at constant concentrations in vitro, using pharmacokinetic parameters. The combinations studied were erythromycin against Staphylococcus aureus (in vitro and in vivo), four cephalosporins against two Gram-negative rods (in vivo), netilmicin against Pseudomonas aeruginosa (in vitro) and vancomycin against S. aureus (in vivo). The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate in the presence of an antibiotic. The relationship between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of exponentially declining concentrations in vitro or of a bi-exponential concentration course in vivo together with the parameters of the Hill equation, the corresponding time course of ER was calculated. By integration with respect to time, an estimate, called ERt, was obtained of the effect on bacterial numbers, called EN, defined as the difference between the number of bacteria in the controls and the number in the presence of the antibiotics. For all antibiotics studied the value of ERt was significantly correlated with the actual values of EN.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cephalosporins; Erythromycin; Gram-Negative Bacteria; Mice; Netilmicin; Pseudomonas aeruginosa; Regression Analysis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

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.

Topics: Adult; Aged; Anemia, Aplastic; Bacterial Infections; Cefmetazole; Drug Therapy, Combination; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Myelodysplastic Syndromes; Netilmicin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Drug Hypersensitivity; Drug Resistance; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Middle Aged; Netilmicin; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefotetan; Clindamycin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Genital Diseases, Female; Humans; Infusions, Intravenous; Netilmicin; Treatment Outcome

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Bacterial Infections; Dose-Response Relationship, Drug; Humans; Netilmicin; Surgical Wound Infection; Urologic Surgical Procedures

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Drug Combinations; Humans; Mezlocillin; Middle Aged; Netilmicin; Pacemaker, Artificial; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Bacterial Infections; Drug Therapy, Combination; Humans; Middle Aged; Neoplasms; Netilmicin; Spiramycin

Enzymuria is a well known parameter of evaluation of drugs nephrotoxicity, particularly of antibiotics. Alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT) and N-acetyl-bêta-D-glucosaminidase activities were measured in native urine. This study included 19 patients treated by an association of netilmicin-vancomycin. Enzymuria was measured on 24 hours urines at J0 then every two days during treatment. Enzymuria increased 24 or 48 hours after the beginning of the treatment. The Principal Components Analysis (PCA) of the results of enzymuria, seric urea and creatininemia shows the presence of two groups of responses. The first principal component exhibits two populations: the patients with pathological seric urea and pathological seric creatinine and the others. The PCA does not allow this discrimination using only the results of enzymuria; in contrast, with these results, the patients may be classified by the PCA on the basis of treatment duration. The enzymuria allows the clear identification of nephrotoxic drugs but does not allow the prediction of renal injury or of its aggravation.

Topics: Acetylglucosaminidase; Adolescent; Adult; Aminopeptidases; Bacterial Infections; CD13 Antigens; Child; Child, Preschool; Creatinine; Drug Therapy, Combination; gamma-Glutamyltransferase; Hexosaminidases; Humans; Kidney; Kidney Diseases; Middle Aged; Netilmicin; Urea; Vancomycin

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.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Dibekacin; Drug Resistance, Microbial; Gentamicins; Microbial Sensitivity Tests; Netilmicin; Sisomicin

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Gentamicins; Gram-Negative Bacteria; Humans; Kidney Diseases; Kidney Function Tests; Middle Aged; Netilmicin; Retrospective Studies; Tobramycin

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.

Topics: Bacteria; Bacterial Infections; Bone Marrow Transplantation; Ceftazidime; Child; Child, Preschool; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Netilmicin; Postoperative Complications; Sepsis; Time Factors; Vancomycin

Sixty infections episodes in granulocytopenic patients have been treated in first line with a piperacillin and netilmicin combination. Treatment has been successful in 78% bacterial infections. So, this antibiotic combination appears as a very effective therapy of infection in neutropenic patients.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Netilmicin; Piperacillin; Sepsis

Tissue penetration may be an important pharmacokinetic determinant to achieve the chemotherapeutic efficacy of antimicrobial agents. We describe a mouse model for the simultaneous study of antibiotic kinetics and efficacy at the site of infection. With the doses tested there was no difference in drug penetration into healthy tissue and tissue at the site of acute bacterial infection. Ampicillin and netilmicin levels over the minimal inhibitory concentration (MIC) were needed to produce significant bacterial killing. During the 6 h observation period susceptible Gram-positive bacteria were eradicated whereas Gram-negative bacteria were reduced in number but not eradicated, even though the antibiotic concentrations exceeded minimal bactericidal concentration (MBC) three times.

Topics: Ampicillin; Animals; Bacterial Infections; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Models, Biological; Netilmicin

Cefotetan is a semi-synthetic cephamycin antibiotic. It has combined activity against aerobes and anaerobes which makes it of particular use in the treatment and prevention of intra-abdominal infections in the surgical patient. In the course of 3 years we have evaluated the therapeutic use of cefotetan in 107 patients. Early in the evaluation of this antibiotic we used cefotetan in combination with aminoglycosides in 35 severely ill patients with intra-abdominal infections. These patients were generally in poor condition. Good results were obtained in this high risk group. A further 72 patients received cefotetan monotherapy, usually at a dose of 2 g twice daily. The majority of these patients presented with intra-abdominal infections. Overall a successful clinical response of 94% was obtained with antibiotic therapy. In conclusion the results obtained support the therapeutic use of cefotetan in the treatment of moderate to severe intra-abdominal infection.

Topics: Adult; Bacterial Infections; Cefotetan; Female; Humans; Male; Netilmicin; Peritonitis; Prognosis

Infection is the most important cause of mortality in leucopenic patients. A broad spectrum antibiotic therapy is imperative in febrile and neutropenic patients. In a multicentric study we have used ceftazidime (100 mg/kg/d) and netilmicin (6 mg/kg/d) in 88 children (fever greater than or equal to 38.5 degrees C, neutropenia less than 500/mm3) treated for acute leukemias (59), non Hodgkin lymphomas (13) or solid tumors (16). Median age was 7 years (2 months-16 years). In patients who continued to remain febrile, vancomycin (40 mg/kg/d) was added after 48 hours. The effective treatment was continued until a neutrophil count greater than 1,000/mm3. The first combination (ceftazidime + netilmicin) was effective in 64 children (73%) and the second combination (ceftazidime + netilmicin + vancomycin) in 11 patients. Bacteria were isolated in 39 children: Escherichia coli: 9, Staphylococcus epidermidis: 9, Staphylococcus aureus: 8, Streptococcus: 6, Pseudomonas aeruginosa: 3, Streptococcus pneumoniae: 1, Haemophilus: 1, Klebsiella pneumoniae: 1, Proteus: 1, Serratia: 1, Flavobacterium: 1. In these 39 patients, 30 became apyretic with ceftazidime and netilmicin and 6 after vancomycin. All blood culture were negative after the first combination. The median duration of antibiotic therapy was 14 days (5-9 days: 28, 10-20 days: 43, greater than 20 days: 17). There were no death, no superinfection. Tolerance was good without kidney or liver or biological perturbation. We conclude that the combination ceftazidime and netilmicin is effective in neutropenic children.

Topics: Adolescent; Agranulocytosis; Bacterial Infections; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Fever; Humans; Infant; Netilmicin; Neutropenia; Vancomycin

Our study aimed to determine the least number of samples that are required to obtain accurate pharmacokinetic parameters in neonates. Patients treated with either netilmicin or ceftazidime had between five and eight samples drawn for drug concentration measurement after the first or the last dose of the drug. Pharmacokinetic parameters were calculated using all the available points as a reference and then recalculated with 2, 3, or 4 points. Systemic clearance and volume of distribution were significantly different from the reference value when 2 points were used for netilmicin after the first dose and ceftazidime after the last dose. Had parameters obtained from 2 points been used, mean dosage would have been underestimated by 15% for ceftazidime and 11% for netilmicin, and some patients would have received only 65% of the dose calculated from all available points. When 3 points were used, dosage would have been underestimated by a mean of only 1% for ceftazidime and 5% for netilmicin when compared with the dosage estimated from the reference parameters. We conclude that 3 concentration time points may be all that are required for estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.

Topics: Bacterial Infections; Blood Specimen Collection; Ceftazidime; Ethics, Medical; Humans; Infant, Newborn; Netilmicin; Pharmacokinetics; Reference Values

Topics: Adult; Bacterial Infections; Cefotaxime; Ceftriaxone; Clindamycin; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Netilmicin; Nitroimidazoles; Ornidazole

Topics: Adult; Bacteria; Bacterial Infections; Cefotetan; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Netilmicin; Peritonitis

Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides remain useful in the treatment of serious, hospital-acquired, gram-negative bacillary infections, especially those caused by Pseudomonas aeruginosa. Formidable nephrotoxicity and ototoxicity have limited the use of neomycin to topical or oral administration. Widespread antimicrobial resistance among Enterobacteriaceae has restricted the use of streptomycin and kanamycin to a few specific clinical situations. Gentamicin, tobramycin, and amikacin are active against a wide range of Enterobacteriaceae and many P. aeruginosa organisms. In medical centers where gentamicin resistance is prevalent, amikacin is the aminoglycoside of choice. Fortunately, amikacin resistance has not seemed to increase substantially, even in institutions where usage has been extensive for a long period. No new aminoglycoside has proved to be superior to amikacin.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Gentamicins; Humans; Netilmicin; Sisomicin; Streptomycin; Tobramycin

Safe use of aminoglycosides requires close monitoring of serum concentrations. Limited information coupled with marked changes in fluid compartments and renal function during the first week of life in premature neonates makes interpretation of peak and trough levels very difficult. This study was designed to measure serum netilmicin levels following a 2.5 mg/kg IV push infusion. Blood samples were taken on the 5th day of therapy 1 hour before and 1, 6, and 11 hours after a dose. Fifteen premature infants weighing 1000-1500 gm at birth and 20 others whose weight ranged from 1501-2750 gm comprised the study population. All premature infants were appropriate for gestational age (AGA) and of them, only two were severely asphyxiated. At the time of the study, 10 neonates were still on respirators. Serum and urine sodium and creatinine, BUN, and urinalysis were obtained in 28 of these infants. No evidence of renal dysfunction was found. All infants received 100 mg/kg IV ampicillin every 12 hours, but none were being treated with diuretics. Serum netilmicin levels were measured by an enzymatic immunoassay, peak and trough were calculated by extrapolating the first order decay curve. Peak levels ranged from 3.4 to 14 micrograms/ml (means 6.1 +/- 2.5 micrograms/ml SD) and 90% of them were above 4 micrograms/ml. Half of the small premature infants (1000-1500 gm birthweight) presented trough values above 3 micrograms/ml. Pharmacokinetic analysis of our data predicts that a 2.5 mg/kg loading dose followed by 2 mg/kg given every 12 hours will decrease by one-half the number of small prematures exceeding the considered "safe" trough level (greater than 3 micrograms/ml).

Topics: Asphyxia Neonatorum; Bacterial Infections; Drug Evaluation; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Kidney; Male; Netilmicin

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.

Topics: Adolescent; Adult; Agranulocytosis; Bacterial Infections; Child; Child, Preschool; Cloxacillin; Drug Therapy, Combination; Fever; Humans; Netilmicin; Neutropenia; Piperacillin

Amikacin was instituted as the primary empiric aminoglycoside at the San Juan Veterans Administration Medical Center in January 1982; at that time, 16 percent of the strains at the hospital were gentamicin-resistant. A prospective surveillance study was designed to correlate detection of bacterial resistance with aminoglycoside use. In the current report, the baseline period, during which gentamicin was the first-line aminoglycoside, accounting for 61 percent of overall aminoglycoside use, is compared with the period from January 1982 to September 1985, during which the first-line aminoglycoside was amikacin, accounting for 85 percent of overall use. This study is ongoing. During the two periods, the patient population did not differ with regard to aminoglycoside therapy, indications, or overall aminoglycoside use (541 versus 680 patient days per month). Among the gram-negative bacilli isolated, the percent of strains resistant to amikacin was as follows: pre-baseline period/baseline period, 0.8/0.2 percent; amikacin-usage period, 3.6 percent. Resistance to gentamicin and tobramycin during the period of amikacin use decreased from 16 to 11 percent for gentamicin and from 17 to 11 percent for tobramycin. The decrease in resistance of the gram-negative bacilli to gentamicin varied among strains: the resistance of Escherichia coli decreased from 8 to 4 percent; that of Proteus mirabilis, from 12 to 5 percent; that of indole-positive Proteus, from 19 to 12 percent; that of Acinetobacter, from 57 to 23 percent; that of Citrobacter, from 15 to 7 percent; and that of Pseudomonas aeruginosa, from 24 to 16 percent. During the amikacin-usage period, amikacin resistance was unchanged for most strains, with the exception of P. aeruginosa, the resistance of which increased from 4.5 to 7.8 percent. Of the 4,795 strains isolated, 174 were resistant to amikacin; of these, 29 Pseudomonas strains were studied for all mechanisms of resistance. Changes in permeability were exhibited by 11 of the 29 strains; 14 strains exhibited the AAC(6')-I enzyme, 10 strains exhibited the APH(3')-II enzyme, and two strains exhibited ANT(2") in addition to some other unidentified mechanism. Multiple enzyme production was found in 15 of the strains. The use of amikacin as a first-line aminoglycoside is associated with a decrease in resistance to other aminoglycosides and a slight increase in overall resistance to amikacin among aerobic gram-negative bacilli. The usefulness of amikacin has no

Topics: Acetyltransferases; Amikacin; Aminoglycosides; Bacterial Infections; Drug Resistance, Microbial; Gentamicins; Gram-Negative Bacteria; Humans; Kanamycin; Kanamycin Kinase; Netilmicin; Nucleotidyltransferases; Phosphotransferases; Population Surveillance; Prospective Studies; Tobramycin

The susceptibility patterns of gram-negative aerobic organisms to aminoglycosides differ widely from one European health care center to another and depend upon local antibiotic prescribing policies. Reports of the susceptibility of Pseudomonas aeruginosa to gentamicin and tobramycin have ranged from as low as 49.8 percent and 77.7 percent, respectively, in Greece, to as high as 96.6 percent and 99.2 percent, respectively, in the United Kingdom. The susceptibility of P. aeruginosa to gentamicin, tobramycin, and amikacin decreased in our hospital from 73.1 percent, 94.8 percent, and 95.6 percent, respectively, in 1982, to 43.1 percent, 70.6 percent, and 74.3 percent, respectively, in 1984. A prospective surveillance study of the susceptibility of gram-negative aerobic bacilli to four aminoglycosides (gentamicin, tobramycin, amikacin, and netilmicin) was performed over a period of 17 months. Gentamicin and tobramycin were freely used, while the use of amikacin was restricted throughout the hospital during a four-month baseline period (May through August 1984). Gentamicin and tobramycin accounted for 94 percent of the aminoglycoside use. During the following 13 months (September 1984 through September 1985), amikacin was used as the first-line aminoglycoside and accounted for more than 97 percent of the aminoglycoside usage. A total of 1,866 organisms were analyzed during the baseline period; 5,429 were analyzed during the amikacin-usage period. The overall susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increased from 86.9 percent, 90.4 percent, 94.2 percent, and 88.3 percent, respectively, to 92.3 percent, 94.0 percent, 97.3 percent, and 92.3 percent, respectively. P. aeruginosa isolates had the most striking changes, with the susceptibility to gentamicin, tobramycin, amikacin, and netilmicin increasing from 43.1 percent, 70.6 percent, 74.3 percent, and 50.6 percent, respectively, during the baseline period, to 64.5 percent, 81.6 percent, 90.8 percent, and 65.1 percent, respectively, during the amikacin-usage period. The use of amikacin as a first-line aminoglycoside, while use of the other aminoglycosides was restricted, seemed to have a favorable influence on the susceptibility pattern of gram-negative aerobic isolates in our hospital.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Belgium; Drug Resistance, Microbial; Europe; Gentamicins; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Netilmicin; Prospective Studies; Pseudomonas aeruginosa; Tobramycin

Both aztreonam and netilmicin showed no toxic effect on alveolar macrophage function when administered at varying concentrations. Killing ability was unchanged as well. The increase of enzyme delivery, assessed at varying concentrations, was very limited and of no relevance in the pathogenesis of possible tissue damage. It can be explained on the basis of a change in the permeability of membranes or to output during phagocytosis. In cultures containing either antibiotic under similar conditions we did not note any substantial differences. The concentrations tested can be used safely in the therapy of infections due to most gram-negative bacteria.

Topics: Acid Phosphatase; Aztreonam; Bacterial Infections; Humans; L-Lactate Dehydrogenase; Macrophages; Netilmicin; Phagocytosis; Potassium; Pulmonary Alveoli

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacterial Infections; Burns; Humans; Netilmicin; Tobramycin

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).

Topics: Adolescent; Adult; Aged; Bacterial Infections; Creatinine; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Netilmicin

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.

Topics: Adult; Aged; Amikacin; Bacterial Infections; Female; Gentamicins; Humans; Infusions, Parenteral; Kanamycin; Keratitis; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Tears; Tobramycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Ear Diseases; Humans; Kidney Diseases; Netilmicin

Five newer beta-lactam antibiotics and two aminoglycosides were tested on 400 freshly isolated clinically significant organisms from specimens at a district general hospital. All the antibiotics had very broad-spectrum activities but none could cover against all probable pathogens. Latamoxef was the best of all against Bacteroides spp. Aminoglycosides, followed by cefotaxime and ceftizoxime, were best against staphylococci. Tobramycin, followed by ceftazidine and netilmicin, had the best activity against Pseudomonas aeruginosa. Of all 7 antibiotics tested only piperacillin demonstrated activity against Streptococcus faecalis. Cefotaxime and ceftizoxime were the best against Escherichia coli, Klebsiella spp. and most of streptococci. The study demonstrated that safer alternatives to aminoglycosides are now available.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Ceftazidime; Humans; Microbial Sensitivity Tests; Moxalactam; Netilmicin; Piperacillin; Tobramycin

Topics: Acute Disease; Bacterial Infections; Child; Child, Preschool; Dysentery, Bacillary; Enteritis; Escherichia coli Infections; Female; Gentamicins; Humans; Infant; Male; Netilmicin; Salmonella Infections

Topics: Adolescent; Adult; Bacterial Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin

Topics: Adult; Animals; Bacteria; Bacterial Infections; Chemical Phenomena; Chemistry; Cochlea; Gentamicins; Humans; Kidney; Netilmicin; Rabbits; Rats; Vestibule, Labyrinth

The value of netilmicin, like that of other antibiotics, is influenced by its antimicrobial specificity, dosage and ease of administration, activity in pus and the underlying condition of the host. Different classes of antibiotics and different members among a group of antibiotics have relative strengths and weaknesses among these clinical factors that affect the results of antibacterial therapy and must be determined by careful clinical investigation.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Drug Evaluation; Gentamicins; Humans; Netilmicin

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.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cardiac Surgical Procedures; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Humans; Netilmicin; Premedication

Topics: Aged; Bacterial Infections; Diabetes Mellitus; Female; Gentamicins; Humans; Kidney; Middle Aged; Netilmicin

Topics: Adolescent; Adult; Aged; Bacterial Infections; Connective Tissue Diseases; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Osteomyelitis; Urinary Tract Infections

Topics: Abdomen, Acute; Adult; Aged; Bacterial Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Osteomyelitis; Surgical Wound Infection

Topics: Bacterial Infections; Drug Evaluation; Gentamicins; Humans; Netilmicin

Despite their toxicity, the aminoglycosides remain useful and are often the first choice in the treatment of serious infections due to gram-negative bacilli. Nephrotoxicity has restricted the indications for neomycin to topical and oral use. Emergence of resistant organisms has limited the use of streptomycin to a few specific conditions. Gentamicin, tobramycin, and amikacin are effective against a broad spectrum of gram-negative bacilli including Pseudomonas aeruginosa. Amikacin is the aminoglycoside of choice when gentamicin resistance is prevalent.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Gentamicins; Humans; Kanamycin; Microbial Sensitivity Tests; Netilmicin; Sisomicin; Streptomycin; Tobramycin

Topics: Bacterial Infections; Drug Interactions; Gentamicins; Humans; Microbial Sensitivity Tests; Netilmicin

The following results were obtained from the bacteriological evaluations of netilmicin (NTL), a newly developed antibiotic agent, with gentamicin (GM), dibekacin (DKB) and amikacin (AMK) as the controls. (1) NTL demonstrated broad antibacterial spectra against both Gram-positive and Gram-negative bacteria, but its antibacterial potency against streptococci was not very strong among other Gram-positive bacteria. (2) In terms of distribution of sensitivity of clinically isolated bacterial strains, NTL proved to have antibacterial potency comparable to that of GM and higher potency than that of DKB of AMK against E. coli K. pneumonia, Enterobacter sp., or H. influenzae. However, its efficacy was inferior to GM against Proteus sp., S. marcescens and P. aeruginosa. (3) In conjunction with the influences of pH of culture media or of addition of horse sera upon the antibacterial efficacy, NTL showed an inclination similar to that of GM, DKB and AKM. Its antibacterial efficacy was fortified on the alkaline side or by addition of sera. In connection with the influences of the amounts of inoculated bacteria upon antibacterial efficacy, there were hardly any appreciable influences on it by any of the tested bacterial strains. (4) The interactions of NTL with carbenicillin were evaluated with the chequerboard titration method to find remarkable cooperative actions in any of E. coli, K. pneumoniae, S. marcescens, A. calcoaceticus and P. aeruginosa. (5) The results of evaluation on the patterns of its antibacterial effects revealed that it acted bactericidal in any tested bacterial strains. (6) As to the therapeutic effects against experimental infections in mice, it was found out that NTL = GM greater than DKB and AMK against E. coli, GM greater than NTL = DKB and AMK against K. pneumoniae and GM and DKB greater than NTL greater than or equal to AMK against A. calcoaceticus and P. aeruginosa in the decreasing order of efficacy.

Topics: Amikacin; Animals; Bacteria; Bacterial Infections; Carbenicillin; Dibekacin; Drug Evaluation, Preclinical; Drug Synergism; Gentamicins; Mice; Netilmicin; Penicillin Resistance

Topics: Adolescent; Adult; Aged; Bacterial Infections; Eye; Female; Gentamicins; Humans; Kidney; Male; Middle Aged; Netilmicin

Topics: Adult; Aged; Bacterial Infections; Drug Evaluation; Female; Gentamicins; Humans; Injections, Intramuscular; Male; Middle Aged; Netilmicin; Respiratory Tract Infections

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.

Topics: Adult; Aged; Bacterial Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Respiratory Tract Infections; Urinary Tract Infections; Wound Infection

The pharmacokinetics of netilmicin were analyzed in 30 children, including 13 premature and seven gestationally mature newborns. Ten were children ranging in age from 3.5 months to 13 years. The newborns exhibited more variation in serum levels than the older children, and the premature babies more than those born at term. The serum half-life (t1/2), tended to show higher values in premature than in mature newborns, although this was not statistically significant. The newborns had a t1/2 of 5.9 hours, compared to 2.5 hours in the older children. There was no statistically significant difference in distribution volumes or coefficients between the two groups of newborns who had an insignificantly higher relative apparent beta-phase distribution volume coefficient of 0.420 l/kg, compared to 0.377 l/kg in the older children. All had distribution coefficient values within the same range. The total body clearance in absolute terms, and when referred to body surface of 1.73 m2, was significantly lower in the newborns than in the older children, but the clearance, when referred to body weight, was of the same order in the babies and older children. The age differences affect dosage. Dosage schedules based on pharmacokinetics are proposed for gestationally premature babies, mature newborns, and older children. Premature infants can receive 2.5 mg/kg body weight and gestationally mature newborns 3.0 mgkg, both every 12 hours; the monitoring of serum concentrations is mandatory. Children aged three months and older can receive 3.0 mg/kg every eight hours.

Topics: Adolescent; Age Factors; Bacterial Infections; Body Surface Area; Body Weight; Child; Child, Preschool; Gentamicins; Gestational Age; Half-Life; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Kinetics; Netilmicin

Topics: Abdomen; Animals; Bacterial Infections; Clindamycin; Drug Therapy, Combination; Male; Netilmicin; Nitroimidazoles; Rats; Rats, Inbred Strains; Specimen Handling; Tinidazole

Twenty-five hospitalized neonates, each with two or more serious symptomatic infections, were given netilmicin by intramuscular injection. The antibiotic was administered usually at 1.5 or 3.0 mg/kg twice a day (q 12 hr) for 7 to 13 days. At the end of therapy the signs and symptoms of infection were completely resolved in twenty-four of the twenty-five patients and markedly improved in the remaining one. Thirty-five causative organisms were isolated from 30 of the 59 infection sites; after netilmicin therapy 31 causative organisms were completely eliminated and 4 were markedly reduced in number. One of the babies had a slight increase in serum creatinine level, possibly related to therapy, and a mild transient rash which was doubtfully related to netilmicin. None of the other neonates had adverse reactions.

Topics: Bacterial Infections; Female; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Netilmicin

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Neoplasms; Netilmicin

Topics: Animals; Bacterial Infections; Congresses as Topic; Gentamicins; Humans; Netilmicin

Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.

Topics: Ampicillin; Animals; Bacteria; Bacterial Infections; Cephalosporins; Cephamycins; Disease Models, Animal; Gentamicins; Male; Meningitis; Moxalactam; Netilmicin; Rabbits; Species Specificity

38 newborn infants, 28 males and 10 females, were treated with netilmicin in doses 6-7 mg/kg/day for suspected or verified infections. 19 patients were mature (mean birth weight 3169 g) and 19 were premature (mean birth weight 1864 g). 32 had moderate or severe underlying diseases. 37 babies survived, 33 were cured or improved markedly and in 4 the results were indeterminate. Pathogenic bacteria were demonstrated in 24 cases and were eliminated in 15. Only one baby died. He suffered from severe respiratory distress syndrome and Escherichia coli septicemia. No E. coli was isolated at autopsy. The mean netilmicin peak serum value was 7.7 micrograms/ml (range 1.0-30.0) and the mean trough concentration 2.1 micrograms/ml (range 0.0-9.2). No adverse effects were seen.

Topics: Bacterial Infections; Drug Evaluation; Enterobacteriaceae Infections; Female; Gentamicins; Haemophilus Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Netilmicin; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections

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.

Topics: Bacterial Infections; Drug Evaluation; Gentamicins; Hearing; Humans; Kidney; Leukemia; Lymphoma; Netilmicin

The efficacy and toxicity of netilmicin was assessed in 15 patients with life-threatening infections, including six with septicaemia. Fourteen patients were cured with no recurrence of infection. The initial dosage of netilmicin was 200 mg twice a day (2.3-4.0 mg/kg/dose), but subsequent adjustment of dosage was made according to the results of serum assay, either to avoid accumulation or to improve therapeutic response. Probable nephrotoxicity occurred in only one patient and there was no evidence of ototoxicity in the twelve patients who could be assessed.

Topics: Adult; Aged; Bacterial Infections; Creatinine; Drug Evaluation; Enterobacteriaceae Infections; Female; Gentamicins; Hearing; Humans; Kidney; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Staphylococcal Infections

Sixteen patients with chronic or recurrent urinary tract infections, 14 with septicaemia, 2 with salmonellosis, 2 with pneumonia and 1 with acute mastitis were treated with 200 mg (2.2-3.6 mg/kg) netilmicin intramuscularly every 8 hours for 7-10 days (mean 8.8 days). 28 patients were cured, 5 showed marked improvement and 2 patients with septicaemia and severe underlying diseases failed to respond to treatment. The bacterial isolates were inhibited by 4.0 mg netilmicin/l or less. Antibiotic serum level determinations were performed in 32 patients. Mean serum concentrations of netilmicin 1 and 8 hours after injection were 12.6 and 2.0 mg/l respectively in 27 patients with normal serum creatinine levels. In 5 patients with elevated serum creatinine, mean peak and trough values were 21.5 and 5.8 mg/l, respectively. Mean netilmicin concentrations in serum and skin blister fluid obtained from 4 patients were equal 2-3 hours after injection, indicating appropriate tissue penetration. Nephrotoxicity occurred in 2 patients. Ototoxicity was not demonstrated. Netilmicin appears to be an effective and safe drug in the treatment of a variety of bacterial infections.

Topics: Adult; Aged; Bacterial Infections; Chronic Disease; Creatinine; Drug Evaluation; Female; Gentamicins; Hearing; Humans; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

49 newborns and infants were treated with netilmicin for verified or suspected infections. Infection was verified in 23 patients (mean gestational age 32 weeks and mean body weight 2100 g) and clinical cure or marked improvement occurred in 20 of these. Of the remaining 3 patients, 2 died, partly due to reasons unassociated with infection. 25 causative organisms were isolated and bacteriological elimination was achieved in 73% of the cases. At an average dose of 2.6 mg/kg twice a day, peak serum concentrations (30 min following injection) were 7.4 +/- 3.4 micrograms/ml. Serum half life was approximately 4.5 hours for infants born at term, and longer at shorter gestational age. Netilmicin is considered a safe and efficient aminoglycoside with a low rate of adverse effects.

Topics: Bacterial Infections; Drug Evaluation; Escherichia coli Infections; Female; Gentamicins; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Klebsiella Infections; Male; Netilmicin; Sepsis; Staphylococcal Infections; Streptococcal Infections

Topics: Adult; Aged; Bacterial Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Phagocytes; Tissue Distribution

40 newborn infants and children were treated with netilmicin. With a 2-mg/kg dose, the average peak serum concentration was 4.4 microgram/ml. Serum concentrations resulting from the first dose were markedly lower than subsequent doses and therapeutically inadequate. Significant drug accumulation did not occur: peak and trough concentrations on days 2 and 7 were the same in patients with normal renal function. The half-life of netilmicin in infants less than 1 week old was 3.8 h in infants older than 1 week. Infants less than 7 days old require a prolonged dose interval (12 h) to adequately clear the administered dose. Recovery of netilmicin in urine ranged from 50 to 100% and correlated with age and duration of treatment. Elimination of netilmicin was prolonged in newborn infants with renal failure and requires dosage adjustment. Transient change in creatinine clearance occurred in 2 patients (4.6%) and ototoxicity was observed on 2 other patients.

Topics: Adolescent; Bacteria; Bacterial Infections; Child; Gentamicins; Half-Life; Hearing; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Netilmicin

Topics: Amikacin; Aminoglycosides; Bacterial Infections; Carbenicillin; Gentamicins; Humans; Microbial Sensitivity Tests; Neoplasms; Netilmicin; Penicillin Resistance; Penicillins; Ticarcillin; Tobramycin

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.

Topics: Bacterial Infections; Escherichia coli Infections; Gentamicins; Humans; Injections, Intravenous; Klebsiella Infections; Neoplasms; Netilmicin; Pseudomonas Infections

Netilmicin, a new semisynthetic aminoglycoside, was evaluated in the therapy of 33 episodes of infection in 30 patients. Eighteen patients had documented bacteremia. Infection sites included pulmonary, urinary tract and soft tissue areas. A complete bacteriologic and clinical cure rate of 85 per cent was achieved. No treatment failures occurred in the bacteremic group. Although netilmicin is less effective than gentamicin in vitro against Pseudomonas, it was clinically and bacteriologically effective. Netilmicin bacteriologic cures occurred in patients whose organisms were inhibited by 6.2 microgram/ml or less of netilmicin. Despite a uniform dosing protocol, a wide range of netilmicin serum levels was obtained. Adverse effects were limited to one case of transient nephrotoxicity and one Candida urinary suprainfection. Netilmicin appears to be an effective, safe agent for the therapy of serious infections.

Topics: Adult; Aged; Amikacin; Bacterial Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections

Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.

Topics: Bacterial Infections; Gentamicins; Gram-Negative Aerobic Bacteria; Humans; Netilmicin

The efficacy and toxicity of netilmicin, a new semisynthetic aminoglycoside, was clinically evaluated in fifty-two patients with moderate to severe infections with Gram-negative rods or Staph. aureus. Average duration of treatment was 14 days and mean total dose 2,960 mg. One-hour mean value of netilmicin serum concentration was 6.4 microgram/ml and mean trough value 1.2 microgram/ml. Forty-four patients were cured or improved. In twenty-one of them the effect could be attributed to netilmicin alone; the other twenty-three had a combined therapy. No improvement took place in five, but four of them could not be regarded as netilmicin failure. One patient with Pseudomonas aeruginosa infection was possible failure. The sensitivity of the causative bacteria to netilmicin was studied and compared with amikacin, gentamicin, sisomicin and tobramycin. Vestibular function and hearing acuity was thoroughly examined by electronystagmography and audiography. Drug-related VIIIth nerve damage could not be confirmed in any of our patients. Five patients showed a rise of serum creatinine of 30 mumol/l. This shows that netilmicin, similar to other aminoglycosides, is a potential nephrotoxic drug. Netilmicin appears to be an efficacious aminoglycoside and the oto- and nephrotoxicity is low, if careful attention is paid to the renal function and the serum concentrations of the drug.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Female; Gentamicins; Hearing; Humans; Kidney; Male; Middle Aged; Netilmicin; Staphylococcal Infections; Staphylococcus; Vestibular Nerve

Pharmacokinetics, nephrotoxicity, and therapeutic efficacy of (2S-cis)-4-O-[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]-2-deoxy-6-O-[3-deoxy-4-C-methyl-3-(methyl-amino)-beta-L-arabinopyranosyl]-N1-ethyl-D-streptamine sulfate (netilmicin) and tobramycin were investigated in rats. The excretion rates of tubular cells and of the urinary enzyme malic dehydrogenase served as parameter of nephrotoxicity. Both compounds were, similar to other aminoglycosides, tubulotoxic within the range of dosages used for human therapy. Netilmicin, however, produced less renal damage than did tobramycin in all dosages applied. Pharmacokinetic studies revealed lower renal concentrations of netilmicin after repetitive administration. Experimental chemotherapy of the chronic E. coli pyelonephritis in rats with both aminoglycosides resulted in a significant reduction of the renal bacterial counts. In spite of approximately identical serum concentration curves and in vitro activity, especially the low dosage of netilmicin led to more favourable therapeutic results than equal doses of tobramycin. These animal experiments suggest higher renal tolerance and efficacy of netilmicin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Female; Gentamicins; Kidney Diseases; Kinetics; Netilmicin; Rats; Time Factors; Tobramycin

Netilmicin sulfate, a new aminoglycoside antibiotic, was administered to ten patients with thermal burns who were suffering from septic complications, usually burn wound sepsis. There were seven survivors. Eighty-three percent of all clinical isolates recovered showed sensitivity to the drug. No renal or auditory side effects were noted in any of the patients.

Topics: Adolescent; Adult; Bacterial Infections; Burns; Gentamicins; Humans; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Prognosis; Wound Infection

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.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Male; Middle Aged; Netilmicin; Pseudomonas Infections; Urinary Tract Infections