netilmicin and Infections

The effectiveness and safety of once-daily versus several-times-daily aminoglycosides were studied in a meta-analysis. MEDLINE for 1988 to 1995 was searched, and additional studies were identified from review articles and references in retrieved articles. Studies selected for meta-analysis were randomized controlled clinical trials in nonneutropenic adult patients comparing the clinical effectiveness or nephrotoxicity or ototoxicity of once-daily with several-times-daily aminoglycosides. Differences between groups were expressed as odds ratios. The results were combined by the procedure of Mantel and Haenszel, and 95% confidence intervals and exact confidence intervals were computed. An odds ratio smaller than 1 would indicate a lesser likelihood of a given endpoint in the once-daily group, and an odds ratio greater than 1 would indicate a greater likelihood. Eighteen studies involving 2317 patients were included in the meta-analysis. Summary odds ratios were 1.47 for effectiveness (95% CI = 1.13-1.94), 0.56 for ototoxicity (95% CI = 0.26-1.16), and 0.60 for nephrotoxicity (95% CI = 0.40-0.86). A meta-analysis showed that treatment with single daily doses of aminoglycosides seems to be more effective, less nephrotoxic, and as ototoxic as multiple doses daily.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Controlled Clinical Trials as Topic; Drug Administration Schedule; Ear Diseases; Gentamicins; Humans; Infections; Kidney Diseases; Middle Aged; Netilmicin

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received i.v. neropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1-30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p = .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

Topics: Amikacin; Anti-Bacterial Agents; Drug Therapy, Combination; Fever; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Infections; Meropenem; Neoplasms; Netilmicin; Neutropenia; Penicillanic Acid; Piperacillin; Tazobactam; Thienamycins

The aim of this study was to validate a simplified high-dosage, extended-interval netilmicin dosage regimen for infants. A total of 129 infants receiving 163 treatment courses of netilmicin (6 mg kg every 24 or 36 h depending on gestational age (GA), postnatal age and postmenstrual age) was analysed. Serum netilmicin concentrations were monitored before (Cmin), 30 min (C0.5h) after and 7.5 h (C7.5h) after the third dose. In 110 patients during first week of life mean C0.5h was 10.5 mg/l. Mean C0.5h was significantly lower (9.0 mg/l) in 38 infants older than 1 week of age. 14 of 15 patients with Cmin levels > or = 2 mg/l receiving netilmicin every 36 h were < 28 weeks of gestation. In the first week of life significant correlations between GA and elimination half-life (p < 0.001) and between plasma creatinine and elevated Cmin (p < 0.002) were found, but no correlation between C0.5h and GA. In this high-dosage regimen a dosing interval of 48 h for GA < 29 weeks, 36 h for GA 29-36 weeks and 24 h for full term babies seems appropriate, during first week of life, to avoid the majority of elevated trough levels and still obtain maximal therapeutic efficacy.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Drug Administration Schedule; Drug Therapy, Combination; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infections; Netilmicin

In the treatment of serious infection by aminoglycoside antibiotics multiple daily treatment with netilmicin is considered to be the least toxic. Studies comparing netilmicin with gentamicin using the less toxic once-daily schedule are lacking. A randomized prospective study was designed to evaluate the efficacy and toxicity of once-daily netilmicin with gentamicin treatment in patients with serious infections. Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg q24h iv or netilmicin 5.5 mg/kg q24h iv. Exclusion criteria were neutropenia or severe renal failure. A good clinical response was observed in 50 of the 54 evaluable patients (92.6%) treated with gentamicin and in 48/52 (92.3%) netilmicin treated patients. Nephrotoxicity developed in 5/72 (6.9%) gentamicin patients and in 10/69 (14.5%) treated with netilmicin. Audiometry was performed with high-frequency audiometry when possible; no significant differences were found between the two aminoglycosides. We conclude that with once-daily treatment no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.

Topics: Adolescent; Adult; Aged; Audiometry; Creatinine; Female; Gentamicins; Hearing Loss, Sensorineural; Humans; Infections; Male; Middle Aged; Netilmicin; Treatment Outcome

The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection-free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P < 0.05 and P < 0.01, respectively) and an increase in FENa and UCa/UCr in group C (P < 0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant.

Topics: Amikacin; Calcium; Case-Control Studies; Creatinine; Gentamicins; Humans; Infant, Newborn; Infant, Premature, Diseases; Infections; Kidney; Kidney Function Tests; Magnesium; Netilmicin; Phosphorus; Potassium; Sodium; Uric Acid

An open randomized study was done to compare the prophylactic value of single doses of netilmycin-metronidazole versus trimethoprim-sulfamethoxazole in the prevention of postoperative infections associated with transrectal prostatic biopsy. Of 117 patients enrolled in the study 101 were evaluated and of these patients 47 received netilmycin-metronidazole and 54 received trimethoprim-sulfamethoxazole. The bacteremia rate in the netilmycin-metronidazole group was 28% (13 of 47 patients) with a 95% confidence interval of 18 to 42% and in the trimethoprim-sulfamethoxazole group it was 37% (20 of 54) with a confidence interval of 26 to 50% (p = 0.43). None of the patients with bacteremia was symptomatic. Urinary tract infection rates were greater in the netilmycin-metronidazole group: 17% (8 of 47 patients) versus 2% (1 of 54) in the trimethoprim-sulfamethoxazole group, p = 0.01. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a better choice as an antimicrobial prophylaxis for patients undergoing transrectal prostatic biopsy.

Topics: Aged; Aged, 80 and over; Biopsy; Drug Combinations; Humans; Infection Control; Infections; Male; Metronidazole; Middle Aged; Netilmicin; Premedication; Prostate; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.

Topics: Adult; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Drug Therapy, Combination; Hearing Loss; Humans; Immune Tolerance; Infections; Middle Aged; Neoplasms; Netilmicin; Piperacillin; Prospective Studies; Random Allocation; Tobramycin

The effect of aminoglycoside administration on kidney functional maturation was evaluated in groups of 30 preterm and 30 fullterm infants who were treated for 7 days because of suspected infection. One of three different aminoglycosides was administered to each subgroup of ten preterm and ten fullterm infants. Changes in tubular function in groups of ten preterm and ten fullterm infants who were not given antibiotics were also compared. The mean gestational age for preterm infants from 32.5 to 33.6 weeks and for fullterm infants between 39.2 and 39.5 weeks. The renal tubular function was assessed by examining the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium (FEMg) and uric acid (FEUA) as well as by the urinary excretion of calcium as the calcium/creatinine (UCa/UCr) ratio. Gentamicin affected the normal plasma creatinine (PCr) decline in both treated groups (fullterm and preterm). Disturbances in FENa and UCa/UCr were more pronounced in treated preterm than in fullterm infants especially after netilmicin and gentamicin administration. FEMg was significantly affected in preterm infants treated with gentamicin. The findings of this study indicate that the effect of aminoglycosides on tubular function is dependent upon kidney maturity and the type of the aminoglycoside used for therapy.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Kidney; Kidney Function Tests; Netilmicin; Phosphorus; Potassium; Sodium; Uric Acid

Despite their ototoxic and other side effects, aminoglycosides are still widely used in the treatment of neonatal infections. A novel method for evaluation of hearing loss is distortion product otoacoustic emission (DPOAE). Physiologic acoustic energy-emission produced by sound stimulus in the inner ear is detected by DPOAE. Existing acoustic emission indicates the functional integrity of the inner ear. DPOAE was performed in 19 newborns treated with netilmicin for different infections. Serum netilmicin levels did not exceed 12 mg/l; renal functions were normal. Existence of emission was detected in 15 newborns. There was no emission found in 4 newborns unilaterally, which was fully restored in 2 months. In conclusion, aminoglycosides have no considerable ototoxic side effects. DPOAE is thought to be an objective, fast, and non-invasive method for hearing screening in the newborn period.

Topics: Anti-Bacterial Agents; Gentamicins; Hearing Loss; Hearing Tests; Humans; Infant, Newborn; Infections; Netilmicin; Otoacoustic Emissions, Spontaneous