netilmicin and Hearing-Loss

The safety and pharmacokinetics of netilmicin (6.6 mg/kg) and amikacin (14.5 mg/kg) once daily (od) have been compared to their corresponding conventional schedules thrice daily (tid), and twice daily (bd), in patients (20 per group) suffering from pelvic inflammatory disease. Sensitive criteria of early renal and auditory alterations, namely urinary excretion of phospholipids and audiometry over a wide frequency range (0.25-18 kHz), respectively, were used. The first criterion (phospholipiduria) was validated by an animal study which demonstrated that rats receiving poly-L-aspartic acid, which protects against gentamicin-induced nephrotoxicity, are also protected against renal phospholipidosis and phospholipiduria caused by this antibiotic. On that basis, netilmicin od was better tolerated than netilmicin tid. Amikacin caused less phospholipiduria than netilmicin, and, given od, resulted in little increase over baseline (95% CI, 95-147% increase). Reduction in threshold by greater than or equal to 15 dB for frequencies between 10-18 kHz occurred in nine of 19 patients receiving netilmicin tid compared with three or four of 19 or 20 patients treated with netilmicin od or amikacin (od or bd). However, changes at lower frequencies (0.25-8 kHz) were infrequent with all regimens (from 0/19 to 2/20). In conclusion, these very sensitive tests of nephro- and oto-toxicity suggest that od dosing of amikacin or netilmicin is, if anything, safer than bd or tid dosing.

Topics: Adult; Amikacin; Animals; Audiometry, Pure-Tone; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Female; Hearing Loss; Humans; Netilmicin; Pelvic Inflammatory Disease; Peptides; Phospholipids; Rats; Rats, Inbred Strains

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

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

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

25 patients were treated with netilmicin because of suspected or verified septicaemia or other severe infections. Netilmicin was administered intramuscularly in a dose of 2 mg/kg body weight every 8 hours. For patients with elevated plasma creatinine the dosage was reduced according to the degree of elevation. Average length of treatment was 7 days (3-12 days). In 22 patients all symptoms and signs of infection disappeared. In one patient antibiotic treatment had to be changed and in two patients abscesses had to be surgically drained. Kidney function was monitored during and after treatment by plasma creatinine measurements and 51Cr-EDTA clearance. Netilmicin was discontinued in 4 patients because of an increase in plasma creatinine but little or no drug related nephrotoxicity was observed. Audio-vestibular function was monitored during and after treatment. Netilmicin was discontinued in one patient because of slight subjective loss of hearing. Subsequent audio-vestibular examination was normal.

Topics: Adult; Aged; Creatinine; Dizziness; Drug Evaluation; Female; Gentamicins; Hearing Loss; Humans; Male; Middle Aged; Netilmicin; Sepsis; Urinary Tract Infections