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 ug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.Netilmicin, a newly developed semisynthetic analog of sisomicin, is active against a wide variety of aerobic gram-negative bacteria. Although its antimicrobial activity in vitro is similar to the other aminoglycosides (2, 4-6, 9, 10, 13, 17), it appears to be less nephrotoxic and ototoxic than these congeners in experimental animals (1,8,11). We undertook the present study to evaluate the efficacy and toxicity of netilmicin in infections in humans. This report is based on our experience with 42 patients.
MATERIALS AND METHODSPatient studies. All patients were hospitalized at the Tufts-New England Medical Center. Patients selected for admission to the study had evidence of gram-negative bacterial infection which required an aminoglycoside for therapy, the only exclusions being children and pregnant women. Informed consent was obtained from each patient or next of kin before netilmicin treatment. Criteria for bacteremia included positive blood cultures with fever 238.3°C, hypotension, or chills. A separate category was suspected sepsis in which fever, hypotension, or chills were present but no growth of gram-negative bacteria was documented from blood cultures. Criteria for the diagnosis of pneumonia included roentgenological evidence of an infiltrate in addition to the presence of leukocytes and gram-negative organisms in secretions obtained by transtracheal aspiration or aspiration from an endotracheal tube. Criteria for urinary tract infection were cultures of 106 organisms per ml from voided urine specimens and fever (238.3°C) or dysuria, frequency, urgency, or pyuria. Criteria for peritonitis were fever, abdominal tenderness (usually with rebound), and polymorphonuclear leukocytes in ascitic fluid. ...