No abstract

A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains ofEnterobacteriaceae and Pseudomonas aeruginosa isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gentamicin and other newer aminoglycoside antibiotics. Cross-resistance to netilmicin was found in 9 of 44 gentamicin-resistant strains. A favorable clinical response was observed in 70% of the patients treated with a dose of netilmicin ranging from 4.5 to 7.5 mg/kg. However, the appearance of granular casts was seen in 7 of 10 patients receiving the higher dosage of netilmicin (7.5 mg/kg) and a rise in blood urea nitrogen or serum creatinine levels was observed in 5 ofthese patients.Netilmicin is a new semisynthetic aminoglycoside antibiotic that is active in vitro against a wide variety of gram-negative bacteria. This new compound is derived from sisomicin by ethylation of the 1-N position ofthe deoxystreptamine ring.For most clinically significant Enterobacteriaceae and Pseudomonas aeruginosa, the activity of netilmicin in vitro was comparable or superior to that of gentamicin, tobramycin, and amikacin with respect to potency by weight and achievable blood levels. Against gentamicinresistant strains, the activity of netilmicin usually paralleled that of amikacin (3). These in vitro studies were repeated here using the strains isolated from clinical material in our hospital, with special attention to gentamicinresistant strains. No reports of clinical experience with netilmicin have yet been published; that is why the present investigation was undertaken as an increasing-dose trial. MATERLALS AND METHODSBacteriological studies. All the aminoglycosides (gentamicin, sisomicin, tobramycin, netilmigin, amikacin) were supplied as sterile powders by the respective manufacturers. Dilutions were prepared in Trypticase soy broth (Difco). The microorganisms examined comprised 163 strains of Klebsiella, 58 strains ofProteus mirabilis, 21 strains ofEnterobacter, 178 strains ofEscherichia coli, and 94 strains of P. aeruginosa. All these gram-negative rods were isolated from patients who were hospitalized at the Institut Bordet, which is the cancer hospital of Brussels University. The microorganisms were isolated from sputum, urine, wounds, and blood cultures. They were identified by the usual methods. The minimum inhibitory concentrations (MICs) were determined for each aminoglycoside by the inocula replicating method of Steers et al. (15) on a MuellerHinton medium (pH 7.4), with an inoculum containing approximately 104 microorganisms per ml. The reading was made after 18 h ofincubation at 37°C.In addition, the cross-resistance between gentamicin and the other aminoglycosides studied was investigated in the microorganisms resistant to gentamicin. All microorganisms that were resistant to one or more ofthe antibiotics sisomicin, tobramycin, netilmicin, and amikacin were also resistant to gentamicin. Resistance to ge...

Sisomicin was administered as a single daily intramuscular injection (160 mg) or as two daily injections (80 mg) to 50 patients with bacteriuria superimposed on chronic urologic diseases in a randomized controlled fashion. The administration of two daily doses was significantly more effective (P less than 0.01) in achieving cure than the injection of a single daily dose. The renal function, as expressed by creatinine clearance, became impaired significantly more often (P less than 0.05) in the patients receiving the single daily dose of sisomicin.

Synergism between amikacin and cefazolin was studied in vitro in 20 strains of Klebsiella isolated from clinical material. Several techniques for the demonstration of synergism in vitro were employed. The checkerboard technique with use of bactericidal end points and the killing curves method showed synergism between amikacin and cefazolin for 13 and 15 strains, respectively. The two techniques were in accordance in 12 instances. The data obtained in vitro were correlated with the bactericidal activity in sera from 10 subjects who had received the usual doses of amikacin and cefazolin, alone or in combination. The sera of subjects who received amikacin plus cefazolin were bactericidal at significantly higher dilutions than sera of patients who received cefazolin alone. The increased serum bactericidal activity in subjects receiving amikacin plus cefazolin was observed only for strains against which these antibiotics were synergistic in vitro.