Clinical and Bacteriological Evaluation of Netilmicin in Gram-Negative Infections

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...

Prospective comparative study of efficacy and toxicity of netilmicin and amikacin

“…However, comparable in vitro data and response to treatment suggest that these two aminoglycosides have similar efficacy with susceptible pathogens. Response rates to both drugs were similar to those noted previously (2,5,11,12,16,18,29,30). Most of the patients who had infections with gentamicin-resistant pathogens responded, but the small number of patients makes comparison between the two drugs difficult.…”

“…Other investigators who used doses of netilmicin comparable to those used our study noted significant nephrotoxicity rates from 14 to 26% (2,5,11,12,22,29,30). In our study netilmicin was definitely associated with nephrotoxicity in more patients (17.6%) than amikacin (3.4%), although the difference was not statistically significant.…”

“…Netilmicin is a new aminoglycoside active in vitro against a wide variety of Enterobacteriaceae and Pseudomonas aeruginosa (4,12,17,21,23,24). It is resistant to two of the enzymes that inactivate gentamicin (17,21) and has significantly less ototoxicity (19) and nephrotoxicity than gentamicin in experimental animals (7,13,15).…”

“…It is resistant to two of the enzymes that inactivate gentamicin (17,21) and has significantly less ototoxicity (19) and nephrotoxicity than gentamicin in experimental animals (7,13,15). In open clinical trials, it has been therapeutically effective and appears to have less cochlear toxicity than other aminoglycosides (2, 5; 11,12,16,22,29,30). In some clinical studies netilmicin has exhibited minimal nephrotoxicity (11,16), whereas in others nephrotoxicity has been appreciable (2,5,12,22,29,30).…”

“…In open clinical trials, it has been therapeutically effective and appears to have less cochlear toxicity than other aminoglycosides (2, 5; 11,12,16,22,29,30). In some clinical studies netilmicin has exhibited minimal nephrotoxicity (11,16), whereas in others nephrotoxicity has been appreciable (2,5,12,22,29,30). Amikacin is effective in therapy of patients with serious gram-negative infections, including those due to gentamicin-resistant organisms (18,19).…”