The in vitro activity of LY-127935, a new beta-lactam antibiotic, was examined by using 370 clinical bacterial strains. In comparison with several other betalactam agents, LY-127935 was the most inhibitory against the Enterobacteriaceae. It was remarkably active against multi-drug-resistant strains of Enterobacter spp., Serratia spp., and Pseadomonas aeruginosa. LY-127935

In vitro properties of 19 antimicrobial agents were tested with 56 isolates of Klebsiella spp. The aminoglycosides and the new beta-lactam compounds cefotaxime and moxalactam were the most inhibitory drugs tested. Chloramphenicol, tetracycline, trimethoprim, and trimethoprim-sulfamethoxazole were moderately active, whereas piperacillin, mezlocillin, and furazlocillin were ineffective against 25% of the isolates. Gentamicin was the only agent tested that was uniformly bactericidal in time-kill experiments with drug concentrations of four times the minimal inhibitory concentration. In combination studies with gentamicin, moxalactam and furazlocillin each increased the rate of bacterial killing for three of five isolates as compared with gentamicin alone, whereas chloramphenicol significantly retarded the rate of bacterial killing for the same number of strains. Furazlocillin was completely inactivated after 24 h of incubation with each of five selected strains. The inactivation of moxalactam, cefoxitin, and cephalothin was 36, 56, and 72%, respectively. In all instances in which these four agents were inactivated to levels below the minimal bactericidal concentration, there was accelerated growth after initial inhibition. However, regrowth also occurred in three instances in which drug levels were higher than the minimal bactericidal concentration. Retesting after drug exposure revealed a 4-to 32-fold rise in the minimal inhibitory concentration and minimal bactericidal concentration in two of these isolates.Infections caused by Klebsiella spp. continue to account for a large portion of nosocomial disease with a high rate of morbidity and mortality (6, 7). Aminoglycosides alone and in combination with cephalosporins are frequently prescribed for these serious infections (1). The purpose of this investigation was (i) to study the in vitro activity of aminoglycosides, beta-lactam agents, and other antimicrobial agents against recent clinical isolates of Klebsiellapneumoniae and Klebsiella oxytoca, (ii) to deternine the bactericidal ability of these agents in time-kill experiments, (iii) to examine the rate of bacterial killing of gentamicin alone and in combination with other antimicrobial agents, and (iv) to deternine the rates of inactivation of the betalactam compounds by Klebsiella spp. during the time-kill experiments. MATERIALS AND METHODSAntimicrobial agents. A total of 19 antimicrobial agents were studied. The aminoglycosides used were streptomycin, gentamicin, tobramycin, amikacin, and netilmicin. The beta-lactam compounds included cephalothin, cefazolin, cephapirin, cefoxitin, cefaman-

The efficacy of moxalactam, a new beta-lactam antibiotic with an expanded spectrum of in vitro activity, was evaluated in 22 patients with 27 sites of infection. The pathogens included six strains of multidrug-resistant Serratia marcescens and one of Pseudomonas aeruginosa. The minimal inhibitory concentration of moxalactam for the study isolates ranged from less than 0.12 to 32 μg/ml. Peak serum levels exceeded the minimal inhibitory concentration of the pathogen in every instance with mean peak serum levels of 43.0, 65.0 and 123 μg/ml for doses of 0.5, 1.0 and 2.0 g, respectively. Pharmacokinetic data was obtained in patients with normal and abnormal renal function and during hemodialysis. Moxalactam was found to have excellent penetration into synovial, peritoneal, pleural and cerebrospinal fluids. 23 of the 27 infections were cured. There were six episodes of recurrent infections at the 4-week follow-up among the 12 patients treated for urinary tract infections. Drug toxicity was not a major problem. There were nine instances of superinfection noted (three each due to Candida spp., enterococci and P. aeruginosa), only one of which was clinically significant.