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The In vitro activity of BMY-28142 was compared with that of cefotaxime, ceftazidime, moxalactam, and imipenem against 639 clinical isolates and a number of in vitro-selected resistant mutants. BMY-28142 was the most potent compound against the members of the family Enterobacteriaceae with a MIC for 90% of the strains of 0.12 ,ug/ml. The activity against Pseudomonas aeruginosa was comparable to that of ceftazidime and imipenem. Strains of staphylococci were moderately susceptible to BMY-28142 (MIC required to inhibit 90% of strains, 4 ,ug/ml), but Streptococcus faecalis isolates were resistant. The activity of the five compounds was inoculum dependent for several gram-negative species. By a single-step selection procedure, resistant mutants were selected from strains of Citrobacter freundii, Enterobacter cloacae, and P. aeruginosa. The mutant frequencies with the cephalosporins, including BMY-28142, ranged between 10-6 and 10-8. BMY-28142 was the most active cephalosporin against these resistant organisms, most of them strong ,-lactamase producers. It inhibited all mutants of C. freundii and E. cloacae at 2 ,ug/ml and all mutants of P. aeruginosa at 32 ,ug/ml. Imipenem on the other hand was as active on all of these resistant organisms as on the parent strains. Fig. 1), is a new extended-spectrum cephalosporin for parenteral use. The compound is structurally similar to cefotaxime but has a 1-methylpyrrolidine instead of the acetoxy group at position 3 of the dihydrothiazine ring.The third-generation cephalosporins combine a highlactamase stability with a broad antibacterial spectrum and potent activities against gram-negative bacteria. However, their antibacterial activity against Pseudomonas aeruginosa is variable, and they are generally less active on gram-positive organisms than their first-generation counterparts. Moreover, several reports have shown the emergence in vitro and in vivo of resistant mutants at relatively high frequency (3,7,12). Most involved strains belong to Enterobacter, Citrobacter, and Pseudomonas spp., genera producing inducible cephalosporinases which can be derepressed to constitutive synthesis.The present study compares the in vitro activity of BMY-28142 with that of currently available third-generation cephalosporins and imipenem. Attention was paid to the rate of in vitro emergence of resistant mutants and the degree of cross-resistance of these mutants to the other compounds.MATERIALS lands. They were identified by standard criteria (4). In addition, a number of known resistant or P-lactamaseproducing strains from our culture collection were also included.Susceptibility studies. MICs were determined by an agar dilution technique. Serial dilutions (ranging from 0.008 to 128 ,ug/ml) of freshly prepared antibiotic were made in Mueller-Hinton agar. This medium was supplemented with 5% defibrinated horse blood for fastidious streptococci. The organisms were grown overnight in tryptic soy broth or Todd-Hewitt broth (streptococci) and diluted to an inoculum density of 107 cells per ml. Th...

Low-level transferable resistance to ceftazidime was detected in seven strains of Klebsiella pneumoniae and one strain of Escherichia coli. Six of the Klebsiella strains and the E. coli strain were shown to produce a novel P-lactamase (CAZ-lo) with a pl of 5.6 that hydrolyzed broad-spectrum cephalosporins at low but comparable levels. One strain of K. pneumoniae was of a serotype different from that of the other strains and produced a plasmid-encoded cefuroximase (FUR) with a pI of 7.5 that mediated moderate levels of resistance to different broad-spectrum cephalosporins. High-level resistance to ceftazidime was detected in one other strain of K. pneumoniae, which produced a ,-lactamase with a pl of 6.5 (CAZ-hi). Apart from its pl, this enzyme differed from CAZ-lo by a specific and high hydrolytic activity against ceftazidime. The epidemiological context suggested that CAZ-hi may be a mutant of CAZ-lo, and this hypothesis was supported by the isolation of laboratory mutants of CAZ-lo showing properties identical to those of the clinical CAZ-hi enzyme.Broad-spectrum cephalosporins have been specifically designed to resist degradation by gram-negative P-lactamases.Initial in vitro tests determining the enzymatic stability of the newer P-lactams showed considerable stability to both chromosomal and R-plasmid-mediated enzymes. However, since the intensive use of broad-spectrum cephalosporins was begun, several failures due to the emergence of mutants that hyperproduce a chromosomal cephalosporinase, known as class I P-lactamase by the classification of Richmond and Sykes, have been described (18,19). More recently, transferable resistance to these agents was also described. Strains of Klebsiella pneumoniae and Serratia marcescens with transferable resistance to broad-spectrum cephalosporins were first described in Germany (12) and found to produce a novel plasmid-determined P-lactamase, designated SHV-2 (11). From 1985 on, nosocomial outbreaks of multiresistant K. pneumoniae and other species were reported in French hospitals (4,10,22). The resistance was ascribed to another new broad-spectrum P-lactamase, CTX-1, that displayed high-level hydrolytic activity against cefotaxime and ceftazidime (13). More recently, strains of K. pneumoniae and Escherichia coli that are resistant to ceftazidime but remain more or less susceptible to other broad-spectrum cephalosporins were reported in France (5, 17), the Federal Republic of Germany (3), and the United Kingdom (24). In this article, we report three novel plasmid-mediated P-lactamases detected in strains from Belgium with decreased susceptibilities to ceftazidime. MATERIALS AND METHODSBacterial strains. During a period of 4 weeks, seven strains of K. pneumoniae and one strain of E. coli with partial resistance to ceftazidime were isolated from several patients in the intensive care unit. These strains were recognized by their intermediate zone diameters on standard antibiograms and by marked synergism when an amoxicillin-clavulanic acid disk was placed beside the ceftazi...

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Detection and intensity of urease activity in enterobacteriaceae greatly varies as a function of the media or techniques used, or both. A comparative investigation on several solid and liquid media led us to the following conclusions. (i) Detection of Proteus spp. can be adequately performed with the highly selective solid medium described by Cook (1948), as well as with the different liquid media described (Stuart standard and rapid media; Elek medium). (ii) Detection of Klebsiella should be based upon urease production on solid media with low buffer capacity (Christensen, 1946). (iii) For the identification of Yersinia , either the solid Christensen urea agar or the rapid Elek technique give optimal results.