Although standard-inoculum MICs were within the susceptible range for all compounds, cefoperazone, cefotaxime, and cefpirome were significantly less effective than imipenem or the combination of cefoperazone and sulbactam in the treatment of rat intra-abdominal abscesses due to an extended-spectrum I-lactamaseproducing strain of Klebsiella pneumonwae.The introduction and widespread clinical use of extendedspectrum cephalosporins have been associated with the discovery of plasmid-mediated enzymes capable of hydrolyzing these newer agents (2). The activity of these extended-spectrum 1-lactamases against ,-lactams which efficiently penetrate the cell membrane, such as cefotaxime, is often difficult to detect by standard-inoculum MIC testing (6) but is demonstrable when higher inocula are employed (2). This inoculum-dependent effect raises serious questions about the potential efficacy of cefotaxime and other extended-spectrum cephalosporins against infections caused by these organisms.We have recently reported an outbreak of infection and colonization with organisms elaborating two distinct broadspectrum ,3-lactamases at a chronic care facility (5). The more common of these two enzymes, YOU-1, a novel extended-spectrum enzyme with an isoelectric point of 5.57, conferred high-level resistance to ceftazidime (MIC = 256 ,ug/ml) but did not confer resistance to cefotaxime (MIC = 1 ,ug/ml) at a standard inoculum of 10i CFU/ml. We designed this study to compare the in vivo efficacies of various P-lactam antibiotics in the treatment of rat intra-abdominal abscesses due to a clinical isolate of YOU-1-producing Klebsiella pneumoniae.K. pneumoniae 5657 was a clinical isolate from sputum. The presence of a TEM-related, plasmid-mediated extendedspectrum 1-lactamase was confirmed as previously described (5 Md.) (4). Abscesses were created by intraperitoneal placement of a gelatin capsule containing sterile rat cecal contents derived from grain-fed rats, killed B. fragilis, and a 1:100 dilution of an overnight culture of K. pneumoniae 5657 (ca. 105 CFU) in a 2:1:1 ratio. Rats weighing between 175 and 200 g were anesthetized with an intraperitoneal injection of ketamine sulfate (ca. 125 mg/kg) (Parke Davis, Morris Plains, N.J.). A small incision was then made in the left lower quadrant of the abdomen, and the infective capsule was placed directly into the peritoneal cavity. Treatment was begun by continuous infusion via the left internal jugular vein (7) 3 to 4 h after the placement of the capsule and continued for 3 days. Animals were randomly assigned to one of seven treatment groups: (i) untreated control, (ii) cefoperazone (600 mg/kg/day), (iii) cefoperazone (600 mg/kg/ day) plus sulbactam (300 mg/kg/day), (iv) cefotaxime (400 mg/kg/day), (v) cefpirome (400 mg/kg/day), (vi) ceftazidime (400 mg/kg/day), and (vii) imipenem-cilastatin (300 mg/kg/ day). On day 2 or 3 of therapy, blood samples were collected for the determination of serum antibiotic levels. Concentrations in serum were measured by high-performance liquid chromatog...

The in vitro activity of the fluoroquinolone CP-99,219 against gram-positive bacteria was compared with those of five other antimicrobial agents. Against ciprofloxacin-susceptible staphylococci and against streptococci, MICs were <0.12 and .0.5 ,ig/ml, respectively. 219 was also more active than ciprofloxacin against ciprofloxacin-resistant staphylococci, most enterococci, Leuconostoc spp., and lactobacilli. Table 1. Against ciprofloxacinsusceptible strains of staphylococci, MICs for 90% of isolates tested (MIC90s) of CP-99,219 were '0.12 ,ug/ml, and the new agent was more active than ciprofloxacin and temafloxacin against these strains. Among the ciprofloxacinsusceptible strains of S. aureus, isolates that were methicillin susceptible or resistant demonstrated comparable susceptibilities to CP-99,219. The new drug was the most active quinolone against ciprofloxacin-resistant isolates, but relatively high concentrations were required for inhibition (MIC0s, 8 to 16 ,ug/ml). CP-99,129 was four-to eightfold more active than temafloxacin or ciprofloxacin against streptococci (groups A, B, and G and viridans group streptococci) and pneumococci. Activity of sparfloxacin against these strains fell between that of CP-99,219 and those of ciprofloxacin and temafloxacin. CP-99,219 was fourfold more active than ciprofloxacin against ciprofloxacin-susceptible Enterococcus faecalis (MIC90s, 0.25 to 0.5 ,g/ml) and against both vancomycin-susceptible and -resistant Enterococcus faecium (MIC90s, 4 ,ug/ml). The new quinolone was the most active drug tested against Leuconostoc spp. and Pediococcus spp. and was the most potent quinolone against Corynebacterium jeikeium. Inhibitory concentrations of CP-99,219 against the latter varied over a wide range, however, and were relatively high. Only vancomycin proved to be uniformly active against these strains. There was no difference in the activity against recent isolates of ciprofloxacin-susceptible S. aureus and that against strains collected more than 10 years ago for either CP-99,219 or ciprofloxacin.Against most species we have tested, CP-99,219 was more active than ciprofloxacin and temafloxacin. While the new quinolone was generally more active than sparfloxacin, MIC90s of these two drugs against the more-common patho-

We reidentified our laboratories' collections of 57 enterococcal isolates previously classified as Enterococcus avium by the API Rapid Strep identification system (Analytab Products, Plainview, N.Y.) with the identification criteria recommended by Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27: 731-734, 1989). Thirty isolates were identified as true E. avium, 25 isolates were identified as E. raffinosus, and 2 isolates were identified as E. pseudoavium. E. raffinosus could be differentiated from E. avium on the basis of penicillin susceptibility, as follows: MIC for 50% of E. raffinosus isolates tested (M1C50), 32 ,ug/ml; MIC90, 64 ,ug/ml (range, 4 to 64 ,ug/ml); E. avium M1C50, 1 ,ug/ml; MIC90, 2 ,ug/ml (range, 0.5 to 2 ,ug/ml Lett. 57:283-288, 1989); however, a number of newly identified PBPs were noted. Of 25 isolates, 13 had an additional PBP of 77 kDa (designated PBP 6*), while all isolates possessed a 52-kDa PBP (PBP 7) and a 46-kDa PBP (PBP 8). The presence or absence of PBP 6* did not correlate with penicillin susceptibility; however, PBP 7 demonstrated many features suggestive of low penicillin-binding affinity and may represent a possible mechanism for the relative resistance of this species to penicillin, although this hypothesis remains speculative since attempts to develop a penicillin-hypersusceptible E. raffinosus mutant were unsuccessful. E. raffinosus isolates were significantly more likely to exhibit high-level resistance to kanamycin than E. avium strains were (P < 0.001; chi-square); however, no strains demonstrated high-level resistance to gentamicin. No trend toward increasing penicillin resistance was noted among this collection of E. avium and E. raffinosus isolates collected over the past 35 and 14 years, respectively. Relative resistance to penicillin may be a helpful differentiating feature between E. avium and E. raffinosus when assessment of raffinose metabolism is not possible or is indeterminant.

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