SUMMARY The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the antibiotic armamentarium. However, more reliable information is needed to determine the optimal dosing of these agents. Also, unanswered questions regarding in vitro testing remain, including questions regarding the reliability of automated systems and the establishment of appropriate breakpoints for defining susceptibility. Most contemporary clinical studies examining the use of these agents have involved patients with infections due to multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been reassuring that polymyxin therapy for resistant bacteria has resulted in clinical responses and toxicity rates similar to those for carbapenem therapy for susceptible isolates. While most surveillance studies demonstrated high rates of susceptibility, several reports noted the emergence of polymyxin-resistant nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for therapy for hospital-acquired infections; further studies defining the optimal use of these agents will likely extend the duration of their clinical usefulness.

Acinetobacter baumannii strains resistant to all ␤-lactams, aminoglycosides, and fluoroquinolones have emerged in many medical centers. Potential mechanisms contributing to antimicrobial resistance were investigated in 40 clinical isolates endemic to New York City. The isolates were examined for the presence of various ␤-lactamases, aminoglycoside-modifying enzymes, and mutations in gyrA and parC. Expression of the genes encoding the ␤-lactamase AmpC, the efflux systems AdeABC and AbeM, and the OmpA-like porin was also examined by real-time reverse transcription-PCR. No VIM, IMP, KPC, OXA-23-type, OXA-24-type, or OXA-58 ␤-lactamases were detected, although several isolates had acquired bla SHV-5 . Most cephalosporin-resistant isolates had increased levels of expression of ampC and/or had acquired bla SHV-5 ; however, isolates without these features still had reduced susceptibility to cefepime that was mediated by the AdeABC efflux system. Although most isolates with ISAba1 upstream of the bla OXA-51 -like carbapenemase gene were resistant to meropenem, several remained susceptible to imipenem. The presence of aminoglycoside-modifying enzymes and gyrase mutations accounted for aminoglycoside and fluoroquinolone resistance, respectively. The increased expression of adeABC was not an important contributor to aminoglycoside or fluoroquinolone resistance but did correlate with reduced susceptibility to tigecycline. The expression of abeM and ompA and phenotypic changes in OmpA did not correlate with antimicrobial resistance. A. baumannii has become a well-equipped nosocomial pathogen; defining the relative contribution of these and other mechanisms of antimicrobial resistance will require further investigation.

The in vitro activity of N-formimidoyl thienamycin (MK0787) was tested against 239 anaerobic bacteria clinical isolates: 70 of Bacteroides fragilis, 18 of B. distasonis, 16 of B. thetaiotaomicron, 10 of B. vulgatus, 24 of Bacteroides spp., 22 of B. melaninogenicus (all three subspecies), 26 of Fusobacterium spp., 10 of Peptococcus spp., 15 of Peptostreptococcus spp., 15 of Clostridium perfringens, and 13 of Clostridium spp. Ninety-five percent of the isolates were inhibited by less than or equal to 0.125 microgram/ml, and all were inhibited by less than or equal to 4 micrograms/ml.