Analysis of Trends in Antimicrobial Resistance Patterns Among Clinical Isolates of Bacteroides fragilis Group Species from 1990 to 1994

Abstract

Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.

Isolation of Metronidazole-Resistant Bacteroides fragilis Carrying the nimA Nitroreductase Gene from a Patient in Washington State

“…Moderate-to high-level 5-nitroimidazole resistance is conferred by these genes, with metronidazole MICs ranging from 4 to 32 g/ml (16). Although multiple antimicrobial resistance determinants may be found clustered together on plasmids, insertion elements, or transposons, this does not seem to be the case for the nim loci (20). Therefore, the finding of metronidazole FIG.…”

“…This action requires intracellular reduction of the nitro group of these prodrugs to produce reactive radical species. Although the 5-nitroimidazole drugs were introduced into clinical practice in 1960, resistance of B. fragilis to these drugs was not described until 1978 (10) and remains rare (1,(20)(21)(22). The first metronidazole-resistant Bacteroides isolates were found to have altered end products of glucose metabolism that conferred distinctive biochemical and growth characteristics along with metronidazole MICs of Ն64 (3,12).…”

“…For clinical isolates of anaerobic bacteria, susceptibility testing is frequently not performed. Rather, treatment is guided by the periodic assessment of susceptibility patterns among stocked isolates or from national surveillance studies (1,(20)(21)(22). Members of the Bacteroides fragilis group, the most common isolates from clinically significant anaerobic infections, have been associated with increased mortality rates, increased length of hospital stay (15), and clinical failures when inappropriately treated (14).…”

“…They can be resistant to some agents used in the treatment of anaerobic infections, such as penicillin and clindamycin (11). However, as seen in large surveillance studies, they have remained almost universally susceptible to metronidazole, a 5-nitroimidazole, despite widespread use of this agent over the past 30 years (1,(20)(21)(22). Metronidazole resistance has been reported in Europe (6) and Africa (11), most commonly attributable to the presence of one of five known nim nitroreductase genes (7), but metronidazole resistance has not previously been reported in B. fragilis isolates from the Western Hemisphere (22).…”

High Incidence of Cefoxitin and Clindamycin Resistance among Anaerobes in Taiwan

“…Compared to the data of our previous report, the rate of resistance to imipenem for B. fragilis has not increased, but the MIC 50 (from 0.12 to 0.5 g/ml) and MIC 90 (from 1 to 4 g/ml) have increased slightly. Resistance to the carbapenems has been occasionally and infrequently recorded (13).…”