Beta Lactam Resistance

Beta-lactams are still useful agents for the treatment of anaerobic infections, even though significant resistance has been noted. The B. fragilis group has the highest prevalence of resistance to beta-lactams as almost all (more than 97%) of B. fragilis group isolates resist penicillin G. In contrast, the cephamycins (e.g., cefoxitin cefotetan) have better activity, although the prevalence of resistance among B. fragilis group has increased. During 1987-2000, resistance to cefoxitin was observed in 8% to 14% of B. fragilis group (15,17). However, variations were noted among individual medical centers, with higher resistance at some (15).

Cefotetan is as active as cefoxitin against B. fragilis, but is much less effective against other members of the B. fragilis group with resistance rates of 30% to 87%, depending on the species. This high prevalence of resistance resulted in recent recommendations against the use of both cephamycins as empirical therapy for intra-abdominal infections (42). However, they, can still be used when susceptible testing shows them to be active. Piperacillin resistance has also increased from less than 10% in 1980 to 25% with significant variability among the B. fragilis group (15,24). This agent is not currently recommended for empirical therapy for intraabdominal infections.

The most active beta-lactam agents against anaerobic bacteria are the carbapenems (imipenem, meropenem, and ertapenem) with resistance of less than 0.2% of B. fragilis group isolates (15,20,43), and the combinations of a beta-lactam agent with a BL inhibitor (ampicillin/ sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam) where less than 4% of B. fragilis group strains were resistant in 2003 (18). When organisms are resistant to penicillins through the production of BL, the addition of a BL inhibitor usually makes them effective against these isolates. However, strains of non-BL-resistant Bacteroides distasonis frequently have higher MICs for all beta-lactam-BL inhibitor combinations.

Resistance to beta-lactam agents among non-Bacteroides anaerobes is variable but is generally lower than the B. fragilis group. In one multicenter study 83% of Prevotella isolates were resistant to penicillin G, whereas resistance was lower for Porphyromonas (21%), Fusobacterium (9%), and Peptostreptococcus (6%) (20). All isolates were susceptible to cefoxitin, beta-lactam/BL inhibitor combinations, and carbapenems, except for Peptostreptococcus isolates (4% were resistant to ampicillin/sulbactam) and Porphyromonas (5% were resistant to cefoxitin) (20).

Resistance to beta-lactam antibiotics is mediated by at least one of three resistance mechanisms: inactivating enzymes (BL); reduced-affinity penicillin-binding proteins; or decreased antimicrobial permeability. The production of BLs is the most common mechanism and mediates the most diverse mechanisms of resistance.

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