BRO beta-lactamase alleles, antibiotic resistance and a test of the BRO-1 selective replacement hypothesis in Moraxella catarrhalis.

OBJECTIVES The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of the Moraxella catarrhalis BRO beta-lactamase was tested by examining the temporal distribution, antibiotic resistance and epidemiological characteristics of isolates from a long-term collection at a single locale. METHODS A rapid, one-step PCR assay conducted on 354 isolates spanning 1984-1994 distinguished bro alleles in over 97% of the beta-lactamase-producing isolates. Probes of dot blots were used to distinguish PCR failure from non-beta-lactamase-mediated penicillin resistance. RESULTS BRO-2 isolates comprised 0-10% of the population per year with no evidence of a decline over time. All beta-lactamase producers exceeded the clinical threshold for penicillin resistance. Bimodality of penicillin MICs for beta-lactamase producers was caused by variation within BRO-1 rather than differences between BRO-1 and BRO-2. Non-beta-lactamase factors also confer resistance to penicillin and may contribute to the BRO-1 bimodality. The 13 BRO-2 isolates were associated with diverse genotypes within which there was evidence of epidemiologically linked clusters. The exclusive association of BRO-2 with four unrelated genotypes suggested maintenance of BRO-2 by recurrent mutation or horizontal exchange. CONCLUSIONS The relative rarity of BRO-2 throughout the study, the absence of a declining temporal trend, and genetic diversity within BRO-2 all failed to support the hypothesis that BRO-2 was more common in the past and has been selectively replaced by BRO-1.