Bro β-Lactamase Alleles, Antibiotic Resistance and a Test of the BRO-1 Selective Replacement Hypothesis in Moraxella Catarrhalis

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Objectives: The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of the Moraxella catarrhalis BRO β-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 β-lactamase-producing isolates. Probes of dot blots were used to distinguish PCR failure from non-β-lactamase-mediated penicillin resistance. Results: BRO-2 isolates comprised 0-10% of the population per year with no evidence of a decline overtime. All β-lactamase producers exceeded the clinical threshold for penicillin resistance. Bimodality of penicillin MICs for β-lactamase producers was caused by variation within BRO-1 rather than differences between BRO-1 and BRO-2. Non-β-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.