Plasmid-Mediated Resistance in Multiply Resistant Haemophilus influenzae Type b Causing Meningitis: Molecular Characterization of One Strain and Review of the Literature

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Abstract
The increasing prevalence of infections due to ampicillin-resistant strains of Haemophilus influenzae type b requires that suspected H. influenzae meningitis in children be initially treated with both ampicillin and chloramphenicol. Previously, the recognition of strains resistant to chloramphenicol but susceptible to ampicillin supported combination chemotherapy. In this study one case of meningitis due to a strain of H. influenzae resistant to ampicillin, chloramphenicol, and tetracycline was analyzed. The patient involved received intravenous trimethoprim-sulfamethoxazole, but putative resistance to this combination prompted the additional administration of intravenous moxalactam. The resistance of this organism was mediated by a conjugative 43-megadalton R plasmid; the determinants of ampicillin and chloramphenicol resistance were transferred as a single unit. However, not all of the multiply resistant transconjugants contained a detectable plasmid; DNA homology studies with R plasmids of H. influenzae confirmed that these extrachromosomal DNA sequences were associated with chromosomal DNA and that an extrachromosomal location was rare.