High-Level Chloramphenicol Resistance inNeisseria meningitidis

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Abstract
Neisseria meningitidis is nearly always susceptible to the penicillins, the cephalosporins, and chloramphenicol. Between 1987 and 1996, however, chloramphenicol-resistant strains were isolated from 11 patients in Vietnam and 1 in France. The minimal inhibitory concentration of chloramphenicol was determined for the 12 isolates. The isolates were analyzed by monoclonal-antibody–based serotyping and subtyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis. Bacterial DNA was analyzed by hybridization, the polymerase chain reaction, and sequencing to identify the resistance gene and determine the origin of the resistance. The isolates were resistant to chloramphenicol (minimal inhibitory concentration, ≥64 mg per liter) and produced an active chloramphenicol acetyltransferase. All 12 strains belonged to serogroup B but had a high degree of diversity, and 10 could not be typed with the use of monoclonal antibodies. The nucleotide sequence of the resistance gene and the flanking regions was identical to that of an internal portion of transposon Tn4451 that carries the catP gene in Clostridium perfringens. Moreover, this gene was located in the same genomic site in the chloramphenicol-resistant isolates. The high-level chloramphenicol resistance that we describe in N. meningitidis isolates is of great concern, since in developing countries, chloramphenicol given intramuscularly is the standard therapy for meningococcal meningitis. The resistance to chloramphenicol is due to the presence of the catP gene on a truncated transposon that has lost mobility because of internal deletions, and the transformation of genetic material between strains of N. meningitidis probably played an important part in the dissemination of the gene.