HIGH-LEVEL CHLORAMPHENICOL RESISTANCE IN NEISSERIA-MENINGITIDIS

Background Neisseria meningitidis is nearly always susceptible to the penicillins, the cephalosporins, and chloramphenicol. Between 1987 and 1996, however, chloramphenicol-resistant strains were isolated from 1 1 patients in Vietnam and 1 in France. Methods The minimal inhibitory concentration of chloramphenicol was determined for the 12 isolates. T he isolates were analyzed by monoclonal-antibody-based serotyping and subtyping, pulsed-field gel electrophoresis, and multilocus enzyme ele ctrophoresis. Bacterial DNA was analyzed by hybridization, the polymer ase chain reaction, and sequencing to identify the resistance gene and determine the origin of the resistance. Results The isolates were res istant to chloramphenicol (minimal inhibitory concentration, greater t han or equal to 64 mg per liter) and produced an active chloramphenico l 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 mo noclonal antibodies. The nucleotide sequence of the resistance gene an d the flanking regions was identical to that of an internal portion of transposon Tn4451 that carries the catP gene in Clostridium perfringe ns. Moreover, this gene was located in the same genomic site in the ch loramphenicol-resistant isolates. Conclusions The high-level chloramph enicol resistance that we describe in N. meningitidis isolates is of g reat concern, since in developing countries, chloramphenicol given int ramuscularly 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 disseminat ion of the gene. (N Engl J Med 1998;339:868-74.) (C)1998, Massachusett s Medical Society.