BackgroundNeisseria meningitidis is nearly always susceptibleto the penicillins, the cephalosporins, and chloramphenicol.Between 1987 and 1996, however, chloramphenicol-resistant strainswere isolated from 11 patients in Vietnam and 1 in France.
Methods The minimal inhibitory concentration of chloramphenicolwas determined for the 12 isolates. The isolates were analyzedby monoclonal-antibody–based serotyping and subtyping,pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis.Bacterial DNA was analyzed by hybridization, the polymerasechain reaction, and sequencing to identify the resistance geneand determine the origin of the resistance.
Results The isolates were resistant to chloramphenicol (minimalinhibitory concentration, 64 mg per liter) and produced an activechloramphenicol acetyltransferase. All 12 strains belonged toserogroup B but had a high degree of diversity, and 10 couldnot be typed with the use of monoclonal antibodies. The nucleotidesequence of the resistance gene and the flanking regions wasidentical to that of an internal portion of transposon Tn4451that carries the catP gene in Clostridium perfringens. Moreover,this gene was located in the same genomic site in the chloramphenicol-resistantisolates.
Conclusions The high-level chloramphenicol resistance that wedescribe in N. meningitidis isolates is of great concern, sincein developing countries, chloramphenicol given intramuscularlyis the standard therapy for meningococcal meningitis. The resistanceto chloramphenicol is due to the presence of the catP gene ona truncated transposon that has lost mobility because of internaldeletions, and the transformation of genetic material betweenstrains of N. meningitidis probably played an important partin the dissemination of the gene.
Source Information
From the National Reference Center for Antibiotics and the Unité des Agents Antibactériens (M. Galimand, G.G., P.C.) and the National Reference Center for Meningococci (M. Guibourdenche, J.-Y.R.), Institut Pasteur, Paris.
Address reprint requests to Dr. Galimand at the Unité des Agents Antibactériens, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris CEDEX 15, France.
Lyras, D., Adams, V., Ballard, S. A., Teng, W. L., Howarth, P. M., Crellin, P. K., Bannam, T. L., Songer, J. G., Rood, J. I.
(2009). tISCpe8, an IS1595-Family Lincomycin Resistance Element Located on a Conjugative Plasmid in Clostridium perfringens. J. Bacteriol.
191: 6345-6351
[Abstract][Full Text]
Hedberg, S. T., Fredlund, H., Nicolas, P., Caugant, D. A., Olcen, P., Unemo, M.
(2009). Antibiotic Susceptibility and Characteristics of Neisseria meningitidis Isolates from the African Meningitis Belt, 2000 to 2006: Phenotypic and Genotypic Perspectives. Antimicrob. Agents Chemother.
53: 1561-1566
[Abstract][Full Text]
du Plessis, M., von Gottberg, A., Cohen, C., de Gouveia, L., Klugman, K. P., for the Group for Enteric Respiratory and Meningea,
(2008). Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005. J. Clin. Microbiol.
46: 3208-3214
[Abstract][Full Text]
Taha, M.-K., Zarantonelli, M. L., Neri, A., Enriquez, R., Vazquez, J. A., Stefanelli, P.
(2006). Interlaboratory Comparison of PCR-Based Methods for Detection of Penicillin G Susceptibility in Neisseria meningitidis. Antimicrob. Agents Chemother.
50: 887-892
[Abstract][Full Text]
Harrison, L. H.
(2006). Prospects for Vaccine Prevention of Meningococcal Infection. Clin. Microbiol. Rev.
19: 142-164
[Abstract][Full Text]
Jorgensen, J. H., Crawford, S. A., Fiebelkorn, K. R.
(2005). Susceptibility of Neisseria meningitidis to 16 Antimicrobial Agents and Characterization of Resistance Mechanisms Affecting Some Agents. J. Clin. Microbiol.
43: 3162-3171
[Abstract][Full Text]
Crawford, S. A., Fiebelkorn, K. R., Patterson, J. E., Jorgensen, J. H.
(2005). International Clone of Neisseria meningitidis Serogroup A with Tetracycline Resistance Due to tet(B). Antimicrob. Agents Chemother.
49: 1198-1200
[Abstract][Full Text]
Shultz, T. R., Tapsall, J. W., White, P. A., Ryan, C. S., Lyras, D., Rood, J. I., Binotto, E., Richardson, C. J. L.
(2003). Chloramphenicol-resistant Neisseria meningitidis containing catP isolated in Australia. J Antimicrob Chemother
52: 856-859
[Abstract][Full Text]
Huovinen, P.
(2002). Macrolide-Resistant Group A Streptococcus -- Now in the United States. NEJM
346: 1243-1245
[Full Text]
Rosenstein, N. E., Perkins, B. A., Stephens, D. S., Popovic, T., Hughes, J. M.
(2001). Meningococcal Disease. NEJM
344: 1378-1388
[Full Text]
Galimand, M., Gerbaud, G., Courvalin, P.
(2000). Spectinomycin Resistance in Neisseria spp. Due to Mutations in 16S rRNA. Antimicrob. Agents Chemother.
44: 1365-1366
[Abstract][Full Text]
van Deuren, M., Brandtzaeg, P., van der Meer, J. W. M.
(2000). Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management. Clin. Microbiol. Rev.
13: 144-166
[Abstract][Full Text]
A correction has been published: N Engl J Med 1999;340(10):824.
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. 
Previous
