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Volume 7, Number 1—February 2001

Letter

Lack of Evidence for Cloramphenicol Resistance in Neisseria meningitidis, Africa

Suggested citation for this article

To the Editor: High-level chloramphenicol resistance has been reported in 11 epidemiologically unrelated Neisseria meningitidis serogroup B strains in Vietnam and in a single strain in France, all isolated between 1987 and 1996 (1). Resistance was mediated by a chloramphenicol acetyltransferase (Cat) encoded by a catP gene homologous to Clostridium perfringens transposon Tn4451. While used infrequently in industrialized countries, chloramphenicol is often used to treat patients with meningococcal disease in Africa, especially during epidemics, when it frequently becomes the drug of choice because it can be administrated intramuscularly (2).

To evaluate the presence of meningococcal chloramphenicol-resistant isolates in Africa, we assessed the frequency of the catP gene in 33 N. meningitidis strains of serogroup A selected from the collection of the Centers for Disease Control and Prevention's Epidemic Investigations Laboratory. The isolates, selected to give the maximum geographic and chronological representation, were collected during 1963 to 1998 from Chad, Egypt, Gambia, Ghana, Niger, Nigeria, South Africa, Tanzania, and Uganda, mostly during outbreaks. Thirteen (39.3%) of the strains were isolated during the 1990s, when chloramphenicol resistance was first described in Vietnam. All isolates were characterized by multilocus enzyme electrophoresis and represented four major electrophoretic subgroups (3,4). Chloramphenicol and penicillin MICs were determined for all isolates, according to the recommendations of the National Committee for Clinical Laboratory Standards, by the broth microdilution method using Mueller-Hinton broth with 5% lysed horse blood incubated in 5% CO2 (5). All isolates were susceptible to both chloramphenicol (MIC <2 µg/mL) and penicillin (MIC <0.06 µg/mL). In addition, we tested all isolates for the presence of catP by polymerase chain reaction (PCR) using primers A, B, C, and D (1). Primers A and B, designed from the sequence of catP, amplify a 300-bp fragment only in chloramphenicol-resistant isolates. Primers C and D, designed on the basis of meningococcal sequences flanking the Tn4451-like insertion, amplify ~1200-bp fragment in resistant isolates and ~200-bp fragment in susceptible strains. Strain LNP13947 (kindly provided by Marc Galimand) was used as a positive control.

The catP gene was not detected in 32 of 33 N. meningitidis serogroup A strains. One isolate that was negative with primers C and D tested positive with primers A and B (M2786, Nigeria, 1963), which could suggest that catP was present but in a different location in the meningococcal genome. However, the chloramphenicol MIC of that strain was 2 µg/mL (susceptible). Repeated attempts to sequence the A/B amplicon were not successful with either primers A and B or another set of primers internal to primers A and B, implying that only a portion of the catP gene was present or (even more likely, given the conserved nature of this gene) that the PCR result was a false-positive.

Chloramphenicol resistance was first described in meningococcal serogroup B isolates (1), but only serogroup A strains were included in this study since A is the most prevalent serogroup in Africa. (It accounts for most epidemics in Sub-Saharan regions.) Although our small sample size limited the chances of detecting a rare event, the data suggest that chloramphenicol resistance in Africa is relatively infrequent and that chloramphenicol is still an appropriate agent to treat meningococcal disease.

The acquisition of plasmids encoding Cat, which enzymatically inactivate choramphenicol, is the most common mechanism of resistance in gram-positive and gram-negative organisms. The catP gene has been found on various bacterial chromosomes and conjugative plasmids as part of the transposable element Tn4451. This transposon is derivative of the Tn6338 that contains six genes, the largest of which, TnpX, is required for the excision of the transposon in both Escherichia coli and C. perfringens (6). The Tn4451 derivative that lacked the functional TnpX gene was completely stable in both organisms because it had lost mobility as a result of these internal deletions (6). The finding of catP in N. meningitidis within such a truncated immobile transposon (1) and the possibility of transfer of this type of resistance among highly transformable organisms such as Neisseria spp. are of great concern. Were the transposon to become a stable part of the meningococcal genome, it could potentially be easily exchanged. Interspecies recombination between antibiotic-resistant genes of N. meningitidis and commensal Neisseria spp. has occurred in penicillin- and sulfonamide-resistant meningococci (710). A similar occurrence may be possible for N. meningitidis chloramphenicol resistance in Africa or other continents where this antibiotic is routinely used for treatment of patients with meningococcal diseases. Studies have not yet demonstrated the clinical significance of chloramphenicol resistance caused by the catP gene in meningococci. However, it is possible that, in developing countries, patients whose illness does not respond to antimicrobial agents may not be detected, or their isolates may not be obtained. Screening a selection of isolates for catP may allow early detection of chloramphenicol-resistant strains. Since detection of increasing chloramphenicol resistance could change recommendations for antimicrobial-drug therapy, surveillance for antimicrobial-drug resistance should be encouraged.

Maria-Lucia C. Tondella, Nancy E. Rosenstein, Leonard W. Mayer, Fred C. Tenover, Sheila A. Stocker, Mike W. Reeves, and Tanja Popovic
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Acknowledgment

We gratefully acknowledge Jasmine M. Mohammed for performing chloramphenicol and penicillin MICs.

References

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  2. World Health Organization. Control of epidemic meningococcal disease. WHO Practical Guidelines. 2nd ed. Geneva: World Health Organization; 1998. p.1-84 (WHO/EMC/BAC/98.3).
  3. Selander RK, Caugant DA, Ochman H, Musser JM, Gilmour MN, Whittam TS. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematic. Appl Environ Microbiol. 1986;51:87384.PubMed
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  6. Bannam TL, Crellin PK, Rood JI. Molecular genetics of the chloramphenicol-resistance transposon Tn4451 from Clostridium perfringens: the TnpX site-specific recombinase excises a circular transposon molecule. Mol Microbiol. 1995;16:53651. DOIPubMed
  7. Spratt BG, Zhang QY, Jones DM, Hutchison A, Brannigan JA, Dowson CG. Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis. Proc Natl Acad Sci U S A. 1989;86:898892. DOIPubMed
  8. Sáez-Nieto JA, Lujan R, Martinez-Soares JV, Berron S, Vazquez JA, Vinas M, Neisseria lactamica and Neisseria polysaccharea as possible sources of meningococcal beta-lactam resistance by genetic transformation. Antimicrob Agents Chemother. 1990;34:226972.PubMed
  9. Bowler LD, Zhang QY, Riou JY, Spratt BG. Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis. J Bacteriol. 1994;176:3337.PubMed
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Suggested citation for this article: Lack of Evidence for Cloramphenicol Resistance in Neisseria meningitidis, Africa . Emerg Infect Dis [serial on the Internet]. 2001 Jan-Feb [date cited] http://wwwnc.cdc.gov/eid/article/7/1/70-0163

DOI: 10.3201/eid0701.700163

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