1 Gram-Positive Bacteria Typing and Research Unit, Curtin University of Technology, School of Biomedical Sciences, Molecular Genetics Research Unit, Perth, Western Australia, Australia; 2 Curtin University of Technology, School of Biomedical Sciences, Molecular Genetics Research Unit, Perth, Western Australia, Australia; 3 Gram-Positive Bacteria Typing and Research Unit, Curtin University of Technology School of Biomedical Sciences and Department of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, Western Australia, Australia; 4 Gram-Positive Bacteria Typing and Research Unit, Department of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, Western Australia, Australia
Keywords: community-acquired infections , resistance genes , plasmids
Sir,
Community methicillin-resistant Staphylococcus aureus (CMRSA) are becoming important community pathogens and, although most are currently resistant to few antibiotics except the ß-lactams, medical practitioners still have limited therapeutic choices for managing infections in the community. The Gram-positive Bacteria Typing and Research Unit in Western Australia (WA) characterizes all MRSA that are isolated in the State using several typing techniques, including multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec) characterization and Panton-Valentine Leukocidin (PVL) detection. Currently, the most frequently encountered CMRSA in WA is the sequence type (ST) 1, SCCmec type IV clone (ST1-MRSA-IV), of which 8% carry the determinant for PVL. This clone comprised 55.6% of WA CMRSA (n = 1248) isolated between 1 July and 31 December 2004. ST1-MRSA-IV is closely related to the PVL-positive CMRSA MW2 strain, that was responsible for the deaths of four children in the USA1 and has recently been reported in Europe.2 In Australian national multicentre surveillance studies in 2000 (n = 293) and 2002 (n = 384), 55.7% of all MRSA investigated were CMRSA and 16.1% of these were ST1-MRSA-IV.3
ST1-MRSA-IV CMRSAs in Australia vary in their resistance to erythromycin. Of 112 that were obtained from people in remote WA communities during community screenings between 1995 and 2003, 63 (56%) were found to have the inducible macrolide, lincosamide, streptogramin B (MLS) resistance phenotype. In routine susceptibility testing, the resistant strains demonstrated resistance to erythromycin and erythromycin-inducible resistance to the lincosamide antibiotics lincomycin and clindamycin, as detected by the D-test. This finding is similar to a study in the USA which found that 100% of erythromycin-resistant, clindamycin-susceptible ST1 CMRSA clones had the inducible MLS phenotype.4
As the inducible erythromycin-resistant isolates are phenotypically susceptible to the lincosamide antibiotics, clindamycin is an attractive therapeutic option. However, concern has been expressed about its use because it has been shown that the strains can mutate from the inducible erythromycin-resistant, clindamycin-susceptible MLS phenotype to the constitutive erythromycin-clindamycin-resistant MLS phenotype in vivo during treatment.5
It has been previously reported that erythromycin resistance in the ST1-MRSA-IV Australian isolates is encoded on an 2 kb plasmid,6 pWBG738, which has now been completely sequenced (accession number NC_007209). Interestingly, pWBG738 (2473 bp) has 99% nucleotide identity with pT48 (2475 bp) (accession number NC_001395) which was harboured by a strain of S. aureus isolated from an infected patient in Florida, USA. pWBG738 encodes the erm(C) MLS-resistance gene whose product is the ErmC methylase that mediates resistance by dimethylation of an adenine residue in 23S rRNA. The erm(C) control region of pWBG738, containing the leader peptide and secondary structures that mediate control by translational attenuation, is functionally intact. As deletions in the erm(C) control region result in the constitutive MLS phenotype, we urge caution in the use of macrolide, lincosamide and streptogramin B antibiotics, such as clindamycin, to treat CMRSA infections.
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None to declare.
Acknowledgements
This study was supported by the National Health and Medical Research Council of Australia and the Health Department of Western Australia.
References
1. Centres for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus: Minnesota and North Dakota, 19971999. MMWR Morb Mortal Wkly Rep 1999; 48: 70710.
2. Witte W, Braulke C, Cuny C et al. Emergence of methicillin-resistant Staphylococcus aureus with Panton-Valentine leukocidin genes in central Europe. Eur J Microbiol Infect Dis 2005; 24: 15.[CrossRef][ISI]
3.
Coombs GW, Nimmo GR, Bell JM et al. Community methicillin-resistant Staphylococcus aureus in Australia: genetic diversity in strains causing outpatient infections. J Clin Microbiol 2004; 42: 473543.
4.
Chavez-Bueno S, Bozdogan B, Katz K et al. Inducible clindamycin resistance and molecular epidemiologic trends of pediatric community-acquired methicillin-resistant Staphylococcus aureus in Dallas, Texas. Antimicrob Agents Chemother 2005; 49: 22838.
5.
Drinkovic D, Fuller ER, Shore KP et al. Clindamycin treatment of Staphylococcus aureus expressing inducible clindamycin resistance. J Antimicrob Chemother 2001; 48: 3156.
6.
O'Brien FG, Pearman JW, Gracey M et al. Community strain of methicillin-resistant Staphylococcus aureus involved in a hospital outbreak. J Clin Microbiol 1999; 37: 285862.
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