JAC Advance Access originally published online on December 21, 2007
Journal of Antimicrobial Chemotherapy 2008 61(2):458-460; doi:10.1093/jac/dkm483
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Research letters |
Prevalence and characterization of macrolide-lincomycin-streptogramin B-resistant Staphylococcus aureus in Korean hospitals
1 Division of Antimicrobial Resistance, Center for Infectious Disease Research, National Institute of Health, 194, Tongil-Lo, Eunpyung-Gu, Seoul 122-701, Republic of Korea 2 Division of Biodefence Research, Center for Infectious Disease Research, National Institute of Health, 194, Tongil-Lo, Eunpyung-Gu, Seoul 122-701, Republic of Korea 3 Food Microbiology Team, Center for Food Safety Evaluation, Korea Food and Drug Administration, 194, Tongil-Lo, Eunpyung-Gu, Seoul 122-704, Republic of Korea
* Corresponding author. Tel: +82-2-380-1478; Fax: +82-2-380-1550; E-mail: yslee07{at}nih.go.kr
Keywords: macrolide resistance genes , double disc diffusion , non-tertiary hospitals
Resistance to macrolide, lincosamide and streptogramin B (MLSB) antibiotics in Staphylococcus spp. is mediated by a methylase encoded by erythromycin ribosome methylation (erm) genes or ATP transporter efflux pumps encoded by the msr or mef genes. The methylation of the 50S ribosomal subunit by erm gene products causes constitutive or inducible resistance to MLSB antibiotics. Constitutively resistant MLSB (MLSBc) strains and inducibly resistant MLSB (MLSBi) strains express erm genes, erm(A) or/and erm(C). In this study, we investigated and characterized the constitutive and inducible resistance, and the susceptibility to clindamycin of Staphylococcus aureus isolated from non-tertiary hospitals.
We collected 508 S. aureus strains from 157 hospitals nationwide from January to June 2005 in Korea. Antimicrobial susceptibility to oxacillin, erythromycin, clindamycin and quinupristin/dalfopristin and the MICs were evaluated according to the guidelines of the CLSI. Of the 508 S. aureus isolates, 46.1% (234 isolates) were resistant to oxacillin, 55.1% (280 isolates) were resistant to erythromycin, which comprised 98.3% (230/234) methicillin-resistant S. aureus (MRSA) strains and 18.2% (50/274) methicillin-susceptible S. aureus (MSSA) strains, and 37.4% (190 isolates) were resistant to clindamycin. No strains were susceptible to erythromycin and resistant to clindamycin. One hundred and eighty-six MRSA (80.9%) and four MSSA (8.0%) were MLSBc (resistant to erythromycin and clindamycin; Table 1). D-test according to Steward’s method was used for isolates with erythromycin resistance and clindamycin susceptibility.1 Forty-three MRSA (18.7%) and 40 MSSA (80.0%) were MLSBi (showing the D form on the D-test), and 1 MRSA (0.4%) and 6 MSSA (12.0%) were MLSBs (susceptible to clindamycin).
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The MLSB resistance genes, erm(A), erm(B), erm(C), msr(A), msr(B) and mef, were detected using a PCR method.2 erm(A) was detected in 250 strains, erm(C) in 14 strains, erm(B) in 1 strain, msr(A) in 3 strains, erm(A) and erm(C) in 2 strains, erm(A) and msr(A) in 3 strains and no genes in 7 strains.
Most MLSBc and MLSBi strains carried the erm(A) or erm(C) gene (Table 1). The erm(A) gene (in 250 isolates) was detected far more frequently than erm(C) (in 14 strains). However, the erm(C) gene was distributed more frequently in MLSBi strains (12 isolates) than in MLSBc strains (2 isolates). Using OLIGO primers designed by Arthur et al.,3 the PCR products were detected in three MLSBc or MLSBi strains lacking erm(A), erm(B) or erm(C). It was possible that the three strains carry an erm gene besides erm(A), erm(B) or erm(C). msr(A) was detected in one MRSA isolate and five MSSA isolates, three MLSBi isolates carried msr(A) together with erm(A) and three MLSBs contained only msr(A).
We also found msr(A) in three of seven MLSBs isolates but did not detect the msr(A) gene in four MLSBs strains. To determine whether the four MLSBs isolates carried the msr(A) gene, Southern hybridization was performed by the Amersham ECL Direct Nucleic Acid Labeling and Detection system (Amersham, GE Healthcare Life Science, USA), but no fragments were detected (data not shown). Also, any resistance genes encoding ATP transporter efflux pumps [msr(B), msr(C) and msr(D)], mef(A/E) genes and the phosphorylase mph(C) gene were not detected in the four strains (data not shown).
The MICs of erythromycin for MLSBc and MLSBi isolates were 
256 mg/L, with the exception of one strain with an MIC of 8 mg/L. The MICs of erythromycin for the MLSBs strains were 4, 8 or 64 mg/L. The MICs of clindamycin for clindamycin-susceptible and clindamycin-resistant strains, determined by agar dilution, were 
1 and 64 mg/L, respectively (Table 1).
It has been reported that MLSBc and MLSBi isolates in Staphylococcus carry erm(A), erm(B) or erm(C), and at times erm together with msr(A), but MLSBs carry the msr(A) gene.4 Although msr(A) and erm(A) were detected together in MLSBi, the msr(A) gene was detected in MLSBs. In Streptococcus, MLSBc and MLSBi strains carried erm(A) and had MICs of erythromycin of 16–256 mg/L; and MLSBs or M phenotype strains had mef(A) and MICs of 16–48 or 8–32 mg/L.5
We propose that MICs of erythromycin of 4–64 mg/L are insufficient to induce resistance to clindamycin, and the erm genes were expressed at high concentrations of erythromycin and the msr(A) gene at low concentrations. If the msr and erm genes are detected together, the erm gene may be expressed more rapidly than the msr gene and the phenotype of the strain may be MLSBc or MLSBi.
In conclusion, the erythromycin resistance rate in S. aureus was high at 55.1%, and 99.6% of erythromycin-resistant MRSA and 88.0% of MSSA strains were MLSBc or MLSBi. Therefore, the treatment of infections caused by erythromycin-resistant S. aureus with clindamycin in non-tertiary hospitals is not effective.
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Funding |
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 Top Funding Transparency declarationsReferences |
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This study was supported by a research grant from the Korea Food and Drug Administration (KFDA) in Republic of Korea in 2005.
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Transparency declarations |
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TopFundingTransparency declarationsReferences |
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None to declare.
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Acknowledgements |
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We would like to thank the researchers in Seoul Clinical Laboratories (SCL) for sending the Staphylococcus isolates isolated from non-tertiary hospitals to our laboratory.
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References |
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TopFundingTransparency declarationsReferences |
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1 Steward CD, Raney PM, Morrell AK, et al. Testing for induction of clindamycin resistance in erythromycin-resistant isolates of Staphylococcus aureus. J Clin Microbiol (2005) 43:1716–21.
2
Lim JA, Kwon AR, Kim SK, et al. Prevalence of resistance to macrolide, lincosamide and streptogramin antibiotics in Gram-positive cocci isolated in a Korean hospital. J Antimicrob Chemother (2002) 49:489–95.
3
Arthur M, Molinas C, Mabilat C, et al. Detection of erythromycin resistance by the polymerase chain reaction using primers in conserved regions of erm rRNA methylase genes. Antimicrob Agents Chemother (1990) 34:2024–6.
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) 49:2283–8.
5
Hesenbein ME, Warner JE, Lambert KG, et al. Detection of multiple macrolide- and lincosamide-resistant strains of Streptococcus pyogenes from patients in the Boston area. J Clin Microbiol (2004) 42:1559–63.
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