Linezolid susceptibility and potential resistance mechanisms among mrsa isolated from two major public hospitals in Malaysia
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Date
2014
Authors
Pulingam, Thiruchelvi
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Abstract
Linezolid is the first antibiotic of a new structural class, the oxazolidinones, to be approved for clinical use in 35 years. This antimicrobial agent is broadly effective against drug-resistant gram-positive pathogens which commonly cause infections. However, the availability of this drug in Malaysian government hospitals is relatively low and the knowledge on linezolid‘s efficacy in MRSA treatment is lacking. The objective of this research was to determine the susceptibility towards linezolid among methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia. From the 100 strains collected from two government hospitals, namely Hospital Universiti Sains Malaysia (HUSM) and Hospital Pulau Pinang (HPP), it was found that all clinical MRSA isolates were fully susceptible to linezolid. The susceptibilities of 100 isolates against 5 other antibiotics were also studied. Three strains from HPP showed intermediate vancomycin resistance with MICs of 3-8μg/ml, 4% of clinical MRSA were resistant to chloramphenicol, 20% were resistant to clindamycin, 33% were resistant to erythromycin and all were resistant to oxacillin (as per microbiological definition of MRSA). Finally, the presence of molecular mechanisms conferring linezolid resistance was investigated. The most common way through which MRSA acquires resistance to linezolid, the G2576U base substitution at 23S ribosomal RNA, was noticeably absent in all isolates. Acquisition of a natural resistance gene, cfr, which encodes for the Cfr methyltransferase enzyme, could render nezolid. However, the presence of this gene in the genetic makeup of clinical MRSA was not detected according to agarose gel analysis of cfr-PCR conducted in this study. DNA sequencing revealed a total of 26 types of base substitutions and one type of base deletion within domain V of 23S rRNA of 11 clinical MRSA isolates. Based on data accumulated in this study, linezolid is recommended as an acceptable alternative to vancomycin for MRSA infections treatment in Malaysian healthcare settings.