ABSTRACT & COMMENTARY

Synopsis: Genotyping of 174 strains of MRSA isolated over a period of 30 years showed that, although 13 major pulsotypes were found, this may actually represent gradual genetic evolution from a single clone of MRSA over time.

Source: Givney, et al. Evolution of an endemic methicillin-resistant Staphylococcus aureus population in an Australian hospital from 1967 to 1996. J Clin Microbiol 1998;36: 552-556.
Mrsa was first isolated at the royal prince Alfred Hospital, a tertiary referral hospital in Sydney, Australia, in 1965. In 1976, a shift in the phage types was noted with one predominating called type A (phage type pattern 83A/85/95)wk88/87M) phage types. Isolates of this endemic strain all produced characteristic grey colonies on tellurite medium and were unlike typicalS. aureus, which produce jet black colonies. The question then arose as to whether all such strains had a common source, which would have particular implications if infection control measures were to be effectively implemented. Givney and colleagues, therefore, used a method of genotyping, namely restriction fragment length polymorphisms (RFLP) with pulse-field gel electrophoresis (PFGE), to investigate the population of MRSA longitudinally. They picked 100 grey strains and 43 other black strains at random from each year between 1978 and 1996, as well as 31 strains isolated during the preceding decade. Their phage typing was repeated and the RFLP-PFGE patterns (pulsotypes) generated using the enzymeSma I were done. The similarity between the nucleotide sequences was then estimated by calculating the proportion of shared fragments, and then the phylogenetic relationship was depicted by generating a dendrogram. Each isolate was typed twice and the patterns were interpreted by two independent observations to ensure reproducibility.

The phage type A grey colony producing strains isolated from 1982-1990 belonged to pulsotypes I, II, III, and VI which all grouped together, whereas the majority of those isolated after this time belonged to pulsotype IV and congregated on another branch of the phylogenetic tree altogether. One particular phagetype A MRSA (38-A/M/96) first isolated in 1996 actually grouped together with methicillin-susceptible S. aureus isolated between 1967 and 1982, which mostly had other phagetypes. Thus, Givney et al conclude that a new clone of MRSA had, in fact, emerged during the early 1980s, and that its descendants preserved their ancestral phagetype while continuing to evolve at the molecular level, resulting in the different pulsotypes.

COMMENT BY J. PETER DONNELLY, PhD

This study indicates that MRSA is endemic and that, although new clones can emerge, they seldom do. Thus, infection control measures should be sufficient to prevent dissemination. By contrast, had there been evidence of new clones emerging frequently, control of antibiotic usage would have had greater impact on lowering MRSA infection rates since the selective pressure would have been reduced. This is not to say that one approach to controlling antibiotic resistance precludes the other, but rather that the chronic persistence of a single clone indicates inadequate infection control measures since the strain is being repeatedly transferred from one person to another over time. The new cone Givney et al identified arose at the beginning of the 1980s and was still present in 1996 alongside the MRSA found before then. Givney and associates also showed that while some clones became endemic, others had actually come and gone during the years. Just as important, the authors showed that reliance on a single method for studying the epidemiology of MRSA outbreaks would have been inadequate. Phagetyping alone would have confirmed the presence of an endemic clone while failing to discriminate sufficiently to allow tracing of contacts. RFLP-PFGE would have led erroneously to the conclusion that several clones were on the loose and perhaps have deflected attention away from preventing cross-infection to other more dramatic but pointless actions such as closing wards selectively in the vain hope of containing the epidemic. Just as important, any hospital that is beset by endemic MRSA needs to know whether this is due to a few clones persisting or to the repeated importation or emergence of new clones, if preventive action is to be focused and effective. However, this will require a proper laboratory service, which is being increasingly viewed as a luxury few can afford. Perhaps a few more papers like this one will persuade those who have to manage scarce health resources that such an attitude is a false economy in the face of the threat of new multidrug resistance such as that which has occurred to vancomycin.