Elsevier

The Lancet

Volume 368, Issue 9538, 2–8 September 2006, Pages 874-885
The Lancet

Review
Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat

https://doi.org/10.1016/S0140-6736(06)68853-3Get rights and content

Summary

Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25–30% of healthy people.1 Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition.2 Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials—the β-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems.

Section snippets

History

In the 1950s, years before meticillin-resistant Staphylococcus aureus (MRSA) was reported for the first time, three independent developments led to appreciation of the potential public-health implications that S aureus might have in store. The first was the slow but persistent rise in penicillin resistance, which was noted soon after its first clinical trials.3 By the end of the 1940s, hospitals in the UK and the USA reported that 50% of S aureus was resistant to penicillin.4, 5 The second was

Worldwide burden of MRSA

By contrast with the assumptions that predicted little or no in vivo relevance of the meticillin-resistant phenotype in the 1960s, MRSA is at present the most commonly identified antibiotic-resistant pathogen in many parts of the world, including Europe, the Americas, north Africa, the middle east, and east Asia. Moreover, MRSA rates have been swiftly increasing worldwide over the past decades, as data from continuing surveillance initiatives such as the National Nosocomial Infection

Evolutionary biology and resistance determinants

The understanding of the evolution of MRSA has benefited from the development of molecular methods that provide characterisation of both the strain phylogeny (evolutionary history) and the meticillin-resistance determinant. Strain phylogenies can be resolved by multilocus sequence typing, which unambiguously identifies a strain on the basis of its sequence at seven housekeeping genes.89 Consistent molecular epidemiological evidence supports the view that the evolution of MRSA and of S aureus as

Screening of patients

Colonised and infected patients represent the most important reservoir of MRSA in health-care facilities.115 However, 35–84% of patients colonised with MRSA are not detected by cultures that are ordered by doctors for clinical reasons.115, 116, 117, 118, 119 Screening of patients by culture of samples from body sites such as the anterior nares alone will identify 80%, and screening from additional body sites will increase the sensitivity to over 92%.115, 117, 120 These patients—who do not have

Future perspectives

In the long evolutionary history of S aureus, strains with special epidemic properties have probably appeared from time to time. The present success of the few pandemic hospital-acquired-MRSA clones has been accounted for by the acquisition of additional fitness traits by already widespread and successful colonising strains, with the view that gaining β-lactam resistance yields a decisive advantage over competitors in hospitals.90 There are also indications that epidemic hospital acquired MRSA

Search strategy and selection criteria

We selected MEDLINE and PubMed hits generated by searches using the search terms: “Staphylococcus” or “Staphylococci” occurring in combination with one of the words “antimicrobial”, “antibiotic”, “susceptibility” or “resistance”. We used available monographies and Index Medicus for historical articles. For the present estimates on worldwide prevalence of MRSA we included search terms such as “surveillance”, “prevalence”, “incidence”, or “trend” occurring together with one or more of the

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