Elsevier

The Lancet

Volume 375, Issue 9725, 1–7 May 2010, Pages 1557-1568
The Lancet

Seminar
Community-associated meticillin-resistant Staphylococcus aureus

https://doi.org/10.1016/S0140-6736(09)61999-1Get rights and content

Summary

Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.

Introduction

Staphylococcus aureus is a leading cause of human bacterial infections worldwide.1 The severity of these infections varies widely—from minor skin infections to fatal necrotising pneumonia. The pathogen is also a commensal organism in people, and about 30% of healthy individuals who are not in institutions are colonised asymptomatically with S aureus in the nostrils.2 These findings are noteworthy because nasal carriage of S aureus has been associated with subsequent infection.3

S aureus has outstanding ability to acquire resistance to antibiotics. Epidemics or pandemics of antibiotic-resistant S aureus have arisen in the past 60 years.4, 5 Benzylpenicillin was no longer effective for treatment of most S aureus infections within 10 years after its introduction for use in people because of the acquisition of plasmid-encoded β lactamase.6 Penicillin-resistant S aureus became pandemic throughout the late 1950s and early 1960s.7 Meticillin-resistant S aureus (MRSA) was first reported in 1961, 2 years after the antibiotic was introduced to treat the penicillin-resistant strain.8 MRSA spread worldwide over the next several decades and is now endemic in most hospitals and health-care facilities in industrialised countries. In the USA, MRSA is among the leading causes of death by any single infectious agent.4, 9 A major concern for treatment of MRSA infections is the increasing prevalence of resistance to several antibiotics (multidrug resistance).

By contrast with health-care-associated MRSA (HA-MRSA) infections, for which there is a predisposing risk factor or illness, community-associated MRSA (CA-MRSA) infections can occur in otherwise healthy individuals,10 suggesting that these bacterial strains have greater virulence than do traditional HA-MRSA strains. In addition to enhanced virulence, some CA-MRSA strains, such as USA300, have the ability to spread readily. These characteristics perhaps partly explain why CA-MRSA is present in many countries (figure 1).11, 12

In this Seminar, we review our current understanding of CA-MRSA emergence, the basis for enhanced transmission and virulence, and provide an update of the most recent strategies for diagnosis and treatment of CA-MRSA infections.

Section snippets

Epidemiology

Since MRSA was first described in 1961, it has been regarded as a nosocomial pathogen that is not normally present in the community. However, this notion has changed greatly in the past 15 years, and CA-MRSA infections are now prevalent and widespread (figure 1). Although MRSA infections acquired from the community were reported in Detroit, MI, USA, in 1982, all patients had predisposing risk factors for infection, such as previous hospital admission or intravenous drug abuse.13 The first

S aureus immune evasion

The ability of bacteria to cause disease in human beings is due largely to evasion of innate immunity, which includes resistance to killing by phagocytic leucocytes. S aureus produces several molecules—some on the cell surface and others freely secreted—that together elicit a robust inflammatory response. In as much as neutrophils are a key component of the inflammatory response and are the most prominent cellular defence against S aureus infections, the pathogen has evolved means to circumvent

Diagnosis

S aureus infection is diagnosed readily by isolating the organism from cultures of blood, tissue, or pus. The organism will grow in virtually any non-selective bacterial culture medium. Unless a patient has been previously treated with an effective antistaphylococcal drug (and generally several days of effective treatment are needed to render a site culture-negative), failure to culture S aureus is strong evidence against staphylococcal infection. If the bacterium is isolated from blood or

Antimicrobial therapy

Emergence of CA-MRSA has profoundly affected the choice of empirical treatment for suspected staphylococcal infection, particularly common skin and soft-tissue infections. β-lactams, which are inexpensive, not toxic, and highly effective, have been the drugs of choice for treatment of such infections, but, like HA-MRSA, CA-MRSA strains are broadly resistant to almost all β-lactam antibiotics, making these an undesirable option when the prevalence of CA-MRSA strains is high. Clinical evidence

Conclusions and future

S aureus has been a cause of human disease throughout recorded history. The antibiotic era was perhaps largely expected to eliminate S aureus (and other bacterial pathogens) as a leading cause of human infections. However, S aureus has extraordinary ability to develop resistance to antibiotics, which have been the impetus for waves of antibiotic resistance over the past 60 years.5 This resistance is perplexing, because antibiotics are absolutely crucial for treatment of many types of bacterial

Search strategy and selection criteria

We searched PubMed using the terms “CA-MRSA”, “Europe and CA-MRSA”, “Panton-Valentine leukocidin”, and “USA300”, without any language restrictions. We selected references mainly from the past 5 years, including cross-references, although landmark or highly regarded references were also included. Review articles were cited when appropriate for further detail about a specific topic. We also included references on the basis of comments from peer reviewers.

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