MRSA in the community

Methicillin resistant Staphylococcus aureus (MRSA)
Methicillin resistant Staphylococcus aureus (MRSA)

Since first reported in 1961 [1] methicillin resistant Staphylococcus aureus (MRSA) has rapidly established itself as one of the most prevalent cause of serious hospital acquired infection becoming endemic in most hospitals in the developed world [2], overtaking methicillin susceptible Staphylococcus aureus (MSSA) in many cases. Until recently MRSA was considered to be almost exclusively a nosocomial pathogen with well defined healthcare related risk factors (e.g. recent surgery, catheters or dialysis) [3]. However, since the early 1990s a growing number of cases of MRSA have been reported in the community, often amongst healthy individuals with no predisposing risk factors [4,5]. This lead to the categorisation of MRSA into community associated (CA-MRSA) and healthcare associated (HA-MRSA) based primarily on epidemiological distribution.

There are several groups considered at higher from CA-MRSA including prison inmates, athletes, children, military recruits and IV drug-users. However, these are not factors in themselves and relate to the CDC’s “5 C’s” - Crowding, skin-to-skin Contact, Compromised skin, Contaminated items and lack of Cleanliness [30].

A number of clinical factors differentiate CA-MRSA, originally an infection in the absence of HA-MRSA associated risk factors [3] sufficed. However, this has become less useful as CA-MRSA strains are increasingly found in hospitals [6,7]. Another difference is the resistance profile of CA-MRSA; most isolates are resistant to ß-lactam antibacterials but susceptible to most other classes. HA-MRSA strains are often resistant to a wider range [3].

Clinical presentations of CA-MRSA also differ with skin and soft tissue infections more common in CA-MRSA and respiratory and urinary tract infections more common in HA-MRSA [3]. There have also been a number of cases which suggest CA-MRSA may be more virulent [8] with manifestations such as necrotizing fasciitis and necrotizing pneumonia [9]. Much research has focused on identifying the virulence factors responsible for these manifestations and a host of toxins and other virulence factors less common in other MRSA strains have been identified [10]. One of these is Panton-Valentine leukocidin (PVL), a pore-forming cytotoxin capable of killing leukocytes. Commonly found in CA-MRSA but almost unheard of in HA-MRSA, PVL was a prime candidate [11]. Whilst epidemiological data suggested a strong correlation between invasive infections, animal studies have produced conflicting results [12,13,14,15]. Recent research does appear to confirm PVL has a role in pathogenesis but this is dependent on species and site [16,17].

The first S. aureus antibacterial resistance was to penicillin soon after its introduction in the 1940s. This was facilitated by the enzyme penicillinase hydrolysing penicillin’s ß-lactam ring [18]. Subsequently, the phage type 80/81 strain of S. aureus reached pandemic proportions in hospitals [19]. The 1960 release of methicillin in which the ß-lactam ring was protected halted this pandemic [1] but success was short-lived. Given the short generation times of bacteria, exposure to antibacterials provides an environment where rapid selection for resistance takes place. Additionally, bacteria possess the ability to (horizontally) transfer genetic material between each other [20] and it is thought that S. aureus acquired methicillin resistance this way from another Staphylococcus species [21].

Unlike penicillin resistance these new strains had a broad spectrum resistance to all ß-lactams as instead of targeting the drug the bacteria’s surface proteins are modified preventing binding [22]. Later molecular studies DNA sequencing MRSA revealed that the gene encoding methicillin resistance (mecA) was carried on highly mobile genetic elements, the staphylococcal chromosomal cassette (SSCmec). SSCmec is a short sequence containing its own recombinases facilitating insertion into the host genome [23]. The first MRSA carried SSCmec I and clones circulated US and European hospitals up to the late 1970s before disappearing [24].

Over the following decade the new SSCmec II and SSCmec III allotypes appeared with MRSA becoming endemic in hospitals throughout the industrialised world. Analysis of the different SSCmec types revealed size differed (34-67Kb), and although all carried the mecA gene, II and III carried additional resistance [28]. This growing resistance has resulted in the reintroduction of vancomycin , the ‘antibacterial of last resort’, however vancomycin resistance has been reported since the late 1990s [25].

CA-MRSA was first reported in remote Western Australia in patients with no recent hospital contact [26]. Between 1997-1999 in Mid-western USA four, otherwise healthy children died from sepsis and necrotizing pneumonia caused by a highly virulent strain [8]. A retrospective study into MRSA cases with no predisposing factors or healthcare contact found evidence of community associated infections dating back to the early 1990s in Chicago [5].

One question to be resolved was the origin of CA-MRSA. In 2002 Ma et al [27] studied a number of CA-MRSA isolates providing evidence that the differences with HA-MRSA were not only clinical but molecular. They identified the novel SCCmec IV element which was much smaller than other SCCmec elements (21-24Kb), and consistent with clinical observations, only ß-lactam resistant. A subsequent study found this was consistent in a sample of 12 diverse CA-MRSA strains tested [29] and suggested that not only where CA-MRSA strains different to HA-MRSA strains, but different to each other, i.e. not evolved from a common ancestor. This in turn provides evidence that the small SCCmec IV has been passed between MSSA strains in a ‘promiscuous’ manner due to increased mobility.

References

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This article was a summary of a recent dissertation I wrote on CA-MRSA as part of a Life Sciences degree I am doing with the Open University. It's pretty up to date and hopefully reflects the potential severity that MRSA in the community could present and the dangers of antibiotic resistance in general

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