MICROBIOLOGY


n Healthcare-acquired MRSA HA-MRSA infections are frequently transmitted within healthcare institutions caring for acutely ill patients. The main mode of MRSA transfer among patients, caregivers, and others in these environments is often attributed to inadequate hand hygiene practices and inconsistent disinfection protocols.3 Within healthcare facilities, devices like catheters, intubation tubes, and other implants serve as conduits for MRSA colonisation in patients. Furthermore, surgical and other invasive procedures that disrupt the skin and mucosal surfaces provide additional pathways for MRSA to enter usually protected body sites.3


n Community-acquired MRSA CA-MRSA infections stem from sources within the community unrelated to healthcare. The predominant CA-MRSA strain persisting in the US is known as USA300. Similar to healthcare settings, MRSA spreads within the community through skin contact or sharing items with significant skin contact, such as cosmetics, towels, razors, hairbrushes, and nail files.3


Individuals participating in high- impact and contact sports like football, soccer, rugby, ice hockey, wrestling and basketball are at a heightened risk of CA-MRSA infection. The risk of infection for both CA- and HA-MRSA is elevated among individuals who carry MRSA or have previously experienced an MRSA infection.


Panton-Valentine leukocidin toxin PVL earned its name from Sir Philip Noel Panton and Francis Valentine in 1932 when they linked it to soft tissue infections.19


PVL toxin is a


bicomponent exotoxin that enhances the pathogenicity of S. aureus through the lysis of leucocytes.8


The genes encoding


PVL, comprised of two co-transcribed open reading frames (lukS and lukF), are on lysogenic bacteriophages that can integrate into specific sites on the S. aureus chromosome. LukS-PV and LukF-PV form a biologically active heptamer that induces lysis in leucocytes (such as granulocytes, neutrophils, monocytes, and macrophages) by creating pores and causing membrane damage.16


by PVL releases inflammatory mediators,


n Dermatological symptoms The dermatological manifestations of PVL- SA are characterised by recurring boils, necrotising skin, and SSTIs in otherwise healthy individuals, especially when other household or community members exhibit similar symptoms.14


Common Leucocyte apoptosis triggered


SSTIs associated with PVL-SA include furunculosis, carbuncles, folliculitis, cellulitis, abscesses, and skin necrosis, often recurring despite multiple antibiotic courses and delays in diagnosis of PVL-SA


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Certain MRSA strains are shared among household members, individuals in athletic clubs, and others in community settings where close contact is common, including dormitories, daycare centres, barracks, correctional facilities, locker rooms, gyms, and facilities used by sports teams.14


Severe infection with a complex course requiring prolonged hospitalisation, eg pneumonia, osteomyelitis or bloodstream infections.


Moderate purulent skin infections affecting larger areas. These could include recurrent boils in multiple locations.


Mild skin and soft tissue infections presenting as small abscesses, boils or


localised skin infections.


Fig 2. Clinical course of PVL-associated infections adapted from refs 14, 16 and 17.


including reactive oxygen species (ROS) and cytokines, which can further damage epithelial cells and surrounding tissues.16 PVL exerts distinct effects on immune cells, influencing the pathogenesis of infections caused by CA-MRSA strains by triggering an exaggerated inflammatory response and causing damage to host tissue that could manifest as necrotic haemorrhagic pneumonia.12 At high concentrations (200 nM), PVL induces lytic cell death, while at sublytic concentrations (5 nM) it appears to activate neutrophils – a phenomenon known as priming. This priming effect releases potent inflammatory mediators, such as leukotriene B4, interleukin-8, and neutrophil granule contents through exocytosis.12 The increased ability of CA-MRSA strains to evade neutrophil killing suggests a heightened virulence capacity. This attribute may be associated with their propensity to cause infections in otherwise healthy individuals.8


Clinical manifestations of PVL-SA infection PVL-SA manifests across a spectrum of diseases, ranging from asymptomatic nasopharyngeal carriage to severe necrotising conditions. These presentations can be categorised into dermatological and non-dermatological manifestations.


disease.14,17 It is important to note that


the associated pain and erythema may be exaggerated compared to the severity of the clinical manifestations.14


n Non-dermatological symptoms The non-dermatological manifestations of PVL-SA can result in invasive infections in previously healthy individuals. In patients with community-acquired pneumonia, the presence of haemoptysis should raise suspicion for necrotising pneumonia,14


prompting further imaging


for clarification. Haemoptysis typically occurs following an influenza-like prodrome, particularly in children and young adults.18


Approximately a quarter


of patients have a history of skin lesions, either personal or in close contact. Other invasive infections associated with PVL-SA include necrotising fasciitis and purpura fulminans. PVL-SA can also manifest as severe musculoskeletal infections such as osteomyelitis, pyomyositis, and septic arthritis, especially in children.14 Compared to PVL-negative-S. aureus infections, these musculoskeletal infections exhibit higher complication rates, increased inflammation levels, prolonged hospital stays, and a greater likelihood of requiring surgical intervention.14,18,19


Current diagnostic approaches PVL testing is not routinely conducted in many local hospital microbiology laboratories unless specifically requested by a clinician, leading to potential underestimation of its prevalence. Diagnosis of PVL relies on clinical history, physical examination, and specific microbiological testing. Notably, specimens from severe diseases are more commonly tested for PVL toxin genes than minor skin and soft tissue infections, introducing bias in retrospective studies.20 Moreover, the broad spectrum of PVL- SA infections is not always suspected,


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