Epidemiology

• The incidence of PVL-positive S. aureus is currently low in the UK.
• 496 cases of PVL-positive S. aureus infections were identified in 2006,^[8] more than twice the number identified in 2005.
• It is not certain if this increase is due to better case identification or an actual increase in prevalence. Provisional figures for subsequent years showed a 2.4-fold year on year increase in 2007 and a 1.4-fold increase in 2008, so the picture is far from clear.^[9]
• Outbreaks have occurred in hospital and community settings.
• The majority have been associated with mild skin/tissue infections.^[8]
• The HPA is aware of 7 deaths in England and Wales associated with PVL-positive MRSA over the last 2 years.^[8]

Presentation^[6]

There is an asymptomatic carrier status.

Infection with PVL-positive S. aureus most commonly causes:^[10]

• Necrotising pyogenic skin infections.
• Cellulitis.
• Tissue necrosis.

It can also cause:

• Septic arthritis.
• Osteomyelitis.
• Pyomyositis.
• Bacteraemia.
• Purpura fulminans (typically characterised by disseminated intravascular coagulation and purpuric skin lesions).^[11]
• Community-acquired necrotising pneumonia.^[12][13]

Clinical infection tends to accompany other risk factors such as:

• Overcrowding.
• Engagement in close contact sports (which can cause skin abrasions), eg rugby, wrestling.
• Being in military, residential home and school settings.
• Using contaminated articles: sharing towels, razors.
• Poor hand hygiene.
• Damaged skin, eg eczema.
• Illicit drug use.^[14]

Skin infection

• Consider screening in anyone if there are recurrent abscesses/furunculosis.
• Management includes drainage of abscesses and sensitivity testing to find appropriate antibiotics.
• Swabs should be taken as indicated and, if there is specific reason to suspect PVL-positive S. aureus such as recent contact, it should be stated on the request form.
• If either MSSA or MRSA is isolated (the latter usually ciprofloxacin susceptible), refer to the Staphylococcal Reference Unit at Colindale for PVL-testing. For urgent requests, please contact the Staphylococcal Reference Unit (Tel: 020 8327 7227).
• A polymerase chain reaction (PCR) test for PVL virulence genes and simultaneous discrimination of MRSA from MSSA has recently been developed.^[15] The unit at Colindale can provide a result within the working day.
• Mild infections may resolve without treatment.
• Moderate infections should be treated with flucloxacillin, erythromycin or clindamycin.^[16]
• If community-acquired MRSA-PVL infection occurs and hospitalisation is not thought appropriate, consider a 5-7-day course of one of the following, depending on microbiological susceptibility:
  • Rifampicin 300 mg bd PLUS doxycycline (100 mg bd - not for children <12 years).
  • Rifampicin 300 mg bd PLUS fusidic acid 500 mg tds.
  • Rifampicin 300 mg bd PLUS trimethoprim 200 mg bd.
  • Clindamycin 450 mg qds.
• Infection control measures include screening of patients for S. aureus carriage (swab nose, throat, perineum, axilla, skin lesions). Decolonisation may be needed as with MRSA.

Necrotising pneumonia^[6]

• General points:
  • Can arise from blood-borne spread of organisms from infected tissue but can also follow viral respiratory infections. A preceding flu-like illness is common.^[17]
  • Necrotising vasculitis with massive areas of pulmonary infarction and haemorrhage can occur.^[17]
  • Infection tends to be rapidly progressive and in young, immunocompetent individuals.^[12]
  • There is a high fatality rate.
  • Some cases have also been identified in people with pre-existing lung disease, eg cystic fibrosis.^[18]
• Diagnosis - the key is prompt diagnosis but this is difficult.
  • In general practice the following features are suggestive in a previously fit young person and admission to hospital is required:^[16]
    • Haemoptysis.
    • Hypotension.
    • Severe sepsis following a flu-like illness.
  • In hospital, these findings strongly suggest the diagnosis:^[16]
    • Multilobar infiltrates on CXR, usually accompanied by effusions and later cavitation.
    • Haemoptysis.
    • Hypotension.
    • Marked leukopenia (PVL toxin destroys white blood cells).
    • Very high C-reactive protein (CRP) level (>250-300 mg/L) - reflecting gross tissue destruction, thrombosis and sepsis.^[17]
    • Staphylococcal-like Gram-positive cocci on Gram film.
    • Features of flu-like illness: fever >39°C, heart rate >140 beats per minute, myalgia, chills.
    • Diarrhoea and vomiting can occur if there is associated toxic shock.
    • Raised creatine kinase may suggest myositis.
• Management:
  • ITU admission is required.
  • Antibiotics: various combinations have been used. Always perform sensitivity testing. Hospital treatment of necrotising pneumonia, usually involves a number of antibiotics given intravenously.
  • Until susceptibility results are available, clindamycin 1.2 g IV qds, linezolid 600 mg IV bd (to suppress PVL and alpha toxin production 12, 28, 29) and rifampicin 600 mg bd (for intracellular clearance of staphylococci) should be commenced.
  • Providing susceptibility results are confirmatory, this combination should be continued until the patient is clinically stable. Continuation therapy should be considered with linezolid plus rifampicin, or with clindamycin plus rifampicin for 10-14 days, guided by the clinical response and infection markers such as CRP.
  • Intravenous immunoglobulin treatment should be considered, especially if there is associated septic shock.^[17]
• Infection control measures:^[16]
  • Wear surgical masks during intubation and physiotherapy.
  • Use only closed tracheal suction.
  • Screen close contacts for carriage of PVL-positive S. aureus with nose, throat, perineum, axilla and skin lesion swabs.

Prognosis

• Necrotising pneumonia has a high mortality rate if not diagnosed early and treated energetically. Mortality can be as high as 75%.^[12]
• Otherwise, prognosis with this infection is generally good and most of the PVL-positive strains of S. aureus identified in the UK are sensitive to many antibiotics.

Prevention^[7]

Surveillance

The HPA recommend that the HPU or CICT should be alerted to new cases of PVL if:

• There is a single case in a patient belonging to a high-risk group (eg a health care worker, residential/care home staff, those involved in gyms or close contact sports such as wrestling and rugby) or in a closed community where onward transmission is possible (eg prison, military camps, nursing homes).
• There is a cluster or outbreak in institutional or community settings.

All significant incidents and potential or actual outbreaks should be reported on the HPA Incident Reporting Information System (IRIS) and HPZone (where available). The Staphylococcus Reference Unit will investigate, using DNA fingerprinting if necessary.

Decolonisation of the index case should be carried out once the infection has been treated. The local HPU or microbiologist will advise about the decolonisation of contacts if necessary.

Practical measures

As with any kind of S. aureus, thorough hand washing and drying, or use of alcoholic hand rubs if hands are not visibly soiled, have been shown to be the most important measures in reducing cross infection in both the community and the hospital.^[19]

Public health advice from the HPA includes:^[6]
In the community:

• Encourage good hygiene measures: regular bathing, regular changing of bedlinen and underwear, hand washing, avoiding sharing personal items (toothbrush, towels, etc.).
• Liquid soap and disposable towels in shared facilities (eg toilets, gyms).
• Regular cleaning and good ventilation in same shared facilities.
• Proper cleaning/disinfection of wounds, with use of appropriate dressings.
• If spread or recurrence occurs, seek medical advice.

In hospitals and community medical settings:

• Thorough hand washing and drying or use of alcohol hand rubs if hands are not visibly soiled.
• Barrier nursing of infected patients in side-rooms or special wards.
• Visitors to wear gloves and aprons and wash hands/clean with alcoholic rub before leaving a ward.