Panton-Valentine Leukocidin (PVL) Positive Staph. Aureus

Panton-Valentine Leukocidin (PVL) is a cytotoxin that can destroy white blood cells and cause extensive tissue necrosis and severe infection. The toxin was first described by Panton and Valentine in 1932.¹

Some Staphylococcus aureus strains carry genes for PVL and at least 14 strains of PVL-positive S. aureus are known.² It is carried by < 2% of isolates of S. aureus, both methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA).³

PVL-positive S. aureus strains are usually associated with community-acquired infections and generally affect previously healthy young children and young adults. Most infection has been associated with PVL-positive MSSA so far in the UK. Community-acquired MRSA is more likely to produce PVL than hospital-acquired MRSA. Carriage of the PVL gene alone may not be the main virulence factor. Factors that up-regulate toxin synthesis in vivo could also contribute to more severe disease and worse outcomes.^4,5

The Health Protection Agency has issued interim guidance on the diagnosis and management of PVL-associated staphylococcal infections in the UK.⁶ This article outlines this guidance. There is a separate article on methicillin-resistant S. aureus (MRSA).

• The incidence of PVL-positive S. aureus is currently low in the UK.
• 496 cases of PVL-positive S.aureus infections were identified in 2006,⁷ 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.
• Outbreaks have occurred in hospital and community settings.
• The majority have been associated with mild skin/tissue infections.⁷
• The Health Protection Agency is aware of 7 deaths in England and Wales associated with PVL-positive MRSA over the last 2 years.⁷

There is an asymptomatic carrier status.
Infection with PVL-positive S. aureus most commonly causes:⁸

• Necrotising pyogenic skin infections
• Cellulitis
• Tissue necrosis

It can also cause:

• Septic arthritis
• Bacteraemia
• Purpura fulminans (typically characterised by disseminated intravascular coagulation and purpuric skin lesions)⁹
• Community-acquired necrotising pneumonia^10,11

Clinical infection tends to accompany other risk factors such as:

• Overcrowding
• Engagement in close contact sports (which can cause skin abrasions) e.g. rugby, wrestling
• Being in military, residential home and school settings
• Using contaminated articles: sharing towels, razors
• Poor hand hygiene
• Damaged skin e.g. eczema
• Illicit drug use¹²

Skin infection

• Consider screening in anyone if there is 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.
• A PCR test for PVL virulence genes and simultaneous discrimination of MRSA from MSSA has recently been developed.¹³
• Most infections are susceptible to flucloxacillin, erythromycin and clindamycin.⁶
• If community-acquired MRSA, consider doxycycline and rifampicin combination.⁶
• 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

• 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.¹⁴
  • Necrotising vasculitis with massive areas of pulmonary infarction and haemorrhage can occur.¹⁴
  • Infection tends to be rapidly progressive and in young, immunocompetent individuals.¹⁰
  • There is a high fatality rate.
  • Some cases have also been identified in people with pre-existing lung disease, e.g. cystic fibrosis.¹⁵
• 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:⁶
    • Haemoptysis
    • Hypotension
    • Severe sepsis following a "flu-like" illness.
  • In hospital, these findings strongly suggest the diagnosis:⁶
    • Multilobar infiltrates on chest X-ray, usually accompanied by effusions and later cavitation
    • Haemoptysis
    • Hypotension
    • Marked leucopenia (PVL toxin destroys white blood cells)
    • Very high C-reactive protein level (>250-300 g/L) - reflecting gross tissue destruction, thrombosis and sepsis¹⁴
    • Staphylococcal-like Gram-positive cocci on gram film
    • Features of flu-like illness: fever > 39, heart rate > 140 bpm, myalgia, chills
    • Diarrhoea and vomiting can occur if there is associated toxic shock
    • Raised creatine kinase may suggest myositis
• Management:⁶
  • 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.
  • Combinations including vancomycin, clindamycin, linezolid, rifampicin +/- co-trimoxazole have been used.^10,11,16 Flucloxacillin in combination with linezolid or rifampicin may also be used. Linezolid can cover MRSA whilst waiting for susceptibility results. Linezolid and clindamycin have the advantage that they decrease production of the PVL toxin which may have improved clinical effects.^17,18,19
  • Consider treatment with activated Protein C (except if active pulmonary haemorrhage).
  • Intravenous immunoglobulin treatment should also be considered, especially if there is associated septic shock.¹⁴
• Infection control measures:⁶
  • 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.

• Necrotising pneumonia has a high mortality rate if not diagnosed early and treated energetically. Mortality can be as high as 75%.¹⁰
• 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.

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.²⁰ Public health advice from the Health Protection Agency includes:

In the community

• Encourage good hygiene measures: regular bathing, regular changing of bed linen and underwear, hand washing, avoid sharing personal items (toothbrush, towels etc)
• Liquid soap and disposable towels in shared facilities (e.g. toilets, gyms)
• Regular cleaning and good ventilation in same shared facilities
• Proper cleaning/disinfection of wounds with 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 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 ward