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.
Some Staphylococcus aureus strains carry genes for PVL and at least 14 strains of PVL-positive S. aureus are known. It is carried by <2% of isolates of S. aureus, both meticillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA).
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.
The Health Protection Agency (HPA) has issued guidance on the diagnosis and management of PVL-associated staphylococcal infections in the UK. National guidance was issued in 2008 with further clarifications for local services in 2010. This article outlines this guidance. There is a separate article Meticillin-resistant Staphylococcus 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, 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.
- Outbreaks have occurred in hospital and community settings.
- The majority have been associated with mild skin/tissue infections.
- The HPA is aware of 7 deaths in England and Wales associated with PVL-positive MRSA over the last 2 years.
There is an asymptomatic carrier status.
Infection with PVL-positive S. aureus most commonly causes:
- Necrotising pyogenic skin infections.
- Tissue necrosis.
It can also cause:
- Septic arthritis.
- Purpura fulminans (typically characterised by disseminated intravascular coagulation and purpuric skin lesions).
- Community-acquired necrotising pneumonia.
Clinical infection tends to accompany other risk factors such as:
- 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.
- 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. 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.
- 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:
- 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.
- 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.
- Necrotising vasculitis with massive areas of pulmonary infarction and haemorrhage can occur.
- Infection tends to be rapidly progressive and in young, immunocompetent individuals.
- There is a high fatality rate.
- Some cases have also been identified in people with pre-existing lung disease, eg cystic fibrosis.
- 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:
- In hospital, these findings strongly suggest the diagnosis:
- Multilobar infiltrates on CXR, usually accompanied by effusions and later cavitation.
- 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.
- 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.
- 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.
- Infection control measures:
- 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.
- If a case of PVL-related disease is suspected, GPs should liaise with the local Health Protection Unit (HPU) or Community Infection Control Team (CICT) with regard to further investigation and treatment.
- Isolates of S. aureus from cases which may be PVL-related (including community-acquired skin infections or pneumonia) should be sent to the Staphylococcus Reference Unit at the HPA Centre for Infections at Colindale. Telephone: 0208 327 7227.
- The GP may be requested to complete a proforma available from the HPA website.
- The patient should be provided with any information also available from the HPA website.
- Necrotising pneumonia has a high mortality rate if not diagnosed early and treated energetically. Mortality can be as high as 75%.
- 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.
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.
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.
Public health advice from the HPA includes:
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.
Further reading & references
- Panton PN, Valentine FC. 1932. Staphylococcal toxin. Lancet 222(i): 506-508
- Dyer O; New MRSA strain is not at epidemic level, expert says. BMJ. 2007 Jan 6;334(7583):10.
- Holmes A, Ganner M, McGuane S, et al; Staphylococcus aureus isolates carrying Panton-Valentine leucocidin genes in England and Wales: frequency, characterization, and association with clinical disease. J Clin Microbiol. 2005 May;43(5):2384-90.
- Hamilton SM, Bryant AE, Carroll KC, et al; In vitro production of panton-valentine leukocidin among strains of methicillin-resistant Staphylococcus aureus causing diverse infections. Clin Infect Dis. 2007 Dec 15;45(12):1550-8.
- Otto M; Basis of virulence in community-associated methicillin-resistant Staphylococcus Annu Rev Microbiol. 2010 Oct 13;64:143-62.
- Steering Group on Healthcare Associated Infection; Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL-SA) in England, 2nd Edition. 2008
- Management of PVL-Staphylococcus aureus, Health Protection Agency, Local and Regional Services; Recommendations for Practice 2010
- Staphylococcus aureus, Health Protection Agency (HPA)
- PVL-SA infections in England and Wales: 2005-2008 data and revised algorithm for referral of suspected cases, Health Protection Agency News Archives; Volume 3 No 35; 2009
- Reichert B, Birrell G, Bignardi G; Severe non-pneumonic necrotising infections in children caused by Panton-Valentine leukocidin producing Staphylococcus aureus strains. J Infect. 2005 Jun;50(5):438-42.
- Kravitz GR, Dries DJ, Peterson ML, et al; Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis. 2005 Apr 1;40(7):941-7. Epub 2005 Mar 2.
- Gillet Y, Issartel B, Vanhems P, et al; Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002 Mar 2;359(9308):753-9.
- Klein JL, Petrovic Z, Treacher D, et al; Severe community-acquired pneumonia caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom. Intensive Care Med. 2003 Aug;29(8):1399. Epub 2003 May 29.
- Gilbert M, MacDonald J, Gregson D, et al; Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness or incarceration. CMAJ. 2006 Jul 18;175(2):149-54. Epub 2006 Jun 27.
- McClure JA, Conly JM, Lau V, et al; Novel multiplex PCR assay for detection of the staphylococcal virulence marker Panton-Valentine leukocidin genes and simultaneous discrimination of methicillin-susceptible from -resistant staphylococci. J Clin Microbiol. 2006 Mar;44(3):1141-4.
- Interim Guidance PVL-positive S. aureus, Chief Medical Officer, Dept of Health; Interim Guidance on diagnosis and management of PVL-associated Staphylococcal infections in the UK
- Morgan M; Staphylococcus aureus, Panton-Valentine leukocidin, and necrotising pneumonia. BMJ. 2005 Oct 8;331(7520):793-4.
- Elizur A, Orscheln RC, Ferkol TW, et al; Panton-Valentine Leukocidin-positive methicillin-resistant Staphylococcus aureus lung infection in patients with cystic fibrosis. Chest. 2007 Jun;131(6):1718-25. Epub 2007 Mar 30.
- Coia JE, Duckworth GJ, Edwards DI, et al; Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities. J Hosp Infect. 2006 May;63 Suppl 1:S1-44. Epub 2006 Apr 3.
|Original Author: Dr Michelle Wright||Current Version: Dr Laurence Knott|
|Last Checked: 19/11/2010||Document ID: 4025 Version: 23||© EMIS|
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