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Interim guidance on diagnosis and management of PVL-associated Staphylococcal infections in the UK

  • Last modified date:
    13 March 2007

This interim guidance was prepared by a Health Protection Agency (HPA) Working Group and is based on a review of the literature and experiences of colleagues in the UK, Europe and the USA. This guidance will be revisited following review of a number of recent cases in the UK.

Background

A new pattern of disease due to Panton - Valentine Leukocidin (PVL) - positive strains of Staphylococcus aureus is emerging in the UK and world-wide. PVL is a toxin, which destroys white blood cells and is carried by <2% of clinical isolates of S. aureus [1]. PVL can be detected in both meticillin sensitive S. aureus (MSSA) and meticillin resistant S. aureus (MRSA) [1]. To date the majority of isolates causing infection in the UK have been MSSA. Community-associated MRSA (CA-MRSA) are more likely to produce PVL than hospital-associated MRSA. PVL-positive S. aureus are normally associated with necrotising pyogenic cutaneous infections and occasionally with cellulitis or tissue necrosis [2]. However, they can cause other severe invasive infections such as septic arthritis, bacteraemia, purpura fulminans [3] or community-acquired necrotising pneumonia [4, 5].

Skin infections

Suspect PVL-associated staphylococcal infection if a patient has recurrent furunculosis or abscesses, especially if in a high risk group e.g. participants in close-contact sports, the military or those in residential homes.

Clinical Management

Abscesses should be drained surgically and then treated with systemic anti-staphylococcal antibiotics - choice depending on susceptibility testing.

Antibiotic Therapy

Currently, most UK PVL-positive Staph aureus strains are susceptible to flucloxacillin and usually sensitive to erythromycin and clindamycin. Consider combinations of doxycycline and rifampicin for CA-MRSA.

Infection Control

Patients should be screened (nose, throat, perineum, axilla, skin lesions) for S. aureus carriage and decolonisation regimens such as those used for MRSA decolonisation may need to be used to eradicate skin or upper respiratory carriage [6].

N.B. Screening swabs should be cultured on non-selective media (e.g. blood agar) to ensure the recovery of S. aureus independent of their meticillin susceptibility.

Necrotising pneumonia

PVL - positive strains of S. aureus have been associated with a rapidly progressive, haemorrhagic, necrotising community-acquired pneumonia in young immunocompetent patients, and a high fatality rate [4]. Most patients developing necrotising pneumonia have no history of skin sepsis but commonly have a preceding 'flu-like' illness.

Early clinical diagnosis is difficult but essential for survival. Typically the following features in a previously fit young patient suggest the diagnosis. In general practice, particularly haemoptysis, hypotension and severe sepsis following a 'flu like' illness warrants prompt referral to hospital. Once admitted, the constellation of findings strongly suggests the diagnosis:

  • Multilobar infiltrates on chest X-ray, usually accompanied by effusions, and later cavitation
  • Haemoptysis
  • Hypotension
  • Marked leucopenia
  • Very high C-reactive protein level (>250-300 g/L) (not found in viral infections)
  • Gram film of sputum reveals sheets of staphylococcal-like Gram-positive cocci
  • Non-specific findings of flu-like illness, (fever of >39oC, tachycardia >140 beats/min, myalgia, chills). Diarrhoea and vomiting may be due to associated toxic shock, which in the setting of a significantly raised serum creatine kinase suggests myositis.

N.B. The CURB score [7] may be misleadingly low in young adults on admission.

Clinical Management (mainly supportive)

  • Admit to Intensive Care
  • Administer aggressive antibiotic therapy - see below
  • Consider treatment with activated Protein C  (but not appropriate in active pulmonary haemorrhage)
  • Give intravenous immunoglobulin (IVIG) - see below

Antibiotic Therapy

There is a wide range of potentially useful antibiotics for treatment. It is important to check the susceptibility of individual isolates. Several publications have reported the value of combination therapy.

Combinations including vancomycin, clindamycin, linezolid, rifampicin and/or co-trimoxazole in high doses have been used [4,5,8,9].

Vancomycin should not be used alone [10]. Intravenous flucloxacillin (2gm 4-6 hourly) may be useful for bactericidal action in combination with linezolid (600 mg bd iv) or rifampicin (300 mg bd iv).

Linezolid can be used to cover MRSA pending antibiotic susceptibility results; clindamycin (1.2 gm qds), like linezolid, has the added advantage of suppressing toxin production.

Infection Control

Surgical masks should be worn during intubation and physiotherapy. Closed tracheal suction should be used since secondary cases may occur.

Screening (nose, throat, perineum, axilla, skin lesions) of close contacts for carriage of PVL-positive S. aureus [6]. See note above on screening swabs.

Adjunctive Treatment - Intravenous Immunoglobulin (IVIG)

IVIG should be considered in addition to intensive care support and high dose antibiotic therapy because of high mortality [4]. The dosage of 2g/kg of IVIG recommended in streptococcal toxic shock syndrome may be useful for PVL-positive S. aureus infections, neutralising exotoxins and superantigens [10,11,12].

Confirmation of clinical diagnosis

Isolates of S. aureus from cases which may be PVL - related (including community - acquired skin infections or pneumonia) should be sent to Dr Angela Kearns at the HPA Laboratory of Healthcare Associated Infection (LHCAI) at Colindale, telephone 0208 327 7227.

References

  1. Holmes A, Ganner M, McGuane s, Pitt TL, Cookson BD, Kearns AM. Staphylococcus aureus carrying Panton-Valentine Leukocidin genes (PVL) in England and Wales: frequency, characterisation and association with clinical disease. Journal of Clinical Microbiology 2005; 43:2384-2390.
  2. Reichert B, Birrell G. Severe non-pneumonic necrotising infections in children caused by Panton-Valentine Leukocidin producing Staphylococcus aureus strains. Journal of Infection 2005; 50:438-442.
  3. Kravitz GR, Dries DJ, Peterson ML, Schlievert PM. Purpura fulminans due to Staphylococcus aureus. Clin. Infect. Dis. 2005 ; 40:941-947
  4. Gillet Y, Issartel B, Vanhems P, Four net J C, Lina G, Bes M, Vandenesch F, Piemont Y, Brousse N, Floret D, Etienne J. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 2002; 359:753-759.
  5. Klein JL, Petrovic Z, Treacher D, Edgeworth J. Severe community-acquired pneumonia caused by Panton-Valentine Leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom. Intensive Care Medicine 2003; 29:1399.
  6. Ayliffe GAJ, Buckles A, Casewell MW et al. on behalf of the working party of the British Society of Antimicrobial Chemotherapy, the Hospital Infection Society and the Infection Control Nurses Association. Revised guidelines for the control of methicillin-resistant Staphylococcus aureus infection in hospitals. J Hosp Infect 1998;39:253-290
  7. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003; 58: 377-382.
  8. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset pneumonia in healthy adults caused by methicillin - resistant Staphylococcus aureus carrying the Panton -Valentine leukocidin genes.
  9. Wargo KA, Eiland EH. Appropriate therapy for community acquired methicillin resistant Staphylococcus aureus carrying the Panton Valentine leukocidin gene. Clin Infect Dis 2005; 40:100-7.
  10. Wargo KA, Eiland EH. Appropriate therapy for community acquired methicillin resistant Staphylococcus aureus carrying the Panton Valentine leukocidin gene. Clin Infect Dis 2005; 40:1376-7.
  11. Micek AT, Dunne M, Kollef MH. Pleuropulmonary complications and Panton-Valentine Leucocidin -Positive Community - Acquired Methicillin-Resistant Staphylococcus aureus: importance of treatment with antimicrobials inhibiting exotoxin production. Chest 2005; 128:2732-2738.
  12. Norrby-Teglund A, Ihendyanne N, Darenberg J. Intravenous immunoglobulin adjunctive therapy in sepsis, with special emphasis on severe invasive Group A streptococcal infections. Scand J. Infect. Dis 2003; 35: 683-689.
  13. Darenberg J, Soderquist B, Normark BN, Norrby-Teglund A. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications and therapy of toxic shock syndrome. Clin Infect Dis 2004; 38: 826-42.

Health Protection Agency PVL Working Group

Dr Christine McCartney (Chair), Interim Deputy Director, HPA Centre for Infections, Colindale.

Prof. Barry Cookson, Director Laboratory of Healthcare Associated Infections, Centre for Infections, Colindale.

Dr David Dance, Regional Microbiologist, HPA, South West.

Dr Chris Day, Consultant in Intensive Care, Royal Devon and Exeter Hospital, Exeter.

Prof. Brian Duerden, Inspector of Microbiology and Infection Control.

Dr Tony Elston, Consultant Microbiologist, Colchester General Hospital, Colchester.

Dr Angela Kearns, Staphylococcal Reference Unit, Laboratory of Healthcare Associated Infection, HPA Centre for Infections, Colindale.

Dr Marina Morgan, Consultant Microbiologist, Royal Devon and Exeter Hospital, Exeter.

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