EDUCATIONAL CASE

Panton–Valentine leukocidin pneumonia: an emerging threat

Background

Panton–Valentine Leukocidin (PVL)-positive staphy-lococcal infection typically presents as soft tissue andbone infection (1, 2). PVL-positive staphylococcalinfection may also lead to necrotising pneumonia, acondition that can even be observed before the onset ofsoft tissue or bone infection (3, 4). Lina et al. reportedthe first case of PVL-positive leukocidin-producingstaphylococcus in pneumonia in 1999 (4). Recentworldwide reports of community-onset skin abscesses,outbreaks of furunculosis and severe pneumonia asso-ciated with methicillin-resistant Staphylococcus aureus(MRSA) carrying PVL genes and the staphylococcalcassette chromosome mec (SCCmec) type IV indicatethat MRSA infections are evolving into a community-related problem. Clonal spread of PVL-positive strainsand horizontal bacteriophage-dependent PVL-genetransfer thus contribute to an emerging health careproblem (5, 6).

We report the case of a 57-year-old previously fitCaucasian, female mathematics and physical educationteacher. The patient presented to our hospital withshortness of breath, fever, cough productive of sputumand confusion. She had been well until 7 days prior tothe admission when she had been sent home fromwork with a sore throat and symptoms of a non-specific viral illness.

Her past medical history was unremarkable exceptfor hypothyroidism. She was on no regular medication.There were no drug allergies and risk factors forendocarditis.

Upon initial examination, the patient presented withtype I respiratory failure and severe sepsis includingrenal failure. Staphylococcal necrotising pneumoniawas diagnosed based on culture results (blood andbroncho-alveolar lavage specimens), clinical criteria,and a high-resolution computed tomography (CT)scan demonstrating signs of severe pulmonary infiltra-tion. Chest radiograph (Fig. 1) showed multifocal

segmental consolidation bilaterally with suggestion ofcavitation in the right upper lobe. CT (Figs. 2–5) ofthe thorax demonstrated severe bilateral cavitatingnodules with surrounding consolidation and air bron-chograms worse in the right lung.

CorrespondenceAndrew Barlow, MSc, FRCP, MBChB Hons, BSc Hons,Watford General Hospital, Vicarage Road, WD18 0HB,Watford, UK.Tel: 01923 217698Fax: 01923 217824email: andybarlow@doctors.org.uk

Figure 1. AP Portable Chest Radiograph on Admission.

Figure 2. High-resolution CT images showing bilateral consoli-dation and cavity formation.

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61The Clinical Respiratory Journal (2010) • ISSN 1752-6981© 2009 Blackwell Publishing Ltd

Within 1 day of antibiotic therapy, the patient devel-oped progressive respiratory and haemodynamicfailure including development of the Acute RespiratoryDistress Syndrome (ARDS) requiring mechanicalventilation for 20 days (FiO2 0.8, paO2 79 mmHg,

positive end-expiratory pressure (PEEP) 15 cmH2O,peak inspiratory pressure 33 cmH2O). Furthermore,vasopressor and haemofiltration support was neces-sary for a subsequent period of more than 2 weeks.

Bronchoscopy revealed no endobronchial lesions;however, thick secretions from bronchoalveolar lavagegrew MRSA.

The patient was diagnosed with a severe necrotisingS. aureus pneumonia. She had no risk factors forinfection. Assessment of an underlying immune dis-order showed normal fasting serum blood glucoselevels (before onset of severe sepsis), normal quanti-tative complement levels (C3, C4) and normal immu-noglobulin (Ig) levels, including Ig subclasses.

Trans-oesophageal echocardiography revealed aprolapsed anterior mitral valve leaflets with mild pos-terior mitral regurgitation detected. A small vegeta-tion was detected. Two days later, the patient wasnoted to have new right-sided hemiparesis and CT ofthe head demonstrated an ill-defined low attenuatingarea seen in relation to the deep left temporal lobe,thalamus and the adjacent basal ganglionic capsularregion. A few low attenuating areas suggestive of inf-arcts are seen in relation to the deep right temporallobe.

She was mechanically ventilated and treated for atotal 63 days with Rifampicin and Flucloxacillin, reha-bilitated and discharged symptom-free and able toperform the activities of daily activities.

Figure 3. High-resolution CT images showing bilateral consoli-dation and cavity formation.

Figure 4. High-resolution CT images showing bilateral consoli-dation and cavity formation.

Figure 5. High-resolution CT images showing bilateral consoli-dation and cavity formation.

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62 The Clinical Respiratory Journal (2010) • ISSN 1752-6981© 2009 Blackwell Publishing Ltd

Discussion

Three characteristic findings are typical of community-onset S. aureus strains. The first is PVL genes of theSCCmec type IV element, belonging to the USA300pulsed-field type. Classically these are associated withnecrotic lesions of the skin and subcutaneous tissues(e.g. furuncles), and also with community-acquiredsevere necrotic pneumonia. However this is thefirst documented case of the PVL gene responsible fordeep-seated infections, such as infective endocarditis(4).

ARDS and acute lung injury (ALI) are multifactoriallife-threatening diseases in which an acute inflamma-tory response leads to increased microvascular lungpermeability, clinically manifesting as severe hypox-emia, diffuse infiltrates on chest radiographs anddecreased lung compliance (7).

The current familiar title was given because of itsmany apparent pathophysiological similarities to theinfant respiratory distress syndrome (8). Surfactantdeficiencies are present in both syndromes but are aconsequence of diffuse lung injury in ARDS, in con-trast to a deficiency as a primary aetiology in the infantrespiratory distress syndrome.

In 1994, the North American European ConsensusConference introduced the current accepted defini-tion for ARDS (9). ARDS is an acute illness charac-terisedby severe hypoxaemia (with a PaO2 : fiO2 ratio of<200 mmHg, regardless of the level of positive endexpiratory pressure applied), bilateral pulmonaryinfiltrates and a pulmonary wedge pressure of lessthan 18 mmHg or no clinical evidence of left atrial

hypertension. ALI can be seen as a milder form ofARDS and is present if the PaO2 : fiO2 ratio is lessthan 300 mmHg but more than 200 mmHg.

The aetiology of ARDS can be associated with directinjury to the lung; for example, the injury may be aconsequence of direct pulmonary damage such as aspi-ration of gastric contents and those that cause indirectlung injury in the setting of a systemic process, asdescribed by Moon in 1936 (10) (see Table 1). Sepsiscarries the highest risk of progression to ALI or theARDS, approximately 40% (11, 12). The presence ofmultiple predisposing disorders substantially increasesthe risk (11), as does the presence of secondary factorsincluding chronic alcohol abuse (12, 13), chronic lungdisease and a low serum pH (7). In the case of ourpatient, she presented with severe sepsis.

In summary, we present a case of PVL S. aureuspneumonia, ARDS with endocarditis and septicemboli causing stroke.

Nada Al-Hadithy1, Zaid Zoumot2, Sabita Parida3

and Andy Barlow4

1 ST1 Plastic Surgery, St John’s Hospital, Livingston,Scotland, UK

2 Royal Brompton Hospital, Royal Brompton andHarefield Trust, London, UK

3 West Hertfordshire Hospitals, NHS Trust, UK4 Watford General Hospital, Watford, UK

References

1. Panton PN, Valentine FCO. Staphylococcal toxin. Lancet.1932;1: 506–8.

Table 1. Causes of Acute Respiratory Distress Syndrome

Direct injury Indirect injury

Common causes Common causesPneumonia (viral, bacterial, O2 toxicity, fungal,

mycolplasma, pneumocystis)Sepsis (especially gram negative)

Aspiration of gastric contents Severe trauma with shock and multiple transfusionsLess common causes Less common causes

Pulmonary contusion Cardiopulmonary bypassFat emboli Acute pancreatitisReperfusion pulmonary oedema NeurogenicAfter lung transplantation or pulmonary embolectomy EclampsiaNear-drowning Surface burnsInhalational injury (smoke or irritant gas) Disseminated intravascular coagulationHigh altitude Thrombotic thrombocytopenic purpuraRadiation Leukaemia

Drug overdose (acetylsalicyclic acid, paraquat toxicity ethchlorvynol,heroin, methadone, propoxyphene, barbituates)

Idiosyncratic drug reaction

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2. Moumile K, Cadilhac C, Lina G, Berche P, Glorion C,Ferroni A. Severe osteoarticular infection associated withPanton-Valentine leukocidin-producing Staphylococcusaureus. Diagn Microbiol Infect Dis. 2006;56(1): 95–7.

3. Gillet Y, Issartel B, Vanhems P, et al. Association betweenStaphylococcus aureus strains carrying gene forPanton-Valentine leukocidin and highly lethal necrotizingpneumonia in young immunocompetent patients. Lancet.2002;359: 753–9.

4. Lina G, Piemont Y, Godailt-Gamot F, Bes M, Peter MO,Gauduchon V, Vandenesch F, Etienne J. Involvement ofPanton-Valentin leukocidin-producing Staphylococcusaureus in primary skin infections and pneumonia. ClinInfect Dis. 1999;29: 1128–32.

5. Chambers HF. Community-associated MRSA-resistanceand virulence converge. N Engl J Med. 2005;352(14):1485–7.

6. Boyle-Vavra S, Daum RS. Community-acquiredmethicillin-resistant Staphylococcus aureus: the role ofPanton-Valentine leukocidin. Lab Invest. 2007;87(1): 3–9.

7. Stevens J, Raffin TA. Adult respiratory distress syndrome.Aetiology and mechanisms. Postgrad Med J. 1984;60:505–13.

8. Ashbaugh DG, Bigelow DB, Petty TL, et al. Acuterespiratory distress in adults. Lancet. 1967;2:319–23.

9. Bernard GR, Artigas A, Brigham KL, et al. TheAmerican-European Consensus Conference on ARDS.Definitions, mechanisms, relevant outcomes, and clinicaltrial coordination. Am J Respir Crit Care Med. 1994;149:818–24.

10. Moon VH. Pathological features following shock withdelayed death. Am J Pathol. 1936;12: 788–92.

11. Pepe PE, Potkin RT, Reus DH, Hudson LD, Carrico CJ.Clinical predictors of the adult respiratory distresssyndrome. Am J Surg. 1982;144: 124–30.

12. Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinicalrisks for development of the acute respiratory distresssyndrome. Am J Respir Crit Care Med. 1995;151:293–301.

13. Moss M, Bucher B, Moore FA, Moore EE, Parsons PE. Therole of chronic alcohol abuse in the development of acuterespiratory distress syndrome in adults. JAMA. 1996;275:

50–4.

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