Panton-Valentine Leucocidin (PVL) Pneumonia: case report
H Venkatesh1, D.Watson2, IF Laurenson1, D Patel3 AJ Simpson4
Specialist Registrar in Microbiology1 Consultant Anaesthetist2 Consultant Microbiologist 1 Consultant Radiologist 3 Consultant in Respiratory Medicine4
Royal Infirmary of Edinburgh.
Corresponding author: Dr H Venkatesh
Specialist Registrar in Microbiology
Royal Infirmary of Edinburgh, 51 Little France, EH16 4SA.
Email: Haripriya.Venkatesh@luht.scot.nhs.uk
A 25 year old previously fit female shop attendant and SCUBA ‘divemaster’ presented to the emergency department with a history of increasing breathlessness over two days. Prior to this she had seen her GP complaining of fever, vomiting and sore throat for which she was prescribed amoxicillin. On examination she had a temperature of 38ºC, Glasgow Coma Scale score of 10, respiratory rate of 30 breaths per minute and pulse oximetry saturation (SpO2) of 90% on high flow supplemental oxygen. An arterial blood gas analysis revealed H+53.7 nmol/L, PaO2 11.1 kPa, PaCO2 6.3 kPa. A chest X ray (Image 1) showed right middle lobe and left lower lobe consolidation. The patient was a New Zealand national, on a six month working holiday in the UK and in a stable relationship. She had not travelled abroad post- arrival, was a non smoker and rarely imbibed alcohol. There were no animal contacts.
The provisional diagnosis was of a severe community acquired pneumonia (CAP) and she soon required intubation and ventilation. Admisssion investigation in the ICU showed a white cell count of 1.8 x 109/L, (neutrophils 1.3 x 109/L and lymphocytes 0.13 x 109/L) and a CRP of 381 mg/L. She had met the criteria for severe sepsis. Further investigations included an endotracheal aspirate, blood cultures and paired sera for Mycoplasma . A diagnostic bronchoalveolar lavage (BAL) was performed, samples taken for viral PCR and urine for legionella antigen were sent. These were all negative except for the viral PCR for influenza A which was positive. She was started on intravenous ceftriaxone and clarithromycin . Invasive monitoring was established.
By day 2 in intensive care her SpO2 remained at 91% on a FiO2 of 1.0. Various lung recruitment manoeuvres were attempted as well as adjustment of ventilator settings to reduce volume induced lung injury. The patient had an admission APACHE II score of 36 which gave a hospital mortality probability of over 85%. The patient had now rapidly progressed to a severe acute lung injury (ALI). Haemodynamic support was instituted and this increased over the day. The patient subsequently required to be prone-ventilated. Sputum grew Staphylococcus aureus and antimicrobials were changed to flucloxacillin 2 g qid and rifampicin 600 bd was added based on sensitivity testing. By day 5 in intensive care the patient remained prone ventilated and the S.aureus was reported to be positive for Panton-Valentine Leucocidin (PVL) 2. A right sided refractory pneumothorax and subsequent broncho pleural fistula developed. Despite two intercostals drains (ICD) and early consultation with a cardio-thoracic surgeon to consider alternative measures, she deteriorated. The patient was re-intubated with a left 37FG double-lumen tube and an attempt was made to provide asynchronous lung ventilation. This was partially successful but after further adjustments to the I: E ratios and mode of lung ventilation, to limit peak airway pressures, there was a gradual improvement but not before a left-sided ICD was necessary for a pneumothorax.
Image 1: Chest x-ray on admission
Image 2: Chest X-ray: Day 9 in intensive care
Image 3: CT Chest showing multiple abscesses.
Management was further complicated by a Clostridium difficile infection and a fungaemia associated with a central venous access device.
Nasogastric metronidazole and intravenous fluconazole were added. Both events were successfully treated.
By day 7 in intensive care, with worsening oxygenation, a further bronchoscopy was performed and all bronchi were noted to be patent but with haemorrhagic lesions crusting and pus visible particularly on the right side. By day 9 the ICDs were still ‘blowing’ consistent with the broncho pleural fistula and radiological imaging (Images 2 and 3) showed multiple lung abscesses and a severe interstitial pneumonia. The treatment with flucloxacillin and rifampicin was continued and by day 14 although highly ventilator dependant, she was more stable haemodynamically. A tracheostomy was successfully carried out during this stable phase. Due to her protracted illness, she developed a polyneuropathy of critical illness but with gradual resolution.
After four weeks of antimicrobials and a further ventilator associated pneumonia caused by meticillin resistant S.aureus treated with linezolid for two weeks, she was finally fit for discharge to a level 1 ward area on day 64. Throughout her intensive care admission there had been close liaison with the respiratory team.
Follow up at the respiratory clinics and subsequent chest x-rays after discharge showed resolving bilateral cystic changes and residual lung scarring consistent with severe necrotising pneumonia. Pulmonary function tests gradually resolved over the subsequent two years but still remain abnormal with an obstructive airway disease pattern consistent with asthma. The patient is continuing to recover and has been fit enough to fly back to New Zealand.
Discussion
Panton-Valentine Leucocidin toxin is carried by less than 2 % of clinical isolates of S.aureus and is detected in both flucloxacillin sensitive and resistant strains. The toxin destroys white blood cell and the marked leucopenia observed is likely to be secondary to the toxin. PVL strains are associated with necrotising cutaneous infections and can also cause septic arthritis, sepsis, purpura fulminans or community acquired necrotising pneumonia.
Pneumonia is a rapidly progressive, haemorrhagic infection preceded by a ‘flu like illness’. The infection typically occurs in young and previously fit patients characterised by haemoptysis, hypotension and septic shock. The findings include multilobar infiltrates with effusions and later cavitation, leucopenia and a very high CRP.
Management may include admission to intensive care, aggressive antimicrobial therapies, activated protein C and high dose intravenous immunoglobulin.
Recommended antimicrobial combinations include vancomycin, clindamycin, linezolid, rifampicin and cotrimoxazole in high doses.
Although flucloxacillin is not recommended in the treatment of PVL-S.aureus pneumonia according to the new guidelines1, we followed the interim version for this sensitive isolate with flucloxacillin as the mainstay of treatment.
Finally, strict infection control precautions are recommended to limit further spread and include surgical masks, closed tracheal suction devices, and screening of all close contacts as well as the judicious attention to hand hygiene.
Patient consent was obtained for this submission.
Acknowledgements and thanks to all of the staff in the Critical Care Unit (ICU) and clinical microbiology, Royal Infirmary of Edinburgh and the reference laboratory at Stobhill hospital.
References
- Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections in (PVL-SA) in England. Report prepared by PVL subgroup of the steering group on Healthcare Associated Infection.
- Panton PN, Valentine FCO, Came MB. Staphylococcal toxin. The Lancet 1932; 1:506-8
- Morgan MS Diagnosis and treatment of Panton-Valentine Leukocidin –associated Pneumonia. Int J Antimicrob Ag and Chemotherapy 2007; 30:289-296.
- Pathirage H. Panton Valentine Leucocidin(PVL) positive staphylococcal Infection: an emerging infection across the world. Sri Lanka Journal of Child Health, 2008; 37:109-111.
- Gillet Y et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. The Lancet 2002; 2:753-759.