Pathogenesis of Staphylococcus aureus Necrotizing Pneumonia

The Role of PVL and an Influenza Coinfection

Bettina Löffler; Silke Niemann; Christina Ehrhardt; Dagmar Horn; Christian Lanckohr; Gerard Lina; Stephan Ludwig; Georg Peters

Disclosures

Expert Rev Anti Infect Ther. 2013;11(10):1041-1051. 

In This Article

A Clinical Case of Necrotizing Pneumonia & Description of the Typical Symptoms and Treatments

Only recently, a clinical case of necrotizing pneumonia occurred at our University Hospital in Münster: A 54-year-old woman with a medical history of hypertension and coronary artery disease presented to her primary-care physician with nausea, emesis, fever and cough since 8 days. Suspecting a respiratory tract infection, she received antimicrobial treatment with amoxicillin. Her condition rapidly worsened in the course of 2 days and she was admitted to the University Hospital in critical condition. On admission to the intensive care unit, the patient was hypotensive (blood pressure 90/40 mm Hg with a frequency of 125/min), obtunded and in respiratory distress (p/F-index 1.1[MK3]). Laboratory investigation found arterial lactate levels of 3 mmol/l, severe hyperglycemia at 744 mg/dl with metabolic acidosis, renal failure and a marked elevation of inflammatory markers (CRP 53, PCT 33, leucocytes 7.45 [MK4]). Radiography of the chest showed large bilateral pneumonic infiltrations (Figure 1A). A diagnosis of septic shock with moderate ARDS secondary to suspected pneumonia was made. Tracheal secretions and blood cultures were taken for microbiological testing. Antimicrobial therapy was started with piperacillin/tazobactam and ciprofloxacin. Due to deteriorating respiratory function despite non-invasive ventilation, the patient had to be sedated and mechanically ventilated after tracheal intubation (Figure 1A). First microscopic analysis of the tracheal secretion revealed a huge accumulation of immune cells and massive overgrowth with staphylococci (Figure 1B). Tracheal secretions and blood cultures yielded a PVL-positive MSSA strain, showing hardly any hemolysis on agar plate (Figure 1C). Therefore, the antibiotic therapy was changed to flucloxacillin, meropenem and clindamycin. Additionally, the tracheal secretion was tested positive for influenza A. Due to the progressive deterioration of respiratory function into severe ARDS (p/F-index >0.9, respiratory acidosis with paCO2 >90 mm Hg), extracorporal membrane oxygenation was started on the second day of therapy. During this phase of the disease, a marked leukopenia of 2560/ml and thrombopenia of 21000/ml was observed. Despite aggressive measures, the patient did not improve and died of multiple organ failure secondary to septic shock after 10 days in the intensive care unit.

Figure 1.

Clinical case of necrotizing pneumonia from a 58-year-old woman. (A) Radiographs show severe bilateral infiltrations upon submission that rapidly increased in the following hours. (B) Tracheal secretion with massive infiltration of immune cells and overgrowth with staphylococci. (C) Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strain that was recovered from tracheal secretion and blood cultures showed hardly any hemolysis on agar plates.

This patient showed many symptoms typically associated with necrotizing pneumonia. Initial symptoms often mimic an influenza infection, with dyspnea, cough, fever, muscle pains and unspecific symptoms, like nausea and vomiting (Table 1). After several days, the situation suddenly worsens and patients become critically ill. In many cases of influenza and PVL-positive S. aureus coinfection, like in the patient described above, low leukocyte counts can be found that appear to be linear predictors of lethal outcome.[3,12] Leukopenia could be directly caused by the cytotoxic action of PVL while we cannot rule out the participation of influenza and systemic inflammatory response syndrome. Hemoptysis or airway hemorrhages at this stage of disease have been defined as further negative prognostic criteria, as they most likely reflect the degree of lung damage.[3] Mortality rates of necrotizing pneumonia are usually high and vary between 40 and 60%.[2] In the 43 reviewed cases, 23 of the patients died (53.5%) (Table 1). Cure of the infection has been reported particularly when therapy was started early before the patients enter into a lung-destructive or septic stage.[13] The best treatment of this specific disease entity has not been clearly defined.[14] Anti-staphylococcal therapy is mostly performed with compounds, such as vancomycin, linezolid or flucloxacillin, in combination with clindamycin or rifampicin that are known to decrease production of staphylococcal exotoxins. A beneficial and toxin suppressing effect has been reported for linezolid, as well.[15,16] As the disease is supposed to be mainly toxin-mediated, an additional approach is targeted at toxin production with anti-toxin antibodies, for example, via intravenous immunoglobulin containing anti-PVL antibodies. Yet, clinical data are still required to prove and guide this therapy.[14,17,18]

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