Markers of treatment failure in hospitalised community acquired pneumonia

Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor alpha, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure.

A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (< or = 72 h) or late failure.

453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (> or = 169 pg/ml), IL8 (> or = 14 pg/ml) and CRP (> or = 21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure.

Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.