New aspects in the management of pneumonia

Randomized controlled trials

Two recent multicenter RCTs have been published regarding the use of corticosteroids in CAP.

In a multicenter, double-blind, randomized, placebo-controlled trial [24], a total of 785 patients with CAP were randomized to receive oral corticosteroids (50 mg of prednisone for 7 days) or placebo as adjunctive treatment. The corticosteroid group reported a shorter time to reach clinical stability in comparison with the placebo group (3 days versus 4.4 days). In the study, the time to clinical stability was defined as the days until reaching stable vital signs for 24 h or longer (including normalization of temperature, heart rate, spontaneous respiratory rate, systolic blood pressure, mental status, ability for oral intake, and adequate oxygenation on room air). The complications related to pneumonia were not significantly different in the groups whereas the prednisone group more frequently presented hyperglycemia needing insulin treatment (19 versus 11 %; OR 1.96; 95 % CI 1.31–2.93; p?=?0.001). However, other adverse events typically associated with corticosteroid use (such as gastrointestinal bleeding, nosocomial infections) were rare and similar in both groups. The mortality rate, considered as a secondary outcome in the study, was not different in the two groups (n?=?16 (4 %) in the prednisone group versus n?=?13 (3 %) in the placebo group; p?=?0.57). This study presented some limitations, in particular the use of a weak outcome such as clinical stability, which included some items such as temperature that could be influenced by the use of corticosteroids. Moreover, the majority of patients had a mild disease presentation, thereby decreasing result validation for the most severe diseases.

We recently published a multicentre RCT [23] where we compared patients with severe CAP and strong inflammatory response (defined by a CRP 150 mg/L) treated with corticosteroids plus antibiotics versus placebo plus antibiotics. We used intravenous methylprednisolone at a dose of 0.5/mg/kg every 12 h for 5 days. We included only patients with severe CAP, defined according to the modified American Thoracic Society criteria or by a Pneumonia Severity Index risk class V [27]. The patients receiving corticosteroids had significantly lower treatment failure in comparison with the placebo group (13 versus 31 %, respectively; p?=?0.02). This difference was due to late treatment failure (developing between 72 and 120 h after treatment initiation) and, in particular, patients in the corticosteroid group showed a more evident effect on the reduction of radiological progression (2 versus 15 %; p?=?0.007). Indeed, the use of corticosteroids reduced the risk of treatment failure by 18 % (95 % CI 3–32 %) in the intention to treat analysis. The association between treatment failure, with radiographic progression as a criterion, and mortality has been shown by Menendez et al. [5]. The protective effect of corticosteroids on radiographic progression could be interpreted as an effect preventing the development of ARDS or blocking the Jarisch–Herxheimer-like reaction [8]. No significant difference was observed in mortality between the two groups (10 % in the methylprednisolone arm versus 15 % in the placebo arm; p?=?0.37); however, the study was not powered for mortality as this was not the primary outcome. Importantly, we detected no significant side effects in patients receiving corticosteroids. The strength of this study is the homogeneous population with severe CAP and a strong inflammatory response and the use of an outcome (treatment failure) closely associated with mortality [5]. The limitation of this study was the prolonged recruitment period.

In Fig. 1 we propose a flowchart for the management of patients with severe CAP.

Flowchart for the management of patients with CAP