Unnecessary antibiotic use importantly contributes to increasing bacterial resistance and increases medical costs and the risks of drug-related adverse events.^1-3 The most frequent indication for antibiotic prescriptions in the northwestern hemisphere is lower respiratory tract infections (LRTIs), which range in severity from self-limited acute bronchitis to severe acute exacerbation of chronic obstructive pulmonary disease (COPD), and to life-threatening bacterial community-acquired pneumonia (CAP).⁴ Clinical signs and symptoms, as well as commonly used laboratory markers, are unreliable in distinguishing viral from bacterial LRTI.^5-7 As many as 75% of patients with LRTI are treated with antibiotics, despite the predominantly viral origin of their infection.⁸

Rationale: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications. Objective: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia. Methods: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 μg/L; discouraged, less than 0.25 μg/L; encouraged, greater than 0.25 μg/L; strongly encouraged, greater than 0.5 μg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome. Results: At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48–0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%. Conclusions: Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.

Rationale: High cortisol levels are of prognostic value in sepsis. The predictive value of cortisol in pneumonia is unknown. Routinely available assays measure serum total cortisol (TC) and not free cortisol (FC). Whether FC concentrations better reflect outcome is uncertain. Objectives: To investigate the predictive value of TC and FC in community-acquired pneumonia (CAP). Methods: Preplanned subanalysis of a prospective intervention study in 278 patients presenting to the emergency department with CAP. Measurements and Main Results: TC, FC, procalcitonin, C-reactive protein, leukocytes, clinical variables, and the pneumonia severity index (PSI) were measured. The major outcome measures were PSI and survival. TC and FC, but not C-reactive protein or leukocytes, increased with increasing severity of CAP according to the PSI (P < 0.001). TC and FC levels on presentation in patients who died during follow-up were significantly higher as compared with levels in survivors. In a receiver operating characteristic analysis to predict survival, the area under the receiver operating characteristic curve (AUC) was 0.76 (95% confidence interval, 0.70–0.81) for TC and 0.69 (0.63–0.74) for FC. This was similar to the AUC of the PSI (0.76 [0.70–0.81]), and better as compared with C-reactive protein, procalcitonin, or leukocytes. In univariate analysis, only TC, FC, and the PSI were predictors of death. In multivariate analysis, the predictive potential of TC equaled the prognostic power of PSI points. Conclusions: Cortisol levels are predictors of severity and outcome in CAP to a similar extent to the PSI, and are better than routinely measured laboratory parameters. In CAP, the prognostic accuracy of FC is not superior to TC. Clinical trial registered with www.controlled-trials.com (ISRCTN04176397).