Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults

Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults

D. F.Postma, C. H. van Werkhoven, L. J.R. van Elden et al

N Engl J Med April 2, 2015. 372:1312-1323

This study investigated empirical antibiotic treatment for patients with suspected community-acquired pneumonia (CAP) admitted to general hospital wards in a cluster-randomized, crossover trial with strategies rotated in 4-month periods. They tested the noninferiority of beta-lactam monotherapy (656 patients) to beta-lactam–macrolide combination (739 patients) and to fluoroquinolone monotherapy (888) strategies with respect to 90-day mortality, in an intention-to-treat analysis, using a noninferiority margin of 3 percentage points and a two-sided 90% confidence interval.
The median age of the patients was 70 years. The crude 90-day mortality was 9.0% (59 patients), 11.1% (82 patients), and 8.8% (78 patients), respectively, during these strategy periods. In the intention-to-treat analysis, the risk of death was higher by 1.9 percentage points (90% confidence interval [CI], −0.6 to 4.4) with the beta-lactam–macrolide strategy than with the beta-lactam strategy and lower by 0.6 percentage points (90% CI, −2.8 to 1.9) with the fluoroquinolone strategy than with the beta-lactam strategy. The median length of hospital stay was 6 days for all strategies, and the median time to starting oral treatment was 3 days (interquartile range, 0 to 4) with the fluoroquinolone strategy and 4 days (interquartile range, 3 to 5) with the other strategies.
They conclude that a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam–macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality.

The current UK National Institute for Health and Clinical Excellence (NICE) evidence based guidelines on Pneumonia; Diagnosis and management of community and hospital acquired pneumonia in adults, recommend a 5-day course of a single antibiotic to patients with low-severity community-acquired pneumonia with amoxicillin used in preference to a macrolide or a tetracycline and that a fluoroquinolone or dual antibiotic therapy should not be used. Dual antibiotic therapy with amoxicillin and a macrolide for patients is recommended only in moderate-severity CAP and dual antibiotic therapy with a beta-lactamase stable beta-lactam and a macrolide in high severity CAP.

Lancet 28 March 2015. Volume 385, No. 9974, p1198–1205.

Preclinical studies suggest that P2X3 receptors are expressed by airway vagal afferent nerves and contribute to the hypersensitisation of sensory neurons so could mediate sensitisation of the cough reflex, leading to chronic cough.
They investigated the efficacy of a first-in-class oral P2X3 antagonist, AF-219, to reduce cough frequency in patients with refractory chronic cough in a double-blind, placebo-controlled, two-period, crossover study at one UK center. The primary analysis used a mixed effects model with the intention-to-treat population.
They randomly assigned 24 patients (mean age 54·5 years; SD 11·1). Cough frequency was reduced by 75% when patients were allocated to AF-219 compared when allocated to placebo (p=0·0003). Daytime cough frequency fell from a mean 37 coughs per h (SD 32) to 11 (8) coughs per h after AF-219 treatment versus 65 (163) coughs per h to 44 (51) coughs per h after placebo. Six patients withdrew before the end of the study because of taste disturbances, which were reported by all patients taking AF-219.
They conclude P2X3 receptors seem to have a key role in mediation of cough neuronal hypersensitivity. Antagonists of P2X3 receptors such as AF-219 are a promising new group of antitussives

Chronic cough is a common complaint that that can be difficult to manage in practice. Current guidelines stress the identification and management of underlying causes such as gastrooesphageal reflux diseaseCur