Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial.

José M Porcel,Luis Valdés,Carmen Civit,Esther Espino-Paisán,Lucia Ferreiro,Laura Rumi,Juan Antonio Schoenenberger-Arnaiz,Marina Pardina,Silvia Bielsa

doi:10.1515/pp-2019-0027

Abstract

BackgroundThe optimal duration of antibiotic treatment for complicated parapneumonic effusions (CPPEs) has not been properly defined. Our aim was to compare the efficacy of amoxicillin-clavulanate for 2 vs. 3 weeks in patients with CPPE (i.e. those which required chest tube drainage).MethodsIn this non-inferiority, randomized, double-blind, controlled trial, patients with community-acquired CPPE were recruited from two centers in Spain and, after having obtained clinical stability following 2 weeks of amoxicillin-clavulanate, they were randomly assigned to placebo or antibiotic for an additional week. The primary objective was clinical success, tested for a non-inferiority margin of<10%. Secondary outcomes were the proportion of residual pleural thickening of>10 mm at 3 months, and adverse events. The study was registered with EudraCT, number 2014-003137-25. We originally planned to randomly assign 284 patients.ResultsAfter recruiting 55 patients, the study was terminated early owing to slow enrolment. A total of 25 patients were assigned to 2 weeks and 30 patients to 3 weeks of amoxicillin-clavulanate. Clinical success occurred in the 25 (100%) patients treated for 2 weeks and 29 (97%) treated for 3 weeks (difference 3%, 95% CI −3 to 9.7%). Respective between-group differences in the rate of residual pleural thickening (−12%, 95%CI −39 to 14%) and adverse events (−7%, 95%CI −16 to 2%) did not reach statistical significance.ConclusionsIn this small series of selected adult patients with community-acquired CPPE, amoxicillin-clavulanate treatment could be safely discontinued by day 14 if clinical stability was obtained.

Highlights

20% of hospitalized patients with community-acquired pneumonia (CAP) have accompanying pleural effusions on chest radiographs, of which about one-third are categorized as complicated parapneumonic effusions (CPPEs) [1]
Among the 183 patients who met the exclusion criteria, the most common reasons for non-eligibility were the prescription of antibiotics other than amoxicillin-clavulanate (20%), the non-parapneumonic cause of the pleural infection (18%), the presence of cancer (15%) or other immunosuppressive states (11.5%), and the lack of clinical stability at randomization (11%)
Patients were treated a median of 5 days with intravenous antibiotics, and received small (80%) chest catheters that remained in place for 2 (1–4) days, along with intrapleural urokinase (96%), non-steroidal anti-inflammatory drugs (NSAID) (75%) and, less often, a concomitant course of oral azithromycin (36%)

Summary

Introduction

20% of hospitalized patients with community-acquired pneumonia (CAP) have accompanying pleural effusions on chest radiographs, of which about one-third are categorized as complicated parapneumonic effusions (CPPEs) (i.e. pleural space drainage is required for cure) [1]. Empirical antibiotics chosen for community-acquired pleural infections usually consist of monotherapy with a β-lactam with activity against anaerobes (e.g. amoxicillin-clavulanate), or a combination of β-lactam (e.g. ceftriaxone) and clindamycin [6]. Methods: In this non-inferiority, randomized, doubleblind, controlled trial, patients with community-acquired CPPE were recruited from two centers in Spain and, after having obtained clinical stability following 2 weeks of amoxicillin-clavulanate, they were randomly assigned to placebo or antibiotic for an additional week. Conclusions: In this small series of selected adult patients with community-acquired CPPE, amoxicillinclavulanate treatment could be safely discontinued by day 14 if clinical stability was obtained

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