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Randomized Controlled Trial
. 2021 Oct 1;4(10):e2129566.
doi: 10.1001/jamanetworkopen.2021.29566.

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial

Aurélien Dinh  1   2 , Clara Duran  1 , Jacques Ropers  3 , Frédérique Bouchand  4 , Benjamin Davido  1 , Laurène Deconinck  5 , Morgan Matt  1 , Olivia Senard  6 , Aurore Lagrange  7 , Guillaume Mellon  1 , Ruxandra Calin  1 , Sabrina Makhloufi  1 , Victoire de Lastours  8 , Emmanuel Mathieu  9 , Jean-Emmanuel Kahn  10 , Elisabeth Rouveix  10 , Julie Grenet  11 , Jennifer Dumoulin  12 , Thierry Chinet  12 , Marion Pépin  13 , Véronique Delcey  14 , Sylvain Diamantis  15 , Daniel Benhamou  16 , Virginie Vitrat  17 , Marie-Christine Dombret  18 , Didier Guillemot  2 , Bertrand Renaud  19 , Yann-Erick Claessens  20 , José Labarère  21 , Philippe Aegerter  22 , Jean-Pierre Bedos  23 , Anne-Claude Crémieux  24 ; Pneumonia Short Treatment (PTC) Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial

Aurélien Dinh et al. JAMA Netw Open. .

Abstract

Importance: Failure of treatment is the most serious complication in community-acquired pneumonia (CAP).

Objective: To assess the potential risk factors for treatment failure in clinically stable patients with CAP.

Design, setting, and participants: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population.

Interventions: Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive β-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days.

Main outcomes and measures: The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of β-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions.

Results: Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis.

Conclusions and relevance: In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Crémieux reported receiving grants from the French Ministry of Health during the conduct of the study and from Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
CAP indicates community-acquired pneumonia; GFR, glomerular filtration rate.
Figure 2.
Figure 2.. Course of Symptom According to Outcome (Community-Acquired Pneumonia [CAP] Score)
Error bars indicate standard deviation. A higher CAP score corresponds to fewer pneumonia symptoms.
See this image and copyright information in PMC

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