A recent study has identified male sex and older age as factors that are likely to increase the risk of treatment failure in clinically stable patients with community-acquired pneumonia (CAP) after 3 days of β-lactam treatment. The study is published in JAMA Network Open.

A secondary analysis of data from the Pneumonia Short Treatment (PTC) trial was carried out on 310 patients with moderately severe CAP with the objective to examine the risk factors for failure of treatment. Patients who were clinically stable after the third day of antibiotic treatment were included in the secondary analysis and were randomly assigned to receive antibiotics (β-lactam amoxicillin-clavulanate) or placebo for a further period of five days. For the purpose of the study, treatment failure after the first antibiotic treatment was defined as fever >100°F and/or persistence of cough, sputum production, dyspnea or crackles on auscultation and/or need for additional antibiotic treatment.

The treatment failure rate at 15 days among 291 patients included in the analysis was 26.8% in both the 3-day and 8-day groups. Failure of resolution of respiratory symptoms was the major cause of treatment failure in nearly 80% patients, while 10.2% participants needed additional antibiotic treatment and around 5% reported fever.

On univariate analysis, treatment failure was found to have a significant association with male sex (odds ratio [OR] 1.74), age per year (OR 1.03), Pneumonia Severe Index score (OR 1.01), presence of chronic lung disease (OR 1.85) and creatinine clearance (OR 0.99). In the multivariable analysis, after adjustment for multiple variables, only male sex (OR 1.92) and age (OR 1.02) showed significant association with increased risk of treatment failure. Antibiotic duration and levels of C-reactive protein (CRP) or procalcitonin had no impact on treatment outcomes.

The PTC trial, which was published earlier this year in The Lancet, compared 3 days vs 8 days of antibiotic treatment in CAP patients in non-critical care wards and did not find any extra advantage of the longer course of antibiotic. Both the treatment groups had comparable cure rates.² This secondary analysis of the same group patients has shown that in patients who become clinically stable after 3 days of antibiotic treatment and therefore could be considered for discharge, men and older patients were particularly at a greater risk of treatment failure independent of antibiotic duration and biomarker levels. These factors therefore must be weighed in when determining prognosis of these patients. Monitoring of these patients is very important to avoid any adverse outcomes.

References

1. Dinh A, et al. Factors associated with treatment failure in moderately severe community-acquired pneumonia: a secondary analysis of a randomized clinical trial. JAMA Netw Open. 2021 Oct 1;4(10):e2129566. doi: 10.1001/jamanetworkopen.2021.29566.
2. Dinh A, et al. Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet. 2021 Mar 27;397(10280):1195-1203.