Male sex and older age are independently associated with treatment failure after antibiotic treatment of community-acquired pneumonia

1. In this secondary analysis of a randomized, controlled trial, 26.8% of community-acquired pneumonia patients who received 3 days of antibiotics to achieve stability and then either 5 more days of antibiotics or 5 days of placebo went on to have treatment failure at day 15.

2. A higher risk of treatment failure in community-acquired pneumonia was associated with older age, being male, having lung disease, a high pneumonia severity index, a low creatinine clearance, or a high urea nitrogen level at baseline.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Community-acquired pneumonia (CAP) treatment failure increases the risk of having to present to hospital and, ultimately, death. Treatment failure occurs in 6-24% of CAP and up to 31% of severe CAP. Age, smoking, malnutrition, previous CAP, and comorbidities like chronic pulmonary disease, asthma, and immunosuppression increase the risk of treatment failure. This trial was a secondary analysis of the randomized, controlled Pneumonia Short Treatment (PTC) trial, designed specifically to determine factors associated with treatment failure in CAP. Patients with moderate CAP were randomized to 3 days of antibiotics + 5 more days of antibiotics or 3 days of antibiotics + 5 days of placebo. The antibiotic used for the additional 5 days was β-lactam oral amoxicillin-clavulanate. All patients were stable by day 3 at the time of randomization to continued antibiotics or placebo groups. Treatment failure rates were reported based on symptom presence at day 15 or negative outcomes like death. Clinical pneumonia symptoms were measured on day 15 as a CAP score. 78 patients experienced treatment failure, mostly due to lack of resolution of symptoms or need for additional treatment; 1.3% of participants experienced death due to CAP after treatment failure. The most common symptoms were purulent sputum, dyspnea, cough, or some combination of those, with crackles being relatively rare. Patients who would go on to have treatment failure at day 15 had lower CAP scores at day 8 and day 15. Being of the male sex, being older, having chronic lung disease, having a higher pneumonia severity index (PSI) or lower creatinine clearance or higher urea nitrogen level at day 0 were associated with a higher risk of treatment failure being found at day 15. One strength of this study is its clear definition of CAP and of treatment failure – however, given that there is large variability in the literature about defining CAP and treatment failure, while clearly reported, it may not be homogenous with other studies given it is different than the US Food and Drug Administration suggestion. Additionally, these results may not be generalizable since the study excluded immunocompromised patients.

Click to read the study in JAMA Network Open

Relevant Reading: Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response

In-Depth [randomized controlled trial]: This study analyzed data from the Pneumonia Short Treatment (PTC) trial, a placebo-controlled, double-blind randomized clinical trial. All participants received 3 days of an antibiotic treatment for moderately severe CAP until they were clinical stability (apyrexia, heart rate of <100, respiratory rate of <24 breaths/min, arterial oxygen saturation of ≥90%, systolic blood pressure of ≥90mmHg, and normal mental status). After this initial stabilizing treatment, they were randomized into 2 groups: 5 days of placebo or β-lactam oral amoxicillin-clavulanate treatment. Participants were stratified by severity on the PSI. The primary outcome was treatment failure on day 15. Pneumonia-related symptoms were scored using the CAP score. 26.8% (n = 78) of the 291 CAP patients (59.8% male; age = 69.6±18.5 years) who received their assigned treatment experienced treatment failure. The most common causes of treatment failure included: lack of resolution of symptoms (79.5%), need for additional treatment (10.2%), fever (5.1%), and death (1.3%). Symptoms that remained at day 15 in participants included: sputum (24.2%), dyspnea (22.6%), cough (21.0%), crackles (3.2%), cough and purulent sputum (17.1%), cough and crackles (4.8%), dyspnea associated with sputum (3.2%), dyspnea associated with cough (3.2%), dyspnea associated with crackles (1.6%), cough associated with purulent sputum (1.6%), and sputum associated with crackles (1.6%). Patients with treatment failure at day 15 had lower CAP scores at day 8 (57.8±22.5 vs 69.0±18.8, P < 0.001). Male sex (OR = 1.74, 95%CI = 1.01-3.07), age (OR = 1.03, 95%CI = 1.01-1.05), chronic lung disease (OR = 1.85, 95%CI = 1.03-3.30), PSI score at day 0 (OR = 1.01, 95%CI = 1.00-1.02), creatinine clearance at day 0 (OR = 0.99, 95%CI = 0.98-1.00), and urea nitrogen level at day 0 (OR = 1.07, 95%CI = 1.00-1.14) were associated with increased risk of treatment failure at day 15.

Image: PD

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