Two Factors Tied to Risk of Antibiotic Failure in Pneumonia Patients

Two factors, age and sex, were associated with a higher risk for antibiotic failure among clinically stable patients hospitalized with community-acquired pneumonia (CAP), a secondary analysis of a randomized trial suggested.

Among nearly 300 CAP patients who were stable after 3 days of beta-lactams, the rate of treatment failure reached 26.8% at 15 days, reported Aurélien Dinh, MD, of the Raymond-Poincare University Hospital in Garches, France, and colleagues.

Multivariable analysis adjusting for Pneumonia Severity Index (PSI) scoring and baseline urea level showed that male sex (OR 1.92, 95% 1.08-3.49) and age (OR 1.02 per year, 95% CI 1.00-1.05) each predicted treatment failure, and these were independent of antibiotic duration or biomarkers (C-reactive protein and procalcitonin levels), according to the findings in JAMA Network Open.

In the study’s primary analysis, CAP cure rate, no difference was observed between a 3-day and 8-day course of beta-lactams. “Thus, the antibiotic treatment durations used had no association with failure in this analysis,” the group noted.

CAP leads to anywhere from 600,000 to 800,000 hospitalizations each year in the U.S., with older people generally considered to be at highest risk. “[Treatment failure] significantly increases the risk of complications, length of hospital stay, and death, especially in patients with severe CAP,” wrote Dinh and colleagues.

For the current study, the group looked at failure patterns from the double-blind Pneumonia Short Treatment trial, which was conducted from 2013 to 2018 at 16 French centers. The trial enrolled 310 patients who were clinically stable after 3 days of beta-lactam therapy and randomized them 1:1 to 5 days additional days of continued antibiotic treatment with amoxicillin-clavulanate (1 g/125 mg; Augmentin) three times daily or placebo.

Stability criteria included normalized vital signs and mental health status. Patients with other diagnoses such as health-care acquired pneumonia, legionellosis, immunosuppression, aspiration pneumonia, or severe CAP were excluded.

The secondary analysis included 291 patients. A majority of the patients were male (60%), and the average age was 70 years. The most common comorbidity was chronic lung disease (23%), followed by heart failure (21%) and diabetes (19%).

The average hospital stay was 10 days for those who failed antibiotics and 8 days for those cured. Non-resolving or non-improving symptoms were the most frequent cause of treatment failure (80%), followed by the need for additional antibiotics (10%) and fever at day 15 (5%). Before day 15, one patient who failed antibiotics died after suspected pulmonary edema.

Common symptoms among patients with treatment failure included purulent sputum (24%), cough (21%), dyspnea (23%), cough with purulent sputum (17%), cough with crackles (5%), and crackles alone (3%).

The analysis had several limitations, the researchers acknowledged. CAP definitions and diagnostic criteria differ by clinical trial, as do definitions of treatment failure, and the study exclusively involved patients who had a favorable prognosis, in that they were clinically stable.