Are There Reasons To Prefer Tetracyclines to Macrolides in Older Patients with Community-Acquired Pneumonia?

LETTER

In a recent meta-analysis, Brown et al. investigated the association between antibiotic class and the risk of community-associated Clostridium difficile infection (CDI). The results demonstrated that the risk of CDI in patients treated with macrolides was more than twice that in patients with no antibiotic exposure (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.92 to 3.64), and yet in those patients receiving tetracyclines, no increased risk was observed (OR, 0.92; 95% CI, 0.61 to 1.40) (1). In another recent study on 3,305 patients exposed to ceftriaxone (24% with pneumonia on admission), the incidence of CDI was 1.67 cases per 10,000 patient-days in those receiving doxycycline compared to 8.11 per 10,000 patient-days in those who did not receive doxycycline (2). In the same study, the hazard ratio for development of CDI in a patient receiving a 5-day course of doxycycline plus ceftriaxone compared to a 5-day course of a macrolide plus ceftriaxone was 0.15 (95% CI, 0.03 to 0.77) (2). Community-acquired pneumonia (CAP) is the third-commonest hospital diagnosis among patients aged ≥65 years and the sixth leading cause of death in developed countries. The mortality rate is 10% to 25% and is particularly high in the elderly population (3). It is estimated that, every year, 4 million people in the United States develop CAP. Of these, 80% are managed in the outpatient setting, whereas the remaining 20% are admitted to hospitals (4). The Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) published guidelines on the management of CAP in adults in 2007 (5). According to these guidelines, for outpatient treatment of CAP, tetracyclines can be used instead of macrolides as monotherapy in previously healthy patients and can also be used as part of combination therapy (e.g., with beta-lactam antibiotics) in patients with comorbidities. However, regarding doxycycline, the strength of recommendation is weaker because a strong evidence base supporting its use is lacking. Treatment decisions should always involve a risk-benefit analysis for each patient and all antibiotics associated with adverse events. Clostridium difficile infection is one such risk factor to consider prior to starting therapy. Recent trends show an increasing incidence in community-onset and community-associated CDI. In a recent large population cohort study, 41% of CDI cases were community acquired (6). Furthermore, although the mean age of patients with community-associated CDI is lower that of those with health care-associated CDI, it still exceeds 65 years (7, 8). Morbidity and mortality associated with community-associated CDI are increasingly reported and are perhaps underestimated (9). As discussed above, patients treated with macrolides may be at higher risk of developing CDI. In addition, a large cohort study reported an increase in cardiovascular deaths (which were most pronounced among patients with a high baseline risk of cardiovascular disease) during azithromycin therapy (10). Given these premises, the risk-benefit analysis for treating CAP may favor doxycycline, especially in patients over 65 years who would be receiving outpatient treatment.