"Empirical Antibiotic Treatment Strategies for Community-Acquired Pneumonia". The New England Journal of Medicine. ClinicalTrials.gov number, NCT01660204.

Clinical Question

In patients with clinically suspected community-acquired pneumonia (CAP) admitted to non-ICU wards, is beta-lactam monotherapy noninferior to beta-lactam–macrolide combination therapy, or fluoroquinolone monotherapy, regarding 90-day mortality?

Bottom Line

Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with beta-lactam–macrolide combination or fluoroquinolone monotherapy in terms of 90-day mortality.

Major Points

This trial investigated empirical antibiotic treatments in patients with clinically suspected CAP admitted to non-ICU wards and aimed to determine whether beta-lactam monotherapy was noninferior to other strategies. The study showed that a beta-lactam strategy did not result in higher mortality compared to combination therapy options and may be considered a viable approach to treat such patients.

Guidelines

Most guidelines recommend combination therapy or fluoroquinolone monotherapy for empirical treatment of patients with clinically suspected CAP who are admitted to a non-ICU ward. This study suggests reconsidering the addition of macrolides or using fluoroquinolones over beta-lactam monotherapy due to noninferiority in outcomes.

Design

- Multicenter, cluster-randomized, crossover trial.
- Periods of 4 months with rotation of treatment strategies.
- Hospitals randomized with each strategy.
- N=2,283 patients with informed consent; median age 70 years.
- Setting: Seven hospitals in the Netherlands, February 2011 through August 2013.

Population

- Adults (age ≥18) with clinically suspected CAP requiring hospitalization in a non-ICU ward.
- Exclusion: Patients with cystic fibrosis, or not meeting clinical criteria.

Interventions

- Comparative empirical treatment strategies: beta-lactam monotherapy, beta-lactam–macrolide combination, fluoroquinolone monotherapy.
- Allowed deviations from assigned treatment for medical reasons.

Outcomes

- Primary: 90-day all-cause mortality.
- Secondary: Time to starting oral treatment, length of hospital stay, minor or major complications during hospital stay.

Criticisms

- Findings may not be generalized to regions with different microbial etiologies and resistance profiles.
- This trial's findings may not apply to patient populations experiencing higher incidence of community-acquired Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus infections, as those would require adaptation of treatment strategies.

Funding

- Funded by the Netherlands Organization for Health Research and Development.
- No conflicts of interest were reported.

Further Reading

- Full text of the study and supplementary material are available at NEJM.org.
- Additional research and guidelines regarding the management of CAP can be found through major health organizations and societies.