Macrolides With Ampicillin vs Ceftriaxone for Community-Acquired Pneumonia

Pneumonia, microbe
Pneumonia, microbe
Researchers compared the effects of macrolides in combination with either ampicillin or ceftriaxone among patients hospitalized with community-acquired pneumonia.

Macrolides in combination with either ampicillin or ceftriaxone resulted in similar clinical outcomes among patients hospitalized with community-acquired pneumonia (CAP), but ampicillin was associated with decreased rates of Clostridioides difficile infection (CDI). These study findings were published in Clinical Microbiology and Infection.

In this single-center, retrospective cohort study, researchers reviewed patient data sourced from the Rabin Medical Center in Israel between 2015 and 2020. The researchers aimed to compare clinical outcomes between hospitalized patients with CAP who received macrolides in combination with either ampicillin (n=233) or ceftriaxone (n=1353). A propensity-score model was used to match patients in the ampicillin group against those in the ceftriaxone group. The researchers also used multivariable logistic regression to adjust for significant confounders. The primary outcome was all-cause mortality at 30 days following initial hospitalization; secondary outcomes included all-cause 90-day mortality, the length of hospitalization for patients discharged alive, mechanical ventilation, intensive care unit transfer, and 90-day CDI rates.

Among patients in the propensity-matched ampicillin (n=197) and ceftriaxone (n=394) groups, the median age was 81 (IQR, 70-88) and 78 (IQR, 65-85) years (P =.02); 46% and 42% were women; 14% and 14% were current smokers. Patients in the ampicillin and ceftriaxone groups were similar in regard to mean CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥65 years) scores (1.6±1 and 1.6±1, respectively).

The median length of hospitalization was 4 days among both patient groups. Patients in the ampicillin group had a significantly lower 90-day CDI rate vs those in the ceftriaxone group (0% vs 2%; P =.044). However, the rate of mechanical ventilation (4% vs 7%; P =.072) and acute kidney infection (9% vs 10%; P =.689) did not significantly differ between the 2 patient groups.

No significant differences were noted between patients in the ampicillin vs ceftriaxone groups in regard to the rate of unadjusted 30-day (10% vs 14%; P =.108) or 90-day (16% vs 20%; P =.252) all-cause mortality.

In the multivariable model, all-cause 30-day mortality was significantly associated with requiring mechanical ventilation (odds ratio [OR], 2.12; 95% CI, 1.2-3.7; P =.009) and CURB-65 score as a continuous variable, with the OR representing a 1-unit increase in the score (OR, 1.87; 95% CI, 1.4-2.5; P <.001).

No significant associations were found between antibiotic treatment type (ampicillin vs ceftriaxone) and the rate of all-cause 30-day mortality (OR, 0.67; 95% CI, 0.37-1.2; P =.189).

Limitations include potential ascertainment bias and significant heterogeneity between the 2 patient groups. In addition, the causative pathogen was unclear for the majority of patients with CAP, and the analysis may have been underpowered.

According to the researchers, “…optimizing antimicrobial usage for hospitalized patients with CAP is important for minimizing the spread of antimicrobial resistance.”


Guz D, Bracha M, Steinberg Y, Kozlovsky D, Gafter-Gvili A, Avni T. Ceftriaxone versus ampicillin for the treatment of community-acquired pneumonia. a propensity matched cohort study. Clin Microbiol Infect. 2022;S1198-743X(22)00390-1. doi:10.1016/j.cmi.2022.07.022