Effect of Combined β-Lactam/Macrolide Therapy on Mortality According to the Microbial Etiology and Inflammatory Status of Patients With Community-Acquired Pneumonia

Chest. 2019 Apr;155(4):795-804. doi: 10.1016/j.chest.2018.11.006. Epub 2018 Nov 22.

Abstract

Background: Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL).

Methods: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause.

Results: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies.

Conclusions: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis.

Keywords: Streptococcus pneumoniae; community-acquired pneumonia; inflammatory response; macrolide; sepsis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use
  • Cause of Death / trends
  • Community-Acquired Infections / drug therapy*
  • Community-Acquired Infections / microbiology
  • Community-Acquired Infections / mortality
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Length of Stay
  • Macrolides / therapeutic use*
  • Male
  • Middle Aged
  • Pneumonia, Pneumococcal / drug therapy*
  • Pneumonia, Pneumococcal / microbiology
  • Pneumonia, Pneumococcal / mortality
  • Propensity Score*
  • Prospective Studies
  • Spain / epidemiology
  • Sputum / microbiology
  • Streptococcus pneumoniae / isolation & purification*
  • Survival Rate / trends
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • beta-Lactams