Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia

  • Geoffrey ShumilakEmail author
  • Wendy I. Sligl
Respiratory Infections (F Arnold, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Respiratory Infections


Purpose of Review

Despite advances in diagnostic microbiology and sepsis management, community-acquired pneumonia (CAP) remains a significant cause of morbidity and mortality. Current recommendations regarding the use of beta-lactams in combination with macrolides published in clinical practice guidelines are variable and based on low-quality evidence that is frequently retrospective, observational, and heterogeneous in nature. While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. In this article, we discuss the historical rationale and current evidence for combination macrolide therapy in the management of CAP.

Recent Findings

Recent randomized controlled trials have assessed the non-inferiority of beta-lactam monotherapy compared to beta-lactam/macrolide combination therapy in adult patients hospitalized with CAP. Beta-lactam monotherapy was associated with equivalent clinical outcomes in patients with mild to moderate CAP. Patients with severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical outcomes when compared to patients treated with combination therapy. In addition, previous beta-lactam exposure prior to hospitalization has not been shown to negatively impact outcomes in patients managed with beta-lactam monotherapy in the hospital.


Current evidence supports the use of beta-lactam monotherapy in adult patients hospitalized with mild to moderate CAP. While existing evidence supports the use of combination therapy in patients with severe pneumonia, further large-scale randomized controlled trials are urgently needed to clarify the role of combination therapy in this population.


Pneumonia Community-acquired pneumonia Antibiotic therapy Macrolides Combination therapy 


Compliance with Ethical Standards

Conflict of Interest

Geoffrey Shumilak and Wendy Sligl declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Department of Critical Care Medicine and Division of Infectious DiseasesUniversity of AlbertaEdmontonCanada

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