Combination Regimens using Beta-lactam plus a Macrolide or Fluoroquinolone Continue to Provide Optimal Therapy in CAP patients

14 February, 2018

Patients around the world continue to present with community-acquired pneumonia (CAP), often requiring hospitalization, and associated with a significant economic burden. While combination therapy is recommended in most international guidelines, data outlining the optimal therapy for the subgroup of patients with pneumococcal bacteremia is limited. To shed light on this, a recent Spanish trial investigated and compared empirical combination therapy (third-generation cephalosporin and a macrolide or a fluoroquinolone) to third-generation cephalosporin monotherapy.

From January 2000 to December 2015, clinical and microbiological data from 681 patients admitted with bacteraemic pneumococcal pneumonia was collected. Of them, 383 (56.2%) were treated with third-generation cephalosporin monotherapy or combined therapy with a macrolide or a fluoroquinolone. Of these patients, 314 (82.0%) were empirically treated with combination therapy (macrolide or a fluoroquinolone) and 69 (18.0%) received monotherapy with a third-generation cephalosporin. Ceftriaxone was the principal cephalosporin used in 97.6%, while the macrolides comprised azithromycin in 87.9%, clarithromycin in 10.4%, and 3 patients received erythromycin. Levofloxacin was the most commonly used fluoroquinolone, being prescribed in 98.5%.

A propensity score (PS) analysis was performed and patients matched to avoid bias. 1:1 matched results demonstrated a 7.7% and 10.8% mortality rate at 7 and 30 days respectively for patients treated with third-generation cephalosporin monotherapy compared to 1.5% and 1.5% for those with combination therapy. Results from the 1:2 matched sample confirmed a higher mortality rate in patients receiving third-generation cephalosporin monotherapy and this remained true even after PS adjustment.

The researchers concluded that combination treatment including a third-generation cephalosporin plus a macrolide or a fluoroquinolone is associated with a decreased mortality rate in comparison to beta-lactam monotherapy. In particular, those receiving combination therapy within the first 24 hours of admission had approximately 3 times higher probability of 30-day survival compared to those receiving monotherapy. Recently there has been interest in using beta-lactam monotherapy in CAP patients, following results from a trial showing its non-inferiority to combination treatment. However this trial only investigated patients with mild disease.

It was also to be noted that this trial found no difference in mortality between patients treated with a macrolide or fluoroquinolone combination regimen. This agrees with recent results from a meta-analysis of over 16,000 patients that found no significant difference in the mortality rate of patients receiving a beta-lactam plus a macrolide or a fluoroquinolone.

PMID: 29360520

J Infect. 2018 Jan 20. pii: S0163-4453(18)30020-3. doi: 10.1016/j.jinf.2018.01.003. [Epub ahead of print]

Source: https://www.ncbi.nlm.nih.gov/pubmed/29360520?dopt=Abstract