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Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time
Thomas M File1, Paul B Eckburg2, George H Talbot3
1Summa Health System, Akron, OH, USA; Northeast Ohio Medical University, Rootstown, OH, USA.
Background:
Therapy directed against atypical pathogens in patients with community-acquired pneumonia (CAP) is often recommended. This post-hoc analysis evaluated the effect of addition of a macrolide to ceftaroline fosamil or ceftriaxone treatment in atypical CAP.
Methods:
Two phase 3, double-blind, comparative safety and efficacy studies of ceftaroline fosamil vs. ceftriaxone, FOCUS 1 and FOCUS 2, enrolled adults with CAP. Only FOCUS 1 included 24-h adjunctive clarithromycin therapy for all patients on day 1. Day 4 and test-of-cure (TOC) outcomes were compared for adjunctive vs. no adjunctive therapy.
Results:
Of 1240 enrolled patients, 130 patients with CAP due to atypical pathogens alone were included (FOCUS 1, n = 64; FOCUS 2, n = 66). Among patients infected with Mycoplasma pneumoniae and/or Chlamydophila pneumoniae alone, a higher clinical response rate was observed with clarithromycin plus ceftaroline fosamil or ceftriaxone compared with treatment without additional clarithromycin at day 4 [38/49 (77.6%; FOCUS 1) vs. 24/43 (55.8%; FOCUS 2)], but not at the TOC assessment [42/49 (85.7%; FOCUS 1) vs. 41/43 (95.3%; FOCUS 2)]. In patients infected with Legionella pneumophila alone, a higher clinical response rate with adjunctive clarithromycin therapy was observed at the TOC assessment alone [12/12 (100%; FOCUS 1) vs. 14/19 (73.7%; FOCUS 2)]. The unadjusted odds ratio of a favourable clinical response at day 4 with adjunctive clarithromycin vs. no adjunctive clarithromycin was 2.4 (95% confidence interval 1.1-5.1; P = 0.0299) for all pathogens combined.
Conclusions:
These results suggest that empirical antibiotic therapy against atypical pathogens may improve early clinical response rate. This hypothesis is best evaluated in a prospective trial.
Insights
Adding a macrolide antibiotic to ceftaroline or ceftriaxone improved early treatment response in patients with atypical community-acquired pneumonia (CAP). Further prospective trials are needed to confirm these findings for atypical CAP therapy.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Medicine
Background:
- Community-acquired pneumonia (CAP) treatment guidelines often recommend targeting atypical pathogens.
- This study investigated the impact of adding a macrolide to ceftaroline fosamil or ceftriaxone in patients with atypical CAP.
Purpose of the Study:
- To evaluate the efficacy of adjunctive macrolide therapy in patients with atypical CAP.
- To compare clinical response rates with and without additional clarithromycin in CAP patients.
Main Methods:
- A post-hoc analysis of two phase 3 clinical trials (FOCUS 1 and FOCUS 2) involving adults with CAP.
- FOCUS 1 included 24-hour adjunctive clarithromycin therapy on day 1 for all patients.
- Clinical outcomes at Day 4 and test-of-cure (TOC) were compared between patients receiving adjunctive therapy versus those who did not.
Main Results:
- Among 130 patients with atypical CAP, adjunctive clarithromycin showed a higher clinical response rate at Day 4 for Mycoplasma pneumoniae and/or Chlamydophila pneumoniae infections (77.6% vs. 55.8%).
- For Legionella pneumophila infections, adjunctive clarithromycin resulted in a higher clinical response rate at TOC (100% vs. 73.7%).
- The overall odds ratio for favorable clinical response at Day 4 with adjunctive clarithromycin was 2.4 (P=0.0299).
Conclusions:
- Empirical antibiotic therapy targeting atypical pathogens may enhance early clinical response rates in CAP.
- The findings suggest a potential benefit of macrolide addition for atypical CAP.
- A prospective trial is recommended to definitively evaluate this hypothesis.
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