Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point.

Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point.

File Thomas M Jr; Eckburg Paul B; Talbot George H; Llorens Lily; Friedland H David

International journal of antimicrobial agents

2017

2017-08

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.

80 and over; Adult; Aged; Anti-Bacterial Agents/adverse effects/*therapeutic use; Atypical pathogen; Bacterial/*drug therapy; Ceftaroline fosamil; Ceftriaxone/adverse effects/*therapeutic use; Cephalosporins/adverse effects/*therapeutic use; Chlamydial Pneumonia; Chlamydophila pneumoniae; Clinical Trials; Combination/adverse effects/methods; Community-Acquired Infections/*drug therapy; Community-acquired pneumonia; Double-Blind Method; Drug Therapy; Female; Humans; Legionella pneumophila; Macrolide; Macrolides/adverse effects/*therapeutic use; Male; Middle Aged; Mycoplasma; Mycoplasma pneumoniae; Phase III as Topic; Pneumonia; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

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