We conducted a “ Legionella pneumonia” query that included search terms to identify fluoroquinolones, macrolides, and individual drugs in each drug category, with other terms for Legionella pneumonia such as “legionnaires’ disease” and “legionellosis.” We also searched for all RCTs comparing fluoroquinolones and macrolides for the treatment of Legionella pneumonia, substituting “pneumonia” for legionellosis and other Legionella pneumonia–related terms to increase the sensitivity of the search. With the help of a research librarian, we searched Scopus, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science from inception through 1 June 2019. We thus undertook a systematic review and meta-analysis to compile data from more recent studies and a larger patient population to evaluate the effectiveness of fluoroquinolones in comparison to macrolides for treatment of Legionella pneumonia.
Since the publication of the 2014 systematic review, newer studies have compared fluoroquinolones and macrolides in Legionella pneumonia treatment. A 2014 systematic review of 879 patients in 12 studies compared macrolides and fluoroquinolones for treating Legionella pneumonia and found that fluoroquinolones were associated with a shorter length of hospital stay (LOS), a trend towards reduced mortality, a greater likelihood of clinical cure, a shorter time to apyrexia, and a lower rate of complications from Legionella pneumonia. Observational studies have compared macrolides and fluoroquinolones for the treatment of Legionella pneumonia, but high-quality evidence to support the choice of macrolides or fluoroquinolones is sparse due to the absence of large randomized controlled trials (RCTs). The frequent use of fluoroquinolones for treatment of Legionella pneumonia has implications for these side effects and antibiotic stewardship. Fluoroquinolones are associated with adverse effects such as increased risk of Clostridioides difficile infection, tendinopathy, and neurologic effects (eg, altered mental status).
This is an important question considering potential drug side effects. Appropriate antibiotic treatment improves clinical outcomes however, it is unknown which antibiotic offers better outcomes. Older macrolides such as erythromycin have been replaced by newer macrolides (eg, azithromycin) and fluoroquinolones including levofloxacin and moxifloxacin. The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as first-line treatment for Legionella pneumonia. Among primarily waterborne diseases, treatment of Legionella pneumonia has the highest cost per episode and totals $434 million per year in the United States, with the cost of a single episode of illness ranging from $26 741 to $38 363. Mortality ranges from 9% to 25% and is higher among intensive care unit (ICU) patients. In the United States, 7500 cases were reported to the Centers for Disease Control and Prevention in 2017, up from 6079 in 20 in 2016. The incidence of Legionella pneumonia continues to increase worldwide. ( See the Editorial Commentary by Torres and Cillóniz on pages 1990–1.)
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