In this episode, I’ll discuss whether a quinolone is really superior to a macrolide for legionella pneumonia.
Traditionally it is thought that a bacteriocidal antibiotic is preferable to a bacteriostatic one, especially in severe infections such as legionella pneumonia. This leads many clinicians to assume that a quinolone such as levofloxacin is superior to a macrolide such as azithromycin for treating legionella. This belief probably persists because macrolides like erythromycin have been considered bacteriostatic vs legionella and while azithromycin is bacteriocidal against legionella it gets lumped in with older macrolides.
However, the IDSA guidelines recommend that either a fluoroquinolone or a macrolide may be used first-line for atypical coverage in treating severe pneumonia, which would include patients with suspected legionella. A systematic review and meta-analysis was completed in 2021 to determine which antibiotic class leads to optimal clinical outcomes in legionella pneumonia.
21 randomized controlled trials and observational studies that compared macrolide vs. fluoroquinolone monotherapy were included. These studies represented over 3500 patients. The authors found:
The mortality rate for patients treated with fluoroquinolones was 6.9% (104/1512) compared to 7.4% (133/1790) among those treated with macrolides. The pooled OR assessing risk of mortality for patients treated with fluoroquinolones vs macrolides was 0.94 (95% CI 0.71-1.25, I2=0%, p= 0.661). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ for patients treated with fluoroquinolones vs. macrolides.
The authors concluded that there was no difference in the effectiveness of fluoroquinolones vs. macrolides in reducing mortality among patients with legionella pneumonia. This study supports the IDSA guideline recommendation in that clinicians may choose either a fluoroquinolone or a macrolide for atypical coverage in treating severe pneumonia that could possibly be due to legionella.
A 2024 systematic review does add a wrinkle to this analysis however. Like the 2021 paper, these authors found no difference in mortality rates overall between the two antibiotics. But when data from three studies that focused on patients with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were not significantly different in this pooled cohort. These findings have not been enough to move the needle for expert guideline recommendations for patients with severe pneumonia but a definitive randomized clinical trial to answer the question is needed to put the issue to rest. Unfortunately, there does not seem to be one currently underway according to clinicaltrials.gov.
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