Clinical outcomes of fluoroquinolones combination therapy in patients with hospital-acquired pneumonia: a retrospective cohort study using national health insurance claims data in Korea

Background: Fluoroquinolones are one of the commonly used antibiotics for the initial empiric combination treatment. However, there is insufficient evidence to support the use of fluoroquinolones combination therapy for the treatment of hospital-acquired pneumonia (HAP). This study aimed to evaluate the effectiveness of fluoroquinolones as part of the empiric combination therapy for HAP using national health insurance claims data in Korea. Methods: We compared the clinical outcomes of patients with HAP who received fluoroquinolones combination and those treated with cefepime or piperacillin/tazobactam monotherapy. The primary outcome was hospital mortality, and the secondary outcome was readmission caused by pneumonia as the primary cause of hospitalization within 7 days after discharge from index hospitalization. The association between the combination with fluoroquinolones and outcomes was evaluated with logistic regression analysis. Results: Among the 9,955 patients with HAP administered with cefepime or piperacillin/tazobactam, 4,918 (49%) received fluoroquinolones combination. During hospitalization, 1,059 (11%) patients with HAP died. Compared with the monotherapy group, the fluoroquinolones combination therapy group was associated with a higher mortality risk (adjusted OR, 1.30; 95% CI: 1.02-1.65). After adjusting for potential confounding factors, the association remained significant in the non-high-risk HAP group (adjusted OR, 1.30; 95% CI: 1.02-1.66). Meanwhile, the mortality risk was similar between the fluoroquinolones combination therapy group and the monotherapy group of patients with high-risk HAP (adjusted OR, 0.99; 95% CI: 0.35-1.16). Among the patients alive and discharged (n=8,896), 152 (1.7%) were readmitted within 7 days after discharge. The fluoroquinolones combination therapy group was more likely to be readmitted because of pneumonia than the monotherapy group in patients with high-risk HAP (adjusted OR, 1.60; 95% CI: Conclusions: Fluoroquinolones combined with beta-lactams was prescribed in nearly half of patients with low-risk HAP, and it was associated with a higher mortality risk in real-world practice. However, it was not associated with hospital mortality even in patients with high-risk HAP.