Association Between Empirical Anti-Pseudomonal Antibiotics for Recurrent Lower Respiratory Tract Infections and Mortality: A Retrospective Cohort Study

Abstract

Purpose

Whether the empirical use of anti-pseudomonal antibiotics actually improves patient outcomes is unclear. Hence, we aimed to determine whether empirical anti-pseudomonal antibiotics are better than anti-pseudomonal antibiotics in treating patients with recurrent lower respiratory tract infections (LRTIs).

Patients and Methods

We extracted data from the Japanese nationwide database of the Real World Data Co., Ltd. Our target population was patients with LRTIs, defined as chronic obstructive pulmonary disease exacerbation and pneumonia. We included patients aged ≥40 years who were admitted for lower respiratory tract infections ≥2 times within 90 days. We excluded patients who had an event (death or transfer) within 24 h after admission. We ran a frailty model adjusted for the following confounding factors: number of recurrences, age, body mass index, activities of daily living, Hugh-Johns classification, altered mental status, oxygen use on admission, blood urea nitrogen, and systemic steroid use.

Results

We included 893 patients with 1362 observations of recurrent LRTIs. There were 897 (66%) observations in the non-anti-pseudomonal antibiotic group and 465 (34%) in the anti-pseudomonal group; the numbers of in-hospital deaths were 86/897 (10%) and 63/465 (14%), respectively. Our frailty model yielded an adjusted hazard ratio (HR) (anti-pseudomonal group/non-anti-pseudomonal group) of 1.49 (95% confidence interval, 1.03–2.14).

Conclusion

The empirical use of anti-pseudomonal antibiotics was associated with a higher HR of in-hospital mortality than the use of non-anti-pseudomonal antibiotics. Physicians might need to consider limiting the prescription of anti-pseudomonal antibiotics based on background factors such as the patient’s baseline function and disease severity. Further studies are needed to evaluate the causal relationship between empirical anti-pseudomonal antibiotics and mortality, and identify specific patient population who benefit from empirical anti-pseudomonal antibiotics.

Keywords:

• clinical epidemiology
• COPD
• Emphysema
• infection and inflammation
• pneumonia

Abbreviations

ADL, activities of daily living; CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; IQR, interquartile range; LRTI, lower respiratory tract infection; MRSA, methicillin-resistant Staphylococcus aureus; PA, Pseudomonas aeruginosa; RWD, Real World Data.

Data Sharing Statement

The data that support the findings of this study are available on request from the corresponding author, AS. The data are not publicly available due to restrictions of the Real World Data Co., Ltd.

Ethics Approval and Informed Consent

The Institutional Review Board (IRB) of Ichinomiyanishi Hospital approved our validation study (approval number: 2021028). The requirement for written informed consent was waived because of the study’s retrospective design and patients were offered an online opt-out option. The IRB of Kyoto City Hospital approved our main study (approval number: 665), and the requirement for written informed consent was waived because the data was already deidentified. Patient data was maintained with confidentiality throughout the study.

Consent for Publication

All authors agree to the publish statements.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.”.

Disclosure

SY received a research grant from Real World Data, Co., Ltd for the study. The other authors have nothing to disclose in this study.

Additional information

Funding

Our study was funded by a grant from Real World Data, Co., Ltd. The funder played no role in the study design, study execution, data analyses, data interpretation, or decision to submit the results.