The Association of Early Antibiotic Use with Prolonged Mechanical Ventilation in Severe Covid-19

ABSTRACT

INTRODUCTION: The appropriate use of empiric antibiotics for patients with severe COVID-19 presents a clinical challenge. Bacterial coinfection can be difficult to exclude, sometimes resulting in empiric antibiotic therapy. However, antibiotics alter the respiratory tract microbiome and these changes in the lung microbiome have been associated with prolonged ARDS in COVID-19. We hypothesized that early antibiotic use increase the risk of prolonged mechanical ventilation in patients hospitalized with COVID-19. METHOD(S) We used the National Covid Cohort Collaborative (N3C) to identify a retrospective cohort of patients admitted between March 2020 and May 2022 with a positive COVID-19 PCR or antigen test 15 days prior or within 48 hours of admission. We collected demographics, Charlson comorbidity index, month of hospitalization, antibiotics received, surgical procedures, details of mechanical ventilation, and diagnoses. We defined early empiric antibiotic use (EEAU) as administration of IV antibiotics for at least three calendar days before the sixth hospital day. Prolonged mechanical ventilation was defined as 14 consecutive days of mechanical ventilation. Our primary analysis used logistic regression after propensity score matching (PSM) with multiple imputation via chained equations for missing data. Sensitivity analyses included varying the required days of antibiotic exposure, using PSM with complete cases only, and using inverse probability of treatment weighting. RESULT(S) Our final cohort included 283,314 admissions. Prolonged mechanical ventilation and EEAU was observed in 1.4% and 13.9% of cases, respectively. In the unadjusted cohort, patients who received EEAU were more likely to be older, obese, and have more comorbidities. These patients were also more likely to have had mechanical ventilation, ECMO, major surgery, or a traumatic diagnosis during the first days of their hospitalization. After PSM, the standardized mean difference for all variables was less than 0.05. Early antibiotic use was associated with an increased risk of prolonged mechanical ventilation (OR 1.86, 95% CI 1.71 - 2.03). This finding was robust to all approaches in our sensitivity analysis. CONCLUSION(S) In our retrospective cohort, EEAU is independently associated with increased risk of prolonged mechanical ventilation.