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.
ABSTRACT
INTRODUCTION: The appropriate use of empiric antibiotics is a clinical challenge for patients with severe COVID-19. Early in the pandemic, there was concern that bacterial coinfection would influence morbidity and mortality. This concern often led to treating patients empirically with antibiotics. Fortunately, early data from the COVID-19 pandemic suggests bacterial coinfection is uncommon. However, there has been little published data on the antibiotic prescribing practices over the course of the pandemic. This study aims to investigate the inter-center variation and temporal trends of early antibiotic prescribing in patients hospitalized with COVID-19. METHOD(S): We performed a retrospective analysis using the National COVID Cohort Collaborative database. We identified patients admitted between March 2020 and December 2021 who had a positive COVID-19 PCR or antigen test 15 days prior or within 48 hours of admission. Age at time of COVID-19 diagnosis, gender, race/ethnicity, Charlson comorbidity index, the month of hospitalization, antibiotics received, labs at the time of hospital admission, and center identifier were collected. A chi-square test was used for categorical data and Wilcoxon rank-sum test for continuous data. Mixed effects logistic regression was used to evaluate predictors of early empiric antibiotic use. RESULT(S): Of 280,601 qualifying first hospitalizations, 30,469 patients received early empiric antibiotics. Antibiotic use declined across all centers over time from the first month (23%) to the last month in (8.1%) in the data collection period (p < 0.01). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (OR 2.25, 95% CI 2.14 - 2.36) and ECMO before day 2 (OR 1.60, 95% CI 1.25 - 2.05) but not region of residence was associated with early empiric antibiotic use. CONCLUSION(S): Although treatment of COVID-19 patients with empiric intravenous antibiotics has declined during the pandemic, the frequency of use remains higher than the reported incidence of bacterial superinfection. There is significant inter-center variation in antibiotic prescribing practices. Future research should focus on comparing outcomes and adverse events among COVID-19 patients treated with and without empiric antibiotics.