Utility of Empiric Antibiotics for Non-intubated Novel Coronavirus Diseases 2019 Patients

Utility of Empiric Antibiotics on Admission for Non-intubated Patients With Novel Coronavirus Diseases 2019 (COVID-19): A Retrospective Cohort Study of Electronic Health Records

This retrospective analysis of inpatient data obtained from administrative and electronic medical records will investigate the role of empiric antibiotics on admission on the mortality for non-intubated patients presenting with Novel Coronavirus Diseases 2019 (COVID-19) associated pneumonia without extra-pulmonary sources of infection or septic shock.

Study Overview

• Status: Withdrawn
• Conditions: Coronavirus Infection; Pneumonia; Covid19
• Intervention / Treatment: Drug: Antibiotic

Detailed Description

This study will examine the impact of empiric antibiotic therapy on patients who present to hospital with an acute lower respiratory illness and a diagnosis of COVID-19 present-on-admission.

The Premier Healthcare Database will be used as the data source for administrative data. In addition, the subset of hospitals reporting microbiology and laboratory data will be used for subset analyses and validation purposes. The primary population to be studied will be non-intubated patients diagnosed with COVID-19 on admission (identified by diagnosis coding and/or polymerase chain reaction result present-on-admission) who have diagnosis codes supportive of acute lung illness (e.g. pneumonia). Patients with extra-pulmonary infections present-on-admission for which antibiotics would be generally administered and/or those requiring vasopressors and/or mechanical ventilation on the day of admission or day after will be excluded.

Patients will be analyzed according to their antibiotic treatment status, using an overlap weight matching strategy. Patients will be matched on age, gender, ethnicity, Elixhauser comorbidity index and month of admission as well as severity of acute illness (need for intensive care unit and acute organ failure score present-on-admission), performance of rapid diagnostic testing for bacterial respiratory pathogens, and receipt of concomitant putative COVID-19 directed therapy (remdesivir, tocilizumab, systemic corticosteroids, hydroxychloroquine) initiated on the day of or day after admission respectively. Logistic regression will be performed downstream to matching to mitigate the impact of residual confounding.The primary outcome and secondary outcomes are reported separately below.

Effect modification of the relationship between empiric antibiotics and outcomes will be examined across clinically relevant subgroups based on antibiotic regimens (separately comparing community and hospital acquired type coverage to no empiric antibiotics respectively), and those with or without need for non-invasive ventilation on admission as well as quartiles of hospital's frequency of empiric antibiotic use and admission procalcitonin level (when available) respectively among patients admitted with COVID-19.

Sensitivity analyses will be performed to examine outcomes with vs without coding for conditions that may or may not suggest a definite indication for antibiotic on admission (e.g. chronic obstructive lung disease exacerbation) and/or explicit diagnosis for "sepsis" (as it remains unclear in whom this code was indicated to represent confirmed viral sepsis). Sensitivity analyses will also be performed to include patients without diagnosis codes for acute lower respiratory illness present-on-admission to include patients with COVID-19 pneumonia who may not have been coded for pneumonia per se.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include patients admitted to hospital with a diagnosis of COVID-19 on arrival as defined by ICD-10 code or legacy coding for coronavirus (prior to implementation of new ICD-10 code) and/or a positive SARS-CoV-2 polymerase chain reaction test on admission. Patients included will have no other sources of infection identified on admission and will be clinically stable.

Description

Inclusion Criteria:

• Adult patients
• Admitted to hospital with International Classification of Diseases Version 10 (ICD-10) diagnosis coding COVID-19 present-on-admission or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test sampled on admission
• Patients admitted to hospital with ICD-10 diagnosis coding for pneumonia present-on-admission

Exclusion Criteria:

• Patients with suspected extra-pulmonary bacterial infection
• Patients receiving mechanical ventilation or vasopressors within 48 hours of arrival
• Patients coded as having septic shock present on admission

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Empiric Antibiotic; All patients with COVID19 diagnosed on admission who received empiric antibiotics within 48 hours of admission without another site of infection identified or suspected septic shock.	Drug: Antibiotic; Empiric antibiotic therapy, subdivided according to Community Acquired Pneumonia coverage vs Hospital Acquired Pneumonia coverage
Control group; All patients admitted with COVID19 who did not receive empiric antibiotics in the first 48 hours of admission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-Hospital Mortality or discharge to hospice	Death during the hospitalization or discharge to hospice	From time of admission to death during the hospitalization or discharge to hospice

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Mechanical Ventilation	Mechanical ventilation initiated after 48 hours into the admission as a marker of clinical deterioration and its relationship to receipt of empiric antibiotic	From 48 hours post admission to discharge or death
Rates of C. difficile infection	Identify the risk of C. difficile infection on patients according to empiric therapy status as captured by diagnosis codes not present-on-admission	not present-on-admission
Length of stay for survivors	As a marker of morbidity and and its relationship to receipt of empiric antibiotic therapy	From admission to discharge (not to hospice)
Rates of ICU Admission	As a marker of clinical deterioration and its relationship to receipt of empiric antibiotic therapy among patients who did not require ICU admission upon arrival	From 48 hours post admission to discharge
Rates of Acute Kidney Injury	Identify the risk of acute kidney injury according to empiric therapy status as captured by diagnosis codes not present-on-admission	not present-on-admission
Days free of antibiotics	For patients in hospital for at least 5 days	5 days from admission to discharge or primary outcome
Rates of secondary infections due to antibiotic resistant pathogens	As above, as captured by diagnosis codes not present-on-admission	not present-on-admission

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Investigators: Principal Investigator: Sameer S Kadri, MD, National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Empiric antibiotics
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: BD022383

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No