First, the overuse of antibiotics can induce antibiotic resistance. Dambroso-Altafini and colleagues2 assessed the possible causes and consequences of rapid increase of carbapenem-resistant Gram-negative bacteria in a teaching hospital. Overuse of empirical antibiotics in a COVID-19 intensive care unit led to the spread of resistant bacteria.2 Kang et al.3 collected metagenomic data of fecal samples from COVID-19 patients who received empirical antibiotics. The abundance of antibiotic-resistant genes increased significantly in intestinal flora.

Second, the empirical antibiotic treatment may result in unnecessary adverse events. In a retrospective cohort study, 533 (59.6%) patients were given antibiotics during the first 48 hours of admission among the patients with COVID-19 admitted. Only 60 (15.3%) patients had bacterial coinfection. On the other hand, the prevalence of antibiotic-associated adverse events was 46.9%.4

Third, the prevalence of bacterial coinfection was relatively low in patients with COVID-19. According to the survey performed in Japan, the complication incidences of community-acquired pneumonia and hospital-acquired pneumonia (including ventilator-associated) were 2.86% and 5.59%.5 In a retrospective observational cohort study performed in London, only 2.7% had clinically important bacterial co-infection within 48 hours of admission.

Fourth, inadequate empiric antibacterial therapy may result in poor outcomes. In a multicenter retrospective study, Puzniak and colleagues6 investigated the effect of inadequate antibiotics treatment in patients with COVID-19. Inadequate empiric therapy was defined as antibiotics not active against the identified bacteria or no antimicrobial treatment in the 48 hours following culture. Patients with inadequate treatment had 21% higher mortality and stayed 16.1 days longer in hospital.

Recently, Park and colleagues7 reported an important result regarding the empirical antibiotics. In a propensity score-matched case-control study, empirical antibiotics therapy did not improve any of clinical outcomes including mortality. This study is valuable in that this is a first study to evaluate the relationship between empirical treatment and prognosis.

What is the solution to overuse of empirical antibiotics in patients with COVID-19? Stewardship interventions can be a good answer. Pettit et al.8 assessed the impact of stewardship of empiric pneumonia antibiotics treatment in patients with COVID-19. The percentage of empirical antibiotics decreased from 74.5% to 42.0% after the intervention. The medial duration of treatment was 1.3 days shorter.8

In conclusion, there are several reasons for saving empirical antibiotics treatment in patients with COVID-19. To prescribe, or not to prescribe, that is still the question. However, clinicians should make an effort to decrease inadequate and unnecessary empirical antibiotics in patients with COVID-19.