The Mystery of Futility of Appropriate Antibiotics for Coinfection in COVID-19

To the Editor:

We read with great interest the article by Rouze and colleagues about comparing early bacterial identification between mechanically ventilated coronavirus disease (COVID-19) and influenza (1). We want to congratulate the authors for their dedication to their work. The lower COVID-19 detection rate of culture suggested that appropriate spectrum antibiotics should be chosen based on microbiological findings at the start of mechanical ventilation. However, when incorporating the results of this study into daily practice, it is necessary to solve the following knowledge gaps, in addition to the methodological issues of this study, such as standardized sampling in the prospective trial.

First, the appropriate use of antibiotics is warranted if early bacterial coinfection is suspected. However, appropriate antibiotic coverage did not modify the prognostic impact of bacterial infection in COVID-19 (1). The definition of appropriate antibiotic treatment included unnecessary use of broad-spectrum antibiotics that was reported to increase mortality (2). The finding in this study may be due to two hypotheses. First, overuse of broad-spectrum antibiotics for early bacterial infection triggers microbiome change, resulting in late-phase ventilator-associated pneumonia and influences the prognosis mediated by ventilator-associated pneumonia (3). Although it was not presented by Rouze and colleagues, investigating the effect of unnecessary initial broad-spectrum antibiotics use on the outcome might be an important future research question. Second, the local antibiotic concentration was inadequate to control the coinfection because of pulmonary macro- and/or microthrombosis (4). Thus, to determine the appropriate antibiotic strategy, both the effect of antibiotics on the prognosis and the capability of the local antimicrobial concentration to reach the effective threshold in COVID-19 should be investigated.

Although the study reported the incidence of bacterial detection, externalization of the result should be cautious for the different populations who receive different treatments. Since the initial COVID-19 pandemic, the treatment and vaccination have rapidly developed. Currently, various antiinflammatory therapies were employed in COVID-19 before intubation. Tocilizumab, for example, was associated with bloodstream infection (5). Antiinflammatory drugs mask signs of infection, making it difficult to diagnose infections in the earlier phase. The rapid distribution of the vaccine effectively addressed the issues of the pandemic. On the other hand, the new population of critically ill patients with COVID-19 will possibly be shifted from relatively healthy individuals into those who have not received the vaccine or have not acquired sufficient immunity due to their comorbidities. Rouze and colleagues reported that chronic obstructive pulmonary disease was less frequent than influenza pneumonia in patients with COVID-19, but gram-negative rods were more frequent (1). Future researchers need to address the following question: “In a world where vaccines and antiinflammatory treatments are ubiquitous, does the type of virus matter, or is the patient background more important?”