key: cord-253250-zet48zcl
authors: Thaden, J.T.; Maskarinec, S.A.
title: When two for the price of one isn’t a bargain: Estimating prevalence and microbiology of bacterial co-infections in patients with COVID-19
date: 2020-09-09
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.09.002
sha: 
doc_id: 253250
cord_uid: zet48zcl

nan

In people with viral respiratory tract infections, the presence of a concomitant bacterial infection has been associated with poor clinical outcomes. For example, in patients with influenza, superimposed bacterial infection is present in 20-30% of patients (1, 2) and has been associated with increased rates of shock, mechanical ventilation, and mortality (1, 2) . Similarly, in children with severe respiratory syncytial virus (RSV) infection, multiple studies have demonstrated rates of superimposed bacterial pneumonia in excess of 30%, and this has been associated with a longer duration of mechanical ventilation (3) . Studying the rates and microbiology of bacterial co-infection in patients with viral respiratory infections can aid in how we determine empiric antibiotic therapy, understand prognosis, and discern pathogenesis in viral-bacterial co-infections.

The prevalence and microbiology of concomitant bacterial infections in patients with SARS-CoV-2 infection are not yet well understood. Therefore, we read with interest the study by Langford and colleagues in which they performed a rapid systematic review of studies that examined rates of bacterial pneumonia or bloodstream infection in patients with COVID-19 (4). In this meta-analysis they identified a large cohort of 3448 patients from 28 studies that primarily consisted of hospitalized adults in Asia. There was heterogeneity in the outcomes of the studies that were included in the meta-analysis, as some reported whether bacterial infection was noted on presentation to the hospital (n=20 studies; termed bacterial co-infection), while the remaining studies reported whether a concomitant bacterial infection developed during the course of the patient's hospitalization (n=8 studies; termed secondary bacterial infection). In a random effects meta-analysis, bacterial co-infection was identified in 3.5% of COVID-19 patients, and secondary bacterial infection was identified in 15.5% of COVID-19 patients. No data on prevalence of bacteremia versus bacterial pneumonia was presented. Interestingly, stratification of patients by illness severity showed that bacterial infections were more prevalent in fatal (11.6%) and ICU (8.1%) cases relative to non-ICU hospitalized patients (5.8%). It is not yet clear if the concomitant bacterial infections are driving poor clinical outcomes or if they are simply more common in sicker patients that are receiving a higher level of care (e.g., ventilator-associated pneumonia in intubated patients). The overall low prevalence of bacterial infection in patients with COVID-19 was similar as that noted in another recent meta-analysis (7%) (5) and rapid review (8%) (6) of the literature, though there is significant overlap in the studies included in these reviews. Taken together, the overall rate of bacterial has been demonstrated to be dependent upon factors such as disruption of the Nox2 inflammatory pathway (7) and increased TLR9 expression (8) . Whether SARS-CoV-2 similarly disrupts such pathways is as yet unknown.

Despite the lower prevalence of bacterial co-infection in patients with SARS-CoV-2 infection relative to other viral respiratory pathogens, many patients with COVID-19 (71%) were treated with antibiotics. Most commonly, these were broad-spectrum agents such as fluoroquinolones or carbapenems. While detailed information on antibiotic use patterns such as timing and duration of antibiotic therapy is not provided, the data from Langford At present we do not have enough data to make firm conclusions on the rates and microbiology of bacterial infections in patients with COVID-19. Yet while the available data is limited, the emerging picture is one of lower bacterial co-infection rates in patients with COVID-19 relative to pandemic influenza. Despite this, the reported use of broad-spectrum antibiotic therapy in patients with COVID-19 is high. At present there is not good evidence to support the broad use of empiric antibiotics in patients with COVID-19, particularly in those without critical illness. Antibiotic therapy should be limited to those with suspected or proven bacterial coinfection, with frequent re-evaluation based on the clinical course, laboratory findings, and imaging findings. 

Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States

Bacterial and viral coinfections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013-14

Viral Bacterial Interactions in Children: Impact on Clinical Outcomes

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

Co-infections in people with COVID-19: a systematic review and meta-analysis

Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia

Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical and immunological features of severe and moderate coronavirus disease 2019

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

Epidemic and pandemic viral infections: impact on tuberculosis and the lung. A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN) and members(#) of ESCMID Study Group for Mycobacterial Infections (ESGMYC)