Compared with patients prescribed only an antiviral, patients who are prescribed both an antiviral and an antibiotic have a lower risk for 3-day respiratory hospitalization, according to a study published in Clinical Infectious Diseases.

The Centers for Disease Control and Prevention has estimated that in the United States, the annual influenza burden is roughly 49 million cases of influenza, 959,000 influenza-related hospitalizations, and 79,400 deaths. Although a majority of individuals recover from influenza infection within 2 weeks, influenza-related morbidity and mortality can also occur 1 to 2 weeks after infection, as a result of superimposed bacterial infections or aggravation of an existing chronic illness. In the last 2 decades, influenza-associated morbidity and mortality have increased, in part as a result of an aging population, which highlights the need for enhanced treatment.

Neuraminidase inhibitor antiviral treatment can be prescribed for the treatment of influenza, but antibiotics are not recommended unless the clinician perceived the patient as high risk for bacterial complications. However, during influenza outbreaks, 98% of deaths have been linked to bacterial coinfections; this raises the question of whether antibacterial treatment among patients with influenza may be clinically important. Previous studies have evaluated the rate of antibiotics prescribed in influenza, but there is a paucity of research regarding the outcome of prescribing. Therefore, this retrospective cohort study explored the association between antivirals, antibiotics, and hospitalization among patients with confirmed influenza.

In total, 12,806 cases of influenza were included using data from the Veterans Association Informatics and Computing Infrastructure (VINCI) from 2011 to 2018. Inpatient hospitalizations (all-cause and respiratory) within 30 days of influenza diagnosis were compared among the following 4 patient cohorts: no treatment (n=4228), antiviral only (n=6492), antibiotic only (n=671), and both antibiotic and antiviral (n=1415). Relative risk (RR) for hospitalization was estimated using Poisson generalized linear model and robust standard errors.

Of the included influenza cases, the majority of whom were white males, the mean age was between 57 and 60 years. Compared with the no-treatment group, the other 3 groups had a statistically significant lower risk for all-cause or respiratory hospitalization both within the first 5 days of illness onset and within 30 days. Although the most protective benefits were observed within the first 5 days, the risk for all-cause hospitalization among patients who received only antiviral treatment was 80% lower than in untreated patients compared with 85% lower among those who received both antiviral and antibiotic treatment (RR, 0.20 and RR, 0.15, respectively). No other differences detected were statistically significant.

Furthermore, a subanalysis of the results was performed to identify groups who may benefit the most from combination therapy. Compared with antiviral therapy alone, patients aged >65 years who had chronic pulmonary disease had a lower risk for respiratory hospitalization with combination antibiotic and antiviral therapy. Results from an antibiotic-specific subanalysis also suggested that certain antibiotics may play a protective role in the course of infection with influenza, and specifically tetracyclines. However, a driving factor of the results of this study may be that administering antibiotics prophylactically to select patients may decrease influenza morbidity via the treatment of co- or superinfections associated with influenza.

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The study authors stated that although these results demonstrate that there is a role for combination antibiotic and antiviral therapy in select patients with confirmed influenza, this should not drive a change in practice for influenza at this time. The study authors concluded that, “Additionally, we hope our data can guide the needed future studies that will identify the patients that would benefit the most from this intervention.”


Sutton SS, Magagnoli J, Cummings T, Hardin J. Association between the use of antibiotics, antivirals, and hospitalizations among patients with laboratory confirmed influenza [published online January 24, 2020]. Clin Infect Dis. doi:10.1093/cid/coaa074/5715206