Impact of Antibacterials on Subsequent Resistance and Clinical Outcomes in Adult Patients With Viral Pneumonia

An Opportunity for Stewardship

Matthew P. Crotty; Shelby Meyers; Nicholas Hampton; Stephanie Bledsoe; David J. Ritchie; Richard S. Buller; Gregory A. Storch; Marin H. Kollef; Scott T. Micek


Crit Care. 2015;19(404) 

In This Article


This study compared a cohort of 174 patients with viral pneumonia and mixed viral–bacterial infection based on exposure to continued empiric antibacterials after respiratory virus identification. More of the subsequent infecting or colonizing bacterial isolates from the group with pure viral pneumonia who received continued long-course antibacterials were defined as MDROs compared with the short-course group (P = 0.027). These findings suggest that more prolonged exposure to broad-spectrum antibacterials in patients with viral pneumonia may have promoted resistance in these patients.

No benefit of continued empiric antibacterials for patients with pure viral pneumonia was seen in this study. The risk of bacterial coinfection in the setting of viral pneumonia, especially with influenza, creates a challenging situation for clinicians. The potential detrimental impact of not treating a bacterial pathogen weighs heavily on the decision process and downstream effects of such therapies may be disregarded. Our findings of similar clinical outcomes between patients with pure viral pneumonia who received long-course antibacterials after virus recognition and those who did not may suggest opportunity for de-escalation of empiric antibacterial therapy when viral pneumonia is identified.

A previous randomized controlled trial by Oosterheert et al.[26] evaluated implementation of real-time PCR rapid diagnostics for respiratory pathogen identification. They found increased diagnostic yield with the assay but no difference in antibiotic use, and hypothesized that reluctance to change treatment based on testing results may have inhibited cost-effectiveness from being demonstrated. In our study, systemic antibacterials were discontinued following identification of a respiratory virus by RVP for several patients; however, whether virus identification directly led to discontinuation of antibacterials cannot be determined. The willingness of prescribers to de-escalate and stop antibacterials in this setting may suggest increased recognition of the role of viral pathogens in pneumonia. Additionally, the expanded panel of viruses detected may have factored into how results were perceived, as prescribers may have been more likely to attribute pneumonia to newly detectable viruses such as human metapneumovirus. However, it is not possible to definitively determine the rationale for stopping antibacterial therapy.

Timely antibiotic administration is crucial for treating hospitalized patients with suspected pneumonia.[33] Antimicrobial de-escalation attempts to balance the use of these essential drugs up front with the emergence of resistance.[34] The optimal strategy for de-escalation of antibacterials in the setting of viral pneumonia without an identified bacterial coinfection is unclear. Our study found no difference in clinical outcomes based on antibiotic duration of therapy in patients with viral pneumonia despite significantly different total antibacterial exposure (DOT/1000PD) between groups. Byington et al.[24] found previously that improved diagnostic technologies enhancing detection of respiratory viruses decreased antibacterial use at a children's hospital. The authors concluded that improved diagnostics are an important tool in decreasing unnecessary antibacterial prescribing. Our study similarly illustrated the potential impact of respiratory virus diagnostics on antibacterial use in an adult population.

C. difficile infection is a major cause of morbidity and mortality in US hospitals and has been directly linked to exposure to broad-spectrum antibiotics.[35,36] In a cohort of hospitalized adult patients, Shiley et al.[37] found that significantly more patients who continued to receive antibacterials after diagnosis of a viral respiratory tract infection developed C. difficile infection. One patient in our study who was treated with long-course antibacterials after identification of a respiratory virus also developed C. difficile infection. Strategies to best limit the use of unneeded antibacterials are important to curtail against the growing issues of C. difficile and resistance, and may be aided by de-escalation approaches using enhanced viral diagnostic technologies.

Limitations of this study should be noted. First, this was a small retrospective cohort study of patients at a single institution and may not be representative of all settings. It is important to note that BJH is a regional specialty referral hospital and not a community hospital. This accounts for the case mix with a high prevalence of immunosuppressed patients and the low prevalence of narrow spectrum empiric antibiotic utilization. The small number of patients meeting inclusion criteria did not allow for definitive conclusions to be made regarding group comparison as a lack of statistically significant differences being found could be due to the lack of sample size. Second, patients were determined to have viral pneumonia based on virus identification and radiographic findings but other markers of illness, such as white blood cell count and fever, were not considered and the retrospective nature of the study did not allow evaluation of what drove continuation of antibacterials in some patients but not others. Moreover, we did not attempt to identify risk factors associated with pure viral pneumonia. Third, although coinfecting bacterial pathogens were not identified in patients with pure viral pneumonia, it is impossible to prove that they were not present. Receipt of antibacterials prior to obtaining bacterial cultures could have limited the diagnostic yield of bacterial cultures in some cases and yield from bacterial cultures is not perfect. Finally, all of the viral pneumonia cases occurred in a 20-month period. Viral epidemiology during this time may not be representative of all seasons. Influenza H1N1 p2009 was the primary influenza virus identified in our study (85 %). Incidence rates of bacterial coinfection and coinfecting organisms may differ from year to year and from virus type to virus type, which may hinder application of de-escalation strategies using the results of this study.

It is not possible to directly link the development of subsequent MDRO infections/colonization and C. difficile infection seen in our study to the continued empiric antibacterials administered. All of the patients included in the cohort received antibacterials at some point during their index hospitalization and infection control measures were not directly assessed in these patients. Additionally, hospitalization itself probably increases the risk of these patients being colonized with MDROs. Use of cephalosporins and vancomycin, two of the most commonly administered empiric agents in our study, have been implicated as increasing the prevalence of VRE, the most commonly identified subsequent MDRO in this study.[38,39] Decreasing exposure to broad-spectrum antibacterials such as third-generation and fourth-generation cephalosporins and vancomycin would be expected to lessen the incidence of VRE and other MDROs as was seen in this study, but the risk of development and transmission of resistance in the hospital cannot be completely eliminated. Antibacterials are extraordinarily important in the treatment of many hospitalized patients and their use is often warranted. Decreasing unnecessary use may help curb acquirement of resistant organism in healthcare settings but even appropriate use can lead to the development of resistance. Only through multifaceted efforts of infection control and antimicrobial stewardship can the spread of MDROs between patients, clinicians, workers, and visitors be diminished.