In this study, we sought to determine whether clinical, laboratory and imaging features of patients hospitalized for CAP and test positive for a respiratory virus are sufficiently distinct to safely avoid empiric antibiotic therapy at admission. Our study differs from previous ones, as we only included patients who provided a high-quality purulent sputum at or shortly after admission, and all cases underwent quantitative bacteriologic testing of sputum with inclusion of recognized bacterial pathogens and commensal bacteria. Admittedly, reliance on a valid sputum sample introduces a selection bias, although with this methodology we were able to achieve an etiologic diagnosis in every case and could, with high likelihood, rule in or out a bacterial infection.
Our results show that, in patients hospitalized for pneumonia, the clinical presentation, laboratory and radiologic findings do not differ sufficiently among those with bacterial or viral infection or bacterial/viral coinfection to exclude the presence of bacterial infection. An exception would be the absence of bacteria on microscopic examination of a truly purulent sputum sample from a patient who has not received an antibiotic. Otherwise, there were no differences among patients that would support a decision to withhold antibiotic treatment. These findings support current ATS/IDSA guidelines that recommend antibiotic therapy in all patients who are sick enough to be hospitalized for CAP even if they test positive for the presence of a respiratory virus [[Jones BE, Ramirez JA, Oren E, Soni NJ, Sullivan LR, Restrepo MI, Musher DM et al, Diagnosis and Management of Community-acquired Pneumonia:An Official American Thoracic Society / Infectious Diseases Society of America Clinical Practice Guideline, Clin Infect Dis, in press, 2024; MAY NOT ADD THIS REF UNTIL AFTER GUIDELINES ARE PUBLISHED]]. Patients with bacterial pneumonia were more likely to have been smokers and to have chronic pulmonary disease. Upper respiratory symptoms were more common in patients with viral pneumonia, and WBC counts were higher in patients with bacterial pneumonia, but there was substantial overlap. The similarity in radiologic findings, with the finding of consolidation in viral pneumonia, is especially worth noting, since it is at odds with earlier reports [26, 27].
A unique feature of this study is the inclusion of patients who were infected with commensal bacteria, a finding that was made possible by the use of quantitative bacteriology and MALDI-TOF idenfication of all organisms. This is also the first study to compare clinical features of pneumonia due to recognized bacterial pathogens and commensal bacteria; interestingly, no differences were observed.
We found that patients with bacterial pneumonia were unlikely to have URI symptoms, and patients with viral pneumonia were more likely to be immunocompromised, as has been reported previously [15]. Interestingly, although this study was confined to patients who produced frankly purulent sputum, 13% of our patients had only viral infection, emphasizing that patients with purely viral pneumonia clearly may produce purulent sputum. Contrary to conventional teaching [27], we did not observe differences in imaging findings such as lobar consolidation, multifocal involvement, pleural effusion, or atelectasis among the three groups. Because previous studies did not have adequate sputum samples on all their patients, they may have diagnosed viral pneumonia when bacterial coinfection was actually present.
Existing literature regarding the utility of peripheral WBC counts in differentiating bacterial from viral pneumonia present inconsistent results. Some studies, including our own [1], found higher median peripheral WBC counts in bacterial than in viral infection, while others have found no significant difference [28]. A very high serum procalcitonin level, observed in 3 patients, suggested bacterial infection but there was great variability in results, and procalcitonin was normal in 29.3% patients with bacterial infection, indicating that a decision to treat with, or to withhold antibiotics can not be based on this test [19, 21].
The primary objective of the present study was to determine, in patients with CAP and a documented respiratory virus by PCR, the possibility of excluding a bacterial etiology in order to avoid prescribing empiric antibiotic therapy. Current guidelines recommend empiric antibiotics for patients who are hospitalized with CAP [5]. However, debate persists regarding the appropriateness of antibiotics in patients with a positive viral PCR test and negative or inconclusive bacterial microbiological testing [[Jones et al after publication of new guuidelines]]. A receiver-operator curve suggested that a patient with a positive viral PCR, known sick contact, normal WBC, and normal procalcitonin might not require immediate antibiotics. However, the negative predictive value of this tool was only 0.38 and therefore can not be used to justify withholding antibiotics. Thus, our study further supports consensus guidelines for initiating empiric antibiotic therapy in all patients who are deemed sufficiently ill to require hospitalization for CAP even if a respiratory virus is shown to be present [[Jones et al after publication of new guidelines]]
This study has several limitations. The total number of patients is small and it was done at a single center, but this kind of intense study is unlikely to be done in large groups of patients, and a single center assures uniform quality of laboratory work. The population consisted largely of older men, many of whom had comorbidities, and all of whom were hospitalized. Patients were only included if they provided high-quality purulent sputum; this inclusion bias was felt to be necessary because, without a high-quality sputum specimen, the diagnosis of bacterial pneumonia can not be established in about one-half of cases. The standard teaching that viral infection does not cause purulent sputum was not supported by our results. Finally, the number of patients with a pure viral pneumonia was too small to allow for meaningful comparisons in some categories, potentially limiting the generalizability of our results, although this degree of overlap in small numbers of cases probably means that a physician caring for an individual patient can not make therapeutic decisions based on any of the criteria studied.
In conclusion, the present study shows modest differences in clinical presentation of patients with bacterial and viral pneumonia or bacterial/viral coinfection, with substantial overlap in symptoms, laboratory, and imaging findings, precluding the ability to identify patients who may not require antibiotic therapy. If empiric antibiotics are to be withheld in patients hospitalized for CAP, further studies are needed to identify potential biomarkers or other clinical signs that can more clearly exclude a bacterial etiology.