By Dean L. Winslow, MD, FACP, FIDSA, FPIDS
Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Dr. Winslow reports no financial relationships relevant to this field of study.
SYNOPSIS: In a retrospective cohort study, 88,605 patients in the Veterans Administration system who were hospitalized with pneumonia were examined. Thirty-eight percent received empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) treatment. Empiric anti-MRSA treatment was not associated with a reduction in mortality in any subgroup of patients studied and appeared to cause harm in many patients.
SOURCE: Jones BE, Ying J, Stevens V, et al. Empirical anti-MRSA vs standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia. JAMA Int Med 2020 Feb. 17. Doi: 10.1001/jamainternmed.2019.7495. [Epub ahead of print].
Researchers conducted a retrospective multicenter cohort study of all hospitalizations in which patients received either anti-methicillin-resistant Staphylococcus aureus (MRSA) or standard therapy for community-acquired pneumonia (CAP) in the Veterans Health Administration healthcare system from Jan. 1, 2008, to Dec. 31, 2013. Subgroups of patients analyzed included those with intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Among 88,605 hospitalized patients (86,851 men; median age, 70 years), empirical anti-MRSA therapy was administered to 33,632 (38%); 8,929 patients (10%) died within 30 days.
Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR]), 1.4), kidney injury (aRR, 1.4), secondary Clostridioides difficile infections (aRR 1.6), vancomycin-resistant Enterococcus spp. infections (aRR, 1.6), and secondary gram-negative rod infections (aRR, 1.5). Similar associations were found between anti-MRSA therapy use and 30-day mortality (aRR, 1.6), and among patients admitted to the intensive care unit (aRR, 1.3), those with a high risk for MRSA (aRR, 1.2), and those with MRSA detected on surveillance testing (aRR, 1.6). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1).
This is an interesting study that certainly casts doubt on the current widely accepted practice of administering empiric anti-MRSA therapy to a large percentage of patients admitted to the hospital with CAP, especially elderly patients, those recently (or remotely) hospitalized, and patients coming from skilled nursing facilities. Although this study certainly has a robust sample size, I cannot help but think that one of the reasons this retrospective study appeared to show “harm” from empiric anti-MRSA therapy is that some subtle factors influenced clinicians to preferentially prescribe empiric anti-MRSA therapy to sicker patients.
The fact that even those who had positive cultures for MRSA and those who had a positive MRSA surveillance screening test did not benefit from empiric anti-MRSA therapy is particularly counter-intuitive. This may be related to the relatively poor positive predictive value of isolation of S. aureus from expectorated sputum and can reflect oropharyngeal colonization rather than the etiologic agent of the pneumonia.
Although this study has limitations (which the authors acknowledge), the results should seriously call into question the common practice of administering empiric anti-MRSA therapy to most patients with CAP, since not only did most patients fail to benefit, but many actually were harmed by this practice. Clearly, we need better diagnostic tests for rapidly determining the etiology of CAP, and, of course, both new and old anti-MRSA antibiotics should be studied in well-designed, prospective, randomized trials.