Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia

Abstract

Importance: Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.

Objective: To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens.

Design, setting, and participants: Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019.

Exposures: Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.

Main outcomes and measures: Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli.

Results: Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 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 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]).

Conclusions and relevance: This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

Conflict of interest statement

Conflict of Interest Disclosures: Dr B. E. Jones reported receiving grants from the Centers for Disease Control and Prevention and Veterans Affairs Health Services Research & Development during the conduct of the study. Ms Nevers reported receiving grants from the Centers for Disease Control and Prevention during the conduct of the study. Dr Sauer reported receiving grants from the Veterans Affairs during the conduct of the study. Dr Greene reported receiving personal fees from Janssen Pharmaceuticals, DURECT Corporation, and Pfizer Inc and grants from AstraZeneca and CSL outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Population

MRSA indicates methicillin-resistant Staphylococcus aureus; VA, Veterans Affairs. aStandard antibiotics were defined as either a β-lactam plus macrolide or tetracycline, or a respiratory fluoroquinolone (moxifloxacin or levofloxacin). β-Lactams included nonpseudomonals (ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillin-clavulanate, cefuroxime, cefotaxime, ceftriaxone, ceftizoxime, cefixime, cefpodoxime, ceftibuten, cefdinir, or ertapenem) or antipseudomonals (piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, cefepime, meropenem, doripenem, or imipenem).

Figure 2.. Relative Distribution of Propensity Scores for Treatment With Anti–Methicillin-Resistant Staphylococcus aureus (MRSA) Therapy

Conditional density curves demonstrating relative distributions of propensity scores for treatment with anti-MRSA therapy with and without standard antibiotics.

Figure 3.. Patient Characteristics Before and After Inverse Probability of Treatment Weighting

Balance plot of patient characteristics for primary analysis before and after inverse probability of treatment weighting using 41 patient characteristics. Dots represent the maximum of pairwise absolute standardized mean difference between 3 treatment groups for each of the covariates. For each variable, lines connect dots for the same variable with and without weighting. BUN indicates blood urea nitrogen.