Chest

Chest

Volume 155, Issue 5, May 2019, Pages 999-1007
Journal home page for Chest

Original Research: Chest Infections
Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial

https://doi.org/10.1016/j.chest.2019.02.007Get rights and content

Background

Guidelines recommend empirical vancomycin or linezolid for patients with suspected pneumonia at risk for methicillin-resistant Staphylococcus aureus (MRSA). Unneeded vancomycin or linezolid use may unnecessarily alter host flora and expose patients to toxicity. We therefore sought to determine if rapid testing for MRSA in BAL can safely decrease use of vancomycin or linezolid for suspected MRSA pneumonia.

Methods

Operating characteristics of the assay were initially validated against culture on residual BAL. A prospective, unblinded, randomized clinical trial to assess the effect of antibiotic management made on the basis of rapid diagnostic testing (RDT) compared with usual care was subsequently conducted, with primary outcome of duration of vancomycin or linezolid administration. Secondary end points focused on safety.

Results

Sensitivity of RPCR was 95.7%, with a negative likelihood ratio of 0.04 for MRSA. The clinical trial randomized 45 patients: 22 to antibiotic management made on the basis of RDT and 23 to usual care. Duration of vancomycin or linezolid administration was significantly reduced in the intervention group (32 h [interquartile range, 22-48] vs 72 h [interquartile range, 50-113], P < .001). Proportions with complications and length of stay trended lower in the intervention group. Hospital mortality was 13.6% in the intervention group and 39.1% for usual care (95% CI of difference, –3.3 to 50.3, P = .06). Standardized mortality ratio was 0.48 for the intervention group and 1.18 for usual care.

Conclusions

A highly sensitive BAL RDT for MRSA significantly reduced use of vancomycin and linezolid in ventilated patients with suspected pneumonia. Management made on the basis of RDT had no adverse effects, with a trend to lower hospital mortality.

Trial Registry

ClinicalTrials.gov; No. NCT02660554; URL: www.clinicaltrials.gov.

Section snippets

Methods

To safely perform the RCT, establishing the operating characteristics for off-label use of the commercially available RPCR assay (MRSA/SA SSTI kit on the Cepheid GeneXpert platform) on BAL was the critical first step.

RPCR Assay Validation Phase

A total of 247 BAL samples were collected and tested using RPCR. Eight samples (3.2%) initially had an indeterminate result. On repeat, all yielded an unequivocal result.

MRSA grew in culture in 23 samples (Table 1). RPCR detected MRSA in 26 of 247 BAL samples. RPCR correlated with positive MRSA cultures in 22 of 26 (84.1%) samples: 4 (1.6%) false positives and 1 (0.4%) false negative compared with culture. The one false-negative MRSA RPCR was a BAL with only 100 CFU/mL growth of MRSA, which was

Discussion

Our RCT demonstrated that rapid diagnostic testing use on BAL fluid for critically ill patients with suspected MRSA pneumonia safely decreased anti-MRSA antibiotic use. Of interest, RPCR use for the initial suspected pneumonia episode had a carryover effect, leading to even greater differences in vancomycin/linezolid use for the entire subsequent 28-day study period. Although not a predefined coprimary end point as has been suggested for studies of antibiotic stewardship,28 all predefined

Conclusions

Use of a rapid PCR-based diagnostic test for MRSA with high sensitivity and excellent NLR resulted in significant reductions in use of anti-MRSA agents in mechanically ventilated patients with suspected MRSA pneumonia. Use of the RPCR was found to have a carryover effect of decreasing anti-MRSA use even for subsequent suspected infections within 28 days. Stopping or avoiding anti-MRSA antibiotic use on the basis of RPCR results not only had no adverse effects, but was actually associated with

Acknowledgments

Author contributions: R. G. W. takes responsibility for the content of the manuscript, including data and analysis. R. D. S., C. Q., and R. G. W. undertook conception and design. J. R. P., R. D. S., C. I. P., B. D. L., H. K. D., M. M., C. Q., and R. G. W. acquired data. J. R. P., B. D. L., and R. G. W. performed analysis and interpretation. J. R. P. and B. D. L. undertook the initial draft. R. D. S., C. I. P., H. K. D., M. M., C. Q., and R. G. W. reviewed and revised for important intellectual

References (43)

  • A.C. Kalil et al.

    Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society

    Clin Infect Dis

    (2016)
  • A. Torres et al.

    International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociacion Latinoamericana del Torax (ALAT)

    Eur Respir J

    (2017)
  • J.D. Chalmers et al.

    Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis

    Clin Infect Dis

    (2014)
  • S. Aliberti et al.

    Multidrug-resistant pathogens in hospitalised patients coming from the community with pneumonia: a European perspective

    Thorax

    (2013)
  • Y. Shindo et al.

    Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia

    Am J Respir Crit Care Med

    (2013)
  • P.K. Ekren et al.

    Evaluation of the 2016 Infectious Diseases Society of America/American Thoracic Society Guideline criteria for risk of multidrug-resistant pathogens in patients with hospital-acquired and ventilator-associated pneumonia in the ICU

    Am J Respir Crit Care Med

    (2018)
  • S.B. Smith et al.

    Trends in pathogens among patients hospitalized for pneumonia from 1993 to 2011

    JAMA Intern Med

    (2014)
  • E.Y. Klein et al.

    Trends in methicillin-resistant staphylococcus aureus hospitalizations in the United States, 2010-2014

    Clin Infect Dis

    (2017)
  • R. Jain et al.

    Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections

    N Engl J Med

    (2011)
  • G.J. Moran et al.

    Prevalence of methicillin-resistant staphylococcus aureus as an etiology of community-acquired pneumonia

    Clin Infect Dis

    (2012)
  • B.E. Jones et al.

    Trends in antibiotic use and nosocomial pathogens in hospitalized veterans with pneumonia at 128 medical centers, 2006-2010

    Clin Infect Dis

    (2015)

    • Cited by (46)

    View all citing articles on Scopus

    FUNDING/SUPPORT: This study was supported by a grant from the Dixon Young Investigator Award (R. D. S., R. G. W.) from the Northwestern Medical Foundation. R. D. S. and C. I. P. were supported by National Institutes of Health/National Heart, Lung, and Blood Institute T32 HL076139 Training Program in Lung Sciences grant.

    View full text
    © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.