Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL

A Pilot Randomized Controlled Trial

Joseph R. Paonessa, Raj D. Shah, Chiagozie I. Pickens, Bryan D. Lizza, Helen K. Donnelly, Michael Malczynski, Chao Qi, Richard G Wunderink*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)999-1007
Number of pages9
JournalCHEST
Volume155
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Linezolid
Dimercaprol
Vancomycin
Methicillin-Resistant Staphylococcus aureus
Randomized Controlled Trials
Hospital Mortality
Pneumonia
Staphylococcal Pneumonia
Anti-Bacterial Agents
Registries
Length of Stay

Keywords

  • Staphylococcus aureus
  • antibiotic stewardship
  • diagnostic testing
  • methicillin-resistance
  • polymerase chain reaction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Paonessa, J. R., Shah, R. D., Pickens, C. I., Lizza, B. D., Donnelly, H. K., Malczynski, M., ... Wunderink, R. G. (2019). Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial. CHEST, 155(5), 999-1007. https://doi.org/10.1016/j.chest.2019.02.007
Paonessa, Joseph R. ; Shah, Raj D. ; Pickens, Chiagozie I. ; Lizza, Bryan D. ; Donnelly, Helen K. ; Malczynski, Michael ; Qi, Chao ; Wunderink, Richard G. / Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL : A Pilot Randomized Controlled Trial. In: CHEST. 2019 ; Vol. 155, No. 5. pp. 999-1007.
@article{045bdfe542364018872bbac475db0cf6,
title = "Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial",
abstract = "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.",
keywords = "Staphylococcus aureus, antibiotic stewardship, diagnostic testing, methicillin-resistance, polymerase chain reaction",
author = "Paonessa, {Joseph R.} and Shah, {Raj D.} and Pickens, {Chiagozie I.} and Lizza, {Bryan D.} and Donnelly, {Helen K.} and Michael Malczynski and Chao Qi and Wunderink, {Richard G}",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.chest.2019.02.007",
language = "English (US)",
volume = "155",
pages = "999--1007",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "5",

}

Paonessa, JR, Shah, RD, Pickens, CI, Lizza, BD, Donnelly, HK, Malczynski, M, Qi, C & Wunderink, RG 2019, 'Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial', CHEST, vol. 155, no. 5, pp. 999-1007. https://doi.org/10.1016/j.chest.2019.02.007

Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL : A Pilot Randomized Controlled Trial. / Paonessa, Joseph R.; Shah, Raj D.; Pickens, Chiagozie I.; Lizza, Bryan D.; Donnelly, Helen K.; Malczynski, Michael; Qi, Chao; Wunderink, Richard G.

In: CHEST, Vol. 155, No. 5, 01.05.2019, p. 999-1007.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL

T2 - A Pilot Randomized Controlled Trial

AU - Paonessa, Joseph R.

AU - Shah, Raj D.

AU - Pickens, Chiagozie I.

AU - Lizza, Bryan D.

AU - Donnelly, Helen K.

AU - Malczynski, Michael

AU - Qi, Chao

AU - Wunderink, Richard G

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Staphylococcus aureus

KW - antibiotic stewardship

KW - diagnostic testing

KW - methicillin-resistance

KW - polymerase chain reaction

UR - http://www.scopus.com/inward/record.url?scp=85064562265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064562265&partnerID=8YFLogxK

U2 - 10.1016/j.chest.2019.02.007

DO - 10.1016/j.chest.2019.02.007

M3 - Article

VL - 155

SP - 999

EP - 1007

JO - Chest

JF - Chest

SN - 0012-3692

IS - 5

ER -

Paonessa JR, Shah RD, Pickens CI, Lizza BD, Donnelly HK, Malczynski M et al. Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial. CHEST. 2019 May 1;155(5):999-1007. https://doi.org/10.1016/j.chest.2019.02.007