Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia: A patient-level analysis of published data

J. Nicholas O'Donnell, Nathaniel J. Rhodes, Lauren R. Biehle, John S. Esterly, Twisha S. Patel, Milena M. McLaughlin, Elizabeth B. Hirsch

Research output: Contribution to journalArticle

Abstract

In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of ‘susceptible’ organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms ‘carbapenem’, ‘meropenem’, ‘imipenem’, ‘doripenem’, ‘ertapenem’, ‘susceptibility’ and ‘outcomes’. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95% CI 1.06–2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.

Original languageEnglish (US)
Article number105849
JournalInternational Journal of Antimicrobial Agents
Volume55
Issue number2
DOIs
StatePublished - Feb 2020

Fingerprint

meropenem
Microbial Sensitivity Tests
Enterobacteriaceae
Bacteremia
Carbapenems
Mortality
Klebsiella pneumoniae
doripenem
Imipenem
PubMed

Keywords

  • Bacteraemia
  • MIC
  • Meropenem
  • Susceptibility

PubMed: MeSH publication types

  • Journal Article

Cite this

Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia : A patient-level analysis of published data. / O'Donnell, J. Nicholas; Rhodes, Nathaniel J.; Biehle, Lauren R.; Esterly, John S.; Patel, Twisha S.; McLaughlin, Milena M.; Hirsch, Elizabeth B.

In: International Journal of Antimicrobial Agents, Vol. 55, No. 2, 105849, 02.2020.

Research output: Contribution to journalArticle

@article{7f138c98ecae4bbba42a958eaa971d28,
title = "Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia: A patient-level analysis of published data",
abstract = "In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of ‘susceptible’ organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms ‘carbapenem’, ‘meropenem’, ‘imipenem’, ‘doripenem’, ‘ertapenem’, ‘susceptibility’ and ‘outcomes’. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95{\%} CI 1.06–2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.",
keywords = "Bacteraemia, MIC, Meropenem, Susceptibility",
author = "O'Donnell, {J. Nicholas} and Rhodes, {Nathaniel J.} and Biehle, {Lauren R.} and Esterly, {John S.} and Patel, {Twisha S.} and McLaughlin, {Milena M.} and Hirsch, {Elizabeth B.}",
year = "2020",
month = "2",
doi = "10.1016/j.ijantimicag.2019.11.006",
language = "English (US)",
volume = "55",
journal = "International Journal of Antimicrobial Agents",
issn = "0924-8579",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia

T2 - A patient-level analysis of published data

AU - O'Donnell, J. Nicholas

AU - Rhodes, Nathaniel J.

AU - Biehle, Lauren R.

AU - Esterly, John S.

AU - Patel, Twisha S.

AU - McLaughlin, Milena M.

AU - Hirsch, Elizabeth B.

PY - 2020/2

Y1 - 2020/2

N2 - In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of ‘susceptible’ organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms ‘carbapenem’, ‘meropenem’, ‘imipenem’, ‘doripenem’, ‘ertapenem’, ‘susceptibility’ and ‘outcomes’. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95% CI 1.06–2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.

AB - In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of ‘susceptible’ organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms ‘carbapenem’, ‘meropenem’, ‘imipenem’, ‘doripenem’, ‘ertapenem’, ‘susceptibility’ and ‘outcomes’. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95% CI 1.06–2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.

KW - Bacteraemia

KW - MIC

KW - Meropenem

KW - Susceptibility

UR - http://www.scopus.com/inward/record.url?scp=85077661327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077661327&partnerID=8YFLogxK

U2 - 10.1016/j.ijantimicag.2019.11.006

DO - 10.1016/j.ijantimicag.2019.11.006

M3 - Article

C2 - 31770628

AN - SCOPUS:85077661327

VL - 55

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

SN - 0924-8579

IS - 2

M1 - 105849

ER -