Evaluation of Clinical Outcomes in Patients with Bloodstream Infections Due to Gram-Negative Bacteria According to Carbapenem MIC Stratification

John S. Esterlya,b, Jamie Wagnerc, Milena M. McLaughlina,d, Michael J. Postelnicka, Chao Qie and Marc H. Scheetza,d

– Author Affiliations


aDepartment of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA

bDepartment of Pharmacy Practice, Chicago State University, Chicago, Illinois, USA

cMidwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USA

dDepartment of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, Illinois, USA

eDepartment of Pathology, Clinical Microbiology Division, Northwestern Memorial Hospital, Chicago, Illinois, USA

ABSTRACT


               Predictive modeling suggests that actual carbapenem MIC results are more predictive of clinical patient outcomes than categorical classification of the MIC as susceptible, intermediate, or resistant. Some have speculated that current CLSI guidelines’ suggested thresholds are too high and that clinical success is more likely if the MIC value is ≤1 mg/liter for certain organisms. Patients treated with carbapenems and with positive blood cultures for Pseudomonas aeruginosa, Acinetobacter baumannii, or extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria were considered for evaluation in this clinical retrospective cohort study. Relevant patient demographics and microbiologic variables were collected, including carbapenem MIC. The primary objective was to define a risk-adjusted all-cause hospital mortality breakpoint for carbapenem MICs. Secondarily, we sought to determine if a similar breakpoint existed for indirect outcomes (e.g., time to mortality and length of stay [LOS] postinfection for survivors). Seventy-one patients met the criteria for study inclusion. Overall, 52 patients survived, and 19 died. Classification and regression tree (CART) analysis determined a split of organism MIC between 2 and 4 mg/liter and predicted differences in mortality (16.1% versus 76.9%; P < 0.01). Logistic regression controlling for confounders identified each imipenem MIC doubling dilution as increasing the probability of death 2-fold (adjusted odds ratio [aOR] 2.0; 95% confidence interval [CI], 1.3 to 3.2). Secondary outcomes were similar between groups. This study revealed that patients with organisms that had a MIC of ≥4 mg/liter had worse outcomes than patients whose isolates had a MIC of ≤2 mg/liter, even after adjustment for confounding variables. We recommend additional clinical studies to better understand the susceptibility breakpoint for carbapenems.


FOOTNOTES


Received 13 December 2011.

Returned for modification 19 February 2012.

Accepted 19 June 2012.

Address correspondence to Marc Scheetz, mscheetz@nmh.org.

Published ahead of print 9 July 2012

Copyright © 2012, American Society for Microbiology. All Rights Reserved.

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