Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies
Introduction
Neutropenic patients with hematologic malignancies are uniquely threatened by multidrug-resistant Gram-negative bacteria because they rely on immediate bactericidal therapy to combat Gram-negative infections. Enterobacteriaceae are the most common causes of Gram-negative bacteremia in this population and have historically been susceptible to recommended β-lactam agents for the treatment of fever and neutropenia.1, 2 However, over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have emerged worldwide as lethal pathogens that are typically resistant to all β-lactam agents due to production of β-lactam-hydrolyzing enzymes such as Klebsiella pneumoniae carbapenemase (KPC).3 Given that currently recommended empirical therapies are inactive against CRE, and identification of CRE by culture typically takes 2–3 days, the spread of CRE into neutropenic patients with hematologic malignancies could have devastating consequences because effective therapy would be delayed.4
We recently reported 18 patients with hematologic malignancies who developed bacteremia due to CRE.5 Nine of 13 neutropenic patients in this study died, there were long delays until receipt of active therapy, and all deaths were related to CRE bacteremia. Given these preliminary findings, we sought to better understand the epidemiology of CRE in this patient population in an area where CRE are endemic nosocomial pathogens. Thus, we conducted a study at two large oncology centers in New York City, USA, a global epicenter for CRE, to determine the prevalence, risk factors, and outcomes of CRE bacteremia in neutropenic patients with hematologic malignancies.
Section snippets
Study design
The study was approved by the Institutional Review Boards of Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center (MSKCC). We first identified all episodes of bloodstream infection (BSI) in adult (age ≥18 years) neutropenic patients (absolute neutrophil count ≤500 cells/mm3) with hematologic malignancies at New York-Presbyterian Hospital/Weill Cornell Medical Center and MSKCC from 2008 to 2012. BSIs where the patient had a prior positive blood culture for the same organism(s)
Prevalence and characteristics of CRE
We identified 1992 BSI episodes in neutropenic patients with hematologic malignancies during the study period, of which 43 (2.2%; 95% confidence interval [CI]: 1.6–2.9%) were caused by CRE (Fig. 1). The proportion of BSIs due to CRE at each hospital was 2.4% and 1.9%, respectively, and varied from 0.8% to 3.0% by study year, with no clear trend over time. CRE caused 4.7% of bacteremias that included a Gram-negative bacterium and 6.5% of bacteremias that included an Enterobacteriaceae. Eighteen
Discussion
To our knowledge, this is the first reported study to assess the prevalence, risk factors, and outcomes of CRE bacteremia in neutropenic patients with hematologic malignancies. We conducted this study at two large oncology centers in New York City, where CRE have been endemic for over a decade,15 and found that CRE represent 2.2% of all BSIs and 4.7% of Gram-negative bacteremias in this population. The number of CRE bacteremia cases was similar to that of candidemia and greater than that of
Conflict of interest
M.J.S. has received research grants/contracts from Allergan and Achaogen. T.J.W. has received research grants/contracts from Allergan and Merck. All other authors report no potential conflicts of interest.
Funding
This work was partially supported by the National Institute of Allergy and Infectious Diseases [K23 AI114994 to M.J.S., R01 AI090155 to B.N.K., and R21 AI117338 to L.C.] and the National Center for Advancing Translational Science [UL1 TR000457] at the National Institutes of Health (NIH), the National Institutes of Health/National Cancer Institute Cancer Center Support Grant [P30 CA008748 to N.C., Z.G., S.K.S], and Save Our Sick Kids Foundation and Sharp Family Foundation [to T.J.W].
Author contributions
M.J.S., N.C., T.J.W., and S.K.S. contributed to the conception and design of the study. M.J.S., N.C., K.M., Z.G., S.K.S. contributed to acquisition of data. M.S., N.C., R.S., G.A., L.C., B.N.K., T.J.W., and S.K.S. contributed to the analysis and interpretation of the data.
Acknowledgments
This study was presented, in part, at IDWeek 2014, Philadelphia, PA, USA (abstract #434). Nine of the 43 CRE bacteremia episodes in this study were included in a previously published manuscript.5
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