Antimicrobial Susceptibility StudyCarbapenem-resistant Enterobacteriaceae and the correlation between carbapenem and fluoroquinolone usage and resistance in the US military health system☆
Introduction
Enterobacteriaceae are leading causes of community- and hospital-acquired infections (Gupta et al., 2011, Nordmann et al., 2011). Antibiotic resistance can rapidly develop and spread in these bacteria through mobile genetic elements readily shared among unrelated species (Gupta et al., 2011, Nordmann et al., 2011).
Carbapenem-resistant Enterobacteriaceae (CRE) have become an especially worrisome global public health crisis (Gupta et al., 2011, Nordmann et al., 2011, Savard and Perl, 2012, Sievert et al., 2013, World Health Organization (WHO), 2000). Infections caused by these bacteria can be associated with a mortality rate as high as 80% (Gupta et al., 2011, Snitkin et al., 2012, Tumbarello et al., 2012). Carbapenem resistance (CR) often arises through mechanisms that involve acquisition of multiple drug resistance genes resulting in extremely drug-resistant or pandrug-resistant infections with few or no treatment options (Nordmann et al., 2011, Magiorakos et al., 2013).
CR is increasing worldwide (Nordmann et al., 2011, Gupta et al., 2011, Savard and Perl, 2012), but the burden of such resistance in 1 large and diverse US population, health care beneficiaries of the Department of Defense (DoD), has not been reported. Furthermore, there is conflicting evidence on whether increased antibiotic consumption, in particular of carbapenems and fluoroquinolones, is correlated with this increased resistance (Mutnick et al., 2004, Bruinsma et al., 2002, Ho et al., 2012, Mouloudi et al., 2010, Manikal et al., 2000, SWAB, 2011, Lee et al., 2013). Of note, correlation between antibiotic consumption and resistance in Enterobacteriaceae throughout an entire health care system in the United States has not been reported (Molton et al., 2013).
Previous antibiotic exposure, especially to fluoroquinolones, was correlated with future isolation of CRE in individual patients in case–control studies (Gupta et al., 2011, Hussein et al., 2009, Marchaim et al., 2012). Other studies have not found that association (Mouloudi et al., 2010).
Our objectives were to determine the level of CRE in a geographically dispersed national managed care system, the health system of the DoD, and to determine if total carbapenem or fluoroquinolone consumption throughout the system was correlated with CR. We also provide proportions and rates because the use of only one may not reflect the true burden of resistance or loss of treatment options and also because a report format most useful for the clinician treating empirically (proportions) may not be as useful to the public health professional (rates) (Rempel and Laupland, 2009, Schwaber et al., 2004, Laxminarayan and Klugman, 2011, Monnet et al., 2001, Sanchez et al., 2013).
Section snippets
Methods
This study was undertaken as a quality improvement initiative authorized by policy memoranda 09-050, 11-035, 13-016, and IRB protocol number #1812.
Overall burden of CR
During 2005–2012, there were 75,529,012 person-years of surveillance and 1,969,315 bacterial organisms identified from 1,823,030 clinical cultures. Those organisms included 667,004 Enterobacteriaceae, of which 368 were classified as CRE for an overall incident proportion of 0.487% (95% confidence interval [CI]: 0.439–0.540) (Table 1). Seventy-seven percent (284) were isolated in outpatient care areas, and 23% (84) were isolated from inpatient care areas. The mean annual incident rate of CRE for
Discussion
With nearly 2 million clinical cultures and 75 million person-years of surveillance, our report is one of the largest to date (Table 2). Proportions and rates of all CRE combined peaked in 2010, with the increase in overall resistance being driven by increases in resistant E. coli. Carbapenem and fluoroquinolone usage were correlated with resistance in certain stratified analyses, but the only statistically significant association was a positive correlation between inpatient fluoroquinolone use
Acknowledgments
Funding: This work was supported by the US Army Medical Command and the Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System, who had no role in the collection or analysis of data, nor the preparation of the manuscript.
Conflicts: There are no associations that might pose a conflict of interest for any of the authors.
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Disclaimer: The views expressed herein are solely those of the authors and not to be construed as official or representing those of the US Army or the Department of Defense.
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