Trends in Klebsiella pneumoniae carbapenemase-positive K. pneumoniae in US hospitals: report from the 2007–2009 SENTRY Antimicrobial Surveillance Program

Abstract

We report the prevalence of carbapenemase-positive Klebsiella pneumoniae among clinical isolates collected from US medical centers (n = 42) from 2007–2009 through the SENTRY Antimicrobial Surveillance Program. Isolates with imipenem or meropenem MIC ≥2 μg/mL were screened by PCR for various carbapenemase genes. Of 2049 K. pneumoniae isolates, 126 (6.1%) were non-susceptible to imipenem or meropenem. bla_KPC was identified in 113 isolates (5.5%). No other carbapenemase genes were identified. For US regions combined, prevalence of K. pneumoniae carbapenemase (KPC)-positive isolates were 5.9% in 2007, 4.9% in 2008, and 5.7% in 2009. Rates were highest in the Mid-Atlantic region (28.6% overall), with fluctuation over time (29%, 23%, and 33% from 2007–2009), followed by the East North Central region (2.4% overall), with a slightly increasing trend (nil, 3.1%, 3.8% from 2007–2009). All KPC-positive organisms were carbapenem non-susceptible according to updated CLSI breakpoints, although all but one was similarly classified according to previous breakpoints.

Introduction

Reports of carbapenem-resistant Enterobacteriaceae have been increasing worldwide, including in the US, over the past 10 years (Gupta et al., 2011, Nordmann et al., 2011). There has been great concern about the ongoing spread of these resistant organisms, as infections caused by these organisms are difficult to treat and have been associated with high morbidity and mortality (Borer et al., 2009, Patel et al., 2008). Carbapenemases, which are beta-lactamase enzymes whose hydrolytic profile includes carbapenems, have become a well-recognized, emerging cause of carbapenem resistance. Multiple carbapenemases have been described and are commonly classified based on their molecular structure into Ambler classes A, B, or D (Queenan and Bush, 2007). Klebsiella pneumoniae carbapenemase (KPC) belongs to Ambler class A and is the most common carbapenemase in the US (Gupta et al., 2011). Other carbapenemases, such as NDM-1 and the IMP or VIM classes of enzymes, are more prevalent in other parts of the world, have now been reported sporadically in the US (Gupta et al., 2011, Limbago et al., 2011). The genes that encode many of the carbapenemase enzymes, including KPC, are typically located on mobile genetic elements (Goren et al., 2010, Mathers et al., 2011, Queenan and Bush, 2007). A patient infected or colonized with a carbapenemase-producing organism may spread the strain to other patients within a healthcare facility or the community.

Carbapenemases not only mediate resistance to other beta-lactam agents, but organisms that harbor carbapenemase genes frequently carry additional resistance mechanisms to other classes of antimicrobial agents resulting in limited treatment options for patients (Castanheira et al., 2010, Endimiani et al., 2009). Because the original Clinical and Laboratory Standards Institute (CLSI) carbapenem breakpoints lacked sensitivity for detecting these resistant organisms, revised interpretive criteria with lowered susceptibility breakpoints for ertapenem, imipenem, and meropenem were developed in additional to new breakpoints for doripenem for Enterobacteriaceae in 2010 (CLSI, 2010). Previous susceptibility breakpoints were ≤4 μg/mL for imipenem and meropenem and ≤2 μg/mL for ertapenem; the updated susceptibility breakpoints are ≤1 μg/mL for imipenem, meropenem, and doripenem (CLSI, 2010) and, as of 2012, ≤0.5 μg/mL for ertapenem (CLSI, 2012). Prior to these updates, there were reports of several KPC-positive K. pneumoniae isolates for which the carbapenem MIC values were in the susceptible range (Endimiani et al., 2009). Several studies noted the failure of automated susceptibility testing systems to detect resistance among carbapenemase-producing organisms (Bratu et al., 2005a, Tenover et al., 2006). Treatment failures of infections caused by KPC-producing K. pneumoniae isolates for which the carbapenem MIC values were in the susceptible range were also noted (Weisenberg et al., 2009).

The KPC enzyme was initially detected in a K. pneumoniae isolate from the US in 1996 (Yigit et al., 2001) and subsequently has been reported with increasing frequency in various gram-negative enteric organisms worldwide (Nordmann et al., 2009). In the US, KPC-producing K. pneumoniae isolates initially spread throughout the Mid-Atlantic states (Bratu et al., 2005b, Woodford et al., 2004) and continue to occur at high rates in that region (Landman et al., 2007, Landman et al., 2012). There have been multiple reports of KPC-producers in other regions in the US over the past 10 years (Deshpande et al., 2006, Gupta et al., 2011, Kitchel et al., 2009), but national trend data are limited (Davies et al., 2011).

In this study, we evaluated the prevalence of carbapenemase-producing K. pneumoniae isolates in the US over a 3-year period and documented their occurrence among various infection sites using data collected as part of a well known nationwide hospital-based surveillance program. We also report on the impact of the updated 2010/2012 CLSI breakpoints for detecting KPC-mediated carbapenem resistance among this group of isolates.