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Trends in Resistance to Carbapenems and Third-Gen. Cephalosporins among Clinical Isolates of Klebsiella pneumoniae in the U.S., 1999–2010
What is the national epidemiology of Klebsiella pneumoniae isolates resistant to carbapenems (CRKP) and third-generation cephalosporins (G3CRKP)? How do resistance patterns compare across patient care settings, isolate source, geographic region, patient location, and demographic characteristics?
The proportion of CRKP increased from less than 0.1% to 4.5% between 2002 and 2010. These pathogens, which were endemic only in hospitals in the northeastern United States in the early 2000s, have spread to neighboring regions and are emerging in or being exported to nonacute care settings. The frequency of G3CRKP more than doubled, increasing from 5.3% to 11.5% between 1999 and 2010. G3CRKP and CRKP were more common among elderly patients (those greater than 65 years of age), isolates recovered in the ICU or inpatient setting, and among patients from the northeastern United States. Of note, there was an uptick in the outpatient prevalence of CRKP after 2006, reaching 1.9% of isolates in our sample in 2010.
The observed national rise in CRKP is particularly disconcerting for several reasons. First, CRKP infection is associated with a fatal outcome in 47%–57% of cases. Second, treatment is limited to older antibiotics known for high kidney toxicity—a limitation that highlights the urgent need to develop drugs active against Gram-negative bacteria. Third, the ability of resistance-encoding genes to spread through plasmid transfer enables the spread of resistance to related species like E. coli, a transfer that may occur even in the same patient. Finally, CRKP genes may escape detection in routine laboratory testing. The epidemiology of carbapenem-resistant bacteria thus has the potential to replicate the endemic spread of MRSA beyond hospitals and into the community.
Objective: Multidrug-resistant Enterobacteriaceae pose a serious infection control challenge and have emerged as a public health threat. We examined national trends in the proportion of Klebsiella pneumoniae isolates resistant to carbapenems (CRKP) and third-generation cephalosporins (G3CRKP).
Design and Setting: Retrospective analysis of approximately 500,000 K. pneumoniae isolates cultured between January 1999 and July 2010 at 287 clinical laboratories throughout the United States.
Methods: Isolates were defined as CRKP if they were nonsusceptible to 1 or more carbapenems and were defined as G3CRKP if they were nonsusceptible to ceftazidime, ceftriaxone, or related antibiotics. A multivariable analysis examined trends in the proportion of resistant isolates, adjusting for age, sex, isolate source, patient location, and geographic region.
Results: The crude proportion of CRKP increased from less than 0.1% to 4.5% between 2002 and 2010; the frequency of G3CRKP increased from 5.3% to 11.5% between 1999 and 2010. G3CRKP and CRKP were more common among elderly patients (those greater than 65 years of age); the adjusted odds ratio (aOR) relative to pediatric patients (those less than 18 years of age) was 1.2 for G3CRKP (95% confidence interval [CI], 1.2–1.3) and 3.3 for CRKP (95% CI, 2.6–4.2). G3CRKP and CRKP were also more common among patients from the northeastern United States (aOR, 2.9 [95% CI, 2.8–3.0] and 9.0 [95% CI, 7.9–10.4]) than among those from the western United States. The prevalence of outpatient CRKP isolates increased after 2006, reaching 1.9% of isolates in our sample in 2010 (95% CI, 1.6%–2.1%).
Conclusions. The frequency of G3CRKP and CRKP is increasing in all regions of the United States, and resistance is emerging among isolates recovered in the outpatient setting. This underscores the need for enhanced laboratory capacity and coordinated surveillance strategies to contain the further spread of these emerging pathogens.