In the ensuing decade, KPC-producing bacteria have spread throughout the US and worldwide. Data regarding nosocomial infections reported to the CDC showed the overall prevalence of carbapenem resistance among K pneumoniae isolates rose from less than one percent in 2000 to eight percent in 2007.
At one academic medical center in New York City, the percentage of carbapenem-resistant K pneumoniae rose from 9% in 2002 to 18% in 2004, then further to 38% in 2008.
In 2005, the first report of a clinical isolate producing a KPC outside of the US occurred in France from a patient who had recently been hospitalized in New York City.
The first outbreak outside the US was in Israel,11 and KPCs are now endemic in both Israel and Greece. Enterobacteriaceae-producing KPCs have also been reported in Brazil, China, Colombia, Norway, United Kingdom, India, Sweden,5 and more recently, Italy and Finland.12
A closer look at the molecular epidemiology of KPC-producing bacteria has revealed that a few fit lineages have been responsible for dissemination of the blaKPC gene.
An examination of all KPC-producing K pneumoniae isolates sent to the CDC between the years 1996-2008 from 18 states as well as Israel and India revealed that a single dominant strain, multilocus sequence type 258 (ST258), accounted for nearly 70% of the isolates in the CDC database as well as an isolate from an Israeli outbreak.
The study also identified another fit strain, ST14, which was isolated in various facilities in the Midwestern states.
Additionally, Endimiani et al performed clonal analysis of 42 KPC-producing K pneumoniae isolates from five different institutions in the eastern US and found 32 (76%) to be clonally related, suggesting interstate transmission of a single dominant clone
Infections caused by KPC-producing K pneumoniae have been associated with increased cost and length of stay as well as frequent treatment failures and death.
Risk factors for infection include advanced age,19 being severely ill,20 previous treatment with antibiotics,7 organ or stem-cell transplantation, mechanical ventilation, and long hospital stays.
Poor outcomes from infections with KPC-producing bacteria have been reported since the first reports of KPC outbreaks in New York City hospitals. A small series of patients with bloodstream infections caused by KPC-producing bacteria from New York City hospitals in 2005 revealed mortality rates of 47% to 66%.7,19 The experience outside the US has been similar, as shown by a matched retrospective historical cohort study of 32 Israeli patients with bacteremia caused by carbapenem-resistant K pneumoniae compared to patients with infections caused by susceptible K pneumoniae that showed a crude mortality of 72%, and an attributable mortality of 50%.
After initial outbreaks in the northeastern United States, KPC-producing bacteria have emerged in multiple species of Gram-negative bacteria across the world. They have created significant clinical challenges for clinicians as they are not consistently identified by routine screening methods and are highly drug-resistant, resulting in delays in effective treatment and a high rate of clinical failures. Effective antibiotics are limited to polymyxins, tigecycline and occasionally aminoglycosides. Hospitals must prepare so that they can identify these organisms early and institute enhanced infection control efforts when necessary. Clinical microbiology laboratories need to recognize the signature of ertapenem resistance as a marker for KPC-producing bacteria, and should alert physicians to assume cross resistance to all carbapenems when it is present. Furthermore, clinicians need to appreciate that KPC-production can occur in many Gram-negative bacilli and become familiar with the limited effective antibiotics against KPC-producing bacteria as the frequency of KPC-producing bacteria is expected to continue to increase.
Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are emerging, highly drug-resistant pathogens whose incidence is rapidly increasing in a variety of clinical settings. This review describes the evolution from sporadic localized outbreaks to international emergence and addresses the difficulties these organisms present to clinicians, particularly in relation to common misidentification by routine susceptibility testing and limited treatment options leading to significant morbidity and mortality.
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