Klebsiella Pneumoniae - Resistant Strains

Resistant Strains

Infection with carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae is emerging as an important challenge in health-care settings. One of many carbapenem-resistant Enterobacteriaceae (CRE) is Carbapenem-Resistant Klebsiella pneumoniae (CRKP). Over the past 10 years, a progressive increase in CRKP has been seen worldwide; however, this new emerging nosocomial pathogen is probably best known for an outbreak in Israel that began around 2006 within the healthcare system there. In the USA, it was first described in North Carolina in 1996; since then CRKP has been identified in 41 states; and is recovered routinely in certain hospitals in New York and New Jersey. It is now the most common CRE species encountered within the United States.

CRKP is resistant to almost all available antimicrobial agents, and infections with CRKP have caused high rates of morbidity and mortality, particularly among persons with prolonged hospitalization and those who are critically ill and exposed to invasive devices (e.g., ventilators or central venous catheters). The concern is that carbapenem is often used as a drug of last resort when battling resistant bacterial strains. The worry is that new slight mutations could result in infections for which there is very little, if anything, healthcare professionals can do to treat patients with resistant organisms.

There are a number of mechanisms of Carbapenem Resistance in Enterobacteriaceae. These include (1) Hyperproduction of ampC beta-lactamase with an outer membrane porin mutation (2) CTX-M extended-spectrum beta-lactamase with a porin mutation or drug efflux, and (3) Carbapenemase production. When bacteria such as Klebsiella pneumoniae produce an enzyme known as a carbapenemase, they are referred to as carbapenem-resistant Klebsiella pneumoniae (CRKP).

Put another way, the most important mechanism of resistance by CRKP is the production of a carbapenemase enzyme, blakpc. The gene that encodes the blakpc enzyme is carried on a mobile piece of genetic material (a transposon; the specific transposon involved is called Tn4401), which increases the risk for dissemination. CRE can be difficult to detect because some strains that harbor blakpc have minimal inhibitory concentrations (MICs) that are elevated but still within the susceptible range for carbapenems. Because these strains are susceptible to carbapenems, they are not identified as potential clinical or infection control risks using standard susceptibility testing guidelines. Patients with unrecognized CRKP colonization have been reservoirs for transmission during nosocomial outbreaks.

The extent and prevalence of CRKP within the environment is currently unknown. The mortality rate is also unknown but is suspected to be within a range of 12.5% to as high as 44%. The likelihood of an epidemic or pandemic in the future remains uncertain.

The Centers for Disease Control and Prevention (CDC) released guidance for aggressive infection control to combat CRKP.

Place all patients colonized or infected with CRE or carbapenemase-producing Enterobacteriaceae on contact precautions. Acute care facilities are to establish a protocol, in conjunction with the guidelines of the Clinical and Laboratory Standards Institute (CLSI), to detect nonsusceptibility and carbapenemase production in Enterobacteriaceae, particularly Klebsiella spp. and Escherichia coli, and immediately alert epidemiology and infection control staff members if identified. All acute care facilities are to review microbiology records for the preceding 6--12 months to ensure that there have not been previously unrecognized CRE cases. If they do identify previously unrecognized cases, a point prevalence survey (a single round of active surveillance cultures) in units with patients at high risk (e.g., intensive care units, units where previous cases have been identified, and units where many patients are exposed to broad-spectrum antimicrobials) is needed to identify any additional patients colonized with carbapenem-resistant or carbapenemase-producing Klebsiella spp. and E. coli. When a case of hospital-associated CRE is identified, facilities should conduct a round of active surveillance testing of patients with epidemiologic links to the CRE case (e.g., those patients in the same unit or patients who have been cared for by the same health-care personnel).

The reasons that the CDC is only recommending the detection of carbapenem resistance or carbapenemase production for Klebsiella spp. and E. coli are 1) this facilitates performing the test in the microbiology laboratory without the use of molecular methods and 2) these organisms represent the majority of CRE encountered in the United States.

Effective sterilization and decontamination procedures are important to keep the infection rate of this antibiotic resistant strain, CRKP as low as possible.