With a combination of severely ill patients, high antibiotic use, and lengths of stay measured in weeks, long-term acute care (LTAC) hospitals have been described as a perfect storm for emergence of multidrug-resistant organisms (MDROs).

Among the panoply of MDROs is one of utmost concern, a group of bacteria that are resistant to virtually all available antibiotics: Carbapenem-resistant Enterobacteriaceae (CRE).

“CRE may be the most serious contemporary antibiotic resistance threat because of the number of different resistance mechanisms, concomitant resistance to all or nearly all alternative antibiotics, high attributable mortality associated with invasive infection, and the ability of these pathogens to spread rapidly across geographic regions,” the authors of a recently published study conclude.1

In that regard, the most widely dispersed type of CRE in the U.S. is carbapenem-resistant Klebsiella pneumoniae (KPC). In giving CRE its highest public health threat rating of “urgent,” the Centers for Disease Control and Prevention emphasized that while some “4% of U.S. short-stay hospitals had at least one patient with a serious CRE infection during the first half of 2012 — about 18% of LTACs had one.”2

Evidence continues to accumulate that the more than 400 LTACs nationally are at risk of becoming CRE reservoirs, as the emerging pathogen establishes an endemic presence that is hard to eradicate. To add historical inevitability to this toxic mix, communication breakdowns between long-term care facilities and hospitals about transferred residents or patients colonized or infected with MDROs has been a longstanding source of controversy. Regardless of whether the CRE originally came in through a hospital patient, the problem is that the care delivery model in LTACs can amplify the effect and serve as a reservoir for future transmission across the continuum.

“LTC facilities have long been documented as ‘reservoirs’ of MDR organisms,” researchers report.3 “LTACHs, where antibiotic use is considerable and patients often come from ICUs requiring mechanical ventilation and invasive devices, add a new and heightened dimension to this problem. Therefore, the dissemination of carbapenem-resistant organisms in these settings is worrisome.”

Given the possibility of a practically pan-resistant pathogen moving across the health care continuum, the CDC recommends “When transferring a patient, require staff to notify the other facility about infections, including CRE. Participate in regional and facility-based prevention efforts designed to stop the transmission of these organisms.”4

In the absence of such measures, CRE can spread throughout regional health systems, as happened in Chicago in 2008 when a cluster of KPC cases at one LTACH formed the epicenter of a regional outbreak that spread to 26 other health care facilities.5 In the aftermath of that outbreak and with increasing prevalence of KPC colonization among patients in Chicago area LTACHs, a regional collaborative and research effort was launched. The latest example of that effort comes in a recently published paper,1 which found that a bundle of infection control interventions that included chlorhexidine baths for patients sharply reduced the rate of colonization and infection in four LTACHs in Chicago with high endemic KPC prevalence.

The bundle intervention included:

• screening patients for KPC rectal colonization upon admission and every other week;

• contact isolation and geographic separation of KPC-positive patients in ward cohorts or single rooms;

• bathing all patients daily with 2% chlorhexidine gluconate (CHG)–impregnated cloths;

• health care worker education and adherence monitoring, with a focus on hand hygiene.

KPC Colonization Drops

The study was conducted between February 1, 2010, and June 30, 2013, with 3,894 patients enrolled during the pre-intervention period (lasting from 16-29 months), and 2,951 patients were enrolled during the intervention period (lasting from 12-19 months).

Though KPC prevalence on admission remained high, the incidence rate of KPC colonization fell 50% during the intervention, going from 4 to 2 acquisitions per 100 patient-weeks. Compared to pre-intervention, average rates of clinical outcomes declined during intervention: KPC in any clinical culture (3.7 to 2.5/1000 patient-days); KPC bacteremia (0.9 to 0.4/1000 patient-days): all-cause bacteremia (11.2 to 7.6/1000 patient-days) and blood culture contamination (4.9 to 2.3/1000 patient-days).

Chlorhexidine Bathing May Be Key Measure

The chlorhexidine bathing was probably the intervention most responsible for the sharp declines in all cause bloodstream infections and skin decolonization, the authors noted.

“We found for the individual patient it was reducing their risk of infection by significantly reducing their skin burden of organisms,” says lead author Mary K. Hayden, MD, infectious disease physician at Rush University Medical. “But really the problem with a bundle is you can’t say with any kind of certainty which component [had the most effect].”

In contrast, declines in KPC incidence and prevalence were more gradual, presumably reflecting the greater effort needed to control cross-colonization in a setting of high KPC rates on admission and ongoing colonization pressure.

In research that preceded the current study, Hayden and colleagues determined that skin colonization of patients was a much bigger factor than environmental contamination.6

“If we had found a lot of environmental contamination, then we would have included enhanced environmental cleaning in our bundle,” she says. “I know that other studies have found environmental contamination, but we really found very little, so we did not include that in our bundle. But we found lots of KPC on patient skin — over 90% who were tested in the previous study had KPC on their skin. And over 50% of the skin sites tested were positive for KPC. So we did include chlorhexidine in the bundle.”

Factors contributing to spread within the facility likely include the acuity of patients, high use of medical devices, and the “hands-on care” these patients require, she adds. “The patients admitted there typically have lots of health care exposure, medical device exposures, and lots of antibiotic exposure,” she explains. “They have had prolonged or sometimes multiple prior hospital stays. So they are already set up for antibiotic resistance organisms. In our paper we found that 20% of patients on average who are admitted to the LTACHs are colonized with KPC at the time of admission.”

Though hand hygiene was emphasized, compliance with infection control measures was not reported in the paper.

“New colonizations were detected in the facility from patients who presumably had acquired KPC from another patient,” Hayden says. “We were able to reduce what we are assuming was cross transmission of KPC in the facility. The rate of new cases of colonizations declined steadily during the intervention, from about 4 cases per 100 patients at risk per week, down to about 2. It was about half by the end of the study.”

Patient transfers have been “a huge part of the problem,” she said, noting that another aspect of their ongoing research is to improve interfacility communication. “Awareness of the problem is really important in order to be able to control it and prevent spread if it enters your facility.”

To address the problem, Illinois public health officials and clinicians developed the Extensively Drug Resistant Organism (XDRO) Registry, which is designed to improve inter-facility communication on patients who have tested positive for CRE. The registry stores CRE surveillance data and has features that can help facilities track their CRE submission history. Creation of the registry required the state public health department to amend the Control of Communicable Diseases Code, which now requires reporting of CRE to state public health.

CRE-positive cultures per patient stay must be reported to the XDRO registry within 7 calendar days after the test result is finalized. All hospitals, hospital-affiliated clinical laboratories, independent or free-standing laboratories, longer-term care facilities, and long-term acute care hospitals in Illinois are required to report CRE isolates.

“So in Illinois it is required that if you have a CRE case you record that information or you send that information electronically to this registry,” Hayden says.

“Now whenever I get a patient in my facility and I am suspicious of them having CRE, I can ping the registry and it is all coded and HIPPA compliant — I can find out if my patient has registered before at another facility. They’re working towards automating that so that instead of the IP having to go manually into the registry, each time she gets a new [patient] it automatically sends the information.”

It is hoped that improved communication and the use of bundles like the one described can reduce the presence of CRE in LTACHs and prevent transmission to downstream facilities. While labor intensive, the bundle could be an option for facilities that are having recurrent CRE problems. “We were very concerned about getting this problem under control as quickly as possible,” Hayden says. “There needs to be more studies, but if you know your LTACH has a problem and you want to get on top of it, this is definitely a way that I would approach it based on our experience.”


  1. Hayden MK, Lin MY, Lolans K, et al. Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae in long-term acute-care hospitals. Clinical Infect Dis Advance Access published January 26, 2015
  2. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Available at: http://1.usa.gov/1FYcc8e.
  3. Perez F, Endimiani A, Ray AJ, et al. Carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae across a hospital system: Impact of post-acute care facilities on dissemination. J Antimicrob Chemother 2011;65:1807–18.
  4. CDC. Healthcare Associated Infections: Facilities/Settings: Carbapenem-resistant Enterobacteriaceae (CRE) Infection: http://1.usa.gov/1DnNH67.
  5. Won SY, Munoz-Price LS, Lolans K, et al. Emergence and rapid regional spread of Klebsiella pneumonia carbapenemase-producing enterobacteriaceae. Clin Infect Dis 2011;53:532–40.
  6. Thurlow CJ, Prabaker K, Lin MY, et al. Anatomic sites of patient colonization and environmental contamination with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae at long-term acute care hospitals. Infect Control Hosp Epidemiol 2013;34:56–61.

CRE Recommendations for Facilities, Clinicians

To meet the threat of CRE, here are some of the basic measures CDC recommends for health facilities and clinicians:

• Require and strictly enforce CDC guidance for CRE detection, prevention, tracking, and reporting.

• Make sure their lab can accurately identify CRE.

• Understand their prevalence in the facility and in the region.

• Identify colonized and infected patients in the facility and ensure precautions are implemented.

• When transferring a patient, require staff to notify the other facility about infections, including CRE.

• Participate in regional and facility-based efforts designed to stop the transmission of these organisms.

• Notify health departments of outbreaks.

Steps clinicians should take:

• Know if patients with CRE are hospitalized at your facility, and stay aware of CRE infection rates. Ask if a patient has received medical care somewhere else, including another country.

• Place patients currently or previously colonized or infected with CRE on Contact Precautions. Whenever possible, dedicate rooms, equipment, and staff to CRE patients.

• Wear a gown and gloves when caring for patients with CRE.

• Perform hand hygiene — use alcohol-based hand rub or wash hands with soap and water before and after contact with patient or their environment.

• Alert the receiving facility when you transfer a CRE patient, and find out when a patient with CRE transfers into your facility.

• Make sure labs immediately alert clinical and infection prevention staff when CRE are identified.

• Prescribe and use antibiotics wisely.

• Discontinue devices like urinary catheters as soon as no longer necessary.


  1. Centers for Disease Control and Prevention. Healthcare Associated Infections: Facilities/Settings: Carbapenem-resistant Enterobacteriaceae (CRE) Infection: http://1.usa.gov/1DnNH67