Carbapenem-resistant Enterobacteriaceae: A menace to our most vulnerable patients

DEADLY IMPACT ON THE MOST VULNERABLE

Regardless of the resistance pattern, Enterobacteriaceae are an important cause of health care-associated infections, including urinary and bloodstream infections in patients with indwelling catheters, pneumonia (often in association with mechanical ventilation), and, less frequently, infections of skin and soft tissues and the central nervous system.^29–31

Several studies have examined the clinical characteristics and outcomes of patients with CRE infections. Those typically affected are elderly and debilitated and have multiple comorbidities, including diabetes mellitus and immunosuppression. They are heavily exposed to health care with frequent antecedent hospitalizations and invasive procedures. Furthermore, they are often severely ill and require intensive care. Patients infected with carbapenem-resistant K pneumoniae, compared with those with carbapenem-susceptible strains, are more likely to have undergone organ or stem cell transplantation or mechanical ventilation, and to have had a longer hospital stay before infection.

They also experience a high mortality rate, which ranges from 30% in patients with nonbacteremic infections to 72% in series of patients with liver transplants or bloodstream infections.^32–37

More recently, CRE has been reported in other vulnerable populations, such as children with critical illness or cancer and in burn patients.^38–40

Elderly and critically ill patients with bacteremia originating from a high-risk source (eg, pneumonia) typically face the most adverse outcomes. With increasing drug resistance, inadequate initial antimicrobial therapy is more commonly seen and may account for some of these poor outcomes.^37,41

LONG-TERM CARE FACILITIES IN THE EYE OF THE STORM

A growing body of evidence suggests that long-term care facilities play a crucial role in the spread of CRE.

In an investigation into carbapenem-resistant A baumanii and K pneumoniae in a hospital system,³⁶ 75% of patients with carbapenem-resistant K pneumoniae were admitted from long-term care facilities, and only 1 of 13 patients was discharged home.

In a series of patients with carbapenem-resistant K pneumoniae bloodstream infections, 42% survived their index hospital stay. Of these patients, only 32% were discharged home, and readmissions were very common.³²

Admission from a long-term care facility or transfer from another hospital is significantly associated with carbapenem resistance in patients with Enterobacteriaceae.⁴² Similarly, in Israel, a large reservoir of CRE was found in postacute care facilities.⁴³

It is clear that long-term care residents are at increased risk of colonization and infection with CRE. However, further studies are needed to evaluate whether this simply refects an overlap in risk factors, or whether significant patient-to-patient transmission occurs in these settings.

INFECTION CONTROL TAKES CENTER STAGE

It is important to note that risk factors for CRE match those of various nosocomial infections, including other resistant gram-negative bacilli, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Candida species, and Clostridium difficile; in fact, CRE often coexist with other multidrug-resistant organisms.^44,45

Common risk factors include residence in a long-term care facility, an intensive care unit stay, use of lines and catheters, and antibiotic exposure. This commonality of risk factors implies that systematic infection-prevention measures will have an impact on the prevalence and incidence rates of multidrug-resistant organism infections across the board, CRE included. It should be emphasized that strict compliance with hand hygiene is still the foundation of any infection-prevention strategy.

Infection prevention and the control of transmission of CRE in long-term care facilities pose unique challenges. Guidelines from the Society for Healthcare Epidemiology and the Association for Professionals in Infection Control recommend the use of contact precautions for patients with multidrug-resistant organisms, including CRE, who are ill and totally dependent on health care workers for activities of daily living or whose secretions or drainage cannot be contained. These same guidelines advise against attempting to eradicate multidrug-resistant organism colonization status.⁴⁶

In acute care facilities, Best Infection Control Practices from the CDC and the Healthcare Infection Control Practices Advisory Committee encourage mechanisms for the rapid recognition and reporting of CRE cases to infection prevention personnel so that contact precautions can be implemented. Furthermore, facilities without CRE cases should carry out periodic laboratory reviews to identify cases, and patients exposed to CRE cases should be screened with surveillance cultures.⁴⁷

Outbreaks of CRE may require extraordinary infection control measures. An approach combining point-prevalence surveillance of colonization, detection of environmental and common-equipment contamination, with the implementation of a bundle consisting of chlorhexidine baths, cohorting of colonized patients and health care personnel, increased environmental cleaning, and staff education may be effective in controlling outbreaks of CRE.⁴⁸

Nevertheless, control of CRE may prove exceptionally difficult. A recent high-profile outbreak of carbapenem-resistant K pneumoniae at the National Institutes of Health Clinical Center in Maryland caused infections in 18 patients, 11 of whom died.⁴⁹ Of note, carbapenem-resistant K pneumoniae was detected in this outbreak in both respiratory equipment and sink drains. The outbreak was ultimately contained by detection through surveillance cultures and by strict cohorting of colonized patients, which minimized common medical equipment and personnel between affected patients and other patients in the hospital. Additionally, rooms were sanitized with hydrogen peroxide vapor, and sinks and drains where carbapenem-resistant K pneumoniae was detected were removed.

CHALLENGES IN THE MICROBIOLOGY LABORATORY

Adequate treatment and control of CRE infections is predicated upon their accurate and prompt diagnosis from patient samples in the clinical microbiology laboratory.⁵⁰

Traditional and current culture-based methods take several days to provide that information, delaying effective antibiotic therapy and permitting the transmission of undetected CRE. Furthermore, interpretative criteria of minimal inhibitory concentrations (MICs) of carbapenems recently required readjustment, as many KPC-producing strains of K pneumoniae had MICs below the previous breakpoint of resistance. In the past, this contributed to instances of “silent” dissemination of KPC-producing K pneumoniae.⁵¹

In contrast, using the new lower breakpoints of resistance for carbapenems without using a phenotypic test such as the modified Hodge test or the carbapenem-EDTA combination tests will result in a lack of differentiation between various mechanisms of carbapenem resistance.^28,52,53 This may be clinically relevant, as the clinical response to carbapenem therapy may vary depending on the mechanism of resistance.

GENERAL PRINCIPLES APPLY

In treating patients infected with CRE, clinicians need to strictly observe general principles of infectious disease management to ensure the best possible outcomes. These include:

Timely and accurate diagnosis, as discussed above.

Source control, which should include drainage of any infected collections, and removal of lines, devices, and urinary catheters.

Distinguishing between infection and colonization. CRE are often encountered as urinary isolates, and the distinction between asymptomatic bacteriuria and urinary tract infection may be extremely difficult, especially in residents of long-term care facilities with chronic indwelling catheters, who are thegroup at highest risk of CRE colonization and infection. Urinalysis may be helpful in the absence of pyuria, as this rules out an infection; however, it must be emphasized that the presence of pyuria is not a helpful feature, as pyuria is common in both asymptomatic bacteriuria and urinary tract infection.⁵⁴ Symptoms should be carefully evaluated in every patient with bacteriuria, and urinary tract infection should be a diagnosis of exclusion in patients with functional symptoms such as confusion or falls.

Selection of the most appropriate antibiotic regimen. While the emphasis is often on the antibiotic regimen, the above elements should not be neglected.