Carbapenem-Resistant Enterobacteriaceae Containing New Delhi Metallo-Beta-Lactamase in Two Patients — Rhode Island, March 2012

U.S. and international efforts to control carabapenem-resistant Enterobacteriaceae (CRE) are critical to protect public health. Clinicians caring for patients infected with such organisms have few, if any, therapeutic options available. CRE containing New Delhi metallo-beta-lactamase (NDM), first reported in a patient who had been hospitalized in New Delhi, India, in 2007 (1), are of particular concern because these enzymes usually are encoded on plasmids that harbor multiple resistance determinants and are transmitted easily to other Enterobacteriaceae and other genera of bacteria (2). A urine specimen collected on March 4, 2012, from a patient who recently had been hospitalized in Viet Nam, but who was receiving care at a hospital in Rhode Island, was found to have a Klebsiella pneumoniae isolate containing NDM. The isolate was susceptible only to tigecycline, colistin, and polymyxin B. Point-prevalence surveys of epidemiologically linked patients revealed transmission to a second patient on the hematology/oncology unit. These two cases bring to 13 the number of cases of NDM reported in the United States. After contact precautions were reinforced and environmental cleaning was implemented, no further cases were identified. Similarly aggressive infection control efforts can limit the spread of NDM in acute-care medical facilities (3,4).

A Rhode Island resident returned to her native Cambodia in May 2011. While there, she was diagnosed with spinal cord compression and was hospitalized December 20–30 in Ho Chi Minh City, Vietnam, where an indwelling catheter was placed in her atonic bladder. She received ceftazidime and metronidazole during that hospitalization. On January 6, 2012, she returned to Rhode Island and was hospitalized the same day. Lymphoma was diagnosed; she underwent chemotherapy and required prolonged bladder catheterization. On January 13, a urine culture grew an extended spectrum, beta-lactamase–producing Escherichia coli. She was placed on contact precautions requiring visitors to her room to don gowns and gloves. She was allowed to walk in the hallway if she was continent, performed hand hygiene before leaving the room, and wore a clean garment, but was incontinent at least once while outside her room. On February 15, a urine culture grew two strains of carbapenemase-producing K. pneumoniae. From hospital admission through March 3, the patient was administered a range of antibiotics, including ceftriaxone, cefazolin, ciprofloxacin, metronidazole, piperacillin/tazobactam, meropenem, colistin, fluconazole, and oral and intravenous vancomycin. On March 4, a second urine culture grew carbapenemase-producing K. pneumoniae. The modified Hodge test, a laboratory test for the presence of carbapenemase, was weakly positive. The patient was asymptomatic; her catheter was replaced and a repeat urine culture was negative, without antibiotic therapy.

In light of the patient's unusual travel history and the weakly positive modified Hodge test, the isolate was sent to CDC and was confirmed as CRE containing NDM. It was susceptible to tigecycline (minimum inhibitory concentration [MIC] = 2 µg/mL), colistin, and polymyxin B (MIC = 1 µg/mL), but resistant to 24 antimicrobials, including aztreonam and several antimicrobial combinations, by cation-adjusted Mueller-Hinton broth dilution. After receiving this information, isolation precautions were changed for this patient, prohibiting her from walking outside her room and limiting diagnostic tests or procedures requiring her to leave her room. The medical director and staff members of the hospital infection control department educated medical and nursing staff members about NDM and needed precautions. Topics reviewed included the epidemiology of CRE, specifically NDM, and modes of transmission, gastrointestinal carriage, and limited treatment options for infected patients. The patient was discharged March 26. A stool specimen collected April 3 was negative for carbapenemase-producing K. pneumoniae using phenotypic methods (5). K. pneumoniae isolates from the urine specimen collected February 15 also were sent to CDC; one was found to be indistinguishable from the isolate from March 4, the other was an epidemiologically related subtype. Surveillance cultures were tested using CDC-recommended methods for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute-care facilities (5,6).

Results were negative for a rectal swab obtained March 30 from the next patient who occupied the same hospital room on March 28. However, one of seven patients on the same hematology/oncology unit at the time of the index patient's stay grew a carbapenemase-producing K. pneumoniae from a rectal swab specimen collected March 30. The specimen was confirmed as containing NDM at CDC. Molecular fingerprinting using pulsed-field gel electrophoresis revealed that it was indistinguishable from the K. pneumoniae isolates collected February 15 and March 4 from the index patient. Point-prevalence surveys of rectal swabs or stool specimens from the five additional patients from the hematology/oncology unit collected April 5 and 6 and from 14 patients on April 23 did not detect carbapenemase-producing K. pneumoniae. All patients housed on the hematology/oncology unit as the two patients harboring CRE were identified and their charts were flagged so that they will have rectal swab screening cultures the first time they are readmitted. Environmental services staff members conducted additional cleaning of patient rooms and hallway high-touch surfaces (e.g., door knobs and hand rails) on the hematology/oncology unit on April 13. The index patient and second patient each were cared for by separate medical teams, of which no physicians or nurse practitioners had provided care to both patients. Nursing records identified 23 nursing staff members of the hematology/oncology unit who had cared for both patients between March 12 and 26; one agreed to be screened by rectal culture and was found to be negative.

Reported by

Erica J. Hardy, MD, Leonard A. Mermel, DO, Dept of Medicine, Kimberle C. Chapin, MD, Dept of Pathology, Warren Alpert Medical School of Brown Univ; Cindy Vanner, Rhode Island Dept of Health. Ekta Gupta, MD, Dept of Medicine, Boston Univ School of Medicine, Massachusetts. Corresponding contributor: Leonard A. Mermel, lmermel@lifespan.org, 401-444-2608.

Editorial Note

Since the first report in 2009, cases involving NDM-producing Enterobacteriaceae have been reported in every continent except South America and Antarctica (7). Among 29 cases in the United Kingdom, at least 17 involved patients who had traveled to India or Pakistan, among whom 14 had been hospitalized in one of those countries (8). Although medical care in the Indian subcontinent was associated with many early reports, recent cases have been described involving persons who traveled to endemic regions* but were not hospitalized (7). The plasmid-carrying NDM is highly transmissible to other bacteria, and bacteria carrying NDM can colonize the gastrointestinal systems of humans for prolonged periods and can spread through contamination of water sources and environmental surfaces (7). Not surprisingly, nosocomial spread also has been documented outside of the Indian subcontinent. Of 77 cases of infection or colonization with CRE containing NDM in Europe, 13 might have been hospital-acquired in Europe (9). Spread of NDM in other parts of Asia also has been reported, including four patients in South Korea without travel history (10), similar to recent reports elsewhere (7).

Based on currently available information, a robust infection control effort is needed to limit or slow the spread of all CRE, including NDM, at the local, national, and international levels. High rates of hand hygiene compliance and adherence to contact precautions, including the use of dedicated devices for monitoring vital signs, are essential, along with minimizing the use of invasive devices and antibiotics. A robust antimicrobial stewardship program can assist in limiting unnecessary antibiotic exposure among hospitalized patients. If NDM is identified, point-prevalence surveys of patients on the affected hospital or skilled nursing facility unit are important to identify patients carrying CRE containing NDM (7). A recent preliminary report from a U.S. hospital documented that an intensive-care unit–based, active surveillance program using nucleic acid amplification for detecting CRE colonization, coupled with contact precautions for all colonized patients, was able to achieve a sustained 53% reduction in the prevalence of CRE colonization across 100 beds in the unit (BP Currie, MD, Montefiore Medical Center, personal communication, May 14, 2012). Because patients frequently are transferred to and from acute- and chronic-care facilities, successful prevention and control of NDM most likely will be achieved by using a regional approach (7), as has been done in Israel (3,4). Because colistin often is the only available antibiotic to treat CRE containing NDM, robust infection control efforts are needed to slow the spread of NDM in the United States.

Acute- and chronic-care facilities should have a written plan that clearly describes how they will detect CRE and limit transmission before it becomes endemic. Clinical specimens will identify only a fraction of cases. Screening cultures of contacts are important during an outbreak. Surveillance cultures might be used in acute-care or long-term–care facilities that admit few patients colonized or infected with such microbes to alert infection control staff members to implement aggressive containment strategies, as noted in the updated CDC guidance.† As described in this report, point-prevalence surveys can identify patients colonized with CRE. Identifying CRE at the facility level and reporting to state departments of health should trigger regional efforts to enhance detection and control of such multiresistant microbes. The continued global emergence of NDM and the manner in which it has become endemic in some regions highlights the importance of preventing the spread of NDM (2–4,6,7). Robust local, regional, and national detection and control efforts will be required to do so.

Acknowledgments

Gary Furtado, Patty McAuley, Meredith Hurley, Rhode Island Hospital. Antimicrobial Resistance and Characterization Laboratory, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

References

1. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53:5046–54.
2. Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging NDM carbapenemases. Trends Microbiol 2011;19:588–95.
3. Ben-David D, Maor Y, Keller N, et al. Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant Klebsiella pneumoniae infection. Infect Control Hosp Epidemiol 2010;31:620–6.
4. Schwaber MJ, Lev B, Israeli A, et al; Israel Carbapenem-Resistant Enterobacteriaceae Working Group. Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. Clin Infect Dis 2011;52:848–55.
5. CDC. Laboratory protocol for detection of carbapenem-resistant or carbapenemase-producing, Klebsiella spp. and E. coli from rectal swabs. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/hai/pdfs/labsettings/klebsiella_or_ecoli.pdf. Accessed June 18, 2012.
6. CDC. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities. MMWR 2009;58:256–60.
7. Wilson ME, Chen LH. NDM-1 and the role of travel in its dissemination. Curr Infect Dis Rep 2012;14:213–26.
8. Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010;10:597–602.
9. Struelens MJ, Monnet DL, Magiorakos AP, Santos O'Connor F, Giesecke J; European NDM-1 survey participants. New Delhi metallo-beta-lactamase 1-producing Enterobacteriaceae: emergence and response in Europe. Euro Surveill 2010;15:pii=19716.
10. Kim MN, Yong D, An D, et al. Nosocomial clustering of NDM-1-producing Klebsiella pneumoniae sequence type 340 strains in four patients at a South Korean tertiary care hospital. J Clin Microbiol 2012;50:1433–6.