Passage from India: New Delhi strain hits U.S.
Contact precautions, assess travel history
Alarming public health officials, a highly drug-resistant gram negative bacterial strain that is emerging rapidly in hospitals in India has been detected in patients in three U.S. states. The New Delhi metallo-beta-lactamase (NDM-1) carries not only the threat of virtually untreatable infections, but contains a transferable plasmid that can impart drug resistance to other pathogens. This is the first report of NDM-1 in the United States.1
Though declining to identify the individual states involved, the Centers for Disease Control and Prevention reports that during January-June 2010 it identified Enterobacteriaceae NDM-1 isolates from three patients who had recently received medical care in India. The three isolates Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae all carry blaNDM-1, which confers resistance to all beta-lactam agents except aztreonam (a monobactam antimicrobial). However, all three of the isolates were aztreonam resistant, presumably by a different mechanism, the CDC reported.
Particularly disturbing is the identification of E. coli, since it essentially makes a common infection that is already potentially deadly impervious to another layer of antibiotics. The CDC has previously warned about the emergence of pan-resistant E. coli in the context of emerging carbapenem-resistant Klebsiella pneumoniae (CRKP).
"The big one to worry about is E. coli, simply because it is such a common cause of infections both in the hospital and the community," says Arjun Srinivasan, MD, a medical epidemiologist in the CDC's division of health care quality promotion (DHQP).
Trying to keep the proverbial genie in the bottle, the CDC is advising clinicians to be aware of the possibility of NDM-1-producing Enterobacteriaceae in patients who have received medical care in India and Pakistan. They should specifically inquire about this travel risk factor when carbapenem-resistant Enterobacteriaceae are identified, placing patients under contact precautions to prevent in-hospital transmission.
"We strongly believe with these carbapenem-resistant gram negatives we are still in a position in many places where we can help prevent transmission and potentially prevent the emergence of these organisms," says Alex Kallen, MD, MPH, outbreak response coordinator in the CDC DHQP. "We think it is a very high priority to work hard to prevent transmission of this organism."
Lab, infection control recommendations
The CDC asks that carbapenem-resistant isolates from patients who have received medical care within 6 months in India or Pakistan be forwarded through state public health laboratories to CDC for further characterization. Infection control interventions aimed at preventing transmission should be implemented when NDM-1-producing isolates are identified, even in areas where other carbapenem-resistance mechanisms are common among Enterobacteriaceae. These include recognizing carbapenem-resistant Enterobacteriaceae when cultured from clinical specimens, placing patients colonized or infected with these isolates in contact precautions, and in some circumstances, conducting point prevalence surveys or active-surveillance testing among other high-risk patients, the CDC recommends.
"Right now there are two issues one is clonal spread of the organism from the patient so an E. coli in one patient's urine gets directly transmitted to another patient," explained Brandi Limbago, PhD, a CDC scientist in the clinical and environmental microbiology branch of the DHQP. "But what we have seen with these NDM-1 producers in the United Kingdom is they can spread from the original bacteria say an E. coli to another specifies like a Klebsiella. So the plasmid itself is transmissible. You can have both clonal spread and horizontal spread of the genetic element."
The infection control measures are the same as those recommended last year for (CRKP).2 Similar to NDM-1, CRKP contains a transferable plasmid the KPC enzyme that can be transferred to other types of bacteria. Laboratory identification of the carbapenem- resistance mechanism is not necessary to guide treatment or infection control practices but should instead be used for surveillance and epidemiologic purposes. Carbapenem resistance and carbapenemase production conferred by NDM-1 is detected reliably with phenotypic testing methods currently recommended by the Clinical and Laboratory Standards Institute, including disk diffusion testing and the modified Hodge test, the CDC reports. Carbapenem resistance in all three of these isolates was detected in the course of routine testing
"The most important thing here is that they will test as resistant to the carbapenems, and for treatment and infection control that is the action point ," Limbago says. "They will be recognized but the additional screening to detect the actual [resistance] mechanism and detect this NDM-1 is not something that clinical labs by and large will be able to do. That's why we are asking for those isolates to be sent to CDC when they are from patients who received medical care in India."
The 'next big thing?'
The situation in India is not completely understood, but appears to be at least in part a classic case of antibiotic pressure spurring resistance. "Carbapenems are widely available in the Indian subcontinent, are widely used owing to prevalent cephalosporin resistance, and have doubtless exerted selection pressure," according to a public health alert issued in the United Kingdom, where NDM-1 is becoming increasingly common.3
"Microbiologists in India say up to 40% of their Enterobacteriaceae produce a metallo-beta lactamase, which is this class of enzyme," Limbago says. "That is a very, very high number. What we don't know is exactly which metallo-beta lactamase they are producing because they are not testing. They don't have systematic surveillance that we are aware of. "
The UK alert states that "carbapenems are the only antibiotics reliably active against many otherwise multi-resistant gram-negative opportunist bacteria, particularly those with extended-spectrum beta-lactamases. The growing emergence and diversity of carbapenemase producing strains is therefore a major concern. Treatment presents major challenges. Most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."
The three U.S. cases were apparently not that severe, though the CDC did not provide case reports. "The important thing to remember here is that a lot of times these are infections related to the use of devices like urinary catheters," Kallen says. "In those situations it is very difficult to sort out if things are really infections or just colonizations. I think in at least two of these cases, patients were felt to be colonized and weren't actually even offered therapy for these infections."
Of course, the concern is that more cases will appear, particularly those in patients who have no history of travel to India or Pakistan.
"That's what they are seeing in the UK," Limbago says. "Initially they were recognized in patients who were returning home from having received some kind of medical care in India or Pakistan. It was limited to those patients only, but now they are seeing it in people who do not have those exposures. So presumably it is transmitting and that is what we are concerned about and trying to prevent here. I only know of two deaths that were attributed to this infection presumably those were treatment failures."
David Patterson, MD, a health care epidemiologist at the University of Queensland Centre for Clinical Research in Brisbane, Australia, warned about the emergence of NDM-1 earlier this year in Atlanta at the Decennial International Conference on health-care associated infections.
"An 87-year-old woman whom I saw recently transferred to a hospital in Australia directly from the airport," Patterson said. "She had recently been in the state of Punjab in India, where she developed a foot ulcer and was treated at home by a general practitioner. She never went to a hospital in India. Her Klebsiella was [extensively] resistant to antibiotics, carbapenems among them. We found that she had the New Deli metallo-beta lactamase. Most [cases] so far have been sporadic occurrences, but India being the second biggest country in the world, this new [NDM-1] could well be the next big thing and may already be bigger than KPC. We just have no idea about surveillance of this particular resistance mechanism in India."
References
- Centers for Disease Control and Prevention. Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta -Lactamase United States, 2010. MMWR 2010;59:750.
- Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities. MMWR 2009; 58(10):256-260.
- Health Protection Agency. Multi-resistant hospital bacteria linked to India and Pakistan. Health Protection Report 2009;3(26):34. Available at http://www.hpa.org.uk/hpr/archives/2009/hpr2609.pdf.
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