
 
 A particularly dangerous type of CRE bacteria is on the rise in the U.S. (Courtesy of CDC) 
 
 This post has been updated. 
 
 A particularly dangerous superbug, dubbed the "phantom menace" by scientists, is on the rise in the United States, according to a report Thursday by the Centers for Disease Control and Prevention. 
 
 This superbug's strains belong to the family of bacteria known as CRE, which are difficult to treat because they are often resistant to most antibiotics. They are often deadly, too, in some instances killing up to 50 percent of patients who become infected, according to the CDC. Health officials have called CRE among the country's most urgent public health threats. 
 
 The target of Thursday's report is relatively new. Unlike more common types of CRE, it carries a plasmid, or mobile piece of DNA, with an enzyme that breaks down antibiotics. And what makes these bacteria even more dangerous is their ability to transfer that plasmid--and that antibiotic resistance--to normal bacteria that are present in our bodies. 
 
 [Amid superbug worries, these states have the highest antibiotic prescribing rates] 
 
 This type of CRE has had a lower profile because it's actually less antibiotic-resistant than other more common types of CRE. As a result, it hasn't been a frequent focus of testing and has largely escaped detection by health officials, prompting some researchers to dub it "the phantom menace." 
 
 "This is a tricky drug-resistant bacteria, and it isn't easily found," CDC Director Thomas Frieden said in an interview. "What we're seeing is an assault by the microbes on the last bastion of antibiotics." 
 
 Bacteria develop antibiotic resistance in two ways. 
 
 Many can evolve their own genome in ways that deactivate antibiotics, although that ability can't be shared with pathogens outside their own family. 
 
 Yet other bacteria rely on a shortcut: They get infected with a plasmid carrying the resistance gene. That makes them more dangerous because plasmids can make copies of themselves and transfer within a family of bugs and as well as jump to other families of bacteria, which can then "catch" the resistance directly without having to develop it through evolution. 
 
 In a related alarming development, Danish researchers announced Thursday that a dangerous new superbug gene discovered in China two weeks ago had been found in bacteria infecting one person in Denmark. The gene makes the bacteria resistant to colistin, the antibiotic of last resort. And similar to the 'phantom menace' type of CRE, the gene is contained in a plasmid. 
 
 Experts warned that the latest development was frightening. "History shows that these mobile resistance genes can spread around the world quickly, silently riding in people, animals and food," said Lance Price, director of the Antibiotic Resistance Action Center at George Washington University's Milken Institute of Public Health, in a statement. 
 
 He said the news that the superbug gene first found in China has now turned up in Denmark "suggests that this scenario is playing out in real time," he said. 
 
 [A superbug emerges in China] 
 
 CDC received reports counting at least 43 patients in 19 states with this type of CRE superbug between June 2010 and August 2015. All cases were confirmed by CDC. Although the numbers are relatively small, Frieden said they are "just the tip of the iceberg." There was one patient with this type of superbug in 2010 and 11 patients each year in 2013, 2014 and 2015. 
 
 Most U.S. clinical laboratories that test for CRE organisms wouldn't identify this particular type of bacteria because it's not part of standard testing. CDC changed its definition of the organism in January to help increase detection. 
 
 CRE stands for carbapenem-resistant Enterobacteriaceae. 
 
 Read more: 
 
 CDC says ‘nightmare bacteria’ a growing threat 
 
 Extra funding sought to fight antibiotic resistant bacteria 
 
 One day, doctors might prescribe viruses instead of antibiotics 
 
 White House opens antibiotic summit 
 
 Chipotle CEO pledges to make restaurants ‘safest place to eat.’ Here’s his plan. ||||| Notes from the Field: Carbapenem-resistant Enterobacteriaceae Producing OXA-48-like Carbapenemases — United States, 2010–2015 
 
 Please note: An erratum has been published for this article. To view the erratum, please click here. 
 
 Meghan Lyman, MD1,2; Maroya Walters, PhD2; David Lonsway, MMSc2; Kamile Rasheed, PhD2; Brandi Limbago, PhD2; Alexander Kallen, MD2 
 
 Carbapenem-resistant Enterobacteriaceae (CRE) are bacteria that are often resistant to most classes of antibiotics and cause health care–associated infections with high mortality rates (1). Among CRE, strains that carry plasmid-encoded carbapenemase enzymes that inactivate carbapenem antibiotics are of greatest public health concern because of their potential for rapid global dissemination, as evidenced by the increasing distribution of CRE that produce the Klebsiella pneumoniae carbapenemase and the New Delhi metallo-β-lactamase. Newly described resistance in Enterobacteriaceae, such as plasmid-mediated resistance to the last-line antimicrobial colistin, recently detected in China, and resistance to the newly approved antimicrobial, ceftazidime-avibactam, identified from a U.S. K. pneumoniae carbapenemase-producing isolate, highlight the continued urgency to delay spread of CRE (2,3). Monitoring the emergence of carbapenemases is crucial to limiting their spread; identification of patients carrying carbapenemase-producing CRE should result in the institution of transmission-based precautions and enhanced environmental cleaning to prevent transmission.* The OXA-48 carbapenemase was first identified in Enterobacteriaceae in Turkey in 2001 (2), and OXA-48-like variants have subsequently been reported around the world. The first U.S. reports of OXA-48-like carbapenemases were published in 2013 and included retrospectively identified isolates from 2009 (3) and two isolates collected in 2012 from patients in Virginia who had recently been hospitalized outside the United States (4). Although there are limited additional published reports from the United States (5), CDC continues to receive reprots of these organisms. This report describes patients identified as carrying CRE producing OXA-48-like carbapenemases in the United States during June 2010–August 2015. 
 
 CDC received reports of 52 CRE isolates producing OXA-48-like carbapenemases collected from 43 patients in 19 states during June 2010–August 2015 (Figure); seven of these isolates were identified retrospectively from six patients. Eight isolates from four patients were part of two different clusters in the United States during 2014. The number of patients from whom CRE isolates producing OXA-48-like carbapenemases were identified ranged from one in 2010 to 11 per year in 2013, 2014, and 2015. Thirty-five patients (81%) had OXA-48-like carbapenemase identified from K. pneumoniae isolates, seven (16%) from Escherichia coli isolates, one (2%) from an Enterobacter aerogenes isolate, and one (2%) from a Klebsiella ozaenae isolate; two of which were isolates of different species from a single patient. Isolates with both New Delhi metallo-β-lactamase and OXA-48-like carbapenemase genes were obtained from five patients (12%). The most common sources were urine (22 patients [51%]) and respiratory specimens (nine patients [21%]). 
 
 The median age among 35 (81%) patients for whom age was reported was 70 years (range = 29–91 years). Among 29 patients for whom a travel history was available, 19 (66%) had traveled internationally during the year before specimen collection, and 16 (55%) were hospitalized outside the United States for ≥1 night; these percentages increased to 76% and 64%, respectively, when cases associated with the two domestic clusters were excluded. India was the most frequently reported destination among patients with international travel (11 of 19 patients) and international hospitalization (nine of 16). 
 
 CRE producing OXA-48-like carbapenemases have demonstrated the ability to spread in other countries (6) and cause outbreaks in health care settings. Factors potentially contributing to the spread of these organisms include the high transfer efficiency of the plasmid containing OXA-48-like genes (6) and challenges in identifying these organisms. These challenges in identification occur because of the limited testing for CRE resistance mechanisms in U.S. clinical laboratories and the different susceptibility profiles of these organisms compared with other carbapenemase-producing CRE, making them difficult to differentiate from CRE that do not produce carbapenemases (organisms producing OXA-48-like carbapenemases might be susceptible to third generation cephalosporins). The modification of the CDC CRE surveillance definition in January 2015 to include organisms that are resistant to ertapenem or that possess a carbapenemase gene should improve sensitivity for detecting OXA-48-producing CRE (7). 
 
 Although clusters of CRE expressing OXA-48-like carbapenemases suggest transmission has occurred in the United States, the majority of identified patients were reported to have had exposure to health care outside the United States. This is consistent with recommendations in the CDC Health Advisory from February 2013 (8), which sought to prevent transmission of isolates producing non-K. pneumoniae carbapenemases by improving their detection in patients recently hospitalized outside the United States. Recommendations include determining the mechanism of resistance for any CRE isolated from such patients and considering CRE screening of these patients on admission. 
 
 1Epidemic Intelligence Service, CDC; 2Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC. 
 
 Corresponding author: Meghan M. Lyman, mmlyman@cdc.gov, 404-639-4241. 
 
 References 
 
 Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011;53:60–7. Liu Y, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet. Epub Nov 18, 2015. Humphries RM, Yang S, Hemarajata P, et al. First report of ceftazidime-avibactam resistance in a KPC-3-expressing Klebsiella pneumoniae isolate. Antimicrob Agents Chemother 2015;59:6605–7. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 2012;67:1597–606. Lascols C, Peirano G, Hackel M, Laupland KB, Pitout JD. Surveillance and molecular epidemiology of Klebsiella pneumoniae isolates that produce carbapenemases: first report of OXA-48-like enzymes in North America. Antimicrob Agents Chemother 2013;57:130–6. Mathers AJ, Hazen KC, Carroll J, et al. First clinical cases of OXA-48-producing carbapenem-resistant Klebsiella pneumoniae in the United States: the "menace" arrives in the new world. J Clin Microbiol 2013;51:680–3. Doi Y, O'Hara JA, Lando JF, et al. Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae. Emerg Infect Dis 2014;20:163–5. Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect 2014;20:821–30. CDC. FAQs about choosing and implementing a CRE definition. CDC Healthcare-associated infections. Atlanta, GA: US Department of Health and Human Services, CDC. Available at http://www.cdc.gov/hai/organisms/cre/definition.html. CDC Health Alert Network. New carbapenem-resistant enterobacteriaceae warrant additional action by healthcare providers. Atlanta, GA: US Department of Health and Human Services, CDC; 2013. Available at http://emergency.cdc.gov/han/han00341.asp. ||||| OXA-48-type carbapenem-hydrolysing class D β-lactamases are increasingly reported in enterobacterial species. To date, six OXA-48-like variants have been identified, with OXA-48 being the most widespread. They differ by a few amino acid substitutions or deletions (one to five amino acids). The enzymes hydrolyse penicillins at a high level and carbapenems at a low level, sparing broad-spectrum cephalosporins, and are not susceptible to β-lactamase inhibitors. When combining permeability defects, OXA-48-like producers may exhibit a high level of resistance to carbapenems. OXA-163 is an exception, hydrolysing broad-spectrum cephalosporins but carbapenems at a very low level, and being susceptible to β-lactamase inhibitors. The bla(OXA-48)-type genes are always plasmid-borne and have been identified in association with insertion sequences involved in their acquisition and expression. The current spread of the bla(OXA-48) gene is mostly linked to the dissemination of a single IncL/M-type self-transferable plasmid of 62 kb that does not carry any additional resistance gene. OXA-48-type carbapenemases have been identified mainly from North African countries, the Middle East, Turkey and India, those areas constituting the most important reservoirs; however, occurrence of OXA-48 producers in European countries is now well documented, with some reported hospital outbreaks. Since many OXA-48-like producers do not exhibit resistance to broad-spectrum cephalosporins, or only decreased susceptibility to carbapenems, their recognition and detection can be challenging. Adequate screening and detection methods are therefore required to prevent and control their dissemination. ||||| This image shows two rod-shaped bacteria called Klebsiella pneumoniae that are resistant to treatment with the antibiotic drug called carbapenem. In this image, the mustard-colored bacteria are interacting with the green-colored human white blood cell. 
 
 Health experts are keeping a close eye on a type of antibiotic-resistant bacteria called CRE that, while still rare, has the potential to become more widespread in the United States. This type of bug includes some strains of Escherichia coli and other bacteria. 
 
 A new report released on Thursday said that in the past five years, researchers have identified 43 patients in the United States who became sick with infections from one type of CRE. (The name is an abbreviation for "carbapenem-resistant Enterobacteriaceae," meaning the bacteria are part of a group called Enterobacteriaceae and are resistant to treatment with antibiotics called carbapenems.) 
 
 These cases all involved CRE that share a particular method of defeating the antibiotics: they have enzymes called OXA-48-like carbapenemases that break down the drugs, said the report from the Centers for Disease Control and Prevention. Other types of CRE have different methods of resisting the antibiotic. [6 Superbugs to Watch Out For] 
 
 This particular type of CRE that is the focus of the new report is "noteworthy" because the enzyme that thwarts the antibiotic is encoded on a piece of genetic material called a plasmid, "which can actually move from one bacteria to another," said Dr. William Schaffner, an infectious disease specialist and professor of preventive medicine at Vanderbilt University Medical Center in Nashville, Tennessee, who was not involved with the CDC report. 
 
 At the moment, this whole group of CRE bacteria is of great interest to researchers, Schaffner told Live Science. 
 
 Recently, for example, researchers discovered bacteria in China whose plasmids give them resistance to an antibiotic called colistin, he said. Some doctors consider colistin one of the last lines of defense against certain "superbugs." 
 
 The bacteria found in China and the ones in the new report — which both have key resistance genes contained on plasmids — "are of greatest public health concern because of their potential for rapid global dissemination," the researchers wrote in the new report. 
 
 Still, Schaffner stressed that, at the moment, these infections are not something the general public needs to worry about. But microbiologists, public health officials and infectious disease specialists are paying attention, he said. 
 
 Researchers have seen a few small clusters of cases around the country, which indicate that the infection likely spread in a hospital, Schaffner said. 
 
 In the new report, the CDC researchers noted that many of the patients with this particular type of infection had recently traveled out of the country, with India being the most frequent travel destination. In addition, among the patients who reported traveling abroad, 16 had been hospitalized outside of the United States, the report said, suggesting that foreign hospitals are a potential source of some infections. 
 
 The CDC is also tracking infections that come from other types of CRE. For example, there have been 118 cases in the United States of infections involving a certain enzyme, different from the one found in the bacteria that are the focus of Thursday's report, the CDC said. 
 
 Carbapenems are not considered the last line of defense against Enterobacteriaceae infections, meaning that if these drugs don't work, there are still other antibiotics available. However, the emerging resistance is still concerning to experts. This resistance reduces the number of antibiotics that doctors can use to treat these infections, Schaffner said. Doctors need multiple antibiotics available, and the more options there are, the better, he said. 
 
 To reduce the problems associated with antibiotic resistance, doctors and patients need to join together to be more prudent about using antibiotics, Schaffner said. 
 
 Follow Sara G. Miller on Twitter @SaraGMiller. Follow Live Science @livescience, Facebook & Google+. Originally published on Live Science.
– The latest strains of antibiotic-resistant bacteria to give researchers sleepless nights aren't the most common—or even the most antibiotic-resistant—but they have an ability that could make them a serious danger to public health. They contain enzymes known as "OXA-48-like carbapenemases" that can break down antibiotics and transfer that ability to normal bacteria in the body through mobile pieces of DNA, reports the Washington Post. and Live Science. The enzymes have been nicknamed the "phantom menace" by researchers because they can be tough to detect. In a report issued this week, the CDC says it identified 43 cases in the US involving the superbug between June 2010 and August of this year, mainly involving people who had traveled overseas, though some cases are thought to have been transmitted in the US. "This is a tricky drug-resistant bacteria, and it isn't easily found," CDC Director Thomas Frieden tells the Post. "What we're seeing is an assault by the microbes on the last bastion of antibiotics." The number of cases is small but rising, Frieden says, warning that what has been detected so far could just be the "tip of the iceberg." An infectious disease specialist tells Live Science that while the bacteria shouldn't be a major worry for the general public right now, doctors and patients should be aware that the best way to combat antibiotic resistance is to try to be more sparing in the use of antibiotics. (A mutation spreading in China has prompted warnings of an "antibiotic apocalypse.")