ChiroACCESS Article

New Killer NDM-1 Superbugs Pose World Threat

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ChiroACCESS Editorial Staff



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April 27, 2011

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BacteriaThrough mutation and horizontal gene transfer, harmful bacteria once controlled through antibiotics are now virtually uncontrollable.  Years of excessive and indiscriminate use of antibiotics have contributed significantly to fostering the problem.  Existing antibiotics are now ineffective.  “The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising."  French and Chinese researchers both herald this as the "end of the antibiotic era".  The excessive use of antibiotics has been discussed and criticized in both medical and chiropractic professional literature for over half a century with little effect.

These superbugs are a new phenomena with first cases being reported in many countries in Asia and Europe during 2010. They are responsible for a high mortality rate.  The spread is rapid and is facilitated primarily through travel to India and sometimes by asymptomatic native travelers from India.  The first case was reported in the United States in June 2010. The CDC is emphasizing prevention including good sanitation practices and curtailing the excessive use of antibiotics.  Many of the extensive prevention strategies are applicable to chiropractic practice as well.

Prevention strategies from the CDC can be found here:
Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006

Note:  These mini-reviews are designed as updates and direct the reader to the full text of current research.  The abstracts presented here are no substitute for reading and critically reviewing the full text of the original research.  Where permitted we will direct the reader to that full text.

Does broad-spectrum {beta}-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria?  [Link]

J Antimicrob Chemother. 2011 Apr;66(4):689-92. Epub 2011 Jan 28.

Nordmann P, Poirel L, Toleman MA, Walsh TR.
Service de Bactériologie-Virologie, INSERM U914 'Emerging Resistance to Antibiotics', Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine et Université Paris-Sud, K.-Bicêtre, France.

The NDM-1 gene, first identified in Sweden in 2008 in Klebsiella pneumoniae from a patient hospitalized in New Delhi, encodes a metallo-ß-lactamase that inactivates all ß-lactams except aztreonam. This bla(NDM-1) gene has been identified in hospital-acquired bacterial species, such as K. pneumoniae, but also in the typical community-acquired species, Escherichia coli. This gene has been identified in strains that possess other resistance mechanisms contributing to their multidrug resistance patterns. It has been recently extensively reported from the UK, India and Pakistan and, albeit to a lesser extent, from a number of other countries worldwide. In most of the cases a link with the Indian subcontinent has also been established. To stem the onslaught of NDM producers, early identification of cases of NDM-related infections and prevention of their spread by implementing screening, hygiene measures and the isolation of carriers is needed.

Emergence of NDM-1-positive capsulated Escherichia coli with high resistance to serum killing in Japan.  [Link]

J Infect Chemother. 2011 Mar 25. [Epub ahead of print]

Yamamoto T, Takano T, Iwao Y, Hishinuma A.
Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,

The New Delhi metallo-ß-lactamase-1 (NDM-1) gene, bla (NDM-1), is an emerging plasmid-borne drug resistance gene, which encodes for exceptionally broad-spectrum ß-lactamase, being able to hydrolyze a wide variety of ß-lactams, including carbapenems, and was first reported in Klebsiella pneumoniae from a Swedish patient of Indian origin in 2009. It is widely distributed among Enterobacteriacae and has geographically exhibited extremely rapid and global spread. In this study, we characterized the bla (NDM-1)-positive ST38 Escherichia coli strain NDM-1 Dok01 (which was isolated from the blood of a 54-year-old Japanese inpatient, who had previously visited India), focusing on bacterial surface structures related to virulence. The E. coli culture contained colony variants, which developed a transparent smooth colony and a rough colony on blood agar plates. The smooth colony-forming cells (substrain M1) possessed a surface capsule and were resistant to serum killing, whereas rough colony-forming mutants (substrain B2) lacked a capsule (and a 5.3-kb plasmid) and were highly susceptible to serum killing. Reflecting the surface structural difference, substrain M1 was more flagellated and motile, whereas substrain B2 was less flagellated and apparently possessed straight pili 5 nm wide, which played a role in adherence to human intestinal cells and bacterial autoaggregation. Data suggest that the bla (NDM-1)-positive ST38 E. coli has emerged in Japan and that it is a capsulated bacterial pathogen with virulence potential in the blood stream.

Emergence of NDM-1-producing Enterobacteriaceae in Belgium.  [Link]

Antimicrob Agents Chemother. 2011 Mar 28. [Epub ahead of print]

Bogaerts P, Bouchahrouf W, Rezende R, Deplano A, Berhin C, Piérard D, Denis O, Glupczynski Y.
Laboratory of Bacteriology, Cliniques universitaires UCL de Mont-Godinne, Yvoir, Belgium; Laboratory of Bacteriology, Hopital universitaire ULB-Erasme, Brussels, Belgium; Laboratory of Clinical Microbiology, Universitair Ziekenhuis Brussel, Brussels, Belgium.

Five multidrug-resistant non-clonally related Enterobacteriaceae isolates were recovered in Belgium in 2010 from 3 patients who had been hospitalised in Pakistan, Montenegro and Serbia/Kosovo. NDM-1 was detected in each of the isolates in addition to several extended-spectrum ß-lactamases (CTX-M-15, SHV-12), plasmidic cephalosporinases (CMY-16, CMY-58), rRNA methylases (ArmA, RmtB), and Qnr genes (QnrA6, QnrB1, QnrB2). One patient died from uncontrolled sepsis while the two others recovered. No secondary cases occurred in any of the hospitals

Emergence of NDM-1-producing Acinetobacter baumannii in China.  [Link]

J Antimicrob Chemother. 2011 Mar 10. [Epub ahead of print]

Chen Y, Zhou Z, Jiang Y, Yu Y.
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.

Objectives To investigate the prevalence of bla(NDM-1) in Gram-negative bacilli in China. Methods A total of 11298 clinical Gram-negative bacilli, covering Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, were collected for PCR-based surveillance of bla(NDM-1) from 57 hospitals representing 18 provinces in China. For bla(NDM-1)-positive isolates, antibiotic susceptibilities were assessed and molecular typing was performed using PFGE. The genetic location of bla(NDM-1) was determined by analysis of PFGE profiles of S1 nuclease-digested genomic DNA and Southern blot hybridization. Plasmid transfer to E. coli recipients was investigated using filter mating and electroporation. Results Four A. baumannii isolates with bla(NDM-1) were identified in four different provinces in China: no positive isolates were detected among E. coli, K. pneumoniae and P. aeruginosa. These bla(NDM-1)-positive A. baumannii were resistant to all carbapenems and cephalosporins, and three remained susceptible to fluoroquinolones, aminoglycosides and colistin. The four NDM-1-producing A. baumannii were clonally diverse and carried bla(NDM-1) on different plasmids. Plasmids carrying bla(NDM-1) were successfully transferred from three of the four isolates to E. coli recipients, although the transconjugants and transformants were prone to lose the transferred plasmids after passage in the absence of ampicillin selection. Conclusions We describe the emergence of A. baumannii producing NDM-1 in China. Systemic surveillance network should be established for monitoring these resistant bacteria.

High burden of antimicrobial resistance in Asia.  [Link]

Int J Antimicrob Agents. 2011 Apr;37(4):291-5. Epub 2011 Mar 5.

Jean SS, Hsueh PR.
Departments of Intensive Care and Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan.

Antimicrobial resistance is associated with high mortality rates and high medical costs. Marked variations in the resistance profiles of bacterial and fungal pathogens as well as the quality of public hygiene have had a considerable impact on the effectiveness of antimicrobial agents in Asian countries. In Asia, one of the epicentres of antimicrobial drug resistance, there is an alarming number of antibiotic-resistant species, including penicillin- and erythromycin-resistant Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, multidrug-resistant (MDR) Acinetobacter baumannii, extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae (particularly mediated by CTX-M-9, CTX-M-14 and CTX-M-15), New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Enterobacteriaceae, MDR Salmonella enterica serotypes Choleraesuis and Typhi, carbapenem-resistant A. baumannii (OXA-58 and OXA-23 carbapenemases) and azole-resistant Candida glabrata. A few clones of MDR A. baumannii and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) have been widely disseminated in hospital settings in Asia, and K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains have been widely distributed in China. In addition, the emergence of extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) has illustrated the need for regular monitoring of resistance profiles of clinical isolates as well as the deliberative use of fluoroquinolones. Continuous surveillance of resistance data from clinical isolates as well as implementation of strict infection control policies in healthcare settings are required to mitigate the progression of antimicrobial resistance.

Multidrug-resistant Enterobacteriaceae including metallo-ß-lactamase producers are predominant pathogens of healthcare-associated infections in an Indian teaching hospital.  [Link]

Indian J Med Microbiol. 2011 Jan-Mar;29(1):22-7

Sarma JB, Bhattacharya PK, Kalita D, Rajbangshi M.
Northumbria Healthcare NHS Foundation Trust, England.

PURPOSE: A study was carried out in an Indian teaching hospital in 2009 to detect the rate of surgical site infections (SSI) and peripheral vascular access site infections.

MATERIALS AND METHODS: The study was a point-prevalence study involving over 300 patients. The presence of infection was determined according to the CDC criteria. Swabs were taken from the infected sites and identification and sensitivity were carried out using VITEK® 2 automated system. Characterisation of ß-lactamase was carried out at ARRML, Colindale, London.

RESULTS: The rate of SSI was 15% for the clean and clean-contaminated categories while that for the dirty contaminated category was 85% (NNIS risk index 0). Cultures yielded definite or probable pathogens from 64% (9/14) of the patients with SSI. In 1/3 rd of the cultures, Staphylococcus aureus was grown and the rest had Enterobacteriaceae, either extended-spectrum ß-lactamase (ESBL) producers or Amp-C hyperproducers and, alarmingly, three isolates were positive for newly recognised New Delhi metallo-ß-lactamase-1 (NDM-1). In medicine, 87% (n = 99) of the patients had a peripheral IV access device, 55% developed associated phlebitis/infection and, in seven, probable pathogens were isolated (Candida species and Escherichia coli producing ESBL and NDM-1, respectively, Staphylococcus aureus and Enterococcus faecium). All ESBL and metallo-ß-lactamase producers were resistant to multiple classes of antimicrobials, the latter being sensitive only to colistin and tigecycline. The study also found that all post-operative patients were on antibiotics, 92% on IV [213 defined daily doses (DDD)/100 post-op patients] limited mainly to the third-generation cephalosporins (26%) and aminoglycosides (24%) and imidazole derivatives (30%). In medicine, 83% (n = 82) were on IV antibiotics (123 DDD/100 bed-days), limited mainly to the third-generation cephalosporins (74%).

CONCLUSION: Indiscriminate use of antibiotics is a major problem predisposing patients to harm by multi-resistant pathogens. Carbapenems were in little use in this hospital, but the selection pressure exerted by cephalosporins and other unrelated classes was sufficient to select NDM-1-producing strains due to co-selection, suggesting a role of single plasmid carrying resistance genes to multiple classes.

[Arms racing between human beings and pathogens: NDM-1 and superbugs]. 

[Article in Chinese]

Sheng Wu Gong Cheng Xue Bao. 2010 Nov;26(11):1461-72.

Sun M, Zheng B, Gao GF, Zhu B.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Throughout human history, pandemic bacterial diseases such as the plague and tuberculosis have posed an enormous threat to human beings. The discovery of antibiotics has provided us with powerful arsenal for the defense against bacterial infections. However, bacteria are acquiring more and more resistance genes to shield off antibiotics through mutation and horizontal gene transfer. Therefore, novel antibiotics must be produced and the arms race between bacterial pathogens and antibiotics is becoming increasingly intense. Recently, researchers have found that plasmids carrying a new metallo-beta-lactamase gene, blaNDM-1, and many other antibiotics resistance genes can easily spread through bacterial populations and confer recipient stains resistance to nearly all of the current antibiotics. It is a threat to the human health and a great challenge for our medical science, which we are facing. We need to find new ways to fight and win this arms racing.

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