On Equilibrium & Balance in Your Microbial Universe

Two recent studies that shed light on the inner workings of our bacterial ecosystems, otherwise known as our microbiota, have me musing on the nature of disease and pathology, of harmony and balance.

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Bacterial Superpowers

The emergence of the New Delhi Metallo-Beta Lactamase (NDM-1) gene in bacteria commonly associated with nosocomial, or hospital-borne, infections this past summer has sparked the latest fears of a “superbug” waging war in hospitals around the world. It may sound like talking about nosocomial infections tends to the hyperbole, with an abundance of unnecessary war-associated terminology. Indeed, there does seem to be an “arms race” of sorts in that the weapons that we have long used again microbes, typically antibiotics and antivirals, are becoming less effective in the face of evolving microbial antibiotic resistance. Penicillin was deemed the “magic bullet” upon its introduction in medicine in XXX; unfortunately, we are rapidly running out of such panacea. NDM-1 is just the latest antibiotic-resistance gene and seems poised to do the most damage to our already beleaguered arsenal of antibiotics.

The narrative of the spread of NDM-1 warrants special interest in particular due to its association with a unique medical trend that has recently emerged in the past few years. Medical tourism has  quickly evolved into a viable alternative for Western consumers seeking cheap medical treatment options (1). In addition, there are also the unlucky few who have fallen ill overseas and returned with unwelcome bacterial souvenirs. The global dissemination of the NDM-1 gene in such an extraordinarily short timespan is attributed to these global travelers. As such, the gene has been found in clinical isolates ranging from India, Pakistan, Bangladesh, Iraq, the United Kingdom, France, and Canada, and research strongly implicates patient carriage of this gene with having received recent medical treatment in the Indian subcontinent (2).

As to the discovery of this novel gene, a Swedish patient of Indian origin returned to Sweden  following a trip to New Delhi after which he had been hospitalized with a large gluteal abscess. In this case, this patient had unfortunately fallen gravely ill from previously existing medical conditions, not as a result of cosmetic surgery. He returned home with an unwelcome souvenir, a urinary tract infection (UTI), that yielded a clinical isolate of Klebsiella pneumoniae. The UTI was unremarkable in that the bacterial load in a urine culture was quite low, but the bacterial isolate truly was unique.

Molecular typing of the isolate indicated that it carried a novel metallo-beta-lactamase (MBL) gene through strangely lacked other common MBL genes. Most unnerving was the isolate’s wide-spread broad resistance to antibiotics upon completion of drug susceptibility profiles. A host of commonly used antibiotics targeting the beta-lactamase systems, including the heavy hitting cephalosporins Ceftazidime, Cefotaxime and Cefepime, were shown to be ineffective against against the Klebsiella pneumoniae clinical isolate of this patient. The isolate was highly resistant not only to beta-lactams but also to aminoglycosides, quinolones, tetracycline, nitrofurantoin, and cotrimoxazole (3).

As of now, the gene is limited to bacteria within the Enterobacteriaceae family, including  the pathogens Klebsiella pneumoniae, Escherichia coli and Enterobacter spp. Regrettably, it is these very organisms that are the source of the majority of nosocomial infections causing considerable morbidity and mortality (4). These opportunistic bacteria tend to cause secondary infections in urinary and respiratory tracts as well as in wounds, and they happen to do so very well.

The international travels of a previously localized pathogen, disease vector or even a pathogenic gene is not uncommon. Globalization has been quite the agreeable force in the spread of disease. The ease of international travel, the necessity of migrating for one’s economic livelihood and the global food trade are just a few examples of the incredible effect that globalization has had upon the geographical spread and introduction of infectious diseases, as well as antibiotic resistance. Diseases previously confined to specific locales are suddenly global travelers, as was the case with hookworm and malaria in Africa prior to their introduction to the Americas during the slave trade (5). The importance of establishing and maintaining rigorous syndromic surveillance sites, such as ProMed, to monitor emerging disease outbreaks, proliferation of antibiotic resistance genes, traveling of disease vectors, and their diffusion across country borders is more crucial than ever.

References

(1) Konrad W. (2009, Mar 20)  Going Abroad to Find Affordable Health Care. New York Times. Retrieved February 26th, 2011 from http://www.nytimes.com/2009/03/21/health/21patient.html
(2) Kumarasamy et al. (2010) Emergence of a new antibiotic resistance in India, Pakistan, and the UK: a molecu- lar, biological, and epidemiological study. Lancet Infect Dis.10: 597–602
(3) Tijet et al. (2011) New Delhi Metallo- ?-Lactamase, Ontario, Canada. EID Journal Online. 17(2): http://www.cdc.gov/eid/content/17/2/306.htm
(4) Fraser et al. (2010) Enterobacter Infections. Retrieved February 26, 2011 from http://emedicine.medscape.com/article/216845-overview
(5 ) Palmer P and Reeder MM. The Imaging of Tropical Diseases: With Epidemiological, Pathological and Clinical Correlation Volume 2. 2nd ed. Birkhäuser, 2001. Accessed here.