A Closer Look At Multidrug-Resistant Organisms And Nosocomial Pathogens

E. Giannin Perez, DPM, MS, Alicia Attanasio and Khurram H. Khan, DPM

   An example of this is colistin, a polymyxin antibiotic discovered in the 1940s and specifically used for Gram-negative infections.15 It works by competitively displacing divalent cations (Mg and Ca), which disrupts the outer membrane and creates leakage leading to cell lysis and subsequent cell death. Colistin has a narrow antibacterial spectrum but offers activity against multidrug resistant, Gram-negative organisms.15 Unfortunately, it carries with it a high risk of nephrotoxicity and neurotoxicity.

   A 2010 study by Lim and colleagues looked at the growing rate of resistance of Gram-negative bacteria to colistin.15 They state that while the mechanism of resistance is poorly understood, it is clear that cases of resistance are growing in numbers. The authors note that it is imperative that one optimizes dosing of colistin. Suboptimal dosing in patients may generate resistance in a number of antibiotic treatments.

What About Future Directions With Antibiotics?

Crane and colleagues recently studied the efficacy of the use of local colistin impregnated beads versus parenteral colistin in soft tissue infection in mice.16 While the authors noted that the parenteral colistin failed to have a measureable effectiveness on the infection, the impregnated beads were significant in reducing it. Further study in human models is necessary to evaluate the effective treatment of common podiatric conditions such as chronic osteomyelitis, chronic diabetic wounds and post-surgical infections.

   As with most areas of medicine and science, up-to-date research will allow clinicians to stay ahead of the multidrug resistance curve. Currently, a compound known as avibactam (Cerexa), which is in phase III clinical trials, provides promise in the fight against multidrug-resistant organisms especially when researchers combine it with cephalosporins such as ceftazidime (Fortaz, GlaxoSmithKline) and ceftaroline (Teflaro, Forest Laboratories). One in vitro study showed that avibactam inhibited 100 percent of the Klebsiella pneumoniae carbapenemase producing K. pneumoniae and ESBL producing E. coli.17

In Conclusion

It is imperative that physicians are aware of the new class of multidrug-resistant organisms, the ESKAPE pathogens, which include Gram-negative organisms. The object of this review was to highlight the most common organisms that are causing such problems, mechanisms of action in regard to ESBLs and Klebsiella pneumoniae carbapenemases, and current treatment options. By emphasizing judicious use of antibiotic regimens based on culture and sensitivity reports, physicians can help prevent the creation of resistant organisms.

   Dr. Perez is a first-year resident at the New York College of Podiatric Medicine Residency Program.

   Ms. Attanasio is a third-year student at the New York College of Podiatric Medicine.

   Dr. Khan is an Associate Professor at the New York College of Podiatric Medicine. He is an attending in the Surgery Department at Metropolitan Hospital in New York City.

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