A Closer Look At Multidrug-Resistant Organisms And Nosocomial Pathogens

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

Determining the best course of treatment for bacterial infections can be a daunting task, especially in the age of multidrug-resistant organisms.

   Perhaps the most well known multidrug resistant organism is methicillin resistant Staphylococcus aureus (MRSA). A survey conducted at 97 hospitals showed the rate of MRSA in diabetic foot infections to have almost doubled between 2003 and 2007, and these numbers have surely increased since then.1

   Recently, there has been a rise of Gram-negative, multidrug-resistant organisms that have caught many physicians off guard. Gram-negative organisms have now evolved from multidrug resistance (resistance to three or more classes of antimicrobials) to extreme drug resistance (susceptibility to two or fewer classes of antimicrobials) to pan-drug resistance (diminished susceptibility to all classes of antimicrobials).2

   These organisms are proliferating at an alarming rate both here and abroad. Antibiotic resistance is a worldwide threat. In a 2011 study in India, researchers collected samples from 102 patients with diabetic foot infections.3 Authors found that 45 percent of patients tested positive for multidrug resistant organisms, 68.5 percent of which had extended spectrum beta-lactamases (ESBLs) producing Gram-negative organisms and 43.2 percent with MRSA.

   As podiatric physicians, we must be aware of such organisms as they severely limit our treatment options and may ultimately lead to higher rates of morbidity and mortality.

What Are The ‘ESKAPE’ Pathogens?

We have focused on organisms that podiatric physicians are most likely to encounter in their patient population. The term “ESKAPE” pathogens has come to encompass the six pathogens with growing multidrug resistant virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter, Pseudomonas aeruginosa and Enterobacter.4

   According to the latest data from the Centers for Disease Control and Prevention, the six ESKAPE bacteria are responsible for two-thirds of all healthcare-associated infections.4

   While each of these organisms has unique mechanistic actions, the common foundation is resistance to antibiotics clinicians previously used to treat them. There are several mechanisms of resistance including: mutations occurring in target enzymes; enzymatic deactivation of the drug; gene acquisition; bypassing the target; prevention of drug access to the target; and lastly via biofilms with dormant “persister” cells.5,6 Two target enzymes play a key role in the ESKAPE pathogens’ ability to become drug resistant, specifically when it comes to Gram negative organisms.

What You Should Know About Extended Spectrum Beta-Lactamases

Named for their ability to hydrolyze extended spectrum cephalosporins, ESBLs first surfaced in Germany in 1983.6E. coli and Klebsiella pneumoniae remain the most common ESBL producers. However, ESBL production may also occur with Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, Citrobacter freundii, Serratia marcescens and Enterobacter cloacae.

   The incidence of ESBL producing organisms is increasing worldwide. In a diabetic foot infection study from India, 44.7 percent of gram negative aerobes cultured were ESBL-positive.7 In a study by Dent and colleagues, nearly 47 percent of surgical patients had evidence of multidrug resistant A. baumannii in their amputation sites and chronic diabetic ulcers.8 Some of the infections persisted for months.

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