Multi-Drug Resistant Organisms

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Strategies to fight against Multi-Drug Resistant Organisms are explored

Vol. 24 • Issue 6 • Page 12

Cover Story

It’s not uncommon to hear warnings of outbreaks of resistant organisms causing serious infections. During the last few weeks, for example, a strain of Shigella resistant to ciprofloxacin, one of the standard antibiotics used to treat this organism, has been reported. This Shigella development was preceded by a report in January of an outbreak of carbapenem-resistant Enterobacteriaceae (CRE) through a procedure called an endoscopic retrograde cholangiopancreatography (ERCP). These events add to the growing concern of the various multi-drug resistant organisms (MDROs) plaguing the country.

The Centers for Disease Control and Prevention (CDC) published “Antibiotic Resistance Threats in the United States 2013.” This 114-page summary was designed to increase awareness of the threat that antibiotic resistance poses and encourage actions to address the threat. The report also discussed particular bacteria that can cause severe human infections and the antibiotics used in their treatment as well as certain fungal resistance and Clostridium difficile (C. diff) concerns.

A Global Concern

Antibiotic resistance is a worldwide problem that can easily cross international boundaries and continents given the multitude of travel options of the last century. In the United States, 2 million people acquire infections with bacteria that are resistant to one or more antibiotics that should have treated the bacteria. Of that, at least 23,000 people die each year as a direct result of these resistant infections. Many more of these patients die from other conditions that were complications of the antibiotic-resistant infections. In addition, C. diff affects 250,000 people each year. In most cases, the use of antibiotics was a major contributing factor. Approximately 14,000 people will die from a C. diff infection that could have been prevented.1

Infections resulting from these antibiotic resistant organisms result in considerable added costs from prolonged and costlier treatments, additional physician visits, increased utilization of healthcare resources and greater disabilities and deaths when compared to organisms with traditional sensitivities. The total economic costs (estimated with 2008 dollar values) has been estimated to approach $20 million in excess direct healthcare costs with additional costs as a result of lost productivity as high as $35 million per year.1

Now that we have considered some of the general information related to MDROs, a brief review of a few of the key ones would be beneficial.

Methicillin-resistant Staphyloccus aureus

MRSA is probably the most commonly known MDRO with an extensive history. Penicillin was used to treat S. aureus infections in the 1940s, but resistance to penicillin soon developed by the late 1940s and early 1950s, resulting in the switch to methicillin to treat skin and soft tissue infections. Then in 1960, the first case of methicillin resistance was reported and continued to occur in healthcare settings until a community-based outbreak occurred among injecting drug abusers in Detroit. The incidence of community-acquired MRSA continued to increase and, in 2008, resulted in risk factors for infection being identified among athletes, military recruits, incarcerated people, emergency room patients, HIV patients and men who had sex with men.

Of note: about one-third of the people in the world have S. aureus on their bodies, primarily in their nose and on their skin. About 1 percent of those people will have MRSA.2 There are now two categories of MRSA: hospital-acquired (HA-MRSA) and community-acquired (CA-MRSA). The hospital-acquired strains are usually sensitive to vancomyin or trimethoprim-sulfamethoxazole, while the community-acquired strains are sensitive to ciprofloxacin, clindamycin, erythromycin, gentamicin, trimethoprim-sulfamethoxazole or vancomycin. The molecular mechanisms for MRSA resistance have been studied. The presence of the mec gene is an absolute requirement for S. aureus to express methicillin resistance. The CDC reports that there have been 80,461 severe MRSA infections with 11,285 deaths in 2011.

Vancomycin-resistant Enterococci

VRE issues started to surface in the early 1950s, when cure rates for endocarditis caused by enterococci treated with penicillin were decreasing. The resistance continued when treatment changed to ampicillin or vancomycin with or without an aminoglycoside antibiotic. It was found that pheromone-responsive plasmids cause plasmid transfer between Enterococcus faecalis isolates. The plasmids can transfer among a broad range of species, but usually at a moderately low frequency. It was also discovered that conjugative transposition transfer of transposons occurs at low frequency, but to a very broad range of different kinds of bacteria. VRE infections now often require treatment with linezolid to eradicate the organism.

Extended-spectrum Beta-lactamases

ESBLs are enzymes that open the beta-lactam ring, resulting in the inactivation of the antibiotic classes of penicillins, cephalosporins and mono-bactam atzreonam. The first plasmid-mediated beta-lactamase was discovered in Greece in the 1960s. It was named “TEM” after the patient in which it was isolated. This was followed by the discovery of another closely related enzyme, TEM-2. These two are the most common plasmid-mediated beta-lactamases. Their resistance affects Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenza and Neisseria gonorrhea.

Newer resistance followed TEM-1 and TEM-2 with the development of SHV-2. This resistance was found first in France in 1984, then later in the U.S. The SHV-2 is found exclusively in gram-negative organisms, such as Klebiella species, Escherichia coli, Acinetobacter, Citrobacter, Pseudomonas and Morganelli to name a few. SHV-2 can be blocked by the beta-lactamase inhibitors, such as clavulante, sulbactam or tazobactam. As a result, these chemicals can be added to antibiotics to help maintain their effectiveness.

Known risk factors for ESBL-producing organisms include the length of hospital stay; length of ICU stay; presence of a central venous or arterial catheter; emergency abdominal surgery; presence of gastrostomy or jejunostomy tube; prior administration of antibiotics; prior residence in a long-term care facility; and presence of urinary catheter, ventilator assistance
and hemodialysis.

Carbapenem-resistant Enterobacteriacae

Per the CDC, CREs were uncommon before 1992. One member of the class, Klebsiella pneumonia carbapenemase (KPC), was first reported in 2001. Specific strains of these organisms are found in certain regions of the country. Hospitals or long-term care facilities are the primary sites for the development for these CREs; risk factors include the use of a beta-lactam antibiotic, mechanical ventilation and diabetes. There are several reported mechanisms by which these bacteria can become carbapenem resistant. Treatment options can be limited and need to be assessed on a case-by-case basis.

Taking Action

What can we do? The CDC suggests four core actions to help prevent antibiotic resistance issues:

  1. preventing infections and the spread of resistance (e.g., immunizations)
  2. tracking and collecting data to develop prevention strategies
  3. improving antibiotic stewardship
  4. developing new drugs and diagnostic tests

References:

  1. Antibiotic Resistance Threats in the United States 2013 published by the Centers for Disease Control and Prevention. Electronic access: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
  2. National Institute of Allergy and Infectious Disease’s Antimicrobial (Drug) Resistance – Section on Methicillin-Resistant Staphylococcus aureus (MRSA). Web site access: http://www.niaid.nih.gov/topics/antimicrobialResistance/Examples/mrsa/Pages/overview.aspx
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About Author

Martha J. Roberts, PharmD

Martha J. Roberts is lead clinical care pharmacist/critical care specialist, St. Joseph Health Services of Rhode Island, Providence.

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