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The occurrence of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem resistance among other gram-negative bacteria (e.g., P. aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophila ) is a growing health-care concern. These pathogens develop resistance to carbapenems through a variety of mechanisms, including production of carbapenemases (broad-spectrum β-lactamases that inactivate all β-lactams, including carbapenems), active efflux of carbapenems out of the cell, and/or prevention of carbapenem entry through porin channels . Similar to concerns with ESBLs, carbapenem-resistant, gram-negative pathogens are usually resistant to multiple classes of antibacterials, and some have even developed pan-resistance (resistance to all available antibacterials). Infections with carbapenem-resistant, gram-negative pathogens commonly occur in health-care settings through interaction with contaminated individuals or medical devices, or as a result of surgery.
The emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant Mycobacterium tuberculosis ( XDR-TB ) is also of significant global concern. MDR-TB strains are resistant to both rifampin and isoniazid , the drug combination typically prescribed for treatment of tuberculosis. XDR-TB strains are additionally resistant to any fluoroquinolone and at least one of three other drugs ( amikacin , kanamycin , or capreomycin ) used as a second line of treatment, leaving these patients very few treatment options. Both types of pathogens are particularly problematic in immunocompromised persons, including those suffering from HIV infection. The development of resistance in these strains often results from the incorrect use of antimicrobials for tuberculosis treatment, selecting for resistance.
To learn more about the top 18 drug-resistant threats to the US, visit the CDC’s website.
Although animal husbandry has long been a major part of agriculture in America, the rise of concentrated animal feeding operations (CAFOs) since the 1950s has brought about some new environmental issues, including the contamination of water and air with biological waste, and ethical issues regarding animal rights also are associated with growing animals in this way. Additionally, the increase in CAFOs involves the extensive use of antimicrobial drugs in raising livestock. Antimicrobials are used to prevent the development of infectious disease in the close quarters of CAFOs; however, the majority of antimicrobials used in factory farming are for the promotion of growth—in other words, to grow larger animals.
The mechanism underlying this enhanced growth remains unclear. These antibiotics may not necessarily be the same as those used clinically for humans, but they are structurally related to drugs used for humans. As a result, use of antimicrobial drugs in animals can select for antimicrobial resistance, with these resistant bacteria becoming cross-resistant to drugs typically used in humans. For example, tylosin use in animals appears to select for bacteria also cross-resistant to other macrolides, including erythromycin, commonly used in humans.
Concentrations of the drug-resistant bacterial strains generated by CAFOs become increased in water and soil surrounding these farms. If not directly pathogenic in humans, these resistant bacteria may serve as a reservoir of mobile genetic elements that can then pass resistance genes to human pathogens. Fortunately, the cooking process typically inactivates any antimicrobials remaining in meat, so humans typically are not directly ingesting these drugs. Nevertheless, many people are calling for more judicious use of these drugs, perhaps charging farmers user fees to reduce indiscriminate use. In fact, in 2012, the FDA published guidelines for farmers who voluntarily phase out the use of antimicrobial drugs except under veterinary supervision and when necessary to ensure animal health. Although following the guidelines is voluntary at this time, the FDA does recommend what it calls “judicious” use of antimicrobial drugs in food-producing animals in an effort to decrease antimicrobial resistance.
Unfortunately, Marisa’s urinary tract infection did not resolve with ciprofloxacin treatment. Laboratory testing showed that her infection was caused by a strain of Klebsiella pneumoniae with significant antimicrobial resistance. The resistance profile of this K. pneumoniae included resistance to the carbapenem class of antibacterials, a group of β-lactams that is typically reserved for the treatment of highly resistant bacteria. K. pneumoniae is an opportunistic, capsulated, gram-negative rod that may be a member of the normal microbiota of the intestinal tract, but may also cause a number of diseases, including pneumonia and UTIs.
Specific laboratory tests looking for carbapenemase production were performed on Marisa’s samples and came back positive. Based upon this result, in combination with her health history, production of a carbapenemase known as the New Delhi Metallo-β-lactamase (NDM) was suspected. Although the origin of the NDM carbapenemase is not completely known, many patients infected with NDM-containing strains have travel histories involving hospitalizations in India or surrounding countries.
Jump to the next Clinical Focus box. Go back to the previous Clinical Focus box.
Staphylococcus aureus , including MRSA strains, may commonly be carried as a normal member of the ________ microbiota in some people.
nasal
Why does the length of time of antimicrobial treatment for tuberculosis contribute to the rise of resistant strains?
What is the difference between multidrug resistance and cross-resistance?
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