Multiple drug resistance

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Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to multiple antimicrobial drugs. The types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, fungi, and parasites (resistant to multiple antifungal, antiviral, and antiparasitic drugs of a wide chemical variety).[1] Recognizing different degrees of MDR, the terms extensively drug resistant (XDR) and pandrug-resistant (PDR) have been introduced. The definitions were published in 2011 in the journal Clinical Microbiology and Infection and are openly accessible.[2]

Common multidrug-resistant organisms (MDROs)

are usually bacteria:

A group of gram positive and gram negative bacteria of particular recent importance have been dubbed as the ESKAPE group (Enterococcus faecium,Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter species)[3]

Bacterial resistance to antibiotics

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Various microorganisms have survived for thousands of years by their ability to adapt to antimicrobial agents. They do so via spontaneous mutation or by DNA transfer. This process enables some bacteria to oppose the action of certain antibiotics, rendering the antibiotics ineffective.[4] These microorganisms employ several mechanisms in attaining multi-drug resistance:

Many different bacteria now exhibit multi-drug resistance, including staphylococci, enterococci, gonococci, streptococci, salmonella, as well as numerous other gram negative bacteria and Mycobacterium tuberculosis. Antibiotic resistant bacteria are able to transfer copies of DNA that code for a mechanism of resistance to other bacteria even distantly related to them, which then are also able to pass on the resistance genes and so generations of antibiotics resistant bacteria are produced.[7] This process is called horizontal gene transfer.

Antifungal resistance

Yeasts such as Candida species can become resistant under long term treatment with azole preparations, requiring treatment with a different drug class. Scedosporium prolificans infections are almost uniformly fatal because of their resistance to multiple antifungal agents.[8]

Antiviral resistance

HIV is the prime example of MDR against antivirals, as it mutates rapidly under monotherapy. Influenza virus has become increasingly MDR; first to amantadenes, then to neuraminidase inhibitors such as oseltamivir, (2008-2009: 98.5% of Influenza A tested resistant), also more commonly in immunoincompetent people Cytomegalovirus can become resistant to ganciclovir and foscarnet under treatment, especially in immunosuppressed patients. Herpes simplex virus rarely becomes resistant to acyclovir preparations, mostly in the form of cross-resistance to famciclovir and valacyclovir, usually in immunosuppressed patients.

Antiparasitic resistance

The prime example for MDR against antiparasitic drugs is malaria. Plasmodium vivax has become chloroquine and sulfadoxine-pyrimethamine resistant a few decades ago, and as of 2012 artemisinin-resistant Plasmodium falciparum has emerged in western Cambodia and western Thailand. Toxoplasma gondii can also become resistant to artemisinin, as well as atovaquone and sulfadiazine, but is not usually MDR[9] Antihelminthic resistance is mainly reported in the veterinary literature, for example in connection with the practice of livestock drenching[10] and has been recent focus of FDA regulation.

Preventing the emergence of antimicrobial resistance

To limit the development of antimicrobial resistance, it has been suggested to:

  • Use the appropriate antimicrobial for an infection; e.g. no antibiotics for viral infections
  • Identify the causative organism whenever possible
  • Select an antimicrobial which targets the specific organism, rather than relying on a broad-spectrum antimicrobial
  • Complete an appropriate duration of antimicrobial treatment (not too short and not too long)
  • Use the correct dose for eradication; subtherapeutic dosing is associated with resistance, as demonstrated in food animals.

The medical community relies on education of its prescribers, and self-regulation in the form of appeals to voluntary antimicrobial stewardship, which at hospitals may take the form of an antimicrobial stewardship program. It has been argued that depending on the cultural context government can aid in educating the public on the importance of restrictive use of antibiotics for human clinical use, but unlike narcotics, there is no regulation of its use anywhere in the world at this time. Antibiotic use has been restricted or regulated for treating animals raised for human consumption with success, in Denmark for example.

Infection prevention is the most efficient strategy of prevention of an infection with a MDR organism within a hospital, because there are few alternatives to antibiotics in the case of an extensively resistant or panresistant infection; if an infection is localized, removal or excision can be attempted (with MDR-TB the lung for example), but in the case of a systemic infection only generic measures like boosting the immune system with immunoglobulins may be possible. The use of bacteriophages (viruses which kill bacteria) has no clinical application at the present time.

See also

References

  1. Drug Resistance, Multiple at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. A.-P. Magiorakos , A. Srinivasan, R. B. Carey, Y. Carmeli, M. E. Falagas, C. G. Giske, S. Harbarth, J. F. Hinndler et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria.... Clinical Microbiology and Infection, Vol 8, Iss. 3 first published 27 July 2011 [via Wiley Online Library]. Retrieved 16 August 2014.
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  7. Hussain, T. Pakistan at the verge of potential epidemics by multi-drug resistant pathogenic bacteria (2015). Adv. Life Sci. 2(2). pp: 46-47
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  9. Doliwa C, Escotte-Binet S, Aubert D, Velard F, Schmid A, Geers R, Villena I. Induction of sulfadiazine resistance in vitro in Toxoplasma gondii.Exp Parasitol. 2013 Feb;133(2):131-6.
  10. Laurenson YC, Bishop SC, Forbes AB, Kyriazakis I.Modelling the short- and long-term impacts of drenching frequency and targeted selective treatment on the performance of grazing lambs and the emergence of antihelmintic resistance.Parasitology. 2013 Feb 1:1-12.

Further reading

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External links

APUA or Alliance for the Prudent Use of Antibiotics http://www.tufts.edu/med/apua/about_issue/multi_drug.shtml