多剤耐性

関: MDR、multidrug resistance、multidrug-resistant、multiple drug resistance、multiple drug-resistant

WordNet

any mechanical force that tends to retard or oppose motion
the capacity of an organism to defend itself against harmful environmental agents; "these trees are widely planted because of their resistance to salt and smog"
the action of opposing something that you disapprove or disagree with; "he encountered a general feeling of resistance from many citizens"; "despite opposition from the newspapers he went ahead" (同)opposition
(psychiatry) an unwillingness to bring repressed feelings into conscious awareness
group action in opposition to those in power
the military action of resisting the enemys advance; "the enemy offered little resistance"
the degree of unresponsiveness of a disease-causing microorganism to antibiotics or other drugs (as in penicillin-resistant bacteria)
use recreational drugs (同)do drugs
administer a drug to; "They drugged the kidnapped tourist" (同)dose
a substance that is used as a medicine or narcotic

PrepTutorEJDIC

〈U〉〈C〉(…に)『抵抗』(『反抗』)『すること』;(…を)『こらえること』《+『to』(『against』)+『名』(do『ing』)》 / 〈U〉(病気などに対する)『抵抗力』《+『against』(『to』)+『名』》 / 〈U〉〈C〉(またresistance movement)(権力・圧制に対する)抵抗運動,レジスタンス / 〈U〉(空気の)抵抗;(電気の)抵抗
『薬』,薬品,薬剤 / 『麻薬』,麻酔剤 / 〈人〉‘に'薬(特に麻酔剤)を与える / 〈飲食物〉‘に'(麻酔薬・毒薬などの)薬を混ぜる

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/19 11:40:51」(JST)

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Multiple drug resistance (MDR), multi-drug resistance or multiresistance is a condition enabling disease-causing microrganisms (bacteria, viruses, fungi or parasites) to resist distinct antimicrobials, first and foremost antibiotics,but also antifungal drugs, antiviral medications, antiparasitic drugs, chemicals of a wide variety^[1] of structure and function targeted at eradicating the organism. 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 a journal called "Clinical Microbiology and Infection" and are openly accessible^[2] This article discusses multi-drug resistance of bacteria, fungi, viruses and parasites, not that of tumor cells, which are discussed in the section of antineoplastic resistance.

Common multi-drug-resistant organisms (MDROs)

are usually bacteria:

Vancomycin-Resistant Enterococci (VRE)
Methicillin-Resistant Staphylococcus aureus (MRSA)
Extended-spectrum β-lactamase (ESBLs) producing Gram-negative bacteria
Klebsiella pneumoniae carbapenemase (KPC) producing Gram-negatives
MultiDrug-Resistant gram negative rods (MDR GNR)MDRGN bacteria such as Enterobacter species, E.coli,Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa

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)^[3]

Multi-drug-resistant tuberculosis

Bacterial resistance to antibiotics

Main article: Antibiotic resistance

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:

No longer relying on a glycoprotein cell wall
Enzymatic deactivation of antibiotics
Decreased cell wall permeability to antibiotics
Altered target sites of antibiotic
Efflux mechanisms to remove antibiotics^[5]
Increased mutation rate as a stress response^[6]

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. Some resistant bacteria are able to transfer copies of DNA that code for a mechanism of resistance to other nearby species of bacteria, thereby conferring resistance to their neighbors, which then are also able to pass on the resistant gene. 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.^[7]

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^[8] Antihelminthic resistance is mainly reported in the veterinary literature, for example in connection with the practice of livestock drenching^[9] 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.

References

^ Drug Resistance, Multiple at the US National Library of Medicine Medical Subject Headings (MeSH)
^ http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03570.x/pdf
^ Boucher, HW, Talbot GH, Bradley JS, Edwards JE, Gilvert D, Rice LB, Schedul M., Spellberg B., Bartlett J. Bad buds, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clincial Infectious Disease (2009); 48: 1-12.
^ Bennett PM (March 2008). "Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria". Br. J. Pharmacol. 153 Suppl 1: S347–57. doi:10.1038/sj.bjp.0707607. PMC 2268074. PMID 18193080.
^ Li XZ, Nikaido H (August 2009). "Efflux-mediated drug resistance in bacteria: an update". Drugs 69 (12): 1555–623. doi:10.2165/11317030-000000000-00000. PMC 2847397. PMID 19678712.
^ Stix G (April 2006). "An antibiotic resistance fighter". Sci. Am. 294 (4): 80–3. PMID 16596883.
^ Howden BP, Slavin MA, Schwarer AP, Mijch AM (February 2003). "Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine". Eur. J. Clin. Microbiol. Infect. Dis. 22 (2): 111–3. doi:10.1007/s10096-002-0877-z. PMID 12627286.
^ 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.
^ 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.

External links

BURDEN of Resistance and Disease in European Nations - An EU-Project to estimate the financial burden of antibiotic resistance in European Hospitals
European Centre of Disease Prevention and Control and (ECDC): Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance http://www.ecdc.europa.eu/en/activities/diseaseprogrammes/ARHAI/Pages/public_consultation_clinical_microbiology_infection_article.aspx
State of Connecticut Department of Public Health MDRO information http://www.ct.gov/dph/cwp/view.asp?a=3136&q=424162

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

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. HIV薬剤耐性検査アッセイの概要 overview of hiv drug resistance testing assays
2. HIV薬剤耐性検査の解釈についての手引 primer on interpretation of hiv drug resistance testing
3. HIV感染の臨床的マネージメントにおける薬剤耐性試験 drug resistance testing in the clinical management of hiv infection
4. 抗マラリア剤：概要 antimalarial drugs an overview
5. 薬物アレルギー患者へのアプローチ an approach to the patient with drug allergy

English Journal

Leishmania is not prone to develop resistance to tamoxifen.

Coelho AC1, Trinconi CT1, Senra L1, Yokoyama-Yasunaka JK1, Uliana SR1.
International journal for parasitology. Drugs and drug resistance.Int J Parasitol Drugs Drug Resist.2015 Jun 17;5(3):77-83. doi: 10.1016/j.ijpddr.2015.05.006. eCollection 2015.
Tamoxifen, an antineoplastic agent, is active in vitro and in vivo against the parasitic protozoa Leishmania. As part of our efforts to unravel this drug's mechanisms of action against the parasite and understand how resistance could arise, we tried to select tamoxifen-resistant Leishmania amazone
PMID 26150922

Anti-tumor activity of the proteasome inhibitor BSc2118 against human multiple myeloma.

Zang M1, Li Z1, Liu L1, Li F2, Li X3, Dai Y4, Li W5, Kuckelkorn U6, Doeppner TR7, Hermann DM7, Zhou W8, Qiu L9, Jin F10.
Cancer letters.Cancer Lett.2015 Oct 1;366(2):173-81. doi: 10.1016/j.canlet.2015.06.011. Epub 2015 Jun 23.
Introduction of bortezomib, the first generation of proteasome inhibitor, has significantly improved the median overall survival of patients with multiple myeloma (MM). However, the dose-limiting adverse events and acquired drug resistance limit its long-term usage. Here, we report in vitro and in v
PMID 26116344

Antimicrobial activity of pomegranate fruit constituents against drug-resistant Mycobacterium tuberculosis and β-lactamase producing Klebsiella pneumoniae.

Dey D1, Ray R, Hazra B.
Pharmaceutical biology.Pharm Biol.2015 Oct;53(10):1474-80. doi: 10.3109/13880209.2014.986687. Epub 2015 Apr 10.
CONTEXT: The global surge in multi-drug resistant bacteria and the imminence of tuberculosis pandemic necessitate alternative therapeutic approaches to augment the existing medications. Pomegranate, the fruit of Punica granatum Linn. (Punicaceae), widely recognized for potency against a broad spectr
PMID 25858784

Japanese Journal

急性前骨髄性白血病におけるレチノイン酸薬物動態の検討

瀧谷公隆,玉井浩
ビタミン 85(12), 631-644, 2011-12-25
… However, development of resistance is a concern in ATRA therapy. … Resistance may be caused by reduced ATRA concentration in the blood, expression of multi-drug resistance 1(MDR-1) gene, and mutation of PML/RAR fusion gene in APL cells. …
NAID 110008898018

Synergistic effect of tetrandrine and ethidium bromide against methicillin-resistant Staphylococcus aureus (MRSA)

LEE Young-Seob,HAN Sin-Hee,LEE Su-Hwan,KIM Young-Guk,PARK Chung-Berm,KANG Ok-Hwa,KEUM Joon-Ho,KIM Sung-Bae,MUN Su-Hyun,SHIN Dong-Won,KWON Dong-Yeul
Journal of toxicological sciences 36(5), 645-651, 2011-10-01
… Recently, the efflux mechanism has been identified as the main contributor to antibiotic resistance in bacteria. … In addition, TET exhibits a synergistic effect when combined with the multi-drug resistance (MDR)-efflux pump substrate ethidium bromide (EtBr). …
NAID 10029481530

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★リンクテーブル★

リンク元	「多剤耐性」「multidrug-resistant」「multiple drug-resistant」「multiple drug resistance」
関連記事	「multi」「drug」「resistance」