POLYMYXINS – ANTIBACTERIAL ACTIVITY, RESISTANCE MECHANISMS AND EPIDEMIOLOGY OF PLASMID MEDIATED RESISTANCE POLIMIKSINI – ANTIBAKTERIJSKA AKTIVNOST, MEHANIZMI REZISTENCIJE I EPIDEMIOLOGIJA REZISTENCIJE POSREDOVANE PLAZMIDOM
Abstract
Sažetak
Pojava i širenje multirezistentnih, ali i panrezistentnih sojeva bakterija predstavlja problem globalnih razmera u savremenoj medicini. Sužen terapijski izbor aktuelizovao je upotrebu “starih” antibiotika, kao što su polimiksini. Korišćenje polimiksina u humanoj medicini smanjeno je šezdesetih godina XX veka zbog otkrića bezbednijih antibiotika. Savremena istraživanja su omogućila bolje razumevanje njihove farmakokinetike i farmakodinamike, kao i doziranje koje minimizira pojavu neželjenih efekata. Povećana upotreba polimiksina u terapiji dovela je, međutim, do pojave rezistencije na ove antibiotike “poslednje linije”. Najveći broj izolata bakterija rezistentnih na polimiksine ima hromozomski posredovanu rezistenciju. Otkriće plazmidskog gena mcr-1 2015. godine u Kini promenilo je paradigmu o poreklu i širenju rezistencije na polimiksine. Glavni rezervoar bakterija nosilaca plazmidskog gena su životinje zbog izuzetno velike primene polimiksina u veterinarskoj medicini, ali i u proizvodnji hrane. U brojnim studijama potvrđen je prenos gena rezistencije na polimiksine sa animalnih bakterijskih izolata na izolate humanog porekla, kao i prenos između različitih bakterijskih vrsta in vivo ili in vitro. Ova saznanja su nametnula potrebu za detaljnim epidemiološkim istraživanjima i nadzorom nad ovim tipom rezistencije, što je i preporuka Evropskog centra za prevenciju i kontrolu bolesti.
Ključne reči: polimiksini, mehanizmi rezistencije, mcr-1 gen, plazmid
Abstract
The occurrence and spreading of multi-resistant, as well as pan-resistant bacterial isolates, presents a global problem of modern medicine. Narrowed therapeutic options actualized the use of “old” antibiotics such as polymyxins. The use of polymyxins in human medicine has been reduced since the 1960s due to the discovery of safer antibiotics. Modern researches provided a better understanding of their pharmacokinetics and pharmacodynamics, as well as dosing regimens with minimum side effects. However, the increased usage in therapy consequently led to the occurrence of resistance to these “last-line” antibiotics. Most of polymyxin resistant bacterial isolates carried chromosomally mediated resistance, but the discovery of the plasmid mcr-1 gene in 2015 in China changed the paradigm of the origin and spreading of polymyxin resistance. Animals are the main reservoirs of bacteria carrying plasmid with the mcr-1 gene, because of widespread polymyxins application in veterinary medicine and in food industry, as well. Many studies confirmed the transfer of polymyxins resistance genes from animal bacterial isolates to human isolates, as well as between different bacterial species in vivo or in vitro. These findings indicated the need for more detailed epidemiological research and surveillance, as the European Centre for Disease Prevention and Control recommended.
Key words: polymyxins, resistance mechanisms, mcr-1 gene, plasmid
References
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug- resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar; 18(3):268-81.
Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A 3rd, et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010 Dec; 30(12):1279-91.
Shahbazi F, Dashti-Khavidaki S. Colistin: efficacy and safety in different populations. Expert Rev Clin Pharmacol. 2015, 8(4):423-48.
Kssamali Z, Danziger L. To B or not to B, that is the question: is it time to replace colistin with polymyxin B? Pharmacotherapy. 2015 Jan; 35(1):17-21.
Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005 May 1; 40(9):1333-41. Epub 2005 Mar 22. Review. Erratum in: Clin Infect Dis. 2006 Jun 15; 42(12):1819. Dosage error in article text.
Poirel L, Jayol A, Nordmann P. Polymyxins: Antibacterial Activity,Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes. Clin Microbiol Rev. 2017, 30(2):557-596.
European Medicines Agency. 2014. Polymyxin Article-31referral- Assessment report. European Medicines Agency, London, United Kingdom. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Polymyxin_31/WC500179664.pdf [cited 21.09.2018.].
Pogue J, Kaye K. Clinical considerations for optimal use of the polymyxins: A focus on agent selection and dosing. Clin Microbiol Infect 2017; 23(4):229-233.
Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, et al. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016 Mar 1; 62(5):552-558.
Osei Sekyere J, Govinden U, Bester LA, Essack SY. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods. J Appl Microbiol. 2016 Sep; 121(3):601-17.
Caniaux I, van Belkum A, Zambardi G, Poirel L, Gros MF. MCR: modern colistin resistance. Eur J Clin Microbiol Infect Dis. 2017 Mar; 36(3):415-420.
Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol. 2014, 26; 5:643.
Jeannot K, Bolard A, Plésiat P. Resistance to polymyxins in Gram-negative organisams. Int J Antimicrob Agents. 2017 May; 49(5):526-535.
Beceiro A, Moreno A, Fernández N, Vallejo JA, Aranda J, Adler B, et al. Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob Agents Chemother. 2014; 58(1):518-26.
Liu YY, Chandler CE, Leung LM, McElheny CL, Mettus RT, Shanks RMQ, et al. Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens. Antimicrob Agents Chemother. 2017 May 24; 61(6).
Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016 Feb; 16(2):161-8.
European Centre for Disease Prevention and Control. Plasmid-mediated colistin resistance in Enterobacteriaceae. Stockholm: ECDC; 2016.
Zurfluh K, Klumpp J, Nüesch-Inderbinen M, Stephan R. Full-Length Nucleotide Sequences of mcr-1-Harboring Plasmids Isolated from Extended-Spectrum-β-Lactamase-Producing Escherichia coli Isolates of Different Origins. Antimicrob Agents Chemother. 2016 Aug 22; 60(9):5589-91.
Li A, Yang Y, Miao M, Chavda KD, Mediavilla JR, Xie X, et al. Complete Sequences of mcr-1-Harboring Plasmids from Extended-Spectrum-β-Lactamase- and Carbapenemase-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016 Jun 20; 60(7):4351-4.
Jayol A, Nordmann P, André C, Dubois V, Poirel L. Increased colistin resistance upon acquisition of the plasmid-mediated mcr-1 gene in Escherichia coli isolates with chromosomally encoded reduced susceptibility to polymyxins. Int J Antimicrob Agents. 2017 Sep; 50(3):503-504.
Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, et al. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Surveill. 2016 Jul 7; 21(27).
Kieffer N, Nordmann P, Poirel L. Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants. Antimicrob Agents Chemother. 2017 May 24;61(6).
Yin W, Li H, Shen Y, Liu Z, Wang S, Shen Z, et al. Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli. MBio. 2017 Jun 27; 8(3).
Carattoli A, Villa L, Feudi C, Curcio L, Orsini S, Luppi A, et al. Novel plasmid mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Eurosurveillance. 2017; 22:31.
Borowiak M, Fischer J, Hammerl JA, Hendriksen RS, Szabo I, Malorny B. Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. J Antimicrob Chemother. 2017; 72:3317–24.
AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, et al. mcr-1 and mcr-2 (mcr-6.1) variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2018 Oct 1; 73(10):2904.
AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, et al. mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2017 Oct 1; 72(10):2745-2749.
Yang YQ, Li YX, Lei CW, Zhang AY, Wang HN. Novel plasmid-mediated colistin resistance gene mcr-7.1 in Klebsiella pneumoniae. J Antimicrob Chemother. 2018 Apr 17. doi: 10.1093/jac/dky111. [Epub ahead of print]
Wang X, Wang Y, Zhou Y, Li J, Yin W, Wang S, et al. Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg Microbes Infect. 2018 Jul 4; 7(1):122.
Shen Z, Wang Y, Shen Y, Shen J, Wu C. Early emergence of mcr-1 in Escherichia coli from food-producing animals. Lancet Infect Dis. 2016 Mar; 16(3):293.
Skov RL, Monnet DL. Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds. Euro Surveill. 2016; 21(9):30155.
ECDC (European Centre for Disease Prevention and Control), EFSA (European Food Safety Authority), and EMA (European Medicines Agency), 2017. ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals – Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report. EFSA Journal 2017; 15(7):4872
Poirel L, Nordmann P. Emerging plasmid-encoded colistin resistance: the animal world as the culprit? J Antimicrob Chemother. 2016 Aug; 71(8):2326-7.
Liu YY, Chandler CE, Leung LM, McElheny CL, Mettus RT, Shanks RMQ, et al. Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens. Antimicrob Agents Chemother. 2017 May 24; 61(6).
Castanheira M, Griffin MA, Deshpande LM, Mendes RE, Jones RN, Flamm RK. Detection of mcr-1 among Escherichia coli Clinical Isolates Collected Worldwide as Part of the SENTRY Antimicrobial Surveillance Program in 2014 and 2015. Antimicrob Agents Chemother. 2016, 60(9):5623-4.
Novović K, Trudić A, Brkić S, Vasiljević Z, Kojić M, Medić D, et al. Molecular Epidemiology of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae in Serbia from 2013 to 2016. Antimicrob Agents Chemother. 2017 Apr 24; 61(5)
Global action plan on antimicrobial resistance. Geneva: World Health Organization; 2015. http://apps.who.int/iris/bitstream/10665/193736/1/9789241509763_eng.pdf?ua=1 [cited 26.09.2018.]