POLYMYXINS – ANTIBACTERIAL ACTIVITY, RESISTANCE MECHANISMS AND EPIDEMIOLOGY OF PLASMID MEDIATED RESISTANCE POLIMIKSINI – ANTIBAKTERIJSKA AKTIVNOST, MEHANIZMI REZISTENCIJE I EPIDEMIOLOGIJA REZISTENCIJE POSREDOVANE PLAZMIDOM
Sažetak
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
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