Nedavne analize i studije generirale su nadu u zaštitu čovječanstva od rezistencije na antibiotike koja brzo postaje globalna prijetnja.
Otkriće antibiotici in mid 1900s was a significant milestone in the history of medicine as it was a miracle therapeutic for many bakterijski infekcije i bakterija-causing diseases. Antibiotici were once termed as a “wonder drug” and now antibiotics are indispensable in both basic healthcare and advanced medical care and technology as they have really changed the world by protecting lives and being an essential part of treating various medical conditions and asassisting in critical surgical procedures.
Otpornost na antibiotike raste velikom brzinom
Antibiotici are medicines which are naturally produced by microorganisms and they stop or kill bakterija from growing. It is of critical importance because bakterijski infections have plagued mankind throughout time. However, “resistant” bakterija develop defences that protect them against the effects of antibiotici when previously they were killed by them. These resistant bacteria then are able to withstand any attacks by antibiotics and consequently if these bakterija are disease-causing standard treatments stop working for that disease persisting the infections which can then easily spread to others. Thus, the “magical” antibiotics have unfortunately started to fail or started becoming ineffective and this is posing immense threat to the healthcare system worldwide. The number of resistant bakterija already cause more than 500,000 deaths every year and are eroding the efficiency of antibiotics for prevention and cure by being a silent killer by residing in almost 60% of the world’s populations in some form. Otpornost na antibiotike threatens our ability to cure many diseases like tuberculosis, pneumonia and carry out advances in surgeries, treatment of cancer etc. It is estimated that approximately 50 million people will die from antibiotic resistant infections by 2050 and the day might actually come when antibiotici can no longer be used for treating critical infections the way they are being used now. This issue of antibiotic resistance is now an important health topic which needs to be addressed with a sense of urgency for a better future and the medical and scientific community and the governments worldwide are taking several steps toward achieving this goal.
Istraživanje WHO-a: 'postantibiotska era'?
Svjetska zdravstvena organizacija (WHO) objavila je otpornost na antibiotike visoko prioritetno i ozbiljno zdravstveno pitanje kroz svoj Globalni sustav za nadzor rezistencije na antimikrobne lijekove (GLASS) koji je pokrenut u listopadu 2015. Ovaj sustav prikuplja, analizira i dijeli podatke o otpornosti na antibiotike širom svijeta. Od 2017. 52 zemlje (25 s visokim dohotkom, 20 sa srednjim dohotkom i sedam zemalja s niskim dohotkom) upisale su GLASS. To je prvo izvješće1 koji sadrži informacije o razinama rezistencije na antibiotike koje su dostavile 22 zemlje (pola milijuna sudionika upisanih u anketu) pokazujući rast uz alarmantnu stopu – ukupno ogromnu rezistenciju od 62 do 82 posto. Ova inicijativa Svjetske zdravstvene organizacije ima za cilj stvoriti svijest i koordinaciju između različitih nacija za rješavanje ovog ozbiljnog problema na globalnoj razini.
Mogli smo spriječiti rezistenciju na antibiotike i još uvijek možemo
How did we reach this phase of humanity where antibiotic resistance has turned into a global threat? The answer to that is quite simple: we have extremely overused and misused antibiotici. The doctors have overly prescribed antibiotici to any or every patient in the past many decades. Also, in many countries, especially the developing countries of Asia and Africa, antibiotici are available over-the-counter at the local pharmacist and can be purchased without even requiring a doctor’s prescription. It is estimated that 50 percent of the time antibiotici are prescribed for virus-causing infection where they basically do no good because the virus will still complete its life span (generally between 3-10 days) whether antibiotici are taken or not. In fact, it’s just incorrect and a mystery for many as to how exactly antibiotici (which target bakterija) will have any effect on viruses! The antibiotici could ‘maybe’ relieve some symptoms associated with the viral infection. Even then this continues to be medically unethical. The correct advice should be that since no treatment is available for most viruses, the infection should just run its course and in the future these infections should be alternatively prevented by following strict hygiene and keeping one’s environment clean. Furthermore, antibiotici are being routinely used in enhancing agricultural output worldwide and feeding to livestock and food-producing animals (chicken, cow, pig) as growth supplements. By doing so humans are also put to huge risk of ingesting antibiotic-resistant bakterija which reside in those food or animals causing rigorous transfer of resistant strain bakterija preko granica.
Ovaj scenarij dodatno je kompliciran činjenicom da farmaceutske tvrtke u posljednjih nekoliko desetljeća nisu razvile nove antibiotike – posljednju novu klasu antibiotika za gram-negativne bakterija jesu kinoloni razvijeni prije četiri desetljeća. Stoga, kako trenutno stojimo, ne možemo baš razmišljati o prevenciji otpornost na antibiotike dodavanjem više i različitih antibiotika jer će to samo dodatno zakomplicirati rezistencije i prijenos. Puno droga tvrtke su istaknule da razvijanje bilo kakvog novog droga je prvo vrlo skupo jer je to dug proces koji zahtijeva velika ulaganja i potencijalnu dobit antibiotici is generally very low that the companies are unable to ‘break even’. This is convoluted by the fact that a resistant strain would develop for a new antibiotic somewhere in the world within two years of its launch since no legal framework is in place to curb antibiotic overuse. This doesn’t exactly sound hopeful from a commercial as well as a medical point of view and thus developing new antibiotici is not the solution for prevention of their resistance.
SZO preporučuje plan djelovanja2 za prevenciju rezistencije na antibiotike:
a) Healthcare professionals and workers should be doing a careful detailed assessment before prescribing antibiotici to humans or animals. A Cochrane review of various methods3 aimed at reducing antibiotic abuse in any clinical set up has concluded that the ‘3-day prescription’ method was fairly successful, in which the patient suffering from an infection (which is not bakterijski) is conveyed that his/her condition will improve in 3 days, else antibiotici can be taken if symptoms get worse – which generally don’t since the viral infection has run its course by that time. b) The general public should be confident to ask questions when they are being prescribed antibiotici and they must take antibiotici only when satisfied that it is absolutely necessary. They must also complete the prescribed dosage to prevent fast growth of resistant bakterijski strains. c) Agriculturists and livestock breeders should follow a regulated, limited use of antibiotics and do so only where it matters (eg. to treat an infection). d) Governments should setup and follow national level plans to curb antibiotic use1. Za razvijene zemlje i zemlje sa srednjim i niskim dohotkom potrebno je uspostaviti prilagođene okvire koji se odnose na njihove potrebe.
Sada kada je šteta učinjena: borba protiv rezistencije na antibiotike
So that we do not plunge into a new ’post antibiotici’ era and return to the pre-penicillin (first antibiotic to be discovered) era, lot of research is happening in this field loaded with failure and occasional successes. Recent multiple studies show ways to tackle and maybe reverse antibiotic resistance. The first study published in Časopis za antimikrobnu kemoterapiju4 pokazuje da kada bakterija become resistant, one of the ways which they adopt to restrict antibiotici action is by producing an enzyme (a β-lactamase) which destroys any antibiotic that is trying to get into the cell (for treatment). Thus, ways to inhibit the action of such enzymes could successfully reverse antibiotic resistance. In a second subsequent study from the same team at University of Bristol, UK but in collaboration with University of Oxford published in Molekularna mikrobiologija5, they analysed the effectiveness of two types of inhibitors of such enzymes. These inhibitors (from the bicyclic boronate class) were seen to be very effective on a particular type of antibiotic (aztreonam) such that in the presence of this inhibitor, the antibiotic was able to kill many resistant bakterija. Two of such inhibitors avibactam and vaborbactam – are now undergoing clinical trial and have been able to save a life of a person suffering from untreatable infection.The authors have succeeded with only a particular type of antibiotik, međutim, njihov rad je stvorio nadu u vraćanje plime otpornosti na antibiotike.
U drugoj studiji objavljenoj u Znanstveni Izvješća6, istraživači sa Université de Montréal osmislili su novi pristup za blokiranje prijenosa rezistencije između bakterija, što je jedan od načina na koji se rezistencija na antibiotike širi u bolnicama i zdravstvenim jedinicama. Geni odgovorni za stvaranje otpornosti bakterija kodirani su na plazmidima (mali DNA fragment koji se može samostalno replicirati) i ti plazmidi se prenose između bakterija, šireći tako rezistentne bakterija nadaleko i naširoko. Istraživači su računalno pregledali biblioteku malih kemijskih molekula koje bi se vezale na protein (TraE) koji je neophodan za ovaj prijenos plazmida. Mjesto vezanja inhibitora poznato je iz 3D molekularne strukture proteina i vidjelo se da je nakon što su potencijalni inhibitori vezani na protein, prijenos plazmida otpornih na antibiotike, koji nose gen, značajno smanjen, što sugerira potencijalnu strategiju za ograničavanje i preokret antibiotika. otpornost. Međutim, za ovu vrstu studija 3D Potrebna je molekularna struktura proteina što je čini malo ograničavajućim jer mnogi proteini tek trebaju biti strukturno okarakterizirani. Ipak, ideja je ohrabrujuća i takvi bi inhibitori vjerojatno mogli igrati važnu ulogu u svakodnevnoj zdravstvenoj skrbi.
Otpornost na antibiotike prijeti i potkopava nekoliko desetljeća poboljšanja i postignuća koja su postignuta u ljudskom tijelu zdravstvene i razvoj a provedba ovog rada imat će ogroman izravan utjecaj na sposobnost ljudi da žive zdrav život.
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Izvor (i)
1. TKO. Izvješće o globalnom sustavu za nadzor rezistencije na antimikrobne lijekove (GLASS). http://www.who.int/glass/resources/publications/early-implementation-report/en/ [Pristupljeno 29. siječnja 2018.].
2. TKO. Kako zaustaviti rezistenciju na antibiotike? Evo recepta SZO. http://www.who.int/mediacentre/commentaries/stop-antibiotic-resistance/en/. [Pristupljeno 10. veljače 2018.].
3. Arnold SR. i Straus SE. 2005. Intervencije za poboljšanje prakse propisivanja antibiotika u ambulantnoj skrbi.Cochrane Database Syst Otk. 19 (4). https://doi.org/10.1002/14651858.CD003539.pub2
4. Jiménez-Castellanos JC. et al. 2017. Promjene proteoma ovojnice uzrokovane prekomjernom proizvodnjom RamA u Klebsiella pneumoniae koje povećavaju stečenu rezistenciju na β-laktam. Časopis za antimikrobnu kemoterapiju. 73 (1) https://doi.org/10.1093/jac/dkx345
5. Calvopiña K. i sur.2017. Strukturni/mehanistički uvidi u učinkovitost neklasičnih inhibitora β-laktamaze protiv kliničkih izolata stenotrophomonasmaltofilije otpornih na lijekove. Molekularna mikrobiologija. 106(3). https://doi.org/10.1111/mmi.13831
6. Casu B. i sur. 2017. Probir na temelju fragmenata identificira nove mete za inhibitore konjugativnog prijenosa antimikrobne rezistencije pomoću plazmida pKM101. Znanstveni Izvješća. 7 (1). https://doi.org/10.1038/s41598-017-14953-1
