Nýlegar greiningar og rannsóknir hafa vakið von um að vernda mannkynið gegn sýklalyfjaónæmi sem er fljótt að verða alþjóðleg ógn.
Uppgötvunin á sýklalyf in mid 1900s was a significant milestone in the history of medicine as it was a miracle therapeutic for many baktería sýkingar og bakteríur-causing diseases. Sýklalyf 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.
Ónæmi gegn sýklalyfjum eykst hratt
Sýklalyf are medicines which are naturally produced by microorganisms and they stop or kill bakteríur from growing. It is of critical importance because baktería infections have plagued mankind throughout time. However, “resistant” bakteríur develop defences that protect them against the effects of sýklalyf when previously they were killed by them. These resistant bacteria then are able to withstand any attacks by antibiotics and consequently if these bakteríur 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 bakteríur 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. Sýklalyfjaónæmi 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 sýklalyf 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.
WHO könnun: „eftir sýklalyfjatímabilið“?
Alþjóðaheilbrigðismálastofnunin (WHO) hefur lýst því yfir sýklalyfjaónæmi hefur mikil forgang og alvarlegt heilbrigðismál í gegnum Global Antimicrobial Resistance Surveillance System (GLASS) sem var sett á markað í október 2015. Þetta kerfi safnar, greinir og deilir gögnum um sýklalyfjaónæmi um allan heim. Frá og með 2017 hafa 52 lönd (25 hátekjulönd, 20 meðaltekjur og sjö lágtekjulönd) skráð sig í GLASS. Það er fyrsta skýrslan1 inniheldur upplýsingar um magn sýklalyfjaónæmis frá 22 löndum (hálf milljón þátttakenda skráðir í könnunina) sem sýnir vöxt á skelfilegum hraða - í heildina gríðarlega 62 til 82 prósent ónæmi. Þetta frumkvæði WHO miðar að því að skapa vitund og samhæfingu milli mismunandi þjóða til að takast á við þetta alvarlega vandamál á heimsvísu.
Við hefðum getað komið í veg fyrir sýklalyfjaónæmi og getum enn
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 sýklalyf. The doctors have overly prescribed sýklalyf to any or every patient in the past many decades. Also, in many countries, especially the developing countries of Asia and Africa, sýklalyf 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 sýklalyf 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 sýklalyf are taken or not. In fact, it’s just incorrect and a mystery for many as to how exactly sýklalyf (which target bakteríur) will have any effect on viruses! The sýklalyf 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, sýklalyf 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 bakteríur which reside in those food or animals causing rigorous transfer of resistant strain bakteríur þvert á landamæri.
Þessi atburðarás er enn flóknari vegna þess að engin ný sýklalyf hafa verið þróuð af lyfjafyrirtækjum á undanförnum áratugum - síðasti nýi sýklalyfjaflokkurinn fyrir gramm-neikvæðar bakteríur var kínólónin þróuð fyrir fjórum áratugum. Þannig, eins og við erum núna, getum við í raun ekki verið að hugsa um að koma í veg fyrir sýklalyfjaónæmi með því að bæta við fleiri og mismunandi sýklalyfjum þar sem þetta mun aðeins torvelda ónæmi og flutning. Margir eiturlyf fyrirtæki hafa bent á að þróa einhverjar nýjar eiturlyf er í fyrsta lagi mjög dýrt þar sem það er langt ferli sem krefst mikillar fjárfestinga og hugsanlegs hagnaðar af sýklalyf 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 sýklalyf is not the solution for prevention of their resistance.
WHO mælir með aðgerðaáætlun2 til að koma í veg fyrir sýklalyfjaónæmi:
a) Healthcare professionals and workers should be doing a careful detailed assessment before prescribing sýklalyf 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 baktería) is conveyed that his/her condition will improve in 3 days, else sýklalyf 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 sýklalyf and they must take sýklalyf only when satisfied that it is absolutely necessary. They must also complete the prescribed dosage to prevent fast growth of resistant baktería 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. Setja þarf upp sérsniðna ramma fyrir þróuð lönd og meðal- og lágtekjulönd sem tengjast þörfum þeirra.
Nú þegar skaðinn er skeður: takast á við sýklalyfjaónæmi
So that we do not plunge into a new ’post sýklalyf’ 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 Journal of Antimicrobial Chemotherapy4 sýnir að hvenær bakteríur become resistant, one of the ways which they adopt to restrict sýklalyf 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 Sameinda örverufræði5, 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 bakteríur. 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 sýklalyf, engu að síður hefur starf þeirra vakið von um að snúa aftur öldu sýklalyfjaónæmis.
Í annarri rannsókn sem birt var í Scientific skýrslur6, vísindamenn við Université de Montréal hafa fundið upp nýja nálgun til að hindra flutning ónæmis milli baktería sem er ein af leiðum sem sýklalyfjaónæmi dreifist á sjúkrahúsum og heilsudeildum. Genin sem bera ábyrgð á því að gera bakteríurnar ónæmar eru kóðaðar á plasmíðum (lítil DNA brot sem getur fjölgað sér sjálfstætt) og þessi plasmíð flytjast á milli baktería og dreifa þannig ónæmum bakteríur víða. Vísindamenn skimuðu með reikningsskilum safn lítilla efnasameinda sem myndu bindast próteininu (TraE) sem er nauðsynlegt fyrir þennan plasmíðflutning. Hindrunarstaðurinn er þekktur úr þrívíddar sameindabyggingu próteins og sást að þegar hugsanlegir hemlar voru bundnir við próteinið minnkaði verulega flutningur á sýklalyfjaónæmum, genaberandi plasmíðum, sem bendir til hugsanlegrar aðferðar til að takmarka og snúa við sýklalyfjum. mótstöðu. Hins vegar, fyrir þessa tegund af rannsóknum 3D Krafist er sameindabyggingar próteins sem gerir það að verkum að það er örlítið takmarkandi þar sem mörg prótein eiga enn eftir að skilgreina uppbyggingu. Engu að síður er hugmyndin uppörvandi og slíkir hemlar gætu líklega gegnt mikilvægu hlutverki í daglegri heilsugæslu.
Sýklalyfjaónæmi ógnar og grefur undan margra áratuga umbótum og ávinningi sem náðst hefur í mönnum heilsugæslu og þróun and implementation of this work will have a huge direct impact on the capability of people to live healthy lives.
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{Þú getur lesið upprunalegu rannsóknarritgerðina með því að smella á DOI hlekkinn sem gefinn er upp hér að neðan á listanum yfir tilvitnaðar heimildir}
Heimildir)
1. HVER. Skýrsla um alþjóðlegt eftirlitskerfi fyrir sýklalyfjaónæmi (GLASS). http://www.who.int/glass/resources/publications/early-implementation-report/en/ [Skoðað 29. janúar 2018].
2. HVER. Hvernig á að stöðva sýklalyfjaónæmi? Hér er lyfseðill frá WHO. http://www.who.int/mediacentre/commentaries/stop-antibiotic-resistance/en/. [Skoðað 10. febrúar 2018].
3. Arnold SR. og Straus SE. 2005. Inngrip til að bæta sýklalyfjaávísun í sjúkraflutningum.Cochrane Database syst Rev. 19 (4). https://doi.org/10.1002/14651858.CD003539.pub2
4. Jiménez-Castellanos JC. o.fl. 2017. Hjúppróteómbreytingar knúnar áfram af RamA offramleiðslu í Klebsiella pneumoniae sem auka áunna β-laktamþol. Journal of Antimicrobial Chemotherapy. 73(1) https://doi.org/10.1093/jac/dkx345
5. Calvopiña K. o.fl.2017. Skipulags-/vélfræðileg innsýn í virkni óklassískra β-laktamasahemla gegn klínískum einangrunum sem eru mjög ónæmar fyrir Stenotrophomonasmaltophilia. Sameinda örverufræði. 106(3). https://doi.org/10.1111/mmi.13831
6. Casu B. o.fl. 2017. Skimun sem byggir á brotum auðkennir ný markmið fyrir hemla á samtengingarflutningi á sýklalyfjaónæmi með plasmíði pKM101. Scientific skýrslur. 7 (1). https://doi.org/10.1038/s41598-017-14953-1
