Analisis dan kajian terkini telah menjana harapan ke arah melindungi manusia daripada rintangan antibiotik yang pantas menjadi ancaman global.
Penemuan mengenai antibiotik in mid 1900s was a significant milestone in the history of medicine as it was a miracle therapeutic for many bakteria jangkitan dan bakteria-causing diseases. Antibiotik 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.
Rintangan terhadap antibiotik berkembang dengan pantas
Antibiotik are medicines which are naturally produced by microorganisms and they stop or kill bakteria from growing. It is of critical importance because bakteria infections have plagued mankind throughout time. However, “resistant” bakteria develop defences that protect them against the effects of antibiotik when previously they were killed by them. These resistant bacteria then are able to withstand any attacks by antibiotics and consequently if these bakteria 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 bakteria 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. Rintangan antibiotik 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 antibiotik 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.
Tinjauan WHO: 'era pasca antibiotik'?
Pertubuhan Kesihatan Sedunia (WHO) telah mengisytiharkan rintangan antibiotik satu keutamaan tinggi dan isu kesihatan yang serius melalui Sistem Pengawasan Kerintangan Antimikrob Global (GLASS) yang dilancarkan pada Okt 2015. Sistem ini mengumpul, menganalisis dan berkongsi data tentang rintangan antibiotik di seluruh dunia. Sehingga 2017, 52 negara (25 negara berpendapatan tinggi, 20 berpendapatan sederhana dan tujuh negara berpendapatan rendah) telah mendaftar dalam GLASS. Ia adalah laporan pertama1 mengandungi maklumat tentang tahap rintangan antibiotik yang disediakan oleh 22 negara (satu-setengah juta peserta yang mendaftar dalam tinjauan) menunjukkan pertumbuhan pada kadar yang membimbangkan– secara keseluruhannya rintangan besar 62 hingga 82 peratus. Inisiatif WHO ini bertujuan untuk mewujudkan kesedaran dan menyelaras antara negara yang berbeza untuk menangani masalah serius ini di peringkat global.
Kita boleh menghalang rintangan antibiotik dan masih boleh
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 antibiotik. The doctors have overly prescribed antibiotik to any or every patient in the past many decades. Also, in many countries, especially the developing countries of Asia and Africa, antibiotik 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 antibiotik 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 antibiotik are taken or not. In fact, it’s just incorrect and a mystery for many as to how exactly antibiotik (which target bakteria) will have any effect on viruses! The antibiotik 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, antibiotik 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 bakteria which reside in those food or animals causing rigorous transfer of resistant strain bakteria merentas sempadan.
Senario ini lebih rumit oleh fakta bahawa tiada antibiotik baru telah dibangunkan oleh syarikat farmasi dalam beberapa dekad yang lalu - kelas antibiotik baharu yang terakhir untuk gram-negatif bakteria adalah kuinolon yang dibangunkan empat dekad yang lalu. Oleh itu, seperti yang kita ada sekarang, kita tidak boleh benar-benar berfikir untuk mencegah rintangan antibiotik dengan menambah lebih banyak antibiotik yang berbeza kerana ini hanya akan merumitkan lagi rintangan dan pemindahan. banyak dadah syarikat telah menegaskan bahawa membangunkan mana-mana yang baru dadah pertama sekali sangat mahal kerana ia merupakan proses yang panjang yang memerlukan pelaburan besar dan potensi keuntungan daripadanya antibiotik 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 antibiotik is not the solution for prevention of their resistance.
WHO mengesyorkan pelan tindakan2 untuk mencegah rintangan antibiotik:
a) Healthcare professionals and workers should be doing a careful detailed assessment before prescribing antibiotik 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 bakteria) is conveyed that his/her condition will improve in 3 days, else antibiotik 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 antibiotik and they must take antibiotik only when satisfied that it is absolutely necessary. They must also complete the prescribed dosage to prevent fast growth of resistant bakteria 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. Rangka kerja tersuai perlu disediakan untuk negara maju dan negara berpendapatan sederhana dan rendah yang berkaitan dengan keperluan mereka.
Sekarang kerosakan telah berlaku: menangani rintangan antibiotik
So that we do not plunge into a new ’post antibiotik’ 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 Jurnal Kemoterapi Antimikrob4 menunjukkan bahawa apabila bakteria become resistant, one of the ways which they adopt to restrict antibiotik 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 Mikrobiologi Molekul5, 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 bakteria. 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, walau bagaimanapun, kerja mereka telah menjana harapan untuk memulihkan gelombang rintangan antibiotik.
Dalam kajian lain yang diterbitkan dalam Laporan Saintifik6, penyelidik di Université de Montréal telah mencipta pendekatan baru untuk menyekat pemindahan rintangan antara bakteria yang merupakan salah satu cara rintangan antibiotik merebak di hospital dan unit kesihatan. Gen yang bertanggungjawab untuk menjadikan bakteria tahan dikodkan pada plasmid (sejenis kecil DNA serpihan yang boleh mereplikasi secara bebas) dan plasmid ini berpindah antara bakteria, dengan itu menyebarkan yang tahan bakteria jauh dan lebar. Penyelidik menyaring perpustakaan molekul kimia kecil secara pengiraan yang akan mengikat protein (TraE) yang penting untuk pemindahan plasmid ini. Tapak pengikat perencat diketahui daripada struktur molekul 3D protein dan dilihat bahawa sebaik sahaja perencat berpotensi terikat pada protein, pemindahan plasmid pembawa gen yang tahan antibiotik telah berkurangan dengan ketara sekali gus mencadangkan strategi yang berpotensi untuk menyekat dan membalikkan antibiotik. rintangan. Walau bagaimanapun, untuk jenis kajian ini 3D struktur molekul protein diperlukan yang menjadikannya sedikit mengehadkan kerana banyak protein masih belum dicirikan secara struktur. Walau bagaimanapun, idea itu menggalakkan dan perencat tersebut mungkin memainkan peranan penting dalam penjagaan kesihatan harian.
Rintangan antibiotik mengancam dan menjejaskan beberapa dekad penambahbaikan dan keuntungan yang telah dibuat pada manusia penjagaan kesihatan and pembangunan and implementation of this work will have a huge direct impact on the capability of people to live healthy lives.
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{Anda boleh membaca kertas penyelidikan asal dengan mengklik pautan DOI yang diberikan di bawah dalam senarai sumber yang dipetik}
Sumber (s)
1. SIAPA. Laporan sistem pengawasan rintangan antimikrob global (GLASS). http://www.who.int/glass/resources/publications/early-implementation-report/en/ [Diakses pada 29 Januari 2018].
2. SIAPA. Bagaimana untuk menghentikan rintangan antibiotik? Berikut adalah preskripsi WHO. http://www.who.int/mediacentre/commentaries/stop-antibiotic-resistance/en/. [Diakses pada 10 Februari 2018].
3. Arnold SR. dan Straus SE. 2005. Intervensi untuk menambah baik amalan preskripsi antibiotik dalam penjagaan ambulatori.Pangkalan Data Cochrane saia Rev. 19(4). https://doi.org/10.1002/14651858.CD003539.pub2
4. Jiménez-Castellanos JC. et al. 2017. Perubahan proteom sampul didorong oleh pengeluaran berlebihan RamA dalam Klebsiella pneumoniae yang meningkatkan rintangan β-laktam yang diperoleh. Jurnal Kemoterapi Antimikrob. 73(1) https://doi.org/10.1093/jac/dkx345
5. Calvopiña K. et al.2017. Pandangan struktur/mekanistik tentang keberkesanan perencat β-laktamase bukan klasik terhadap pencilan klinikal Stenotrophomonasmaltophilia yang tahan dadah secara meluas. Mikrobiologi Molekul. 106(3). https://doi.org/10.1111/mmi.13831
6. Casu B. et al. 2017. Penyaringan berasaskan serpihan mengenal pasti sasaran baru untuk perencat pemindahan konjugatif rintangan antimikrob oleh plasmid pKM101. Laporan Saintifik. 7(1). https://doi.org/10.1038/s41598-017-14953-1
