Dawa mpya iliyogunduliwa inafuata utaratibu wa kipekee katika kupambana na bakteria sugu ya dawa zinazohusika na UTI.
Antibiotic resistance is a major global threat to healthcare. Antibiotic resistance occurs when bacteria modify themselves in some manner which then either reduces or completely removes the effectiveness of an antibiotic drug which were originally developed and designed to prevent or cure infections caused by this bacterium. The ‘changed’ bacteria survive and continue to grow/multiply and same drugs now become ineffective on them. Many existing antibiotics are no longer able to combat most bacterial infections after developing high resistance against them. With time many different strains of bacteria have become or are becoming resistant to antibiotics. Misuse and uncontrolled overuse of antibiotics had further compounded this problem. Few new antibiotics which have been made available in the last several years or the ones which are currently undergoing trials rely on existing mechanisms of killing bacteria clearly indicating that most bacteria might already be resistant to them. World Health Organisation (WHO) has labelled gram-negative bacteria like Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae – carbapenem-resistant strains- as responsible for difficult-to-treat infections in clinical care and they are in the highest resistance category and are hardest to treat. For such bacterial strains no alternative antibiotics are available and the ones available have serious and drastic side effects.There is an urgent need for new strategies and novel antibiotics which will have unique modes of action.
Antibiotiki mpya
Antibiotiki mpya imegunduliwa ambayo ni nzuri sana katika kutibu tata na ya juu maambukizi ya njia ya mkojo (UTI) ambayo husababishwa na bakteria nyingi za gram-negative ambazo hustahimili dawa nyingi. Utafiti huu, jaribio la kimatibabu la awamu ya pili, umeongozwa na watafiti katika kampuni ya dawa ya Shionogi Inc nchini Japan na umechapishwa katika Magonjwa ya Kuambukiza ya Lancet. Dawa ya antibiotic inaitwa cefiderocol is a siderophore-based drug which can eradicate higher levels of ‘stubborn’ bacteria (pathogen) and is seen to be not only very similar to standard antibiotics clinically used called imipenem-cilastatin but the new drug outperforms its effects.
Kesi hiyo iliendeshwa na watu wazima 448 wamelazwa hospitalini kutokana na hali ngumu ICU maambukizi au kuvimba kwa figo kutokana na maambukizi makali ya bakteria. Wagonjwa wengi waliambukizwa na bakteria E. koli, klebsiella na bakteria wengine wa kundi-hasi ambao ni sugu kwa dawa nyingi za kawaida za viuavijasumu. Watu wazima 300 walipokea dozi tatu za kila siku za cefiderocol na watu wazima 148 walipata matibabu ya kawaida ya imipenem-cilastatin kwa jumla ya siku 14. Dawa hii mpya ni ya kipekee sana katika mbinu yake ya kukabiliana na ukinzani wa viuavijasumu unaotumiwa na gram-negative vimelea in comparison to all therapies known so far. It targets main three mechanisms (or barriers) which are used by bacteria to cause strong resistance to antibiotics in the first place. The drug succeeds in bypassing all defence mechanisms of the bacteria. The barriers are firstly, two outer membranes of the bacteria that create difficulty for antibiotics to infiltrate the bacterial cell. Secondly, porin channels which readily acclimatize blocking entry of antibiotics and thirdly, efflux pump of the bacteria which expels the antibiotic out of the bacterial cell rendering the antibiotic drug ineffective.
Utaratibu mzuri
Maambukizi ya bakteria yanapotokea katika mwili wetu, mfumo wetu wa kinga hujibu kwa kuunda mazingira ya chini ya chuma ambayo yanaweza kuzuia uwezo wa bakteria kukua. Bakteria pia ni mahiri, kwa mfano E Coli., kwani hujibu kwa kukusanya chuma nyingi kadri wawezavyo. Dawa hii mpya ya antibiotiki iliyogunduliwa hutumia utaratibu wa kipekee kuingiza bakteria kwa kutumia utaratibu huu wenyewe wa bakteria wanaojaribu kupata chuma ili waendelee kuishi. Kwanza, dawa hufunga chuma na kusafirishwa kwa akili kupitia utando wa nje wa njia za kusafirisha chuma za bakteria hadi kwenye seli ambapo inaweza kuvuruga na kuharibu bakteria. Njia hizi za usafirishaji wa chuma pia huwezesha dawa kukwepa njia za porini za bakteria zinazopinga utaratibu wa kizuizi cha pili cha bakteria. Hali hii husaidia dawa kupata upatikanaji wa mara kwa mara hata mbele ya pampu za efflux.
The adverse effects of this new drug cefiderocol were similar to earlier therapies and most common symptoms were nausea, diarrhoea, constipation and abdominal pain. The drug was found to be effective, safe and well tolerated especially in older patients who were multi-drug resistant and had serious urinary tract or kidney infections. Cefiderocol was as effective as the standard antibiotic but whilst showing a sustained and superior antibacterial activity. Further clinical trials are ongoing to evaluate this new drug in patients suffering from hospital-acquired pneumonia and ventilator-associated pneumonia which is a common infection problem in healthcare settings. Authors stated that patients with carbapenem-resistant infections were not included in the current study because carbapenem was a comparator and this is being considered as one critical limitation of the study. This study has brought immense hope in fighting drug resistance and is seen as an initial first important step towards creating novel antibiotics.
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Chanzo (s)
Portsmouth S et al. 2018. Cefiderocol dhidi ya imipenem-cilastatin kwa ajili ya matibabu ya maambukizo magumu ya njia ya mkojo yanayosababishwa na uropathojeni ya Gram-negative: awamu ya 2, majaribio ya randomised, upofu-mbili, yasiyo ya chini. Magonjwa ya Kuambukiza ya Lancet. https://doi.org/10.1016/S1473-3099(18)30554-1
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