The Spread of 𝛽-Lactamases and Extended Spectrum 𝛽-Lactamase Enzymes among Bacteria: A Threat to Effective Health Care Delivery

I. Rabiu, I. Abdullahi, Aminu Abdullahi Mahmoud
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Abstract

Antibiotic discovery continue to play a critical role in disease containment. Misuse and overuse of these drugs are the main drivers in the development of drug resistant pathogens. The World Health Organisation has declared that Antimicrobial resistance is one of the top 10 global public health threats facing humanity. There is the fears that if nothing is done, it might end the antibiotic era soon. In 2017 alone, over 9000 human deaths were caused by ESBL-producing Enterobacteriaceae in the USA. The ability of bacteria to develop newer strategies to acquire and disseminate resistance, can be traced as far back to 1940s when (R-factor) plasmid mediated antibiotic resistance was observed. They become resistant via the production of 𝛽-Lactamases and ESBLs enzymes which inactivate or modify antibiotics. Extended Spectrum 𝛽-Lactamases are enzymes whose rates of hydrolysis of the extended-spectrum 𝛽-Lactam antibiotics are >10 % than that for benzylpenicillin. Some bacteria may produce multiple ß-lactamases, which may reduce the effectiveness of ß-lactam/ ß-lactamase inhibitor combinations. These enzymes are susceptible to inhibition by 𝛽-Lactam inhibitors such as clavulanic acid, tazobactam, or sulbactam but have no hydrolytic activity against cephamycins and carbapenems. The production of acquired 𝛽-Lactamase and ESBL makes the choice of antibiotic treatment of infections caused by Gram-negative bacteria very limited, these have been the major causes of treatment failures, outbreaks of both community and hospital acquired infections, surgical failures, long hospital stay and huge economic losses, which continue to claim uncountable lives, especially in Nigeria and Africa where the health system are weak. The emergence of drug resistannt strains may be minimized by maintaining high levels of the drug in the tissues to inhibit mutants, administering two drugs that do not give cross-resistance, and by limiting the use of valuable second line ‘reserve drugs’ such .....
细菌中𝛽-Lactamases和延伸谱𝛽-Lactamase酶的传播:对有效医疗服务的威胁
抗生素的发现继续在疾病控制中发挥关键作用。这些药物的误用和过度使用是产生耐药病原体的主要驱动因素。世界卫生组织宣布,抗菌素耐药性是人类面临的十大全球公共卫生威胁之一。有人担心,如果不采取任何措施,抗生素时代可能很快就会结束。仅在2017年,美国就有9000多人死于产esbl的肠杆菌科。细菌开发获得和传播耐药性的新策略的能力可以追溯到20世纪40年代,当时观察到(r因子)质粒介导的抗生素耐药性。它们通过产生𝛽-Lactamases和ESBLs酶产生耐药性,这些酶灭活或修饰抗生素。延伸谱𝛽-Lactamases是指其延伸谱𝛽-Lactam抗生素的水解率比青霉素的水解率> 10%的酶。有些细菌可能产生多种ß-内酰胺酶,这可能会降低ß-内酰胺/ ß-内酰胺酶抑制剂联合使用的有效性。这些酶易受𝛽-Lactam抑制剂(如克拉维酸、他唑巴坦或舒巴坦)的抑制,但对头孢霉素和碳青霉烯类没有水解活性。获得性𝛽-Lactamase和ESBL的生产使得革兰氏阴性菌引起的感染的抗生素治疗选择非常有限,这些是治疗失败、社区和医院获得性感染暴发、手术失败、长期住院和巨大经济损失的主要原因,这些原因继续夺去无数人的生命,特别是在卫生系统薄弱的尼日利亚和非洲。通过在组织中保持高水平的药物来抑制突变体,给予两种不会产生交叉耐药性的药物,以及限制使用有价值的二线“储备药物”(如.....),可以最大限度地减少耐药菌株的出现
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