Haydom Lutheran Hospital, Haydom, United Republic of Tanzania.
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands.
Antimicrob Resist Infect Control. 2023 Apr 19;12(1):37. doi: 10.1186/s13756-023-01238-8.
Fixed-dose combinations (FDC) are medicine formulations that combine two or more ingredients in fixed ratios in a single dose form. Although advantageous in tuberculosis and malaria (efficacy, adherence, protection against resistance), only a few antibiotic FDC (FDC-AB) have been developed along full microbiological, pharmacological and clinical validation and safety studies. The World Health Organization (WHO) database of Access, Watch and Reserve (AWaRe) antibiotics contains, since 2021, a list of "Not Recommended" FDC-AB (n = 103) which are rejected for use in clinical practice. BODY: The share of non-recommended FDC-AB in global antimicrobial use (2000-2015) was < 3% but substantially higher in middle income countries. The share increases over time, but recent data particular concerning sub-Saharan Africa are rare. Along three non-recommended FDC-AB listed in the Tanzanian National Essential Medicine List (ampicillin-cloxacillin, flucloxacillin-amoxicillin and ceftriaxone-sulbactam) we discuss the concerns and reasons behind use of these products. Non-recommended FDC-AB have poor rationale (ratios of both ingredients), lack evidence of efficacy (pharmacological, microbiological and clinical), have difficulties in dosing (underdosing of the single ingredients, absence of pediatric dosing) and risks of safety (additive toxicity). They are expected to fuel antimicrobial resistance (unnecessary broad spectrum coverage) and are incompatible with antimicrobial stewardship. The specific context of low- and middle-income countries contributes to their increased use: at the side of prescriber and supplier are the lack of diagnostics, poor training in antibiotic prescribing, patients' preferences, role-model of senior prescribers and pharmaceutical promotion. International market mechanisms include economic motivation for development, branding and promotion, poor access to the single antibiotic forms and weak national regulatory capacity.
There is an urgent need for monitoring consumption of non-recommended FDC-AB in low- and middle-income countries, particular in Sub-Saharan Africa. A multinational and multisectoral antimicrobial stewardship strategy is needed in order to abolish the use of non-recommended FDC-AB.
固定剂量组合（FDC）是将两种或多种成分以固定比例组合在单一剂量形式中的药物制剂。尽管在结核病和疟疾方面具有优势（疗效、依从性、耐药性保护），但只有少数抗生素 FDC（FDC-AB）经过全面的微生物学、药理学和临床验证以及安全性研究开发。世界卫生组织（WHO）的准入、观察和保留（AWaRe）抗生素数据库自 2021 年以来包含了“不推荐”的 FDC-AB 清单（n=103），这些药物被拒绝用于临床实践。
在全球抗菌药物使用中（2000-2015 年），不推荐的 FDC-AB 比例<3%，但在中等收入国家中比例要高得多。随着时间的推移，这一比例在增加，但最近的数据，特别是关于撒哈拉以南非洲的数据很少。我们讨论了在坦桑尼亚国家基本药物清单中列出的三种不推荐的 FDC-AB（氨苄西林-氯唑西林、氟氯西林-阿莫西林和头孢曲松-舒巴坦）的使用问题和原因。不推荐的 FDC-AB 的使用缺乏合理的理由（两种成分的比例），缺乏疗效的证据（药理学、微生物学和临床），在剂量方面存在困难（单一成分剂量不足，缺乏儿科剂量），存在安全性风险（附加毒性）。它们预计会助长抗菌药物耐药性（不必要的广谱覆盖），并且与抗菌药物管理不相容。低收入和中等收入国家的具体情况导致了它们的使用增加：在处方者和供应者方面，缺乏诊断、抗生素处方培训不足、患者偏好、高级处方者的榜样作用和药品促销等因素都起到了作用。国际市场机制包括开发的经济动机、品牌和促销、单一抗生素形式的获取困难以及国家监管能力薄弱。
迫切需要监测低收入和中等收入国家，特别是撒哈拉以南非洲地区不推荐的 FDC-AB 的消费情况。需要采取跨国和多部门的抗菌药物管理策略，以消除不推荐的 FDC-AB 的使用。
