BACKGROUND Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs). METHODS AND FINDINGS We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders. CONCLUSIONS We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.

中文翻译：

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低收入和中等收入国家抗生素耐药细菌引起的住院患者血流感染的影响：系统评价和荟萃分析。

背景技术由抗生素抗性细菌(ARB)产生的血流感染(BSI)在全世界造成巨大的疾病负担。然而，大多数估计来自高收入环境，因此不具有全球代表性。本研究量化了中低收入成人住院患者与抗生素敏感细菌 (ASB) 相比，与 ARB BSI 相关的超额死亡率、住院时间 (LOS)、重症监护病房 (ICU) 入住以及经济成本。收入国家（LMIC）。方法和结果 我们通过检索 4 个医学数据库（PubMed、SCIELO、Scopus 和 WHO 的全球 Index Medicus；从成立到 2022 年 8 月 1 日的初始检索 n = 13,012）进行了系统评价。我们只纳入了定量研究。我们的最终样本由 n = 109 篇文章组成，不包括来自高收入国家的研究，没有我们感兴趣的结果，或者没有明确的血流感染源。使用逆方差异质性模型对粗死亡率、ICU入院率和LOS进行荟萃分析，进行一般分析和亚组分析，包括细菌革兰氏菌类型、家族和耐药类型。对于经济成本，每床日的直接医疗费用来自 WHO-CHOICE。死亡率成本是根据过早死亡导致的潜在寿命损失年数所造成的生产力损失来估算的。所有成本均以 2020 年美元为单位。我们使用 MASTER 框架评估研究的质量和发表偏倚风险。多变量元回归仅用于死亡率和 ICU 入院结果。大多数纳入的研究显示粗死亡率显着增加（比值比 (OR) 1.58，95% CI [1.35 至 1.80]，p < 0.001），ARB 与 ASB BSI 的总 LOS（标准化平均差“SMD”0.49，95% CI [0.20 至 0.78]，p < 0.001）和 ICU 入住（OR 1.96，95% CI [1.56 至 2.47]，p < 0.001） 。对非洲和西太平洋地区中高收入国家的肠杆菌科细菌、鲍曼不动杆菌和金黄色葡萄球菌进行分析的研究表明，与 ASB BSI 相比，ARB 患者的超额死亡率、LOS 和 ICU 入住率最高。多变量荟萃回归表明，与 ARB BSI 患者相比，耐药鲍曼不动杆菌 BSI 患者的死亡率更高（OR 1.67，95% CI [1.18 至 2.36]，p < 0.004）。ARB 与 ASB BSI 相比，每位患者的额外直接医疗费用估计为 12,442 美元（95% CI [6,693 至 18,191 美元]），平均费用为 41,103 美元（95% CI [30,931 美元至 51 美元]，274]）由于过早死亡。局限性包括一些审查研究的质量较差，涉及选择性抽样的高风险或未能充分考虑相关混杂因素。结论 我们根据现有文献概述了 ARB BSI 在有限资源环境中的影响。耐药性与中低收入国家的巨大疾病和经济负担相关。尽管如此，我们的结果显示世卫组织区域、收入群体和病原体药物组合之间存在广泛的异质性。总体而言，中低收入国家的 BSI 数据较少，这阻碍了具体国家政策的实施和卫生进展的跟踪。局限性包括一些审查研究的质量较差，涉及选择性抽样的高风险或未能充分考虑相关混杂因素。结论 我们根据现有文献概述了 ARB BSI 在有限资源环境中的影响。耐药性与中低收入国家的巨大疾病和经济负担相关。尽管如此，我们的结果显示世卫组织区域、收入群体和病原体药物组合之间存在广泛的异质性。总体而言，中低收入国家的 BSI 数据较少，这阻碍了具体国家政策的实施和卫生进展的跟踪。局限性包括一些审查研究的质量较差，涉及选择性抽样的高风险或未能充分考虑相关混杂因素。结论 我们根据现有文献概述了 ARB BSI 在有限资源环境中的影响。耐药性与中低收入国家的巨大疾病和经济负担相关。尽管如此，我们的结果显示世卫组织区域、收入群体和病原体药物组合之间存在广泛的异质性。总体而言，中低收入国家的 BSI 数据较少，这阻碍了具体国家政策的实施和卫生进展的跟踪。耐药性与中低收入国家的巨大疾病和经济负担相关。尽管如此，我们的结果显示世卫组织区域、收入群体和病原体药物组合之间存在广泛的异质性。总体而言，中低收入国家的 BSI 数据较少，这阻碍了具体国家政策的实施和卫生进展的跟踪。耐药性与中低收入国家的巨大疾病和经济负担相关。尽管如此，我们的结果显示世卫组织区域、收入群体和病原体药物组合之间存在广泛的异质性。总体而言，中低收入国家的 BSI 数据较少，这阻碍了具体国家政策的实施和卫生进展的跟踪。