The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis

Abstract

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 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. Kasim Allel and colleagues systematically review published literature from low- and middle-income countries and meta-analyse data extracted from 109 articles to explore the impact of bloodstream infections caused by antibiotic-resistant bacteria. Author summary Why was this study done? Bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) have multifaceted impacts, including higher admission to intensive care units (ICUs), prolonged hospitalisations, and high economic and societal costs worldwide. Despite the global burden, most evidence on the excess burden of ARB BSIs has been derived from high-income countries; comparatively, there are limited data from low- and middle-income countries (LMICs). What did the researchers do and find? We employed a systematic literature review and subsequent meta-analysis of 109 individual studies to quantify the impact of ARB BSIs in hospitalised patients from LMICs. Based mostly on crude data comparisons ignoring the possible influence of confounding factors, we found that ARB BSIs, compared to BSIs caused by antibiotic-sensitive bacteria (ASB), were associated with substantially longer stays in hospitals and ICUs, higher mortality, and increased direct medical and productivity costs. What do these findings mean? Our findings highlight the excess morbidity, mortality, and costs associated with ARB BSIs and the sparsity of data from LMICs. Targeted strategies to improve the prevention, detection, and treatment of resistant BSIs in LMICs are required to reduce the economic and disease burden.