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

<h4>Background</h4>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, leng...

Full description

Saved in:
Bibliographic Details
Main Authors: Kasim Allel, Jennifer Stone, Eduardo A Undurraga, Lucy Day, Catrin E Moore, Leesa Lin, Luis Furuya-Kanamori, Laith Yakob
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-06-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004199&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850163930966523904
author Kasim Allel
Jennifer Stone
Eduardo A Undurraga
Lucy Day
Catrin E Moore
Leesa Lin
Luis Furuya-Kanamori
Laith Yakob
author_facet Kasim Allel
Jennifer Stone
Eduardo A Undurraga
Lucy Day
Catrin E Moore
Leesa Lin
Luis Furuya-Kanamori
Laith Yakob
author_sort Kasim Allel
collection DOAJ
description <h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.
format Article
id doaj-art-5c4e76bc18bc45dcb448d7c986cec0fb
institution OA Journals
issn 1549-1277
1549-1676
language English
publishDate 2023-06-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Medicine
spelling doaj-art-5c4e76bc18bc45dcb448d7c986cec0fb2025-08-20T02:22:06ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762023-06-01206e100419910.1371/journal.pmed.1004199The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.Kasim AllelJennifer StoneEduardo A UndurragaLucy DayCatrin E MooreLeesa LinLuis Furuya-KanamoriLaith Yakob<h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004199&type=printable
spellingShingle Kasim Allel
Jennifer Stone
Eduardo A Undurraga
Lucy Day
Catrin E Moore
Leesa Lin
Luis Furuya-Kanamori
Laith Yakob
The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
PLoS Medicine
title The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
title_full The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
title_fullStr The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
title_full_unstemmed The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
title_short The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.
title_sort impact of inpatient bloodstream infections caused by antibiotic resistant bacteria in low and middle income countries a systematic review and meta analysis
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004199&type=printable
work_keys_str_mv AT kasimallel theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT jenniferstone theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT eduardoaundurraga theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT lucyday theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT catrinemoore theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT leesalin theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT luisfuruyakanamori theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT laithyakob theimpactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT kasimallel impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT jenniferstone impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT eduardoaundurraga impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT lucyday impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT catrinemoore impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT leesalin impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT luisfuruyakanamori impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis
AT laithyakob impactofinpatientbloodstreaminfectionscausedbyantibioticresistantbacteriainlowandmiddleincomecountriesasystematicreviewandmetaanalysis