In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa

<b>Background</b>: In vitro synergy testing (ST) is a useful means to gauge the performance ofantibiotic combinations against multidrug-resistant (MDR) Gram-negative bacteria (GNB). This study aimed to determine synergy of antibiotics against paediatric bloodstream (BS) carbapenem-resist...

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Main Authors: Prenika Jaglal, Sithembiso Christopher Velaphi, Colin Nigel Menezes, Khine Swe Swe-Han
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/7/630
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author Prenika Jaglal
Sithembiso Christopher Velaphi
Colin Nigel Menezes
Khine Swe Swe-Han
author_facet Prenika Jaglal
Sithembiso Christopher Velaphi
Colin Nigel Menezes
Khine Swe Swe-Han
author_sort Prenika Jaglal
collection DOAJ
description <b>Background</b>: In vitro synergy testing (ST) is a useful means to gauge the performance ofantibiotic combinations against multidrug-resistant (MDR) Gram-negative bacteria (GNB). This study aimed to determine synergy of antibiotics against paediatric bloodstream (BS) carbapenem-resistant Enterobacterales (CRE) and extremely drug-resistant (XDR) <i>Acinetobacter</i> species. <b>Methods</b>: This cross-sectional study was conducted at a public tertiary hospital in South Africa, from January 2023 to December 2023. Sixty-eight isolates from children with bloodstream infections (BSI), comprising 55.9% (38/68) CRE and 44.1% (30/68) XDR <i>Acinetobacter</i> species, were performed ST using the fixed-ratio Epsilometer-test method. Combinations of colistin and meropenem, colistin and fosfomycin, colistin and tigecycline, meropenem and fosfomycin, meropenem and tigecycline, and fosfomycin and tigecycline were tested. <b>Results</b>: In vitro synergy for CRE was best demonstrated with tigecycline and meropenem, at 92.1% (35/38), and fosfomycin and meropenem at 73.7% (28/38). Among the XDR <i>Acinetobacter</i> species, the highest rates of synergy of 76.7% (23/30) were observed with tigecycline and meropenem. The absence of synergy was noted with colistin and meropenem for the CRE, with many displaying indifference and antagonism at rates of 65.8% and 22%. Most XDR <i>Acinetobacter</i> species (56.7%; 17/30) expressed indifference to colistin and meropenem with synergy and antagonism displayed in 23.3% and 10% of isolates. <b>Conclusions</b>: This study highlights tigecycline and meropenem displaying impressive in vitro synergy when compared to the in-use colistin and meropenem for CRE and XDR <i>Acinetobacter</i> species. Tigecycline and meropenem may be a viable salvage therapeutic option for MDR Gram-negative paediatric infections. Future research is warranted to confirm in vivo synergy clinically.
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spelling doaj-art-5866801d5e454fe59b2f79a4c2b14b312025-08-20T03:13:42ZengMDPI AGAntibiotics2079-63822025-06-0114763010.3390/antibiotics14070630In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South AfricaPrenika Jaglal0Sithembiso Christopher Velaphi1Colin Nigel Menezes2Khine Swe Swe-Han3Department of Clinical Microbiology and Infectious Diseases, National Health Laboratory Service and Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2050, South AfricaDepartment of Paediatrics and Child Health, Chris Hani Baragwanath Academic Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South AfricaDivision of Infectious Diseases, Department of Internal Medicine, University of the Witwatersrand, Johannesburg 2050, South AfricaDepartment of Medical Microbiology, Inkosi Albert Luthuli Central Hospital, National Health Laboratory Service, University of KwaZulu-Natal, Durban 4000, South Africa<b>Background</b>: In vitro synergy testing (ST) is a useful means to gauge the performance ofantibiotic combinations against multidrug-resistant (MDR) Gram-negative bacteria (GNB). This study aimed to determine synergy of antibiotics against paediatric bloodstream (BS) carbapenem-resistant Enterobacterales (CRE) and extremely drug-resistant (XDR) <i>Acinetobacter</i> species. <b>Methods</b>: This cross-sectional study was conducted at a public tertiary hospital in South Africa, from January 2023 to December 2023. Sixty-eight isolates from children with bloodstream infections (BSI), comprising 55.9% (38/68) CRE and 44.1% (30/68) XDR <i>Acinetobacter</i> species, were performed ST using the fixed-ratio Epsilometer-test method. Combinations of colistin and meropenem, colistin and fosfomycin, colistin and tigecycline, meropenem and fosfomycin, meropenem and tigecycline, and fosfomycin and tigecycline were tested. <b>Results</b>: In vitro synergy for CRE was best demonstrated with tigecycline and meropenem, at 92.1% (35/38), and fosfomycin and meropenem at 73.7% (28/38). Among the XDR <i>Acinetobacter</i> species, the highest rates of synergy of 76.7% (23/30) were observed with tigecycline and meropenem. The absence of synergy was noted with colistin and meropenem for the CRE, with many displaying indifference and antagonism at rates of 65.8% and 22%. Most XDR <i>Acinetobacter</i> species (56.7%; 17/30) expressed indifference to colistin and meropenem with synergy and antagonism displayed in 23.3% and 10% of isolates. <b>Conclusions</b>: This study highlights tigecycline and meropenem displaying impressive in vitro synergy when compared to the in-use colistin and meropenem for CRE and XDR <i>Acinetobacter</i> species. Tigecycline and meropenem may be a viable salvage therapeutic option for MDR Gram-negative paediatric infections. Future research is warranted to confirm in vivo synergy clinically.https://www.mdpi.com/2079-6382/14/7/630synergy testingtigecyclinemeropenemcarbapenem-resistantEnterobacterales<i>Acinetobacter</i> species
spellingShingle Prenika Jaglal
Sithembiso Christopher Velaphi
Colin Nigel Menezes
Khine Swe Swe-Han
In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
Antibiotics
synergy testing
tigecycline
meropenem
carbapenem-resistant
Enterobacterales
<i>Acinetobacter</i> species
title In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
title_full In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
title_fullStr In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
title_full_unstemmed In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
title_short In Vitro Evaluation of Antimicrobial Synergy Against Multidrug-Resistant Gram-Negative Paediatric Bloodstream Pathogens in South Africa
title_sort in vitro evaluation of antimicrobial synergy against multidrug resistant gram negative paediatric bloodstream pathogens in south africa
topic synergy testing
tigecycline
meropenem
carbapenem-resistant
Enterobacterales
<i>Acinetobacter</i> species
url https://www.mdpi.com/2079-6382/14/7/630
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AT colinnigelmenezes invitroevaluationofantimicrobialsynergyagainstmultidrugresistantgramnegativepaediatricbloodstreampathogensinsouthafrica
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