Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2024
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| _version_ | 1811139855495725056 |
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| author | Kakaraskoska Boceska, B Vilken, T Xavier, BB Kostyanev, T Lin, Q Lammens, C Ellis, S O’Brien, S da Costa, RMA Cook, A Russell, N Bielicki, J Riddell, A Stohr, W Walker, AS Berezin, EN Roilides, E De Luca, M Romani, L Ballot, D Dramowski, A Wadula, J Lochindarat, S Boonkasidecha, S Namiiro, F Ngoc, HTB Tran, MD Cressey, TR Preedisripipat, K Berkley, JA Musyimi, R Zarras, C Nana, T Whitelaw, A da Silva, CB Jaglal, P Ssengooba, W Saha, SK Islam, MS Mussi-Pinhata, MM Carvalheiro, CG Piddock, LJV Heath, PT Malhotra-Kumar, S Sharland, M Glupczynski, Y Goossens, H |
| author_facet | Kakaraskoska Boceska, B Vilken, T Xavier, BB Kostyanev, T Lin, Q Lammens, C Ellis, S O’Brien, S da Costa, RMA Cook, A Russell, N Bielicki, J Riddell, A Stohr, W Walker, AS Berezin, EN Roilides, E De Luca, M Romani, L Ballot, D Dramowski, A Wadula, J Lochindarat, S Boonkasidecha, S Namiiro, F Ngoc, HTB Tran, MD Cressey, TR Preedisripipat, K Berkley, JA Musyimi, R Zarras, C Nana, T Whitelaw, A da Silva, CB Jaglal, P Ssengooba, W Saha, SK Islam, MS Mussi-Pinhata, MM Carvalheiro, CG Piddock, LJV Heath, PT Malhotra-Kumar, S Sharland, M Glupczynski, Y Goossens, H |
| author_sort | Kakaraskoska Boceska, B |
| collection | OXFORD |
| description | Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria. |
| first_indexed | 2024-09-25T04:12:43Z |
| format | Journal article |
| id | oxford-uuid:c41ec4ba-4b9e-42c3-87ee-e417b7cb541d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:12:43Z |
| publishDate | 2024 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:c41ec4ba-4b9e-42c3-87ee-e417b7cb541d2024-07-02T12:07:08ZAssessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countriesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c41ec4ba-4b9e-42c3-87ee-e417b7cb541dEnglishSymplectic ElementsSpringer Nature2024Kakaraskoska Boceska, BVilken, TXavier, BBKostyanev, TLin, QLammens, CEllis, SO’Brien, Sda Costa, RMACook, ARussell, NBielicki, JRiddell, AStohr, WWalker, ASBerezin, ENRoilides, EDe Luca, MRomani, LBallot, DDramowski, AWadula, JLochindarat, SBoonkasidecha, SNamiiro, FNgoc, HTBTran, MDCressey, TRPreedisripipat, KBerkley, JAMusyimi, RZarras, CNana, TWhitelaw, Ada Silva, CBJaglal, PSsengooba, WSaha, SKIslam, MSMussi-Pinhata, MMCarvalheiro, CGPiddock, LJVHeath, PTMalhotra-Kumar, SSharland, MGlupczynski, YGoossens, HGram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria. |
| spellingShingle | Kakaraskoska Boceska, B Vilken, T Xavier, BB Kostyanev, T Lin, Q Lammens, C Ellis, S O’Brien, S da Costa, RMA Cook, A Russell, N Bielicki, J Riddell, A Stohr, W Walker, AS Berezin, EN Roilides, E De Luca, M Romani, L Ballot, D Dramowski, A Wadula, J Lochindarat, S Boonkasidecha, S Namiiro, F Ngoc, HTB Tran, MD Cressey, TR Preedisripipat, K Berkley, JA Musyimi, R Zarras, C Nana, T Whitelaw, A da Silva, CB Jaglal, P Ssengooba, W Saha, SK Islam, MS Mussi-Pinhata, MM Carvalheiro, CG Piddock, LJV Heath, PT Malhotra-Kumar, S Sharland, M Glupczynski, Y Goossens, H Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title_full | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title_fullStr | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title_full_unstemmed | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title_short | Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries |
| title_sort | assessment of three antibiotic combination regimens against gram negative bacteria causing neonatal sepsis in low and middle income countries |
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