Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Drug Resistance, Multiple, Bacterial*; Anti-Bacterial Agents/*pharmacology ; Gram-Negative Bacteria/*growth & development ; Gram-Negative Bacterial Infections/*epidemiology ; Neonatal Sepsis/*microbiology; Ampicillin/pharmacology ; Cephalosporins/pharmacology ; Ethiopia/epidemiology ; Female ; Gentamicins/pharmacology ; Gram-Negative Bacteria/drug effects ; Gram-Negative Bacterial Infections/microbiology ; Humans ; Infant, Newborn ; Male ; Microbial Viability/drug effects ; Neonatal Sepsis/epidemiology ; Penicillin G/pharmacology ; Pregnancy ; Prevalence ; Tertiary Care Centers

Introduction: Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics.
Objectives: Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis.
Methods: At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression.
Results: Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics.
Conclusion: There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.
Competing Interests: The authors have declared that no competing interests exist.

PLoS One. 2019 May 8;14(5):e0215666. (PMID: 31067232)
Environ Health Prev Med. 2015 Jul;20(4):243-52. (PMID: 25921603)
Acta Paediatr. 2017 Jun;106(6):904-911. (PMID: 28240381)
Medicine (Baltimore). 2019 Jan;98(4):e14285. (PMID: 30681632)
Evol Appl. 2019 May 14;12(6):1079-1091. (PMID: 31297143)
Antimicrob Resist Infect Control. 2017 Jun 13;6:63. (PMID: 28630687)
Lancet. 2016 Jan 9;387(10014):168-75. (PMID: 26603918)
Pediatrics. 2002 Oct;110(4):690-5. (PMID: 12359781)
BMC Pediatr. 2018 Jun 27;18(1):208. (PMID: 29950162)
Scand J Infect Dis. 2006;38(1):36-42. (PMID: 16338836)
Ethiop Med J. 2010 Oct;48(4):293-300. (PMID: 21280431)
Front Pediatr. 2018 Oct 04;6:277. (PMID: 30356806)
Paediatr Int Child Health. 2015 Aug;35(3):265-72. (PMID: 25940506)
GMS Hyg Infect Control. 2017 Apr 10;12:Doc05. (PMID: 28451516)
J Lab Physicians. 2011 Jan;3(1):37-42. (PMID: 21701662)
BMC Res Notes. 2013 Jul 22;6:283. (PMID: 23875886)
Arch Dis Child Fetal Neonatal Ed. 2015 Sep;100(5):F439-47. (PMID: 25972443)
S Afr Med J. 2018 Feb 01;108(2):99-104. (PMID: 29429440)
Interdiscip Perspect Infect Dis. 2018 Feb 28;2018:4323769. (PMID: 29681933)
PLoS Med. 2013 Aug;10(8):e1001502. (PMID: 23976885)
Ethiop J Health Sci. 2019 May;29(3):333-342. (PMID: 31447501)
Pediatr Neonatol. 2018 Feb;59(1):35-41. (PMID: 28642139)
Emerg Infect Dis. 2002 Apr;8(4):347-54. (PMID: 11971765)
Clin Pediatr (Phila). 2011 Sep;50(9):827-33. (PMID: 21885435)
Pediatr Infect Dis J. 2016 Jul;35(7):e191-8. (PMID: 27031259)
Neonatology. 2013;103(1):48-53. (PMID: 23095252)
Ther Adv Infect Dis. 2016 Feb;3(1):15-21. (PMID: 26862399)
Am J Obstet Gynecol. 1999 Oct;181(4):816-21. (PMID: 10521735)
East Afr Med J. 2007 Mar;84(3):136-40. (PMID: 17600983)
BMC Pediatr. 2017 Jun 6;17(1):137. (PMID: 28587631)
JAC Antimicrob Resist. 2021 Feb 03;3(1):dlab001. (PMID: 34223080)
Pediatrics. 2006 Aug;118(2):570-6. (PMID: 16882809)
Lancet Infect Dis. 2019 Nov;19(11):1219-1234. (PMID: 31522858)
Clin Microbiol Infect. 2012 Mar;18(3):268-81. (PMID: 21793988)
Int J Biol Med Res. 2015 Nov;6(1):4709-4717. (PMID: 26997847)
Virulence. 2020 Dec;11(1):1215-1224. (PMID: 32921250)
Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F391-F394. (PMID: 29382648)
Antibiotics (Basel). 2020 Oct 16;9(10):. (PMID: 33081087)
Antimicrob Resist Infect Control. 2019 Feb 20;8:42. (PMID: 30828446)
J Paediatr Child Health. 2020 Jun;56(6):864-872. (PMID: 32294306)
Antimicrob Agents Chemother. 2013 Nov;57(11):5315-9. (PMID: 23939903)
Interdiscip Perspect Infect Dis. 2012;2012:286703. (PMID: 23118747)
J Taibah Univ Med Sci. 2020 Feb 04;15(1):39-47. (PMID: 32110181)
Source Code Biol Med. 2008 Dec 16;3:17. (PMID: 19087314)
J Perinatol. 2013 Jul;33(7):529-32. (PMID: 23328923)
Microbiol Spectr. 2016 Apr;4(2):. (PMID: 27227291)
Clin Microbiol Rev. 2014 Jan;27(1):21-47. (PMID: 24396135)
Pediatrics. 2005 Sep;116(3):696-702. (PMID: 16140710)
New Microbes New Infect. 2015 Feb 09;5:1-4. (PMID: 25834737)
BMC Infect Dis. 2007 May 22;7:43. (PMID: 17519011)
Pediatr Clin North Am. 2013 Apr;60(2):367-89. (PMID: 23481106)
Nat Microbiol. 2021 Apr;6(4):512-523. (PMID: 33782558)
BMC Microbiol. 2020 Jan 14;20(1):12. (PMID: 31937244)

MR/P007295/1 United Kingdom MRC_ Medical Research Council; MR/S013768/1 United Kingdom MRC_ Medical Research Council

0 (Anti-Bacterial Agents)
0 (Cephalosporins)
0 (Gentamicins)
7C782967RD (Ampicillin)
Q42T66VG0C (Penicillin G)

Date Created: 20210803 Date Completed: 20211123 Latest Revision: 20240928

20240928

PMC8330902

10.1371/journal.pone.0255410

34343185