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Changing Landscape of Antimicrobial Resistance in Neonatal Sepsis: An in silico Analyses of Multidrug Resistance in Klebsiella pneumoniae.
Vijayakumar, Santhiya; Kumar, Hithesh; Basu, Soumya; Chandy, Sara; Anbarasu, Anand; Manoharan, Anand; Ramaiah, Sudha.
Afiliación
  • Vijayakumar S; From the Department of Integrative Biology.
  • Kumar H; Medical and Biological Computing Laboratory.
  • Basu S; Medical and Biological Computing Laboratory.
  • Chandy S; Department of Bio-Sciences, School of Biosciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore.
  • Anbarasu A; Department of Biotechnology, NIST University, Brahmapur.
  • Manoharan A; Department of Research, The CHILDS Trust Medical Research Foundation and Kanchi Kamakoti CHILDS Trust Hospital, Chennai.
  • Ramaiah S; Medical and Biological Computing Laboratory.
Pediatr Infect Dis J ; 43(8): 777-784, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38621154
ABSTRACT

BACKGROUND:

Neonatal sepsis poses a critical healthcare concern, as multidrug-resistant Klebsiella pneumoniae ( K. pneumoniae ) infections are on the rise. Understanding the antimicrobial susceptibility patterns and underlying resistance mechanism is crucial for effective treatment.

OBJECTIVES:

This study aimed to comprehensively investigate the antimicrobial susceptibility patterns of K. pneumoniae strains responsible for neonatal sepsis using in silico tools. We sought to identify trends and explore reasons for varying resistance levels, particularly for ß-lactams and fluoroquinolone.

METHODS:

K. pneumoniae isolated from neonates at Kanchi Kamakoti CHILDS Trust Hospital (2017-2020) were analyzed for antimicrobial resistance. Elevated resistance to ß-lactam and fluoroquinolone antibiotics was further investigated through molecular docking and interaction analysis. ß-lactam affinity with penicillin-binding proteins and ß-lactamases was examined. Mutations in ParC and GyrA responsible for quinolone resistance were introduced to investigate ciprofloxacin interactions.

RESULTS:

Of 111 K. pneumoniae blood sepsis isolates in neonates, high resistance was detected to ß-lactams such as cefixime (85.91%, n = 71), ceftriaxone (84.9%, n = 106), cefotaxime (84.9%, n = 82) and fluoroquinolone (ciprofloxacin- 79.44%, n = 107). Molecular docking revealed low ß-lactam binding toward penicillin-binding proteins and higher affinities for ß-lactamases, attributing to the reduced ß-lactam efficiency. Additionally, ciprofloxacin showed decreased affinity toward mutant ParC and GyrA in comparison to their corresponding wild-type proteins.

CONCLUSION:

Our study elucidates altered resistance profiles in neonatal sepsis caused by K. pneumoniae , highlighting mechanisms of ß-lactam and fluoroquinolone resistance. It underscores the urgent need for the development of sustainable therapeutic alternatives to address the rising antimicrobial resistance in neonatal sepsis.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por Klebsiella / Pruebas de Sensibilidad Microbiana / Farmacorresistencia Bacteriana Múltiple / Simulación del Acoplamiento Molecular / Sepsis Neonatal / Klebsiella pneumoniae / Antibacterianos Límite: Humans / Newborn Idioma: En Revista: Pediatr Infect Dis J Asunto de la revista: DOENCAS TRANSMISSIVEIS / PEDIATRIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por Klebsiella / Pruebas de Sensibilidad Microbiana / Farmacorresistencia Bacteriana Múltiple / Simulación del Acoplamiento Molecular / Sepsis Neonatal / Klebsiella pneumoniae / Antibacterianos Límite: Humans / Newborn Idioma: En Revista: Pediatr Infect Dis J Asunto de la revista: DOENCAS TRANSMISSIVEIS / PEDIATRIA Año: 2024 Tipo del documento: Article