#Bicarbonate Resensitization of #MRSA to #betaLactam #Antibiotics (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureusto β-Lactam Antibiotics

Selvi C. Ersoy, Wessam Abdelhady, Liang Li, Henry F. Chambers, Yan Q. Xiong, Arnold S. Bayer

DOI: 10.1128/AAC.00496-19

 

ABSTRACT

Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as ‘resistant’ to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3) supplementation: one highly susceptible to the anti-staphylococcal β-lactams, oxacillin and cefazolin (‘NaHCO3-responsive’) and one resistant to such agents (‘NaHCO3-nonresponsive’). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO3 reduced expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein (PBP) 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media. These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for β-lactam therapy.

Copyright © 2019 Ersoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylococcus aureus; Endocarditis; Bicarbonate; Oxacillin; Cefazolin; Beta-lactams.

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#Klebsiella pneumoniae ST307 with #blaOXA-181, #SouthAfrica, 2014–2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 4—April 2019 / Research

Klebsiella pneumoniae ST307 with blaOXA-181, South Africa, 2014–2016

Michelle Lowe1, Marleen M. Kock, Jennifer Coetzee, Ebrahim Hoosien, Gisele Peirano, Kathy-Ann Strydom, Marthie M. Ehlers, Nontombi M. Mbelle, Elena Shashkina, David B. Haslam, Puneet Dhawan, Robert J. Donnelly, Liang Chen1, Barry N. Kreiswirth, and Johann D.D. Pitout

Author affiliations: University of Pretoria, Pretoria, South Africa (M. Lowe, M.M. Kock, K.-A. Strydom, M.M. Ehlers, N.M. Mbelle, J.D.D. Pitout); National Health Laboratory Service, Pretoria (M. Lowe, M.M. Kock, K.-A. Strydom, M.M. Ehlers, N.M. Mbelle); Ampath Laboratories, Pretoria (J. Coetzee, E. Hoosien); Calgary Laboratory Services, Calgary, Alberta, Canada (G. Peirano, J.D.D. Pitout); University of Calgary, Calgary (G. Peirano, J.D.D. Pitout); Rutgers University, Newark, New Jersey, USA (E. Shashkina, L. Chen, B.N. Kreiswirth); Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA (D.B. Haslam); New Jersey Medical School, Newark (P. Dhawan, R.J. Donnelly)

 

Abstract

Klebsiella pneumoniae sequence type (ST) 307 is an emerging global antimicrobial drug–resistant clone. We used whole-genome sequencing and PCR to characterize K. pneumoniae ST307 with oxacillinase (OXA) 181 carbapenemase across several private hospitals in South Africa during 2014–16. The South Africa ST307 belonged to a different clade (clade VI) with unique genomic characteristics when compared with global ST307 (clades I–V). Bayesian evolution analysis showed that clade VI emerged around March 2013 in Gauteng Province, South Africa, and then evolved during 2014 into 2 distinct lineages. K. pneumoniae ST307 clade VI with OXA-181 disseminated over a 15-month period within 42 hospitals in 23 cities across 6 northeastern provinces, affecting 350 patients. The rapid expansion of ST307 was most likely due to intrahospital, interhospital, intercity, and interprovince movements of patients. This study highlights the importance of molecular surveillance for tracking emerging antimicrobial clones.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Oxacillin; Klebsiella pneumoniae; South Africa.

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