Daptomycin and vancomycin heteroresistance revealed among CC5-SCCmecII MRSA clone and in vitro evaluation of treatment alternatives

Jessica Baleiro Okado; Juliana Sposto Avaca-Crusca; Alexandre Lima Oliveira; Andrei Nicoli Gebieluca Dabul; Ilana Lopes Baratella da Cunha Camargo

doi:10.1016/j.jgar.2018.05.001

Daptomycin and vancomycin heteroresistance revealed among CC5-SCCmecII MRSA clone and in vitro evaluation of treatment alternatives

J Glob Antimicrob Resist. 2018 Sep:14:209-216. doi: 10.1016/j.jgar.2018.05.001. Epub 2018 May 9.

Authors

Jessica Baleiro Okado¹, Juliana Sposto Avaca-Crusca¹, Alexandre Lima Oliveira², Andrei Nicoli Gebieluca Dabul¹, Ilana Lopes Baratella da Cunha Camargo³

Affiliations

¹ São Carlos Institute of Physics, University of São Paulo, P.O. Box 369, 13569-970 São Carlos, SP, Brazil.
² São Carlos Institute of Physics, University of São Paulo, P.O. Box 369, 13569-970 São Carlos, SP, Brazil; Department of Evolutionary Genetics and Molecular Biology, Federal University of São Carlos, Rodovia Washington Luiz km 235, 13565-905 São Carlos, SP, Brazil.
³ São Carlos Institute of Physics, University of São Paulo, P.O. Box 369, 13569-970 São Carlos, SP, Brazil; Department of Evolutionary Genetics and Molecular Biology, Federal University of São Carlos, Rodovia Washington Luiz km 235, 13565-905 São Carlos, SP, Brazil. Electronic address: ilanacamargo@ifsc.usp.br.

PMID: 29753135
DOI: 10.1016/j.jgar.2018.05.001

Abstract

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to the success of clinical treatment. Besides high antimicrobial resistance rates, the presence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and heterogeneous daptomycin-non-susceptible S. aureus (hDNSSA) in the hospital environment is underestimated and is associated with treatment failure. The aim of this study was to investigate MRSA dissemination in a Brazilian hospital and to evaluate the efficacy of various treatment options in vitro.

Methods: MRSA strains were typed by MLST, PFGE and SCCmec typing. Minimum inhibitory concentrations (MICs) to daptomycin, linezolid, quinupristin/dalfopristin, teicoplanin, tetracycline, tigecycline, vancomycin and tedizolid were determined by broth microdilution. The presence of a heterogeneous population was detected by population analysis profile (PAP). Regarding hVISA and hDNSSA strains, the sequences and expression levels of genes involved in resistance to daptomycin and vancomycin were determined as well as cell wall thickness and autolysis.

Results: ST5/ST105-SCCmecII lineage was prevalent amongst 27 clinical MRSA characterised in this study. Two hDNSSA strains (one also hVISA) were detected and were confirmed by PAP. Isolate SCMSC29 (hVISA and hDNSSA) showed increased expression of genes involved in cell wall metabolism, slight cell wall thickening, reduction of autolysis, and single nucleotide polymorphisms (SNPs) in the rpoB and mprF genes compared with the susceptible strain SCMSC31. SCMSC35 (hDNSSA) presented SNPs in the rpoB and mprF genes as well as a thickened cell wall.

Conclusions: Despite this worrying and hard to detect phenotype, treatment alternatives such as teicoplanin, linezolid, tetracycline, tigecycline, quinupristin/dalfopristin and tedizolid were all active against these isolates.

Keywords: Heterogeneous daptomycin-non-susceptibility; MRSA; hVISA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacterial Proteins / genetics*
Bacteriolysis
Brazil
Cell Wall / genetics
Cell Wall / metabolism
Daptomycin / pharmacology*
Drug Resistance, Bacterial
Humans
Linezolid / pharmacology
Methicillin-Resistant Staphylococcus aureus / drug effects
Methicillin-Resistant Staphylococcus aureus / genetics*
Microbial Sensitivity Tests
Multilocus Sequence Typing
Oxazolidinones / pharmacology
Polymorphism, Single Nucleotide
Staphylococcal Infections / drug therapy
Staphylococcal Infections / microbiology*
Tetrazoles / pharmacology
Vancomycin / pharmacology*

Substances

Bacterial Proteins
Oxazolidinones
Tetrazoles
Vancomycin
tedizolid
Linezolid
Daptomycin