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

Okado, Jessica Baleiro; Avaca-Crusca, Juliana Sposto; Oliveira, A. L.; Dabul, Andrei Nicoli Gebieluca; Camargo, Ilana Lopes Baratella da Cunha

doi:10.1016/j.jgar.2018.05.001

Cited by 14 publications

(7 citation statements)

References 28 publications

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“…It should be noted that daptomycin non-susceptible isolates belonging to the USA100 lineage have already been reported in Brazil. 3 In addition, there was an association between the MRSA phenotype and resistance to vancomycin and daptomycin ( p ≤ 0.05). This result is of concern once daptomycin is an important alternative for the treatment of BSI by MRSA, VISA or hVISA, phenotypes that were all found in the present study.…”

mentioning

confidence: 98%

“…In Brazil and in other developing countries, data about antimicrobial resistance rates and genotypic characteristics of S. aureus isolates from BSI are still scarce and performed with very few isolates. 3 In a previous study, we analyzed clinical and microbiological characteristics of S. aureus from bloodstream infections (BSI) in a Brazilian teaching hospital, between 2011 and 2013, focusing on their susceptibility to vancomycin. 4 Here, we continued analyzing S. aureus isolates from BSI in the same hospital in order to provide more conclusive data about antimicrobial resistance profiles and clonal lineages to help the infection control and prevention team cope with this type of staphylococcal infection.…”

mentioning

confidence: 99%

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Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital

Damasco¹,

Costa²,

Morgado³

et al. 2019

The Brazilian Journal of Infectious Diseases

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confidence: 98%

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confidence: 99%

Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital

Damasco¹,

Costa²,

Morgado³

et al. 2019

The Brazilian Journal of Infectious Diseases

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“…In a study by Okado and colleagues, DAP HR was reported in clinical methicillin-resistant S . aureus (MRSA) at a frequency of 7.4% using PAP methods [ 51 ]. However, another study focusing on clinical MRSA isolates from 3 endocarditis patients found a much higher prevalence of DAP HR, nearly 30% [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

High prevalence of heteroresistance in Staphylococcus aureus is caused by a multitude of mutations in core genes

Heidarian,

Guliaev,

Nicoloff

et al. 2024

PLoS Biol

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Heteroresistance (HR) is an enigmatic phenotype where, in a main population of susceptible cells, small subpopulations of resistant cells exist. This is a cause for concern, as this small subpopulation is difficult to detect by standard antibiotic susceptibility tests, and upon antibiotic exposure the resistant subpopulation may increase in frequency and potentially lead to treatment complications or failure. Here, we determined the prevalence and mechanisms of HR for 40 clinical Staphylococcus aureus isolates, against 6 clinically important antibiotics: daptomycin, gentamicin, linezolid, oxacillin, teicoplanin, and vancomycin. High frequencies of HR were observed for gentamicin (69.2%), oxacillin (27%), daptomycin (25.6%), and teicoplanin (15.4%) while none of the isolates showed HR toward linezolid or vancomycin. Point mutations in various chromosomal core genes, including those involved in membrane and peptidoglycan/teichoic acid biosynthesis and transport, tRNA charging, menaquinone and chorismite biosynthesis and cyclic-di-AMP biosynthesis, were the mechanisms responsible for generating the resistant subpopulations. This finding is in contrast to gram-negative bacteria, where increased copy number of bona fide resistance genes via tandem gene amplification is the most prevalent mechanism. This difference can be explained by the observation that S. aureus has a low content of resistance genes and absence of the repeat sequences that allow tandem gene amplification of these genes as compared to gram-negative species.

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“…HR to daptomycin, a cyclic lipopeptide used as alternative to treat MRSA infections, has been increasingly seen in MRSA isolates. This HR has been linked to changes in cell wall composition, charge, and fluidity (Capone et al 2016;Okado et al 2018), as well as to mutations in the mprF gene, resulting in increased lysyl-phosphatidyl glycerol production, and in the rpoB/C genes, encoding bacterial RNA polymerase subunits (Chen et al 2015;Okado et al 2018), in addition to a number of other gene mutations (Ji et al 2020).…”

Section: Staphylococcus Aureusmentioning

confidence: 99%

Discerning the role of polymicrobial biofilms in the ascent, prevalence, and extent of heteroresistance in clinical practice

Lopes

Jorge

Sousa

2021

Critical Reviews in Microbiology

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Antimicrobial therapy is facing a worrisome and underappreciated challenge, the phenomenon of heteroresistance (HR). HR has been gradually documented in clinically relevant pathogens (e.g. Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia spp., Acinetobacter baumannii, Klebsiella pneumoniae, Candida spp.) towards several drugs and is believed to complicate the clinical picture of chronic infections. This type of infections are typically mediated by polymicrobial biofilms, wherein microorganisms inherently display a wide range of physiological states, distinct metabolic pathways, diverging refractory levels of stress responses, and a complex network of chemical signals exchange. This review aims to provide an overview on the relevance, prevalence, and implications of HR in clinical settings. Firstly, related terminologies (e.g. resistance, tolerance, persistence), sometimes misunderstood and overlapped, were clarified. Factors generating misleading HR definitions were also uncovered. Secondly, the recent HR incidences reported in clinically relevant pathogens towards different antimicrobials were annotated. The potential mechanisms underlying such occurrences were further elucidated. Finally, the link between HR and biofilms was discussed. The focus was to recognize the presence of heterogeneous levels of resistance within most biofilms, as well as the relevance of polymicrobial biofilms in chronic infectious diseases and their role in resistance spreading. These topics were subject of a critical appraisal, gaining insights into the ascending clinical implications of HR in antimicrobial resistance spreading, which could ultimately help designing effective therapeutic options.

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

Cited by 14 publications

References 28 publications

Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital

Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital

High prevalence of heteroresistance in Staphylococcus aureus is caused by a multitude of mutations in core genes

Discerning the role of polymicrobial biofilms in the ascent, prevalence, and extent of heteroresistance in clinical practice

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