Acquired Genetic Elements that Contribute to Antimicrobial Resistance in Frequent Gram-Negative Causative Agents of Healthcare-Associated Infections

Cruz-López, Flora; Villarreal-Treviño, Licet; Camacho-Ortíz, Adrián; Morfín‐Otero, Rayo; Flores-Treviño, Samantha; Garza‐González, Elvira

doi:10.1016/j.amjms.2020.06.028

Cited by 6 publications

(4 citation statements)

References 112 publications

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“…Likewise, in local pockets where MDR clones are common, NPAs for ceftriaxone susceptibility in E. coli and K. pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively ( 40 ), suggesting that, depending on local epidemiology, formulary, and stewardship practices, the absence of a resistance gene can guide antimicrobial deescalation. Negative results for these select antimicrobial resistance gene assays do not indicate susceptibility, as there are multiple mechanisms of resistance ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Clinical Study To Demonstrate the Diagnostic Accuracy of the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panel

Wolk

Young

Whitfield³

et al. 2021

J Clin Microbiol

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Bacteremia can progress to septic shock and death without appropriate medical intervention. Increasing evidence supports the role of molecular diagnostic panels in reducing the clinical impact of these infections through rapid identification of the infecting organism and associated antimicrobial resistance genes. We report the results of a multicenter clinical study assessing the performance of the GenMark Dx ePlex ® Investigational Use Only Blood Culture Identification Gram-Negative Panel (BCID-GN), a rapid diagnostic assay for detection of bloodstream pathogens in positive blood culture (PBC) bottles. Prospective, retrospective, and contrived samples were tested. Results from the BCID-GN were compared to standard of care bacterial identification methods. Antimicrobial resistance genes (ARGs) were identified using PCR and sequence analysis. The final BCID-GN analysis included 2,444 PBC samples, of which 926 were clinical samples with gram-negative Gram stain results. Of these, 109 samples had false negative and/or positive results, resulting in an overall sample accuracy of 88.2% (817/926). After discordant resolution, overall sample accuracy increased to 92.9% (860/926). Pre- and post-discordant resolution sample accuracy excludes 37 gram-negative organisms representing 20 uncommon genera, 10 gram-positive organisms, and 1 Candida sp. present in 5% of samples that are not targeted by the BCID-GN. The overall weighted PPA, which averages the individual PPAs from the 27 targets (gram-negative and ARG), was 94.9%. The limit of detection ranged from 10 4 to 10 7 CFU/mL, except for one strain of Fusobacterium necrophorum at 10 8 CFU/mL.

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Section: Discussionmentioning

confidence: 99%

A Multicenter Clinical Study To Demonstrate the Diagnostic Accuracy of the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panel

Wolk

Young

Whitfield³

et al. 2021

J Clin Microbiol

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“…Thus, the change in the susceptibility pattern of pathogens and the multidrug resistance (MDR) presented by Gram-negative bacilli has become a threat to the medical and scientific community worldwide [ 5 ]. Indeed, between 2000 and 2010, approximately 70 billion doses of antibiotics were administered globally and 50% of doses are used incorrectly or unnecessarily, thus facilitating the development of AMR [ 1 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, antimicrobial resistance (AMR) has become a critical factor in public health due to the reduction in therapeutic options associated with increased morbidity and mortality rates [1,2]. First, with the development and commercialization of antimicrobials, along with the increase in the prevalence rates of bacterial resistance, the scientific community has focused on Gram-positive pathogens [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Gram-negative bacilli carrying mcr gene in Brazil: a pathogen on the rise

et al. 2023

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The incidence of infections caused by resistant Gram-negative pathogens has become a critical factor in public health due to the limitation of therapeutic options for the control of infections caused, especially, by Enterobacteriaceae ( Escherichia coli and Klebsiella pneumoniae ), Pseudomonas spp., and Acinetobacter spp. Thus, given the increase in resistant pathogens and the reduction of therapeutic options, polymyxins were reintroduced into the clinic. As the last treatment option, polymyxins were regarded as the therapeutic key, since they were one of the few classes of antimicrobials that had activity against multidrug-resistant Gram-negative bacilli. Nonetheless, over the years, the frequent use of this antimicrobial has led to reports of resistance cases. In 2015, mcr ( mobile colistin resistanc e), a colistin resistance gene, was described in China. Due to its location on carrier plasmids, this gene is characterized by rapid spread through conjugation. It has thus been classified as a rising threat to public health worldwide. In conclusion, based on several reports that show the emergence of mcr in different regional and climatic contexts and species of isolates, this work aims to review the literature on the incidence of the mcr gene in Brazil in different regions, types of samples identified, species of isolates, and type of carrier plasmid.

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“…A. baumannii is thought to be a rapidly evolving species, showing high rates of recombination and horizontal gene transfer (HGT) (5)(6)(7). Indeed, clinically-relevant resistance levels are largely the result of horizontally acquired antibiotic resistance genes (ARGs) which are hitchhiking on mobile genetic elements (MGEs) (8,9). Widespread carriers of ARGs and transposable elements (TEs) are the transposon-derived and closely-related genomic islands AbaR-type and AbGRI-type (hereafter collectively called A. baumannii resistance islands, AbaRs) (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance inAcinetobacter baumanniipopulations

Tuffet,

Carvalho,

Godeux

et al. 2023

Preprint

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International public health organizations consider the multidrug resistant and opportunistic pathogenAcinetobacter baumannii, as a major global health concern. This species hosts multiple variants of AbaR-type genomic islands which carry several antibiotic resistance, including to carbapenems (AbaR4 variant). How these islands, conferring multidrug resistance, persist inA. baumanniipopulations remains elusive.Using complementary approaches, we investigated whether the manipulation of natural transformation by AbaRs, via their insertion strategy in the bacterial chromosome, might give them a selective advantage and contribute to the persistence of antibiotic resistance genes inA. baumanniipopulations. Natural transformation is a process through which bacteria can import and recombine exogenous DNA, facilitating gene transfer and allelic recombination. Although transformation promotes acquisition of mobile genetic elements (MGEs), it is also proposed to serve as a mechanism to purge them from the chromosome. Several MGEs inhibit transformation, suggesting that natural transformation can impede their evolutionary dynamics.We established an experimental model in which natural transformation spontaneously occurs inA. baumanniipopulations, allowing us to determine the rate of acquisition and removal of MGEs. We found that the majority of AbaRs disrupt thecomMgene, causing differential inhibition of MGE acquisition, removal and allelic transfer events. A mathematical evolutionary model shows that AbaRs inserting into thecomMgene gain a selective advantage over AbaRs whose insertion site either do not inhibit or completely inhibit transformation. ThecomMinsertion strategy is clearly advantageous when the model incorporates some degree of environmental complexity, such as combined antibiotic stress or changes in environmental resources.Our work highlights how AbaRs, and potentially other MGEs, can manipulate natural transformation to persist in populations, resulting in the high prevalence of multidrug resistance.

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Acquired Genetic Elements that Contribute to Antimicrobial Resistance in Frequent Gram-Negative Causative Agents of Healthcare-Associated Infections

Cited by 6 publications

References 112 publications

A Multicenter Clinical Study To Demonstrate the Diagnostic Accuracy of the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panel

A Multicenter Clinical Study To Demonstrate the Diagnostic Accuracy of the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panel

Gram-negative bacilli carrying mcr gene in Brazil: a pathogen on the rise

Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance inAcinetobacter baumanniipopulations

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