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    Geographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes
    (American Society for Microbiology, 2025-04-09)
    Jose R. W. Martínez
    ;
    Manuel Alcalde-Rico
    ;
    Estefanía Jara-Videla
    ;
    Jinnethe Reyes
    ;
    Lina P. Carvajal
    (MRSA) is a major public health menace. The global spread of MRSA is characterized by successive waves of epidemic clones dominating specific geographical regions. The acquisition of genes encoding resistance to heavy metals (HMRGs) is thought to be a key feature in the geographic divergence of MRSA. However, the cause-effect relationship between the presence of HMRGs and the divergence of MRSA clones remains to be clarified. In this study, we assessed the role that HMRGs may have played in the evolutionary divergence of the MRSA ST5-SCC <jats:italic>mec</jats:italic> I lineage in Latin America. We conducted a genomic characterization of 113 MRSA clinical isolates from six Latin American healthcare centers, including 53 isolates collected from two cities in Chile (Santiago and Concepción). We found a plasmid (pSCL4752) harboring arsenic, cadmium, and mercury resistance genes in 65% ( <jats:italic>n</jats:italic> = 71) of the ST5-SCC <jats:italic>mec</jats:italic> I isolates. We also observed a geographic divergence associated with the presence of pSCL4752 in Chilean isolates, with a higher frequency in isolates from Concepción (88%) compared to Santiago (29%). Interestingly, a molecular clock analysis revealed that this divergence occurred in the aftermath of an 8.8 Mw earthquake and tsunami that struck the Concepción area in 2010. Moreover, our results demonstrate that the carriage of pSCL4752 can be beneficial or detrimental for ST5-SCC <jats:italic>mec</jats:italic> I isolates, depending on the environmental availability of these heavy metals. Our results suggest that the divergence of the ST5-SCC <jats:italic>mec</jats:italic> I MRSA lineage in Latin America could have been fostered by environmental disasters and influenced by the presence/absence of HMRGs harbored in a plasmid. </jats:p> <jats:sec> <jats:title>IMPORTANCE</jats:title> <jats:p> Methicillin-resistant <jats:italic>Staphylococcus aureus</jats:italic> (MRSA) is a major cause of life-threatening infections worldwide and a growing public health concern. The rise of antibiotic-resistant bacteria, such as MRSA, is often linked to genetic adaptations that enhance their survival. Our research sheds light on how environmental changes, such as those triggered by a natural disaster, can influence the evolution and geographic spread of a highly resistant MRSA lineage in Latin America. We identified a plasmid carrying genes for resistance to arsenic, cadmium, and mercury, which was associated with the geographic divergence of the ST5-SCC <jats:italic>mec</jats:italic> I MRSA lineage, with striking differences in its prevalence between regions affected by a major earthquake and tsunami. By linking environmental events to pathogen evolution, our study highlights the role of ecological pressures in the spread of MRSA. These findings emphasize the need to integrate environmental monitoring into public health strategies to better understand the global challenge of antimicrobial resistance.
      4
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    Item type:Publication,
    Excess burden of antibiotic-resistant bloodstream infections: evidence from a multicentre retrospective cohort study in Chile, 2018–2022
    (2024)
    Kasim Allel
    ;
    Anne Peters
    ;
    Hassan Haghparast-Bidgoli
    ;
    Maria Spencer-Sandino
    ;
    Jose Conejeros
    Scopus© Citations 2  4
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    Item type:Publication,
    Daptomycin-Resistant Enterococcus faecalis Diverts the Antibiotic Molecule from the Division Septum and Remodels Cell Membrane Phospholipids
    (2013)
    Truc T. Tran
    ;
    Diana Panesso
    ;
    Nagendra N. Mishra
    ;
    Eugenia Mileykovskaya
    ;
    Ziqianq Guan
    <jats:title>ABSTRACT</jats:title> <jats:p> Treatment of multidrug-resistant enterococci has become a challenging clinical problem in hospitals around the world due to the lack of reliable therapeutic options. Daptomycin (DAP), a cell membrane-targeting cationic antimicrobial lipopeptide, is the only antibiotic with <jats:italic>in vitro</jats:italic> bactericidal activity against vancomycin-resistant enterococci (VRE). However, the clinical use of DAP against VRE is threatened by emergence of resistance during therapy, but the mechanisms leading to DAP resistance are not fully understood. The mechanism of action of DAP involves interactions with the cell membrane in a calcium-dependent manner, mainly at the level of the bacterial septum. Previously, we demonstrated that development of DAP resistance in vancomycin-resistant <jats:named-content content-type="genus-species">Enterococcus faecalis</jats:named-content> is associated with mutations in genes encoding proteins with two main functions, (i) control of the cell envelope stress response to antibiotics and antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase). In this work, we show that these VRE can resist DAP-elicited cell membrane damage by diverting the antibiotic away from its principal target (division septum) to other distinct cell membrane regions. DAP septal diversion by DAP-resistant <jats:named-content content-type="genus-species">E. faecalis</jats:named-content> is mediated by initial redistribution of cell membrane cardiolipin-rich microdomains associated with a single amino acid deletion within the transmembrane protein LiaF (a member of a three-component regulatory system [LiaFSR] involved in cell envelope homeostasis). Full expression of DAP resistance requires additional mutations in enzymes (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase) that alter cell membrane phospholipid content. Our findings describe a novel mechanism of bacterial resistance to cationic antimicrobial peptides. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> The emergence of antibiotic resistance in bacterial pathogens is a threat to public health. Understanding the mechanisms of resistance is of crucial importance to develop new strategies to combat multidrug-resistant microorganisms. Vancomycin-resistant enterococci (VRE) are one of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. Daptomycin (DAP) is a calcium-decorated antimicrobial lipopeptide whose target is the bacterial cell membrane. A current paradigm suggests that Gram-positive bacteria become resistant to cationic antimicrobial peptides via an electrostatic repulsion of the antibiotic molecule from a more positively charged cell surface. In this work, we provide evidence that VRE use a novel strategy to avoid DAP-elicited killing. Instead of “repelling” the antibiotic from the cell surface, VRE diverts the antibiotic molecule from the septum and “traps” it in distinct membrane regions. We provide genetic and biochemical bases responsible for the mechanism of resistance and disclose new targets for potential antimicrobial development. </jats:p>
      5Scopus© Citations 142
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    Item type:Publication,
    Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review
    (2023)
    Sarah B Doernberg
    ;
    Cesar A Arias
    ;
    Deena R Altman
    ;
    Ahmed Babiker
    ;
    Helen W Boucher
    <jats:title>Abstract</jats:title><jats:p>The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.</jats:p>
      8Scopus© Citations 7
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    Item type:Publication,
    Head-to-head comparison of CAMPYAIR aerobic culture medium versus standard microaerophilic culture for Campylobacter isolation from clinical samples
    (2023)
    Arturo Levican
    ;
    Carmen Varela
    ;
    ; ;
    Isabel Briceño
    <jats:p><jats:italic>Campylobacter</jats:italic> spp. are considered the most frequent cause of acute gastroenteritis worldwide. However, outside high-income countries, its burden is poorly understood. Limited published data suggest that <jats:italic>Campylobacter</jats:italic> prevalence in low- and middle-income countries is high, but their reservoirs and age distribution are different. Culturing <jats:italic>Campylobacter</jats:italic> is expensive due to laboratory equipment and supplies needed to grow the bacterium (e.g., selective culture media, microaerophilic atmosphere, and a 42°C incubator). These requirements limit the diagnostic capacity of clinical laboratories in many resource-poor regions, leading to significant underdiagnosis and underreporting of isolation of the pathogen. CAMPYAIR, a newly developed selective differential medium, permits <jats:italic>Campylobacter</jats:italic> isolation without the need for microaerophilic incubation. The medium is supplemented with antibiotics to allow <jats:italic>Campylobacter</jats:italic> isolation in complex matrices such as human feces. The present study aims to evaluate the ability of the medium to recover <jats:italic>Campylobacter</jats:italic> from routine clinical samples. A total of 191 human stool samples were used to compare the ability of CAMPYAIR (aerobic incubation) and a commercial <jats:italic>Campylobacter</jats:italic> medium (CASA, microaerophilic incubation) to recover <jats:italic>Campylobacter</jats:italic>. All <jats:italic>Campylobacter</jats:italic> isolates were then identified by MALDI-TOF MS. CAMPYAIR showed sensitivity and specificity values of 87.5% (95% CI 47.4%–99.7%) and 100% (95% CI 98%–100%), respectively. The positive predictive value of CAMPYAIR was 100% and its negative predictive value was 99.5% (95% CI 96.7%–99.9%); Kappa Cohen coefficient was 0.93 (95% CI 0.79–1.0). The high diagnostic performance and low technical requirements of the CAMPYAIR medium could permit <jats:italic>Campylobacter</jats:italic> culture in countries with limited resources.</jats:p>
    Scopus© Citations 3  1
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    Item type:Publication,
    Vancomycin presoaking of hamstring autografts to prevent infection in anterior cruciate ligament reconstruction: a narrative review
    <jats:p> Hamstring autograft use has been linked to an increased risk of infection after anterior cruciate (ACL) reconstruction compared to other grafts. The absolute reason for this remains unclear, with contamination after harvesting and preparation of the graft being the most accepted hypothesis. Using the rationale that a contaminated graft could be the main factor in postoperative septic arthritis and in an effort to maximize the antibiotic efficacy of the graft, the Vancomycin presoaking technique was developed. It has shown success in decreasing the infection rate in ACL reconstruction. In recent years, an important number of research articles using this protocol have appeared, but the technique is still not widely implemented. Recent literature shows that Vancomycin presoaking of the graft has shown a successful decrease in the infection rate after hamstring autograft ACL reconstruction. It has also shown efficacy decreasing the infection rate in other types of grafts (patellar tendon, quadriceps tendon, allograft) and also in patients with concomitant ligament procedures or open surgeries. Despite the positive effects of Vancomycin presoaking reducing the infection rate after ACL reconstruction, the lack of prospective randomized control trials and the heterogeneity of the different studies mean it is not feasible to recommend Vancomycin presoaking of the graft universally for every ACL reconstruction patient. </jats:p><jats:p> Cite this article: EFORT Open Rev 2021;6:211-216. DOI: 10.1302/2058-5241.6.200059 </jats:p>
      1Scopus© Citations 7
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    Item type:Publication,
    Multisite Detection of Tn
    <i>1549</i>
    -Mediated
    <i>vanB</i>
    Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida
    (2023)
    Shelby R. Simar
    ;
    Truc T. Tran
    ;
    Kirsten B. Rydell
    ;
    Diana Panesso
    ;
    German A. Contreras
    <jats:p> In the United States, <jats:italic>vanB</jats:italic> -mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant <jats:named-content content-type="genus-species">Enterococcus faecalis</jats:named-content> isolates causing bacteremia in unique patients in spatiotemporally distinct settings. </jats:p>
      7  1Scopus© Citations 3
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    International Survey of Practice for Prophylactic Systemic Antibiotic Therapy in Hip and Knee Arthroplasty
    (2022)
    Thomas Parsons
    ;
    Jonathan French
    ;
    Takeshi Oshima
    ;
    ;
    Thomas Neri
    <jats:p>(1) Background: Prophylactic systemic antibiotics are acknowledged to be an important part of mitigating prosthetic joint infections. Controversy persists regarding optimal antibiotic regimes. We sought to evaluate current international antibiotics guidelines for total joint arthroplasty (TJA) of the hip and knee. (2) Methods: 42 arthroplasty societies across 6 continents were contacted and their published literature reviewed. (3) Results: 17 societies had guidelines; of which 11 recommended an antibiotic agent or antibiotic class (10—cephalosporin; 1—cloxacillin); 15 recommended antibiotic infusion within an hour of incision and 10 advised for post-operative doses (8—up to 24 h; 1—up to 36 h; 1—up to 48 h). (4) Conclusions: Prophylactic antibiotic guidelines for TJA are often absent or heterogenous in their advice.</jats:p>
    Scopus© Citations 6  1
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    Scopus© Citations 8  4
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    Item type:Publication,
    Antimicrobial Susceptibility Testing for Enterococci
    (2022)
    Ayesha Khan
    ;
    William R. Miller
    ;
    Dierdre Axell-House
    ;
    ;
    Cesar A. Arias
    <jats:p>Enterococci are major, recalcitrant nosocomial pathogens with a wide repertoire of intrinsic and acquired resistance determinants and the potential of developing resistance to all clinically available antimicrobials. As such, multidrug-resistant enterococci are considered a serious public health threat.</jats:p>
      1Scopus© Citations 57  1