Browsing by Author "Tran, Truc T."

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    Ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant staphylococcus aureus causing infective endocarditis
    (American Society for Microbiology, 2017) Nigo, Masayuki; Diaz, Lorena; Carvajal, Lina P.; Tran, Truc T.; Rios, Rafael; Panesso, Diana; Garavito, Juan D; Miller, William; Wagner, Audrey
    We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.
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    Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure
    (2020) Rios, Rafael; Reyes, Jinnethe; Carvajal, Lina P.; Rincon, Sandra; Panesso, Diana; Echeverri, Aura M.; Dinh, An; Kolokotronis, Sergios-Orestis; Narechania, Apurva; Tran, Truc T.; Munita, José; Murray, Bárbara E.; Planet, Paul J.; Arias, Cesar A.; Díaz, Lorena
    Little is known about the population structure of vancomycin-resistant Enterococcus faecium (VREfm) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998–2015 in 5 countries. The LATAM VREfm population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VREfm by including 285 genomes from 36 countries spanning from 1946 to 2017. In contrast to previous studies, our results show an early branching of animal related isolates and a further split of clinical isolates into two sub-clades within clade A. The overall phylogenomic structure of clade A was highly dependent on recombination (54% of the genome) and the split between clades A and B was estimated to have occurred more than 2,765 years ago. Furthermore, our molecular clock calculations suggest the branching of animal isolates and clinical clades occurred ~502 years ago whereas the split within the clinical clade occurred ~302 years ago (previous studies showed a more recent split between clinical an animal branches around ~74 years ago). By including isolates from Latin America, we present novel insights into the population structure of VREfm and revisit the evolution of these pathogens.
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    Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with -Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions
    (2018) Kebriaei, Razieh; Rice, Seth A.; Singh, Kavindra V.; Stamper, Kyle C.; Dinh, An Q.; Rios, Rafael; Díaz, Lorena; Murray, Bárbara E.; Munita, José; Tran, Truc T.; Arias, Cesar A.; Rybak, Michael J.
    Enterococcus faecium isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problem- atic, since predisposition to resistance may lead to therapeutic failure. Using a simu- lated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as mono- therapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). Of interest, the efficacy of DAP monotherapy, at any dose regimen, was dependent on the size of the inoculum. At an inoculum of 109 CFU/g, DAP doses of 6 to 8 mg/ kg/day were not effective and led to significant regrowth with emergence of resis- tant derivatives. In contrast, at an inoculum of 107 CFU/g, marked reductions in bacterial counts were observed with DAP at 6 mg/kg/day, with no resistance. The in- oculum effect was confirmed in a rat model using humanized DAP exposures. Com- binations of DAP with AMP, CPT, or ERT demonstrated enhanced eradication and re- duced potential for resistance, allowing de-escalation of the DAP dose. Persistence of the LiaRS substitutions was identified in DAP-resistant isolates recovered from the SEV model and in DAP-resistant derivatives of an initially DAP-susceptible clinical isolate of E. faecium (HOU668) harboring LiaSR substitutions that was recovered from a patient with a recurrent bloodstream infection. Our results provide novel data for the use of DAP monotherapy and combinations for recalcitrant E. faecium infections and pave the way for testing these approaches in humans.

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