Browsing by Author "Dinh, An"
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Publication Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA(2023) Tran, Truc; Cabrera, Nicolo; Gonzales, Anne; Carlson, Travis; Alnezary, Faris; Miller, William; Sakurai, Aki; Dinh, An; Rydell, Kirsten; Rios, Rafael; Diaz, Lorena; Hanson, Blake; Munita, Jose M.; Pedroza, Claudia; Shelburne, Samuel; Aitken, Samuel; Garey, Kevin; Dillon, Ryan; Puzniak, Laura; Arias, CesarBackground: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods: We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results: A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions: Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.Item Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America(2020-06) Castro, Betsy E.; Berrio, Maritza; Vargas, Mónica L.; Carvajal, Lina P.; Millan, Lina V.; Rios, Rafael; Hernández, Angie K.; Rincon, Sandra; Cubides, Paola; Forero, Erika; Dinh, An; Seas, Carlos; Munita, José; Arias, Cesar A.; Reyes, Jinnethe; Díaz, LorenaBackground: Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISAisolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures. Objectives: To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine LatinAmerican countries. Methods: We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection ofhVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjectedto population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogatedalterations in predicted proteins associated with the development of the VISA phenotype in both hVISA andvancomycin-susceptible S. aureus (VSSA) genomes. Results: A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off(0.9). The majority of the 39 hVISA isolates exhibited the Leu-14!Ile (90%) and VraT Glu-156!Gly (90%) aminoacid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involvingWalK, VraS, RpoB and RpoC proteins. Conclusions: The hVISA phenotype exhibits low frequency in Latin America. Aminoacid substitutions in proteinsinvolved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest thatEtest-based methods are an important alternative for the detection of hVISA clinical isolatesItem 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, LorenaLittle 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.Publication Multisite Detection of Tn 1549-Mediated vanB Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida(2023) Simar, Shelby; Tran, Truc; Rydell, Kirsten; Panesso, Diana; Contreras, German; Munita, Jose M.; Cifuentes. Renzo; Abbo, Lilian; Sahasrabhojane, Pranoti; Dinh, An; Axell-House, Dierdre; Savidge, Tor; Shelburne, Samuel; Hanson, Blake; Arias, CesarIn the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.