Universidad del Desarrollo

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Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
(2021)
Mauricio Salvo
;
Evelin González-Feliú
;
Jessica Toro
;
Iván Gallegos
;
Ignacio Maureira
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
2Scopus© Citations 13
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Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile
(2021)
Stella M. Chenet
;
Alan Oyarce
;
Jorge Fernandez
;
Rafael Tapia-Limonchi
;
WEITZEL, THOMAS
<jats:title>ABSTRACT</jats:title><jats:p>In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria. The patient was then treated with oral mefloquine, followed by clinical recovery and resolution of parasitemia. Analysis of day 0 and follow-up blood samples, collected on days 9, 29, 34, 64, and 83, revealed that parasitemia had initially decreased but then increased on day 29. Sequencing confirmed Tyr268Cys mutation in the <jats:italic>cytochrome b</jats:italic> gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and <jats:italic>P. falciparum dihydrofolate reductase</jats:italic> mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples. Molecular characterization of imported malaria contributes to clinical management in non-endemic countries, helps ascertain the appropriateness of antimalarial treatment policies, and contributes to the reporting of drug resistance patterns from endemic regions.</jats:p>
4Scopus© Citations 5
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Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA
(2022)
Truc T Tran
;
Nicolo L Cabrera
;
Anne J Gonzales-Luna
;
Travis J Carlson
;
Faris Alnezary
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
Scopus© Citations 3 2

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