Browsing by Author "Martinez, Jose R. W."

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    Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis
    (2023) Allel, Kasim; Peters, Anne; Conejeros, Jose; Martinez, Jose R. W.; Spencer-Sandino, Maria; Riquelme-Neira, Roberto; Rivas, Lina; Rojas, Pamela; Orellana Chea, Cristian; Garcia, Patricia; Araos, Rafael; McGovern, Olivia; Patel, Twisha S.; Arias, Cesar A.; Lessa, Fernanda C.; Undurraga, Eduardo A.; Munita, Jose M.
    The increased usage of carbapenems and broad-spectrum & beta;-lactams during the COVID-19 pandemic was associated with a higher prevalence of carbapenemase-producing Klebsiella pneumoniae in a public hospital in Chile. We observed emergence and spread of bla(NDM) ST45 during the pandemic.
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    Dynamics of the MRSA Population in a Chilean Hospital: a Phylogenomic Analysis (2000-2016)
    (2023) Martinez, Jose R. W.; Planet, Paul J.; Spencer-Sandino, Maria; Rivas, Lina; Diaz, Lorena; Moustafa, Ahmed M.; Quesille-Villalobos, Ana; Riquelme-Neira, Roberto; Alcalde-Rico, Manuel; Hanson, Blake; Carvajal, Lina P.; Rincon, Sandra; Reyes, Jinnethe; Lam, Marusella; Calderon, Juan F.; Araos, Rafael; Garcia, Patricia; Arias, Cesar A.; Munita, Jose M.
    Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape.
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    Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
    (2022) Jose Contreras-Gomez, Maria; Martinez, Jose R. W.; Rivas, Lina; Riquelme-Neira, Roberto; Ugalde, Juan A.; Wozniak, Aniela; Garcia, Patricia; Munita, Jose M.; Olivares-Pacheco, Jorge; Alcalde-Rico, Manuel
    Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is one of the pathogens that urgently needs new drugs and new alternatives for its control. The primary strategy to combat this bacterium is combining treatments of beta-lactam with a beta-lactamase inhibitor. The most used combinations against P. aeruginosa are ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T). Although mechanisms leading to CZA and C/T resistance have already been described, among which are the resistance-nodulation-division (RND) efflux pumps, the role that these extrusion systems may play in CZA, and C/T baseline susceptibility of clinical isolates remains unknown. For this purpose, 161 isolates of non-carbapenemase-producing (Non-CP) CRPA were selected, and susceptibility tests to CZA and C/T were performed in the presence and absence of the RND efflux pumps inhibitor, Phenylalanine-arginine beta-naphthylamide (PA beta N). In the absence of PA beta N, C/T showed markedly higher activity against Non-CP-CRPA isolates than observed for CZA. These results were even more evident in isolates classified as extremely-drug resistant (XDR) or with difficult-to-treat resistance (DTR), where CZA decreased its activity up to 55.2% and 20.0%, respectively, whereas C/T did it up to 82.8% (XDR), and 73.3% (DTR). The presence of PA beta N showed an increase in both CZA (37.6%) and C/T (44.6%) activity, and 25.5% of Non-CP-CRPA isolates increased their susceptibility to these two combined antibiotics. However, statistical analysis showed that only the C/T susceptibility of Non-CP-CRPA isolates was significantly increased. Although the contribution of RND activity to CZA and C/T baseline susceptibility was generally low (two-fold decrease of minimal inhibitory concentrations [MIC]), a more evident contribution was observed in a non-minor proportion of the Non-CP-CRPA isolates affected by PA beta N [CZA: 25.4% (15/59); C/T: 30% (21/70)]. These isolates presented significantly higher MIC values for C/T. Therefore, we conclude that RND efflux pumps are participating in the phenomenon of baseline susceptibility to CZA and, even more, to C/T. However, the genomic diversity of clinical isolates is so great that deeper analyzes are necessary to determine which elements are directly involved in this phenomenon.
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    The Combination of RET, BRAF and Demographic Data Identifies Subsets of Patients with Aggressive Papillary Thyroid Cancer
    (2019) Martinez, Jose R. W.; Vargas-Salas, Sergio; Urra Gamboa, Soledad; Munoz, Estefania; Miguel Dominguez, Jose; Leon, Augusto; Droppelmann, Nicolas; Solar, Antonieta; Zafereo, Mark; Holsinger, F. Christopher; Gonzalez, Hernan E.
    The use of BRAFV600E and RET/PTC1 as biomarkers to guide the extent of surgery in patients with papillary thyroid cancer (PTC) remains controversial. We assessed the combined use of demographic data (sex and age) with mRNA expression levels and/or mutational status (BRAFV600E and RET/PTC1) to identify potential subsets of patients with aggressive histopathological features (lymph node metastases and extrathyroidal extension). In a cohort of 126 consecutive patients, BRAFV600E and RET/PTC1 mutations were found in 52 and 18%, respectively. By conditional bivariate analysis (CBVA), a high activity' profile of BRAF (BRAFV600E positive or high expression) and low activity' profile of RET (RET/PTC1 negative or low expression) was associated with extrathyroidal extension (ETE) (OR 4.48). Alternatively, a high activity' profile of RET (RET/PTC1 positive or high expression) and low activity' profile of BRAF (BRAFV600E negative or low expression) were associated with lymph node metastasis (LNM) (OR 12.80). Furthermore, in patients younger than 55years, a low expression of BRAF was associated with LNM (OR 17.65) and the presence of BRAFV600E mutation was associated with ETE (OR 2.76). Our results suggest that the analysis of demographic and molecular variables by CBVA could contribute to identify subsets of patients with aggressive histopathologic features, providing a potential guide to personalised surgical management of PTC.