Browsing by Author "Kontoyiannis, Dimitrios"
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Item Dissecting the mechanisms of linezolid resistance in a drosophila melanogaster infection model of staphylococcus aureus(Oxford University Press, 2013) Diaz, Lorena; Kontoyiannis, Dimitrios; Panesso, Diana; Albert, Nathaniel; Singh, Kavindra; Tran, Truc; Munita, José; Murray, Barbara; Arias, CesarBACKGROUND: Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. METHODS: Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15-500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. RESULTS: LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15-250 µg/mL failed to protect against NRS119 (survival, 1.6%-20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. CONCLUSIONS: The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis model.Item Fungal empyema thoracis in cancer patients(Elsevier, 2016) Nigo, Masayuki; Vial, Macarena; Munita, José; Jiang, Ying; Tarrand, Jeffrey; Jimenez, Carlos; Kontoyiannis, DimitriosOBJECTIVES: Fungal empyema thoracis (FET) is a rare life-threatening infection. We sought to describe the clinical characteristics of FET in a large academic cancer center. METHODS: We conducted a retrospective chart review of all cancer patients who had a fungal isolate from the pleural fluid culture between 1/2005 and 8/2013. RESULTS: A total of 106 fungal isolates were identified in 97 patients. Yeasts accounted for 62% of the isolates whereas 38% were identified as molds. The most frequent pathogens were Candida spp. (58%) and Aspergillus spp. (12%). All patients with Aspergillus and 83% with Candida met criteria for proven fungal disease. Compared to the Aspergillus group, Candida FET was associated with recent abdominal or thoracic surgical procedures (44% vs. 0%, p = 0.01). Overall, 6-week mortality was high, with no significant differences between Candida and Aspergillus (31% vs. 45%, respectively [p = 0.48]). Only 1 out of 11 patients with uncommon molds died at 6 weeks, despite only 2 of them received appropriate antifungal therapy. CONCLUSIONS: Development of FET carries a high mortality in cancer patients. A history of a recent surgical procedure is a risk factor for FET due to Candida. Isolation of uncommon molds is likely to represent a contamination of the pleural fluid.