Browsing by Author "Nigo, Masayuki"
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Item 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, AudreyWe 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.Item Deletion of liaR reverses daptomycin resistance in enterococcus faecium independent of the genetic background(American Society for Microbiology, 2015) Panesso, Diana; Reyes, Jinnethe; Gaston, Elizabeth; Deal, Morgan; Londoño, Alejandra; Nigo, Masayuki; Munita, José; Miller, William; Shamoo, Yousif; Tran, Truc; Arias, CesarWe have shown previously that changes in LiaFSR, a three-component regulatory system predicted to orchestrate the cell membrane stress response, are important mediators of daptomycin (DAP) resistance in enterococci. Indeed, deletion of the gene encoding the response regulator LiaR in a clinical strain of Enterococcus faecalis reversed DAP resistance (DAP-R) and produced a strain hypersusceptible to antimicrobial peptides. Since LiaFSR is conserved in Enterococcus faecium, we investigated the role of LiaR in a variety of clinical E. faecium strains representing the most common DAP-R genetic backgrounds. Deletion of liaR in DAP-R E. faecium R446F (DAP MIC of 16 μg/ml) and R497F (MIC of 24 μg/ml; harboring changes in LiaRS) strains fully reversed resistance (DAP MICs decreasing to 0.25 and 0.094 μg/ml, respectively). Moreover, DAP at concentrations of 13 μg/ml (achieved with human doses of 12 mg/kg body weight) retained bactericidal activity against the mutants. Furthermore, the liaR deletion derivatives of these two DAP-R strains exhibited increased binding of boron-dipyrromethene difluoride (BODIPY)-daptomycin, suggesting that high-level DAP-R mediated by LiaR in E. faecium involves repulsion of the calcium-DAP complex from the cell surface. In DAP-tolerant strains HOU503F and HOU515F (DAP MICs within the susceptible range but bacteria not killed by DAP concentrations of 5× the MIC), deletion of liaR not only markedly decreased the DAP MICs (0.064 and 0.047 μg/ml, respectively) but also restored the bactericidal activity of DAP at concentrations as low as 4 μg/ml (achieved with human doses of 4 mg/kg). Our results suggest that LiaR plays a relevant role in the enterococcal cell membrane adaptive response to antimicrobial peptides independent of the genetic background and emerges as an attractive target to restore the activity of DAP against multidrug-resistant strains.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.Item Multicenter evaluation of ceftolozane/tazobactam for serious infections caused by carbapenem-resistant pseudomonas aeruginosa(Oxford University Press, 2017) Munita, José; Aitken, Samuel; Miller, William; Perez, Federico; Rosa, Rossana; Shimose, Luis; Lichtenberger, Paola; Abbo, Lilian; Jain, Rupali; Nigo, Masayuki; Wanger, Audrey; Araos, Rafael; Tran, Truc; Adachi, Javier; Rakita, Robert; Shelburne, Samuel; Bonomo, Robert; Arias, CesarA multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.Item What's New in the Treatment of Enterococcal Endocarditis?(Springer, 2014) Nigo, Masayuki; Munita, José; Arias, Cesar; Murray, BarbaraEnterococcus spp. are among the common pathogens causing infective endocarditis (IE). Despite major medical advances and new potent antimicrobial agents, the mortality has not significantly improved for several decades. The usual lack of bactericidal activity of penicillin or ampicillin, the toxicity from the combination of penicillin plus aminoglycosides, and the increased reports of high-level resistance to aminoglycosides have led to the exploration of other regimens for treatment of Enterococcus faecalis IE. As an example, ampicillin plus ceftriaxone is now a well-recognized regimen for this organism. However, the emerging of new drug resistances in Enterococcus faecium dramatically reduces the therapeutic alternatives for this organism in IE which continues to be an immense challenge for clinicians even with the availability of newer antimicrobial agents. This article summarizes the current treatment options for enterococcal endocarditis and reviews of recent publications on the topic.