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Tamás Kardos, Qasem Saleh, Renátó Kovács, Rudolf Gesztelyi, Gábor Kardos, Aliz Bozó, Zoltán Tóth, László Majoros
We compared the micafungin killing rate and postantifungal effect (PAFE) at 4, 16 and 32 mg/L in RPMI-1640 and in 50% serum against the C. albicans complex. In RPMI-1640 PAFEs were 1.5 - >19.4, 9.7 - >20.1 and 15.9 - >18.5 hours for C. albicans, C. africana and C. dubliniensis, respectively. In 50% serum PAFEs decreased sharply to 0 - 1.7 hours for all three species; killing rates were always negative. Short growth inhibition without killing in 50% serum suggests that micafungin PAFE has a limited role in the eradication of the C...
October 10, 2017: New Microbiologica
Laura Bedin Denardi, Jéssica Tairine Keller, Maria Isabel de Azevedo, Vanessa Oliveira, Fernanda Baldissera Piasentin, Cecília Bittencourt Severo, Janio Morais Santurio, Sydney Hartz Alves
The checkerboard broth microdilution assay (BMD) is the most frequently used method for the in vitro evaluation of drug combinations. However, its use to evaluate the effect of antifungal drugs on filamentous fungi is sometimes associated with endpoint-reading difficulties, and different degrees of interaction are assigned to the same drug combination. We evaluated combinations of the azoles, itraconazole, posaconazole, and voriconazole, with the echinocandins, anidulafungin, caspofungin, and micafungin, against 15 itraconazole-resistant Aspergillus fumigatus clinical strains via the checkerboard BMD and Etest assay...
October 9, 2017: Mycopathologia
Yan Wang, Jiao Xie, Yuanming Xing, Lu Chen, Ying Li, Ti Meng, Weihua Dong, Xue Wang, Yalin Dong
The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed as well as the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that have compared untargeted antifungal treatments applied to non-neutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon...
October 9, 2017: Antimicrobial Agents and Chemotherapy
Fruzsina Nagy, Aliz Bozó, Zoltán Tóth, Lajos Daróczi, László Majoros, Renátó Kovács
The activity of fluconazole, amphotericin B, caspofungin and micafungin was determined using XTT-based fungal damage assays against planktonic cells, early and mature biofilms of Candida kefyr. Median MICs of planktonic cells were 0.25 mg/l, 0.25 mg/l, 0.5 mg/l, and 0.06 mg/l for fluconazole, amphotericin B, caspofungin, and micafungin, respectively. Fluconazole showed at least 50% fungal damage at ≥4 mg/l (51.5% ± 6.63% to 78.38% ± 1.44%) and at ≥128 mg/l (57.88% ± 9.2% to 67.25% ± 9...
August 4, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Mihai Mares, Bogdan Minea, Valentin Nastasa, Irina Rosca, Andra-Cristina Bostanaru, Iosif Marincu, Vasilica Toma, Violeta Corina Cristea, Carmen Murariu, Mariana Pinteala
The study presents the echinocandin susceptibility profile of a multi-centre collection of pathogenic yeast isolates from Romanian tertiary hospitals. The 562 isolates were identified using ID32C strips, MALDI-TOF MS and DNA sequencing. Minimal inhibitory concentrations (MICs) of caspofungin (CAS), micafungin (MCA), and anidulafungin (ANI) were assessed and interpreted according to EUCAST guidelines. Minimal fungicidal concentrations (MFC) were determined by plating content from the clear MIC wells. The activity was considered fungicidal at MFC/MIC ≤ 4...
August 4, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Hanni Turan, Müge Demirbilek
Infections related to Candida albicans biofilms and subsequent antifungal resistance have become more common with the increased use of indwelling medical devices. Regimens for preventing fungal biofilm formation are needed, particularly in high-risk patients. In this study, we investigated the biofilm formation rate of multiple strains of Candida albicans (n=162 clinical isolates), their antifungal susceptibility patterns, and the efficacy of certain antifungals for preventing biofilm formation. Biofilm formation was graded using a modified Christensen's 96-well plate method...
October 5, 2017: Revista Argentina de Microbiología
Simone S Schüller, Carina Bauer, Lukas Unterasinger, Angelika Berger
Little is known about side effects of micafungin in extremely low birthweight (ELBW) infants. In a retrospective single center study 19 ELBW infants were analyzed for micafungin efficacy and safety. At a mean±SD daily dosage of 7.5 ± 2.0mg/kg no clinically relevant side effects were observed. A significant increase of liver enzymes was reversible after treatment.
September 28, 2017: Pediatric Infectious Disease Journal
Małgorzata Prażyńska, Tomasz Bogiel, Eugenia Gospodarek-Komkowska
Candida spp. is able to form a biofilm, which is considered resistant to the majority of antifungals used in medicine. The aim of this study was to evaluate the in vitro activity of micafungin against Candida spp. biofilms at different stages of their maturation (2, 6, and 24 h). We assessed the inhibitory effect of micafungin against 78 clinical isolates of Candida spp., growing as planktonic or sessile cells, by widely recommended broth microdilution method. The in vitro effect on sessile cells viability was evaluated by colorimetric reduction assay...
October 5, 2017: Folia Microbiologica
Kevin M Watt, Michael Cohen-Wolkowiez, Duane C Williams, Desiree K Bonadonna, Ira M Cheifetz, Dhiren Thakker, Daniel K Benjamin, Kim L R Brouwer
Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction...
September 2017: Journal of Extra-corporeal Technology
Deanna Horner, Diana Altshuler, Chris Droege, Joel Feih, Kevin Ferguson, Mallory Fiorenza, Kasey Greathouse, Leslie Hamilton, Caitlin Pfaff, Lauren Roller, Joanna Stollings, Adrian Wong
PURPOSE: To summarize select critical care pharmacotherapy guidelines and studies published in 2016. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 31 journals monthly for relevant pharmacotherapy articles and selected 107 articles for review over the course of 2016. Of those included in the monthly CCPLU, three guidelines and seven primary literature studies are reviewed here. The guideline updates included are as follows: hospital-acquired pneumonia and ventilator-associated pneumonia management, sustained neuromuscular blocking agent use, and reversal of antithrombotics in intracranial hemorrhage (ICH)...
September 22, 2017: Journal of Critical Care
J M Boonstra, K C van der Elst, A Veringa, E M Jongedijk, R J Brüggemann, R A Koster, G A Kampinga, J G Kosterink, T S van der Werf, J G Zijlstra, D J Touw, J W C Alffenaar
Background: The estimated attributable mortality rate for invasive candidiasis (IC) in the Intensive Care Unit (ICU) setting varies from 30-40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin and therefore dosing adjustments might be mandatory. Objective: To determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment (PTA). Methods: Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin...
October 2, 2017: Antimicrobial Agents and Chemotherapy
Sanjay R Mehta, Scott Johns, Paul Stark, Joshua Fierer
INTRODUCTION: Aureobasidium pullulans is a saprophytic fungus that is widely distributed in the environment, and in the right host can be an opportunistic human pathogen. PRESENTATION OF CASE: A 66-year-old man with Crohn's disease with a single kidney, and requiring total parenteral nutrition via a Hickman catheter, was admitted with a 10-week history of progressive shortness of breath, fevers and weight loss. Chest imaging demonstrated new multifocal lung parenchymal opacities compatible with septic pulmonary emboli...
2017: IDCases
B Almirante, J Garnacho-Montero, E Maseda, F J Candel, S Grau, J Guinea, I Moreno, P Muñoz, S Ruiz-Santana
OBJECTIVE: Invasive infections caused by Candida spp. in critically ill patients may significantly worsen their prognosis, so it is of great importance to establish an early detection and a suitable therapeutic strategy. The objective of this study was to define the differential role of echinocandins in treating certain critical patient profiles. METHODS: A scientific committee of 9 experts in infectious diseases, critical care, microbiology, and hospital pharmacy reviewed the existing evidence on the treatment of candidemia and invasive candidiasis in critically ill patients...
September 25, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Kengo Tejima, Masanori Ishiai, Somay O Murayama, Shun Iwatani, Susumu Kajiwara
Fatty acyl-CoA synthetase (Faa) activates fatty acid (FA) by converting the FA into the CoA ester in the cell. In the present study, we characterized a FAA homologue (CaFAA4) from the opportunistic pathogen Candida albicans. Most organisms can not only synthesize long-chain fatty acyl-CoAs (LCFA-CoAs) endogenously using a fatty acid synthase (Fas) activity but also can uptake long-chain fatty acids (LCFAs) from the extracellular environment and convert them into LCFA-CoAs via a vectorial acylation system. The budding yeast Saccharomyces cerevisiae possesses two LCFA-CoA synthetases, ScFaa1p and ScFaa4p...
September 23, 2017: Current Genetics
Cristina Jiménez-Ortigosa, Caroline Moore, David W Denning, David S Perlin
We have identified the first case of a fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy, and then subsequently failed micafungin treatment.
September 18, 2017: Antimicrobial Agents and Chemotherapy
Hervé Dupont, Yazine Mahjoub, Taieb Chouaki, Emmanuel Lorne, Elie Zogheib
OBJECTIVES: The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection. DATA SOURCES: A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed. STUDY SELECTION: Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials...
November 2017: Critical Care Medicine
Wiley A Schell, A M Jones, Katyna Borroto-Esoda, Barbara D Alexander
SCY-078 in vitro activity was determined for 178 isolates of resistant and susceptible C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, and C. parapsilosis, including 44 Candida isolates having known genotypic (FKS1 or FKS2 mutations), phenotypic or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species...
August 21, 2017: Antimicrobial Agents and Chemotherapy
Yuk-Yam Cheung, Mamie Hui
The in vitro and in vivo effects of nikkomycin Z combined with an echinocandin (anidulafungin or micafungin) against two Candida albicans isolates and their lab-derived echinocandin-resistant fks mutants with FKS1 S645Y and FKS1 S645P were evaluated. Synergistic effects were observed in all tested strains (FICI < 0.5). Enhanced survival were observed in an immunocompromised murine model (log-rank test, P < 0.02). Our study demonstrated the therapeutic potential of nikkomycin Z-echinocandin combinations in managing echinocandin resistance...
August 21, 2017: Antimicrobial Agents and Chemotherapy
Maria Helena Galdino Figueiredo-Carvalho, Lívia de Souza Ramos, Leonardo Silva Barbedo, Jean Carlos Almeida de Oliveira, André Luis Souza Dos Santos, Rodrigo Almeida-Paes, Rosely Maria Zancopé-Oliveira
Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C...
2017: Mediators of Inflammation
Roeland E Wasmann, Eline W Muilwijk, David M Burger, Paul E Verweij, Catherijne A Knibbe, Roger J Brüggemann
Micafungin is a selective inhibitor of the synthesis of fungal 1,3-β-D-glucan, an essential component of the fungal cell wall. It is available as a powder for infusion only and is registered for the treatment of invasive and esophageal candidiasis in addition to prophylaxis of Candida infections in both adults and children. Average exposure after a single intravenous 100 mg dose in healthy adults is 133 mg h/L. Both exposure and maximum plasma concentration show linear dose proportional pharmacokinetics (PK) over a 0...
August 8, 2017: Clinical Pharmacokinetics
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