Abdullah M S Al-Hatmi1, Joseph Meletiadis2, Ilse Curfs-Breuker3, Alexandro Bonifaz4, Jacques F Meis5, G Sybren De Hoog6. 1. CBS-KNAW Fungal Biodiversity Centre, PO Box 85167, 3508 AD Utrecht, The Netherlands Institutes of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands Directorate General of Health Services, Ibri Hospital, Ministry of Health, Muscat, Oman a.alhatmi@cbs.knaw.nl. 2. Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 3. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. 4. Hospital General de México, O.D, Mexico City, Mexico. 5. Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands. 6. CBS-KNAW Fungal Biodiversity Centre, PO Box 85167, 3508 AD Utrecht, The Netherlands Institutes of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands Basic Pathology Department, Federal University of Paraná State, Curitiba, Paraná, Brazil Biology Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Abstract
OBJECTIVES: Fusarium species cause a broad spectrum of infections, from superficial to disseminated disease. Because Fusarium species are intrinsically resistant to most antifungal drugs, new approaches are needed. The aim of the present study was to evaluate the in vitro combination of natamycin with currently used antifungal drugs. METHODS: The in vitro interactions of combinations between natamycin and voriconazole, itraconazole and micafungin applied to 20 clinical Fusarium strains (members of Fusarium falciforme, Fusarium napiforme, Fusarium petroliphilum, Fusarium proliferatum, Fusarium pseudensiforme and Fusarium sacchari) were evaluated using a chequerboard microdilution method. The MICs of all drugs alone and in combination were determined visually after 48 h and interactions were assessed using fractional inhibitory concentration index (FICI) analysis. RESULTS: MICs of voriconazole and natamycin alone were 4 to >16 and 4-8 mg/L, respectively. Values were reduced 3.5-10-fold to 0.02-0.5 mg/L and 0.5-5-fold to 0.13-2 mg/L in combination, for the currently used antifungals and natamycin, respectively, demonstrating additive to synergistic interactions. The combinations natamycin/voriconazole, natamycin/itraconazole and natamycin/micafungin were synergistic (FICI ≤0.5) for 70%, 15% and 5% of the strains, respectively. No antagonism was found. CONCLUSIONS: The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations.
OBJECTIVES:Fusarium species cause a broad spectrum of infections, from superficial to disseminated disease. Because Fusarium species are intrinsically resistant to most antifungal drugs, new approaches are needed. The aim of the present study was to evaluate the in vitro combination of natamycin with currently used antifungal drugs. METHODS: The in vitro interactions of combinations between natamycin and voriconazole, itraconazole and micafungin applied to 20 clinical Fusarium strains (members of Fusarium falciforme, Fusarium napiforme, Fusarium petroliphilum, Fusarium proliferatum, Fusarium pseudensiforme and Fusarium sacchari) were evaluated using a chequerboard microdilution method. The MICs of all drugs alone and in combination were determined visually after 48 h and interactions were assessed using fractional inhibitory concentration index (FICI) analysis. RESULTS: MICs of voriconazole and natamycin alone were 4 to >16 and 4-8 mg/L, respectively. Values were reduced 3.5-10-fold to 0.02-0.5 mg/L and 0.5-5-fold to 0.13-2 mg/L in combination, for the currently used antifungals and natamycin, respectively, demonstrating additive to synergistic interactions. The combinations natamycin/voriconazole, natamycin/itraconazole and natamycin/micafungin were synergistic (FICI ≤0.5) for 70%, 15% and 5% of the strains, respectively. No antagonism was found. CONCLUSIONS: The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations.
Authors: N Venkatesh Prajna; Tiruvengada Krishnan; Revathi Rajaraman; Sushila Patel; Ranjeet Shah; Muthiah Srinivasan; Lumbini Devi; Manoranjan Das; Kathryn J Ray; Kieran S O'Brien; Catherine E Oldenburg; Stephen D McLeod; Michael E Zegans; Nisha R Acharya; Thomas M Lietman; Jennifer Rose-Nussbaumer Journal: JAMA Ophthalmol Date: 2017-06-01 Impact factor: 7.389
Authors: Mahdi Abastabar; Abdullah M S Al-Hatmi; Mohammad Vafaei Moghaddam; G Sybren de Hoog; Iman Haghani; Seyed Reza Aghili; Tahereh Shokohi; Mohammad Taghi Hedayati; Roshanak Daie Ghazvini; Reza Kachuei; Ali Rezaei-Matehkolaei; Koichi Makimura; Jacques F Meis; Hamid Badali Journal: Antimicrob Agents Chemother Date: 2018-04-26 Impact factor: 5.191
Authors: Abdullah M S Al-Hatmi; Anne-Cécile Normand; Stephane Ranque; Renaud Piarroux; G Sybren de Hoog; Joseph Meletiadis; Jacques F Meis Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191
Authors: Hazal Boral; Anne van Diepeningen; Elif Erdem; Meltem Yağmur; G Sybren de Hoog; Macit Ilkit; Jacques F Meis; Abdullah M S Al-Hatmi Journal: Mycopathologia Date: 2018-06-21 Impact factor: 2.574
Authors: Yanping Jiang; Abdullah M S Al-Hatmi; Yining Xiang; Yu Cao; Albert H G Gerrits van den Ende; Ilse Curfs-Breuker; Jacques F Meis; Hongguang Lu; G Sybren de Hoog Journal: Mycopathologia Date: 2016-06-21 Impact factor: 2.574
Authors: Abdullah Ms Al-Hatmi; Ferry Hagen; Steph Bj Menken; Jacques F Meis; G Sybren de Hoog Journal: Emerg Microbes Infect Date: 2016-12-07 Impact factor: 7.163