1149. In vitro Synergy of Tigecycline Plus Fluconazole Against Candida glabrata
Session: Poster Abstract Session: Pharmacological Studies of Antifungals
Friday, October 9, 2015
Room: Poster Hall
Background: Candida glabrata is a pathogen of increasing clinical importance. C. glabrata’s resistance to fluconazole and also echinocandins is a growing problem. Synergy between doxycycline and fluconazole has been described in laboratory strains of Candida albicans. Our previous studies showed in vitro synergy with doxycycline plus fluconazole in 5/20 C. glabrata blood isolates. Tigecycline, a synthetic tetracycline (glycylcycline) less susceptible to known tetracycline resistance mechanisms, has been found to inhibit biofilm formation when combined with fluconazole in one strain of C. albicans. We studied our same 20 blood isolates of C. glabrata for evidence of in vitro synergy of tigecycline plus fluconazole using an Etest® method. Methods: Twenty blood isolates of C. glabrata were collected from the Ochsner Medical Center in New Orleans, LA from 2009-2011. Isolates were identified with the API 20C yeast identification system and genetically fingerprinted by rep-PCR. A MIC:MIC Etest synergy method, (Pankey et al, 2014, AAC 58:5795-800) was used for synergy testing. All tests were done in triplicate (mean value used) and read at 24 h. A summation fractional inhibitory concentration (∑FIC) was calculated for each isolate: synergy ≤ 0.5; additivity >0.5-1; indifference >1-4; antagonism >4. Results: Ten of the 20 isolates were susceptible, dose-dependent, to fluconazole at 24 h with Etest MICs ≤ 32 μg/mL; the remainder were resistant (MICs 48 to >256 μg/mL). All isolates had tigecycline MICs >256 μg/mL. We detected synergy (∑FICs 0.001 - 0.45) in 17 out of 20 isolates. One isolate each showed additivity (ΣFIC 0.52), indifference (∑FIC 2.00) or antagonism (mean ∑FIC 6.42). The antagonism was noted in all three repeats (∑FIC 8.50, 4.50, 6.26, median 6.50). Conclusion: Synergy (17) or additivity (1) was demonstrated in vitro with tigecycline plus fluconazole in 90% of our C. glabrata blood isolates using an Etest method. Antagonism was repeatedly found in one isolate. The mechanism of synergy or antagonism is unclear at this time but may involve interference with C. glabrata fluconazole efflux pumps. More C. glabrata isolates should be tested for synergy via Etest and other methods for comparison. These in vitro results may or may not have clinical utility.
Randol Hooper II, MS, MD1,2, Deborah S. Ashcraft, BS, MT3 and George a. Pankey, MD, FIDSA3, (1)University of Queensland Ochsner Clinical School, Brisbane, Australia, (2)Ochsner Clinic Foundation, New Orleans, LA, (3)Infectious Diseases, Ochsner Clinic Foundation, New Orleans, LA

Disclosures:

R. Hooper II, None

D. S. Ashcraft, None

G. A. Pankey, None

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