Antibiotic Exposure as a Risk Factor for Fluconazole-Resistant Candida Bloodstream Infection

Abstract

ABSTRACTRecent exposure to azoles is an important risk factor for infection with fluconazole-resistantCandidaspp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistantCandida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection withC. glabrataand fluconazole-resistantCandidaisolates. Four hundred forty-four episodes of candidemia (450Candidaisolates, 69 [15%]C. glabrataisolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included.C. glabratabloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2;P< 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8;P= 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistantCandidabloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.