Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia?

Kovacicova, G.; Krupova, Y.; Lovaszova, Marcela; Roidová, A.; Trupl, J.; Líšková, Anna; Hanzen, Juraj; Milosovic, P; Lamosová, M; Macekova, Lubica; Szovenyiova, Zuzana; Purgelová, Anna; Obertik, Tanya; Billé, Jacques; Krčméry, V.

doi:10.1007/s101560070006

Cited by 38 publications

(28 citation statements)

References 9 publications

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“…Moreover, the 24-h AUC/MIC target of Ͼ25 has been associated with efficacy in animal models of Candida albicans infection (2,3,12,13). Analysis of clinical outcomes in patients with mucosal candidiasis suggests that a fluconazole AUC/MIC target near 25 is similarly predictive of a favorable outcome in patients (4,5,10,11,15,22). Importantly, these pharmacodynamic data are supportive of the CLSI fluconazole susceptibility breakpoints and the creation of the susceptible dose-dependent category.…”

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confidence: 75%

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia

Baddley

Patel

Bhavnani

et al. 2008

Antimicrob Agents Chemother

147

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Recent studies of nonneutropenic patients with candidemia or candidiasis suggest that fluconazole pharmacodynamic parameters correlate with clinical outcomes; however, additional data of correlation to mortality in patients with candidemia would be valuable. We assessed the impact of MICs for Candida, fluconazole pharmacodynamics, and patient characteristics on all-cause mortality with use of a prospective cohort of 96 hospitalized patients with candidemia. Among 84 patients for whom Candida isolates were available for testing, the most frequent Candida species isolated were Candida albicans (44%), followed by Candida parapsilosis (20.2%), and Candida glabrata (20.2%). Fluconazole resistance (MIC of >64 g/ml) was present in 7 (8.3%) to 10 (11.9%) of 84 isolates, depending on the MIC endpoint determination method (50% or 80% inhibition read at 24 or 48 h). Overall mortality occurred in 27 (28.1%) of 96 patients, and nonsurvivors were more likely to have fluconazole-resistant isolates (25% versus 6.7%; P ‫؍‬ 0.02). Multivariable analysis demonstrated an association between fluconazole resistance and mortality, but it did not reach statistical significance (odds ratio, 5.3; 95% confidence interval, 0.8 to 33.4; P ‫؍‬ 0.08). By pharmacodynamic analysis, a fluconazole area under the concentration-time curve/MIC of <11.5 or MIC of >64 was associated with increased patient mortality (P < 0.09). These data support previous findings of an antifungal exposure-response relationship to mortality in patients with candidemia. In addition, similar MICs were obtained using a 24-or 48-h MIC endpoint determination, thus providing the opportunity to assess earlier the impact of isolate susceptibility on therapy.

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confidence: 75%

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia

Baddley

Patel

Bhavnani

et al. 2008

Antimicrob Agents Chemother

147

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“…Since their publication, the NCCLS interpretative breakpoints have been supported by further data on oropharyngeal candidiasis (5-7, 21, 22, 25, 30, 34). A correlation between in vitro susceptibility and the response to therapy of nonmucosal candidiasis has been demonstrated in some studies (11,12) but not others (26).…”

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confidence: 98%

“…In reassessing the oropharyngeal candidiasis data originally used to establish the NCCLS breakpoint MICs, Rex et al demonstrated that a fluconazole dose/48-h MIC ratio of Ͻ25 correlated with an increased likelihood of therapeutic failure (28). The ability to extrapolate these findings to the settings of candidemia or other types of nonmucosal candidiasis is limited by the paucity of clinical data (11,12,26,27). In particular, data evaluating a range of drug dosages to outcome for infections due to isolates with elevated MICs are lacking (28).…”

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confidence: 99%

Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia

Clancy

Morris³

et al. 2005

Antimicrob Agents Chemother

159

114

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We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (<200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 g/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 g/ml and 219.36 [P ‫؍‬ 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC < 8 g/ml), susceptible-dose dependent (S-DD) (MIC ‫؍‬ 16 or 32 g/ml), and resistant (MIC > 64 g/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio <50 (P ‫؍‬ 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.Candida spp. emerged as common causes of mucosal and systemic diseases with the onset of the AIDS epidemic and increasing populations of immunosuppressed individuals (18). The introduction of fluconazole revolutionized the therapy of candidal infections in the 1990s by offering a well-tolerated alternative to amphotericin B, the long-standing and significantly toxic antifungal of choice (23). Despite the recent development of newer antifungal drugs, fluconazole remains an attractive front-line agent against candidiasis because of its excellent oral bioavailability and overall clinical efficacy.The increasing importance of candidal infections created the need for reliable methods of testing clinical isolates for susceptibility to fluconazole and other antifungal agents. After 15 years of collaborative research, the National Committee for Clinical Laboratory Standards (NCCLS) approved a standardized reference method for testing of yeasts that demonstrated excellent intra-and interlaboratory reproducibility (17). With this method, the NCCLS proposed interpretive breakpoint MICs of fluconazole that correlated with the response to therapy in vivo, largely based upon the experience in treating human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis caused by Candida albicans (27). Since their publication, the NCCLS interpretative breakpoints have been supported by further data on oropharyngeal candidiasis (5-7, 21, 22, 25, 30, 34). A correlation between in vitro susceptibility and the response to therapy of nonmucosal candidiasis has been demonstrated in some studi...

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“…[9,10] Isolates with an M27 amphotericin B MIC of ≥1µg/ml is considered likely resistant to CAB. [3] …”

Section: Identification and Antifungal Susceptibility Test Of Candidamentioning

confidence: 99%

Comparison Of Antifungal Susceptibilities In Candidemic Newborns According To Their Body Weights

Yıldıran¹,

Belet²,

Günaydın³

et al. 2009

TUTFD

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Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia?

Cited by 38 publications

References 9 publications

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia

Association of Fluconazole Pharmacodynamics with Mortality in Patients with Candidemia

Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia

Comparison Of Antifungal Susceptibilities In Candidemic Newborns According To Their Body Weights

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