Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance

Fernández‐Ruiz, Mario; Lora-Pablos, David; Puig-Asensio, Mireia; Padilla, Belén; Muñóz, Patricia; Guinea, Jesús; Pardo, Julio; García-Rodríguez, Julio; Cerrada, C. García; Fortün, Jesús; Martin, Peter; Gómez, Elia; Ryan, Pablo; Campelo, C.; Gil, Ignacio de los Santos; Buendía, V.; Gorricho, B. Pérez; Alonso, Manuel; Sanz, Francisca; Aguado, José María; Merino, Paloma; Romo, Fernando González; Górgolas, Miguel; Gadea, Ignacio; Losa, Juan Emilio; Delgado‐Iribarren, Alberto; Ramos, Antonio; Romero, Yolanda; Romero, Isabel Sánchez; Zaragoza, Óscar; Cuenca‐Estrella, Manuel; Rodríguez-Baño, Jesús; Suarez, A.I.; Loza, Ana; Garcia, Alejandro; Martín-Mazuelos, Estrella; Pipaón, Maite Ruiz Pérez de; Garnacho, José; Ortíz, Carlos; Chávez, Mariana; Maroto, F.L.; Salavert, M; Pemán, Javier; Blanquer, José; Navarro, David; Camarena, Juan J.; Zaragoza, Rafael; Abril, Vicente; Gimeno, Cristina Verdejo; Hernández, Sara; Ezpeleta, Guillermo; Bereciartúa, Elena; Almaraz, J.L. Hernández; Montejo, Miguel; Rivas, Raúl; Ayarza, R.; Planes, Ana María; Ruiz‐Camps, Isabel; Almirante, Benito; Mensa, José; Almela, Manuel; Gurguí, M.; Sánchez-Reus, Ferran; Martínez‐Montauti, Joaquin; Sierra, Montserrat; Horcajada, Juan Pablo; Sorlí, Luisa; Gómez, Juana Carretero; Gené, A.; Urrea, Mireya; Mularoni, Alessandra; Valerio, Maricela; Díaz-Martín, Ana; Gimeno, Francesc Puchades

doi:10.1016/j.cmi.2017.01.014

Cited by 22 publications

(15 citation statements)

References 38 publications

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“…Likewise, in a study by Fernández-Ruiz and colleagues (9) of 249 patients with candidemia (including 23 infected with C. glabrata), no specific AUC/MIC threshold was significantly associated with fluconazole failure, defined as a composite of 30-day death and/or persistent candidemia, in multivariate analyses. The study did not assess the impact of fluconazole dose on outcomes (9). Therefore, our study provides novel data regarding the relationship between various measures of fluconazole exposure and outcomes in C. glabrata fungemia.…”

Section: Discussionmentioning

confidence: 91%

“…This imprecision in AUC estimates might have contributed to our findings. This is a limitation shared by other retrospective analyses of fluconazole pharmacodynamics (8,9,(13)(14)(15). Another limitation of our study is that, since the included patients were treated between 2002 and 2011, improvements in supportive care and treatment of comorbid conditions may limit the applicability of our results to present-day practice.…”

Section: Discussionmentioning

confidence: 92%

“…Previous unadjusted analyses found various correlations between fluconazole pharmacodynamic indices and clinical outcomes for patients with invasive Candida infections (6). Only two previous studies of fluconazole pharmacodynamics in candidemia performed adjusted analyses to control for confounding variables (8,9). In a study by Brosh-Nissimov and Ben-Ami (8), AUC/MIC thresholds were not associated with 30-day death in a Cox proportional hazards model for a cohort of 75 patients with candidemia (including 8 infected with C. glabrata).…”

Section: Discussionmentioning

confidence: 99%

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Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose

Eschenauer

Carver

Patel

et al. 2018

Antimicrob Agents Chemother

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Robust pharmacodynamic indices that align fluconazole dose or exposure with outcomes in invasive candidiasis due to remain elusive. The purpose of this retrospective multicenter study was to evaluate a cohort of 127 patients with fungemia treated with fluconazole, using adjusted analyses to identify risk factors for 28-day death. No significant correlations were found between fluconazole area under the curve (AUC), AUC/MIC ratio, or MIC and survival. In multivariate logistic regression analyses, however, higher average fluconazole dose (odds ratio [OR], 1.006 [95% confidence interval [CI], 1.001 to 1.010]; = 0.008), average fluconazole dose of ≥400 mg (OR, 3.965 [95% CI, 1.509 to 10.418]; = 0.005), and higher fluconazole dose on day 1 of therapy (OR, 1.007 [95% CI, 1.002 to 1.011]; = 0.002) were found to be independent predictors of 28-day survival. Additionally, the presence of a central venous catheter at the time of infection was found to be a significant risk factor for death. In conclusion, we found fluconazole dose to be an independent predictor of 28-day survival for patients with fungemia, with doses of ≥400 mg/day being associated with 28-day survival rates approaching 90%. These data indicate the use and efficacy of fluconazole in the treatment of this serious infection. Aggressive dosing appears to be necessary when fluconazole is used for the treatment of fungemia, irrespective of MIC.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose

Eschenauer

Carver

Patel

et al. 2018

Antimicrob Agents Chemother

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“…While these studies allow more robust examination of patients with invasive infections, they continued to suffer from limitations similar to those of the Rex et al data set, that is, they included small (Ͻ15%) numbers of isolates with MICs in the SDD category, they grouped all Candida species together (thus precluding analysis of individual species, such as C. glabrata, for example), and they included patients treated with a wide range of doses (12). Similarly, to explore the role of azole pharmacodynamics, several investigators have investigated correlations between AUC/MIC (or dose/MIC) and outcome in patients with candidemia (Table 2) (10,(13)(14)(15)(16)(17)(18)(19)(20). These studies were unable to identify a definitive AUC/MIC or dose/MIC threshold that correlates with treatment success for all patients.…”

Section: Fluconazole Susceptibility and Treatment Successmentioning

confidence: 99%

“…These studies were unable to identify a definitive AUC/MIC or dose/MIC threshold that correlates with treatment success for all patients. Notably, few studies used adjusted analyses to account for differences in severity of illness (18)(19)(20). This is an important distinction, as candidemia generally occurs in patients with multiple comorbidities that can significantly influence patient outcomes (21).…”

Section: Fluconazole Susceptibility and Treatment Successmentioning

confidence: 99%

Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

2018

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The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for species. Studies evaluating the relationship between treatment efficacy and susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than and , and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on susceptibility are growing, particularly for and Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.

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Issues and Concerns in the Management of Systemic Candidiasis

Fong

2020

Current Trends and Concerns in Infectious Diseases

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Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance

Abstract: High fluconazole MIC values did not negatively impact outcome of patients with candidaemia treated with fluconazole. No effect of PK/PD targets on the risk of clinical failure was found.

Cited by 22 publications

References 38 publications

Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose

Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose

Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

Issues and Concerns in the Management of Systemic Candidiasis

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