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

M. Fernández-Ruiz; J. Guinea; D. Lora-Pablos; O. Zaragoza; M. Puig-Asensio; B. Almirante; M. Cuenca-Estrella; J. M. Aguado; B. Padilla; P. Muñoz; J. Guinea; J. R. Paño Pardo; J. García-Rodríguez; C. G. Cerrada; J. Fortún; P. Martín; E. Gómez; P. Ryan; C. Campelo; I. de los Santos Gil; V. Buendía; B. P. Gorricho; M. Alonso; F. S. Sanz; J. M. Aguado; P. Merino; F. González Romo; M. Gorgolas; I. Gadea; J. E. Losa; A. Delgado-Iribarren; A. Ramos; Y. Romero; I. S. Romero; O. Zaragoza; M. Cuenca-Estrella; J. Rodríguez-Baño; A. I. Suarez; A. Loza; A. I. Aller García; E. Martín-Mazuelos; M. R. Pérez de Pipaón; J. Garnacho; C. Ortiz; M. Chávez; F. L. Maroto; M. Salavert; J. Pemán; J. Blanquer; D. Navarro; J. J. Camarena; R. Zaragoza; V. Abril; C. Gimeno; S. Hernández; G. Ezpeleta; E. Bereciartua; J. L. Hernández Almaraz; M. Montejo; R. A. Rivas; R. Ayarza; A. M. Planes; I. R. Camps; J. Mensa; M. Almela; M. Gurgui; F. Sánchez-Reus; J. Martínez-Montauti; M. Sierra; J. P. Horcajada; L. Sorli; J. Gómez; A. Gené; M. Urrea; A. Mularoni; M. Valerio; A. Díaz-Martín; F. Puchades

doi:10.1016/j.cmi.2017.01.014

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

M. Fernández-Ruiz, J. Guinea, D. Lora-Pablos, O. Zaragoza, M. Puig-Asensio, B. Almirante, M. Cuenca-Estrella, J. M. Aguado, B. Padilla, P. Muñoz, J. Guinea, J. R. Paño Pardo, J. García-Rodríguez, C. G. Cerrada, J. Fortún, P. Martín, E. Gómez, P. Ryan, C. Campelo, I. de los Santos GilV. Buendía, B. P. Gorricho, M. Alonso, F. S. Sanz, J. M. Aguado, P. Merino, F. González Romo, M. Gorgolas, I. Gadea, J. E. Losa, A. Delgado-Iribarren, A. Ramos, Y. Romero, I. S. Romero, O. Zaragoza, M. Cuenca-Estrella, J. Rodríguez-Baño, A. I. Suarez, A. Loza, A. I. Aller García, E. Martín-Mazuelos, M. R. Pérez de Pipaón, J. Garnacho, C. Ortiz, M. Chávez, F. L. Maroto, M. Salavert, J. Pemán, J. Blanquer, D. Navarro, J. J. Camarena, R. Zaragoza, V. Abril, C. Gimeno, S. Hernández, G. Ezpeleta, E. Bereciartua, J. L. Hernández Almaraz, M. Montejo, R. A. Rivas, R. Ayarza, A. M. Planes, I. R. Camps, J. Mensa, M. Almela, M. Gurgui, F. Sánchez-Reus, J. Martínez-Montauti, M. Sierra, J. P. Horcajada, L. Sorli, J. Gómez, A. Gené, M. Urrea, A. Mularoni, M. Valerio, A. Díaz-Martín, F. Puchades

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© 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients. Methods We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality. Results Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026). Conclusions 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.

Idioma original	Anglès
Pàgines (de-a)	672.e1-672.e11
Revista	Clinical Microbiology and Infection
Volum	23
Número	9
DOIs	https://doi.org/10.1016/j.cmi.2017.01.014
Estat de la publicació	Publicada - 1 de set. 2017

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10.1016/j.cmi.2017.01.014

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Fernández-Ruiz, M., Guinea, J., Lora-Pablos, D., Zaragoza, O., Puig-Asensio, M., Almirante, B., Cuenca-Estrella, M., Aguado, J. M., Padilla, B., Muñoz, P., Guinea, J., Paño Pardo, J. R., García-Rodríguez, J., Cerrada, C. G., Fortún, J., Martín, P., Gómez, E., Ryan, P., Campelo, C., ... Puchades, F. (2017). Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance. Clinical Microbiology and Infection, 23(9), 672.e1-672.e11. https://doi.org/10.1016/j.cmi.2017.01.014

@article{065ffc4aa58b4a5c85a191b4df5d53d1,

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

abstract = "{\textcopyright} 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients. Methods We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality. Results Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026). Conclusions 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.",

keywords = "Candidaemia, Fluconazole, Outcome, PK/PD parameters, Susceptibility",

author = "M. Fern{\'a}ndez-Ruiz and J. Guinea and D. Lora-Pablos and O. Zaragoza and M. Puig-Asensio and B. Almirante and M. Cuenca-Estrella and Aguado, {J. M.} and B. Padilla and P. Mu{\~n}oz and J. Guinea and {Pa{\~n}o Pardo}, {J. R.} and J. Garc{\'i}a-Rodr{\'i}guez and Cerrada, {C. G.} and J. Fort{\'u}n and P. Mart{\'i}n and E. G{\'o}mez and P. Ryan and C. Campelo and {de los Santos Gil}, I. and V. Buend{\'i}a and Gorricho, {B. P.} and M. Alonso and Sanz, {F. S.} and Aguado, {J. M.} and P. Merino and {Gonz{\'a}lez Romo}, F. and M. Gorgolas and I. Gadea and Losa, {J. E.} and A. Delgado-Iribarren and A. Ramos and Y. Romero and Romero, {I. S.} and O. Zaragoza and M. Cuenca-Estrella and J. Rodr{\'i}guez-Ba{\~n}o and Suarez, {A. I.} and A. Loza and {Aller Garc{\'i}a}, {A. I.} and E. Mart{\'i}n-Mazuelos and {P{\'e}rez de Pipa{\'o}n}, {M. R.} and J. Garnacho and C. Ortiz and M. Ch{\'a}vez and Maroto, {F. L.} and M. Salavert and J. Pem{\'a}n and J. Blanquer and D. Navarro and Camarena, {J. J.} and R. Zaragoza and V. Abril and C. Gimeno and S. Hern{\'a}ndez and G. Ezpeleta and E. Bereciartua and {Hern{\'a}ndez Almaraz}, {J. L.} and M. Montejo and Rivas, {R. A.} and R. Ayarza and Planes, {A. M.} and Camps, {I. R.} and J. Mensa and M. Almela and M. Gurgui and F. S{\'a}nchez-Reus and J. Mart{\'i}nez-Montauti and M. Sierra and Horcajada, {J. P.} and L. Sorli and J. G{\'o}mez and A. Gen{\'e} and M. Urrea and A. Mularoni and M. Valerio and A. D{\'i}az-Mart{\'i}n and F. Puchades",

year = "2017",

month = sep,

day = "1",

doi = "10.1016/j.cmi.2017.01.014",

language = "English",

volume = "23",

pages = "672.e1--672.e11",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier Limited",

number = "9",

}

Fernández-Ruiz, M, Guinea, J, Lora-Pablos, D, Zaragoza, O, Puig-Asensio, M, Almirante, B, Cuenca-Estrella, M, Aguado, JM, Padilla, B, Muñoz, P, Guinea, J, Paño Pardo, JR, García-Rodríguez, J, Cerrada, CG, Fortún, J, Martín, P, Gómez, E, Ryan, P, Campelo, C, de los Santos Gil, I, Buendía, V, Gorricho, BP, Alonso, M, Sanz, FS, Aguado, JM, Merino, P, González Romo, F, Gorgolas, M, Gadea, I, Losa, JE, Delgado-Iribarren, A, Ramos, A, Romero, Y, Romero, IS, Zaragoza, O, Cuenca-Estrella, M, Rodríguez-Baño, J, Suarez, AI, Loza, A, Aller García, AI, Martín-Mazuelos, E, Pérez de Pipaón, MR, Garnacho, J, Ortiz, C, Chávez, M, Maroto, FL, Salavert, M, Pemán, J, Blanquer, J, Navarro, D, Camarena, JJ, Zaragoza, R, Abril, V, Gimeno, C, Hernández, S, Ezpeleta, G, Bereciartua, E, Hernández Almaraz, JL, Montejo, M, Rivas, RA, Ayarza, R, Planes, AM, Camps, IR, Mensa, J, Almela, M, Gurgui, M, Sánchez-Reus, F, Martínez-Montauti, J, Sierra, M, Horcajada, JP, Sorli, L, Gómez, J, Gené, A, Urrea, M, Mularoni, A, Valerio, M, Díaz-Martín, A & Puchades, F 2017, 'Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance', Clinical Microbiology and Infection, vol. 23, núm. 9, pàg. 672.e1-672.e11. https://doi.org/10.1016/j.cmi.2017.01.014

TY - JOUR

T1 - Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance

AU - Fernández-Ruiz, M.

AU - Guinea, J.

AU - Lora-Pablos, D.

AU - Zaragoza, O.

AU - Puig-Asensio, M.

AU - Almirante, B.

AU - Cuenca-Estrella, M.

AU - Aguado, J. M.

AU - Padilla, B.

AU - Muñoz, P.

AU - Guinea, J.

AU - Paño Pardo, J. R.

AU - García-Rodríguez, J.

AU - Cerrada, C. G.

AU - Fortún, J.

AU - Martín, P.

AU - Gómez, E.

AU - Ryan, P.

AU - Campelo, C.

AU - de los Santos Gil, I.

AU - Buendía, V.

AU - Gorricho, B. P.

AU - Alonso, M.

AU - Sanz, F. S.

AU - Aguado, J. M.

AU - Merino, P.

AU - González Romo, F.

AU - Gorgolas, M.

AU - Gadea, I.

AU - Losa, J. E.

AU - Delgado-Iribarren, A.

AU - Ramos, A.

AU - Romero, Y.

AU - Romero, I. S.

AU - Zaragoza, O.

AU - Cuenca-Estrella, M.

AU - Rodríguez-Baño, J.

AU - Suarez, A. I.

AU - Loza, A.

AU - Aller García, A. I.

AU - Martín-Mazuelos, E.

AU - Pérez de Pipaón, M. R.

AU - Garnacho, J.

AU - Ortiz, C.

AU - Chávez, M.

AU - Maroto, F. L.

AU - Salavert, M.

AU - Pemán, J.

AU - Blanquer, J.

AU - Navarro, D.

AU - Camarena, J. J.

AU - Zaragoza, R.

AU - Abril, V.

AU - Gimeno, C.

AU - Hernández, S.

AU - Ezpeleta, G.

AU - Bereciartua, E.

AU - Hernández Almaraz, J. L.

AU - Montejo, M.

AU - Rivas, R. A.

AU - Ayarza, R.

AU - Planes, A. M.

AU - Camps, I. R.

AU - Mensa, J.

AU - Almela, M.

AU - Gurgui, M.

AU - Sánchez-Reus, F.

AU - Martínez-Montauti, J.

AU - Sierra, M.

AU - Horcajada, J. P.

AU - Sorli, L.

AU - Gómez, J.

AU - Gené, A.

AU - Urrea, M.

AU - Mularoni, A.

AU - Valerio, M.

AU - Díaz-Martín, A.

AU - Puchades, F.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - © 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients. Methods We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality. Results Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026). Conclusions 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.

AB - © 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives The clinical correlation of fluconazole antifungal susceptibility testing (AST) for Candida isolates and its integration with pharmacokinetics/pharmacodynamics (PK/PD) parameters is unclear. We analysed the impact of fluconazole minimum inhibitory concentration (MIC) values, 24-hour area under the concentration–time curve (AUC24) and AUC24/MIC ratio on the outcome of candidemic patients. Methods We included 257 episodes of candidaemia treated with fluconazole monotherapy for ≥72 hours from a population-based surveillance conducted in 29 hospitals (CANDIPOP Project). AST was centrally performed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) microdilution methods. Primary outcome was clinical failure (30-day mortality and/or persistent candidaemia for ≥72 hours from initiation of therapy). Secondary outcomes included early (3–7 days) and late (3–30 days) mortality. Results Rates of clinical failure, early and late mortality among evaluable episodes were 32.3% (80/248), 3.1% (8/257) and 23.4% (59/248). There was no relationship between fluconazole MIC values or PK/PD parameters and clinical failure. Although MIC values ≥2 mg/L by EUCAST (positive predictive value 32.1%, negative predictive value 68.7%) and ≥0.5 mg/L by CLSI (positive predictive value 34.8%, negative predictive value 74.4%) appeared to be optimal for predicting clinical failure, no significant associations remained after multivariate adjustment (odds ratio 1.67; 95% confidence interval 0.48–5.79; p 0.423). Lack of association was consistent for alternative thresholds (including proposed clinical breakpoints). The only association found for secondary outcomes was between an AUC24/MIC ratio >400 h by CLSI and early mortality (odds ratio 0.18; 95% confidence interval 0.04–0.98; p 0.026). Conclusions 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.

KW - Candidaemia

KW - Fluconazole

KW - Outcome

KW - PK/PD parameters

KW - Susceptibility

U2 - 10.1016/j.cmi.2017.01.014

DO - 10.1016/j.cmi.2017.01.014

M3 - Article

SN - 1198-743X

VL - 23

SP - 672.e1-672.e11

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 9

ER -

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

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