Candidemia is one of the four most
common nosocomial blood infections and is the most common hospital-acquired fungemia
in a recent multi-institutional study
from the US. The mortality of Candidemia can be up to 50%. Fluconazole is a triazole derivative widely used for the treatment of invasive
candidiasis. It was recommended as first-line drugs for the treatment and
prevention of mycoses. In our study, we aimed to optimise the dosage of
fluconazole with gender against Candida spp. based on
pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published
data about pharmacokinetic parameters of fluconazole and the MIC distribution
of Candida spp. on fluconazole. We
decided to evaluate the gender between males and females with the
pharmacokinetics of fluconazole. Using probability of target attainment (PTA)
and cumulative fraction of response (CFR) as indexes, crystal
ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage
regimens of different males and females. For C. albicans, C. tropicalis and C. lusitaniae,
when doses of regimen are 100 mg IV, 200 mg IV and MIC was lower than 1 g/ml, PTA was higher than 90%.
For C. tropicalis, each dosing regimen and MIC was less than 2 g/ml.PTA was
higher than 90%. As C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii for PTA with
more than 90%, MIC of fluconazole 200 mg were less than 32 g/ml, 64 g/ml and 64
g/ml, respectively. For
References
[1]
Pfaller, M.A. and Diekema, D.J. (2007) Epidemiology of Invasive Candidiasis: A Persistent Public Health Problem. Clinical Microbiology Reviews, 20, 133-163. https://doi.org/10.1128/CMR.00029-06
[2]
Berdal, J.E., Haagensen, R., Ranheim, T., et al. (2014) Nosocomial Candidemia; Risk Factors and Prognosis Revisited: 11 Years Experience from a Norwegian Secondary Hospital. PLOS ONE, 9, e103916. https://doi.org/10.1371/journal.pone.0103916
[3]
Wu, Z., Liu, Y., Feng, X., et al. (2014) Candidemia: Incidence Rates, Type of Species, and Risk Factors at a Tertiary Care Academic Hospital in China. International Journal of Infectious Diseases, 22, 4-8. https://doi.org/10.1016/j.ijid.2013.11.011
[4]
Pfaller, M., Neofytos, D., Diekema, D., et al. (2012) Epidemiology and Outcomes of Candidemia in 3648 Patients: Data from the Prospective Antifungal Therapy (PATH Alliance®) Registry, 2004-2008. Diagnostic Microbiology and Infectious Disease, 74, 323-331. https://doi.org/10.1016/j.diagmicrobio.2012.10.003
[5]
Wang, Y., et al. (2020) Analysis of Pharmacokinetic/Pharmacodynamic Parameters and Dosage Regimen of Posaconazole against Candida spp. and Aspergillus spp. Using Monte Carlo Simulation. Pharmacology & Pharmacy, 11, 17-28. https://doi.org/10.4236/pp.2020.111003
[6]
Wang, Y., et al. (2020) Optimizing the Dosage Regimen of Micafungin against Candida spp in HIV Positive Patients with EC Based on Mote Carlo Simulation. Open Journal of Preventive Medicine, 10, 120-125. https://doi.org/10.4236/ojpm.2020.106009
[7]
Guo, T., Sun, W.J., Xia, D.Y., et al. (2010) The Pharmacokinetics of Fluconazole in Healthy Chinese Adult Volunteers: Influence of Ethnicity and Gender. Journal of Clinical Pharmacy and Therapeutics, 35, 231-237. https://doi.org/10.1111/j.1365-2710.2009.01097.x
[8]
Miriam del, C., et al. (2007) Gender Differences in the Oral Pharmacokinetics of Fluconazole. Clinical Drug Investigation, 27, 851-855. https://doi.org/10.2165/00044011-200727120-00007
[9]
Michael, A., Mariana, C., Danrel, J., et al. (2010) Wild-Type MIC Distributions, Epidemiological Cutoff Values and Species-Specific Clinical Breakpoints for Fluconazole and Candida: Time for Harmonization of CLSI and EUCAST Broth Microdilution Methods. Drug Resistance Updates, 13, 180-195. https://doi.org/10.1016/j.drup.2010.09.002
[10]
Brammer, K.W., Farrow, P.R. and Faulkner, J.K. (1990) Pharmacokinetics and Tissue Penetration of Fluconazole in Humans. Clinical Infectious Diseases, 12, S318-S326. https://doi.org/10.1093/clinids/12.Supplement_3.S318
[11]
Maria, C.B., Stefania, F., Marco, D.M., et al. (2021) Maternal Use of Fluconazole and Congenital Malformations in the Progeny: A Meta-Analysis of the Literature. Reproductive Toxicology, 100, 42-51. https://doi.org/10.1016/j.reprotox.2020.12.018
[12]
Turpin, R.S., Pai, M.P. and Garey, K.W. (2007) Association of Fluconazole Area under the Concentration-Time Curve/MIC and Dose/MIC Ratios with Mortality in Nonneutropenic Patients with Candidemia. Antimicrobial Agents and Chemotherapy, 51, 35-39. https://doi.org/10.1128/AAC.00474-06
[13]
Jarvis, W.R. (1998) Epidemiology, Appropriateness, and Cost of Vancomycin Use. Clinical Infectious Diseases, 26, 1200-1203. https://doi.org/10.1086/520284
[14]
Pfaller, M.A., Jones, R.N., Doerll, G.V., et al. (2000) Bloodstream Infections Due to Candida Species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998. Antimicrobial Agents and Chemotherapy, 44, 747-751. https://doi.org/10.1128/AAC.44.3.747-751.2000
[15]
Abi-Said, D., Anaissie, E., Uzun, O., et al. (1997) The Epidemiology of Hematogenous Candidiasis Caused by Different Candida Species. Clinical Infectious Diseases, 24, 1122-1128. https://doi.org/10.1086/513663
[16]
Aisner, J., Schimpff, S.C., Sutherland, J.C., et al. (1976) Torulopsis glabrata Infections in Patients with Cancer. Increasing Incidence and Relationship to Colonization. The American Journal of Medicine, 61, 23-28. https://doi.org/10.1016/0002-9343(76)90026-7
[17]
Arif, S., Barkham, T., Power, E.G., et al. (1996) Techniques for Investigation of an Apparent Outbreak of Infections with Candida glabrata. Journal of Clinical Microbiology, 34, 2205-2209. https://doi.org/10.1128/jcm.34.9.2205-2209.1996
[18]
John, O.S. (2018) Candida auris: A Systematic Review and Meta-Analysis of Current Updates on an Emerging Multidrug-Resistant Pathogen. Microbiology Open, 7, 578-607. https://doi.org/10.1002/mbo3.578
