Challenges in Antifungal Therapy in Diabetes Mellitus
Abstract
:1. Introduction
2. Effect of Diabetes Mellitus on the Pharmacokinetics of Antifungal
3. Challenges in the Treatment of Candida sp. Infections in Diabetic Patients
3.1. Antifungal Resistance
3.2. Biofilm Formation
4. Application of PK/PD Concepts in Optimisation of Antifungal Dosing
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Reference | Antifungal Tested | Study Design | Patient Population | Dosing Regimens Tested/Simulated | PK/PD Target | Finding |
---|---|---|---|---|---|---|
Martial (2017) [49] | Micafungin | PK study, in silico | ICU, critically ill | (I) 100 mg QD for 14 days and (II) 100 mg QD the first 4 days with 200 mg QD from day 5 (labelled indication for non-responders); alternative regimens included (III) 200 mg loading dose on day 1 followed by 100 mg QD from day 2, (IV) 200 mg loading dose followed by 150 mg QD from day 2 and (V) 200 mg QD. | AUC/MIC >3000 | PTA was >91% on day 14 for MIC 0.016 mg/L for all of the dosing regimens but decreased to (I) 44%, (II) 91%, (III) 44%, (IV) 78% and (V) 91% for MIC 0.032 mg/L. |
AUC/MIC >5000 | PTA varied between 62 and 96% on day 14 for MIC 0.016 mg/L. | |||||
Jullien (2017) [50] | Micafungin | PK study, in silico | ICU, critically ill | 100, 150, 200, 250 and 300 mg QD | AUC/MIC >5000 | For MICs ≥ 0.015–0.016 mg/L, high PTA necessitated doses between 150 and 300 mg. |
Grau (2015) [51] | Micafungin | PK study, in silico | ICU, critically ill | 100, 150 and 200 mg QD | AUC/MIC >285 or >3000 | ≥90% PTA can be achieved for Candida spp. and C. parapsilosis MICs of 0.008–0.016 and 0.125–0.25 mg/L, respectively for all dosing regimens. |
Pérez Civantos (2019) [52] | Anidulafungin | PK study | ICU, critically ill, peritonitis | 200 mg on day 1, then 100 mg QD | - | Anidulafungin at conventional doses reaches peritoneal fluid concentrations that exceed the minimum inhibitory concentration of the usual Candida spp. |
García-de-Lorenzo (2016) [53] | Micafungin | PK study, in silico | ICU, critically ill, burns | 100, 150 and 200 mg QD | AUC/MIC >285 or >3000 | Micafungin at 100 mg/day achieved the PTA for MIC values of ≤0.008 mg/L and ≤0.064 mg/L for non-parapsilosis Candida spp. and C. parapsilosis isolates, respectively |
Sinnollareddy (2015) [54] | Fluconazole | PK study, in silico | ICU, critically ill | 400 mg QD | AUC/MIC >100 | PTA was 92% and 67% in plasma and subcutaneous-tissue interstitial fluid, respectively, for C. albican isolates with MIC of 1 mg/L. Higher doses is required in order to achieve the PK/PD target in the subcutaneous-tissue interstitial fluid. |
Bergner (2006) [55] | Fluconazole | PK study | ICU, critically ill, CVVHF | 800 mg QD | - | A dosage of 800 mg/day is required in patients receiving CVVHF to achieve Cmax of 16 to 32 mg/L. |
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Mohd Sazlly Lim, S.; Sinnollareddy, M.; Sime, F.B. Challenges in Antifungal Therapy in Diabetes Mellitus. J. Clin. Med. 2020, 9, 2878. https://doi.org/10.3390/jcm9092878
Mohd Sazlly Lim S, Sinnollareddy M, Sime FB. Challenges in Antifungal Therapy in Diabetes Mellitus. Journal of Clinical Medicine. 2020; 9(9):2878. https://doi.org/10.3390/jcm9092878
Chicago/Turabian StyleMohd Sazlly Lim, Sazlyna, Mahipal Sinnollareddy, and Fekade Bruck Sime. 2020. "Challenges in Antifungal Therapy in Diabetes Mellitus" Journal of Clinical Medicine 9, no. 9: 2878. https://doi.org/10.3390/jcm9092878