Population Pharmacokinetic Model and Optimal Sampling Strategies for Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis

Boonstra, Jasper; Elst, Kim Cm van der; Zijlstra, Jan G.; Werf, Tjip S van der; Alffenaar, Jan-Willem; Touw, Daan

doi:10.1128/aac.01113-22

Cited by 1 publication

(1 citation statement)

References 38 publications

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“…Echinocandins are highly bound to albumin (> 95%) [ 37 , 46 , 47 ]; thus, considering that only the unbound fraction is active and passively diffuses to the extravascular space, penetration into the peritoneal fluid is highly compromised for these antifungals. Recently, in a population PK model in critically ill patients, several factors with potential impact on micafungin exposure has been proposed, such as increased bodyweight, decreased plasma proteins, higher disease severity score, renal failure and renal replacement therapy, and liver impairment [ 48 ].…”

Section: Pk/pd Analysis Of Antifungal Options For the Treatment Of Iacmentioning

confidence: 99%

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Maseda,

Martín-Loeches,

Zaragoza

et al. 2023

Crit Care

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Background Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians. Main body This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed. Conclusion There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.

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