Fig. 1

PK/PD alterations during intra-abdominal candidiasis. PK: pharmacokinetic; PD: pharmacodynamic; Vd: volume of distribution; CL: clearance; ICU: intensive care unit; ATF: antifungal; TDM: therapeutic drug monitoring. Figure 1 is split twice: vertically, where left side represents the per-operative phase and right side the post-operative period, and horizontally, where the upper case described the sources of pharmacokinetic alterations, and the lower case, the sources of pharmacodynamic alterations. In the operating room, sources of PK variability are driven by the sepsis/shock, the resuscitation (fluid resuscitation and catecholamines), the anaesthesia, and inflammation caused by the surgical trauma. Together they contribute to a high risk of suboptimal antifungal concentrations by increase in volume of distribution and clearance in both the plasma and the peritoneum. From a pharmacodynamic perspective, before the source control is performed by the surgeon, high inoculum potentially protect by Candida biofilm and low tissue penetration could promote antifungal resistance. Thus, increased PK/PD target and high dose of antifungal are required. During the post-operative period, the source control is supposed to be achieved and thereby the sepsis/shock should be less important. However, organ failures caused by the abdominal sepsis could occur, and provide the need for extracorporeal support such as renal replacement therapy or ECMO. The presence of surgical drains could increase drug clearance. Therefore, antifungal concentrations are highly unpredictable, from low to high concentration. From a pharmacodynamic perspective, source control has been performed but an immunoparalysis could be present and candidemia and/or abscess/tertiary peritonitis could occur. Therefore, therapeutic drug monitoring of antifungal should be considered