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• The methodological quality of guidelines for treatment on candidiasis is suboptimal. • Only the ESCMID guideline had a quality score >70% in all domains except applicability. • The CPGs noted an important role for fluconazole as an initial drug in prophylaxis. • Echinocandins are considered preferred in both empirical and targeted therapy. • The timing of initiating prophylaxis and empirical/pre-emptive therapy are unclear. Recommendations in clinical practice guidelines (CPG) may differ and cause confusion. Our objective was to appraise CPGs for antifungal treatment of invasive candidiasis (IC) in non-neutropenic critically ill adult patients. We systematically searched the literature for CPGs published between 2008 and 2018. We assessed the quality of each guideline using six domains of the AGREE II instrument. We extracted and compared recommendations for different treatment strategies and assessed content quality. Of 19 guidelines, the mean overall AGREE II score was 58%. The domain 'clarity of presentation' received the highest scores (88%) and 'applicability' the lowest (18%). CPGs provided detailed recommendations on antifungal prophylaxis (n = 10), with fluconazole recommended as initial prophylaxis in all seven CPGs citing a specific drug. Echinocandin was recommended as the initial drug in all 16 CPGs supporting empirical/pre-emptive treatment; and in 18 of 19 for targeted invasive candidiasis treatment. However, it remains unclear when to initiate prophylaxis, empirical or pre-emptive therapy or when to step down. The methodological quality of CPGs for antifungal treatment of IC in non-neutropenic critically ill patients is suboptimal. Some treatment recommendations were inconsistent across indications and require local guidance to help clinicians make better informed decisions. [ABSTRACT FROM AUTHOR]

Summary: Objectives: This study evaluated the efficacy of the pharmacokinetic/pharmacodynamic (PK/PD) index for increasing the success rate of linezolid treatment based on Monte Carlo simulation, and compared differences between the calculated PK/PD breakpoints and those defined by committee for critically ill patients with linezolid treatment. Methods: A Monte Carlo simulation involving 10000 subjects was used to analyze the pharmacokinetic parameters and microbiological data of linezolid for an effectiveness evaluation at the corresponding AUC24/MIC values (area under the serum concentration–time curve over 24h/minimum inhibitory concentration). Results: As the PK/PD index of linezolid increased from 80 to 120, the corresponding probability of target attainment (PTA) decreased from 99.91% to 18.97%, with a MIC of 2mg/l. Furthermore, the cumulative fraction of response (CFR) reached <90% for several pathogens at an AUC24/MIC of 100–120, revealing a relatively lower efficacy with recommended linezolid dosing. Conclusions: These findings reveal that the target AUC24/MIC value of 80–120 requires further classification for more accurate assessment of the linezolid dose regimen. At a MIC of ≥2mg/l, the clinical outcome varies greatly for different AUC24/MIC values when applying the same dose of linezolid. In such cases, we suggest optimized adjustment of the linezolid dosage regimen. [Copyright &y& Elsevier]