Monitoring
Blood cultures should be obtained daily to confirm that negative status has been achieved. If blood cultures remain positive, rather than assuming treatment change is indicated or that resistance has developed, attention should be paid to ensuring that all intravascular catheters have been removed, as well as searching for metastatic foci, such as abscesses. Persistently positive cultures mandates excluding endovascular infections, including Candida endocarditis.
Antifungal susceptibility testing, primarily to azoles, is recommended for all bloodstream isolates.[32] This is particularly relevant for Candida glabrata, Candida parapsilosis and Candida auris , which have increasing rates of resistance to azoles and variable rates of resistance to echinocandins.[4][72][97]
C auris is highly fluconazole-resistant (86% to 100% of isolates) due to ERG11 mutations. Resistance to amphotericin-B is also commonly reported in 43% of isolates in the US. Echinocandins are the treatment of choice; however, resistance can develop and has been reported in 2% to 5% of isolates.[98]
C glabrata is frequently resistant to azoles, this resistance is mediated by efflux pumps (overexpression of CDR1/CDR2). Although echinocandins are the recommended first-line of therapy, resistance to this class of antifungals can develop in C glabrata.
Candida krusei is resistant to fluconazole due to ERG11 mutations. Both C krusei and Candida lusitaniae can show resistance to amphotericin-B.
C parapsilosis can have elevated minimum inhibitory concentrations to echinocandins due to a naturally occurring mutation in FKS1p.[20]
The Clinical and Laboratory Standards Institute (CLSI) interpretive criteria for fluconazole against Candida species include susceptible (S), susceptible dose-dependent (SDD) which means that a higher than standard dose needs to be used for treatment, and resistant (R). SDD is not applicable for other antifungals. Overall it is important for susceptibility testing to correlate with patient clinical outcomes, which is not always demonstrated in the different studies that have attempted to look at this correlation.[99] Observing response to therapy as demonstrated by repeat cultures and clinical and radiographic evaluation is important to consider in addition to susceptibility testing in clinical practice. Over the recent years growing evidence of antifungal tolerance and heteroresistance in Candida has emerged and may have an impact on response to therapy. Currently, these phenomena are not readily measurable in the laboratory.[100][101]
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