Personalized antifungal susceptibility testing

In recent years, the remarkable increase in the number of infections caused by fungal pathogens, especially in immunocompromised people, has stimulated interest in medical mycology in general and in antifungal susceptibility testing in particular. 1,2 In-vitro procedures for determining the activity of drugs against mould and yeast isolates involve clinicians in the choice and monitoring of anti-fungal chemotherapy. A number of factors, however, may influence the evaluation of the sensitivity of fungi to anti-fungal drugs, even in the most standardized procedures such as the determination of the MIC and minimal fungici-dal concentration (MFC) in optically read microautomated systems. The nature and the form of the involved fungus, the preparation of the inoculum, the solubility and stability of the antifungal drugs tested, the pH and composition of the test medium, the duration and the temperature of incubation and the criteria for determining endpoints are variables that significantly affect the reproducibility of the test. 2–7 The NCCLS has proposed reference parameters for antifungal susceptibility testing, which were recently amended. 8,9 The original procedure, which was based on macrodilutions of the drug in the synthetic medium RPMI 1640 buffered at pH 7.0 in morpholinopropansulphonic acid (MOPS) 0.165 M, is very laborious. Comparative studies have been carried out to modify the NCCLS's procedure to a miniaturized microtitre plate system that may be effectively automated. 10–16 Despite the equivalency of the achievable results, the micromethod cannot be readily adopted in many laboratories and thus, the commercially available systems have been based on different methods such as the Etest or ATB fungus tests. Major advances in intralaboratory and interlaboratory reproducibility have been achieved, particularly through the NCCLS's guidelines, and commercial kits have rendered antifungal susceptibility testing feasible in every mycological laboratory. Current methods, however, do not fulfil completely the crucial need for correlation between the results of in-vitro susceptibility testing and in-vivo response. If the goal of obtaining reproducible tests has been only partially achieved, the one of providing reliable results to clinicians as a guide for antifungal therapy still poses problems. The next critical step to be taken should be to ensure the clinical relevance of any proposed method for antifungal susceptibility testing by determining the relationship between the MIC and MFC of antifungal agents and clinical response. In addition to the variables associated with the fungal organisms per se and the antifungal agents, other factors may affect how reliably the in-vitro tests predict …