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ABSTRACT: Diagnosis of invasive aspergillosis (IA) requires increasingly rapid molecular methods that enable sensitive detection and discrimination between species. We designed and evaluated a real-time PCR-based method that combined melting temperature (T(m)) calling analysis of a specific probe with high-resolution melting analysis of the full amplicon. The test correctly identified 78 isolates of Aspergillus section Fumigati and non-Fumigati sections of Aspergillus with a limit of detection of 10(2) conidia/ml (10(2) fg/ml). No cross-reactivity with other fungi was found. The assay was further validated on lower respiratory tract specimens containing Aspergillus or not. It successfully identified Aspergillus to section level in 56 of 59 specimens. With culture as the gold standard, our assay shows 100% sensitivity and specificity and constitutes an efficient alternative for identification of Aspergillus in lower respiratory tract samples.
Journal of clinical microbiology 07/2012; 50(10):3238-43. · 4.16 Impact Factor
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ABSTRACT: Suspected or proven invasive candidiasis is an important indication for antifungal drugs and a leading cause of death. Prompt initiation of effective therapy has a marked effect on survival, but the indiscriminate application of different risk-factor-based prediction models is massively increasing the number of patients treated unnecessarily. Fluconazole resistance levels are <5% in most European centres and the use of low doses is still common. Candins are fungicidal, have efficacy against device-related infections, have few interactions and are well tolerated. Accordingly, the use of newer, more expensive drugs must be carefully balanced in each case. Campaigns directed towards stewardship in antifungal drug use must take into consideration the choice of the drug, the dose and route of administration, and the length of therapy. Early microbiological information and medical education may contribute to better use of these important drugs. We review the characteristics of the new antifungals used for the treatment of candidaemia.
International journal of antimicrobial agents 12/2010; 36 Suppl 2:S63-9. · 3.03 Impact Factor
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ABSTRACT: Opportunistic invasive fungal infections (IFIs) have changed. Moreover, a significantly greater therapeutic armamentarium is now available, with liposomal amphotericin B (L-AmB) administered in new ways, for example in higher doses, in combination with other compounds or inhaled. The objective of this study was to review these three aspects. The AmBiLoad study was designed to clarify whether higher doses of L-AmB could be more efficacious than the licensed dose of 3-5 mg/kg. It was a multicentric study where patients were randomised to receive a 14-day course of 3 mg/kg/day or 10 mg/kg/day L-AmB. A total of 339 patients were enrolled during the study period (April 2003 to October 2004). Discontinuation of treatment, mainly due to adverse events, was frequent (13% in the standard dose group vs. 24% in the high dose group), and only 66% and 50%, respectively, completed 14 days of randomised treatment. There was no statistically significant difference with regard to favourable overall responses between the treatment groups (50% in the standard dose group vs. 46% in the high dose group; P = 0.65). In addition, there was no significant difference according to type of IFI (invasive aspergillosis, 50% vs. 46% in the standard and high dose groups, respectively). The obvious conclusion of this study was that administration of 10 mg/kg/day L-AmB to patients with IFI does not improve efficacy but increases toxicity and price. In vitro and experimental data suggest that the combination of AmB with other antifungal agents may be more effective than monotherapy; however, data regarding the clinical efficacy of L-AmB in combination with other agents are scarce. The use of inhaled L-AmB has shown promising results for use as antifungal prophylaxis in high-risk patients.
International Journal of Antimicrobial Agents 11/2008; 32 Suppl 2:S125-31. · 4.13 Impact Factor
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ABSTRACT: The fear of candidemia caused by a fluconazole-resistant species of Candida is causing many intensive care units (ICUs) to switch empiric therapy from this drug to broad-spectrum antifungal agents. We studied the epidemiology and antifungal susceptibility of Candida isolates involved in cases of candidemia among adult and pediatric patients in ICUs from 1984 to 2006. We documented 307 episodes of candidemia in 307 patients, of which only eight episodes (2.6%) were caused by a fluconazole-resistant isolate. At least three of the eight patients from whom fluconazole-resistant strains were recovered had recently received fluconazole. Overall, only 1.6% of the episodes of candidemia caused by fluconazole-resistant strains (five patients) occurred in individuals with no evidence of previous fluconazole administration. In conclusion, the use of broad-spectrum antifungal agents is not justified in ICUs with a low proportion of candidemia episodes caused by fluconazole-resistant strains of Candida.
Medical mycology: official publication of the International Society for Human and Animal Mycology 11/2008; 47(5):515-20. · 2.13 Impact Factor
