How to: interpret MICs of antifungal compounds according to the revised clinical breakpoints v. 10.0 European committee on antimicrobial susceptibility testing (EUCAST)

BACKGROUND: EUCAST has revised the definition of the susceptibility category "I" from "Intermediate" to "Susceptible, Increased exposure". This implies that "I" can be used where the drug-concentration at the site of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, "I" is no longer used as a buffer-zone to prevent technical fact

Invasive pulmonary aspergillosis 10 years post bone marrow transplantation: a case report

Abstract Introduction Invasive pulmonary aspergillosis is a leading cause of mortality and morbidity in bone marrow transplant recipients. Establishing the diagnosis remains a challenge for clinicians working in acute care setting. However, prompt diagnosis and treatment can lead to favourable outcomes Case presentation We report a case of invasive aspergillosis occurring in a 39-year-old Caucasian female 10 years after an allogeneic haematopoietic bone marrow transplant, and 5 years after stopping all immunosuppression. Possible risk factors include bronchiolitis obliterans and exposure to building dust (for example, handling her husband's dusty overalls). There are no similar case reports in the literature at this time. Conclusion High clinical suspicion, especially in the setting of failure to respond to broad-spectrum antibiotics, should alert clinicians to the possibility of invasive pulmonary aspergillosis, which, in this case, responded to antifungal therapy.</p

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis

Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU)

Prisutnost Candida sp. u svježem voćnom soku

Fruit juices are popular soft drinks with an important role in human nutrition. Fruit juices are often infested by yeast species that can survive different storage conditions. The aim of this study was to determine the degree of yeast contamination of freshly squeezed juices in three large supermarkets in Zagreb, Croatia. The analysis included 84 juice samples obtained from freshly squeezed orange, lemon, grapefruit, and apples. Their acidity varied between pH 2.1 and pH 4.9. Juice samples were plated directly on Sabouraud 4 % glucose Agar (Merck, 1.05438) and processed according to standardised methods (HRN ISO 7954:2002). Yeasts were isolated in all 84 samples and ranged between 0.005x103 and 23x103 colony forming units per mL (CFU mL-1). The most common yeasts identifi ed using the API 20C AUX yeast kit included Candida guillermondii, C. krusei, C. famata, C. spherica, C. colliculosa, C. albicans, Trichosporon mucoides, Kloeckera spp. and yeast-like fungus Cryptococcus neoformans. C. guillermondii prevailed in 55.95 % of all samples.Voćni su sokovi tekući ekstrakti voća dobiveni cijeđenjem zrelog voća te su vrlo važan čimbenik u svakodnevnoj prehrani ljudi. Najčešće zastupljeni mikroorganizmi u svježem voćnom soku su kvasci koji preživljavaju niske temperature skladištenja. Svrha ovog istraživanja bila je odrediti prisutnost i brojnost kvasaca u svježim voćnim sokovima uzorkovanim u supermarketima na području Republike Hrvatske, odnosno glavnom gradu Zagrebu. Ukupno su uzorkovana i pregledana 84 uzorka svježe iscijeđenih naranči, limuna, grejpfruta i jabuka. pH-vrijednost se kretala od 2.1 do 4.9. Uzorci su nacijepljivani direktno na Sabouraudov agar s 4 % glukoze (Merck, Njemačka) u skladu s propisanom normom HRN ISO 7954:2002. U sva 84 uzorka utvrđena je prisutnost kvasaca u broju od 0.005x103 do 23x103 CFU mL-1. Identifi kacija je provedena testom API 20 C AUX (bioMérieux, 20 210). Najčešće su izolirani sljedeći kvasci: Candida guillermondii, C. krusei, C. famata, C. spherica, C. colliculosa, C. albicans, Trichosporon mucoides, Kloeckera spp. i kvascu slična gljivica Cryptococcus neoformans. U svim uzorcima C. guillermondii bila je najčešće izolirani kvasac (55.95 %)

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment

Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU)

The one health problem of azole resistance in Aspergillus fumigatus: current insights and future research agenda

Azole resistance is a concern for the management of diseases caused by Aspergillus fumigatus in humans. Azole fungicide use in the environment has been identified as a possible cause for development of resistance, which increases the complexity and number of stakeholders involved in this emerging problem. A workshop was held in Amsterdam early 2019 in which stakeholders, including medical and agricultural researchers, representatives from the government, public health, fungicide producers and end-users, reviewed the current evidence supporting environmental selection for resistance and to discuss which research and measures are needed to retain the effectiveness of the azole class for environmental and medical applications. This paper provides an overview of the latest insights and understanding of azole resistance development in the clinical setting and the wider environment. A One Health problem approach was undertaken to list and prioritize which research will be needed to provide missing evidence and to enable preventive intervention

On the isoperimetric problem for the Laplacian with Robin and Wentzell boundary conditions

Doctor of PhilosophyWe consider the problem of minimising the eigenvalues of the Laplacian with Robin boundary conditions $\frac{\partial u}{\partial \nu} + \alpha u = 0$ and generalised Wentzell boundary conditions $\Delta u + \beta \frac{\partial u}{\partial \nu} + \gamma u = 0$ with respect to the domain $\Omega \subset \mathbb R^N$ on which the problem is defined. For the Robin problem, when $\alpha > 0$ we extend the Faber-Krahn inequality of Daners [Math. Ann. 335 (2006), 767--785], which states that the ball minimises the first eigenvalue, to prove that the minimiser is unique amongst domains of class $C^2$. The method of proof uses a functional of the level sets to estimate the first eigenvalue from below, together with a rearrangement of the ball's eigenfunction onto the domain $\Omega$ and the usual isoperimetric inequality. We then prove that the second eigenvalue attains its minimum only on the disjoint union of two equal balls, and set the proof up so it works for the Robin $p$-Laplacian. For the higher eigenvalues, we show that it is in general impossible for a minimiser to exist independently of $\alpha > 0$. When $\alpha < 0$, we prove that every eigenvalue behaves like $-\alpha^2$ as $\alpha \to -\infty$, provided only that $\Omega$ is bounded with $C^1$ boundary. This generalises a result of Lou and Zhu [Pacific J. Math. 214 (2004), 323--334] for the first eigenvalue. For the Wentzell problem, we (re-)prove general operator properties, including for the less-studied case $\beta 0$ establish a type of equivalence property between the Wentzell and Robin minimisers for all eigenvalues. This yields a minimiser of the second Wentzell eigenvalue. We also prove a Cheeger-type inequality for the first eigenvalue in this case

Novel, synergistic antifungal combinations that target translation fidelity

There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8 fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone