In vitro interactions between farnesol and fluconazole, amphotericin B or micafungin against Candida albicans biofilms.

Objectives: Biofilm formation by Candida albicans poses an important therapeutic challenge in human diseases. Typically, conventional antifungal agents encounter difficulty in treating and fully eradicating biofilm-related infections. Novel therapeutic approaches are needed to treat recalcitrant Candida biofilms.

Host genetics and opportunistic fungal infections.

Current knowledge on the human pathophysiology of fungal infections highlights the crucial role of genetic pitfalls in specific immunity pathways that determine, together with other risk factors, the predisposition to and clinical outcome of fungal disease. In several studies, associations between gene polymorphisms and genetic errors have been implicated in an immunodeficiency phenotype and an increased incidence of opportunistic fungal diseases. The major challenge is to fully understand the complex interactions between genetic variations and multiple factors, and their relative contributions to the final clinical fungal disease phenotype.

Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-β-lactamase-producing Escherichia coli.

Urinary tract infections (UTIs) due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy.

Pathogenesis and host defence against Mucorales: the role of cytokines and interaction with antifungal drugs.

Innate immune response, including macrophages, neutrophils and dendritic cells and their respective receptors, plays an important role in host defences against Mucorales with differential activity against specific fungal species, while adaptive immunity is not the first line of defence. A number of endogenous and exogenous factors, such as cytokines and growth factors as well as certain antifungal agents have been found that they influence innate immune response to these organisms. Used alone or especially in combination have been shown to exert antifungal effects against Mucorales species.

In vitro combination of isavuconazole with micafungin or amphotericin B deoxycholate against medically important molds.

Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Our in vitro combination studies showed that isavuconazole and micafungin are synergistically active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation.

Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum.

Exserohilum rostratum caused a multistate fungal meningitis outbreak following iatrogenic inoculation of contaminated methylprednisolone in the United States. To gain insight into the immunopathogenesis of this infection, we studied the innate host responses of human neutrophils against E. rostratum conidia and hyphae with or without methylprednisolone.

Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system.

Micafungin in premature and non-premature infants: a systematic review of 9 clinical trials.

Background: Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants.

Methods: Safety and efficacy outcomes of micafungin were compared between prematurely and non-prematurely born infants <2 years of age. Data were obtained from all completed phase I-III clinical trials with micafungin that had enrolled infants (<2 years of age) that were listed in the Astellas Clinical Study Database.

Caspofungin at catheter lock concentrations eradicates mature biofilms of Candida lusitaniae and Candida guilliermondii.

The antibiofilm activities of caspofungin, anidulafungin, micafungin, and liposomal amphotericin B were studied against Candida lusitaniae, Candida guilliermondii, and a Candida albicans control strain. While anidulafungin and micafungin (0.007 to 2,048 mg/liter) showed reduced activity against biofilms of both test species, caspofungin displayed concentration-dependent antibiofilm activity, reaching complete and persistent eradication at concentrations achievable during lock therapy (512 to 2,048 mg/liter, P < 0.

Fungal DNA detected in blood samples of patients who received contaminated methylprednisolone injections reveals increased complexity of causative agents.

Using Exserohilum rostratum-specific and panfungal real-time PCR, we studied 24 blood samples and 2 synovial fluid specimens from 20 patients with persistent or worsening pain following injections of contaminated methylprednisolone. Seven blood specimens from 6 patients were significantly positive for fungal DNA by panfungal PCR, with multiple fungal species identified.

Immediate provisionalization and nonfunctional loading of a single implant in the maxillary esthetic zone: a clinical presentation and parameters for consideration.

Restoration of single tooth loss with implant supported prosthesis is now considered a highly predictable treatment. However, the maxillary anterior region still presents a challenge for both the prosthodontist and the periodontist because of the inherent difficulties encountered in the provisionalization and harmonic incorporation of the definitive prosthesis into patient's dentogingival complex. This paper presents a clinical case of a single implant placed immediately after the extraction of a maxillary central incisor, followed by immediate provisionalization and nonfunctional loading.

Aspergillus osteomyelitis: epidemiology, clinical manifestations, management, and outcome.

Background: The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood.

Methods: Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome.

Results: Among 180 evaluable patients, 127 (71%) were males.

Why is mucormycosis more difficult to cure than more common mycoses?

Although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. Despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. Successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents.