Disseminated Invasive Aspergillosis with Cerebral Involvement Successfully Treated with Caspofungin and Voriconazole

We describe a case of cerebral aspergillosis which was successfully treated with a combination of caspofungin and voriconazole. The patient remains in remission 18 months after stopping antifungal treatment. We discuss primary and salvage therapy of invasive aspergillosis with focus on cerebral involvement. Since historical data showed a fatal outcome in most cases, amphotericin B does not cross the blood brain barrier while voriconazole does, we chose a combination of voriconazole plus caspofungin as primary therap

Nitric Oxide and Infection: Another View

Nitric oxide (NO) has been nicknamed "murderer” and "mediator” because it has toxic and signaling properties. We review these two aspects of NO synthesis from the perspective of the clinical infectious disease specialist by considering the potential of NO as an endothelium-derived relaxing factor (EDRF) in inflammation and sepsis and its potential as an antimicrobial system. We deviate from observations in recent authoritative reviews and point to important speciesdifferences that make it unlikely that NO serves as an EDRF mediating inflammatory vasodilatation in humans or that NO synthesized by human phagocytes has an antimicrobial function.We propose that in humans, NOsynthesis is moreconfined and compartmentalized than in certain other animal species, and therefore, unwelcome toxicity, vasodilatation, or disturbance of paracrine signaling mechanisms (i.e., modulation of phagocytic cell functions) are avoided during inflammatio

Nitrite Generation in Interleukin-4—Treated Human Macrophage Cultures Does Not Involve the Nitric Oxide Synthase Pathway

The search continues for high-output nitric oxide biosynthesis in human macrophages analogous to murine phagocytes. Recently, generation of nitrite in culture supernatants of human macrophages exposed to interferon-γ and interleukin-4 (IFN-γ/IL-4) was reported. The present study reproduces these findings and shows that L-arginine is not consumed and L-citrulline is not produced during this process. Furthermore, the biosynthesis of the obligatory cofactor tetrahydrobiopterin is not coinduced. These biochemical data provide support against a nitric oxide synthase contribution to nitrite accumulation. Nitrite was generated from nitrate salts even in cell-free media. Nitric oxide synthase activity but not nitrate reduction depended on molecular oxygen. Nitrite accumulation in experiments with IFN-γ/IL-4 in human monocytes appears to be an in vitro artifact produced by nitrate-reducing activities contained in cytokine preparation

Life-threatening envenoming by the Saharan horned viper (Cerastes cerastes) causing micro-angiopathic haemolysis, coagulopathy and acute renal failure: clinical cases and review

Background: The desert horned vipers (Cerastes cerastes and C. gasperettii) are the most familiar snakes of the great deserts of North Africa and the Middle East, including the plains of Iraq. They are responsible for many human snake bites. In Western countries, they are popular among exotic-snake keepers. Aim: To investigate mechanisms of life-threatening envenoming and treatment. Design: Clinical investigation. Methods: Clinical and laboratory studies with measurement of serum venom antigen concentrations by enzyme immunoassay. Results: Two men bitten while handling captive Saharan horned vipers (Cerastes cerastes) in Europe developed extensive local swelling and life-threatening systemic envenoming, characterized by coagulopathy, increased fibrinolysis, thrombocytopenia, micro-angiopathic haemolytic anaemia and acute renal failure. The clinical picture is explicable by the presence in C. cerastes venom of several thrombin-like, Factor-X-activating, platelet-aggregating, haemorrhagic and nephrotoxic components. In one case, prophylactic use of subcutaneous epinephrine may have contributed to intracranial haemorrhage. The roles in treatment of heparin (rejected) and specific antivenom (recommended) are discussed. Discussion: Cerastes cerastes is capable of life-threatening envenoming in humans. Optimal treatment of envenoming is by early administration of specific antivenom, and avoidance of ineffective and potentially-dangerous ancillary method

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

Abstract : A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalizatio

Rapid Detection of Pathogenic Fungi from Clinical Specimens Using LightCycler Real-Time Fluorescence PCR

In the study presented here a LightCycler real-time PCR system was used for the diagnosis of fungal infections from clinical tissue samples. Nine specimens were investigated from six patients with suspected or proven invasive fungal infections. Seven of nine samples were positive in a broad-range fungal PCR assay. In four samples, Aspergillus fumigatus was detected both by a species-specific hybridization assay as well as by sequencing of amplification products. In addition, the broad-range fungal PCR assay and PCR sequencing detected and identified, respectively, the following organisms in the specimens noted: Candida albicans in a culture-negative liver biopsy, Histoplasma capsulatum in a bone marrow sample, and Conidiobolus coronatus in a facial soft tissue specimen. Real-time PCR is a promising tool for the diagnosis of invasive fungal infections in human tissue samples and offers some advantages over culture methods, such as rapid analysis and increased sensitivit