Mediastinal Mucormycosis: Case report, review of literature and treatment with continuous liposomal amphotericin B irrigation.

Mediastinal mucormycosis is an uncommon but lethal infection associated with an 83% mortality. We describe a case of fatal Rhizopus microsporus mediastinitis despite three exploratory mediastinal surgeries and complementary systemic and mediastinal irrigation with liposomal amphotericin B. We further review the literature on surgical and antifungal management of mediastinal mucormycosis.

Stability of isoniazid injection in i.v. solutions.

Purpose: Results of an assessment of the chemical stability of isoniazid injection in 0.9% sodium chloride injection and 5% dextrose injection are reported.

Methods: Triplicate solutions of isoniazid (0.

Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia.

Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America and the American Thoracic Society recommend a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence, and fewer antibiotic treatment days, counterbalanced with a higher relapse rate for patients whose pathogen is a nonfermenter.

Successful Treatment of Invasive Conidiobolus Infection During Therapy for Acute Lymphoblastic Leukemia.

Invasive fungal infections are a serious cause of morbidity and mortality in patients with hematologic malignancies. Conidiobolus species are molds within the order Entomophthorales and may disseminate to become rapidly fatal in immunocompromised individuals. This species of fungal infections are often multidrug resistant (MDR) and present unique therapeutic challenges.

Combination therapy for the treatment of pulmonary mold infections.

Pulmonary mold infections are caused by ubiquitous organisms found in soil, water, and decaying vegetation, including Aspergillus spp., the Mucormycetes, hyaline molds, and dematiaceous (black) molds. Areas covered: These infections are often a challenge to diagnose and even more difficult to treat.

Diagnosis, classification, and therapeutic interventions for sinopulmonary Aspergillosis.

Sinopulmonary aspergillosis represents a diverse collection of allergic, invasive, and chronic sinus and respiratory conditions. These diseases can affect patients with and without immune impairment and in some cases may be life-threatening. Areas covered: We review the diagnosis, classification, and therapeutic options available to treat sinopulmonary aspergillosis and look ahead to emerging diagnostic and therapeutic options that may soon play an important role in clinical practice.

Bone and joint infections caused by mucormycetes: A challenging osteoarticular mycosis of the twenty-first century.

Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy.

Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.

Therapeutic Drug Monitoring and Genotypic Screening in the Clinical Use of Voriconazole.

Voriconazole is an antifungal triazole that is the first line agent for treatment of invasive aspergillosis. It is metabolized by CYP2C19, CYP2C9, and CYP3A4 and demonstrates wide interpatient variability in serum concentrations. Polymorphisms in CYP2C19 contribute to variability in voriconazole pharmacokinetics.

Osteoarticular Infections Caused by Non-Aspergillus Filamentous Fungi in Adult and Pediatric Patients: A Systematic Review.

Osteoarticular mycoses due to non-Aspergillus moulds are uncommon and challenging infections. A systematic literature review of non-Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013. Among 145 patients were 111 adults (median age 48.

Effects of fluconazole on the metabolomic profile of Candida albicans.

Background: Little is known about the effects of fluconazole on the metabolism of Candida albicans. We performed LC/MS-based metabolomic profiling of the response of C. albicans cells to increasing doses of fluconazole.

Differential effects of antifungal agents on expression of genes related to formation of Candida albicans biofilms.

The purpose of this study was to analyse specific molecular mechanisms involved in the intrinsic resistance of C. albicans biofilms to antifungals. We investigated the transcriptional profile of three genes (BGL2, SUN41, ECE1) involved in Candida cell wall formation in response to voriconazole or anidulafungin after the production of intermediate and mature biofilms.

Intermittent Dosing of Micafungin Is Effective for Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits.

Background: The current standard of treatment of invasive candidiasis with echinocandins requires once-daily therapy. To improve quality of life, reduce costs, and improve outcome, we studied the pharmacokinetics (PK), efficacy, and safety of alternate dosing regimens of micafungin (MFG) for the treatment of experimental subacute disseminated candidiasis.

Methods: MFG was administered for 12 days starting 24 hours after intravenous inoculation of 1 × 10(3) Candida albicans blastoconidia.

Role of Echinocandins in Fungal Biofilm-Related Disease: Vascular Catheter-Related Infections, Immunomodulation, and Mucosal Surfaces.

Biofilm-related infections have become an increasingly important clinical problem. Many of these infections occur in patients with multiple comorbidities or with impaired immunity. Echinocandins (caspofungin, micafungin, and anidulafungin) exert their fungicidal activity by inhibition of the synthesis of the (1→3)-β-d-glucan.

The Role of Echinocandins in Candida Biofilm-Related Vascular Catheter Infections: In Vitro and In Vivo Model Systems.

Candida biofilm-associated infections of central venous catheters are a challenging therapeutic problem. Recent in vitro and in vivo studies of the structure, formation, pathogenesis, and treatment establish a rationale for new approaches to management of these tenacious infections.

Echinocandins: The Expanding Antifungal Armamentarium.

The echinocandins are large lipopeptide molecules that, since their discovery approximately 41 years ago, have emerged as important additions to the expanding armamentarium against invasive fungal diseases. Echinocandins exert in vitro and in vivo fungicidal action against most Candida species and fungistatic action against Aspergillus species. However, the population of patients at risk for developing invasive fungal infections continues to increase.

Development of New Strategies for Echinocandins: Progress in Translational Research.

Echinocandins are N-acyl-substituted cyclic hexapeptides with potent in vitro and in vivo activity against Candida species that are used for primary treatment and prevention of candidemia and invasive candidiasis. Recent progress in the translational research of echinocandins has led to new approaches for treatment of central venous catheter Candida biofilms. Other studies have laid the experimental and clinical foundation for use of extended dosing intervals for administration of echinocandins in treatment and prevention of candidemia and invasive candidiasis.

(1→3)-β-d-Glucan in Cerebrospinal Fluid as a Biomarker for Candida and Aspergillus Infections of the Central Nervous System in Pediatric Patients.

Background: Fungal infections of the central nervous system (FICNS) are important causes of morbidity and mortality among immunocompromised pediatric patients. Standard diagnostic modalities lack the sensitivity for detecting and therapeutically monitoring these life-threatening diseases. Current molecular methods remain investigational.

18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan for monitoring the therapeutic response in experimental Staphylococcus aureus foreign-body osteomyelitis.

Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography ((18)F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether (18)F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop (18)F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis.

How Biofilms Evade Host Defenses.

The steps involved during the biofilm growth cycle include attachment to a substrate followed by more permanent adherence of the microorganisms, microcolony arrangement, and cell detachment required for the dissemination of single or clustered cells to other organ systems. Various methods have been developed for biofilm detection and quantitation. Biofilm-producing microorganisms can be detected in tissue culture plates, using silicone tubes and staining methods, and by visual assessment using scanning electron microscopy or confocal scanning laser microscopy.

Effects of host response and antifungal therapy on serum and BAL levels of galactomannan and (1→3)-β-D-glucan in experimental invasive pulmonary aspergillosis.

Galactomannan and (1→3)-β-D-glucan are useful biomarkers of invasive pulmonary aspergillosis (IPA). However, the effects of immunosuppression on levels of galactomannan or (1→3)-β-D-glucan in IPA are not well understood or quantified. We therefore studied the simultaneous levels of galactomannan and (1→3)-β-D-glucan in two rabbit models of experimental IPA: (1) AraC-induced neutropenia in untreated (UC-AraC) and liposomal amphotericin B-treated (LAMB-AraC) rabbits; and (2) nonneutropenic cyclosporine-methylprednisolone immunosuppression in untreated (UC-CsA+M) and LAMB-treated (LAMB-CsA+M) rabbits.

Antipseudomonal agents exhibit differential pharmacodynamic interactions with human polymorphonuclear leukocytes against established biofilms of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is the most common pathogen infecting the lower respiratory tract of cystic fibrosis (CF) patients, where it forms tracheobronchial biofilms. Pseudomonas biofilms are refractory to antibacterials and to phagocytic cells with innate immunity, leading to refractory infection. Little is known about the interaction between antipseudomonal agents and phagocytic cells in eradication of P.