amphotericin-b--deoxycholate-drug-combination and Fungemia

Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib.. A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired.. This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cellulitis; Coinfection; Cryptococcosis; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Male; Mycobacterium haemophilum; Mycobacterium Infections; Nitriles; Opportunistic Infections; Primary Myelofibrosis; Pyrazoles; Pyrimidines

Emergent fungal infections are uncommon conditions which frequently lead to death. To our knowledge, only a few cases of invasive infection by Cystobasidium minutum (previously known as Rhodotorula minuta) have been reported. Moreover, several factors are responsible for deep site infections, such as catheter-related fungemia. This report describes the first case report of Cystobasidium minutum causing fungemia in Brazil. The pathogens fungemia was demonstrated by catheter and blood culture-proven, and both yeasts were identified by sequences of D1/D2 rDNA region. After the end of antifungal therapy and catheter removal, a second blood culture was found to be negative and the clinical signs and symptoms of the patient improved.

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Brazil; Catheter-Related Infections; Deoxycholic Acid; DNA, Fungal; DNA, Ribosomal; Drug Combinations; Female; Fungemia; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia

Fungal urinary tract infections (funguria) are rare in community medicine, but common in hospitals where 10 to 30% of urine cultures isolate Candida species. Clinical features vary from asymptomatic urinary tract colonization (the most common situation) to cystitis, pyelonephritis, or even severe sepsis with fungemia. The pathologic nature of funguria is closely related to host factors, and management depends mainly on the patient's underlying health status. Microbiological diagnosis of funguria is usually based on a fungal concentration of more than 10(3)/mm(3) in urine. No cutoff point has been defined for leukocyte concentration in urine. Candida albicans is the most commonly isolated species, but previous antifungal treatment and previous hospitalization affect both species and susceptibility to antifungal agents. Treatment is recommended only when funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia. The antifungal agents used for funguria are mainly fluconazole and amphotericin B deoxycholate, because other drugs have extremely low concentrations in urine. Primary and secondary preventions are essential. The reduction of risk factors requires removing urinary catheters, limiting antibiotic treatment, and optimizing diabetes mellitus treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Cross Infection; Cystitis; Deoxycholic Acid; Drug Combinations; Female; Fluconazole; Fungemia; Fungi; Health Status; Hospital Mortality; Humans; Male; Mycoses; Primary Prevention; Pyelonephritis; Risk Factors; Urinary Catheterization; Urinary Tract Infections; Urine

Rhodotorula spp. are emergent opportunistic pathogens, particularly in immunocompromised individuals. They have been associated with endocarditis, peritonitis, meningitis endophthalmitis and catheter-associated fungemia. The aim of this study was to review all cases of central venous catheter-related fungemia due to Rhodotorula spp. reported in the literature in order to determine the best management of this uncommon infection. All patients but one in the 88 cases examined had some form of underlying disease including sixty-nine (78.4%) who had cancer. Rhodotorula mucilaginosa was the species most frequently recovered (75%), followed by Rhodotorula glutinis (6%). Amphotericin B deoxycholate was the most common antifungal agent used as treatment and the overall mortality was 9.1% in this review. This fungemia is a rare disease which can be found in immunocompromised and in the intensive care patients. The use of specific antifungal therapy may be associated with an increase in the survival. It should be noted that Rhodotorula spp. is resistant to fluconazole.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Catheters, Indwelling; Deoxycholic Acid; Drug Combinations; Female; Fungemia; Humans; Male; Rhodotorula

Persistent or recurrent unexplained fever in neutropenic patients receiving antibiotics can be caused by invasive fungal infections, which are often difficult to diagnose. Early trials of empirical antifungal therapy with amphotericin B deoxycholate (AmB) documented reductions in the frequency of and the morbidity and mortality associated with invasive fungal infections. Because of AmB's infusional and renal toxicities, subsequent trials used newer, less toxic agents, such as the lipid formulations of AmB, the extended-spectrum azoles, and, more recently, the echinocandins. To date, alternatives to AmB have shown less toxicity, but improved efficacy has been less clear. Overall, empirical antifungal therapy can help prevent the morbidity associated with many fungal infections, eliminate concerns about diagnostic pitfalls, and prevent breakthrough undetected infections. However, its potential shortcomings are overtreatment, toxicity, and increased treatment-related costs when treatment is given to persons not needing it. Newer diagnostic tools are needed to target those most in need of antifungal therapy.

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Deoxycholic Acid; Drug Combinations; Fever; Fluconazole; Fungemia; Humans; Immunocompromised Host; Neutropenia; Opportunistic Infections

Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fluconazole; Flucytosine; Fungemia; Histoplasmosis; Humans; Immunocompromised Host; Mycoses; Zygomycosis

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Fluconazole; Fungemia; Humans; Male; Middle Aged; Schizophyllum

Although guidelines for the treatment of Malassezia furfur fungemia are not yet defined, clinical data suggest that amphotericin B (AmB) is effective for treating systemic infections. In the absence of clinical breakpoints for Malassezia yeasts, epidemiological cut-off values (ECVs) are useful to discriminate between isolates with and without drug resistance. This study aimed to compare the distribution of minimal inhibitory concentration (MIC) and the ECVs for AmB of both deoxycholate (d-AmB) and liposomal (l-AmB) formulations of M. furfur isolates. The 84 M. furfur strains analyzed, which included 56 from blood, sterile sites and catheters, and 28 from skin, were isolated from patients with bloodstream infections. MICs were determined by the modified broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). The l-AmB MIC and the ECVs were two-fold lower than those of d-AmB and a lower l-AmB mean MIC value was found for blood isolates than from skin. The ECVs for l-AmB and d-AmB were 8 mg/l and 32 mg/l, respectively. Three strains (3.6%) showed l-AmB MIC higher than ECV (MIC > 8 mg/l) of which two were isolated from the catheter tip of patients treated with micafugin, l-Amb and fluconazole, and one from skin. The results showed that the l-AmB might be employed for assessing the in vitro antifungal susceptibility of M. furfur by a modified CLSI protocol and that ECVs might be useful for detecting the emergence of resistance.

Topics: Amphotericin B; Antifungal Agents; Blood; Catheters; Deoxycholic Acid; Drug Combinations; Fungemia; Humans; Malassezia; Microbial Sensitivity Tests; Skin

Topics: Amphotericin B; Antifungal Agents; Brain; Brain Abscess; Candidiasis; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Echoencephalography; Female; Flucytosine; Follow-Up Studies; Fungemia; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Magnetic Resonance Imaging

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Fungemia; Hepatitis B, Chronic; Hepatomegaly; Herpes Zoster; Histoplasmosis; Humans; Male; Splenomegaly; Toxoplasmosis; Ultrasonography; Uremia

The incidence and severity of fungal infections in children with malignant diseases treated with intensive chemotherapy or allogeneic hematopoietic cell transplantation on the hematology-oncology department Children's Hospital Salata Medical School University of Zagreb is analyzed. The efficacy of antifungal therapy is presented.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Croatia; Deoxycholic Acid; Drug Combinations; Fungemia; Hematopoietic Stem Cell Transplantation; Hospitals, Pediatric; Hospitals, Teaching; Humans; Immunocompromised Host; Infant; Liposomes; Lung Diseases, Fungal; Mycoses; Neoplasms; Postoperative Complications; Retrospective Studies; Treatment Outcome

The purpose of this study was to identify the pharmacokinetics of Amphotericin B Colloidal Dispersion in patients undergoing bone marrow transplantations with systemic fungal infections and to assess the influence of ABCD on renal function. Seventy-five patients (42 females, 33 males) with a median age of 34.5 years and median weight of 70.0 kg were enrolled in the study. The plasma concentration data was available in 51/75 patients and was best described by a two-compartment model; both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Serum creatinine values over the duration of therapy were available in 59/75 patients. Overall, there was no net change in renal function over the duration of therapy.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Creatinine; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Female; Fungemia; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Mycoses; Treatment Outcome