amphotericin-b--deoxycholate-drug-combination and Opportunistic-Infections

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

Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature.. Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole.. Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.

Topics: Adult; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Humans; Itraconazole; Kidney Transplantation; Male; Meningitis, Fungal; Middle Aged; Opportunistic Infections; Skin Ulcer; Sporotrichosis; Transplant Recipients

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

A review of series of > or = 4 cases of invasive aspergillosis (total, 1,223 cases) was undertaken to establish the crude mortality and rate of response to therapy with amphotericin B in the major at-risk host groups. In association with pulmonary, sinus, and cerebral aspergillosis in immunocompromised patients, the crude mortality rates were 86%, 66%, and 99%, respectively. No untreated patient survived. Among 84 patients treated for 1-13 days, only one survived. Among those with invasive pulmonary aspergillosis treated for > or = 14 days, the response rates to amphotericin B deoxycholate were 83% (in cases of heart and renal transplantation), 54% (leukemia), 33% (bone marrow transplantation) and 20% (liver transplantation). Patients with AIDS mostly received both amphotericin B and itraconazole, and 37% of those treated for > or = 14 days responded to therapy. Substantial variation in outcome from series to series was related to underlying disease status, site of disease, and management. Invasive aspergillosis remains a devastating opportunistic infection despite current treatment.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Deoxycholic Acid; Drug Combinations; Humans; Itraconazole; Opportunistic Infections

Nebulized amphotericin B deoxycholate (n-ABD) is used to prevent Aspergillus infection in lung transplantation. Nebulized liposomal amphotericin B (n-LAB) is another option; however, no clinical data are available on the results of n-LAB for this purpose.. In an observational study performed in 2 centers to assess the feasibility, tolerability, and outcomes of n-LAB prophylaxis, 104 consecutive patients undergoing prophylaxis with n-LAB were compared with 49 historical controls who received n-ABD. Patient follow-up lasted 12 months. The n-LAB prophylaxis regimen was 25 mg thrice weekly starting on the first post-operative day and continuing to 60 days, 25 mg once weekly from 60 to 180 days, and the same dose once every 2 weeks thereafter.. Aspergillus infection developed in 8 of 104 patients (7.7%) with n-LAB prophylaxis (5 colonization, 1 simple tracheobronchitis, 1 ulcerative tracheobronchitis, and 1 invasive pulmonary infection). Ulcerative tracheobronchitis and invasive pulmonary aspergillosis were regarded as invasive disease; hence, the rate of invasive disease was 1.9% (2 patients). The control group had similar rates of Aspergillus infection (10.2%; p = 0.6) and invasive disease (4.1%; p = 0.43). In 3 patients (2.9%), n-LAB was withdrawn due to bronchospasm in 2 and nausea in 1. In the control group, prophylaxis was stopped in 2 patients (4.1%) because of bronchospasm (p = 0.7).. At the dose and frequency described, n-LAB seems effective, safe, and convenient for the prevention of Aspergillus infection in lung transplant patients.

Topics: Administration, Inhalation; Adult; Amphotericin B; Antifungal Agents; Cohort Studies; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Immunosuppressive Agents; Liposomes; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pulmonary Aspergillosis

Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs.. In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia.. The median duration of neutropenia (neutrophil count, <500 cells/mm3) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; P < .05), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; P < .01). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%.. Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.

Topics: Adult; Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Chi-Square Distribution; Deoxycholic Acid; Drug Combinations; Female; Fever; Humans; Male; Middle Aged; Multicenter Studies as Topic; Mycoses; Neutropenia; Opportunistic Infections; Risk Factors; Statistics, Nonparametric

To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion.. Randomised, controlled, non-blinded, single centre study.. University hospital providing tertiary clinical care.. 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections.. Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours.. Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis.. Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months' follow up in the rapid infusion than in the continuous infusion group.. Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Prospective Studies; Survival Rate

Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting.. To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.. An open randomized, controlled, multicenter trial, powered for equivalence.. 60 oncology centers in 10 countries.. 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy.. Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.. Defervescence, breakthrough fungal infection, drug-related adverse events, and death.. For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days.. Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Humans; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Survival Analysis; Treatment Outcome

Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy.. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André.. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D.. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles.. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Retrospective Studies; Treatment Outcome

Amphotericin B deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/day) was gradually increased to 2.0 mg/kg/day when renal function remained stable and the drug was tolerated. Dose escalation was possible without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied <18% of AmB-d infusions. Twenty-seven patients had a decrease in creatinine clearance while receiving AmB-d therapy. A >2-fold decrease in creatine clearance was observed in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to be well tolerated by most patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Cohort Studies; Deoxycholic Acid; Drug Combinations; Female; Humans; Immunocompromised Host; Infusion Pumps; Male; Middle Aged; Mycoses; Nausea; Neutropenia; Opportunistic Infections; Treatment Outcome

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure