deoxycholic-acid and Fever

The incidence of invasive fungal infections has increased globally as a result of several factors. Conventional amphotericin B (sodium deoxycholate) has been used as standard therapy for the treatment of invasive fungal infections; however, it is associated with adverse drug reactions, including acute kidney injury (AKI). New formulations of amphotericin B have aimed to improve the safety profile of the conventional formulation.. This review aimed to assess the effects of amphotericin B deoxycholate versus liposomal amphotericin B on kidney function.. We searched Cochrane Kidney and Transplant's Specialised Register to 10 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.. We included randomised controlled trials (RCTs) that compared amphotericin B sodium deoxycholate with liposomal amphotericin B.. Two authors independently assessed studies for eligibility and conducted risk of bias evaluation.. We included 12 studies (2298 participants) in this review. Of these, 10 were meta-analysed (2172 participants). Liposomal amphotericin B was found to be significantly safer than conventional amphotericin B in terms of serum creatinine increase (RR 0.49, 95% CI 0.40 to 0.59). There was significant decrease in all infusion-related reactions in the liposomal group compared with the conventional group: fever (4 studies, 1092 participants): RR 0.39, 95% CI 0.28 to 0.55; I(2) = 32%); chills and/or rigours (5 studies, 1081 participants): RR 0.27, 95% CI 0.15 to 0.48; I(2) = 75%); fever and/or rigours (2 studies, 720 participants): RR 0.68, 95% CI 0.52 to 0.90; I(2) = 58%); nausea (6 studies, 1187 participants): RR 0.50, 95% CI 0.35 to 0.72; I(2) = 0%); and vomiting (3 studies, 1019 participants): RR 0.51, 95% CI 0.27 to 0.95; I(2) = 61%). Overall, risk of bias in included studies was low or unclear for most domains. However, blinding of participants and personnel, blinding of outcome assessment and other bias (funding) tended to have a high risk of bias. The sensitivity analysis performed did not change the significance of difference in favour of the liposomal formulation. Assessment for publication bias found that review results were robust.. Current evidence suggests that liposomal amphotericin B is less nephrotoxic than conventional amphotericin B (when the effect on kidney function is measured as an increase in serum creatinine level equal to or greater than two-fold from the baseline level). We also found that there were fewer infusion-related reactions associated with the liposomal formulation.

Topics: Adult; Amphotericin B; Antifungal Agents; Child; Chills; Creatinine; Deoxycholic Acid; Drug Combinations; Female; Fever; Humans; Kidney; Male; Nausea; Randomized Controlled Trials as Topic; Vomiting

Fusarium species are the second leading cause of disseminated mold infections in immunocompromised patients. The high mortality caused by such infections is attributed to the high resistance of Fusarium species to current antifungal agents. We report the first case of disseminated fusariosis after the use of alemtuzumab, an anti-CD52 monoclonal antibody, in a patient who presented with striking cutaneous and oral cavity lesions. Case reports of combination antifungal therapy for disseminated fusariosis in immunocompromised patients were reviewed. Among 19 published cases in the last 10 years plus this patient, the patients in 14 cases (70%) responded positively to combination antifungal therapy. A clinical response was achieved in seven cases before resolution of neutropenia.

Topics: Adult; Alemtuzumab; Amphotericin B; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antineoplastic Agents; Combined Modality Therapy; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fever; Fusariosis; Fusarium; Granulocytes; Humans; Immunocompromised Host; Leukocyte Transfusion; Lymphoma, T-Cell, Cutaneous; Male; Microbial Sensitivity Tests; Neutropenia; Pyrimidines; Skin Neoplasms; Triazoles; Voriconazole

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

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

Fungal infections are a major cause of morbidity and mortality in patients with hematological malignancies. Candida and Aspergillus species are the most important opportunistic fungal pathogens in this patient population. Amphotericin B is the treatment of choice, but its administration is often hampered by severe side-effects, which may be reduced by continuous infusion of this drug. We describe 17 consecutive patients with hematological malignancies, suffering from fever of unknown origin with possible fungal infections, treated with amphotericin B as continuous infusion compared with a control group of 10 patients treated with conventional rapid infusion of amphotericin B over 2 - 6 h. No acute side-effects or severe nephrotoxicity were observed during continuous infusion of amphotericin B. Target doses were reached faster in patients with continuous infusion of amphotericin B than in patients with rapid infusion. We conclude that continuous infusion of amphotericin B is safe in neutropenic patients with hematological malignancies.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; C-Reactive Protein; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Combinations; Female; Fever; Hematologic Neoplasms; Humans; Infusions, Intravenous; Male; Middle Aged; Mycoses; Neutropenia; Treatment Outcome

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

Topics: Adolescent; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Dermatomycoses; Drug Combinations; Fever; Histoplasmosis; Humans; Itraconazole; Lung Diseases, Fungal; Male; Nepal; Rural Population

To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.. 目的：比较肺型与进展播散型组织胞浆菌病的临床特点、诊断及预后差异。 方法：回顾性分析中南大学湘雅医院2009年2月至2015年10月期间收治的组织胞浆菌病住院患者12例，其中肺型4例，进展播散型8例。从临床表现、影像学、确诊途径及预后等方面分析两者之间的差异性。 结果：肺型组织胞浆菌病临床表现轻微，干咳多见。进展播散型患者全身症状明显，极易出现反复高热、全身浅表淋巴结肿大、肝脾肿大，可合并咳嗽、腹痛、关节痛、皮肤改变等。实验室检查示全血细胞减少、肝功能异常、凝血功能异常等。1例肺型患者给予了左下肺切除术，其余3例肺型及6例进展播散型患者分别给予两性霉素B脱氧胆酸盐、伊曲康唑、伏立康唑或氟康唑抗真菌感染治疗，好转出院，1例播散型确诊后暂未治疗即出院，1例播散型因合并重症肺炎及活动性肺结核治疗无效死亡。结论：组织胞浆菌病临床少见，极易漏诊或误诊，依靠骨髓涂片、病理组织切片特殊染色明确病原学是目前确诊的主要依据，推荐两性霉素B脂质体、两性霉素B脱氧胆酸盐及伊曲康唑抗感染治疗。.

Topics: Abdominal Pain; Amphotericin B; Antifungal Agents; Biopsy; Cough; Death; Deoxycholic Acid; Diagnostic Errors; Drug Combinations; Fever; Hepatomegaly; Histoplasma; Histoplasmosis; Humans; Invasive Fungal Infections; Itraconazole; Lung; Lung Diseases, Fungal; Pneumonia; Recurrence; Retrospective Studies; Splenomegaly; Treatment Outcome; Tuberculosis

Visceral leishmaniasis or kala-azar is an endemic parasitic disease in some parts of the world which is characterized by fever, splenomegaly, and pancytopenia in most of the cases. Herein we report an 11 month-old male infant with diagnosis of kala-azar who presented with pallor, hepatosplenomegaly, failure to gain weight, and no history of fever. Surprisingly, fever started after beginning of meglumine antimoniate treatment in this patient. As far as we are aware of, this is a rare presentation of visceral leishmaniasis. Therefore, clinicians especially in endemic areas are highly recommended to include kala-azar among differential diagnosis of unexplained anemia without fever to prevent misdiagnosis of this potentially fatal, but treatable condition.

Topics: Amphotericin B; Anemia; Antiprotozoal Agents; Deoxycholic Acid; Diagnosis, Differential; Drug Combinations; Endemic Diseases; Fever; Humans; Infant; Iran; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Splenomegaly

The 2010 trivalent influenza vaccine (TIV) manufactured by CSL Biotherapies (CSL) was associated with increased febrile reactions, including febrile convulsions, among Australian children. CSL is one of the few manufacturers that use deoxycholate as the virus-splitting agent in the manufacture of TIV. Clusters of adverse events following immunisation (AEFI) have been previously linked to other deoxycholate-split TIV formulations in Europe and Canada. We hypothesise that suboptimal virus splitting or other mechanisms related to the use of deoxycholate may have played a role in adverse events linked to the 2010 CSL TIV. This hypothesis garners support from a recent United States Food and Drug Administration warning letter indicating that CSL failed to determine optimal splitting conditions for new virus strains and that assays to assess virus splitting had not been validated. While there may be other causes, the use of deoxycholate should be further explored. Comprehensive and timely investigations of AEFI, especially those involving children, are necessary to prevent their recurrence and to maintain public confidence in vaccination programs.

Topics: Australia; Child; Child, Preschool; Deoxycholic Acid; Evidence-Based Medicine; Fever; Humans; Infant; Influenza Vaccines; Influenza, Human; Product Surveillance, Postmarketing; Risk Factors; Seizures, Febrile; Solvents; Vaccination; World Health Organization

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second-line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future.

Topics: Administration, Oral; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cephalosporins; Data Collection; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fever; Fluoroquinolones; Hematopoietic Stem Cell Transplantation; Humans; Korea; Neoplasms; Neutropenia; Prospective Studies; Surveys and Questionnaires; Time Factors; Treatment Failure

Because of the large number of cases of visceral leishmaniasis (VL) recorded in Brazil over the last few years, this disease has been showing characteristics different from previously known ones. We report cases of pregnant women treated for VL, describing their course and outcome and the chemotherapeutic medication used according to the clinical signs and symptoms of each patient.. We report five cases of pregnant women treated for VL in a central-western region of Brazil.. No case of vertical transmission was observed, even in patients who were treated after delivery. One of the patients with a late diagnosis made after the onset of symptoms died. Thus, the treatment of VL during pregnancy reduces maternal mortality and the rate of vertical transmission of the disease, being safe and effective as long as the disease is diagnosed early.. At present, amphotericin B and its derivatives appear to be the best therapeutic option for the mother-child binomial.

Topics: Adult; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Brazil; Deoxycholic Acid; Drug Combinations; Female; Fever; Hepatomegaly; Humans; Leishmaniasis, Visceral; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Splenomegaly

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Deoxycholic Acid; Drug Combinations; Echinocandins; Fever; Humans; Infusions, Intravenous; Lipopeptides; Mycoses; Neutropenia; Peptides, Cyclic

Formulations of amphotericin include a deoxycholate suspension (d-Amph), an amphotericin-B lipid complex (Ablc), and a liposomal product (L-Amph). Fever is most frequent with d-Amph, intermediate with Ablc, and lowest with L-Amph.. To determine if the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1) from brain endothelium corresponds to the incidence of amphotericin fever.. Release of TNF-alpha and IL-1beta after L-Amph treatment was similar to negative controls while after d-Amph treatment release was similar to lipopolysaccharide. Ablc treatment produced intermediate pyrogen release.NF-kappaB expression, a transcriptional regulator for TNF-alpha and IL-1beta genes, corresponded to this secretion pattern. TNF-alpha release was elevated 2 hours (p = 0.0021) after treatment while significant elevations in IL-1beta required 6 hours (p = 0.0009).. Results from this in vitro study suggest that amphotericin fever may be directly mediated by brain endothelium. These experiments also suggest that amphotericin fever is initially mediated by TNF-alpha.

Topics: Amphotericin B; Animals; Brain; Chemistry, Pharmaceutical; Deoxycholic Acid; Endothelium; Fever; Interleukin-1; Lipids; Liposomes; NF-kappa B; Pyrogens; Stereoisomerism; Suspensions; Swine; Time Factors; Tumor Necrosis Factor-alpha

Topics: Amphotericin B; Antifungal Agents; Aspergillus; Deoxycholic Acid; Drug Combinations; Fever; Fluconazole; Humans; Mycoses; Neutropenia

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

Ultraviolet light-inactivated, non-infectious influenza virus is pyrogenic; virion components are probably responsible for this pyrogenicity. To try to identify the pyrogenic component, influenza virions were disrupted with either bromelain or sodium deoxycholate (DOC). Treatment of infectious virions with bromelain, under conditions that removed the surface glycoproteins (spikes), destroyed their pyrogenicity. The supernatant, containing non-aggregated and modified glycoproteins, was also non-pyrogenic. Disruption of virions with DOC considerably reduced pyrogenicity; however, some was retained by the sub-viral cores. Viral nucleoprotein and matrix protein, purified from the supernatant, were non-pyrogenic. Aggregated stellate clusters of surface glycoproteins separated on sucrose gradients were pyrogenic in half of numerous tests performed with different batches of material. Treatment of virus with ether resulted in complete loss of pyrogenicity. Liposomes made from extracted viral lipid were non-pyrogenic. In contrast, virosomes made from the viral lipid and the aggregated stellate clusters of surface glycoproteins were pyrogenic. Hence, optimum pyrogenicity depends upon the integrity of the virus particle, but haemagglutinin and/or neuraminidase appear essential, and lipid may be involved.

Topics: Animals; Blotting, Western; Bromelains; Deoxycholic Acid; Electrophoresis, Polyacrylamide Gel; Ferrets; Fever; Influenza A virus; Lipids; Liposomes; Male; Microscopy, Electron; Orthomyxoviridae Infections; Pyrogens; Viral Envelope Proteins

Topics: Animals; Cisterna Magna; Deoxycholic Acid; Fever; Male; Molecular Weight; Polysaccharides, Bacterial; Pyrogens; Rabbits; Structure-Activity Relationship