amphotericin-b and Hematologic-Diseases

The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry ( www.chictr.org.cn ) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Topics: Amphotericin B; China; Databases, Factual; Hematologic Diseases; Humans; Neutropenia

Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.

Topics: Amphotericin B; Anidulafungin; Animals; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Azoles; Candidiasis; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Therapy, Combination; Echinocandins; Fungemia; Hematologic Diseases; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Kidney Diseases; Liver Diseases; Mice; Neutropenia; Risk Factors

Invasive fungal infections (IFI) are the main cause of infectious death in cancer patients, especially in hematological malignancies and hematopoietic transplant recipients. Current epidemiology is characterized by a predominance of IFI caused by molds, mainly aspergillosis, along with a emergence of hard-to-treat fungi such are Zygomicetes, Fusarium and Scedosporium. Voriconazole is a broad spectrum antifungal agent with oral and intravenous formulations, approved by the EMEA for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, IFI caused by fluconazole-resistant species of Candida as well as Scedosporium and Fusarium infections. However, its use in clinical practice is broader, as empirical antifungal treatment and as secondary prophylaxis. It should be kept in mind the possibility of breakthrough IFI, particularly zygomycosis, in patients treated with voriconazole for long periods.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Drug Resistance, Fungal; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Multicenter Studies as Topic; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Salvage Therapy; Spain; Triazoles; Voriconazole; Zygomycosis

Zygomycosis is an opportunistic fungal infection that is increasingly reported in hematological patients. We describe 2 cases of successfully treated rhino-cerebral zygomycosis and give an overview of 120 patients from the literature with underlying hematological or oncological disorders. These data document the improved survival in sinus (15/17 patients surviving) and cutaneous (6/9 patients surviving) disease. Hematological patients with pulmonary (9/30 patients surviving) or disseminated (4/38 patients surviving) zygomycosis still have a poor prognosis. The clinical course of sinus-orbital involvement (4/11 patients surviving) follows sinus-cerebral (2/3 patients surviving) or cerebral (3/6 patients surviving) disease. Besides deoxycholate amphotericin B (AmB) (24/62 patients surviving), patients seem to benefit from liposomal amphotericin B (L-AmB) (10/16 patients surviving) or sequential AmB/L-AmB treatment (6/8 patients surviving). Alternative treatment options lead only in a few patients to success.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus fumigatus; Combined Modality Therapy; Deoxycholic Acid; Ethmoid Sinusitis; Female; Hematologic Diseases; Humans; Immunocompromised Host; Itraconazole; Ketoconazole; Liposomes; Lymphoma, Large B-Cell, Diffuse; Male; Maxillary Sinusitis; Middle Aged; Mucor; Mucormycosis; Multiple Myeloma; Nose Diseases; Opportunistic Infections; Prognosis; Treatment Outcome; Zygomycosis

The last decade has been remarkable for the dramatic increase in the prevalence of serious fungal infections in patients with haematological disorders and neutropenic cancer patients. The mortality rate of deep-seated infection has been in excess of 90% and there is no doubt that this is one of the greatest challenges currently facing haematologists and oncologists. The development of the lipid-based drugs - liposomal amphotericin (AmBisome(R)), amphotericin B lipid complex, ABLC (Abelcet(R)), amphotericin B colloidal dispersion, Amphocil (ABCD(R)), has meant that doses of amphotericin B can be safely escalated for the first time whilst the problems of nephrotoxicity, infusion related reactions (including chills, rigors, fevers and hypoxia) can be reduced. These toxicities are variably reduced with AmBisome more than Abelcet and more than Amphocil and there is little information from randomised trials other than for AmBisome. AmBisome used in the setting of persistent fever and neutropenia not responding after 3-4 days of intravenous antibiotics, is associated with less breakthrough systemic fungal infections. There is also much less need for premedication, including steroids, compared with amphotericin B and Abelcet. The use of intermittent doses of Ambisome given prophylactically is now being explored. A new and exciting era of antifungal therapy is opening up with new compounds, such as itraconazole voriconazole, posaconazole and echinocandins, being investigated and for the first time, we also have options for combination therapy and prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Costs and Cost Analysis; Hematologic Diseases; Humans; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Chemistry, Pharmaceutical; Fluconazole; Flucytosine; Hematologic Diseases; Humans; Itraconazole; Mycoses

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Fluconazole; Flucytosine; Hematologic Diseases; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney; Mycoses; Thrombophlebitis

Disseminated fungal infection causes significant morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). The widespread use of prophylactic oral triazoles has limitations of poor absorption, interindividual variability in metabolism, and hepatic toxicity. AmBisome (amphotericin B liposomal complex) has a better safety profile than the parent drug amphotericin B and produces higher plasma and tissue concentrations. We hypothesized that once-weekly high-dose AmBisome therapy could provide adequate fungal prophylaxis for immunocompromised children undergoing HSCT. We performed a pharmacokinetic pilot study to determine whether once-weekly high-dose AmBisome administration would result in effective concentrations throughout the dosing interval. A total of 14 children (median age, 3 years, 1 month; range, 4.5 months-9 years, 9 months) undergoing HSCT received once-weekly intravenous AmBisome prophylaxis (10 mg/kg as a 2-hour infusion). Blood samples for pharmacokinetic measurements were drawn around the first and the fourth weekly doses. The concentration of non-lipid-complexed amphotericin in plasma was determined by a validated bioassay. Pharmacokinetic parameters after single doses and during steady state were calculated using standard noncompartmental methods. AmBisome was well tolerated at this dose. Complete pharmacokinetic profiles for weeks 1 and 4 were obtained in 12 patients. The half-life calculated in this pediatric population was shorter on average than reported in adults (45 hours vs 152 hours). The volume of distribution correlated best with body weight (R(2) = .55), and clearance was best predicted by initial serum creatinine level (R(2) = .19). Mean (+/- standard deviation) individual plasma trough concentrations were 0.23 (0.13) mg/L after single doses and 0.47 (0.41) mg/L after multiple doses. Mean steady-state area under the curve was higher at week 4 than after a single dose (P < .05). Single-dose and steady-state pharmacokinetic profiles were similar in 8 patients, whereas in 4 patients the week 4 profile showed nonlinear elimination. However, plasma concentrations at 7 days (Cmin) were not significantly different after the first and fourth doses, suggesting no significant accumulation over the course of therapy. Our data show measurable amphotericin B plasma concentrations 7 days after high-dose infusion of AmBisome. This suggests that once-weekly dosing, as described in this study, may provide usef

Topics: Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Mycoses; Prospective Studies; Time Factors

Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis.. In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome.. A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients).. In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Pyrimidines; Survival Rate; Triazoles; Voriconazole

To evaluate the usefulness of a 20% lipid emulsion as a delivery system for amphotericin B (1 mg/mL) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B (0.1 mg/mL) administered in dextrose 5% solution over the same time.. A prospective, comparative, randomized, labeled study.. Hematology unit, pharmacy service, university general hospital.. Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections, 10 in the fat emulsion group (group 1) and 10 in the dextrose 5% group (group 2).. Clinical tolerance (i.e., fever, shaking chills, nausea, blood pressure, pulse rate) and biologic tolerance (i.e., urea, creatinine, sodium, potassium).. Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated. Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2. There was a statistically significant difference in the urea concentrations between the 2 groups (p = 0.023); there was an observed increase between the initial and the final serum urea (56.8 mg/d in group 1, 79.8 mg/dL in group 2). Statistically significant differences in creatinine serum concentrations (84.9 mumol/L in group 1, 123.8 mumol/L in group 2) (p = 0.047) were found. No differences were found in the antifungal efficacy of the treatment. However, as amphotericin B was started in the majority of cases (75%) as empiric treatment for fever unresponsive to antibiotic therapy, it is difficult to compare the efficacy of both preparations.. The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Fat Emulsions, Intravenous; Female; Glucose; Hematologic Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Mycoses; Neutropenia; Prospective Studies; Solutions

A randomized, comparative study was conducted in 502 patients in 23 centres world-wide to assess the efficacy and safety of fluconazole versus nystatin and amphotericin B for prevention of fungal infection in a severely immunocompromised pediatric population. Patients scheduled within 48 hours to undergo chemotherapy or radiotherapy for hematological or oncological malignancies were randomly allocated to receive 3 mg/kg oral fluconazole once daily, 50,000 U/kg oral nystatin four times daily or 25 mg/kg oral amphotericin B four times daily. Prophylaxis began with the initiation of chemotherapy or radiotherapy and continued throughout a patient's hospital stay or period of neutropenia as necessary. The mean duration of fluconazole prophylaxis was 27.8 days and of the oral polyenes 29.2 days. The outcome of prophylaxis with fluconazole was significantly superior to that with the polyenes (p = 0.01). Mycologically verified infections occurred in 5 patients (2.1%) given fluconazole and in 21 (8.4%) given polyenes (p = 0.002). Clinical evaluation at the end of prophylaxis showed that the clinical outcome was definitely or possibly successful in 87% in the fluconazole group and 82% in the polyenes group with no significant differences between the treatment groups. Mycological evaluation demonstrated reduction or control of colonization in 84% in the fluconazole group and 85% in the polyenes group, again with no significant between-group differences. Possibly drug-related side effects, mainly mild to moderate gastrointestinal disturbances, were reported in 38 patients given fluconazole, with eight subsequent withdrawals, and in 21 patients given oral polyenes, with three subsequent withdrawals. Laboratory test abnormalities occurred in 28 patients given fluconazole and 24 given polyenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Amphotericin B; Candida; Child; Child, Preschool; Female; Fluconazole; Hematologic Diseases; Humans; Immunocompromised Host; Infant; Infant, Newborn; Male; Mycoses; Neoplasms; Nystatin

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Topics: Adolescent; Adult; Aged; Amikacin; Amphotericin B; Bacteremia; Ceftazidime; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Teicoplanin; Vancomycin

The association between colonization with Candida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67% of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31% of patients colonized in single or contiguous sites (monocolonized) and in 21% of non-colonized patients (p = 0.0037 and p = 0.00026, respectively). Invasive candidiasis was documented in 22.2% of multicolonized versus 4.8% of monocolonized patients and in none of the non-colonized patients (p = 0.035 and p = 0.0036, respectively). Analysis of the spectrum of colonizing Candida spp. showed that multicolonized subjects were colonized with increased frequently by Candida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized by Candida albicans but not in patients colonized by other Candida species. The association between Candida multicolonization and the occurrence of Candida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole.

Topics: Adolescent; Adult; Aged; Amphotericin B; Candida; Candidiasis; Child; Child, Preschool; Colony Count, Microbial; Double-Blind Method; Female; Fluconazole; Hematologic Diseases; Humans; Male; Middle Aged; Neutropenia; Prospective Studies

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Amphotericin B; Drug Evaluation; Female; Hematologic Diseases; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multicenter Studies as Topic; Multiple Myeloma; Mycoses

Therapeutic effectiveness of 5-fluorocytosine (5-FC), amphotericin B (Am B) and both in combined administration were retrospectively assessed and compared with one another in 28 patients with cryptococcal meningitis. Combined administration was significantly superior to Am B alone and to 5-FC alone, and these agents were suggested to afford a synergetic effect in combined administration. Adverse reactions associated with combined administration did not essentially differ from those with Am B or 5-FC alone. Combined administration was able to decrease the incidence and severity of adverse reactions by employing lower doses of Am B, and this combined administration reduced the duration of treatment. An appropriate dose for each agent in combined administration was deemed to be about 0.350 mg/kg/day Am B i.v. and 150 mg/kg/day 5-FC p. o. based on the results of this study.

Topics: Adult; Aged; Amphotericin B; Clinical Trials as Topic; Cryptococcosis; Cytosine; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Flucytosine; Gastrointestinal Diseases; Hematologic Diseases; Humans; Injections, Intravenous; Male; Meningitis; Middle Aged; Time Factors

To investigate the clinical characteristics, prevention and treatment of invasive fungal disease (IFD).. The clinical data of 164 patients who met the diagnostic criteria of IFD in our center from January 2012 to January 2015 were retrospectively analyzed. The incidence, clinical characteristics, related factors, treatment methods and prognosis were analyzed.. Among 1289 cases of blood diseases, 164 cases suffered from IFD with inciduce of 12.7%. The main infection sites were as followed: lung, blood and gastrointestinal tract, with incidence of 84.2%, 5.5% and 3% respectively. The funge was found in 35 cases by detection; among fungi, the detected rate of candida albicans. aspergillus and candida glabrata was more high with 51.5%, 20% and 14.3% respectively. Among 164 childen with blood deseases complicated by IFD, 36 cases gained complete remission, 97 cases gained partial remission, 10 cases were stable, 11 cases were progressive and 10 cases died, the overall effective rate reached 81.1%. The univariate analysis showed that the gramulopenia, granulocyte recovery, long-term use of corticosteroid and immuno-suppressive agents, as well as different grades of diagnosis were significant factors affecting the efficacy of antifungal therapy for blood disease children with IFD, the multivariate analysis further showed that the granulocyte recovery and diagnosis grades were independent prognostic factors affecting the therapeutic efficacy for IFD children. The overall survival rate of IFD children with 12 weeks of antifungal treatnment was 81.7%, out of which the survival rate of IFD children at 12 weeks of treatment with itraconazole, voriconazole, amphotericin B and caspofungin was 81.4%, 80%, 69.4% and 97.1% respectively, there were significant differences in survival rate between each other by long rank test. In addition of caspofungin, the other 3 kinds of drugs had toxic side effects of different degrees, but IFD children could tolerated these effects after symptomatic treatment.. The incidence of IFD in children with blood deseases in our hospital is 12.7%, the lung is most common infective site, moreover patogens of IFD mainly is candida. The promotion of granulocyte recovery and early stratified diagnosis can contribule to the treatment of IFD. For the IFD children with better economic condition, the caspofungin is a potent antifungal agent with high efficacy, low toxicity and better prognosis.. 儿童血液病合并侵袭性真菌病164例临床分析.. 探讨儿童侵袭性真菌病（invasive fungal disease，IFD）的临床特点和防治方法。.. 回顾性分析本中心2012年1月至2015年1月符合IFD诊断标准的164例临床资料，了解其发病率、临床特征、相关因素，治疗方法和预后。.. 在本院收治的1 289例血液病患儿中164例发生IFD，发病率为12.7%；感染部位主要为单纯肺部、血液和胃肠道，发生率分别为84.2%、5.5%和3%；共检出真菌35例，其中白色假丝酵母菌、曲霉菌和光滑假丝酵母菌检出率较高，分别为51.5%、20%和14.3%；164例患儿完全缓解36例，部分缓解97例，疾病稳定10例，进展11例，死亡10例，总有效率达81.1%。单因素分析表明，粒细胞缺乏、粒细胞恢复、长期使用糖皮质激素和免疫抑制剂及不同的诊断级别是影响患儿抗真菌疗效的显著因素；多因素分析结果则进一步表明，粒细胞恢复和诊断级别为影响IFD患儿疗效的独立预后因素。164例患儿抗真菌治疗，在开始的12周内的总体活存率为81.7%，其中伊曲康唑、伏立康唑、两性霉素B和卡泊芬净治疗的患儿12周生存率分别为81.4%、80%、69.4%和97.1%，Log-rank检验显示差异具有显著性意义。除卡泊芬净外，其余3种药物均出现不同程度的毒副作用，经对症治疗后患儿均可耐受。.. 本院血液病患儿IFD的发生率为12.7%，肺部为最常见感染部位，且以念珠菌居多。促进粒细胞恢复和尽早的分层诊断有助于IFD的治疗。对于经济条件较好的患儿，卡泊芬净是一种高效、低毒和预后好的抗真菌药物，值得临床推荐使用。.

Topics: Amphotericin B; Antifungal Agents; Child; Hematologic Diseases; Humans; Invasive Fungal Infections; Retrospective Studies

Invasive fungal disease (IFD) has a poor prognosis in children with hematological disorders after hematopoietic stem cell transplantation (HSCT). We assessed if drug combinations with different targets may improve the outcome.. Retrospective study to assess the outcome of combination antifungal therapy (CAT) for proven-probable IFD (PP-IFD) in children with hematological disorders after HSCT from January 2008 to June 2018.. Over the 10-year period, 95 PP-IFD were diagnosed in pediatric recipients, median age of 5.6 years. Twenty-seven patients received combinations of caspofungin and voriconazole, 28 patients received combinations of caspofungin and amphotericin B, and 40 patients received combinations of voriconazole and amphotericin B. The overall response rate of PP-IFD was 77.9%, while the 100-day overall survival rates were 66.8%. Univariate analysis showed that factors that significantly affected the response to combination treatments were type of combination (P = 0.02), the stem cell source (P = 0.04), the donor type (P = 0.03), HLA-match (P = 0.03), aGVHD (P = 0.02), period of treatment (P = 0.044), use of corticosteroids (0.036), CD4:CD8 ratio (P = 0.014), and CMV viremia (P = 0.033). In addition, multivariate analysis demonstrated that only the type of combination remained a significant factor (odds ratio = 0.335, 95% confidence interval: 0.071-0.812, P = 0.042). Forty-three children suffered from mild and reversible adverse reactions, no serious side effects during treatment.. A variety of factors can affect the outcome of CAT. Combination of caspofungin with voriconazole is a safe and helpful treatment option for HSCT recipients with IFD.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Caspofungin; Child; Child, Preschool; Drug Therapy, Combination; Female; Hematologic Diseases; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Invasive Fungal Infections; Male; Mycoses; Retrospective Studies; Survival Analysis; Transplantation, Homologous; Treatment Outcome; Voriconazole

Recent years have seen important advances in the diagnosis of invasive pulmonary aspergillosis (IPA), complemented by the introduction of new therapies. Despite this, IPA remains a major cause of infection-related mortality in patients with haematological diseases. There are two main reasons for this. First, diagnosis of IPA remains a challenge, since risk factors and the clinical, radiological and mycological presentations vary not only by fungal disease stage, but also by patient group (eg neutropenic vs non-neutropenic patients). Diagnosis is particularly challenging in patients receiving mould-active prophylactic or empirical treatment, which reduces the sensitivity of all diagnostic tests for IPA. Second, treatment of IPA is complex due to unpredictable pharmacokinetic profiles of antifungal agents, small therapeutic window in terms of exposure and adverse events, and multiple drug-drug interactions through the CYP450 system. Here we report a case of a 23-year-old male with severe aplastic anaemia and subpleural nodules. Diagnostic tests for IPA obtained during ongoing mould-active empirical treatment were negative. Intravenous voriconazole was stopped after visual disturbances and hallucinations. The patient then had an anaphylactic reaction to liposomal amphotericin B and was switched to intravenous posaconazole, which had to be discontinued due to a significant increase in transaminase levels. He was treated with oral isavuconazole with reduced dosage, triggered by increasing transaminases under the standard dosage. Even under reduced dosage, blood concentrations of isavuconazole were high and treatment was successful. The case illustrates real-world challenges and unmet needs in the diagnosis and treatment of IPA in patients with haematological diseases.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillus; Hematologic Diseases; Humans; Invasive Pulmonary Aspergillosis; Male; Neutropenia; Nitriles; Pyridines; Transaminases; Treatment Outcome; Triazoles; Voriconazole; Young Adult

Liposomal amphotericin B (L-AMB) has the potential to cause two major adverse events, renal dysfunction and serum potassium abnormality; however, appropriate clinical management of these events remains unclear. We retrospectively analyzed data regarding 128 hematology patients who received L-AMB in our institute and examined the association between clinical characteristics and renal dysfunction or serum potassium abnormality. We found that the median weight-normalized dose of L-AMB was 2.69mg/kg and the median administration period was 16days. The overall occurrence rates of renal dysfunction and hypokalemia were 55.7% and 76.6%, respectively. Multivariate analysis revealed that pre-existing renal dysfunction (P=0.017) and concomitant use of nephrotoxic (P<0.0001) or antifungal drugs (P=0.012) were independent risk factors for renal dysfunction. A higher infusion volume did not mitigate the risk of renal dysfunction. Hypokalemia occurred significantly less often in men (P=0.028) and in patients who concomitantly used nephrotoxic drugs (P=0.013). Approximately 40% of the adverse events were improved at 30days after L-AMB termination and there was no significant association between these adverse events improvement and L-AMB dosage or infusion volume. Of note, hyperkalemia was observed in more patients who received allogeneic hematopoietic stem cell transplantation (P=0.0303) and concomitant treatment with nephrotoxic drugs (P=0.0281). These results suggest that imprudent reduction of L-AMB dose or redundant intravenous infusion may have minimal benefit for critical patients with suspected invasive fungal infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Hematologic Diseases; Humans; Hyperkalemia; Hypokalemia; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Mycoses; Retrospective Studies; Risk Factors; Young Adult

Cryptococcal infection has become a public health challenge globally. However, information about cryptococcal infection in patients with hematological diseases remains relatively rare.. HIV-uninfected cryptococcosis cases with hematological diseases admitted to Huashan Hospital from January 2001 to December 2014 were reviewed.. In total, 33 cryptococcosis patients were enrolled, including 12 malignant and 21 non-malignant hematological cases. Twenty-six patients had central nervous system (CNS) involvement, which was observed more often in patients with non-malignancies than with malignancies (20/21 vs. 6/12, P = 0.001) Most patients (25/26) with CNS infection were confirmed by cerebrospinal fluid (CSF) culture or smear, and 100% (20/20) of them tested positive for the CSF cryptococcal antigen test. Eighteen out of 26 cryptococcal meningitis patients were treated with amphotericin B (AmB)-based therapy, 16 of them with AmB deoxycholate (d-AmB) and 2 patients with liposomal AmB. The clinical success rate was 55.6%. D-AmB was well-tolerated at 0.35-0.59 mg/kg/d (median 0.43 mg/kg/d) and only 12 patients had mild adverse events.. CNS cryptococcal infection was more frequent in patients with hematological non-malignancies, and cryptococcal antigen test as well as the CSF fungal culture or smear are suggested for early diagnosis. D-AmB could be used as an alternative therapy for CNS-infected patients with hematological diseases.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Central Nervous System Fungal Infections; Cryptococcosis; Deoxycholic Acid; Drug Combinations; Female; Hematologic Diseases; Hematologic Neoplasms; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Tertiary Care Centers; Young Adult

The safety and efficacy of treatment with liposomal amphotericin B (L-AMB) in elderly patients has not been clarified, especially in Japanese patients. Therefore, we retrospectively analyzed 33 elderly patients with hematological diseases of at least 65 years old who received L-AMB between 2009 and 2012. Their clinical outcomes were compared to those of 21 patients who were younger than 65 years. L-AMB was administered for empirical therapy (n = 2) or target therapy for possible (n = 14) or probable/proven (n = 17) invasive fungal infection. There was no discontinuation of L-AMB due to adverse events. More than 2-fold increases from the baseline Cre, AST, and ALT values were observed in 21.2%, 39.4%, and 45.5% of the older group and 38.1%, 61.9%, and 52.4% of the younger group, respectively. The concurrent use of nephrotoxic antibiotics was the only risk factor for the development of a 2-fold increase in the serum Cre level. The duration of L-AMB was significantly longer in patients who developed grade III-IV hypokalemia. A partial or complete response was observed in 54.8% and 62.5% of the elderly and younger groups, respectively. In conclusion, L-AMB therapy appeared to be acceptably safe as empirical therapy or treatment for invasive fungal infection.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Hematologic Diseases; Humans; Immunocompromised Host; Invasive Fungal Infections; Male; Middle Aged; Retrospective Studies

Even though amphotericin B is associated with considerable hematological toxicity, this subject has been poorly studied. This retrospective cohort study assessed the incidence and predictors of hematological toxicity in patients treated with different amphotericin B formulations: amphotericin B deoxycholate (d-AmB), liposomal amphotericin B (L-AmB) and amphotericin B lipid complex (ABLC). A total of 497 patients were included. Severe anemia was independently associated with human immunodeficiency virus (HIV) infection (odds ratio [OR] 1.79; 95% confidence interval [CI]: 1.03-3.06). L-AmB use was marginally associated with reduced risk for severe anemia (OR 0.61; CI: 0.32-1.11). Severe leukopenia was associated with ABLC use (OR 2.58; CI: 1.05-6.21) and hematological cancer (OR 4.61; CI: 2.07-10.38). Hematological cancer (OR 5.00; CI 2.79-8.97) was independently associated with risk of severe thrombocytopenia. In this study, significant hematological toxicity was associated with amphotericin B treatment, along with previous hematological disease and use of myelotoxic drugs. Close monitoring is required when managing patients receiving amphotericin B formulations.

Topics: Adult; Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Cohort Studies; Comorbidity; Deoxycholic Acid; Drug Combinations; Female; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Middle Aged; Organ Transplantation; Retrospective Studies; Young Adult

To evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).. A retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.. Overall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.. For IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.

Topics: Amphotericin B; Antifungal Agents; Child; Drug Therapy, Combination; Echinocandins; Hematologic Diseases; Humans; Mycoses; Retrospective Studies; Survival Rate; Treatment Outcome

The current healthcare climate demands pharmacoeconomic evaluations for different treatment strategies incorporating drug acquisition costs, costs incurred for hospitalisation, drug administration and preparation, diagnostic and laboratory testing and drug-related adverse events (AEs). Here we evaluate the pharmacoeconomics of voriconazole versus liposomal amphotericin B as first-line therapies for invasive aspergillosis (IA) in patients with haematological malignancy and prolonged neutropenia or who were undergoing haematopoietic stem-cell transplantation in Germany or Spain.. A decision analytic model based on a decision tree was constructed to estimate the potential treatment costs of voriconazole versus liposomal amphotericin B. Each model pathway was defined by the probability of an event occurring and the costs of clinical outcomes. Outcome probabilities and cost inputs were derived from the published literature, clinical trials, expert panels and local database costs. In the base case, patients who failed to respond to first-line therapy were assumed to experience a single switch between comparator drugs or the other drug was added as second-line treatment. Base-case evaluation included only drug-management costs and additional hospitalisation costs due to severe AEs associated with first- and second-line therapies. Sensitivity analyses were conducted to assess the robustness of the results. Cost estimates were inflated to 2011 euros (€).. Based on clinical trial success rates of 52.8% (voriconazole) and 50.0% (liposomal amphotericin B), voriconazole had lower total treatment costs compared with liposomal amphotericin B in both Germany (€ 12,256 versus € 18,133; length of therapy [LOT] = 10-day intravenous [IV] + 5-day oral voriconazole and 15-day IV liposomal amphotericin B) and Spain (€ 8,032 versus € 10,516; LOT = 7-day IV + 8-day oral voriconazole and 15-day IV liposomal amphotericin B). Assuming the same efficacy (50.0%) in first-line therapy, voriconazole maintained a lower total treatment cost compared with liposomal amphotericin B. Cost savings were primarily due to the lower drug acquisition costs and shorter IV LOT associated with voriconazole. Sensitivity analyses showed that the results were sensitive to drug price, particularly the cost of liposomal amphotericin B.. Voriconazole is likely to be cost-saving compared with liposomal amphotericin B when used as a first-line treatment for IA in Germany and Spain.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Costs and Cost Analysis; Germany; Hematologic Diseases; Spain; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Follow-Up Studies; Hematologic Diseases; Humans; Mucormycosis; Registries; Treatment Outcome; Triazoles

To investigate the risk factors, clinical features, efficacy and adverse reactions in patients of hematologic diseases with invasive fungal infections (IFI).. The risk factors and clinical features were retrospectively analyzed to compare the efficacy and safety of itraconazole with amphotericin B in treatment of IFI in 76 patients with hematologic diseases.. Of the 76 patients, 68 (89.5%) used broad-spectrum antibiotics, 64 (84.2%) were treated with more than 2 courses chemotherapy, 43 (56.6%) were under agranulocytosis, 34 (44.7%) were using glucocorticoid for long terms, 27 (35.5%) were with peripheral or central venous catheter. The overall effective rates of itraconazole and amphotericin B were 60.5% and 61.5% respectively (P = 0.929). There was a significant difference between itraconazole and amphotericin B in hypokalemia (14.0% vs 42.4%, P = 0.005) while no other differences in adverse reactions were found.. The risk factors of patients in hematologic diseases with IFI include chemotherapy, using broad septum antibiotics and agranulocysis. The therapeutic effect of itraconazole and amphotericin B in treatment of IFI is similar. The adverse reactions of itraconazole is less and slighter than amphotericin B.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Hematologic Diseases; Humans; Itraconazole; Male; Middle Aged; Mycoses; Retrospective Studies; Risk Factors; Treatment Outcome; Young Adult

The detection of serum 1,3-β-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG-positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; beta-Glucans; Echinocandins; Female; Fluconazole; Fungemia; Hematologic Diseases; Humans; Immunocompromised Host; Lipopeptides; Male; Micafungin; Miconazole; Middle Aged; Proteoglycans; Retrospective Studies; Treatment Outcome; Trichosporon; Young Adult

To compare the differences in clinical therapeutic effect and safety between amphotericin B and its liposome form in treating invasive fungal infection (IFI) in hematological disorder with neutrocytopenia.. Of 111 patients with IFI, 82 were treated with amphotericin B and 29 with amphotericin B liposome. The mean cumulative dose of amphotericin B was 617 (60-1895) mg and the mean course was 18 (7-60) d, and those for amphotericin B liposome was 925 (140-3420) mg and 13 (7-50) d, respectively.. The total effective rates of amphotericin B and its liposome groups were 69% and 58%, respectively (P>0.05). The adverse effect rates of chill and fever in amphotericin B and its liposome groups were 21% and 10% (P>0.05), hypopotassemia 34% and 14% (P=0.03), hepatic impairment 22% and 17% (P>0.05), and renal impairment 9% and 3%, respectively (P>0.05).. The therapeutic effect for IFI of amphotericin B and its liposome was similar. The severe adverse reaction of amphotericin B liposome was slightly lower than that of amphotericin B.

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Hematologic Diseases; Humans; Liposomes; Mycoses; Retrospective Studies; Treatment Outcome

Invasive mold infections (IMI) are a leading cause of infectious mortality in allogeneic stem cell transplant (AlloSCT) recipients. Fluconazole, the current standard for fungal prophylaxis, is ineffective against molds. We initiated a pilot study to determine the safety and activity of prophylactic liposomal amphotericin B (AMB) in preventing IMI in pediatric and adolescent AlloSCT recipients during the first 100 days.. Fifty-one patients (57 AlloSCT) were given AMB (3 mg/kg/day) intravenously, day 0-100. Median age 6 years, 32 males, 19 females. Donors: 33 unrelated and 2 related cord blood, 13 related and 1 unrelated peripheral blood stem cell and 8 related bone marrow (BM); 30 received myeloablative and 27 reduced intensity conditioning. Graft-versus-host disease (GVHD) prophylaxis comprised tacrolimus and mycophenolate mofetil.. Median follow-up is 557 days. AMB was generally well tolerated. The probability of developing >/=grade II acute GVHD and extensive chronic GVHD was 45% and 7%, respectively. Estimated 1-year OS is 62.4% for all patients with 78.8% and 26.7% for average-risk and poor-risk, respectively. The incidence of IMI was 0%.. These results suggest prophylactic AMB is tolerable and may prevent IMI, especially Aspergillus, during the first 100 days post AlloSCT in pediatric and adolescent patients. A randomized study is needed to determine the efficacy of this approach.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematologic Diseases; Humans; Infant; Male; Mycoses; Postoperative Complications; Stem Cell Transplantation

We report 2 pediatric cases of cerebral fungal infection. A patient with severe aplastic anemia developed an Aspergillus species brain abscess and pulmonary aspergillosis after peripheral blood stem cell transplantation. Despite administration of micafungin, amphotericin B, and flucytosine, the patient died 2 months after the transplantation because of underlying pulmonary aspergillosis. Another patient with acute myelogenous leukemia developed a huge brain abscess with histopathologic findings suspicious of mucormycosis. This patient was cured with combination therapy of antifungal agents and intensive surgery, without sequelae. It is important to perform aggressive multimodality treatment, when indicated, including surgical intervention, even if in myelosuppression.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Central Nervous System Fungal Infections; Child; Drug Combinations; Echinocandins; Fatal Outcome; Female; Flucytosine; Follow-Up Studies; Graft Rejection; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lipoproteins; Magnetic Resonance Imaging; Male; Micafungin; Mucormycosis; Peripheral Blood Stem Cell Transplantation; Remission Induction; Treatment Outcome

A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure.. Physical examination, blood and urine analyses, kidney biopsy and tonicity balance.. Fanconi syndrome with proximal (type II) renal tubular acidosis caused by myeloma kidney. Renal tubular acidosis was complicated by probable nephrogenic diabetes insipidus and acute renal failure.. Potassium supplementation, sodium bicarbonate therapy, intravenous fluid therapy and dialysis.

Topics: Acidosis, Renal Tubular; Acute Kidney Injury; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Diabetes Insipidus, Nephrogenic; Fanconi Syndrome; Hematologic Diseases; Humans; Male; Multiple Myeloma; Myelodysplastic Syndromes

A case of sinus-orbital Rhizopus microsporus var. rhizopodiformis infection in a patient with graft versus host disease following allogeneic blood stem cell transplantation is reported. Commercially available pea straw compost used for gardening was suspected to be the source of the infection. After an initial relapse, treatment with surgical debridement, liposomal amphotericin B and posaconazole was successful.

Topics: Adult; Amphotericin B; Eye Infections, Fungal; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Orbital Diseases; Paranasal Sinus Diseases; Rhizopus; Soil; Soil Microbiology; Transplantation, Homologous; Triazoles; Zygomycosis

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Administration Schedule; Drug Combinations; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney; Middle Aged; Mycoses; Treatment Outcome

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the 'proven' group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Cyclosporine; Female; Graft Survival; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Infant; Liposomes; Male; Middle Aged; Mycoses; Opportunistic Infections

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney Diseases; Middle Aged; Mycoses

To assess whether a continuous infusion of amphotericin B (CI-AmB) is less nephrotoxic than a 4 h infusion in haematology patients with fever and neutropenia, including bone-marrow transplant recipients. Efficacy was assessed as a secondary end-point.. We conducted a retrospective cohort study over a 2 year period. A total of 1073 haematology admissions were reviewed (98.3% complete) and 81 admissions were eligible for study entry; 39 received CI-AmB and 42 a 4 h infusion of AmB.. Renal impairment occurred significantly less frequently with CI-AmB compared with a 4 h infusion of AmB [10% versus 45%, respectively, odds ratio (OR) 0.14; 95% confidence interval (CI) 0.04-0.5, P < 0.001]. The difference was maintained among allogeneic transplant recipients (P = 0.007) and patients receiving concurrent nephrotoxic drugs (P < 0.001). An AmB infusion rate of <0.08 mg/kg/h was associated with a significant reduction in renal impairment (P < 0.001). A difference in survival was observed between the continuous and 4 h infusion of AmB (95% versus 79%, respectively, OR 5.1; 95% CI 1.02-25.1, P = 0.03).. CI-AmB appears to be significantly less nephrotoxic than 4 h infusion AmB in haematology patients with fever and neutropenia--including high-risk bone-marrow transplant recipients--without increasing mortality. An AmB infusion rate of <0.08 mg/kg/h appears to be a safe threshold, associated with reduced renal impairment.

Topics: Amphotericin B; Antifungal Agents; Cohort Studies; Drug Administration Schedule; Female; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Mycoses; Retrospective Studies; Time Factors

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Drug Combinations; Female; Hematologic Diseases; Humans; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Follow-Up Studies; Hematologic Diseases; Hospital Mortality; Humans; Immunocompromised Host; Liver Transplantation; Lung; Lung Diseases, Fungal; Male; Pneumonectomy; Retrospective Studies; Time Factors; Tomography, X-Ray Computed

Conventional amphotericin B (Amph-B) is the drug of choice for treating systemic fungal infections. Recently, a new formulation has become available, encapsulated in liposomes (Amph-lip). This new form of administration was developed in order to lower the acute side effects and to offer the possibility of administering high doses of amphotericin B. Experience with Amph-lip is limited, especially in children. We treated four children with documented systemic fungal infections with Amph-lip and administered it empirically to 12 children. Fifteen of these 16 children were severely granulocytopenic oncologic patients. One 3-month-old baby suffered from systemic candidiasis. Amph-lip was preferred to conventional Amph-B in children with organ dysfunction developing as a consequence of conventional chemotherapy or bone marrow transplantation, after failure of conventional Amph-B to improve a fungal infection, and after adverse drug reactions had occurred. The daily doses of Amph-lip ranged from 1 to 6 mg/kg (median 3 mg/kg), the cumulative doses from 13 to 311 mg/kg (median 75 mg/kg). Acute adverse reactions or organ function abnormalities attributable to Amph-lip did not occur in 402 administrations. Amph-lip has proven to be well tolerated by children in terms of acute toxicity and in the long term. Although large cumulative doses were given, organ function abnormalities attributable to Amph-lip doses were not detected in any of ten long-term survivors over a median observation time of 36 months (range 30-44 months). Amph-lip appears to be a promising alternative antifungal treatment, especially for patients with impaired organ function, when high doses of amphotericin B are necessary.

Topics: Adolescent; Agranulocytosis; Amphotericin B; Bone Marrow Transplantation; Child; Child, Preschool; Drug Carriers; Hematologic Diseases; Humans; Immunocompromised Host; Infant; Leukemia; Liposomes; Lymphoma; Mycoses; Time Factors; Treatment Outcome

Topics: Acyclovir; Amphotericin B; Bacteremia; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Herpesviridae Infections; Humans; Immunocompromised Host; Mycobacterium Infections; Mycoses

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; gamma-Globulins; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematologic Diseases; Humans; Leukopenia; Mycoses; Sepsis

This report reviews 48 episodes of hospital-acquired fungemia that occurred over a four-year period at a large community teaching hospital. The incidence of hospital-acquired fungemia increased eightfold during the study period. Candida albicans (58%), Candida tropicalis (25%), and Candida parapsilosis (15%) were the most common fungal pathogens isolated from blood cultures. Twenty-one patients (44%) had concomitant bacteremia. Intravascular catheters (100%), antibiotic administration (98%), urinary catheters (81%), surgical procedures (65%), parenteral alimentation (60%), and corticosteroid administration (54%) were the most common predisposing factors. The overall mortality rate was 75%. Hospitalization on the medical service, age greater than 60 years, and hospital stay less than 100 days were associated with a significantly increased mortality rate.

Topics: Adult; Amphotericin B; Candidiasis; Cross Infection; Hematologic Diseases; Hospitals, Community; Hospitals, Teaching; Humans; Middle Aged; Retrospective Studies; Sepsis

Topics: Acute Disease; Administration, Oral; Adult; Amphotericin B; Female; Hematologic Diseases; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma; Mycoses

In a prospective study from May 1971 to November 1973, 20 consecutive patients with a diagnosis of disseminated cryptococcosis were treated for six weeks with a combination of amphotericin B (20 mg daily) intravenously and flucytosine (150 mg/kg daily) orally. Fifteen patients has culturally docummented Cryptococcus neoformans meningitis, and three died of infection early in therapy. Of the remaining 12 patients, eight were alive and well eight to 34 months after therapy, and four died of other causes. None of the surviving patients has relapsed. Hematologic complications developed in nine patients, three of whom had no underlying lymphoreticular disorder or therapy with known cytotoxic agents. Renal insufficiency of mild degree occurred in only six patients. A shorter period of hospitalization and reduction in toxicity of amphotericin B suggest that combined therapy is a safe and efficacious alternative to other regimens.

Topics: Adult; Aged; Amphotericin B; Cryptococcosis; Cytosine; Drug Therapy, Combination; Female; Flucytosine; Hematologic Diseases; Humans; Kidney; Male; Meningitis; Middle Aged; Prospective Studies

Topics: Amphotericin B; Brain Diseases; Cryptococcosis; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Meningitis