amphotericin-b and Hematologic-Neoplasms

Mucormycosis has emerged as an increasingly important fungal disease for immunocompromised children and neonates, with the cutaneous form being one of its most common presentations.. We present a cutaneous mucormycosis case in a 10-year-old girl and analyse reports of single cases and case series of cutaneous mucormycosis in ≤16-year-old patients, recorded in PUBMED from 1953 to 2020, for epidemiology, risk factors, diagnostic and therapeutic procedures and outcome.. 113 cases were enrolled. Median age was 5 years (Interquartile Range [IQR] 10.9), without gender predominance. Underlying conditions were haematologic malignancies/disorders (25.7%), prematurity (23%), solid organ transplantation (3.5%), diabetes mellitus type 1 (4.4%), immunodeficiency and other diseases (14.2%), and no underlying conditions (29.2%). Inoculation occurred through major trauma (12.4%), including surgery and motor vehicle accidents, catheter sites (27.4%), dressings, patches and probes (11.5%), burns and farm-related accidents (8.8%). Rhizopus spp. was most frequently isolated (43.4%), followed by Lichtheimia corymbifera (9.7%), Saksenaea vasiformis (8%), Mucor and Rhizomucor spp. (5.3% each), other species/combinations (7.2%) and unspecified isolates (21.2%). Surgery was combined with antifungals in 62.8%. Each was performed solely in 27.4% and 6.2%, respectively. Amphotericin B was used in 78% (alone in 55.8% and combined with other antifungals in 22.2%) of the cases. Overall mortality was 26.5%. In regression analysis, prematurity and haematologic malignancies/disorders were associated with increased mortality, whereas combination of antifungals and surgery with improved survival.. Cutaneous mucormycosis mainly affects premature infants and children with haematologic malignancies/disorders. Outcome is improved when active antifungal therapy and surgery are combined.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Infant, Newborn; Mucormycosis; Neoplasms; Rhizopus

Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients.. To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections.. A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis.. We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived.. Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Hematologic Neoplasms; Humans; Registries; Trichoderma; Voriconazole

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Brain Abscess; Central Nervous System; Female; Hematologic Neoplasms; Humans; Mucormycosis; Voriconazole

Topics: Adolescent; Adult; Allografts; Amphotericin B; Central Nervous System Fungal Infections; Child; Disease-Free Survival; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Survival Rate; Voriconazole

Cases of invasive Trichosporon infections have increasingly emerged; it is now the second leading cause of yeast bloodstream infections after Candida spp., particularly in the immunosuppressed population, where it often causes breakthrough fungemia with high mortality.. We present a case report of a breakthrough Trichosporon asahii infection in a patient with acute myeloid leukemia and review all of the cases of breakthrough Trichosporon spp. infections published in the literature to date.. We extracted 68 cases of breakthrough Trichosporon spp. infections, wherein 95.5% patients had hematological malignancy, 61.8% of them occurred in the presence of echinocandins, 22% of triazoles, 13.2% of amphotericin and 3% of other combinations of antifungals. The most prevalent manifestation was fungemia (94%); 82.8% of these were associated with the presence of a central venous catheter. The overall mortality was 68.7%; the patients who survived recovered from the neutropenic event.. Invasive trichosporonosis is an acute fatal condition that occurs in immunosuppressed patients, usually under antifungal selective pressure. Typically, neutropenia and its underlying diseases are associated with adverse outcomes.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Venous Catheters; Echinocandins; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Mortality; Neutropenia; Triazoles; Trichosporon; Trichosporonosis; Voriconazole

Invasive fungal diseases carry high morbidity and mortality in patients undergoing chemotherapy for hematological malignancies or allogeneic hematopoietic stem cell transplantation. In order to prevent these life-threatening infections, antifungal chemoprophylaxis plays an important role in daily clinical practice. Broad-spectrum antifungal triazoles are widely used but exhibit disadvantages such as relevant drug-drug interactions. Therefore, amphotericin B products or echinocandins can be an alternative in selected patient populations. As these compounds are available as intravenous formulations only, there is growing interest in extended dosing regimens. Although not approved for these agents, this strategy is a rational option, as these compounds have properties suitable for this strategy, including dose-proportional pharmacokinetics, prolonged elimination half-life, and a large therapeutic window. As the use of extended dosing regimens in antifungal prophylaxis is expanding in clinical practice, we reviewed the pharmacokinetic and pharmacodynamic rationale for this strategy, animal model data, dose escalation studies, and clinical trials supporting this concept.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Echinocandins; Hematologic Neoplasms; Humans; Mycoses; Transplant Recipients; Transplantation, Homologous

Mucormycosis is a severe infection that affects a variety of patients, including immunocompromised children and neonates. Given improved survival rates from advances in the treatment of malignancies, the population at risk for mucormycosis is increasing. We conducted a systematic review of cases of mucormycosis in children in the English-language literature reported between August 2008 and June 2017 and analyzed the clinical characteristics, diagnosis, management, and outcome of those infections. The most common underlying diagnoses included neutropenia (41%), hematologic malignancy (39%), prematurity (13%), and hematopoietic stem cell transplant (11%). Sinus disease (28%) and disseminated disease (24%) were the most common presentations. Rhizopus spp were the most common organisms isolated (22%). Amphotericin B remains the backbone of treatment and was prescribed in 86% of these cases. The resulting mortality rate remains high (32%). We provide here the results of a literature review of mucormycosis in children, including its epidemiology and clinical manifestations, and describe current advances in its diagnosis and treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Databases, Factual; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Male; Mucormycosis; Neutropenia; Paranasal Sinus Diseases; Rhizopus; Treatment Outcome

Invasive fusariosis in solid organ transplant is uncommon and usually presents as localized infection with favorable outcomes compared to hematologic malignancies or bone marrow transplants. We report the first case of Fusarium osteomyelitis in a patient following multi-visceral transplant and review Fusarium in organ transplant recipients and Fusarium bone and joint infections. Our case underscores the importance of early recognition and multidisciplinary approach to treatment and highlights potential failure to eradicate with amphotericin B monotherapy.

Topics: Abdomen; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Fatal Outcome; Fusariosis; Fusarium; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Osteomyelitis; Tomography, X-Ray Computed; Transplants; Voriconazole

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Hematologic Neoplasms; Humans; Lymphoma; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine-based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin-B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.

Topics: Adult; Amphotericin B; Antifungal Agents; Central Venous Catheters; Drug Resistance, Fungal; Echinocandins; Fatal Outcome; Female; Geotrichosis; Geotrichum; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Italy; Leukemia, Myeloid, Acute; Liver; Lung; Lymphoma, Mantle-Cell; Male; Microbial Sensitivity Tests; Middle Aged; Spleen; Tomography, X-Ray Computed; Young Adult

Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Biomarkers; Echinocandins; Hematologic Neoplasms; Humans; Neutropenia; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Tomography, X-Ray Computed; Voriconazole

The risk of invasive fungal infections (IFIs) is extremely high in patients with hematological malignancies due to the prolonged and profound neutropenia and immunosuppression after chemotherapy and hematopoietic stem cell transplantation. There has been increasing interest in mucormycosis despite its relatively uncommon occurrence, because occasional breakthrough infections have been observed under anti-aspergillus prophylaxis. The aggressive nature of mucormycosis easily leads to high mortality because of delays in diagnosis and incorrect treatment decisions, which are due in part to lack of adjunctive diagnostic tools and having similar clinical and radiological features with aspergillosis. The only currently available antifungals against Mucorales in Japan are amphotericin B formulations. Thus, comprehensive therapeutic strategies, including surgery, should be considered in order to achieve a successful outcome.

Topics: Amphotericin B; Didanosine; Early Diagnosis; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lung Diseases, Fungal; Mucormycosis; Neutropenia; Risk; Surgical Procedures, Operative

The process of allogeneic HSCT in children is associated with frequent AKI and mortality, but the epidemiology is not widely reported. The aim of this review was to summarize the available evidence on incidence, risk factors, timing, and prognosis of AKI in children following HSCT. We systematically reviewed all observational studies reporting incidence and outcomes of AKI in pediatric allogenic HSCT recipients. The minimum criteria for AKI were defined as an increase in sCr ≥ x1.5 or urine output ≤0.5 mL/kg/min over six h. Medline and Embase were searched until March 2014. From 993 electronic records, five were eligible for inclusion (n = 571 patients). The average incidence of AKI within the first 100 days following HSCT was 21.7% (range 11-42%), and the average time of onset was 4-6 wk post-transplant. Risk factors for AKI included cyclosporine toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There were conflicting reports on whether AKI was associated with the development of CKD. AKI is a common and potentially life-threatening complication following HSCT in children. Further quality observational studies are needed to accurately determine the epidemiology and prognosis of AKI in this population.

Topics: Acute Kidney Injury; Adolescent; Amphotericin B; Biomarkers; Child; Cyclosporine; Foscarnet; Glomerular Filtration Rate; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Prognosis; Risk Factors; Transplantation, Homologous; Treatment Outcome

Treatment with Amphotericin B (AmB) deoxycholate, which is still used widely, particularly in low-resource countries, has been challenged due to nephrotoxicity. We sought to study whether continuous infusion of AmB deoxycholate reduces nephrotoxicity retaining, however, the effectiveness of the drug.. PubMed and Scopus databases were systematically searched to identify studies comparing the outcomes of patients receiving 24-h infusion of AmB ("continuous group") and those receiving 2-6-h infusion of AmB ("conventional group"). Nephrotoxicity and all-cause mortality were the primary outcomes of the review, while treatment failure was the secondary outcome.. Five studies met the inclusion criteria; one randomized controlled trial, two prospective cohort studies, and two retrospective cohort studies. The majority of patients were neutropenic with an underlying hematologic malignancy. All 5 studies (392 patients) provided data regarding the development of nephrotoxicity. A non-significant trend towards lower nephrotoxicity was observed for patients receiving continuous infusion of AmB compared with those receiving conventional infusion [RR = 0.61 (95% CI 0.36, 1.02)]. Four studies (365 patients) provided data regarding mortality; no relevant difference was detected between patients receiving continuous and those receiving conventional infusion of AmB [RR = 0.81 (95% CI 0.36, 1.83)]. Data on treatment failure of the two methods of administration was insufficient for meaningful conclusions.. The available evidence from mainly non-randomized studies suggests that continuous infusion of AmB deoxycholate might offer an advantage over the conventional infusion regarding the development of nephrotoxicity, without compromising patient survival. Further randomized studies are needed to investigate this issue.

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Hematologic Neoplasms; Humans; Infusions, Intravenous; Kidney Diseases; Mycoses; Neutropenia; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Treatment Outcome

Patients with acute leukemia and hematopoietic stem cell transplant recipients are at risk of a spectrum of invasive fungal diseases corresponding to the type and intensity of immunosuppression. The development of newer antifungal agents has broadened therapeutic options. In the 1990s, lipid formulations of amphotericin B became widely used as safer alternatives to amphotericin B deoxycholate. In addition, fluconazole was shown to be beneficial as a yeast-active prophylaxis in hematopoietic stem cell transplant recipients. In the past decade, the antifungal armamentarium was further enhanced with the availability of extended-spectrum azoles and echinocandins. The development of effective broad-spectrum antifungal agents has led to their use as prophylaxis rather than delaying treatment until clinical signs of infection manifest. Antigen-based and PCR-based diagnostic adjuncts facilitate earlier detection of invasive fungal diseases compared with conventional culture, and have been incorporated into strategies in which initiation or modification of an antifungal regimen is targeted to patients with the highest likelihood of having fungal disease. Here, we review the pharmacological data and major clinical trials that guide the use of antifungals, as well as areas of uncertainty and future perspectives.

Topics: Amphotericin B; Antifungal Agents; Azoles; Clinical Trials as Topic; Echinocandins; Fluconazole; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mycoses; Yeasts

Zygomycosis is an invasive infection that can occur particularly in patients with haematological malignancy. The causative fungi are members of the order Mucorales, and individual species within this group require a high level of laboratory skill to be identified. Zygomycosis can present as rhinocerebral, pulmonary, or disseminated disease, with a rapid clinical course. The optimal management of these cases requires early diagnosis, aggressive antifungal therapy and, when possible, surgical debridement. Founded on clinical experience, but without the benefit of comparative studies, liposomal amphotericin B has become the therapeutic agent of choice. Posaconazole is an orally administered triazole with a demonstrated in vitro and in vivo activity against most Zygomycetes that is comparable to that of amphotericin B. Studies on salvage therapy with posaconazole have yielded promising results, and successful case reports are also available. As an adjuvant approach, iron chelation with deferasirox has shown promising results, although clinical experience is still limited.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Granulocytes; Hematologic Neoplasms; Humans; Hyperbaric Oxygenation; Iron Chelating Agents; Neutrophils; Risk Factors; Triazoles; Zygomycosis

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

The respiratory tract is the most common system affected by aspergillosis in children with hematologic malignancies. However, Aspergillus spp. tend to invade blood vessels, resulting in systemic dissemination to multiple organs including, but not limited to, the brain, bones, liver, kidneys, and skin. Because early diagnosis and treatment are critical to the patient's outcome, a high index of suspicion should be maintained in children with hematologic malignancies who are neutropenic and have prolonged fever that is unresponsive to systemic antibacterials. Several diagnostic modalities should be used simultaneously in order to establish the diagnosis in an expeditious manner. Detailed radiographic evaluations with plain radiographs, and CT scans of the chest, sinuses, brain, and other organs should be performed as soon as clinical suspicion is raised. Detection of circulating antigens, such as galactomannan and 1,3-beta-glucan, and polymerase chain reaction appear promising in aiding in the diagnosis. A definitive diagnosis requires both a positive culture from a sterile site and evidence of tissue damage demonstrated by imaging studies or microscopic evaluations of sites of infection. Because the mortality rate is very high, empiric systemic antifungal therapy with amphotericin B, or one of its lipid formulations, should be initiated while laboratory investigations to substantiate or refute the diagnosis are continued. Surgical intervention is associated with a high mortality rate but may be of benefit in children with localized disease.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Drug Therapy, Combination; Hematologic Neoplasms; Humans; Triazoles

Invasive fungal infections are an important cause of morbidity and mortality in patients with hematological malignancies. In particular, patients with neutropenia and those who have undergone allogeneic hematopoietic stem cell transplantation are at highest risk, with fungal pneumonia being the main clinical manifestation in these patients. The most common pathogens associated with fungal pneumonia are Aspergillus spp. and Zygomycetes. However, other pathogens have also been observed in fungal pneumonia, including Cryptococcus spp., Pneumocystis jirovecii, and Candida spp. This comprehensive review will focus on the important practical aspects relevant to the epidemiology, clinical diagnosis, and therapeutic management of pneumonia due to filamentous fungi in patients affected by hematological malignancies.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Pneumonia; Zygomycosis

Topics: Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Hematologic Neoplasms; Humans; Infusions, Intravenous; Kidney; Mycoses; Time Factors

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Deoxycholic Acid; Drug Combinations; Echinocandins; Hematologic Neoplasms; Humans; Itraconazole; Lipopeptides; Liposomes; Mycoses; Organ Transplantation; Peptides, Cyclic; Pyrimidines; Risk Factors; Stem Cell Transplantation; Triazoles; Voriconazole; Zygomycosis

Aspergillosis is a potentially lethal infection of immunocompromised patients. Until 10 years ago, antifungal therapy was largely limited to amphotericin B deoxycholate. Perceived poor response rates and inherent toxicities with amphotericin B deoxycholate were a major stimulus for the development of newer antifungals, including lipid-formulated amphotericin B, broad spectrum azoles, and echinocandins. Response rates to antifungals are highly dependent on the underlying diagnosis and degree of immune suppression of the patient. Patients at highest risk of death from aspergillosis also have very high mortality rates from other causes as well. Outcomes reported in historical literature reviews fail to distinguish between overall mortality and death attributable to aspergillosis. While this distinction can often be difficult to assess clinically, the net effect is to underestimate the therapeutic success rates of antifungals. The CLEAR (Collaborative Exchange of Antifungal Research) project started as a post approval survey to monitor clinical use of amphotericin B lipid complex (ABLC). The scope of the CLEAR project included collection of clinical data to assess outcomes in patients with invasive fungal infections treated with ABLC. Clinical data from more than 3500 patients were entered into the CLEAR database. Outcomes were assessed for 509 patients with documented aspergillosis and complete data records. Overall response rate was 63% (cured/improved/stable) with site-specific response rates of 61%, 59%, and 32% for lung, sinus, and central nervous system infections, respectively. Solid organ transplant recipients had higher response rates than patients with hematological malignancies. Bone marrow transplant recipients had the lowest response rates. Clinical response rates with ABLC reported in the CLEAR trial are higher than response rates reported for amphotericin B deoxycholate in other trials. Since it is unlikely we will see any new comparative Phase III trials for aspergillosis, CLEAR-type outcome studies will prove useful for the foreseeable future to guide clinical management of aspergillosis.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Clinical Trials as Topic; Databases, Factual; Hematologic Neoplasms; Humans; Immunocompromised Host; Organ Transplantation; Treatment Outcome

There is still no consensus on the efficacy of antifungal prophylaxis in neutropenic patients after more than 50 clinical trials.. This review evaluates the current evidence from all available meta-analyses of the use of intravenous amphotericin B, fluconazole and itraconazole for this indication.. Four systematic reviews with meta-analysis and one evidence-based review without meta-analysis were evaluated. Efficacy of fluconazole has been shown on short-term follow-up after allogeneic stem cell transplantation but only itraconazole was effective in neutropenic patients with haematological malignancies for prolonged prophylaxis after allogeneic stem cell transplantation. Direct comparison between fluconazole and itraconazole for this indication shows the superiority of itraconazole which was the only drug able to prevent invasive Aspergillus infections in our previously published meta-analysis of 13 trials and 3597 patients. Efficacy of itraconazole correlates closely with its dose; an effect was seen only in clinical trials using at least 400 mg/day oral solution or 200 mg/day intravenous solution. With this dose, invasive fungal infections were reduced by 53% and mortality from invasive fungal infections was reduced by 47% (P<0.05). Toxicity of itraconazole is rare and usually not severe and drug interactions are easily manageable.. Itraconazole is recommended for antifungal prophylaxis in high-risk neutropenic patients with haematological malignancies or for prolonged prophylaxis after allogeneic stem cell transplantation based on unambiguous evidence of efficacy and low toxicity from clinical trials and systematic reviews.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Hematologic Neoplasms; Humans; Itraconazole; Mycoses; Neutropenia; Stem Cell Transplantation

To evaluate the clinical characteristics of patients affected by hematologic malignancies who developed mucormycosis and to ascertain the factors which influenced the outcome following mycotic infection.. This was a retrospective study conducted over a 15-year period (1987-2001). The study included 59 patients with hematologic malignancies with a proven or probable mucormycosis admitted in 18 Hematology Divisions in tertiary care or university hospitals.. The most frequent sites of infection were lung (64%) and orbito-sinus-facial (24%); cerebral involvement observed in 19% of cases was always associated with other sites of infection. Antifungal treatment was empirically administered in 49 patients (83%); 7 patients underwent radical surgical debridement (12%). Therapy was successful for only 18 patients (37%). Forty-seven patients died within 3 months of the diagnosis of fungal infection: the cause of death was mucormycosis in 41 patients (87%) and progression of hematologic disease in 6 patients (13%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: male sex, amphotericin B treatment, neutrophil recovery from post-chemotherapy aplasia. At multivariate analysis, the only factor that significantly correlated with recovery from infection was the liposomal amphotericin B treatment.. Mucormycosis is a rare filamentous fungal infection that occurs most frequently in neutropenic patients with acute leukemia. It does not seem to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential in order to improve the prognosis in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Encephalitis; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Italy; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Neutropenia; Retrospective Studies; Risk Factors; Sinusitis; Treatment Outcome; Triazoles

Invasive fungal infection is an increasing source of morbidity and mortality in patients with hematologic malignancies, particularly those with prolonged and severe neutropenia (absolute white blood cell count < 100/microL). Early diagnosis of invasive fungal infection is difficult, suggesting that antifungal prophylaxis could be the best approach for neutropenic patients undergoing intensive myelosuppressive chemotherapy. Consequently, antifungal prophylaxis has been extensively studied for more than 20 years. Nonabsorbable polyenes reduce superficial mycoses but are not effective in preventing or treating invasive fungal infections. Intravenous amphotericin B and the newer azoles were used in numerous clinical trials, but the value of antifungal prophylaxis in defined risk groups with cancer is still open to discussion. Recipients of allogeneic stem cell transplants and patients with a relapsed leukemia are high-risk patient populations. In addition, certain risk factors are well defined, for example, neutropenia more than 10 days, corticosteroid therapy, sustained immunosuppression, and graft-versus-host disease. In contrast to study efforts, evidence-based recommendations on the clinical use of antifungal prophylaxis according to risk groups are rare. The objective of this review of 50 studies accumulating more than 9000 patients is to assess evidence-based criteria with regard to the efficacy of antifungal prophylaxis in neutropenic cancer patients.

Topics: Adrenal Cortex Hormones; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Clinical Trials as Topic; Disease Susceptibility; Drug Carriers; Evidence-Based Medicine; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Liposomes; Mycoses; Neutropenia; Recurrence; Risk Factors; Triazoles

A number of recent developments in the supportive care of hematological malignancies have been selected for critical discussion. The first section focuses on the role of evidence-based guidelines in influencing the use of hematopoietic growth factors in medical practice. The next section updates the current clinical status of amifostine (Ethyol, Alza Corp., Palo Alto CA, USA, and US Bioscience, West Conshohocken, PA, USA) the first broad-spectrum cytoprotective agent available. The management of invasive fungal infections and the use of liposomal antifungal agents are reviewed next. Finally, the current status of transfusion support is presented.

Topics: Adult; Amifostine; Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Blood Transfusion; Bone Marrow; Clinical Trials, Phase I as Topic; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Infection Control; Neutropenia; Patient Care; Practice Guidelines as Topic; Radiation-Protective Agents; Societies, Medical; Transfusion Reaction

Patients with haematological malignancies form one of the most susceptible host groups for microbial infection, especially during neutropenia. The incidence of invasive fungal infections has increased in recent years, highlighting the need for better diagnosis and more effective antifungal therapies. Amphotericin B is the drug of choice for many fungal infections, although toxicity and the need for intravenous infusion restrict its use. When possible, oral administration of antifungal agents is preferable but intravenous administration is often needed and current oral agents have their limitations: fluconazole because of a narrow spectrum of activity; itraconazole capsules because of erratic absorption. In this review, prophylactic and treatment options for systemic fungal infections are discussed. The specific needs of patients with different types of leukaemia and the benefits of new amphotericin B and itraconazole formulations are examined.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Hematologic Neoplasms; Humans; Itraconazole; Leukemia; Mycoses

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Bone Marrow Transplantation; Disease Management; Hematologic Neoplasms; Humans; Hyperbaric Oxygenation; Itraconazole

Febrile neutropenia, a serious complication that can occur during the treatment of hematological malignancies, can sometimes be fatal owing to fungal infection. Prospective randomized trials indicated the utility of liposomal amphotericin B or caspofungin as an empirical antifungal therapy. Itraconazole, a broad-spectrum tri azole antifungal agent, is poorly absorbed in the intestines after oral absorption and makes it difficult to achieve a stable serum drug concentration. Therefore, an intravenous formulation might offer a potentially safer and more effective alternative. To compare the efficacy and safety of empirical antifungal therapy, patients will be randomly assigned to either the liposomal amphotericin B 3.0 mg/kg once daily group or the intravenous itraconazole 200 mg dose group with five stratification factors (disease risk, previous antifungal prophylaxis, age, sex, and institute). The primary endpoint will be overall favorable response, comprising five secondary endpoints: successful treatment of baseline infection by the end of the treatment; absence of breakthrough infection; no discontinuation of the antifungal treatment due to drug-related toxicity; fever resolution during neutropenia; and 7-day survival after termination of the antifungal treatment. The target sample size of 850 subjects is sufficient to prove the non inferiority of itraconazole compared with liposomal amphotericin B, with a non-inferiority margin of 10%, one sided significance level of 5%, and power of 90%.

Topics: Amphotericin B; Antifungal Agents; Equivalence Trials as Topic; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Itraconazole; Multicenter Studies as Topic; Neutropenia; Prospective Studies; Randomized Controlled Trials as Topic

Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required.. We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever.. Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d).. Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07).. ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.

Topics: Administration, Intravenous; Adult; Aged; Amphotericin B; Antifungal Agents; Chemotherapy-Induced Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Mycoses; Young Adult

Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycoses; Prospective Studies; Young Adult

Febrile neutropenic patients are at greater risk of getting bacterial and fungal infections. Empirical antifungal therapy is considered if the fever persists despite broad-spectrum antibiotics including vancomycin. However, the timing of initiating empirical antifungal therapy can vary from 3 to 8 days of non-response to antibiotics. We choose to determine the response of empirical amphotericin B deoxycholate (dAMB) starting either on day 4 or day 8 in febrile neutropenic patients not responding to broad-spectrum antibiotics and without localisation of fever. Fifty-six patients with persistent neutropenic fever despite 72 h of antibiotic therapy were randomly assigned to receive dAMB either starting on day 4 (group A, n = 27, median age 23 years) or starting on day 8 (group B, n = 29, median age 25 years). Satisfactory response (patient remaining afebrile for 48 h and maintaining absolute neutrophil count >500 μl(-1) ) occurred in 85.2% of patients in group A vs. 69.5% in group B (P = 0.209). Patients in group A took significantly fewer days to become afebrile than group B (5.4 ± 3.9 days vs. 11.3 ± 4.0 days, P = 0.0001). The adverse side effects of dAMB (nephrotoxicity, hypokalemia and hypomagnesemia) occurred at similar rates in both groups. Early addition of empirical dAMB in febrile neutropenic patients leads to their early defervescence and decreased dose requirement.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Drug Therapy; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Time Factors; Treatment Outcome; Young Adult

An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Biomarkers; Female; Fungal Polysaccharides; Galactose; Hematologic Neoplasms; Humans; Male; Mannans; Pyrimidines; Survival Analysis; Treatment Outcome; Triazoles; Voriconazole

In patients with hematologic malignancy, invasive aspergillosis continues to be associated with high mortality even when treated with conventional antifungal therapy. To investigate novel antifungal agents, we compared 53 patients who received posaconazole salvage therapy to 52 contemporary control patients who received high-dose lipid formulation of amphotericin B (HD-LPD/AMB at > or = 7.5 mg kg(-1) per day) and 38 other control patients who received caspofungin plus HD-LPD/AMB. Patients in the three groups had similar. The overall response rate to salvage therapy was 40% for posaconazole, 8% for HD-LPD/AMB (P < or = 0.001) and 11% for combination therapy (P < 0.002). Aspergillosis contributed to the death of 40% of posaconazole group, 65% of the HD-LPD/AMB group and 68% of the combination group (P < or = 0.008). By multivariate analysis, posaconazole therapy independently improved response (9.5; 95% confidence interval, 2.8-32.5; P < 0.001). HD-LPD/AMB alone or in combination was associated with a significantly higher rate of nephrotoxicity (P < or = 0.02) and hepatotoxicity (P < 0.03). In conclusion, posaconazole salvage therapy demonstrated greater efficacy and safety than HD-LPD/AMB alone or in combination with caspofungin in the salvage therapy of invasive aspergillosis in hematologic malignancy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Caspofungin; Combined Modality Therapy; Drug Combinations; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Itraconazole; Lipopeptides; Male; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Pyrimidines; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly high-dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (>1.5 times from baseline values; n=5), hypotension and pain (n=1), and violent chest pain and arrhythmia (n=1). The overall frequency of infusion-related reactions was 29% (n=6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycoses; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous

Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients.. In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups.. Significantly fewer itraconazole patients discontinued treatment due to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001). The main reason for discontinuation was a rise in serum creatinine (1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability.. Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cross-Over Studies; Empiricism; Female; Fever of Unknown Origin; Germany; Hematologic Neoplasms; Humans; Infusions, Intravenous; Itraconazole; Male; Middle Aged; Mycoses; Neutropenia; Opportunistic Infections; Patient Dropouts; Treatment Outcome

Despite improved supportive care, and the introduction of less toxic lipid-formulations of amphotericin B deoxycholate and other new antifungal agents the mortality from invasive fungal infection (IFI) in hematology patients remains high. New management strategies are therefore required to improve outcome.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Kidney Diseases; Liposomes; Male; Middle Aged; Mycoses; Postoperative Complications; Treatment Outcome

Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds.. Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high-dose AmB regimen (10 mg/kg daily).. Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high-dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high-dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion-related reactions occurred in 3 patients in the high-dose monotherapy group. A 2-fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high-dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively.. The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Hematologic Neoplasms; Humans; Lipopeptides; Male; Middle Aged; Pilot Projects; Treatment Outcome

Invasive mold infections continue to account for significant morbidity and mortality in immunocompromised patients; outcomes are dependent on both underlying host factors and appropriate therapy. The antifungal armamentarium has gradually increased during the past, with liposomal amphotericin B (L-AMB) being an important representative. Still, the question of what dose to use - a maximum tolerated or a minimum effective - has yet to be answered. On this basis, a randomized trial comparing a high-loading dose regimen with a standard dosing of L-AMB (AmBiLoad trial) for primary therapy of mold infections was initiated. No significant differences in response between the treatment groups were detected, although recipients of the 10-mg/kg daily dose experienced higher rates of nephrotoxicity and hypokalemia. Uncontrolled malignancy and allogeneic stem cell transplantation were significantly associated with poor survival. This article analyzes the study, discusses the rationale and the results and concludes that this study supports the routine application of L-AMB.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Dose-Response Relationship, Drug; Double-Blind Method; Hematologic Neoplasms; Humans; Hypokalemia; Nephrotic Syndrome; Neutropenia; Survival Rate; Treatment Outcome

In a recently reported randomized trial, low-dose intravenous liposomal amphotericin B (L-AmB) reduced the incidence of invasive fungal infections (20.2 vs. 4.6%, p < 0.001) in high-risk patients with hematological malignancies and prolonged neutropenia.. In the present study, we performed a retrospective cost-benefit analysis of L-AmB prophylaxis from the hospital perspective.. Ninety-nine patients were eligible; baseline characteristics were balanced for age, sex, underlying disease, and duration of neutropenia. The mean duration of hospitalization was 42.9 days and 52.3 days in the prophylaxis arm and in patients without antifungal prophylaxis, respectively (p = 0.096). The L-AmB prophylaxis was associated with additional costs of approximately EUR 630 per patient. However, total medication costs (including L-AmB prophylaxis) were EUR 1,219 and EUR 2,815 in patients with L-AmB prophylaxis and in patients in the control arm, respectively (p < 0.001). When involving also costs for medical procedures, the L-AmB prophylaxis reaches a positive net benefit of EUR 1,094 per patient.. Our data shows that antifungal prophylaxis, e.g. with L-AmB, can be a safe and effective strategy to reduce the frequency of invasive fungal infections in selected high-risk patients and to obtain significant cost savings for the hospital.

Topics: Amphotericin B; Antifungal Agents; Comorbidity; Cost of Illness; Cost-Benefit Analysis; Female; Germany; Hematologic Neoplasms; Humans; Incidence; Male; Middle Aged; Mycoses; Neutropenia; Risk Assessment; Risk Factors; Treatment Outcome

We performed a prospective, randomized, open-label trial to evaluate the efficacy of low-dose liposomal amphotericin B (L-AmB) to reduce the incidence of invasive fungal infections (IFI) in patients with hematological malignancies and prolonged neutropenia (>10 days) following intensive chemotherapy.. In 219 neutropenic episodes (NE) of 132 patients randomization was performed. Patients received either 50 mg L-AmB every other day (arm A) or no systemic antifungal prophylaxis (arm B).. In the first NE of each patient the incidence of proven or probable IFI (primary end point) was five of 75 patients (6.7%) in arm A and 20 of 57 patients (35%) in arm B (P=0.001). Invasive aspergillosis occurred less frequently in patients receiving L-AmB-prophylaxis (P=0.0057), whereas the reduction of invasive candidiasis did not reach statistical significance (P=0.0655). In all NE the incidence of IFI was five of 110 NE (4.6%) in arm A versus 22 of 109 NE (20.2%) in arm B (P<0.01). Adverse events, possibly related to L-AmB, were observed in five NE (4.6%) and L-AmB was discontinued in three NE (2.8%). No grade 3 or 4 toxicities were observed.. Antifungal prophylaxis with low-dose L-AmB proved to be feasible and effective in our trial.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Female; Hematologic Neoplasms; Humans; Injections, Intravenous; Male; Middle Aged; Neutropenia

Amphotericin B dexoycholate is currently the standard empirical antifungal therapy for neutropenic patients with hematologic malignancies and who also have persistent fever that does not respond to antibacterial therapy. The antifungal triazoles offer a potentially safer and effective treatment alternative to Amphotericin B dexoycholate.. We assessed the efficacy and safety of intravenous itraconazole, as compared with the efficacy and safety of amphotericin B deoxycholate, as an empirical antifungal therapeutic agent in a matched case-control clinical trial from June 2004 to August 2005.. Efficacy was evaluated in 96 patients (48 received itraconazole and 48 received amphotericin B deoxycholate) and all the patients who received the study drugs were evaluated for safety. The baseline demographic characteristics were well matched. The overall success rates were 47.9% for itraconazole and 43.8% for amphotericin B deoxycholate (% difference: 4.1% [95% confidence interval for the difference: -15.8 to 24]), which fulfilled the statistical criteria for the non-inferiority of itraconazole. The proportions of patients who survived for at least seven days after discontinuation of therapy or who were prematurely discontinued from the study were not significantly different between the two groups. The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in both groups. More patients who received amphotericin B deoxycholate developed nephrotoxicity, hypokalemia or infusion-related events than did those patients who received itraconazole (nephrotoxicity: 16.7% vs. 1.8%, hypokalemia: 66.7% vs. 24.6%, and infusion-related events: 41.7% vs. 3.5%, respectively).. Intravenous itraconazole is as effective as amphotericin B deoxycholate and it is generally better tolerated than amphotericin B deoxycholate when it is given as empirical antifungal therapy for Korean patients with persistent neutropenic fever.

Topics: Adult; Amphotericin B; Antifungal Agents; Case-Control Studies; Chronic Disease; Female; Fever; Hematologic Neoplasms; Humans; Infusions, Intravenous; Itraconazole; Male; Neutropenia

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibody Specificity; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; False Positive Reactions; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Hepatitis; Humans; Liposomes; Male; Middle Aged; Neutropenia; Patient Isolation; Predictive Value of Tests; Sensitivity and Specificity

Invasive candidiasis is a common and serious complication of cancer and its therapy.. We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication.. 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors.. Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Female; Fungemia; Gastrointestinal Neoplasms; Hematologic Neoplasms; Humans; Leukemia; Lipopeptides; Male; Middle Aged; Neoplasms; Neutropenia; Peptides, Cyclic; Retrospective Studies; Species Specificity; United States

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

We treated 74 adults with a hematological malignancy and documented or suspected invasive fungal infection (IFI) with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Forty-five patients (61%) received upfront therapy and 29 patients (39%) received salvage therapy for their IFI. Forty-eight of 71 evaluable patients responded [complete responses in 40 (56%) and partial responses in 8 (11%)] and 15 (21%) died as a consequence of the IFI. Response rates in invasive aspergillosis were 33 out of 49 (67%) for probable/definite cases and 6 out of 11 (55%) for invasive candidiasis. In 40 patients with neutropenia-associated IFI, rapid neutropenic recovery ( < 10 days from study entry) was essential for response to therapy (90% vs. 32%, P < 0.01). Treatment was well tolerated, with 15% infusions followed by infusion-related adverse events, nephrotoxicity in 7% of patients and 11% of withdrawals due to toxicity. These data suggest that intermediate-doses of ABLC may be of similar efficacy than higher doses with less toxicity, making it a cost-effective alternative worthy of study in future trials.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Hematologic Neoplasms; Humans; Lipids; Male; Middle Aged; Mycoses; Salvage Therapy

Conventional amphotericin B (c-AmB) remains the empirical antifungal treatment of choice for neutropenic patients with persistent fever of unknown origin (FUO). Unfortunately, empirical treatment with c-AmB is hampered by its safety profile, with frequent infusion-related adverse events (IRAEs) and renal toxicity. Amphotericin B lipid complex (ABLC) has been investigated for this indication due to its low toxicity profile. The recommended dose of ABLC is 5 mg/kg/d, which is five to seven times higher than the recommended dose of c-AmB.. This randomized, controlled trial includes 105 adult patients with hematologic malignancies and with FUO after receiving chemotherapy or autologous stem cell transplantation. Patients were randomly allocated to receive ABLC at 1 mg/kg/d or c-AmB at 0.6 mg/kg/d for empirical antifungal therapy.. The incidence of renal toxicity was significantly lower in the ABLC group, compared with c-AmB group: 8% vs. 32%, respectively (P = 0.003). The rates of IRAEs were similar in both groups (73% for ABLC vs. 77% for c-AmB). The overall response rate was 72% for ABLC compared with 48% for c-AmB (P = 0.018). This difference was mainly due to the significantly higher renal toxicity in the c-AmB group. The number of emergent fungal infections and overall mortality were similar in both groups.. This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Drug Combinations; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Hypokalemia; Immunocompromised Host; Incidence; Kidney Diseases; Male; Middle Aged; Mycoses; Neutropenia; Peripheral Blood Stem Cell Transplantation; Phosphatidylcholines; Phosphatidylglycerols; Treatment Outcome

We assessed the impact of prophylaxis with the oral itraconazole solution and amphotericin B solution on fungal colonization and infection in a randomized study among patients with hematological malignancies and neutropenia. Infecting and colonizing Candida strains of patients suffering from candidiasis were genotyped by random amplification of polymorphic DNA (RAPD) analysis. A total of 106 patients were evaluated in this study: 52 patients in the itraconazole and 54 in the amphotericin B arm. During neutropenia fungal colonization in the oropharynx occurred in 11 (19.6%) and 24 (40.6%) and in the rectum in 11 (19.6%) and 23 (38.9%) courses in the itraconazole and amphotericin B groups ( P<0.05), respectively. Candida albicans was the most prevalent species in both study groups. Mixed fungal colonization with Candida krusei and Candida glabrata was increased in the amphotericin B group, yet without clinical importance since infections were due to C. albicans. The occurrence of invasive candidiasis was significantly increased in multicolonized compared to monocolonized patients. In the amphotericin B group 20 and in the itraconazole group 2 neutropenic patients showed multicolonization with Candida spp. ( P<0.05). Overall fungal infections were 3.8% in the itraconazole and 14.8% in the amphotericin B group ( P<0.05). RAPD typing showed oropharynx strains involved in superficial infections in four of five patients. In all four patients with deep fungal infections, it appears that the colonizing rectum strains were identical to infecting strains of Candida spp. Itraconazole solution significantly reduced Candida colonization and infection compared to amphotericin B solution. Most patients remained infected with the colonized strains for the entire study period, irrespective of antifungal prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida; Candidiasis; Genotype; Hematologic Neoplasms; Humans; Itraconazole; Neutropenia; Oropharynx; Random Amplified Polymorphic DNA Technique; Rectum

Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; Biomarkers; Enzyme-Linked Immunosorbent Assay; False Negative Reactions; Female; Fungemia; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Transplantation Conditioning; Transplantation, Homologous

To observe the therapeutic effect and side effects of amphotericin B for fungal infections in patients with malignant hematologic diseases.. 40 patients (male 27, female 13; average age 35.5 years) with malignant hematologic diseases were given amphotericin B, 5-50 mg/d per day for 5-85 days (average time 21 days).. The clinical efficacy rate of amphotericin B was 52.5%, and the fungal elimination rate was 56.2%. Among the side effects, rigor and fever were present in 2.5% of the patients. Hypokalaemia was found in 12.5%, hepatotoxicity in 15.0% and nephrotoxicity in 15.0%.. As amphotericin B has a broad anti-fungal spectrum and relatively good efficacy, it is still a high-efficiency drug in treatment of systematical fungal infections. However, the use of drug is limited because of its many side effects. Our study indicates that if it is used properly and hepatic and renal function tests are carried out regularly, amphotericin B is a relatively safe and effective drug.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Kidney; Liver; Male; Middle Aged; Mycoses; Treatment Outcome

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Fungemia; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Rate; Transplantation, Autologous; Treatment Outcome

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Bilirubin; Bone Marrow Transplantation; Creatinine; Drug Combinations; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Scandinavian and Nordic Countries

We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of >/=2 degrees C in 4/16 patients and of >/=1 degrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bilirubin; Consumer Product Safety; Contraindications; Female; Fluconazole; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Male; Middle Aged; Morphine; Mycoses; Neutropenia; Respiratory Tract Diseases; Shivering; Survival; Time Factors; Transaminases

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of p

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Double-Blind Method; Female; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Neutropenia

Topics: Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Drug Combinations; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Phosphatidylcholines; Phosphatidylglycerols

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Fluconazole; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections

The tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily (t.i.d.), but only 20 (48%) patients managed to complete the scheduled regimen. One patient tolerated the full dose initially, but had to discontinue treatment when dyspnea developed as a result of pneumonia and acute respiratory distress. Another 22 patients (52%) experienced side effects, including eight (19%) who reported mild coughing and dyspnea but who tolerated the full dose and three (7%) patients whose dose was reduced to 5 mg t.i.d. Another six (14%) patients could tolerate only 5 mg t.i.d., and five (12%) others stopped treatment because of intolerance. Elderly patients (p < 0.05) and those with a history of chronic pulmonary obstructive disease (p = 0.09) were more likely to develop side effects during inhalation. Twelve (28%) patients developed proven of possible invasive fungal infections, but no correlation was established between infection and the total amount of amphotericin B inhaled. Inhalation of aerosolised amphotericin B is poorly tolerated and does not appear useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Chi-Square Distribution; Confidence Intervals; Dose-Response Relationship, Drug; Female; Fungemia; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Middle Aged; Treatment Outcome

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but the effective drugs for the treatment are limited. Hence, the study aimed to summarize the characteristics of mucormycosis in patients with hematological malignancies, and investigate the efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) in treating mucormycosis.. In this study, patients with mucormycosis complicated by hematological malignancies who received ABCD at the First Affiliated Hospital of Zhengzhou University from April 2021 to May 2022 were retrospectively enrolled. The clinical data of the enrolled patients were collected, and then, the drug response at 2 weeks, 4 weeks, and the end of treatment; the survival rate at 4, 8, and 12 weeks; and the laboratory-related indicators and adverse events (AEs) associated with ABCD were evaluated.. In total, 9 patients with mucormycosis complicated by hematological malignancies were enrolled. The main symptoms were fever, cough, and chest pain. In addition, reversed halo signs (RHS) were found on chest CTs. The responses to ABCD at 2 weeks, 4 weeks, and the end of treatment were 100% (9/9), 77.8% (7/9), and 77.8% (7/9), respectively. The survival rates of the patients at 4, 8, and 12 weeks were 77.8% (7/9), 66.7% (6/9), and 66.7% (6/9), respectively. Among laboratory-related indicators, white blood cell (WBC) counts were significantly increased from baseline after 1 and 2 weeks of ABCD treatment (. ABCD is a promising treatment strategy for patients with mucormycosis complicated by hematologic malignancies, showing remarkable efficacy and safety.

Topics: Amphotericin B; Antifungal Agents; China; Hematologic Neoplasms; Humans; Mucormycosis; Retrospective Studies

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.. This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Topics: Amphotericin B; Antifungal Agents; Burns; Febrile Neutropenia; Fusariosis; Fusarium; Hematologic Neoplasms; Humans; Mexico; Retrospective Studies; Voriconazole

Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2%) were confirmed for oral candidiasis [mean ± SD age 39 ± 14 years; female 31 (62%) and male 19 (38%)]. C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 µg/mL, 12.55 µg/mL, 0.75 µg/mL and 798 µg/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs.

Topics: Adult; Amphotericin B; Antifungal Agents; Biofilms; Candida; Candida albicans; Candidiasis, Oral; Eucalyptol; Female; Hematologic Neoplasms; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Nystatin

Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Mucor; Mucorales; Mucormycosis; Rhizopus oryzae

<b>Background:</b> Mucormycosis is a rare fungal infection affecting people with impaired immunity. The aim of this study is to shed light on the epidemiology, incidence, and outcome of patients with mucormycosis hospitalized at a tertiary care center in Pondicherry. <br><b>Methods:</b> We conducted a retrospective chart review between January 2008 and January 2018. All patients with proven or probable mucormycosis were included. <br><b>Results:</b> A total of 24 patients were included. Their median age was 49 years and the majority were males. Comorbidities included mainly hematologic malignancy and diabetes mellitus. A liposomal amphotericin B formulation alone or in combination with other antifungals was used as a first line agent in all patients. <br><b>Conclusion:</b> The incidence of mucormycosis has significantly increased over the past 10 years at our institution, most likely due to increased risk factors.

Topics: Adult; Amphotericin B; Antifungal Agents; Diabetes Complications; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mucormycosis; Retrospective Studies

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brazil; Child; Child, Preschool; Female; Fusariosis; Fusarium; Hematologic Neoplasms; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Voriconazole; Young Adult

This study identified 8-azaguanine (8-AG) as a novel immunomodulatory drug (IMiD) through a high-throughput screen of the Preswick Chemical Library in a model of human NK cell cytotoxicity against blood cancer cells. 8-AG, originally developed as an antineoplastic agent, significantly increased the cytotoxicity of NK cells and was superior in this activity to previously known IMiDs, such as fluoxetine and amphotericin B, identified from the same library. IFN-γ expression was also slightly increased by 8-AG. Mechanistically, 8-AG increased conjugate formation between NK and target cells and subsequent cytolytic granule polarization, but not calcium mobilization, regulation of activating receptors, or expression of perforin or granzyme B. Thus, the antineoplastic activity of 8-AG should be re-evaluated in light of this novel potentiating effect on NK cells.

Topics: Amphotericin B; Antineoplastic Agents; Azaguanine; Cells, Cultured; Cytoplasmic Granules; Cytotoxicity, Immunologic; Drug Screening Assays, Antitumor; Fluoxetine; Granzymes; Hematologic Neoplasms; Humans; Immunologic Factors; Killer Cells, Natural; Lymphocyte Activation; Perforin; Small Molecule Libraries

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

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cancer Care Facilities; Child; Child, Preschool; Egypt; Female; Hematologic Neoplasms; Hospitals, Pediatric; Humans; Immunocompromised Host; Male; Mucormycosis; Neoplasms; Opportunistic Infections; Retrospective Studies; Risk Factors; Treatment Outcome; Triazoles

Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak.. Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months.. During a 10-month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%-100%).. In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Asymptomatic Diseases; Cohort Studies; Disease Outbreaks; Echinocandins; Female; Galactose; Heart Transplantation; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Mass Screening; Micafungin; Middle Aged; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Transplant Recipients; Voriconazole

Mucormycosis (MCM) is a rare fungal infection affecting people with impaired immunity. Data related to MCM from Lebanon are scarce. The aim of this study is to shed light on the epidemiology, incidence, and outcome of patients with MCM hospitalized at a tertiary care center in Lebanon.. We conducted a retrospective chart review between Jan 1, 2008 and Jan 10, 2018. All patients with proven or probable MCM were included.. A total of 20 patients were included. Their median age was 49 years and the majority were males. Comorbidities included mainly hematologic malignancy and diabetes mellitus. Most common sites of involvement were rhino-orbital and pulmonary, respectively. The number of MCM cases/10.000 hospital admissions increased significantly between 2008 and 2017 (0.47 vs. 1.18; P < 0.05). A liposomal amphotericin B formulation alone or in combination with other antifungals was used as a first line agent in all patients. All-cause mortality was 60%; however, death was attributed to MCM in 20% of cases.. The incidence of MCM has significantly increased over the past 10 years at our institution, most likely due to the increasing patient population at risk. Understanding the epidemiology of MCM in our setting would help guide antifungal therapy.

Topics: Amphotericin B; Diabetes Mellitus; Fungicides, Industrial; Hematologic Neoplasms; Incidence; Lebanon; Mucormycosis; Retrospective Studies; Tertiary Care Centers; Treatment Outcome

Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Cunninghamella; Female; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Polymerase Chain Reaction

To assess compliance with international guidelines for costly antifungal prescriptions and to compare these results with a first study performed in 2007.. Retrospective study including all costly antifungal prescriptions made in surgical and medical intensive care units and in a hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were assessed in terms of indication, dosage, and antifungal de-escalation.. Seventy-four treatments were analyzed. Treatments were prescribed for prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%). Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%) and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%, and inappropriate in 23%. Prescriptions were inappropriate for the following reasons: lack of dosage adjustment in light of the hepatic function (10 cases), underdosage or excessive dosage by>25% of the recommended dose in seven cases. De-escalation to fluconazole was implemented in 40% of patients presenting with a fluconazole-susceptible candidiasis.. The overall incidence of appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively, P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in particular for empirical therapy, dosage adjustment, and potential de-escalation to fluconazole.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lipopeptides; Male; Middle Aged; Multiple Organ Failure; Mycoses; Organ Transplantation; Retrospective Studies; Survival Rate; Treatment Outcome; Voriconazole; Young Adult

We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in culture and in direct staining. The microorganisms identified were Lichtheimia spp. (42%), Rhizopus spp. (21%), Cunninghamella bertholletiae (16%), and others (21%). Liposomal amphotericin B was always more active than the other drugs against all the microorganisms except C. bertholletiae. All patients received antifungal treatment with 1 or more antifungal agents, mainly liposomal amphotericin B (17/19). Mortality was 47.4%, although this was significantly lower in the 11 patients in whom debridement was performed (18% vs. 87.5%) (P = 0.015). The incidence of mucormycosis has risen in recent years. The proportion of cases with soft tissue involvement was high, and Lichtheimia was the most frequently involved species. The highest antifungal activity was observed with liposomal amphotericin B.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Azoles; Child, Preschool; Cunninghamella; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mucormycosis; Rhizopus; Surgical Wound

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

To evaluate the efficacy and safety of low-dose amphotericin B (AmB) in different antifungal strategies for treatment of invasive fungal disease(IFD) in patients with hematologic malignancies. Metheds: The clinical dada of the patients were collected and analyzed retrospectively and the levels of creatinine (Cr), urea nitrogen (BUN) and potassium (K. Among 97 cases, 2 cases were diagnosed as invasive fungal disease (IFD), 11 cases were diagnosed as clinical probable IFD, 15 cases were diagnosed as possible IFD, 69 cases were undefined IFD. The response rate of all patients treated with low-dose AmB was 69.4%, the response rate for targed therapy was 72.7%, the response rate for diagnosis-driven therapy was 63.6%, the response rate of empirical therapy was 75%, the efficacy of the combination with other antibiotics was 50%, 66.7% and 75%. According to all the patients received AmB, only 7 cases was detected with higher level of Cr (7.2) than normal and this level come back to normal with in 7 days after drug withdrew. Although the Cr level in serum after 1 day of drug withdrew was higher than that before administration of drug(64.86±3.00 vs 58.76±1.67 µmol/L) and was with statistical difference(P<0.05), but did not show significant difference in comparison with the level after drug withdrew 7 days (58.43±1.68 µmol/L,P>0.05).. AmB injection is an effective and safe method in empirical therapy and diagnosis-driven antifungal therapy for neutropenic, febrile patients with hematological malignancies.

Topics: Amphotericin B; Antifungal Agents; Creatinine; Hematologic Neoplasms; Humans; Mycoses; Retrospective Studies

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC.. In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated.. Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned.. This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.

Topics: Adult; Amphotericin B; Antifungal Agents; Candidiasis; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Retrospective Studies; Young Adult

Mucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking.. Two large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ≤19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12.. Sixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp. (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival.. Paediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Diabetes Mellitus; Europe; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lung Diseases, Fungal; Male; Mucormycosis; Neutropenia; Prospective Studies; Registries; Rhizopus; Treatment Outcome

Mould-active antifungal prophylaxis is increasingly used in patients at risk for invasive fungal disease. Between June 2011 and June 2012, one hundred patients with various haematological malignancies at risk for invasive fungal disease received primary antifungal prophylaxis with intravenous micafungin at a daily dosage of 50 mg during neutropenia. The median number of days on micafungin prophylaxis was 14 (range, 6-48 d). The incidence of proven and probable breakthrough invasive fungal diseases (bIFDs) was 6% and 3%, respectively. There were two bloodstream infections caused by yeasts or yeast-like fungi (Candida krusei, Trichosporon asahii) in two patients during the neutropenic phase after allogeneic haematopoietic stem cell transplantation. Four proven bIFDs caused by non-Aspergillus moulds and three cases of probable pulmonary bIFDs were documented during the neutropenic phase after induction/consolidation chemotherapy for acute leukaemia. Colonisation with Candida spp. was documented in 51% of the patients with none of the isolates being in vitro micafungin resistant. Compared to a historical control, receiving primary prophylaxis with posaconazole micafungin is at least as effective in preventing IFD. In both cohorts, bIFDs were exclusively caused by emerging pathogens with a highly preserved in vitro sensitivity to amphotericin B.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Administration Schedule; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Lipopeptides; Male; Micafungin; Middle Aged; Retrospective Studies; Transplantation, Homologous; Triazoles; Trichosporon; Trichosporonosis

We undertook the present study to ascertain the contributing risk factors and explore the epidemiological and mycological characteristics of opportunistic candidemia among patients with hematological malignancies.. Observational cross-sectional study in a tertiary care center.. Consecutive patients with hematological malignancies reporting to the collaborating medical and pediatric units with a febrile episode were recruited and screened for candidemia by blood culture. Recovered Candida isolates were speciated and antifungal susceptibility testing was performed as per Clinical and Laboratory Standards Institute guideline (CLSI) guidelines M44-A. Further analysis was done for potential risk factors and compared between culture positive and negative patients.. Of 150 patients recruited, the majority (n=27) were between 51 and 60 years and the male to female ratio was 1.63:1. Fifteen patients (10%) were culture positive. The culture positivity was significantly higher in acute lymphocytic leukemia (ALL) than in non-ALL patients (p=0.03). There was significant association of candidaemia with leucopenia, chemotherapeutic drugs, corticosteroids and presence of indwelling devices. Duration of disease (p=0.032) and duration of hospitalization (p=0.003) were significantly prolonged in culture positive patients. C. tropicalis was the commonest isolate (46.67%), with non- Candida albicans outnumbering C. albicans in all categories of hematological malignancies (2.75:1). All isolates of C. albicans were uniformly sensitive to all the azoles, but only 50% were sensitive to amphotericin B and none to nystatin and flucytosine.. This observational study identifies ALL and chronic lymphocytic leukemia (CLL) as the forms of hematological malignancy predominantly associated with candidemia; specifies risk factors and chemotherapeutic agents predisposing patients towards its occurrence; reports a preponderance of C. tropicalis among the causative agents and finds voriconazole to be the most effective antifungal agent against the recovered isolates. This information could assist in tailoring prophylactic and therapeutic antifungal practices for this infection, according to local epidemiological and mycological characteristics.

Topics: Amphotericin B; Candida albicans; Candida tropicalis; Candidemia; Cross-Sectional Studies; Female; Hematologic Neoplasms; Humans; India; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Nystatin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Risk Factors; Tertiary Care Centers; Voriconazole

We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Fungemia; Hematologic Neoplasms; Humans; Lipopeptides; Lung; Male; Microbial Sensitivity Tests; Microbiological Techniques; Microscopy; Radiography, Thoracic; Saccharomycetales; Treatment Outcome; Voriconazole

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Topics: Administration, Oral; Adult; Aged; Allografts; Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Cause of Death; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Lipopeptides; Male; Medication Adherence; Middle Aged; Mycoses; Neutropenia; Patient Compliance; Premedication; Retrospective Studies; Risk Assessment; Risk Factors; Survival Analysis; Transplantation Conditioning; Treatment Failure; Triazoles; Young Adult

Although amphotericin B (AmB) and its lipid formulations are used for the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF after intravenous administration of liposomal amphotericin B (LAmB) are not well characterized.. From 14 paediatric haemato-oncological patients (aged 0.4-19.5 years, median 7.6 years), we obtained 30 CSF samples by means of routine punctures (performed for intrathecal treatment of the underlying diseases) at different timepoints after the prophylactic intravenous infusion of LAmB (AmBisome, 3 mg/kg/day). Concurrent serum samples were obtained to calculate the transfer rates. An HPLC method was used for AmB detection.. CSF levels of AmB 1-100 h after the intravenous infusion of LAmB were between 10 and 120 ng/mL, except in one case with a level of 529 ng/mL. Concurrent serum levels were about 1000-fold higher, ranging between 3 and 75 μg/mL. CSF levels did not show a clear time-dependent concentration profile, but remained at a steady-state for longer than 48 h after infusion. The transfer rate ranged from 0.02% to 0.92% (median 0.13%) and correlated significantly (r=0.801, P<0.001) with increasing time after infusion.. After the intravenous administration of LAmB, AmB CSF levels were low, confirming published animal data. CSF levels remained at a steady-state level for longer than 48 h. As indicated by published post mortem data, higher levels in brain tissue, which would be necessary for the successful treatment of CNS infections, might be possible.

Topics: Adolescent; Amphotericin B; Animals; Antifungal Agents; Cerebrospinal Fluid; Chemoprevention; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Infant; Infusions, Intravenous; Male; Mycoses; Serum; Young Adult

Acremonium species are filamentous, cosmopolitan fungi frequently isolated from plant debris and soil that have emerged as an important cause of morbidity and mortality in immunocompromised patients. We present data from two hematologic malignancy patients with Acremonium fungemia who had refractory disease despite initial treatment with Amphotericin B with clinical response after changing therapy to Voriconazole. Acremonium should be considered in the differential diagnosis of patients with clinical presentation suggestive of fungal infection and special attention should be given to the treatment challenge it represents.

Topics: Acremonium; Aged; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Treatment Outcome; Voriconazole

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Candidiasis, Invasive; Child; Child, Preschool; Combined Modality Therapy; Cross Infection; Drug Evaluation; Female; Fungemia; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Postoperative Complications; Retrospective Studies; Risk; Transplantation, Homologous; Treatment Outcome; Triazoles; Young Adult

In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Chemotherapy-Induced Febrile Neutropenia; Clinical Trials as Topic; Drug Administration Schedule; Drug Resistance, Fungal; Drug Therapy, Combination; Febrile Neutropenia; Fungi; Hematologic Neoplasms; Humans; Immunocompromised Host; Multicenter Studies as Topic; Mycoses; Premedication; Prospective Studies; Randomized Controlled Trials as Topic; Transplantation Conditioning; Triazoles

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Candida; Candidemia; Child; Child, Preschool; Cross Infection; Female; Hematologic Neoplasms; Hospital Mortality; Humans; Infant; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tertiary Care Centers; Young Adult

Rhinocerebral mucormycosis is a rare, rapidly progressive life threatening opportunistic fungal disease that usually occurs in immunocompromised patients.. The aim of the study is to present a case series of six immunocompromised patients who were diagnosed with rhinocerebral mucormycosis, review the diagnostic criteria and treatment approach.. Six patients were treated in our department between the years 2005-2010. Their diagnostic criteria, surgical treatment and mortality rate are analyzed and discussed.. All six immunocompromised patients suffered from a primary hematological malignancy and received chemotherapy to treat their primary disease. Symptoms such as pain mimicking sinusitis, facial swelling, oral or dental pain, and fever were found in most patients. The diagnosis was based on both clinical signs and a biopsy for microbiological culture and histological examination. All patients underwent aggressive surgical resection and were treated simultaneously with anti fungal therapy. Four patients died from their primary illness. One patient died due to uncontrolled spreading of mucormycosis and one patient, the youngest and with the most extensive form of the disease (brain invasion) survived and clinically recovered with no evidence of recurrent disease following the surgical management.. Rhinocerebral mucormycosis is a rapidly progressing disease with a high mortality rate, which requires immediate surgical and medical intervention. It seems from the data presented that the presence of mucormycosis is an ominous sign in immunocompromised patients. The extent of the disease is of less prognostic value, since the only patients in our series who survived had the most extensive disease, yet his primary haemato-oncological disease was under control. Controlling the underlying disease with early diagnosis and aggressive surgical intervention appears to be the most important factor for survival.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Brain Diseases; Cause of Death; Combined Modality Therapy; Diagnosis, Differential; Fatal Outcome; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Maxillary Sinusitis; Middle Aged; Mucormycosis; Nose Diseases; Paranasal Sinus Diseases; Pyrimidines; Triazoles; Voriconazole; Young Adult

Liposomal amphotericin B (L-AmB) is recommended as an empirical antifungal treatment for patients at increased risk of fungal infections although renal toxicity remains a clinical problem. We therefore conducted a pilot study to evaluate the safety and efficacy of low-dose L-AmB as an empirical antifungal therapy for patients with prolonged neutropenia.. High-risk patients with hematological malignancies were eligible to enroll in this study provided they had: exhibited neutropenia for at least 1 week; suffered from high-grade fever for 4 days despite treatment with a broad-spectrum antibacterial; and no identified fever-causing pathogen. Low-dose L-AmB (1 mg/kg) was administrated as empirical antifungal therapy.. Sixteen patients were registered and, of these, data from the13 patients who did not receive allogeneic stem cell transplantation were analyzed. The median duration of low-dose L-AmB treatment was 8 days. Hypokalemia was seen in one patient: administration of potassium supplements for 10 days restored potassium levels to the normal range. A two-fold increase in creatinine levels was not found in any patients even those taking concomitant nephrotoxic drugs (e.g., amynoglycoside) during the study. One patient stopped receiving the drug due to an infusion-related adverse event. No patients showed breakthrough fungal infections or died during therapy or within 7 days after the end of the study. Increase in the L-AmB dose was necessary due to persistent fever in three patients who withdrew from the study. The satisfactory response rate for low-dose L-AmB was 69 %.. This study suggests that low-dose L-AmB may be an effective option as empirical antifungal therapy for high-risk patients with febrile neutropenia.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Fever; Hematologic Neoplasms; Humans; Liposomes; Male; Middle Aged; Mycoses; Neutropenia

There have been no published studies evaluating the efficacy and safety of weekly liposomal amphotericin B as secondary prophylaxis in leukemic patients with invasive fungal infections (IFIs). We found in a retrospective review of our experience with 14 such patients admitted from 2003-2009 that the use of this approach was associated with frequent relapse of IFIs (36%) and kidney injury (36%).

Topics: Adult; Aged; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Female; Hematologic Neoplasms; Humans; Leukemia; Male; Middle Aged; Mycoses; Treatment Outcome; Young Adult

Mucormycosis is a deadly invasive fungal infection whose characteristics are only partially understood.. Data on mucormycosis obtained in France between 2005 and 2007 from 2 notification systems were merged. The 2008 European Organisation for Research and Treatment of Cancer/Mycoses Study Group definition criteria were applied and risk factors for death were analyzed by hazard ratios (HRs) calculated from the Cox proportional hazards regression model.. A total of 101 cases (60 proven, 41 probable), mostly in men (58%) >50 years (mean age, 50.7 ± 19.9) were recorded. Hematological malignancies represented 50% (median time for occurrence, 8.8 months after disease onset), diabetes 23%, and trauma 18% of cases. Sites of infection were lungs (28%; 79% in hematology patients), rhinocerebral (25%; 64% in diabetic patients), skin (20%), and disseminated (18%). Median time between first symptoms and diagnosis was 2 weeks. The main fungal species were Rhizopus oryzae (32%) and Lichtheimia species (29%). In cases where the causative species was identified, R. oryzae was present in 85% of rhinocerebral forms compared with only 17% of nonrhinocerebral forms (P < .001). Treatment consisted of surgery in 59% and antifungals in 87% of cases (liposomal amphotericin B in 61%). Ninety-day survival was 56%; it was reduced in cases of dissemination compared with rhinocerebral (HR, 5.38 [2.0-14.1]; P < .001), pulmonary (HR, 2.2 [1.0-4.7]; P = .04), or skin localization (HR, 5.73 [1.9-17.5]; P = .002); survival was reduced in cases of hematological malignancies compared with diabetes mellitus (HR, 2.3 [1.0-5.2]; P < .05) or trauma (HR, 6.9 [1.6-28.6], P = .008) and if ≥2 underlying conditions (HR, 5.9 [1.8-19.0]; P = .004). Mucormycosis localization remained the only independent factor associated with survival.. This 3-year study performed in one country shows the diverse clinical presentation of mucormycosis with a high prevalence of primary skin infection following trauma and a prognosis significantly influenced by localization.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Cerebellar Diseases; Child; Data Collection; Dermatomycoses; Diabetes Mellitus; Female; France; Hematologic Neoplasms; Humans; Lung; Male; Middle Aged; Mucormycosis; Prognosis; Proportional Hazards Models; Retrospective Studies; Rhizopus; Risk Factors; Survival Analysis; Treatment Outcome; Wounds and Injuries; Young Adult

Although there is evidence that liposomal amphotericin B (AmBisome) is non-inferior to amphotericin B (AmB) in terms of in vivo efficacy, in vitro data regarding the activity of AmBisome against clinical isolates of Aspergillus are rare. In this study, the susceptibilities to AmB and AmBisome of 103 Aspergillus complex isolates (48 Aspergillus flavus, 33 Aspergillus fumigatus, 13 Aspergillus terreus and 9 Aspergillus niger) recovered from haematological patients with invasive infection were compared. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution (BMD) method according to the Clinical and Laboratory Standards Institute (CLSI), whilst AmB susceptibility was also determined by Etest. Using a susceptible/resistant MIC cut-off of 1mg/L, all A. fumigatus and A. niger complexes isolates were susceptible to both AmB and AmBisome. In contrast, 38.5% and 30.8% of the A. terreus complex isolates were resistant to AmB and AmBisome, respectively, with good agreement between BMD and Etest methods. With respect to A. flavus complex isolates, 43.7% and 16.7% were resistant by the BMD method to AmBisome and AmB, respectively. For isolates with discrepant results, AmB MICs obtained by Etest were higher than those obtained for AmB by the BMD method and they were closer to those obtained for AmBisome by BMD. Aspergillus flavus AmB MICs ranged from 0.5 mg/L to 2 mg/L by the BMD method and from 1 mg/L to >16 mg/L by the Etest method, and AmBisome MICs ranged from 0.06 mg/L to >16 mg/L by the BMD method. Etest appears to be superior to the CLSI BMD method using AmB in detecting AmB resistance of Aspergillus spp., although the CLSI BMD method might be a suitable procedure if AmBisome is used as the test drug.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Drug Resistance, Fungal; Hematologic Neoplasms; Humans; Italy; Microbial Sensitivity Tests

Whether in vitro antifungal susceptibility findings correlate with the outcome of patients with invasive aspergillosis (IA) remains debated. This study aimed to test whether IA patients' outcomes were associated with in vitro susceptibility results. To do so, we determined the in vitro susceptibility to amphotericin B (AMB) of 37 Aspergillus flavus isolates from 14 patients with haematological malignancies diagnosed with proven or probable IA, of which 13 were treated with AMB deoxycholate. Minimal inhibitory concentrations (MICs) were determined by Etest with the isolates classified as in vitro sensitive (AMB-S) or resistant (AMB-R) if their MICs were < 2 or ≥ 2 mg/l, respectively. The association of the patients' death with primary disease, administered antifungal treatment, and infection with AMB-R A. flavus was tested using generalized estimating equations logistic regression. We assessed AMB-R in 31/37 (84%) isolates. In the patients treated with AMB, the survival rate was 2/3 (67%) and 2/9 (22%) for those infected with AMB-S or AMB-R A. flavus, respectively. Both infection with AMB-R A. flavus (P = 0.014) strain and acute myelocytic leukaemia as the underlying primary disease (P = 0.036) were independent predictors of death. Our findings indicate that in vitro resistance predicts a poor outcome in patients with A. flavus invasive disease treated with AMB. Recent advances in non-culture-based microbiological methods should not discourage efforts to obtain in vitro antifungal susceptibility results, which are critical for the choice of antifungal therapy in patients with IA.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillus flavus; Cohort Studies; Drug Resistance, Fungal; Female; Hematologic Neoplasms; Humans; Invasive Pulmonary Aspergillosis; Male; Microbial Sensitivity Tests; Middle Aged; Survival Analysis; Treatment Outcome; Young Adult

Antifungal prophylaxis in the haematological patient is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukaemias, myelodysplastic syndromes and autologous or allogenic hematopoietic stem cell transplantation. Over the years, different scientific societies have established a series of recommendations on antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each one of the agents must be personalised, adapted to the characteristics of each patient and to possible interactions with concomitant medication.

Topics: Algorithms; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Biological Availability; Decision Trees; Drug Interactions; Echinocandins; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Diseases; Mycoses; Myelodysplastic Syndromes; Postoperative Complications; Practice Guidelines as Topic; Premedication; Triazoles

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5-17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3-69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the combination was switched to caspofungin + voriconazole. The median (range) and total duration of the therapy were 7 (3-14) days and 91 patient days for LAmB + caspofungin combination and 49 (7-126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable response rate of 68.4% in 16 proven or probable IFI episodes. Twelve-week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Caspofungin; Child; Child, Preschool; Drug Resistance, Fungal; Drug Therapy, Combination; Echinocandins; Female; Fungi; Hematologic Neoplasms; Humans; Infant; Lipopeptides; Male; Mycoses; Pyrimidines; Salvage Therapy; Treatment Outcome; Triazoles; Voriconazole

Mucormycosis is a rare but emerging group of life-threatening opportunistic mycoses. We described experience of eight patients who developed mucormycosis. These patients had developed hematologic malignancies, and none achieved complete remission. Six of the eight patients presented with neutropenia, five received corticosteroid, and four had concomitant hyperglycemia. The most frequent physical finding was fever, and five patients complained of facial pain, headache, or chest pain. Four patients presented with concomitant bacterial infection, pulmonary aspergillosis, or intestinal candidiasis. Premortal diagnosis of mucormycosis was made in only one patient. Postmortem biopsy or autopsy was the diagnostic tool for the other patients. Although patients who were treated with amphotericin B survived longer than those treated with micafungin or voriconazole, all patients died due to the progression of mucormycosis. Estimated median survival was 23 days. Premortal diagnosis was rarely achieved as biopsy of infected tissues was the only diagnostic tool, and four patients who revealed dual infection were diagnosed with aspergillosis or bacterial infections. In patients with a high risk of mucormycosis presenting with pain and uncontrollable fever, mucormycosis should be included in the differential diagnosis. High dosages of liposomal amphotericin B should be given and surgical debridement should be performed promptly in cases highly suggestive of mucormycosis.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Biopsy; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Mucormycosis; Neutropenia; Pyrimidines; Retrospective Studies; Survival Rate; Triazoles; Voriconazole

Aspergillus terreus may be resistant to amphotericin B and is associated with significant morbidity and mortality in immunocompromised patients. Local incidence is influenced by the density of airborne Aspergillus spp. spores which may in turn depend on meteorological factors. Once-weekly environmental samples were collected prospectively inside and outside the University Hospital of Cologne, Germany (UHC) and haematological patients were screened for nasal Aspergillus spp. colonisation and monitored for invasive fungal disease (IFD). RAPD (rapid amplification of polymorphic DNA)-polymerase chain reaction (PCR) and amphotericin B susceptibility testing were performed on all A. terreus isolates. A total of 4919 colony-forming units (cfu) were isolated (2212 indoors, 2707 outdoors). Further identification revealed A. fumigatus (73.5%), A. niger (4.3%), A. flavus (1.7%), A. terreus (0.2%) and non-Aspergillus fungi (20.3%). RAPD-PCR did not reveal clonal relationships between the A. terreus isolates. All A. terreus isolates displayed complete resistance to amphotericin. The B. Aspergillus spp. conidia exposure was lowest in June and highest in November inside and outside UHC. Conidia load correlated with the season and the relative humidity, with increasing spore counts during dry periods. One out of 855 nasal swabs was positive for A. niger. The patient did not develop IFD. A. terreus is unlikely to be a relevant pathogen at the UHC. Results from RAPD-PCR suggested a wide epidemiological variety of strains rather than a common source of contamination. Nasal swab surveillance cultures for early detection of Aspergillus spp. colonisation were not useful in identifying patients who may develop IFD. The risk of IFD at the UHC may increase in autumn and during dry periods.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Carrier State; Cluster Analysis; Drug Resistance, Fungal; Environmental Microbiology; Female; Genotype; Germany; Hematologic Neoplasms; Hospitals; Humans; Incidence; Male; Middle Aged; Molecular Typing; Mycological Typing Techniques; Nasal Mucosa; Prospective Studies; Random Amplified Polymorphic DNA Technique; Seasons

Febrile neutropenia (FN) is a serious complication associated with morbidity and mortality. To manage infections in neutropenic patients, it is necessary to administer empirical antibiotic therapy in a timely and efficient manner. We developed an electronic critical pathway system for a computer-stored medical record system (EGMAIN-GX, Fujitsu), which matches FN patients to either: i) the first-line therapy with meropenem (3 g/day) alone, or ii) the second-line therapy with meropenem plus vancomycin (2 g/day). If patients do not respond to the first-line therapy within 72 hours, then they are provided with the second-line therapy. A total of 28 FN events were treated in 14 patients presenting with hematological malignancies. The mean and median neutrophil counts were 42 (0-300)/microl and 0/microl, respectively. The response rates with the first-line and second-line therapies were 57% and 93%, respectively. There were no serious adverse events. Meropenem is a highly effective treatment for FN. Use of an electronic critical pathway system could ensure that neutropenic patients receive this necessary empiric therapy in a timely manner so as to prevent the serious complications associated with FN.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Critical Pathways; Drug Therapy, Combination; Electronic Health Records; Female; Fever; Hematologic Neoplasms; Humans; Liposomes; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins; Treatment Outcome; Vancomycin; Young Adult

Mortality due to mucormycosis is high. We assessed clinical characteristics and mortality among stem cell transplant and hematologic malignancy patients diagnosed with mucormycosis from 2001 to 2009. Thirty patients were diagnosed with probable or proven mucormycosis during the study. Twenty-six were diagnosed premortem, and most were treated with liposomal amphotericin B single-agent antifungal therapy initially. While the initial antifungal and surgical treatment approach remained stable throughout the study period, 6-week mortality significantly declined over time (67% in 2001 to 2003 versus 45% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.04]), as did 12-week mortality (78% in 2001 to 2003 versus 55% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.01]).

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mucormycosis; Retrospective Studies; Treatment Outcome; Young Adult

Data on antifungal prophylaxis in paediatric cancer patients at high risk for invasive fungal disease (IFD) are scant. Intermittent administration of liposomal amphotericin B (LAMB) has been shown to be safe and effective in adult patients with haematological malignancies. We prospectively evaluated the safety and efficacy of prophylactic LAMB at a dosage of 2.5 mg/kg twice weekly in children at high risk for IFD. Efficacy was compared with that in a historical control group of patients with similar demographic characteristics not receiving LAMB prophylaxis. A total of 46 high-risk patients (24 boys; mean age, 7.7 years) with 187 episodes of antifungal prophylaxis were analysed. The median duration of neutropenia (<500/μL) was 10 days. LAMB was discontinued in four patients because of acute allergic reactions. Median values for creatinine and liver enzymes at end of treatment did not differ significantly from those at baseline. Hypokalaemia (<3.0 mmol/L) occurred with 13.5% of the prophylactic episodes, but was usually mild and always reversible. No proven/probable IFD occurred in patients receiving LAMB prophylaxis. In comparison, five proven and two probable IFDs were observed in 45 historical controls not receiving LAMB prophylaxis (p 0.01). LAMB prophylaxis had no impact on the use of empirical antifungal therapy. Systemic antifungal prophylaxis with LAMB 2.5 mg/kg twice weekly is feasible and safe, and seems to be an effective approach for antifungal prophylaxis in high-risk paediatric cancer patients.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Chemoprevention; Child; Child, Preschool; Creatinine; Enzymes; Female; Hematologic Neoplasms; Humans; Infant; Liver; Liver Function Tests; Male; Mycoses; Prospective Studies; Siphoviridae; Treatment Outcome; Young Adult

We report two cases of invasive zygomycoses occurring in severely immunocompromised patients with haematological malignancies that were successfully treated with liposomal amphotericin B and surgical debridement, followed by oral administration of posaconazole. These cases demonstrated that an early instituted, aggressive and combined therapeutic approach results in a recovery from invasive fungal infection, without any relapse of infection, thanks to secondary prophylaxis using posaconazole.

Topics: Aged; Amphotericin B; Antifungal Agents; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Treatment Outcome; Triazoles; Zygomycosis

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Caspofungin; Deoxycholic Acid; Drug Combinations; Drug Resistance, Fungal; Echinocandins; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Immunocompromised Host; Lipopeptides; Male; Middle Aged; Neutropenia; Young Adult

This study aimed to document outcome of invasive respiratory aspergillosis (IRA) in pediatric malignancy patients. Patients with febrile neutropenia episodes followed between January 2003 and May 2007 were enrolled. Antifungal therapy was added to those who were still febrile on the 5th day of febrile neutropenia treatment. Patients were screened with computerized tomographies. IRA was identified in 22 of 98 patients. There were 13 males and the mean age was 97 months. Proven infection was established in 3, probable in 7, and possible in 12 patients. Liposomal amphotericin B was administered to all patients and was successful in 10 patients. Modifications with caspofungin or voriconazole were done in liposomal amphotericin B failures. The median duration of antifungal therapy was 5.5 months. The median follow-up time was 29 months. There was no evidence of IRA in 12 patients after completion of cancer chemotherapy. Six patients died due to underlying disease, whereas IRA was either in remission or stable disease. Four patients were lost due to IRA. The remission rate for IRA was 82%. Survival at 37 months was 55% (95% confidence interval 25-47 months). The amount of time that absolute neutrophil count after initiation of treatment for IRA remained at zero was found to be an independent prognostic factor on survival (P = .01). These results suggest that early diagnosis and aggressive treatment may increase the successful outcome of IRA.

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Child; Early Diagnosis; Echinocandins; Female; Fever; Hematologic Neoplasms; Humans; Lipopeptides; Male; Neutropenia; Prognosis; Pulmonary Aspergillosis; Pyrimidines; Retrospective Studies; Treatment Outcome; Triazoles; Voriconazole

In vitro and in vivo studies suggested that combination of lipid formulation of amphotericin B (L-AMB) and echinocandins may have a synergistic or additive effect against Aspergillus. Furthermore, clinical studies suggested that this combination may improve response of invasive aspergillosis (IA).. Between August 1993 and June 2008, the authors identified a total of 159 patients with hematological malignancies who received salvage therapy for IA, with L-AMB alone, echinocandins alone, or a combination of L-AMB and echinocandins. Clinical characteristics, response to salvage therapy, and death up to 12 weeks after initiation of salvage therapy were retrospectively determined for all patients.. Seventy patients received salvage therapy with L-AMB, 18 patients received echinocandins alone (89% of whom received caspofungin), and 71 patients received the combination therapy of amphotericin B and echinocandins (90% of who received caspofungin). The 3 salvage treatment groups were comparable in regard to clinical characteristics; graft versus host disease was more frequently encountered in the echinocandin group, whereas more patients in the L-AMB and combination groups had neutropenia and received immunotherapy. The response to salvage therapy was better in the echinocandin group (9% L-AMB, 28% echinocandins, and 21% for combination therapy). The 3 groups had a comparable rate of Aspergillus-related death (58%-64%) and overall mortality (61%-67%).. The combination of L-AMB and echinocandins offered no advantage in terms of improving response or reducing mortality over either drug alone. Hence, this combination will only add to the cost of therapy without any improvement in outcome in patients with hematological malignancies.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Drug Therapy, Combination; Echinocandins; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Salvage Therapy; Treatment Outcome

Systemic candidiasis is a significant cause of morbidity and mortality in patients with hematologic disorders. The aim of this study was to determine the prevalence of systemic candidiasis and the efficiency of the polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELIZA) method for the early detection of Candida spp. in patients with hematologic malignancies. From 2004 to 2006, 194 patients with hematologic malignancies were evaluated for systemic candidiasis. Collected blood samples were assayed using the PCR-ELISA method for the presence of the bands on ethidium bromide stained gel, and for hybridization with Candida spp. as well. The female-to-male ratio was 61:133, the mean age was 33.7 years, and the mean hospitalization period was 21.2 days. Twenty-five patients (12.9%) had positive PCR-ELISA results for systemic candidiasis. The etiologic agents were Candida albicans (21 cases), C. tropicalis (3 cases), and C. krusei (1 case). The mean interval of PCR-ELISA positivity in blood samples before the manifestation of clinical signs was 12.6 days. Fungal PCR-ELISA assay became negative after 14 days when patients were treated successfully with amphotericin B, and the assay remained positive until death when the treatment failed. The PCR-ELISA method can potentially serve as a useful tool for the management of patients suffering from hematologic malignancies and at risk for systemic candidiasis.

Topics: Adolescent; Adult; Amphotericin B; Antibodies, Fungal; Antifungal Agents; Antigens, Fungal; Candida; Candidiasis; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Female; Hematologic Neoplasms; Humans; Length of Stay; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Time Factors

Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis.. We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment.. Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome.. Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Drug Administration Schedule; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Mortality; Multivariate Analysis; ROC Curve; Time Factors; Zygomycosis

With its broad spectrum of activity and better tolerability profile than conventional amphotericin B, liposomal amphotericin B (L-AmB) may be the drug of choice for antifungal prophylaxis in haematological patients. An open-label, multicentre, prospective, pilot study was conducted in adult patients receiving chemotherapy for acute leukaemia (AL) or myeloablative allogeneic stem cell transplantation (SCT). Patients received weekly 10mg/kg infusions of L-AmB for 4 weeks for AL and 8 weeks for SCT. The primary objective was safety, with particular attention to infusion-related reactions and nephrotoxicity. Twenty-nine adult patients were included: 21 AL (median age 52 years) and 8 SCT (median age 37 years). The most frequent adverse events (AEs) related to study drug were infusion-related reactions, 12 of which (from a total of 76 infusions) led to increased infusion duration for better tolerance. No AE related to the study drug led to discontinuation of prophylactic treatment in AL patients. In SCT patients, eight AEs (in six patients) reported to be related to study treatment led to treatment discontinuation. Enrolment was discontinued in the SCT group as recommended by the independent data review committee in accordance with the 10% limit of AEs (CTC grade 3-4) fixed by the protocol. The appropriate timing of high-dose prophylactic L-AmB remains to be determined in the SCT setting to optimise the safety profile of this regimen. For AL, a 10mg/kg weekly dose appears to be well tolerated during chemotherapy and may represent an important tool towards improving AL patient outcome.

Topics: Adult; Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Pilot Projects; Prospective Studies; Safety

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with hematologic malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer.. The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n=106) or ABLC (n=52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases.. Risk factors for IA, such as underlying malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7-15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P<.001).. Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Combinations; Female; Hematologic Neoplasms; Humans; Liposomes; Male; Middle Aged; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies; Risk Factors; Salvage Therapy; Treatment Outcome

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST).. The medical and electronic records of all patients with cancer who had candidemia at the authors' institution from 1993 to 2003 were reviewed for demographic data and clinical information, including the use of prophylactic fluconazole, the infecting Candida species, and the source of candidemia (catheter-related vs other apparent sources).. Six hundred thirty-five patients with candidemia were analyzed. C. glabrata and C. krusei were the leading causes of candidemia in 31% and 24% of patients with HM, respectively, and in 18% and 2% of patients with ST, respectively (P < .001). A catheter was the source of candidemia in 36% of the patients with ST and in 12% of the patients with HM (P < .001). Response to antifungal therapy occurred in 73% of the ST group compared with 49% of the HM group (P < .001). Multivariate logistic regression analysis revealed that fluconazole prophylaxis was a risk factor for both C. glabrata and C. krusei candidemia. The analysis also identified neutropenia as a risk factor for all candidemia and catheter-related infection as a risk factor for C. parapsilosis candidemia.. The results of this study indicated that C. glabrata and C. krusei were the leading causes of candidemia in patients with HM. Neutropenia was the leading risk factor for all candidemia, whereas the catheter was the leading risk factor for C. parapsilosis candidemia.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Catheterization, Central Venous; Cohort Studies; Drug Resistance, Fungal; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Retrospective Studies; Risk Factors

Zygomycosis is increasingly reported as a cause of life-threatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fifty-eight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Child, Preschool; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole; Zygomycosis

Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy.. This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA.. Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan.. The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients).. Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Bronchoscopy; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Therapy, Combination; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Radiography; Retrospective Studies; Treatment Outcome

Abnormal liver function test (LFT) results are common in patients with hematologic abnormalities, making the assessment of drug-related hepatotoxicity difficult. Studies based on elevated LFT levels have found that use of liposomal amphotericin B (L-AMB) was associated with increased hepatotoxicity compared with amphotericin B (AMB)/deoxycholate or amphotericin B lipid complex (ABLC). Because LFT abnormalities are multifactorial in severely immunocompromised patients, uncertainty remains regarding the clinical significance of these laboratory findings.. The aim of this study was to present the hepatic histopathologic findings on autopsy in patients who had hematologic malignancies and fungal infections and had received L-AMB or ABLC.. This study was conducted at The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Records from 1995 to 2004 of patients who had received L-AMB or ABLC for > or =7 days, within 30 days before death, were reviewed by 1 investigator. Hepatic autopsy slides were independently reviewed by another investigator (pathologist) in a blinded fashion. Histopathologic evidence of amphotericin-related hepatotoxicity was predetermined based on histopathologic abnormalities reported in animal studies (eg, macrophage vacuolation, multifocal hepatocellular necrosis). Based on data from animal studies and in view of the lack of studies in humans, multifocal necrosis, fatty infiltration, macrophage vacuolation, and/or "foamy macrophage" accumulation were all considered histopathologic abnormalities associated with the use of lipid formulations of AMB.. Data from 64 patients were included (32 patients per group). The demographic characteristics were comparable between the ABLC and L-AMB groups (median ages, 47.5 and 53.0 years, respectively; male, 44% and 53%; white, 75% and 78%; median weight, 67 and 78 kg; active underlying malignancy, 84% and 78%). There were no significant between-group differences in cumulative dose (6 and 7 g), median daily dose (both, 5 mg/kg), or median duration of treatment (19.5 and 19.0 days). Abnormal results (>5 x from baseline) on LFT were found in 12 (38%) and 10 (31%) patients who received ABLC and L-AMB, respectively, but these findings were thought to be associated with concomitant use of triazoles (4/12 [33%] and 1/10 [10%] patients, respectively), hepatotoxic antibiotics (8/12 [67%] and 5/10 [50%]), and/or other hepatotoxic medications (2/12 [17%] and 1/10 [10%]). Nonspecific abnormalities were observed on histopathology in 94% of patients. There was no evidence of histopathologic abnormalities reported in animal toxicity studies of lipid AMB, such as macrophage vacuolation or multifocal hepatocellular necrosis.. Although abnormal results on LFT and/or histopathologic changes in liver were found in 92% of these debilitated patients with hematologic malignancy, direct histopathologic evidence of toxicity associated with lipid formulations of AMB was not established in our study.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Autopsy; Chemical and Drug Induced Liver Injury; Drug Carriers; Drug Combinations; Female; Hematologic Neoplasms; Humans; Liposomes; Liver; Male; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies

Micafungin is a newly approved antifungal agent in the echinocandin class that is active against Candida species and Aspergillus species. However, this agent has limited activity against a number of fungi, including Trichosporon species. We describe 4 patients who developed disseminated trichosporonosis during the use of micafungin. No cases of trichosporonosis had been seen in the 2 years prior to January 2003, when micafungin became available in our hospital.. We reviewed microbiological records of patients at Kameda General Hospital (Kamogawa City, Chiba, Japan) from 1 January 2002 to 31 July 2005, and identified 4 patients whose blood culture results were positive for Trichosporon species.. Since January 2003, four patients--3 with acute myelocytic leukemia and 1 with myelodysplastic syndrome--developed disseminated trichosporonosis while receiving treatment with micafungin with or without amphotericin B. The initial 2 isolates were identified as Trichosporon beigelii, and the later 2 isolates were identified as Trichosporon asahii. All 4 patients received micafungin, and 2 also received amphotericin B concomitantly. Minimal inhibitory concentrations of micafungin were >16 microg/mL for the 2 isolates available for susceptibility testing. One patient with hematologic recovery (neutrophils >500 cells/mm3) showed elimination of the fungus after receiving treatment with voriconazole. However, the 3 other patients without hematologic or immunological recovery died of disseminated infection.. The rarity of trichosporonosis in our hospital and its emergence after the introduction of micafungin therapy support the idea that micafungin may exert a significant, selective pressure toward resistant fungi, such as Trichosporon species. Therefore, care should be taken regarding the possibility of trichosporonosis in patients receiving micafungin with or without amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Drug Resistance, Fungal; Drug Therapy, Combination; Echinocandins; Hematologic Neoplasms; Humans; Japan; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Mycoses; Peptides, Cyclic; Selection, Genetic; Trichosporon

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Female; Fever; Hematologic Neoplasms; Hospitals; Humans; Lipopeptides; Liposomes; Logistic Models; Male; Mycoses; Neutropenia; Peptides, Cyclic; Retrospective Studies; Treatment Outcome; United Arab Emirates

Survival after myeloablative therapy followed by hematopoietic cell transplant (HCT) is limited by substantial treatment-related toxicities. Acute renal failure (ARF) develops in 25% to 50% of patients after HCT.. One hundred forty-seven patients were followed prospectively from time of transplant. ARF was defined as a doubling of baseline serum creatinine at any time during the first 100 days post-transplant. We conducted a nested case-control study to identify precipitants of ARF. For each person who developed ARF, 2 controls were selected at random from patients who had not developed ARF as of that time. An exposure period was defined for each case as the 2 weeks prior to the day on which the matched case met the criteria for ARF. The risk of ARF in relation to demographic and anthropometric characteristics, and to types of treatment and comorbidity, was examined using univariable and multivariable conditional logistic regression models. Odds ratios for the associations with ARF were estimated, taking into account the matching.. Fifty-three patients (36%) developed ARF at a median of 33 days after transplant (range 1 to 97). Elevated risks were observed in patients who received liposomal amphotericin (OR 6.58; 95%CI 1.45-29.95) and conventional (OR 3.60; 95%CI 0.79-16.55), and in those patients with sinusoidal obstruction syndrome (SOS) (previously termed veno-occlusive disease) (OR 9.37; 95%CI 2.29-38.38). For every 0.1 mg/dL increase in baseline serum Cr, the risk of ARF decreased by 30%. Neither total body irradiation (TBI) dose, levels of metabolites of cyclophosphamide, sepsis, acute graft versus host disease (GVHD), nor cyclosporine (CSA) levels was associated with an increased risk of ARF.. The cumulative incidence of ARF after HCT remains high. Amphotericin use during the 2-week exposure period and presence of hepatic sinuosoidal injury increased the risk of ARF within the first 100 days after HCT. Higher levels of serum creatinine at baseline were associated with a lower risk of ARF.

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Case-Control Studies; Child; Child, Preschool; Creatinine; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Liposomes; Male; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Transplantation Conditioning

Several studies have suggested that hydration and sodium load might reduce nephrotoxicity related to amphotericin B-deoxycholate (AmB-d). However, a schedule of these nephroprotective measures has not been standardized until now. A protocol of hydration and electrolyte supplementation was used prospectively in patients with hematological malignancies receiving empirical AmB-d treatment to evaluate its effect on AmB-d-related renal toxicity.. A total of 77 consecutive patients received AmB-d (1 mg/kg per day) in association with an initial intravenous hydration of at least 1 l/m2 body surface, containing at least 1 l of 0.9% saline daily. Hydration was increased when serum creatinine levels showed a 20% increase from baseline. Serum electrolytes were replaced when indicated.. The median duration of AmB-d therapy was 14 days. The mean intravenous hydration and the mean diuresis were 1530 and 1970 ml/m2 of body surface per day, respectively. Overall, 55 patients (71.4%) received a mean of 18.5 days of therapy without dose-limiting adverse events. Despite significant increases in mean creatinine serum levels and decreases in mean creatinine clearance observed early in the whole population, in only six patients (7.8%) was therapy discontinued due to renal failure, which always recovered after treatment discontinuation. In eight patients (10.4%) therapy was stopped due to infusion-related side effects. Seven patients died while under antifungal therapy without relevant signs of AmB-d-associated toxicity.. Our prospective experience confirms that adequate hydration (about 1500 ml/m2 of body surface) and careful electrolyte supplementation are simple measures able to contain nephrotoxicity and to permit adequate antifungal therapy at least in the empirical setting.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Dehydration; Female; Hematologic Neoplasms; Humans; Kidney; Male; Middle Aged; Potassium Deficiency; Prospective Studies; Water-Electrolyte Balance

Invasive aspergillosis (IA) is associated with poor outcome in patients with hematologic malignancy treated with amphotericin B (AMB)-based therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the treatment of IA, although the efficacy of this strategy is uncertain.. To determine whether the addition of ITC to LipoAMB improves outcome of IA, the authors retrospectively studied 179 consecutive patients with hematologic malignancies and definite or probable IA who received primary antifungal therapy with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and June 2003. In view of the erratic absorption of ITC tablets, only patients who received either intravenous or liquid ITC were analyzed. Patients who received < 1 week of treatment were excluded.. Evaluable patients in both groups (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk factors of poor outcome such as neutropenia at onset of IA, persistent neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the intensive care unit, disseminated IA, previous bone marrow transplant, and IA due to infection by a non-fumigatus Aspergillus species. Response to primary antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and LipoAMB group: 0%; P = not significant).. In the authors' 10-year study of patients with hematologic malignancy and IA, the response rate to LipoAMB given as primary therapy was very poor. In a comparable group of patients, the addition of ITC did not result in a therapeutic benefit.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Female; Hematologic Neoplasms; Humans; Injections, Intravenous; Itraconazole; Lipids; Male; Middle Aged; Pharmaceutical Preparations; Retrospective Studies; Risk Factors; Treatment Outcome

As the failure of amphotericin B therapy in patients with invasive aspergillosis often exceeds 50%, we sought to determine the relationship between in vitro amphotericin B resistance and clinical failure of amphotericin B against invasive aspergillosis.. Retrospective study.. University cancer center.. One hundred sixteen patients with cancer and invasive aspergillosis.. The correlation between in vitro amphotericin B susceptibility, defined by both the National Committee for Clinical Laboratory Standards and Etest methods, and other prognostic factors with failure of initial amphotericin B therapy was retrospectively evaluated. Data for correlation could be clearly assessed in only 18 (16%) of the 116 patients. Admission to the intensive care unit was the only prognostic factor associated with failure of initial amphotericin B treatment in these 18 patients (p = 0.01).. Several important obstacles underlie the correlation of in vitro susceptibility testing with in vivo efficacy of individual antifungal agents in the treatment of invasive aspergillosis. Such correlations could be determined in only a small subset of patients.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Drug Resistance, Fungal; Female; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Retrospective Studies; Treatment Outcome

Aspergillus terreus, a less common pathogen, appears to be an emerging cause of infection at our institution, the Medical University Hospital of Innsbruck. Thus the epidemiology and outcome of A. terreus infections over the past 10 years was assessed. We analysed 67 cases of proven invasive aspergillosis (IA) according to the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria, investigated antifungal susceptibility of amphotericin B (AMB), voriconazole and caspofungin and performed molecular typing of A. terreus. Patients with proven IA caused by A. terreus (n = 32) and non-A. terreus (n = 35) were evaluated. The two groups were comparable in terms of age, gender, underlying disease, antifungal prophylaxis and duration of neutropenia (P > 0.05). Leukaemia was the most common underlying malignancy. Fungal dissemination occurred in 63% of the patients. Aspergillus terreus infections were associated with a lower response rate to AMB therapy (20%), compared with 47% for patients with non-A. terreus infections (P < 0.05). In vitro, A. terreus was found to be resistant to AMB and molecular typing discriminated between patients isolates, showing a high strain diversity with 26 distinct types (I-XXVI) identified by combination of three primers. Aspergillus terreus infections displayed evidence of AMB resistance in vitro and in vivo and were associated with a high rate of dissemination and poor outcome; A. terreus causes systemic infections of endemic character in Tyrol, Austria. The onset of A. terreus infection depends not on the degree of immunosuppression but on environmental Aspergillus spp. exposure.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Austria; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Genes, Fungal; Hematologic Neoplasms; Humans; Lipopeptides; Lung Diseases, Fungal; Male; Middle Aged; Opportunistic Infections; Organ Transplantation; Peptides, Cyclic; Prevalence; Pyrimidines; Retrospective Studies; Treatment Outcome; Triazoles; Voriconazole

Mucormycoses are seen with an increasing incidence in immunocompromised patients. Most common presentations are rhinocerebral and pulmonary. We here report the experience of a single center with mucormycoses in patients with hematologic malignancies.. Mucormycoses were diagnosed in six patients, (median age of 52 years; range, 26-74) treated between 2001-2004. Diagnoses included acute myeloid leukemia (AML) (n=3), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1) and multiple myeloma (n=1). Mucormycosis was diagnosed in the neutropenic state following allogeneic hematopoietic cell transplantation (n=3) or intense chemotherapy (n=3). Sites of infections were rhinocerebral, facial and pulmonary involvement in one patient each and disseminated mucormycosis in three patients. The diagnosis was established by computed tomography followed by surgical interventions and histological diagnosis in 4 patients and post-mortem in two patients. Species identified were Rhizopus (n=3), Rhizomucor (n=2) and Absidia (n=1). Treatment responses were best if surgical resection was followed by aggressive antifungal chemotherapy. Five of six 6 patients died, all of complications of mucormycosis or their underlying disease. Only one patient with facial mucormycosis is still alive.. This experience demonstrates that patient with mucormycoses have a high mortality rate and early recognition followed by aggressive surgical debridement, high dose antifungal therapy and attempts to correct the underlying immunocompromised state are crucial in the treatment of this fatal infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Communicable Diseases, Emerging; Dermatomycoses; Disease Susceptibility; Female; Fluconazole; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis; Neutropenia; Pyrimidines; Sinusitis; Transplantation Conditioning; Triazoles; Viscera; Voriconazole

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

Time-kill and postantifungal effect (PAFE) of amphotericin B, caspofungin, fluconazole, and voriconazole were determined against clinical isolates of Candida guilliermondii, Candida kefyr, and Candida lusitaniae. Azoles displayed fungistatic activity and no measurable PAFE, regardless of the concentration tested. Amphotericin B and caspofungin demonstrated concentration-dependent fungicidal activity, although amphotericin B only produced a significant dose-dependent PAFE against all isolates tested.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Echinocandins; Fluconazole; Hematologic Neoplasms; Humans; Kinetics; Lipopeptides; Microbial Sensitivity Tests; Models, Biological; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

In order to optimise the use of new forms of Amphotericine B (Ampho B), a decisional tree was created at the end of 2001 in the paediatric hemato-oncology unit for the empirical antifungal treatment in febrile neutropenic children: the standard remained conventional Ampho B and Abelcet was proposed in case of antecedent or occurrence of a deterioration of the renal function (DRF). In order to validate the place of Abelcet we initiated a retrospective study over year 2002.. 21 treatments were begun in 14 children for a median duration of 8 days (1-48 days). Three kind of indications were found: DRF antecedent (10 episodes: A group), DRF occurrence during a treatment with conventional Ampho B (7 episodes: B group), age lower than 1 year (3 episodes). 81% of the children were thus treated according to the decisional tree. The clinical tolerance was good in 90% of the cases, with a premedication in half of the cases. The study of the renal function showed a good renal tolerance for 6 episodes out of 9 evaluable in A group, 3 resolutions and 2 stabilisation of the renal failure for the 5 evaluable episodes of the B group. Seven to ten days of treatment by Abelcet were necessary to obtain the renal failure resolved.. This study confirms the interest of Abelcet in the empirical antifungal treatment in febrile neutropenic children and specially in children having antecedents of DRF related or not to a treatment with conventional Ampho B.

Topics: Amphotericin B; Antifungal Agents; Child; Creatinine; Drug Combinations; Fever; Hematologic Neoplasms; Humans; Kidney Function Tests; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies

Invasive infection by Fusarium sp. is associated with high mortality in patients with hematologic cancer. Yet to the authors' knowledge, little is known regarding predictors of adverse outcome.. The authors conducted a retrospective review of the records of patients with hematologic carcinoma and invasive fusariosis who were treated at one institution in the U.S. and at 11 centers in Brazil.. The records of 84 patients were evaluated. Neutropenia was present in 83% and 33 patients had undergone stem cell transplantation. Only 18 patients (21%) were alive 90 days after the diagnosis of fusariosis. Multivariate predictors of poor outcome were persistent neutropenia (hazard ratio [HR] of 5.43; 95% confidence interval [95% CI], 2.64-11.11) and use of corticosteroids (HR of 2.18; 95% CI, 1.98-3.96). The actuarial survival rate of patients without any of these factors was 67% compared with 30% for patients who recovered from neutropenia but were receiving corticosteroids and 4% for patients with persistent neutropenia only. None of the patients with both risk factors survived (P<0.0001).. Measures to reduce the duration of neutropenia, as well as the judicious use of corticosteroids, may reduce the high mortality rate of fusariosis in patients with hematologic cancer.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Fusarium; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Mycoses; Prognosis; Retrospective Studies; Stem Cell Transplantation; Survival Analysis

Voriconazole is a new triazole active orally and parenterally that recently proved effective in the treatment of invasive aspergillosis and in empirical antifungal therapy for persistently febrile neutropenic patients. Limited data are available for pediatric patients. We report our experience with voriconazole in seven children with invasive aspergillosis, i.e., four girls and three boys with a median age of 5 (range 2-13) years affected by acute lymphoblastic leukemia (3), acute myeloid leukemia (2), refractory anemia with excess of blasts (1), and severe aplastic anemia (1). First-line therapy in all patients was liposomal amphotericin B (AmBisome) administered at a dosage of 3-5 mg/kg day. Voriconazole was administered for a median 8 (range 2-15) weeks. Response was complete and partial in two patients, respectively, stable in one, and there was no response (failure) in two. The voriconazole treatment was well tolerated. Four patients died-two of progressive aspergillosis. Three patients are alive and well 6, 5, and 4 months after the diagnosis of aspergillosis. Voriconazole appears to be an effective salvage treatment for invasive aspergillosis in pediatric patients, with good responses in patients who recover from neutropenia or are not relapsing.

Topics: Adolescent; Amphotericin B; Anemia, Aplastic; Anemia, Refractory; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Bone Marrow Transplantation; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic Neoplasms; Humans; Leukemia, Myelomonocytic, Acute; Male; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Time Factors; Treatment Outcome; Triazoles; Voriconazole

The role of antifungal prophylaxis remains controversial and concerns exist that the use of azoles may potentiate the emergence of resistant Candida species. We used a strategy of combining the latest azole/triazole with oral amphotericin B to reduce this risk. We analysed data on Candida colonization and candidaemia in neutropenic patients from four prophylaxis periods (1985/6: ketoconazole and amphotericin B suspension; 1991/2 & 1997: fluconazole and amphotericin B suspension; 1998/9: itraconazole) to look for evidence of the emergence of potentially resistant species. Overall, the percentage of patients colonized with Candida fell significantly (69.3%, 57.5%, 43.2% and 46%, respectively, P < 0.001) due to a decrease in colonization with C. albicans (49%, 23.1%, 22.2% and 25.2%, respectively, P < 0.001). However, in 1998/9, increased colonization, particularly with C. glabrata in the lower gastrointestinal tract, was noted to coincide with the omission of oral amphotericin B. Despite an increasing population of 'high risk' patients, the incidence of candidaemia has not changed significantly (2%, 1.4%, 1.2% and 2% respectively). However, species causing candidaemia have changed, with resistant organisms now predominating. Our findings support the use of azole prophylaxis although, in view of the trends noted when itraconazole was used alone, we would recommend the additional use of oral amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Azoles; Bone Marrow Transplantation; Candida; Candidiasis; Drug Resistance, Microbial; Drug Therapy, Combination; Fluconazole; Hematologic Neoplasms; Humans; Itraconazole; Ketoconazole; Neutropenia; Prospective Studies; Retrospective Studies

Candida lusitaniae is an infrequent cause of fungemia. We identified 12 cases of C. lusitaniae fungemia that occurred at the University of Texas M. D. Anderson Cancer Center from 1988 to 1999. The mean age of patients was 48 years (range 20--70 years). Eight patients had hematologic malignancy or had received a bone marrow transplant, and 4 had a solid tumor. Most patients (75%) were neutropenic (<10(3)/mm(3)). Treatment with amphotericin B alone failed for 3 of 6 patients, irrespective of neutropenic status. Fluconazole was effective as a single agent in 3 patients with solid tumors. The combination of amphotericin B plus fluconazole was effective treatment for two-thirds of patients with hematologic malignancy, despite persistence of neutropenia. The mortality rate associated with C. lusitaniae infection was 25%. C. lusitaniae presents as breakthrough fungemia in immunocompromised patients and is associated with failure of amphotericin B therapy. Fluconazole may be a useful agent in the treatment of this infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candida; Candidiasis; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Neutropenia; Treatment Failure

Amphotericin B lipid complex (ABLC) has been investigated as an empirical antifungal treatment for neutropenic patients with persistent fever of unknown origin (FUO). We studied the safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of neutropenic FUO. Sixty-one patients with hematologic malignancies developing 69 episodes of neutropenic FUO after chemotherapy or hematopoietic stem cell transplantation were included in the study. The median patient age was 47 years (18-68). The median duration of neutropenia (< 0.5 x 10(9)/l) was 17 days (7-45) and the median duration of ABLC therapy was 8 days (2-19). Thirteen patients (19%) suffered from mild to moderate infusion-related adverse events. Creatinine levels were stable in 42 cases (61%), improved in 9 (13%) and deteriorated in 18 (26%), with no other significant toxicities. Among 67 evaluable episodes, the response rate (resolution of fever during the period of neutropenia without developing a fungal infection) was 67%, while 33% were treatment failures. Low-dose ABLC is safe, well tolerated and seems to be at least as effective as c-AmB for empirical antifungal therapy of FUO. Randomized trials at this dose level comparing ABLC with c-AmB or other lipid formulations are warranted.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antiviral Agents; Drug Combinations; Female; Fever; Hematologic Neoplasms; Humans; Hypokalemia; Kidney; Liver; Male; Middle Aged; Neutropenia; Phosphatidylcholines; Phosphatidylglycerols

To investigate diagnostic aspects of invasive aspergillosis (IA) in allogeneic BMT recipients, the charts of 22 consecutive patients with IA transplanted in 1989-1995 were reviewed. IA was diagnosed 69-466 days (median 131 days) post BMT. In 16 patients (73%), a definite or probable diagnosis of IA was made during life. Respiratory symptoms were the presenting feature in half of the patients followed by neurological symptoms (27%). Chest X-ray revealed single or multiple nodular lesions in 10 patients; cavitation was observed in five patients. Tissue biopsy was the most common method of diagnosis (nine patients: lungs 6, liver 1, subcutaneous tissue 1, brain 1). Five IA cases were detected by nine guided fine needle lung biopsies in eight patients and without complications. Bronchoalveolar lavage was performed in 14 patients with findings suggestive of invasive pulmonary aspergillosis in eight cases. Lungs were the most common organ affected (90%) followed by central nervous system (41%). The diagnosis of IA is still difficult, and a large number of patients have advanced infection at diagnosis. Methods for early diagnosis are needed. Patients with a clinical suspicion of IA should be treated vigorously with antifungal agents during the diagnostic work-up.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Aspergillus niger; Autopsy; Biopsy, Needle; Bone Marrow Transplantation; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Cohort Studies; Female; Fever; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Hemoptysis; Humans; Lung; Male; Middle Aged; Nervous System Diseases; Neutropenia; Radiography, Thoracic; Respiratory Tract Diseases; Tomography, X-Ray Computed; Transplantation, Homologous

Fungal colonization during cytotoxic chemotherapy was studied in 42 patients with a recent diagnosis of a haematological malignancy. In total, 2759 surveillance cultures were taken from the nostrils, throat, urine, stool and perineal region. Seven hundred and ninety-six positive surveillance cultures (28.9%) yielded 968 fungal isolates. The rate of fungal colonization did not differ between patients with acute leukaemia, patients with other haematological malignancies and control patients in the same ward at admission (71% vs. 67% vs. 80%). Patients with acute leukaemia were colonized at a significantly lower rate in samples from the throat (32%), urine (10%), stool (45%) and perineum (29%) taken during hospitalization when compared with other haematological patients (respective values 58%, 21%, 67% and 45%; P-values 0.001). This could be attributed to differences in the use of antifungal drugs. Although 21/42 (50%) of our patients had multiple-site fungal colonization at the end of follow-up, only one systemic Candida infection was diagnosed. Extensive use of antifungal treatment may have influenced the low incidence of systemic fungal infections during the follow-up. In addition to Candida species, Malassezia furfur, Geotrichum candidum and Saccharomyces cerevisiae were frequently isolated. The rate of S. cerevisiae isolation increased significantly over time after admission (1%, vs. 18% of isolates, P<0.001), suggesting hospital-acquired transmission. These isolates were highly resistant to azole antifungals (MIC90 128 microg/mL for fluconazole and 16 microg/ml, for itraconazole), and caused persistent multiple site colonization in 12 patients. Extensive use of antifungal agents in a haematological ward may keep the incidence of invasive fungal infections low in spite of heavy fungal colonization. However, there may be a risk of emergence of resistant fungal strains.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Cross Infection; Drug Resistance, Microbial; Female; Finland; Fluconazole; Hematologic Neoplasms; Hospital Units; Humans; Infection Control; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Neutropenia; Saccharomyces cerevisiae

Candida krusei is inherently resistant to fluconazole and is emerging as a frequent cause of fungemia in patients with hematologic malignant neoplasms.. To determine the risk and prognostic factors associated with C krusei fungemia in comparison with Candida albicans fungemia in patients with cancer.. Retrospective study of 57 cases of C krusei fungemia occurring at the M. D. Anderson Cancer Center, Houston, Tex, from 1989 to 1996. The C krusei cases were compared with 57 cases of C albicans fungemia with respect to demographics, underlying cancer, Acute Physiology and Chronic Health Evaluation II score, immunosuppression status, chemotherapy, and the use of central venous catheters, as well as fluconazole prophylaxis.. At our institution, C krusei accounted for 5% of fungemias during 1989 through 1992 and for 10% during 1993 through 1996. Patients with C krusei fungemia more often had leukemia than patients with C albicans (77% vs 11%; P =.02), whereas catheter-related infections were more common among patients with C albicans fungemia (42% vs 0%; P<.001). Patients with C krusei fungemia had a lower response rate (51% vs 69%; P =.05), largely because they more frequently were neutropenic and had disseminated infection. Mortality related to fungemia was 49% in the cases with C krusei vs 28% in C albicans. Multiple logistic regression analysis showed that persistent neutropenia (P =.02) and septic shock (P =.002) were predictors of poor prognosis.. In neutropenic patients, C krusei fungemia is associated with high mortality. It should be suspected in patients with leukemia who are receiving fluconazole prophylaxis and should be treated aggressively with an amphotericin B regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida albicans; Case-Control Studies; Catheterization, Central Venous; Catheters, Indwelling; Child; Child, Preschool; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Logistic Models; Male; Middle Aged; Neutropenia; Prognosis; Retrospective Studies; Risk Factors; Shock, Septic; Treatment Outcome

Eighty-seven patients with hematologic malignancies and invasive pulmonary aspergillosis (IPA) were identified between 1982 and 1995. Of these, 39 underwent lung resection on the basis of radiological detection of at least 1 lesion with imaging suggestive of aspergillosis (LISA). IPA was confirmed histologically in 35. The presence of LISA had 90% positive predictive value for IPA. The actuarial survival at 2 years was 36% for 37 patients treated surgically, 20% for 12 patients with unresected LISA but no cultures of Aspergillus species, and 5% for 21 patients diagnosed only by isolation of Aspergillus from respiratory secretions. Analysis by proportional hazard models showed a significant independent negative association between the radiological appearance of LISA and death from all causes. Relapsed hematologic disease was independently significantly associated with death. Age, sex, surgery, previous bone marrow transplantation, or Aspergillus isolation were not independent predictors of death. IPA presenting as LISA carries a relatively good prognosis, possibly explaining the better survival of patients undergoing surgery for such lesions.

Topics: Adolescent; Adult; Aged; Algorithms; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Neoplasms; Humans; Lung Diseases, Fungal; Male; Middle Aged; Predictive Value of Tests; Prognosis; Risk Factors

The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i.v. therapy; under CT guidance, a median of 10 cm3 per session of a 1 mg/cm3 diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Injections, Intralesional; Lung Diseases, Fungal; Male; Middle Aged; Punctures; Radiography, Interventional; Recurrence; Retrospective Studies; Tomography, X-Ray Computed

Blood samples were drawn daily from 72 patients who had hematological malignancies, neutropenia, and fever and who had failed to respond to broad-spectrum antibiotics. Each sample was used for conventional fungal blood cultures and for detection and identification of Candida DNA by a PCR method with subsequent restriction enzyme analysis (REA) recently developed in our laboratory. The PCR method was able to detect five CFU of Candida spp. per ml of blood, and subsequent REA of the amplicons allowed the identification of the Candida species most commonly implicated in cases of candidiasis. Thirty-one patients were PCR-REA positive, and four of these patients were also culture positive. The ultimate diagnosis for 13 of these patients and 1 patient who was PCR-REA negative was disseminated candidiasis (confirmed by clinical data, multiple cultures, histology, autopsy, and/or ultrasonographic evidence of hepatosplenic candidiasis). The molecular method is significantly more sensitive than conventional fungal blood cultures and has a high negative predictive value (97.5%) for the development of disseminated candidiasis in neutropenic patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; DNA, Fungal; Female; Fever; Hematologic Neoplasms; Humans; Male; Mycology; Mycoses; Neutropenia; Polymerase Chain Reaction; Prohibitins; Reproducibility of Results; Restriction Mapping; Sensitivity and Specificity

A retrospective study of 76 episodes of candidemia in 73 patients with underlying hematological malignancy, from 1988 until 1997, has been conducted to evaluate the clinical characteristics and to ascertain the variables related to the onset and the outcome of candidemia. The most frequent malignancy was acute myeloid leukemia (29 episodes). Candidemia developed mainly during aplasia in patients refractory to chemotherapy (42%). In 65 episodes (86%) the patients were neutropenic (ANC <1 x 10(9)/l) before the candidemia diagnosis for a median time of 13 d, and in 53 episodes (70%) at microbiological diagnosis of candidemia ANC was <1 x 10(9)/l. Candida albicans was the most frequently isolated etiologic agent (31 episodes), but C. non-albicans species sustained the majority of candidemia. Seventeen candidemias developed during azoles prophylaxis. One month after the diagnosis of candidemia, 26 patients died. In 19 cases, death was attributable to candidemia. The case-control study demonstrated, at univariate analysis, that the colonization with Candida. spp. (p=0.004), antimycotic prophylaxis (p=0.01), presence of central venous catheter (p=0.01), neutropenia (p=0.002), and the use of glycopeptide (p=0.0001) increased the risk of candidemia. Using multivariate regression analysis only colonization with Candida spp. and the previous therapy with glycopeptide were associated with a significantly increased risk. Acute mortality, expressed by a cumulative probability of survival at 30 d from diagnosis of candidemia, was 0.67 (95% C.I. 0.55-0.77) and was significantly reduced in patients with neutrophils <1 x 10(9)/l when compared to those with neutrophils >1 x 10(9)/l (p at Mantel-Cox=0.029). Overall cumulative probability of survival at 1 yr was 0.38 (95% C.I. 0.27-0.49) and only the treatment with Amfotericin B significantly reduced the risk of death.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Case-Control Studies; Catheterization, Central Venous; Female; Fungemia; Glycopeptides; Hematologic Neoplasms; Humans; Life Tables; Male; Middle Aged; Neutropenia; Parenteral Nutrition, Total; Proportional Hazards Models; Regression Analysis; Retrospective Studies; Risk Factors; Superinfection; Survival Analysis; Survival Rate; Treatment Outcome

Topics: Amphotericin B; Antifungal Agents; Child; Cytarabine; Female; Fusarium; Hematologic Neoplasms; Humans; Mycoses; Neutropenia; Opportunistic Infections

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Topics: Administration, Intranasal; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Combined Modality Therapy; Environment, Controlled; Female; Filtration; Hematologic Neoplasms; Hospital Units; Humans; Male; Neutropenia; Treatment Outcome

No comparative clinical information on the properties of lipid-associated amphotericin preparations is presently available. In this single-centre retrospective analysis over a 5-year period the indications, efficacy and toxicity of true liposomal amphotericin (AmBisome) were compared with a lipid complexed preparation (Abelcet). In a novel approach APACHE III scores were used in addition to neutrophil counts, disease status and additional immunosuppression to accurately assess the severity of illness in both groups and enable valid comparison. Overall, AmBisome at a median dose of 1.9 mg/kg/d was found to have similar clinical outcome to Abelcet at a median dose of 4.8 mg/kg/d. Nephrotoxicity and electrolyte abnormalities were similar in both groups. Rigors and febrile episodes were more common with Abelcet. Prospective randomized comparative trials are required to clarify the optimum dosages and therapeutic and economic issues associated with these agents.

Topics: Adult; Amphotericin B; Antifungal Agents; Creatinine; Drug Combinations; Female; Hematologic Neoplasms; Humans; Immune Tolerance; Leukocyte Count; Male; Mycoses; Neutrophils; Opportunistic Infections; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies; Treatment Outcome; Water-Electrolyte Imbalance

The EORTC Invasive Fungal Infections Cooperative Group (IFICG) conducted a prospective survey by questionnaire of all cases of invasive aspergillosis (IA) in cancer patients to ascertain current diagnostic and therapeutic approaches.. All members of the IFICG were asked prospectively to complete a detailed questionnaire for each IA case identified in their institution over a 12-month period.. One hundred and thirty questionnaires were returned. All cases were independently evaluated (DWD & JC) and 123 were eligible. Cases came from 20 hospitals in eight countries and the number of cases per institution varied from 1-21. Acute myeloid leukaemia (AML) (60, 49%), acute lymphoblastic leukaemia (ALL) (21, 17%) and lymphoma (11, 9%) were the most frequent underlying diseases, and 16 (12%) patients had received an allogeneic bone marrow transplant. Pulmonary involvement was present in 87%, infection of sinuses/nose in 16% and brain in 8%. The chest radiograph was initially normal in 9% of those with primary pulmonary disease. The diagnosis was confirmed in 50%, probable in 31% and possible in 19%. The evidence for IA was on the basis of clinical and radiological features alone in 28%, with culture or histology in another 31% and 9%, respectively, and with both culture and histology in 29%. In three (2%) patients with diagnosis was based on culture or histology alone. Treatment was given to 120 patients (98%)-amphotericin B 75%, lipid-associated amphotericin B 36%, itraconazole 40%, flucytosine 12%, growth factors 33%, lobectomy 5%. At 3 months after diagnosis or first suspicion of IA, 44 (36%) patients were alive and 79 (64%) dead. Outcome was best in those with AML (30% death and 46% with a complete antifungal response or cure). Growth factors (mostly granulocyte colony stimulating factor) appeared not to influence outcome (P = 0.99).. IA remains a considerable diagnostic and therapeutic challenge. No single diagnostic procedure was universally successful and a multifaceted approach including surgery is necessary. There was no discernable difference in outcome between initial therapy with amphotericin B, itraconazole or lipid-associated amphotericin B, although numbers are limited and the study was retrospective.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Female; Hematologic Neoplasms; Humans; Itraconazole; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Survival Analysis

Patients with hematology disease in post-chemotherapy medullary aplasia are susceptible to life-threatening bronchopulmonary mycoses, especially aspergillosis. Other less common pulmonary mycoses are also observed. We report 4 cases due to Penicillium purpurogenum, Acromonium strictum and Scedosporium apiospermum (n = 2) infections. These unusual fungi appear to be emerging as pathogens in this population. They have common ubiquitous, opportunistic and low pathogenicity characteristics in immunocompetent subjects. The major risk factor is neutropenia. Isolating one of these fungi in an immunodepressed patient modifies management protocols since certain unusual fungi such as Scedosporium are resistant to amphotericin B.

Topics: Acremonium; Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Bone Marrow Transplantation; Female; Hematologic Neoplasms; Humans; Imidazoles; Leukemia, Myeloid, Acute; Lung; Lung Diseases, Fungal; Male; Middle Aged; Multiple Myeloma; Neutropenia; Penicillium; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudallescheria; Pyrimidines; Risk Factors; Triazoles; Voriconazole

The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Hematologic Neoplasms; HIV Infections; Humans; Itraconazole; Logistic Models; Male; Middle Aged; Multivariate Analysis; Opportunistic Infections; Prognosis; Prospective Studies; Risk Factors; Survival Analysis

Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Drug Combinations; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Transplantation, Autologous; Transplantation, Homologous

The treatment of deep fungal infection in haematological malignancy remains controversial due to the limited number of antifungal agents available and problems over their spectrum and dose-limiting side-effects. Difficulties in diagnosis mean that most treatments are begun empirically; amphotericin B remains the drug of choice. Emerging resistance may limit the usefulness of fluconazole and other azoles in some areas. Lipid preparations of amphotericin B have reduced the toxicity of this agent, but some issues of dosage and efficacy remain. Adjunctive treatments aimed at augmenting the host response to infection may have a role to play in deep fungal infection.

Topics: Amphotericin B; Antifungal Agents; Flucytosine; Hematologic Neoplasms; Humans; Mycoses

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Blood Pressure; Fat Emulsions, Intravenous; Fever; Heart Rate; Hematologic Neoplasms; Humans; Mycoses