amphotericin-b and Leukemia

Mucormycosis is an opportunistic and aggressive fungal infection that mainly affects immunocompromised patients who generally suffer from diabetes mellitus, immune impairment, hematological disease. It is a life-threatening infection and the management is not standardized. The literature proposes aggressive and early surgical approach, even at the expense of mutilation. We report a case of rhino-orbital mucormycosis in a child with myeloblastic leukemia and the successful treatment using the instill negative pressure wound therapy combined with reconstructive surgery in order to reduce mortality and to avoid disfigurement. KEY WORDS: Amphotericin B, Apex syndrome, Forehead flap, Instill NPWT, Myeloaplasia Mucormycosis.. La mucormicosi è un’infezione fungina opportunistica e aggressiva che colpisce principalmente i pazienti immunocompromessi che generalmente soffrono di diabete mellito, compromissione immunitaria, malattie ematologiche. È un’infezione pericolosa per la vita e la gestione non è standardizzata. La letteratura propone un approccio chirurgico aggressivo e precoce, anche a scapito della mutilazione. Segnaliamo un caso di mucormicosi rino-orbitale in un bambino con leucemia mieloblastica e il trattamento di successo utilizzando il trattamento delle ferite a pressione negativa instillata combinata con la chirurgia ricostruttiva al fine di ridurre la mortalità ed evitare deturpazioni.

Topics: Amphotericin B; Antifungal Agents; Child; Humans; Leukemia; Mucormycosis

Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review.. We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included. Demographics, treatment and outcomes were analyzed using R Gui statistical software.. Twelve studies met inclusion criteria (103 patients). There was male preponderance of 48.5% with median age of 11 years old. Majority of patients had underlying leukemia (44.6%). Aspergillus was the predominant organism (47%). Isolated nasal findings occurred in 14% of patients and nasal findings occurred in 49% overall. Absolute neutrophil count (ANC) of immunocompromised patients was below 600 in most patients (99%). Average and median length of neutropenia was 2 weeks. All patients were prescribed amphoterocin with 50% as single medicinal therapy. Surgery occurred in 82.8% of cases. The mortality rate was 46%. Univariate analysis identified presenting with facial pain as a negative predictor of overall mortality (OR 0.296, 95% CI: 0.104-0.843, p < 0.05).. Mortality remains high in pediatric patients with IFS. An ANC of <600 occurred in the majority of immunocompromised patients at a duration of 2 weeks. Presenting with facial pain was a negative predictor of mortality. Many studies label this condition as invasive fungal sinusitis; however, approximately one seventh presented with only nasal findings and half overall had nasal involvement.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Burkitt Lymphoma; Candidiasis, Invasive; Child; Facial Pain; Female; Fusariosis; Humans; Immunocompromised Host; Leukemia; Male; Mucormycosis; Mycoses; Neutropenia; Otorhinolaryngologic Surgical Procedures; Prognosis; Retrospective Studies; Sinusitis

Zygomycoses are rare invasive mould infections which mainly occur in immunocompromised patients, especially during prolonged neutropenia. The high mortality rate is due to a high failure rate of both intravital diagnosis and treatment. Exact diagnosis requires microscopic examination and proof by culture. The treatment consists of amphotericin B and surgical debridement. We report four recent cases of zygomycosis among 89 patients with intensively treated acute leukaemia at our institution. Three cases were breakthrough infections since the patients were under voriconazole treatment prior to diagnosis of zygomycosis. Only one patient had premortal diagnosis (paranasal sinus infection) and showed clinical response with amphotericin B and surgical debridement. A review of the literature of these emerging fungal infections is given and is focused on patients with acute leukaemia. In addition, the importance of autopsy as a tool for quality control and epidemiological studies is pointed out.

Topics: Amphotericin B; Antifungal Agents; Female; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Neutropenia; Pyrimidines; Triazoles; Voriconazole; Zygomycosis

Aspergillus fumigatus is the most common mould pathogen of human beings and unusually causes both invasive disease in immunocompromised patients and allergic disease in patients with atopic immune systems. 4% of patients dying in modern European teaching hospitals have invasive aspergillosis and it is the leading infectious cause of death in leukaemia and bone marrow transplant patients. Until 2001, only two licensed antifungal drugs were available to treat aspergillosis-amphotericin B and itraconazole. Its 28-30Mb genome is being sequenced in an international collaboration, with the Wellcome Trust Sanger Institute (UK) and The Institute for Genomic Research (TIGR, USA) as the two main centres. A whole-genome shotgun approach was adopted and initiated in 2001 with an expected completion date in 2003. The complete sequence will permit identification of pathways specific to pathogenic Aspergillus species, help identify new targets for antifungal drugs, and enable investigations into the basic biology of fungi. Numerous secondary metabolic pathways with biotechnological applications and pharmacological properties are found in the Aspergilli and the genome sequence will facilitate research in this area.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Bone Marrow Transplantation; Drug Design; Genome, Fungal; Immunocompromised Host; Itraconazole; Leukemia

Invasive fungal infections remain a common cause of morbidity and mortality among patients with leukemia who become further compromised by neutropenia. Candida and Aspergillus spp account for the vast majority of these infections, but other, less commonly recognized fungi can cause life-threatening infection in these hosts as well. The earlier, more limited antifungal armamentarium of ketoconazole, flucytosine, and amphotericin B has been substantially augmented by the availability of fluconazole, itraconazole, and the lipid-associated amphotericin formulations. Intense clinical study has focused on the use of these agents in empiric treatment, treatment of suspected or proven infection, and prophylaxis. Recognition of the limitations of antifungal therapy in the neutropenic host has led to evaluation of the adjunctive role of immunotherapy.

Topics: Amphotericin B; Aspergillosis; Azoles; Candidiasis; Fluconazole; Humans; Immunotherapy; Leukemia; Mycoses; Neutropenia

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

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.

Topics: Amphotericin B; Animals; Animals, Domestic; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Fusarium; Humans; Immunocompromised Host; Infant; Leukemia; Male; Mycoses

Geotrichum capitatum sepsis are rare, occurring exclusively in immunocompromised patients.. We report the case of a patient with acute leukemia, presenting with chemotherapy-induced neutropenia and hospitalized in an intensive care unit for a severe sepsis. In spite of an antibiotic and antifungal treatment, the patient died of cardiorespiratory failure. Later on, blood cultures proved to be positive for Geotrichum capitatum.. If fungal infections are common in neutropenic patients, Geotrichum capitatum sepsis remain exceptional. The portal of entry is digestive or respiratory, and the invasion is favored by immunodepression and suppression of the normal microbial flora. Induced lesions can be multiorganic. The treatment is not well established, and the association of either amphotericine B and 5-fluorocytosine or amphotericine B and itraconazole would lead to better results. Nevertheless, the prognosis is still unfavorable, with a mortality rate of approximately 75%.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Combinations; Fatal Outcome; Flucytosine; Geotrichosis; Humans; Immunocompromised Host; Itraconazole; Leukemia; Male; Middle Aged; Neutropenia; Opportunistic Infections

We report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well-documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico-pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.

Topics: Amphotericin B; Child, Preschool; Female; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Multiple Myeloma; Mycoses; Opportunistic Infections; Treatment Outcome

Fungal infections have become an important cause of mortality in patients with hematological malignancies. In recent years, fungi such as Candida tropicalis, Aspergillus spp, Fusarium spp and Trichosporon spp have emerged as important pathogens. Amphotericin B remains the antifungal agent with the broadest spectrum of activity, although some of the newer pathogens may be resistant. The administration of this drug in lipid vehicles reduces the toxicities, permitting the administration of higher doses that may be more effective. The new agents, fluconazole and itraconazole, have activity against some fungal pathogens, although their role in therapy has not been fully determined. Fluconazole has been shown to be effective for prophylaxis of Candida infections.

Topics: Amphotericin B; Drug Resistance, Microbial; Humans; Leukemia; Mycoses

Neutropenic patients are at high risk of developing invasive fungal diseases. A number of studies, both randomized and historical, have demonstrated that empiric therapy with amphotericin B in neutropenic patients with fever, refractory to antibiotics, results in a decrease in the frequency and mortality of deep fungal infections. Recent years have seen a number of advances in the management of neutropenic patients. Reasonably effective antifungal prophylaxis now exists and in many centres forms part of the routine care of neutropenic patients. Other centres advocate the use of selective decontamination and/or protective isolation. Furthermore the duration of neutropenia can be reduced with the use of haematopoetic growth factors. The impact of empiric amphotericin B in patients already benefiting from such treatments has not been adequately studied. The optimum dose of empiric amphotericin B is not defined. The criteria for commencing amphotericin B therapy in febrile neutropenic patients must therefore be redefined on the basis of further studies carried out in the context of these developments. We offer an approach to the use of empiric amphotericin B based on risk factors and prophylaxis.

Topics: Amphotericin B; Bone Marrow Transplantation; Clinical Trials as Topic; Fever of Unknown Origin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunologic Factors; Leukemia; Multicenter Studies as Topic; Mycoses; Neutropenia; Patient Isolation; Randomized Controlled Trials as Topic; Risk

The Candida species account for approximately three-fourths of fungal infections in patients with cancer. Although Candida albicans is the most frequent cause, C. tropicalis is increasingly implicated as an important pathogen. Over a 12 year period 19 children treated for leukemia at our institution developed C. tropicalis infections. We describe their clinical presentation, extent of fungal infection, treatment, and outcome. Fungemia without meningitis in 11 children was treated successfully, whereas C. tropicalis meningitis in 7 children was uniformly fatal. An additional patient had unsuspected, widespread infection detected at autopsy. Multiple sites, including the cerebrospinal fluid yielded C. tropicalis. Previously reported risk factors including neutropenia, broad-spectrum antibiotic usage, corticosteroid therapy, and total parenteral nutrition were observed in our cases. A high index of suspicion and the early use of aggressive antifungal therapy are critical to the successful management of C. tropicalis infections in children with leukemia.

Topics: Abscess; Adolescent; Amphotericin B; Candida; Candidiasis; Cerebrospinal Fluid; Child; Child, Preschool; Combined Modality Therapy; Drainage; Female; Fluconazole; Fungemia; Humans; Infant; Leukemia; Male; Meningitis, Fungal; Neutropenia; Parenteral Nutrition, Total; Retrospective Studies; Risk Factors; Superinfection; Tennessee

Invasive fungal sinusitis is becoming increasingly common in patients undergoing BMT. This study was undertaken to evaluate the incidence, presenting symptoms, diagnosis procedures, treatment and outcome of invasive fungal sinusitis. The study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eleven patients (2.6%) developed invasive fungal sinusitis, 8 had underlying hematologic malignancies and 3 severe aplastic anemia (SAA). Median interval between BMT and fungal sinusitis was 22.5 days (range 2-106 days). Eight of 11 patients had protracted neutropenia (median 8 days with median neutrophil count at the time of fungal sinusitis diagnosis of 0.25 x 10(9)/l). Four patients developed GVHD before fungal sinusitis was diagnosed. Presenting symptoms were fever (100%), orbital swelling (63%), facial pain (54%) and nasal congestion (36%). In 8 patients Aspergillus species were isolated (A. flavus in 7, A. quadrilineatus in 1); in 1 patient Candida albicans was isolated and in the other 2 fungal elements were detected histologically (Fusarium and Mucor, respectively). Six of the patients underwent surgical debridement at diagnosis. Three received granulocyte transfusions. All patients received systemic amphotericin B (7 conventional and 4 amphotericin B colloidal dispersion (ABCD)). Only 2 of the 11 patients responded completely to therapy with a follow-up of 15 months. It appears that invasive fungal sinusitis is a potentially fatal complication in immunocompromised patients post-BMT. Current treatment approaches are largely ineffective and new methods of management of this serious problem are needed.

Topics: Adolescent; Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Purging; Bone Marrow Transplantation; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Debridement; Drainage; Female; Follow-Up Studies; Graft vs Host Disease; Granulocytes; Humans; Immunocompromised Host; Incidence; Infant; Leukemia; Leukocyte Transfusion; Lymphoma; Male; Middle Aged; Mitosporic Fungi; Mycoses; Neutropenia; Sinusitis; Survival Rate; Treatment Outcome

Among the opportunistic infections in patients with leukemias systemic fungal infections contribute a major part if not the majority. This results from autopsy data and is supported clinically when using new criteria by imaging techniques, while microbiological documentation shows a low sensitivity in this situation. Those lessons require a change in strategy toward an earlier and empiric use of systemic antifungal drugs in the frequent infections appearing as fever of unknown origin. By its high systemic activity and low toxicity Fluconazole facilitates this approach. Amphotericin B with 5-Flucytosine remain as the most established standard. Liposomal Amphotericin B allowing higher dosage by lower toxicity appears effective as salvage treatment especially in aspergillosis which also responds to Itraconazole available as oral formulation so far.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Leukemia; Mycoses; Tomography, X-Ray Computed

Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad-spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations.

Topics: Acute Disease; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Bacterial Infections; Clinical Trials as Topic; Fever; Humans; Leukemia; Mycoses; Neutropenia; Remission Induction

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Catheters, Indwelling; Female; Hepatic Artery; Humans; Leukemia; Liver Abscess; Male; Mycoses; Portal Vein; Splenic Artery; Splenic Diseases

We present six cases of fusariosis caused by Fusarium solani that were diagnosed over a three-year period in 166 adult patients undergoing chemotherapy for acute leukemia. Necrotic skin lesions were evident in four patients, fungemia in three, and a deep cellulitis around a great toe nail at the time of a febrile illness in two. The mean minimal inhibitory concentration (MIC) of amphotericin B was 3.3 micrograms/mL and of miconazole, 5.3 micrograms/mL; all isolates were resistant to 5-fluorocytosine. All patients received amphotericin B (1.0-1.5 mg/kg per d) plus 5-fluorocytosine. In contrast to results found in the literature, five patients had resolution of their infections, and the one patient who died had necropsy evidence of disseminated fusariosis. Review of our cases and of the literature did not reveal a definitive source for the organism or its portal of entry. Fusarium spp. must be recognized as opportunistic pathogens that cause a potentially fatal infection in compromised patients.

Topics: Adult; Amphotericin B; Female; Flucytosine; Fusarium; Humans; Immune Tolerance; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Prolymphocytic; Male; Middle Aged; Mycoses; Opportunistic Infections

Topics: Amphotericin B; Antifungal Agents; Blood Donors; Blood Transfusion; Granulocytes; Hemorrhage; Infection Control; Leukemia; Platelet Transfusion; Transfusion Reaction; Vancomycin

Topics: Aminoglycosides; Amphotericin B; Anemia, Aplastic; Bacterial Infections; Bone Marrow Transplantation; Graft Survival; Graft vs Host Disease; Humans; Immunosuppression Therapy; Leukemia; Mycoses; Patient Isolation; Postoperative Complications; Sulfamethoxazole; Time Factors; Trimethoprim; Virus Diseases

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amphotericin B; Blood Group Incompatibility; Blood Transfusion; Granulocytes; Histocompatibility Antigens; Humans; Immunization; Indium; Infection Control; Leukapheresis; Leukemia; Methods; Mycoses; Radioisotopes

The term mucormycosis encompasses a distinctive group of infections caused by fungi belonging to genera within the taxonomic order Mucorales, usually Rhizopus, Absidia, Mortierella, and Mucor. These fungi are widespread in nature, subsisting on decaying vegetation and diverse organic materials. Although the fungi and spores of Mucorales show minimal intrinsic pathogenicity toward normal persons, they can initiate aggressive and fulminant infections under certain clinical conditions. Ketoacidotic diabetics are predisposed to rhinocerebral mucormycosis, whereas patients with leukemia or lymphoma are susceptible to pulmonary or disseminated infections. These infections, which often result in devastating long-term sequelae for surviving patients, pose difficult diagnostic and therapeutic challenges.

Topics: Amphotericin B; Dermatomycoses; Diabetic Ketoacidosis; Facial Dermatoses; Female; Gastrointestinal Diseases; Humans; Leukemia; Lung Diseases, Fungal; Lymphoma; Male; Mucorales; Mucormycosis

Topics: Acute Disease; Adrenal Cortex Hormones; Amphotericin B; Aspergillosis; Blood Transfusion; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Flucytosine; Hodgkin Disease; Humans; Iron; Leukemia; Leukemia, Lymphoid; Lymphoma; Mucor; Multiple Myeloma; Mycoses; Neutropenia; Rhizopus

Topics: Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Child; Child, Preschool; Corticosterone; Diabetes Complications; Female; Humans; Infant; Infant, Newborn; Leukemia; Lung Diseases, Fungal; Male; Meningoencephalitis; Middle Aged; Mucormycosis; Postoperative Complications; Sinusitis; Substance-Related Disorders; Syndrome; Transplantation, Homologous

Topics: Amphotericin B; Ampicillin; Antifungal Agents; Bacterial Infections; Blood Transfusion; Bone Marrow Transplantation; Carbenicillin; Cephalothin; Diagnosis, Differential; Fever; Gentamicins; Humans; Infections; Leukemia; Leukocytes; Lymphoma; Methicillin; Mycoses; Patient Isolators; Penicillin Resistance; Pneumonia, Pneumocystis; Polymyxins; Sepsis; Toxoplasmosis; Virus Diseases

Topics: Adult; Amphotericin B; Candidiasis; Female; Gastrointestinal Diseases; Histoplasmosis; Humans; Infant; Leukemia; Lymphoma; Male; Mucormycosis; Mycoses; Nystatin

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.

Topics: Amphotericin B; Aspergillosis; Aspergillus; Child; Child, Preschool; Female; Fluconazole; Humans; Leukemia; Male; Retrospective Studies; Risk Factors

Antifungal prophylaxis is shown to decrease the risk of invasive fungal infection (IFI) after hematopoietic stem-cell transplantation (HSCT). Posaconazole has been approved for prophylaxis in HSCT. However, it is only available orally given three times per day. We evaluated once weekly intravenous amphotericin B lipid complex (ABLC), given its broad-spectrum antifungal activity and prolonged half-life (172 hr), as an alternative prophylaxis in HSCT.. We prospectively randomized allogeneic HSCT patients to receive 7.5 mg/kg of intravenous ABLC weekly or 200 mg of posaconazole orally three times per day as prophylaxis for up to 6 weeks. Endpoints were the incidence of IFI and drug-related toxicities. ABLC was discontinued if creatinine level increased to two times the baseline or greater.. A total of 46 patients were randomized; 40 received at least one dose of the drug and were included in the analysis: 19 received ABLC and 21 received posaconazole. All patients received tacrolimus. Apache II score, neutropenia, and creatinine, bilirubin, and alanine aminotransferase levels were similar in both groups at baseline. One patient in the ABLC arm and none in posaconazole arm developed IFI (5% vs. 0%, P=0.48). More patients in the ABLC arm doubled their serum creatinine (53% vs. 5%, P=0.001) necessitating discontinuation of the study drug.. High-dose prophylactic ABLC in HSCT was associated with nephrotoxicity that could be aggravated by the concomitant use of other nephrotoxic agents. Further studies are needed to evaluate the role of weekly high-dose ABLC as antifungal prophylaxis in patients at lower risk for nephrotoxicity.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Leukemia; Lipids; Lymphoma; Male; Middle Aged; Mycoses; Prospective Studies; Risk; Tacrolimus; Time Factors; Transplantation, Homologous; Triazoles

The aim of this study was to evaluate the influence of malignancy and the impact of nephrotoxic drugs used in bone marrow transplantation (BMT) on the circulating levels of cystatin C in leukemia.. We studied nineteen patients (eleven men and eight women; mean age 30.1 +/- 11.2, 27.9 +/- 7.1 years) with acute lymphoblastic leukemia, acute myeloid leukemia and chronic myeloid leukemia. Cystatin C, urea, creatinine and creatinine clearance (CrCl) were measured 24 h before BMT, 1 week after BMT, 2 weeks after BMT and 3 weeks after BMT. The control group consisted of twenty healthy adults, and the mean age was 29.1 +/- 8.9.. At the pretransplantation period, values of cystatin C were significantly higher than in the control group (P < 0.05). Urea, creatinine and CrCl values were not statistically different from the controls. One week after BMT, the level of cystatin C was significantly low as compared to the levels measured 24 h before BMT, but was still significantly higher than the controls (P < 0.05), whereas the levels of urea, creatinine and CrCl were in accordance with the levels of the controls. Two and three weeks after BMT, cystatin C values maintained the significant increase (P < 0.05), whereas the values of urea, creatinine and CrCl still corresponded with those of the controls in both group.. Our preliminary data expose that cystatin C is not a reliable GFR marker in patients during leukemia or for monitoring nephrotoxic drugs used in BMT, but we can not reach definitive conclusion due to no gold standard for comparing the diagnostic accuracy of cystatin C. Further study is needed to elucidate the precise mechanism underlying this observation.

Topics: Acyclovir; Adult; Amikacin; Amphotericin B; Biomarkers; Bone Marrow Transplantation; Creatinine; Cyclosporine; Cystatin C; Cystatins; Female; Glomerular Filtration Rate; Humans; Leukemia; Male; Metabolic Clearance Rate

Conventional amphotericin B-based antifungal therapy for invasive fusariosis in patients with a hematologic malignancy results in a > or = 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species.. In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis. Twenty-one patients with proven or probable invasive fusariosis who had disease refractory to or who were intolerant of standard antifungal therapy received oral posaconazole suspension (800 mg per day in divided doses) as salvage therapy.. Successful outcome occurred in 10 (48%) of all 21 patients. Among patients with leukemia who received posaconazole therapy for >3 days, the overall success rate was 50%; for patients who recovered from myelosuppression, the success rate was 67%, compared with 20% for those with persistent neutropenia.. These results suggest that posaconazole is useful for the treatment of invasive fusariosis.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Fusarium; Humans; Leukemia; Male; Middle Aged; Mycoses; Retrospective Studies; Salvage Therapy; Treatment Outcome; Triazoles

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 remain a major cause of treatment failure and death in acute leukemia. New liposomal preparations of amphotericin B are now available. While less toxic, their comparative efficacy and toxicity profiles are unknown. In this study the comparative efficacy and safety of ABLC vs. AmBisome was evaluated in seventy-five patients with leukemia who developed 82 episodes of suspected or documented mycosis, and were treated (1:1) with either ABLC (n=43) or AmBisome (n=39). Both drugs were dosed accordingly from 3 to 5 mg/kg/day. Using an intent-to-treat analysis, the overall response to therapy was 27/43 (63%) for ABLC and 15/39 (39%) for AmBisome (p=0.03). Median dose and duration of treatment was 10 days at 3 mg/kg for ABLC and 15 days at 4 mg/kg for AmBisome. Acute, not dose-limiting infusion side effects were seen in 70% vs. 36% (p=0.002), ABLC vs. AmBisome. Increase of bilirubin > 1.5 times from baseline was 38% vs. 59%, ABLC vs. AmBisome (p=0.05). ABLC and AmBisome were equally effective for the treatment of suspected or documented fungal infections. While, acute infusion-toxicity was greater with ABLC, infusion toxicity requiring discontinuation was similar for both drugs. AmBisome was better tolerated than ABLC but was associated with mild abnormalities in liver function tests at the end of therapy.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Drug Combinations; Humans; Leukemia; Mycoses; Phosphatidylcholines; Phosphatidylglycerols

Topics: Amphotericin B; Antifungal Agents; Drug Interactions; Humans; Itraconazole; Leukemia; Liver; Liver Function Tests

We performed a prospective, randomized, multicenter trial to evaluate the effectiveness of prophylactic inhalations with aerosolized amphotericin B (aeroAmB) to reduce the incidence of invasive aspergillus (IA) infections in patients after chemotherapy or autologous bone marrow transplantation and an expected duration of neutropenia of at least 10 days. From March 1993 until April 1996, 382 patients with leukemias, relapsed high-grade non-Hodgkin lymphomas, or solid tumors were randomized with a 13:10 ratio to receive either prophylactic aeroAmB inhalations at a dose of 10 mg twice daily or no inhalation prophylaxis in an unblinded fashion. The incidence of proven, probable, or possible IA infections was 10 of 227 (4%) in patients who received prophylactic aeroAmB. This did not differ significantly from the 11 of 155 (7%) incidence in patients who received no inhalation prophylaxis (P =.37). Moreover, no differences in the overall mortality (13% v 10%; P =.37) or in the infection-related mortality (8% v 7%; P =.79) were found. In contrast to other nonrandomized trials, we observed no benefit from prophylactic aeroAmB inhalations, but the overall incidence of IA infections was low.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Bone Marrow Transplantation; Combined Modality Therapy; Female; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Transplantation, Autologous; Treatment Outcome

Invasive fungal infections are an increasingly common problem in cancer patients and in other vulnerable groups. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. Against the background of a recognized problem of invasive aspergillosis in haematology/oncology patients treated at the Christie Hospital, we undertook a prospective study in patients at risk for IPA. The aim of the study was to improve outcome by using the linked strategies of first, early diagnosis, and secondly, early aggressive therapy with a lipid-associated formulation of amphotericin B, amphotericin B colloidal dispersion ('Amphocil'). Early investigation comprised the use of high-resolution computerized tomography scanning of the thorax and fibreoptic bronchoscopy to obtain bronchoalveolar lavage specimens, processed using conventional detection and culture methods. Using this approach, the incidence of proven or probable IPA in patients with acute leukaemia was 9%. Prompt initiation of amphotericin B colloidal dispersion therapy led to a successful outcome in 11 of 13 patients, compared with a mortality of 100% in historical controls.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Female; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged

Invasive aspergillosis is a life-threatening fungal infection which, in neutropenic patients, is associated with an extremely high mortality rate despite optimal treatment. In order to investigate microbiological risk factors for treatment failures in more detail, Aspergillus spp. obtained from 29 patients with haematological diseases after myelo-ablative chemotherapy and bone marrow transplantation were analysed for their susceptibility to amphotericin B in vitro and this was compared with clinical outcome to see if there was a correlation. Aspergillus flavus was present in 12 (41 %) of the 29 patients, Aspergillus terreus in nine (31%) and Aspergillus fumigatus in eight (28%). The susceptibility of these isolates to amphotericin B varied between and within the three species. A. terreus was the only organism against which the MIC was consistently high, A. fumigatus and A. flavus showing variation between isolates in the degree of resistance to amphotericin B. The degree of in-vitro resistance was the only parameter correlating with clinical outcome in a univariate analysis and the only prognostic value in a multivariate analysis considering known risk factors. Irrespective of the species, all six patients with isolates against which the MIC was <2 mg/L survived, whereas most (22/23) of those with isolates resistant to > or = 2 mg/L died. Infections among the six survivors were caused by amphotericin B-susceptible A. fumigatus and A. flavus, but not A. terreus. We conclude that the outcome of aspergillus infection depends on the in-vitro susceptibility of the isolates to amphotericin B. Survival was poor in patients with isolates resistant to amphotericin B and good in those with amphotericin B-susceptible specimens. A. terreus was always associated with high resistance to amphotericin B and with poor survival.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Aspergillus; Burkitt Lymphoma; Cells, Cultured; Humans; Leukemia; Microbial Sensitivity Tests; Multiple Myeloma; Multivariate Analysis; Predictive Value of Tests; Prognosis; Risk Factors; Treatment Outcome

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 microgram/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (P = 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (P = 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (P = 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Dopamine; Female; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Mycoses; Prospective Studies

115 patients undergoing allogeneic or autologous bone marrow or peripheral blood stem cell transplantation were treated empirically or for documented fungal infection with liposomal amphotericin-B in doses up to 10mg/kg bodyweight for a duration up to 61 days. The therapy was excellent tolerated and clinical side effects occurred in only eight patients. The drug had to be withdrawn in one episode. A significant influence of liposomal amphotericin-B on laboratory parameters was not observed. Creatinine increased under therapy from a median base point of 1,0 (0,2-3,5) mg/dl to the upper normal value of 1,4 (0,4-4,2) mg/dl. Heavy increases of creatinine as well as of bilirubin, OT and PT were mostly associated with GvHD or regimen related toxicity. Considering the high-risk state of the patients the overall response rate was favourable with 62,9%. However, despite administration of liposomal amphotericin-B culture-proven mycoses were associated with a high morbidity (93,3%). Only one of fourteen patients was cured from Candida lambica septicaemia. We conclude that the antimycotic therapy with liposomal amphotericin-B has a low incidence of side effects. This should, considering the high mortality of fungal infections in BMT recipients, encourage investigators to perform dose escalating studies against the conventional formulation.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia; Male; Middle Aged; Mycoses

Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count > 0.5 x 10(9)/L, toxicity precluding further fluconazole use, and death. By Kaplan-Meier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01).

Topics: Adult; Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Aspergillosis; Bacteremia; Candidiasis, Oral; Double-Blind Method; Drug Therapy, Combination; Fever; Fluconazole; Humans; Incidence; Infusions, Intravenous; Leukemia; Lymphoma; Middle Aged; Mycoses; Neutropenia; Treatment Outcome

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Bone Marrow Transplantation; Female; Fever; Fluconazole; Humans; Leukemia; Male; Mycoses; Neutropenia; Pilot Projects; Prospective Studies; Treatment Outcome

To determine the value of aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis (IPA), we initiated a prospective randomized multicenter trial. The scheduled intent-to-treat interim analysis included 115 patients (30%) with prolonged neutropenia after chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia/high-grade non-Hodgkin's lymphoma, or solid tumors undergoing autologous stem cell transplantation. Sixty-five patients had been randomized to receive prophylactic aerosol amphotericin B inhalations at a dose of 10 mg twice daily (group A); for the remaining 50 patients no aerosol amphotericin B prophylaxis was used (group B). No serious side effects from amphotericin B inhalations occurred, but coughing (54%), bad taste (51%), and nausea (37%) caused early cessation of aerosol amphotericin B prophylaxis in 23% (15/65) of courses. In group A, the incidence of proven, probably, or possible IPA was 5% (3/65) as compared with 12% (6/50) in group B (p > 0.05). Microbiologically documented bacterial pneumonias were observed in 5/65 (8%) patients in group A and in 1/50 (2%) patients in group B (p > 0.05). Thus, no reduction in incidence of IPA from use of prophylactic aerosol amphotericin B inhalations was found in this interim analysis. As there were no serious side effects from aerosol amphotericin B prophylaxis, accrual in the study will continue for a total of 380 patients.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Female; Humans; Leukemia; Lung Diseases, Fungal; Lymphoma; Male; Middle Aged; Neutropenia

To investigate the influence of infusion duration on infusion-related adverse effects (IRAEs) associated with prophylactic or treatment regimens of amphotericin B in patients with leukemia/bone marrow transplant (BMT).. Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial.. A university-affiliated tertiary care teaching hospital.. The study population consisted of 25 consecutive patients with leukemia/BMT who received 162 prophylactic regimen infusions and 169 treatment regimen infusions of amphotericin B via a central line. Prior to each infusion all patients received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were administered. Patients were monitored closely for IRAEs, which were documented by using a standardized data collection form.. The incidence and nature of IRAEs during a 6-hour monitoring period following the initiation of each infusion was measured. Patients served as their own controls. IRAEs were compared according to infusion duration and therapeutic indication.. Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were administered. We found no difference between 2- and 4-hour infusions in the incidence and severity of IRAEs, including overall events (29% of 166 2-hour infusions vs. 25% of 165 4-hour infusions), chill scores (8% of 166 2-hour infusions vs. 7% of 165 4-hour infusions; highest score 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 degrees C), systolic hypotension (6% vs. 2%), greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05).. This study demonstrates that patients with leukemia/BMT without myocardial or renal dysfunction who receive hydrocortisone and diphenhydramine as premedications can tolerate 2-hour central line infusions of prophylactic or treatment regimens of amphotericin B as well as 4-hour infusions.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Hospitals, University; Humans; Immunocompromised Host; Infusions, Intravenous; Leukemia; Male; Middle Aged; Mycoses; Prospective Studies; Time Factors

Our previous experiences with liposomal amphotericin have suggested that it is an effective antifungal agent in neutropaenic patients with relatively few toxicity problems compared with conventional amphotericin B. This interim report presents early data from a single-centre, prospective randomised study with AmBisome. The study was designed to compare the early initiation of AmBisome in febrile neutropaenic patients (with haematological malignancy) with its later use, and to examine the efficacy and toxicity of different doses of this antifungal agent. Our experiences from the first 137 patients recruited (n = 200) are discussed, in addition to some of the difficulties that have arisen during the study.

Topics: Amphotericin B; Ceftazidime; Fever; Humans; Leukemia; Lymphoma; Neutropenia; Prospective Studies

Patients with haematological malignancies requiring an antifungal therapy were randomly assigned to receive amphotericin B diluted in either 5% dextrose or in fat emulsion (Intralipid). Twenty-one patients were included in each group. Mean duration of amphotericin B therapy was 8.4 days in the dextrose group and 12.8 days in the Intralipid group. Amphotericin B infusion induced chills in 16 of 21 patients in the dextrose group and in 5 of 21 in the Intralipid group (P = 0.0008). Serum creatinine increased > 75% from baseline in ten patients in the dextrose group compared with only two in the Intralipid group (P = 0.007). A > or = 50% decrease of creatinine clearance was observed in 14 of 21 patients in the dextrose group compared with seven of 21 patients in the Intralipid group (P = 0.025). No difference was found between the two groups with regard to potassium and sodium requirement. Among patients who did not receive magnesium before antifungal therapy, magnesium supplementation was required more frequently in the dextrose group (8/12 vs 2/11; P = 0.02). Concomitant amikacin dosage reduction was more frequent in the dextrose group due to nephrotoxicity (7/19 vs 2/20; P = 0.045). A similar difference in vancomycin dosage reduction was observed between the two groups (12/20 vs 5/19; P = 0.03).

Topics: Adult; Aged; Amphotericin B; Fat Emulsions, Intravenous; Female; Glucose; Humans; Kidney; Leukemia; Lymphoma; Male; Middle Aged

Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.. Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.. Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).. At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Blast Crisis; Female; Fluconazole; Humans; Kidney Diseases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mycoses; Premedication; Prospective Studies; Remission Induction

To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.. A randomized, controlled, multicenter trial.. 30 hematologic units in tertiary care or university hospitals.. 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.. Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.. An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.. Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).. Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Mycoses; Neutropenia; Patient Compliance; Treatment Outcome

The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P < 0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.

Topics: Administration, Oral; Adult; Amphotericin B; Antineoplastic Agents; Bacterial Infections; Drug Combinations; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Leukemia; Male; Middle Aged; Mycoses; Norfloxacin

Topics: Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Candidiasis; Female; Humans; Incidence; Leukemia; Liposomes; Male; Metabolic Diseases; Neoplasms; Transplantation, Autologous; Transplantation, Homologous

Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.

Topics: Adult; Aerosols; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Female; Humans; Immunocompromised Host; Incidence; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Neutropenia; Opportunistic Infections; Pilot Projects

Topics: Adult; Aged; Amphotericin B; Double-Blind Method; Drug Administration Schedule; Fever; Humans; Immune Tolerance; Infusions, Intravenous; Leukemia; Middle Aged; Mycoses; Nausea; Prospective Studies; Vomiting

A prospective, randomized, double-blind crossover study was performed to compare the incidence and severity of amphotericin-B-induced acute toxicity (chills, fever, nausea and vomiting) after two- and four-hour infusions in 33 leukemic patients with suspected or microbiologically proven systemic fungal infections. Each patient was treated in an alternating fashion of two- and four-hour infusions every other day. Toxicity was graded according to modified WHO-criteria. Evaluation of 264 infusions revealed no difference between the two schedules neither in incidence nor severity of acute toxic reactions. These data indicate that amphotericin B given over 2 hours is equally well--or poorly (!)--tolerated than the four-hour regimen.

Topics: Adult; Aged; Amphotericin B; Double-Blind Method; Fever; Humans; Infusions, Intravenous; Leukemia; Middle Aged; Mycoses; Nausea; Prospective Studies; Shivering; Time Factors; Vomiting

In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Mycoses; Prospective Studies; Remission Induction

Forty patients with acute leukemia (age 16-71 years, 13 females, 27 males) with induced neutropenia due to chemotherapy received either 50 mg fluconazole or 800 mg amphotericin B per day orally as prophylaxis against fungal infection. Nasal and genital swabs, mouth washings, urine, stool and blood serum were taken for mycological and serological examination before and weekly during one episode of neutropenia (less than 10(9) granulocytes/l) per patient. The quantitative determination of the yeast concentration in stool specimens demonstrated that amphotericin B led to intestinal yeast count reduction in only one third of the patients and could not prevent the increase of the intestinal yeast flora in another third of the patients. Beyond that the quantitative determination of yeast colonization in oropharynx, genital region, blood and stool did not prove to be a reliable tool for evaluating the host-fungus relationship during neutropenia. On the other hand mycoserology reflected episodes of candidosis well. 19 patients treated with fluconazole showed only minor titer increases. In 21 patients treated with amphotericin B, four fungemias were found: two by both hemagglutination (HAT) and immunofluorescence (IFT), one by IFT and one by antigen detection (Ramco Cand-Tec) alone. In only one of these cases yeast cells were released in urine. From these results is concluded that control of serology is essential in studies of that type and that fluconazole seems to provide better protection from candidosis than amphotericin B during induced neutropenia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Agents; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Mycoses; Neutropenia

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

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

Because gram-positive infections cause morbidity following intensive antileukemic chemotherapy, the effects of vancomycin versus placebo were evaluated in a randomized, double-blind, placebo-controlled trial in 60 adult patients with acute leukemia and first infectious fever during prolonged (mean of 32 days) granulocytopenia. Gram-positive sepsis was associated with first fever in 17 (28 percent) of the 60 patients. None of 31 patients randomly assigned to receive vancomycin demonstrated gram-positive infection, whereas 16 of 22 patients randomly assigned to receive placebo subsequently had gram-positive infection (seven had sepsis, and nine had local infections; p less than 0.005). All patients with gram-positive infection were then given vancomycin, and all showed prompt clinical responses. The predominant gram-positive organism causing infection was beta-lactam-resistant Staphylococcus epidermis (19 of 44 isolates). Patients randomly assigned to receive vancomycin had more rapid resolution of first infectious fever and fewer total febrile days during the granulocytopenic course than did patients randomly assigned to receive placebo. Although vancomycin had no effect on the presence or absence of documented fungal infection, patients treated with vancomycin received empiric amphotericin B for recurrent or persistent fever later (mean of 14 days after initial antibiotic coverage was begun) than did patients receiving placebo (mean of 9.9 days; p less than 0.005), and thus received fewer total days of empiric amphotericin B therapy (mean of 16.3 days) than did patients given placebo (mean of 24.6 days; p less than 0.01). These data demonstrate that empiric use of vancomycin reduces the morbidity of gram-positive infections following intensive antileukemic therapy and decreases the need for empiric use of toxic amphotericin B.

Topics: Adult; Agranulocytosis; Amphotericin B; Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Gram-Positive Bacteria; Humans; Leukemia; Middle Aged; Random Allocation; Vancomycin

In a prospective study the efficacy of two regimens for selective decontamination of the digestive tract was studied in patients with acute leukaemia during remission induction therapy. Seventy-eight patients were randomized to receive either a combination of cotrimoxazole, polymyxin B and nystatin (group A) or a combination of nalidixic acid, polymyxin B, neomycin and nystatin. With both regimens the gastrointestinal tract could be decontaminated equally effectively from potential pathogens. In the oropharyngeal region the decontamination from Enterobacteriaceae was significantly better in group A (P less than 0.01). In both groups less than 10% of the acquired infections were caused by gram-negative bacilli and no gram-negative septicaemia occurred in either group. The median time interval until the first acquired infection was 17 days in group A and 36 days in group B, respectively (P less than 0.05). It is concluded that regimen A might be more effective than regimen B though both regimens prevent reliably severe gram-negative infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Cephalosporins; Enterobacteriaceae Infections; Female; Flucytosine; Humans; Leukemia; Male; Middle Aged; Oxacillin; Penicillins; Prospective Studies; Staphylococcal Infections; Streptococcal Infections

72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.

Topics: Amphotericin B; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Imidazoles; Immunosuppressive Agents; Ketoconazole; Leukemia; Mycoses; Neutropenia; Nystatin; Piperazines; Random Allocation

Fifty-two patients with nonlymphocytic leukaemia were studied during remission induction treatment in a randomized trial to ascertain the effect of prophylactic oral trimethoprim-sulfamethoxazole on infection and fever rate. A decrease in the total number of acquired infections was found (16 infections in the group given trimethoprim-sulfamethoxazole versus 31 in the control group, p less than 0.01). The number of patients without any infection in the trimethoprim-sulfamethoxazole group was 13 compared to only three in the control group (p less than 0.01). Patients in the trimethoprim-sulfamethoxazole group needed parenteral antibiotics during 33% of the days they were granulocytopenic compared to 61% of these days for patients in the control group. However, six of nine bacteriologically documented infections in the trimethoprim-sulfamethoxazole group were caused by resistant microorganisms compared to two out of 20 in the control group.

Topics: Acute Disease; Agranulocytosis; Amphotericin B; Drug Combinations; Drug Therapy, Combination; Fever; Humans; Infection Control; Infections; Leukemia; Middle Aged; Random Allocation; Sulfamethoxazole; Trimethoprim

Autopsy examinations were conducted in 72 patients with hematologic malignant neoplasms who received antibacterial therapy before their deaths. These patients were participants in a large double-blind study designed to assess the efficacy of oral amphotericin B in decreasing the incidence of candidal infection. The patients received either 50 mg of amphotericin B orally four times a day, or they received a matching placebo. Eight of 33 patients (24%) who had received placebo and two of 39 (5%) who had received amphotericin had histopathologic evidence of disseminated candidiasis. We conclude that in these patients with hematologic malignant neoplasms who received antibiotics within two weeks of death, the concomitant oral administration of amphotericin was effective in decreasing the incidence of systemic candidal infections, indicating that the gastrointestinal tract serves as a portal of entry for Candida albicans.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Autopsy; Candidiasis; Clinical Trials as Topic; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged

Liposomal amphotericin-B (L-AmB) prophylaxis is used in children with leukemia when azoles are contraindicated, but its effect is debated. We reviewed cases of invasive aspergillosis despite L-AmB 2.5 mg/kg twice weekly in children with high-risk leukemia during 2012-2019. Ten (16%) of 62 children had proven or probable aspergillosis. Thus, L-AmB prophylaxis offered insufficient protection for Aspergillus, in particular for Aspergillus flavus.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Child; Child, Preschool; Denmark; Hospitals, Pediatric; Humans; Infant; Leukemia; Retrospective Studies

Invasive fungal infections are one of the vital complications among acute leukemia patients undergoing induction chemotherapy. Among them, Geotrichum clavatum infections present extremely rarely with atypical clinical symptoms which make them difficult to diagnose. In this paper, we report a case of infection caused by Geotrichum clavatum in a 10-year old child with acute leukemia, which is the first documented case from mainland China. With underlying childhood leukemia, the child suffered from recurrent bacterial and fungal infection and even underwent abdominal surgery during the treatment. Fortunately, the therapeutic effect was finally achieved by adjusting the treatment program to dual anti-fungal treatment with micafungin and amphotericin B. Information regarding the epidemiological, clinical, and therapeutic features, in this case, shows significant perspectives for anti-fungal treatment for immunocompromised individuals, wherefore the rate of recovery and survival can be achieved.

Topics: Amphotericin B; Antifungal Agents; Child; China; Geotrichosis; Geotrichum; Humans; Invasive Fungal Infections; Leukemia; Male; Micafungin; Treatment Outcome

We describe an outbreak of mucormycosis in a pediatric oncology hospital during December 2010 and the measures taken to stop it. The outbreak began with two consecutive cases of laboratory-documented mucormycosis infections within 1 week. Investigations to track the source were conducted immediately. Air plate cultures from machines and ducts supplying patients' rooms revealed the growth of Rhizomucor. Of five affected patients, all had acute leukemia and three were histopathologically proven. All patients were treated with liposomal amphotericin B after mucormycosis was diagnosed. Posaconazole was used as a secondary prophylaxis in one case. Three patients died.

Topics: Air Microbiology; Amphotericin B; Cancer Care Facilities; Child; Child, Preschool; Disease Outbreaks; Egypt; Female; Hospitals, Pediatric; Humans; Infant; Leukemia; Male; Mucormycosis; Rhizomucor

Topics: Adult; Aged; Allografts; Amphotericin B; Hematopoietic Stem Cell Transplantation; Humans; Lebanon; Leukemia; Middle Aged; Neutropenia

Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a rare invasive fungal agent that may lead to mortal clinical course in patients with hematological malignancies. This agent can be colonized in skin, lungs and intestines, and it can cause major opportunistic infections. Invasive systemic infections due to S.capitata have been reported in immunosuppressed patients. In this report, two patients with invasive S.capitata infections detected during the course of persistent neutropenic fever in acute leukemia, were presented. In both cases empirical caspofungin was added to the treatment, as no response was obtained by board-spectrum antibacterial therapy in neutropenic fever. In the first patient, there were no significant findings except the chronic inflammation observed in the biopsies which was performed for the symptoms of lymphadenitis, myositis, and hepatosplenic candidiasis. While persistent fever was on going, S.capitata was isolated from the blood and catheter cultures. There was no response after catheter removing and the introduction of amphotericin B and voriconazole therapy, therefore allogeneic stem cell transplantation plan for the second time for bone marrow aplasia was taken an earlier time. However, the patient died due to progressive pericardial and pleural effusion and multiorgan failure, although an afebrile process after stem cell transplantation could be obtained. Similarly the second patient had persistent fever despite empirical caspofungin treatment. The additional symptoms of diarrhea, abdominal pain and subileus have indicated an intraabdominal infection. During the follow up, S.capitata was isolated from the blood and catheter cultures. Catheter was removed and amphotericin B was initiated. No response was obtained, and voriconazole was added to treatment. Despite of an afebrile and culture-negative period, the patient died as a result of Acinetobacter sepsis and multiorgan failure. Minimal inhibitory concentration values for both of the Saprochete strains were found as 0.25 µg/ml for amfoterisin B, 1 µg/ml for flukonazol, 0.125 µg/ml for vorikonazol and 0.25 µg/ml for itrakonazol. Virulence model was created by injecting the isolates to the Galleria mellonella larvae, and the life cycle of the larvae were determined. The observation revealed that the infected larvae began to die on the second day and there was no live larvae remained on the eleventh day. In conclusion, S.capitata sho

Topics: Adult; Amphotericin B; Animals; Antifungal Agents; Caspofungin; Catheter-Related Infections; Echinocandins; Fatal Outcome; Female; Fungemia; Humans; Leukemia; Lipopeptides; Moths; Mycoses; Opportunistic Infections; Saccharomycetales; Voriconazole; Young Adult

The occurrence of nephrotoxicity with vancomycin is approximately 17%, but can increase to 35% when combined with other nephrotoxic agents. Patients with hematologic malignancies may be at greater risk for vancomycin-induced nephrotoxicity due to nephrotoxic chemotherapy and tumor lysis syndrome.. The primary objective of this study was to determine the occurrence of nephrotoxicity in adult patients with leukemia receiving vancomycin.. A retrospective review approved by the Institutional Review Board was conducted on adult patients with leukemia who received at least one dose of vancomycin during hospital admission between 1 January 2009 and 30 April 2009.. Forty patients had an occurrence of nephrotoxicity (16%) while 210 patients did not have an occurrence of nephrotoxicity. In multivariate analysis, variables significantly associated with development of nephrotoxicity included active disease status (odds ratio, 4.38 [95% CI 1.1-29.4], p = 0.0291), concomitant intravenous acyclovir administration (odds ratio, 3.83 [95% CI, 1.6-8.9]; p = 0.0022), and concomitant amphotericin administration (odds ratio, 4.26 [95% CI, 1.9-9.4]; p = 0.0004).. The occurrence of nephrotoxicity in patients with leukemia treated with vancomycin was 16% in our study, similar to previously published reports. Active disease status and concomitant use of intravenous acyclovir and amphotericin were identified as significant risk factors for development of nephrotoxicity. The presence of risk factors for vancomycin nephrotoxicity should be evaluated prior to initiation of therapy to determine appropriateness of use.

Topics: Acyclovir; Administration, Intravenous; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Female; Humans; Kidney Diseases; Leukemia; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Vancomycin

Aspergillus pneumonia often is a fatal consequence of prolonged neutropenia in patients with acute leukemia. Despite prompt diagnosis and adequate antifungal therapy, mortality remains high among these patients. Recognizing early signs and symptoms, as well as risk factors, is the key to reducing morbidity and mortality.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Humans; Leukemia; Pneumonia

A yeast strain was isolated from the sputum sample of a leukaemia patient in the Spirito Santo Hospital of Pescara, Italy. The fungus produced a pigment that formed a reddish halo around colonies, and was identified and deposited as a Metschnikowia spp. (accession number IHEM 25107-GenBank accession number JQ921016) in the BCCM/IHEM collection of biomedical fungi and yeasts (Bruxelles, Belgium). Although the physiology of the strain was close to that of Metschnikowia sinensis, the D1/D2 sequence did not correspond to any previously described Metschnikowia species. Phylogeny of the genus Metschnikowia is complex and requires far more analysis. We present the first non-M. pulcherrima Metschnikowia spp. isolate recovered from a human, and emphasize the role of man as a transient carrier of environmental yeasts, the pathogenicity of which still needs to be defined.

Topics: Amphotericin B; Antifungal Agents; Base Sequence; DNA, Fungal; DNA, Ribosomal; Fluconazole; Humans; Italy; Leukemia; Male; Metschnikowia; Microbial Sensitivity Tests; Molecular Sequence Data; Mycoses; Phylogeny; Pigments, Biological; Pyrazines; Sequence Analysis, DNA; Sputum; Voriconazole

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

Invasive fungal infections are a major cause of morbidity and mortality in hematopoietic stem cell transplantation patients. In recent years, new resistant fungal strains have emerged, requiring physicians to use new generation antifungal drugs or drug combinations. We report a case of invasive Fusarium infection involving the nasopharynx, skin and lungs, following haploidentical hematopoietic stem cell transplantation in an 8-year old patient with recurrent leukemia. The patient was treated with combination antifungal treatment of amphotericin B and voriconazole, as well as supportive care, with the improvement of his symptoms and home discharge. We reviewed the history of combination antifungal therapy. Combination antifungal treatment has been used since 1979, especially in immunocompromised patients. Although randomized controlled trials are lacking, reports favoring combination, especially for invasive mold infections, are increasingly published.

Topics: Amphotericin B; Antifungal Agents; Child; Dermatomycoses; Drug Therapy, Combination; Fusariosis; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Male; Nasopharyngeal Diseases; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Cord Blood Stem Cell Transplantation; Echinocandins; Humans; Leukemia; Lung; Male; Middle Aged; Neutropenia; Postoperative Complications; Pulmonary Aspergillosis; Pyrimidines; Triazoles; Voriconazole

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with haematological malignancies. Antifungal combination therapy is a promising treatment option. However, available data on feasibility, toxicity and efficacy of this therapy are limited. Therefore, this study was conducted to evaluate the feasibility, toxicity and outcome of different antifungal combination therapies. Patients with haematological malignancies receiving antifungal combination therapy for IFI were retrospectively analysed. Toxicity and response were documented at the end of therapy. Survival was evaluated at the end of therapy and after 12 weeks. Fifty-six patients were treated with different antifungal combinations in the period between 2001 and 2007. The majority of patients (63%) received a combination of liposomal amphotericin B and caspofungin as antifungal combination treatment. Toxicity of all applied combinations was tolerable. At the end of combination therapy, favourable response was 65%, whereas unfavourable outcome occurred in 35% of the cases. Mortality at the end of treatment was 11% and 34% 3 months after initiation of combination therapy. Antifungal combination therapy is feasible and efficient in haematological cancer patients and allogeneic stem cell transplant recipients with IFI. Prospective studies to evaluate the optimal combinations are needed.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Caspofungin; Cohort Studies; Drug Therapy, Combination; Echinocandins; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lipopeptides; Male; Middle Aged; Mycoses; Myeloablative Agonists; Myelodysplastic Syndromes; Retrospective Studies; Survival Analysis; Transplantation, Homologous

We retrospectively analyzed 542 proven/probable mould infections registered, in the course of 2 studies, in 8,633 patients with acute leukemia, focusing on scedosporiosis. We aimed to define scedosporiosis incidence and mortality rate over a 15-year period. Only 5 cases of scedosporiosis were identified, all of them involving patients with acute myeloid leukemia (AML). We also reviewed all cases of Scedosporium spp. infections in acute leukemia reported to date in the international literature. The 52 cases analyzed confirmed that acute myeloid leukemia is the category with the highest risk of scedosporiosis. Clinical features of scedosporiosis were extremely variable and closely related to patient immune status. Infection disseminated to multiple sites in a very high percentage of patients and outcome was confirmed to be very poor. In our surveys all patients died, in spite of Amphotericin B compounds or voriconazole administration. Our review of literature found scedosporiosis attributable mortality rate (AMR) to be 77%. In conclusion, scedosporiosis, although extremely rare, represents a big problem for clinicians because of its aggressive clinical presentation and the lack of an effective therapy. New drugs with in vitro activity against Scedosporium spp (voriconazole, posaconazole) should be considered. However, their clinical activity should be more widely demonstrated.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Child; Child, Preschool; Humans; Leukemia; Male; Middle Aged; Mycetoma; Pyrimidines; Retrospective Studies; Scedosporium; Triazoles; Voriconazole

We describe drug-drug interactions (DDIs) encountered with antifungals in clinical practice.. Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug-drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI.. There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug-drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%).. In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Cyclosporine; Drug Interactions; Female; Fluconazole; France; Furosemide; HIV Infections; Hospitals, University; Humans; Hydrocortisone; Hypokalemia; Intensive Care Units; Itraconazole; Kidney Diseases; Leukemia; Male; Middle Aged; Neoplasms; Retrospective Studies

Topics: Acute Disease; Aged; Amphotericin B; Aspergillosis; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Mucormycosis

We report a pulmonary mucormycosis due to Absidia corymbifera. It occurred in a leukemic patient treated for a probable aspergillosis regressing after voriconazole treatment. The patient responded to surgery and a combination of liposomal amphotericin B and itraconazole. He was alive and well after 7-months of follow up.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Humans; Itraconazole; Leukemia; Male; Radiography, Thoracic; Respiratory Tract Infections; Treatment Outcome; Zygomycosis

Zygomycosis is a highly aggressive infection observed in immunocompromised patients, such as those with haematological malignancies. The sites most frequently involved are the sinuses and the lungs. New diagnostic tools and new antifungal treatments are essential in order to diagnose early and treat efficiently infections due to moulds. We report a case of sinusitis due to Absidia corymbifera occurring during chemotherapy-induced bone marrow aplasia in a patient with acute leukaemia. The sinusitis was successfully treated with AmBisome, and surgical debridement.

Topics: Absidia; Acute Disease; Aerosols; Amphotericin B; Amsacrine; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Debridement; Drug Resistance, Fungal; Drug Resistance, Neoplasm; Etoposide; Fluconazole; Humans; Immunocompromised Host; Leukemia; Liposomes; Middle Aged; Mucormycosis; Sinusitis; Tomography, X-Ray Computed

We report a leukemic patient with C. krusei fungemia who failed to respond to liposomal amphotericin B therapy alone. The addition of caspofungin eradicated infection and was well tolerated. Our report is the first to describe successful treatment of a patient with invasive C. krusei infection using this combination of antifungals. Combination therapy could be a useful treatment option for invasive candidosis, particularly when caused by more resistant species such as C. krusei.

Topics: Adult; Amphotericin B; Candida; Candidiasis; Caspofungin; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Leukemia; Lipopeptides; Male; Peptides, Cyclic; Treatment Outcome

Invasive Acremonium infection in humans is rare. We report a patient with leukemia who developed pyomyositis due to Acremonium species. Painful cutaneous nodules and severe myalgia were the first clinical manifestations during the neutropenic stage after chemotherapy. Magnetic resonance image (MRI) revealed multiple nodular lesions scattered along the intramuscular regions of the lower legs. Culture of an aspiration grew Acremonium species. Surgical drainage was performed. Although all antifungal agents tested showed no in vitro inhibitory activity, we successfully treated this patient with amphotericin B, granulocyte colony-stimulating factor (G-CSF), and surgical drainage.

Topics: Acremonium; Acute Disease; Adolescent; Amphotericin B; Drainage; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Mycoses; Neutropenia; Opportunistic Infections

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus flavus; Dermatomycoses; Fatal Outcome; Female; Fluconazole; Humans; Leukemia; Thumb

Mucormycosis is a rare fungal infection that can involve the sino-orbito-cerebral region. Sino-orbito-cerebral mucormycosis is most common in patients who are immunocompromised or have diabetes mellitus, severe malnutrition or burns. This condition can be fatal if it is not diagnosed early and treated aggressively. This article presents 4 cases of mucormycosis, including 2 with orbital apex syndrome, 1 with cavernous sinus syndrome, and 1 with multiple cranial nerve involvement. All of the patients were presented with painful ophthalmoplegia. The predisposing factors for mucormycosis included diabetes mellitus (three patients) and chronic leukemia (one patient). In all cases, mucormycosis was diagnosed by examining endoscopic sinus drainage material and was treated with surgical debridement and amphotericin B. Two patients with central nervous system involvement died. The others have survived, but still exhibiting various neurologic abnormalities after aggressive treatment. Patients with mucormycosis rarely present with orbital apex syndrome. The possibility of mucormycosis should be investigated in any patient with painful ophthalmoplegia, and prompt otorhinolaryngologic examination is recommended to ensure rapid diagnosis and treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Cavernous Sinus; Central Nervous System Fungal Infections; Chronic Disease; Cranial Nerve Diseases; Debridement; Diabetes Complications; Female; Humans; Leukemia; Male; Middle Aged; Mucormycosis; Ophthalmoplegia; Orbital Diseases

Caspofungin, in association with other antifungal drugs, was administered as rescue therapy in two cases of documented and one case of possible invasive fungal infection in children with acute leukaemia or undergoing allogeneic bone marrow transplant. The combined therapy was well-tolerated and seemed to be effective in all three patients. A combination antifungal therapy including caspofungin could represent an effective therapy for children with invasive mycoses refractory to single-agent antifungal therapy.

Topics: Adolescent; Amphotericin B; Bone Marrow Transplantation; Caspofungin; Child; Drug Therapy, Combination; Echinocandins; Humans; Leukemia; Lipopeptides; Liposomes; Male; Peptides; Peptides, Cyclic; Pneumonia; Pyrimidines; Transplantation, Homologous; Triazoles; Voriconazole

The clinical relevance of mold isolated from blood cultures, even in severely immunosuppressed allogeneic hematopoietic stem cell transplantation (HSCT) recipients, remains uncertain. The authors hypothesized that isolation of non-Candida fungi from blood cultures in patients undergoing high-risk HSCT would have clinical significance.. The authors reviewed the records of 73 allogeneic HSCT recipients between January 1, 1993 and January 1, 2001 in whom fungal species were isolated from blood cultures.. Fifty-two episodes of non-Candida fungemia occurred in 48 patients (66%) after a median of 10 days (range, 2-341) after transplantation. All 48 patients had indwelling intravascular catheters, and 23 patients (48%) had profound neutropenia. Thirty-five of 48 patients had received partially matched, related donor stem cell grafts (19 patients had 3-antigen-mismatched grafts); 35 patients had undergone T-cell depleted transplantation and 9 patients were receiving treatment for acute graft-versus-host disease. In 5 of 48 patients (10%), death was attributed to fungemia that occurred 8-11 days after the initial fungal blood culture was obtained; all 5 patients were age > 30 years. No deaths occurred in the younger age group (n = 22 patients; P = 0.05). In the 24 patients who did not receive systemic antifungal therapy, 4 deaths (17%) were attributed to infections with Penicillium (n = 2 patients), Epicoccum (n = 1 patient), or Penicillium plus Cladosporium species (n = 1 patient). Of the 24 patients who received amphotericin B, only 1 patient (4%) died as a result of a probable hematogenous Aspergillus species infection; this difference in outcome, however, was not significant (P = 0.2).. Most of the non-Candida fungal blood culture isolates in recipients of high-risk, mismatched donor transplantation were clinically nonsignificant. However, because these low-virulence saprophytes occasionally may cause life-threatening disease, a reevaluation of the existing diagnostic paradigm is needed so that clinically significant fungemia may be differentiated from pseudofungemia.

Topics: Adolescent; Adult; Amphotericin B; Aspergillus; Child; Child, Preschool; Cladosporium; Culture Techniques; Female; Fungemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Male; Middle Aged; Penicillium; Retrospective Studies; Risk Factors; Transplantation, Homologous; Treatment Outcome

We evaluated the value of Aspergillus PCR as a tool for diagnosing invasive aspergillosis from whole-blood samples during antifungal therapy. In a 3-year study, 36 patients receiving antifungal therapy due to chest radiographic findings highly suggestive of fungal pneumonia were evaluated. The PCR results from whole-blood samples were compared to those obtained from bronchoalveolar lavage fluids and/or tissue specimens. A total of 205 whole-blood samples, 15 fine-needle aspirations or tissue biopsy specimens, and 21 bronchoalveolar lavage fluids and tracheal secretions were analyzed using PCR. Of the 36 patients, 15 had proven, 9 had probable, and 12 had possible invasive Aspergillus infection according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. For patients with proven infection the sensitivity values of PCR in lung and blood samples were 100 and 40%, respectively. The negative predictive value of blood monitoring under conditions of antifungal treatment was 44%. Clearance of fungal DNA from blood was associated with resolution of clinical symptoms in six of nine patients with proven infection. Repeated positive PCR results for Aspergillus were associated with fatal outcome, as three of six patients died. For patients with probable infection the sensitivity values of PCR in lung fluid and blood were 66 and 44%, respectively. The benefit of PCR diagnosis using whole-blood samples is limited when sampling takes place after treatment has been started. Performance of Aspergillus PCR using tissue samples is recommended in addition to microscopic examination and culture technique for sensitive detection of fungal infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Base Sequence; Bronchoalveolar Lavage Fluid; DNA Primers; DNA, Fungal; Humans; Leukemia; Middle Aged; Neoplasms; Polymerase Chain Reaction; Pyrimidines; Transplantation; Triazoles; Voriconazole

Invasive aspergillosis (IA) has emerged as a common cause of morbidity and mortality among immunocompromised patients. At The University of Texas M. D. Anderson Cancer Center (Houston, TX), Aspergillus terreus is second to A. fumigatus as the most common cause of IA. In the current study, the authors compared the risk factors and outcomes associated with IA caused by A. terreus and IA caused by A. fumigatus.. The authors retrospectively reviewed the medical records of 300 patients who received care at our institution between 1995 and 2001 and who had cultures that were positive for Aspergillus infection, including 90 patients whose cultures were positive for A. fumigatus and 70 patients whose cultures were positive for A. terreus.. Thirty-two patients with IA caused by A. terreus and 33 patients with IA caused by A. fumigatus were evaluated. The two groups were comparable in terms of age, gender, and underlying disease. Leukemia was the most common underlying malignancy (84%). More than 40% of patients in each group had undergone bone marrow transplantation. There was a trend toward a higher frequency of neutropenia among patients with IA caused by A. terreus (P = 0.12). IA caused by A. terreus was considered to be nosocomial in origin significantly more frequently compared with IA caused by A. fumigatus (P = 0.03). In vitro, A. terreus was found to be more resistant to amphotericin B (minimal inhibitory concentration [MIC90], 4.0 microg/mL) than to antifungal therapy (MIC90, 1.0 Hg/mL) in the isolates that were tested (< 50% of all isolates). The overall rate of response to antifungal therapy was 39% for patients with A. fumigatus infection, compared with 28% for patients with A. terreus infection (P = 0.43).. Despite the decreased in vitro susceptibility of A. terreus (relative to A. fumigatus) to amphotericin B, the two groups within the current patient population had comparably poor responses to amphotericin B preparation and somewhat improved responses to posaconazole.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Aspergillus; Aspergillus fumigatus; Cross Infection; Drug Resistance, Fungal; Female; Humans; Leukemia; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Risk Factors; Triazoles

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Dermatomycoses; Fusarium; Humans; Immunocompromised Host; Immunosuppressive Agents; Leukemia; Male; Middle Aged

Pulmonary aspergillosis and other invasive fungal infections (IFIs) commonly complicate the management of patients with acute leukemia. Standard amphotericin-based therapies may be ineffective for many patients and the available salvage agents (itraconazole and caspofungin) are reported to possess only moderate activity against resistant infections. Laboratory evidence suggests a synergistic interaction between amphotericin and caspofungin. The authors treated a group of patients with amphotericin-refractory IFIs with the combination of caspofungin and amphotericin (or liposomal amphotericin).. A retrospective evaluation of patients with amphotericin-resistant IFIs was conducted. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable.. Thirty patients were included in this analysis. Twenty-six patients had acute leukemia. Based on recently published criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4-65 days) and 7.8 mg/kg (range, 4.2-66.1 mg/kg), respectively. The median duration of combination therapy was 24 days (range, 3-74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Mild to moderate nephrotoxicity was noted in 50% of patients, necessitating the substitution of liposomal amphotericin. Mild elevation of alkaline phosphatase levels occurred in 30% of patients. Caspofungin was temporarily withheld from one patient who developed moderate but reversible biochemical hepatotoxicity.. The antifungal combination of caspofungin and amphotericin can be administered safely to high-risk patients with hematologic malignancies. Although an absolute assessment of efficacy is limited by the design of this study, encouraging outcomes were noted for many patients. The authors plan to evaluate this regimen further in a randomized clinical trial.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Caspofungin; Drug Therapy, Combination; Echinocandins; Female; Humans; Leukemia; Lipopeptides; Lung Diseases, Fungal; Male; Middle Aged; Peptides; Peptides, Cyclic; Pneumonia; Retrospective Studies

Invasive pulmonary aspergillosis is difficult to diagnose and a critical ill with high mortality. In this paper, the diagnosis and treatment of invasive pulmonary aspergillosis complicated in 3 cases of hematological malignancy (2 acute leukemias and 1 MDS-RA) were retrospectively analysed. All patients had histories of hypoimmunity and were received prophylactic antifungal treatment. Pulmonary aspergillosis infection still occurred and confirmedly diagnosed by sputum examination. After 7 to 14 days of combination treatment of liposomal amphotericin B, itraconazole and flucytosine, 2 cases were cured and another showed effective. In conclusion, early diagnosis and treatment of invasive pulmonary aspergillosis are very critical and the therapeutic effectiveness of combined scheme with liposomal amphotericin B, itraconazole and flucytosine is very effective for pulmonary aspergillosis.

Topics: Adult; Amphotericin B; Anemia, Refractory; Aspergillosis; Female; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Candida albicans; Candidiasis; Chemoprevention; Drug Resistance, Microbial; Female; Fluconazole; Fungemia; Humans; Leukemia; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia

Hepatosplenic microabscesses secondary to invasion by various organisms may result in life-threatening conditions, especially in patients with cancer. Whether these patients should continue ongoing cytotoxic therapy, which might result in neutropenia, with the risk of progressive abscess formation or fungemia, remains a dilemma. We report five cases of pediatric acute leukemia with hepatosplenic microabscesses in children aged 4 years to 18 years. These patients presented with prolonged fever and neutropenia after antineoplastic chemotherapy, followed by abdominal pain, hepatosplenomegaly and hepatic dysfunction. Abdominal ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated multiple small lesions compatible with hepatosplenic candidiasis in all of the patients. Cultures, including blood or stool cultures, were positive in only two cases. Treatment with intravenous antifungal agents, including amphotericin B, liposomal amphotericin B, and/or fluconazole were successful in two cases. These two patients remained event-free and survived for more than 24 months (20 months and 22 months after infection was diagnosed). The duration of systemic antifungal medication administration ranged from 3 months to 22 months. The serial image examinations revealed drastic reductions in small residual lesions in the two patients who survived the longest. The major issues for these patients were how long the antifungal therapy should be administered for, and how to select the optimal drug and dosage to avoid hepatic and renal toxicity. Among our patients, alternative therapy with amphotericin B, liposomal amphotericin B, and fluconazole was used according to the patients' conditions, and the duration of antifungal therapy was determined by clinical manifestations and imaging study changes.

Topics: Abscess; Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Drug Administration Schedule; Humans; Leukemia; Liver Abscess; Male; Splenic Diseases

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.

Topics: Acute Disease; Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Combined Modality Therapy; Debridement; Drug Therapy, Combination; Female; Hepatitis; Humans; Leukemia; Lung Diseases, Fungal; Opportunistic Infections; Osteomyelitis; Pyrimidines; Remission Induction; Sacroiliac Joint; Splenic Diseases; Triazoles; Voriconazole

A 64-year-old male was treated for acute myeloid leukemia with idarubicin and cytarabin. He developed pulmonary mycosis (radiologically consistent with aspergillosis), which responded to intravenous amphotericin B.

Topics: Amphotericin B; Antibiotics, Antineoplastic; Antifungal Agents; Antimetabolites, Antineoplastic; Cytarabine; Fever; Humans; Idarubicin; Leukemia; Lung; Lung Diseases, Fungal; Male; Middle Aged; Radiography

We report the chest radiographic and CT findings in 21 immunocompromised patients with invasive pulmonary aspergillosis (IPA) and describe the outcome when the early diagnosis was linked to treatment with liposomal amphotericin B.. Chest radiographs and CT examinations were analyzed retrospectively in 53 consecutive neutropenic patients with suspected early IPA.. Twenty-one of 244 patients admitted for chemotherapy of hematologic malignancy fulfilled the definition for IPA - incidence of 8.6%. The incidence of normal and non-specific chest radiographic findings was high (29% and 71%, respectively) during the early stages of IPA. The CT halo sign was seen in 20 of the 21 patients (95%), and occurred within 5 days of neutropenic fever that was unresponsive to antibiotics in 5 patients. Crescent signs or cavitations were seen in 7 patients (33%). Treatment with liposomal amphotericin B was associated with an attributable mortality of 9.5%. Two patients died from IPA having a high fungal burden.. Early chest CT in neutropenic patients at risk for IPA is an important diagnostic and management tool and should be included in the investigative protocol even when chest radiographs are normal or non-specific.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Female; Humans; Immunocompromised Host; Leukemia; Liposomes; Male; Middle Aged; Neutropenia; Radiography, Thoracic; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome

Between September 1993 and December 1993, during extensive hospital construction and indoor renovation, a nosocomial outbreak of invasive pulmonary aspergillosis occurred in acute leukemia patients treated in a regular ward that has only natural ventilation. The observed infection rate was 50%. Chemoprophylaxis with intravenous continuous low-dose amphotericin B was then instituted as a preventive measure. During the next 18 months invasive pulmonary aspergillosis developed in 43% of acute leukemia patients. After that period a new hematology ward was opened with an air filtration system through high-efficiency particulate air filtration (HEPA) filters, and a bone marrow transplantation program was started on the hematology service. During the following three years, none of the acute leukemia or bone marrow transplantation patients who were hospitalized exclusively in the hematology ward developed invasive pulmonary aspergillosis, although 29% of acute leukemia patients who were housed in a regular ward, because of shortage of space in the new facility, still contracted invasive pulmonary aspergillosis. Overall, 31 patients were diagnosed with invasive pulmonary aspergillosis during almost five years: 74% of patients recovered from invasive pulmonary aspergillosis, and 42% are long-term survivors; 26% of patients died of resistant leukemia with aspergillosis, but no one died of invasive pulmonary aspergillosis alone. In conclusion, during an on-going construction period, an extremely high incidence rate of invasive pulmonary aspergillosis in acute leukemia patients undergoing intensive chemotherapy was observed. Institution of low-dose intravenous amphotericin B prophylaxis marginally reduced the incidence rate of invasive pulmonary aspergillosis. Keeping patients in a special ward with air filtration through a HEPA system eliminated invasive pulmonary aspergillosis completely. Among patients who developed invasive pulmonary aspergillosis, early diagnosis and treatment are probably the explanation for the favorable outcome.

Topics: Adult; Air Microbiology; Air Pollution, Indoor; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Cross Infection; Disease Susceptibility; Filtration; Hematology; Hospital Design and Construction; Hospital Units; Hospitals, Teaching; Humans; Immunocompromised Host; Incidence; Israel; Leukemia; Lung Diseases, Fungal; Neutropenia; Patients' Rooms; Spores, Fungal; Treatment Outcome; Ventilation

The safety and efficacy of amphotericin B lipid complex (ABLC) were evaluated in a retrospective study of 46 paediatric patients with invasive infections. The study included a large proportion of patients who were refractory to or intolerant of conventional antifungal therapy. The mean age of the children was 9.7 +/- 4.8 years. Primary underlying conditions included mainly haematopoietic stem cell transplantation, leukaemia and lung transplantation. The mean daily dose given was 4.11 mg/kg for a mean duration of 38.7 days. At the end of therapy, 38 of 46 (83%) patients responded successfully to treatment with ABLC, including 18 of 23 (78%) with aspergillosis and 17 of 19 (89%) with candidiasis. ABLC was well tolerated, with a low incidence of adverse events. The mean creatinine value was 74.5 microl/mol/l at baseline and 78.2 micromol/l at the end of therapy. These results support the use of ABLC in the treatment of invasive fungal infections in children, including patients who have previously failed, or are intolerant of, traditional antifungal regimens.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Creatinine; Drug Combinations; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Leukemia; Lung Transplantation; Male; Mycoses; Phosphatidylcholines; Phosphatidylglycerols; Retrospective Studies

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4-12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0.5 x 109/l after a median of 11.5 d (range 11-13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18-59 d) and are alive and well after a median follow-up of > 390 d (range 336-417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Aortic Aneurysm; Arteriosclerosis; Aspergillosis, Allergic Bronchopulmonary; Bone Marrow Transplantation; Cell Count; Diabetes Complications; Diabetes Mellitus; Granulocyte Colony-Stimulating Factor; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Chronic-Phase; Lung Diseases, Fungal; Male; Middle Aged; Neutrophils; Platelet Count; Recurrence; Remission Induction; Tomography, X-Ray Computed; Transplantation, Homologous; Treatment Outcome

Invasive fungal disease is a major cause of death in immunocompromised patients. The filamentous fungus Scedosporium consists of two species, S. prolificans and S. apiospermum, which can cause infections in immunocompromised patients that are often fatal. A significant feature of this pathogen is its broad resistance to many antifungal agents, including amphotericin B.. Five cases of infection with Scedosporium spp. occurred in patients with haematologic malignancies over a 10-month period. Three patients with S. prolificans were severely immunosuppressed and neutropenic; two were in relapse and another was early post-matched unrelated bone marrow transplant. All three died despite treatment with various combinations of amphotericin B and itraconazole. Two patients who were less immunosuppressed and had a normal neutrophil count developed S. apiospermum infection. Both were successfully treated with liposomal amphotericin B and itraconazole.. Disseminated infection in immunocompromised hosts with Scedosporium spp. is often fatal. However, in patients with a lesser degree of immunocompromise and particularly in those infected with the less virulent S. apiospermum, intensive antifungal therapy with liposomal amphotericin B and itraconazole may be associated with complete eradication of infection. Med Pediatr Oncol 2001;37:122-125.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Fatal Outcome; Female; Humans; Immunocompromised Host; Itraconazole; Leukemia; Liposomes; Male; Mycetoma; Scedosporium

Fusarium is a newly emerging fungal pathogen associated with significant morbidity and mortality in the immunocompromised host. We have reviewed our hospital's experience with Fusarium between 1985 and 1995. Fusarium species were isolated from 22 specimens, representing 11 patients. Cases were not clustered by time period. The median age of the patients was 36.5 years (range 17-69 years). The sources of the organism were 12 skin lesions from eight patients, seven blood cultures from two patients and one specimen each from a Hickman catheter tip, nail clippings and a bronchoalveolar lavage. Seven of the patients had chemotherapy-induced neutropenia when the Fusarium was isolated. Five of them developed invasive fusarosis during acute leukaemia induction treatment. They remained neutropenic, and none survived. The other two patients recovered from neutropenia and were treated successfully for this infection. The remaining four patients were not neutropenic or immunocompromised. Three grew Fusarium from skin or nail clippings and one from bronchial alveolar lavage (BAL). There was no evidence of invasive disease in any of the four. None of them received antifungal therapy, and they were all alive at last follow-up. We conclude that Fusarium is a newly emerging infection in neutropenic patients. A high index of suspicion, especially for skin lesions, will help in early diagnosis before systemic and visceral dissemination. Excision of the initial focus of infection and antifungal therapy, aided by speedy neutrophil recovery, are likely to protect patients threatened with these fatal infections. Fusarium isolated from non-neutropenic, non-immunosuppressed patients is not significant and does not merit systemic antifungal treatment.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Dermatomycoses; Female; Foot Dermatoses; Fusarium; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Necrosis; Neutropenia; Retrospective Studies; Skin

Topics: Amphotericin B; Child; Drug Combinations; Humans; Immunosuppression Therapy; Leukemia; Mycoses; Myeloproliferative Disorders; Phosphatidylcholines; Phosphatidylglycerols

Blastoschizomyces capitatus (BC), a filamentous fungus of genus Trichosporum, is as an important opportunistic pathogen in the compromised host. Within the past 10 years, 47 cases of BC infection have been published. Most of the patients had acute leukemia (AL) or related disorders and had received chemotherapy treatment. Due to BC's resistance to currently used antifungal agents, this infection represents a therapeutic challenge and serious complication in the treatment of hematology malignancies. Here we report our experience with BC infection in four patients with acute leukemia or related disorders.

Topics: Acute Disease; Adult; Amphotericin B; Antifungal Agents; Female; Humans; Immunosuppression Therapy; Leukemia; Male; Middle Aged; Mycoses; Neutropenia; Trichosporon

The aim of this study was to evaluate the relevance of in vitro antifungal susceptibility to clinical response in neutropenic patients with invasive oral aspergillosis.. Nine isolates of Aspergillus species were obtained from invasive oral infections in 9 patients with hematologic malignancies and tested for their in vitro susceptibility to amphotericin B, fluconazole, miconazole, 5-fluorocytosine, and itraconazole. Minimal inhibitory concentration values of the 5 drugs were obtained for each fungus through use of a microdilution broth method. The patients were treated with intravenous amphotericin B (30-50 mg/day) in combination with oral 5-fluorocytosine (3000-6000 mg/day) and/or oral itraconazole (200 mg/day).. Amphotericin B and itraconazole were found to be very active, with minimal inhibitory concentration values of 0.861 and 0.194 microg/mL, respectively. Miconazole and 5-fluorocytosine showed minimal inhibitory concentration values of 1.72 and 3.56 microg/mL, respectively. On the other hand, fluconazole FCZ showed low activity, with a minimal inhibitory concentration value in excess of 64.0 microg/mL. During neutropenia, combined antifungal chemotherapy stabilized oral aspergillosis and prevented the spread of oral lesions in 8 patients in whom neutrophil counts eventually recovered.. The results imply that in vitro susceptibility testing may serve as an informative parameter with respect to the efficacy of these antifungals in the treatment of invasive oral aspergillosis, inducing fungal stasis until the neutrophils recover.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Aspergillus; Drug Combinations; Drug Evaluation; Female; Fluconazole; Flucytosine; Humans; Immunocompromised Host; Itraconazole; Leukemia; Lymphoma; Male; Miconazole; Microbial Sensitivity Tests; Middle Aged; Mouth Diseases; Neutropenia

We treated 10 consecutive adults with a haematological malignancy, and an invasive aspergillosis (n = 8) or invasive candidosis (n = 2), with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Nine patients responded (five complete and four partial responses), and one died with invasive aspergillosis. Treatment was well tolerated, with only 4% of infusions followed by infusion-related adverse events, and the renal function improved in six patients who had an elevated serum creatinine before therapy. These data suggest that lower doses of ABLC may be equally effective but less toxic than higher doses. However, a controlled study is required to confirm these observations.

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

Topics: Acute Disease; Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Cholangitis; Female; Humans; Leukemia

Topics: Adolescent; Amphotericin B; Antifungal Agents; Brain Diseases; Fatal Outcome; Humans; Leukemia; Male; Mucormycosis; Orbital Diseases; Paranasal Sinus Diseases

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.

Topics: Acute Disease; Amphotericin B; Antifungal Agents; Child; Combined Modality Therapy; Debridement; Humans; Leukemia; Male; Mucormycosis; Muscular Diseases

To describe the MR appearance of necrotizing fungal granulomas occurring in the liver of leukemic patients with hepatosplenic fungal disease and transfusional hemosiderosis on antifungal antibiotics.. Four patients with acute myelogenous leukemia (n = 2) or acute lymphocytic leukemia (n = 2) who developed hepatosplenic fungal disease, and were treated with antifungal medication, underwent MRI examination on a 1.5 T MR imager. MR images were prospectively evaluated and correlated with liver biopsy (three patients), and clinical picture (one patient).. Multiple liver lesions measuring approximately 1 cm in diameter were identified in all patients. Lesions possessed a distinctive MR appearance: central mild hyperintensity with a peripheral ring of very low signal intensity on precontrast T1- and T2-weighted images. The central region of the lesions enhanced following gadolinium administration with the peripheral ring remaining low in signal intensity.. Necrotizing fungal granulomas in the liver of patients with transfusional hemosiderosis on treatment with antifungal antibiotics have a distinctive appearance of moderate high signal intensity center on T1- and T2-weighted and postgadolinium MR images with a peripheral rim of low signal intensity. This appearance reflects the presence of iron-laden macrophages in the periphery of granulomas and may be expected in processes that initiate an immune response involving aggregation of macrophages in the liver of patients with transfusional iron overload.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Antifungal Agents; Candidiasis; Child; Female; Granuloma; Hemosiderosis; Humans; Itraconazole; Leukemia; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Opportunistic Infections; Transfusion Reaction

The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases have resulted in an increased incidence of fungal infections. These infections are associated with a high mortality rate. There are several predisposing factors including broad-spectrum antibiotic, central venous access. Diagnosis remains difficult. Characteristic clinical manifestations are not constant and they appear only after neutrophil recovery. Responsible organisms are infrequently isolated. The use of invasive procedures is far from being justified in patients who suffering usual severe thrombocytopenia. The unique drug with proven efficiency in the treatment of fungal infections is amphotericin B or liposomal amphotericin B. A favourable outcome strongly correlated with complete leukemia remission. We describe our findings in seven leukemic patients with fungal infections.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; Child; Female; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Neutropenia; Retrospective Studies; Thrombocytopenia

To evaluate the following: the incidence of invasive Aspergillus sinusitis (AS); the value of surveillance nasal cultures and screening radiologic studies in predicting AS; the clinical criteria used to decide on surgical biopsy in patients suspected of having AS; the surgical and medical management of AS; and the outcome of AS in the peritransplantation period of children who underwent bone marrow transplantation.. Retrospective medical chart review.. Tertiary care children's hospital.. Eighty pediatric patients who underwent bone marrow transplantation for a variety of refractory malignant neoplasms or lymphohematopoietic disorders at the Children's National Medical Center, Washington, DC, from April 1, 1988, to September 30, 1993.. Diagnostic surgical biopsies, surgical débridement, and treatment with amphotericin B.. Resolution of AS and discharge from the hospital.. Seventy-two patients had screening sinus radiographs, 27 of which showed abnormalities. Aspergillus sinusitis developed in three of the patients with abnormal screening radiographs. Fifty-eight patients had screening nasal cultures. One culture was positive for Aspergillus, and histopathologically proved AS developed in this patient. Twelve diagnostic biopsies were done in nine patients. Three biopsy specimens showed histopathologic evidence of AS. The three patients with AS were successfully treated with aggressive surgical and medical therapy and were discharged from the hospital.. The incidence of AS was 4% (3/80) in the patients who underwent bone marrow transplantation. Screening radiographs, while not a good predictor of AS, have a role in evaluation of patients undergoing bone marrow transplantation to define preexisting sinus disease. Screening nasal cultures do not reliably predict AS. When AS is suspected and diagnostic biopsy is considered, the seven clinical criteria outlined in this article should be used. Survival of immunocompromised patients with AS requires early diagnosis and aggressive surgical and medical therapy.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Biopsy; Bone Marrow Transplantation; Child; Child, Preschool; Debridement; Female; Follow-Up Studies; Forecasting; Humans; Immunocompromised Host; Incidence; Infant; Leukemia; Male; Nose; Postoperative Complications; Radiography; Retrospective Studies; Sinusitis; Treatment Outcome

Topics: Administration, Inhalation; Aerosols; Agranulocytosis; Amphotericin B; Asthma; Bone Marrow Transplantation; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Time Factors

Our institution used an experimental protocol for the use of inhaled amphotericin B as a prophylactic measure to prevent fungal disease in severely immunocompromised patients. We did a prospective study of the physiologic effects of amphotericin B administration. We looked specifically at oxygen saturation levels, peak flow values, and symptoms of patients given amphotericin B. We collected data on a series of 18 patients and of 132 amphotericin B administrations. Four (22%) of the patients stopped treatments because of nausea and vomiting which were believed to be due to the inhaled amphotericin B. For the remaining patients, no treatment was stopped because of symptoms or physiologic changes caused by amphotericin B, although there were 9 instances of clinically significant bronchospasm as defined by a drop in peak flow of 20% or more, 9 clinically relevant increases in cough, and 3 clinically relevant increases in dyspnea. Forty-eight percent of the clinically relevant changes occurred in patient 8. Another 16% occurred in asthmatic subjects who were significantly more likely (p = 0.03) to experience a 20% or more drop in peak flow than were patients without asthma. The physiologic profile of the response to inhaled amphotericin B is acceptable.

Topics: Administration, Inhalation; Adult; Aerosols; Agranulocytosis; Amphotericin B; Asthma; Bone Marrow Transplantation; Cough; Dyspnea; Humans; Immunocompromised Host; Leukemia; Lung Diseases, Fungal; Nausea; Nebulizers and Vaporizers; Oxygen; Prospective Studies; Pulmonary Ventilation; Vomiting

The Authors report a case history of rhinocerebral mucormycosis in a patient with chronic lymphatic leukaemia and recommend that therapy be based on three different approaches: treatment for the underlying disease, systematic antifungal treatment with Amphotericine B, and surgical asportation of diseased tissue. They affirm that results may be surprisingly successful, even in cases with signs of orbital-cerebral involvement which are indicative of a poor prognosis and the concomitant presence of a serous disease such as leukaemia.

Topics: Aged; Amphotericin B; Antifungal Agents; Brain; Humans; Klebsiella; Leukemia; Male; Mucormycosis; Orbit; Staphylococcus aureus

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

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

The clinicopathologic characteristics of invasive oral aspergillosis in 16 immunocompromised patients who developed this infection during antileukemic chemotherapy are described. The primary site of the infection was the marginal gingiva, there was severe spontaneous pain, and the patients developed spiking fever and granulocytopenia. Necrotic ulceration of the gingiva rapidly extended to the contiguous mucosa, muscle, and bone. Microscopically, the necrotic tissue contained thrombotic vascular infarcts and there were hyphae that showed frequent transverse septa and dichotomous branching. The invasive organisms were not responsive to amphotericin B in the absence of remission of the leukemia and restoration of the depressed host defenses. In 15 patients who showed improvement of hematologic status, oral aspergillosis was controlled by the combination of antifungal chemotherapy and debridement of necrotic tissues.

Topics: Adult; Aged; Agranulocytosis; Amphotericin B; Aspergillosis; Female; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Mouth Diseases; Necrosis; Nystatin

This is a retrospective study comparing the methods of preventing fungal infection in a total of 420 episodes of chemotherapy-induced neutropenia of more than 10 days' duration between 1986 and 1992 in 104 patients with acute leukemia and 62 patients who underwent bone marrow transplantation. The episodes were divided into five groups according to the prophylactic regimens (group 1, oral amphotericin B (OA) only; 2, OA and nebulization of amphotericin B (NA); 3, OA and NA with a laminar air flow system (LAF); 4, oral fluconazole (OF) and NA; 5, OF, NA, and LAF. The total numbers of neutropenic episodes were 115, 141, 95, 37, and 32, respectively. A total of 15 episode of invasive fungal infections were documented. Aspergillosis was seen on two occasions each in groups 1 and 2, while none was seen in the patients who were under the LAF system. Nebulization of amphotericin B did not have a significant preventive effect in this study and it needs to be evaluated further by a randomized study.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Bone Marrow Transplantation; Fluconazole; Humans; Leukemia; Middle Aged; Neutropenia; Retrospective Studies

The study objective was to identify prognostic factors associated with survival in patients treated for acute leukemias who developed invasive aspergillosis (IA) during induction therapy. This retrospective analysis involved 21 patients treated in two hematologic centers over a six-year period. All were treated in protective isolated rooms with high-dose amphotericin B as soon as fungal infection was suspected. Ten (45%) of the twenty-one patients died. There was no statistical difference between the patients who survived and those who died in relation to the mean time of onset of IA or the total and mean daily dose of amphotericin B. On the other hand a favourable outcome correlated strongly with complete leukemic remission (p < 0.0001): all but one of the patients with objective residual leukemia died of IA, whereas all those who achieved complete hematological remission survived. In conclusion, it seems that the main vital prognostic factor in these leukemic patients with IA was the achievement of complete remission. We were unable to control IA in 10 of 11 patients with refractory leukemia, regardless of neutropenic status, despite early administration of high-dose amphotericin B. All the patients who achieved complete remission were successfully treated with amphotericin B.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Humans; Leukemia; Lung Diseases, Fungal; Middle Aged; Neutropenia; Patient Isolation; Prognosis; Remission Induction; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome

The use of oral itraconazole (200 mg daily) plus nasal amphotericin B (10 mg daily) for prophylaxis of invasive aspergillosis was evaluated in 164 patients with hematological malignancies at risk due to presence of neutropenia and/or steroid therapy. This prophylactic regimen was evaluated for a period of two years. Two hundred and ninety patients with similar characteristics who were observed over the three-year period prior to the introduction of prophylaxis served as historical control group. Environmental surveillance during the study period showed constant contamination of the air with Aspergillus. Prophylaxis significantly reduced the incidence of proven invasive aspergillosis from 12/290 to 0/164 (p = 0.004), and reduced the mortality rate from 8/290 to 0/164. The incidence of proven plus probable aspergillosis amounted to 34/290 in the control group and 8/164 in the study group (p = 0.01); the mortality rates were 11/290 (3.7%) and 2/164 (1.2%) respectively. All nasal cultures in the study group were negative for Aspergillus. The prophylactic regimen was well tolerated. Larger studies assessing each agent alone and in combination are necessary to confirm these observations.

Topics: Administration, Intranasal; Administration, Oral; Adult; Air Microbiology; Amphotericin B; Aspergillosis; Aspergillus; Humans; Itraconazole; Leukemia; Lymphoma; Pilot Projects

Because the use of fluconazole prophylaxis had been associated with an increased rate of Candida krusei infections at The John Hopkins Oncology Center, early empiric amphotericin B plus flucytosine were given to febrile neutropenic patients colonized by C. krusei. By this practice, the proportion of fungemias attributable to C. krusei was low (12.5%) in patients receiving fluconazole over a 6-month interval. However, Torulopsis (Candida) glabrata assumed a much higher proportion of fungemias (75%) among patients receiving fluconazole. In vitro susceptibility testing combined with this clinical experience suggests that some T. glabrata isolates are not susceptible to fluconazole and can cause breakthrough infections in patients receiving fluconazole.

Topics: Amphotericin B; Bacterial Infections; Bone Marrow Transplantation; Candida; Candidiasis; Fluconazole; Flucytosine; Humans; Leukemia; Microbial Sensitivity Tests; Neutropenia

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 136 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the interval to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41% respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18 other patients with graft-versus-host disease, 5 with splenomegaly and 3 with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore, the need for retransfusion within 24 hours was significantly increased with stored platelets. In 19 patients with anti-HLA allo-immunization who were transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36% and D4/D3). This study indicates that the storage has a major detrimental effect on platelet recovery and survival in patients with certain clinical conditions.

Topics: Adolescent; Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Blood Preservation; Bone Marrow Purging; Cell Survival; Evaluation Studies as Topic; Female; Graft vs Host Disease; Hepatic Veno-Occlusive Disease; Histocompatibility; Humans; Infections; Leukemia; Male; Middle Aged; Platelet Count; Platelet Transfusion; Prospective Studies; Splenomegaly; Thrombocytopenia; Treatment Outcome

Reports of the concurrent isolation of more than one non-albicans species of Candida from blood cultures of immunocompromised patients with disseminated candidiasis are extremely infrequent. We report on the isolation of Candida krusei and Candida tropicalis from 17 blood cultures that were taken from a 67-year-old white man with a diagnosis of acute biphenotypic leukemia during a 2-week period of hospitalization for induction chemotherapy. Despite receiving high-dose amphotericin B throughout this period, the status of the patient worsened, and he experienced pancytopenia, hypernatremia, azotemia, and disseminated intravascular coagulation, which led to his death. Candida krusei and C tropicalis were isolated concurrently from 10 of the 17 blood cultures, while C krusei was the single isolate in three cultures and C tropicalis was isolated alone in four cultures. Each species manifested markedly different colonial morphological features. This case report serves to emphasize to microbiologists that they must exercise extreme suspicion when non-albicans species of Candida are isolated singly or concurrently from blood cultures in neutropenic patients, given the increasing clinical significance of these yeasts.

Topics: Acute Disease; Aged; Amphotericin B; Candida; Candidiasis; Dose-Response Relationship, Drug; Humans; Leukemia; Male

Mucormycosis is known to cause rhinocerebral and pulmonary disease in patients with diabetes, leukemia, and lymphoma. However, the characteristics and outcome of these infections have not been well described in the BMT population. In a 17-year consecutive series of BMT patients, 13 of 1500 patients (0.9%) developed mucormycosis. Ten of the transplants were allogeneic and three autologous. Six infections occurred within 90 days of transplant, and six occurred at or within several days of autopsy. Seven patients were neutropenic and another patient had just engrafted at diagnosis of infection. Sites of infection were lung-brain (n = 4), sinonasal region (n = 3), lung (n = 2), disseminated (n = 2), lung-kidney (n = 1), and bone-muscle (n = 1). All patients were treated with prolonged amphotericin B therapy. Surgical debridement was employed in the three sinonasal infections. Death from mucormycosis occurred in ten of 13 (77%) patients. Two patients are alive, including one who had resolution of sinonasal infection. Mucormycosis may occur in both neutropenic and non-neutropenic patients, and may occur long after hospital discharge for BMT. These infections are often fatal, although patients with limited sinonasal disease may have a better prognosis, especially with early diagnosis and aggressive antifungal therapy.

Topics: Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Brain Diseases; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Leukemia; Lung Diseases; Male; Mucormycosis; Paranasal Sinuses; Prospective Studies; Treatment Outcome

In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants.. To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990.. The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro.. In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.

Topics: Adult; Amphotericin B; Bone Marrow Transplantation; Candidiasis; Drug Therapy, Combination; Fluconazole; Humans; Leukemia; Mycoses; Opportunistic Infections; Postoperative Complications; Retrospective Studies

The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects.

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Drug Carriers; Humans; Leukemia; Liposomes; Liver Diseases; Male; Opportunistic Infections; Splenic Diseases

To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment.. Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole.. All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis.. Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Candidiasis; Child; Child, Preschool; Fluconazole; Flucytosine; Humans; Leukemia; Liver Diseases; Remission Induction; Splenic Diseases; Tomography, X-Ray Computed

To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified.. Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined.. Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period.. Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Air Microbiology; Amphotericin B; Aspergillosis; Child, Preschool; Environmental Monitoring; Female; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Nasal Mucosa; Neutropenia; Retrospective Studies

In patients with leukemia or lymphoma, the role of preventive oral hygiene in reducing infectious periodontal complications during aggressive chemotherapy is well documented. However, the effectiveness of these measures in preventing further dental or periodontal degradation remains to be demonstrated. 34 hospitalized patients with malignant heamatological diseases were observed. During chemotherapy, tooth brushing was replaced by 3 daily mouth-rinses with 0.2% chlorhexidine digluconate. The periodontal status of these patients, appears unchanged after 12 months. This suggests that the prophylactic measures do prevent a measurable periodontal degradation, even in the presence of pre-existing periodontal disease.

Topics: Acyclovir; Amphotericin B; Ceftazidime; Chlorhexidine; Dental Plaque Index; Fluconazole; Humans; Immunosuppression Therapy; Ketoconazole; Leukemia; Lymphoma; Miconazole; Norfloxacin; Periodontal Diseases; Periodontal Index; Tooth Loss; Vancomycin

Topics: Acute Disease; Adult; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Ciprofloxacin; Combined Modality Therapy; Drug Evaluation; Drug Therapy, Combination; Humans; Leukemia; Roxithromycin; Sepsis; Streptococcal Infections

An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9-136 days), and mean cumulative dose per patient was 1117 mg (range, 231-7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level greater than or equal to 2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Glomerular Filtration Rate; Humans; Kidney; Leukemia; Middle Aged; Neoplasms; Opportunistic Infections; Saline Solution, Hypertonic

We tested the efficiency of a nasal spray of Amphotericin B (AmB) in leukemic patients, in an attempt to prevent pulmonary Aspergillosis. From January to July, 8 cases of invasive Aspergillosis (IA) in 19 new leukemic patients were identified. Between July and September 15 patients were treated by prophylactic nasal spray of AmB (daily dose 5 mg). Compliance was excellent, but nevertheless typical IA developed in 5 patients. We conclude that at the dosage used prophylactic administration of nasal spray of (AmB) does not prevent IA.

Topics: Administration, Intranasal; Agranulocytosis; Amphotericin B; Aspergillosis; Humans; Leukemia; Lung Diseases, Fungal

One hundred twenty-five granulocyte transfusions were given concurrently with amphotericin B to 31 granulocytopenic patients with acute leukemia during a four year period. Twenty-six patients had culture-documented, and 5 had presumed fungal infections; pulmonary infiltrates were present in 26 patient courses. Eight patients developed pulmonary deterioration temporally related to therapy with amphotericin, granulocyte transfusions, or both. One event occurred following amphotericin alone. Three additional reactions occurred in alloimmunized patients with antibodies to human leukocyte antigens (HLA) who received random donor granulocytes, which may indicate a potential mechanism for the pulmonary reactions. Two reactions potentially represent an adverse interaction between amphotericin and granulocytes, but these were reversible and were not unlike reactions expected with each modality alone. Our data fail to document a specific detrimental interaction between granulocyte transfusions and amphotericin beyond the reactions associated with each modality, and the data suggest that other clinical factors, particularly infection and alloimmunization, also contribute to pulmonary decompensation. We nevertheless recommend great care and attention be given to administering these modalities in the setting of severely ill patients.

Topics: Adolescent; Adult; Agranulocytosis; Amphotericin B; Female; Granulocytes; Humans; Infections; Leukemia; Lung; Lung Diseases; Male; Middle Aged; Radiography, Thoracic; Transfusion Reaction

Topics: Adolescent; Amphotericin B; Bone Marrow Transplantation; Child; Child, Preschool; Female; Humans; Infection Control; Intestines; Leukemia; Male; Nystatin; Polymyxin B; Polymyxins; Premedication; Vancomycin

Twelve leukemic patients (19%) receiving amphotericin B and aminoglycosides had nephrotoxicity (creatinine value greater than 2.0 mg/dl). Patients with nephrotoxicity tended to be older than patients without nephrotoxicity; gender and total amphotericin B dose were not related to nephrotoxicity. Sodium administration has previously been shown to reverse amphotericin B nephrotoxicity. In this series, among patients receiving ticarcillin at greater than or equal to 18 gm/day (93.6 mEq of sodium per day) the incidence of nephrotoxicity was significantly decreased (1/30, or 3.3%). A multivariate analysis showed that this protective effect of ticarcillin was not dependent on the fact that patients receiving ticarcillin were less likely to receive vancomycin. There were insufficient patients receiving sodium in the absence of ticarcillin to study the effect of sodium alone. However, our observations are consistent with the hypothesis that sodium can prevent renal dysfunction in this clinical situation.

Topics: Adult; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Drug Administration Schedule; Female; Humans; Kidney Diseases; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Sodium; Statistics as Topic; Ticarcillin; Vancomycin

Using serial examination and oral cytology, 50 adult patients undergoing induction therapy for acute leukemia were studied for oral colonization with candida species. Ninety percent of patients were found to be colonized with Candida, with most of these colonizations present by day 14. The 30 patients exhibiting colonization with pseudohyphae received ketoconazole 400 mg daily by mouth. Of 20 patients in this group treated for 5 or more days, Candida organisms were eradicated in nine. Sixteen patients from the above group with persistent colonization on ketoconazole were treated by independent clinical decision for sustained fever and neutropenia with Amphotericin B, but only one responded by elimination of colonization. Seven of the 15 patients who did not initially receive ketoconazole developed Candida dissemination in contrast to two of 30 who received ketoconazole initially (P = 0.003, Fisher's exact test). No patient who initially had or acquired a negative cytology developed oral or disseminated candidiasis. Clinical oral candidiasis occurred in three patients, all of whom were receiving amphotericin B. Approximately 90% of these patients have or develop oral colonization with Candida organisms as identified by oral cytology. Those with colonization, both with and without pseudohyphae present, are at risk for dissemination. Amphotericin B does not eliminate colonization remaining after treatment with 400 mg of ketoconazole daily. More effective diagnostic and therapeutic strategies are needed to identify and eliminate Candida organisms and to prevent disseminated candidiasis in this population of patients.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Candida; Candidiasis, Oral; Female; Humans; Ketoconazole; Leukemia; Male; Middle Aged

A rate on autopsy of up to 30% systemic fungal infections and difficulties in diagnosing systemic mycosis antemortem have led to the empiric use of amphotericin B in patients with hematological malignancies, prolonged fever, and neutropenia. Routine empiric antifungal treatment was initiated in our institution in 1982. Amphotericin B was given to granulocytopenic patients with hematological malignancies with (a) unremitting fever after 48-72 h of antibiotic treatment, (b) recurrent fever during antibiotic treatment, or (c) with newly detected pulmonary infiltrates, sinusitis, skin and retinal lesions suggestive of a fungal infection. With this approach the rate of systemic fungal infections decreased significantly from 10% (27 of 270 patients; 1973-1981) to 4% (6 of 153 patients; 1982-1986, P less than 0.02). The reduction of systemic fungal infections was most prominent in patients with acute myelogenous leukemia, where its proportion decreased from 16% (16 of 98 patients; 1973-1981) to 4% (2 of 50 patients; 1982-1986, P less than 0.023). Our data support the hypothesis that the incidence of systemic fungal infections in patients with hematological malignancies and especially in acute myelogenous leukemia can be reduced significantly by empirical treatment with amphotericin B.

Topics: Adult; Aged; Agranulocytosis; Amphotericin B; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Leukemia; Lung Diseases, Fungal; Lymphoma; Male; Middle Aged; Mycoses; Neutropenia; Retrospective Studies

Topics: Adolescent; Adult; Amphotericin B; Candidiasis; Female; Humans; Leukemia; Liver Diseases; Middle Aged; Splenic Diseases

Therapy of systemic fungal infection with amphotericin B (AmB) must be continued for several months and is usually performed on an inpatient basis because of the risk of drug toxicity. Between 1983 and 1987 we treated 14 outpatients with a total of 164 AmB infusions. Side effects were generally mild and easy to control. Progressive impairment of renal function led to dose reduction and interruption of therapy in only one patient. Ambulatory therapy with AmB is feasible in an outpatient unit with adequate experience, and a significant reduction of treatment costs can result. Outpatient therapy is an acceptable alternative to inpatient treatment. Patients with malignant diseases under palliative therapy will profit most from the reduced duration of hospital stay.

Topics: Adolescent; Adult; Ambulatory Care; Amphotericin B; Female; Humans; Leukemia; Male; Middle Aged; Mycoses; Retrospective Studies

The authors report the case of 5 1/2 year-old boy with insulin-dependent diabetes mellitus revealed during the induction therapy of an acute leukemia of the mixed type, and who presented with an unusual type of pulmonary fungal infection: mucormycosis. It had a favourable outcome with surgical excision preceded and followed by amphotericin B treatment.

Topics: Acute Disease; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Diabetes Mellitus, Type 1; Humans; Leukemia; Male; Mucormycosis; Postoperative Care; Remission Induction

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Drug Administration Schedule; Female; Humans; Leukemia; Male; Middle Aged; Mycoses

Eight patients with haematologic malignancies contracted fatal invasive aspergillosis during an outbreak. Five patients were neutropenic. Bronchofiberoscopic examination with microbiology specimen brush and bronchoalveolar lavage yielded Aspergillus fumigatus in only 2/5 patients examined. The specific diagnosis reached during lifetime in 5 patients was based on a combination of invasive procedures (lung biopsy in 2, percutaneous lung puncture in 1), the presence of a lung abscess (3 patients), seroconversion (1 patient), and purulent maxillary sinusitis caused by A. fumigatus together with repeated abundant growth of A. fumigatus in the sputum (1 patient). Six patients received amphotericin B. The infection was temporarily controlled only in 2 bone marrow transplant recipients whose granulocyte counts recovered. In 3/8 patients the pneumonia was of polymicrobial aetiology, Mycobacterium tuberculosis (2 patients), Pneumocystis carinii (1 patient), and Legionella pneumophila (1 patient) being the other microbes involved. 3/4 bone marrow transplant recipients with aspergillosis had been transplanted for chronic myeloid leukaemia, supporting the previously reported association of bone marrow transplantation for chronic myeloid leukaemia and the risk of invasive aspergillosis. Improved diagnostic methods for earlier definitive diagnosis of invasive aspergillosis as well as more efficacious and less toxic antifungal agents are needed to allow early treatment.

Topics: Adult; Amphotericin B; Aspergillosis; Aspergillus fumigatus; Cross Infection; Humans; Immunosuppression Therapy; Leukemia; Lung Diseases, Fungal; Middle Aged; Prognosis

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Topics: Acute Disease; Adolescent; Adult; Amphotericin B; Bone Marrow Transplantation; Humans; Immune Tolerance; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mitosporic Fungi; Mycoses; Opportunistic Infections; Remission Induction

Topics: Acute Disease; Administration, Oral; Adult; Aged; Amphotericin B; Female; Fungi; Humans; Leukemia; Male; Middle Aged; Mycoses

Over 80 percent of patients with invasive pulmonary aspergillosis (IPA) undergoing intensive antileukemic chemotherapy in a recent two-year period survived the pulmonary infection as a result of early diagnosis and aggressive therapy with high-dose amphotericin B and 5-fluorocytosine. CT played an important role in establishing the early diagnosis of IPA and affected management. Since our original communication describing the CT findings of IPA, we have added ten new cases, each subsequently substantiated by lung biopsy (two), autopsy (two), and/or positive cultures of sputum or extrapulmonary sites (seven). The CT halo sign, or zone of lower attenuation surrounding a pulmonary mass, was present in eight of nine patients with early CT scans obtained during bone marrow aplasia. Characteristic CT progression from multiple fluffy masses to cavitation or air crescent formation suggested IPA in five of seven patients with serial CT scans. CT directly affected patient management in seven of ten cases. Scan findings were one criterion for increasing to high-dose amphotericin B or for adding 5-fluorocytosine. CT characteristics of healing IPA lesions were similar to resolving pulmonary infarcts and were used to monitor disease activity in patients on long-term amphotericin B and prior to retreatment chemotherapy.

Topics: Acute Disease; Adult; Aged; Amphotericin B; Aspergillosis; Female; Flucytosine; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Tomography, X-Ray Computed

Invasive sinonasal aspergillosis is a severe and frequently fatal infection in immunosuppressed patients with hematologic malignancies. Seven patients with sinonasal aspergillosis who failed to respond to conventional amphotericin B (AmpB) were treated with liposomal AmpB (L-AmpB).AmpB was incorporated into multilamellar vesicles consisting of dimyristoyl phosphatidyl-choline and dimyristoyl phosphatidylglycerol in a 7:3 molar ratio. Five patients had underlying hematologic malignancies, one patient had aplastic anemia, and one patient had no underlying disease. All patients had biopsy-proven invasive Aspergillus sinusitis, and had failed conventional antifungal therapy including AmpB. Five patients were cured and two did not respond to treatment. Fever and chills were infrequent and, when they occurred, mild, and responded well to conventional management. No severe renal or central nervous system toxicity was observed. L-AmpB is effective and less toxic than conventional AmpB in the treatment of invasive Aspergillus sinusitis.

Topics: Amphotericin B; Aspergillosis; Drug Evaluation; Humans; Leukemia; Liposomes; Methods; Opportunistic Infections; Sinusitis; Time Factors

A total of 10 episodes in 7 patients with leukemia or related disorders was treated with oral amphotericin B (AMPH). In 8 episodes AMPH were used prophylactically for severe neutropenia, and in the remaining 2 it was given when the patients were feverish. A daily dose of 2,400 mg of AMPH was given orally once a day and serum concentrations of AMPH were determined serially with bioassay. Two hours after administration, the mean serum concentration of AMPH rose to 0.15 microgram/ml, and reached 0.27 microgram/ml after 24 hours. The concentration was maintained between 0.23 microgram/ml and 0.39 microgram/ml through the following 7 days. These concentrations exceed the minimal inhibitory concentrations of most strains of Candida albicans. In 8 occasions of prophylactic use, no fungal infection was encountered. In a patient with pneumonia, chest X-ray and physical findings improved with administration of oral AMPH. Side effect of AMPH was seen in 1 patient, which was mild proteinuria and was eased rapidly after the withdrawal of AMPH. Clinical laboratory tests showed 1 case of proteinuria and disorder of kidney but did not clear under influence of AMPH. These results suggest that oral administration of AMPH is clinically and therapeutically effective and relatively safe for the prophylaxis or the treatment of fungal infection in patients with leukemia or related disorders.

Topics: Administration, Oral; Adult; Amphotericin B; Female; Humans; Leukemia; Male; Middle Aged; Mycoses

Nine patients with hematologic malignancies developed fungal infections, predominantly involving the liver and spleen. Eight patients had biopsy-documented progressive candidiasis and one had an unclassified fungus. The patients were treated with liposomal-amphotericin B (L-AmpB) after their fungal infection progressed during treatment with standard intravenous (IV) AmpB (Fungizone; E. R. Squibb & Son, Princeton, NJ) and/or other antifungals. Eight patients (88.8%) were cured of their fungal infection, and one showed improvement after treatment. Minor acute toxicity and no chronic toxicity were associated with the administration of L-AmpB. L-AmpB is a safe and effective therapeutic method for treating fungal infections that have invaded the liver and spleen even when they are refractory to conventional anti-fungal therapy.

Topics: Adolescent; Adult; Amphotericin B; Candidiasis; Child, Preschool; Female; Humans; Leukemia; Liposomes; Liver Diseases; Lymphoma; Male; Middle Aged; Splenic Diseases

Topics: Adult; Aminoglycosides; Amphotericin B; Female; Humans; Leukemia; Magnesium; Tetany

Invasive pulmonary aspergillosis as a cause of mortality and morbidity in patients with haematological malignancies is becoming more common. Predisposing factors are powerful immunosuppressive chemotherapy, neutropenia and synergistic combinations of antibiotics of great potency and wide spectrum of activity. Clinical and radiological signs are heterogeneous, sometimes misleading and often absent. Treatment is often empirical on suspicion alone. Amphotericin B is the only effective drug but it has marked toxicity, mainly renal. Infection is usually fatal without adequate treatment. This paper describes eight cases of invasive pulmonary aspergillosis seen in one centre in two years, reviews the literature and assesses associated problems.

Topics: Adolescent; Adult; Aged; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Female; Hodgkin Disease; Humans; Immunosuppression Therapy; Leukemia; Lung; Male; Middle Aged; Radiography

Systemic aspergillosis is encountered with increasing prevalence in immunocompromised patients undergoing chemotherapy. The current communication describes the clinical and postmortem findings in three leukemic patients who developed myocardial infarction secondary to Aspergillus embolization of the coronary arteries. They were all immunosuppressed owing to previous chemotherapy and had been treated for suspected fungal infection with amphotericin B (0.6 mg/kg) for at least 1 week prior to this episode. It is postulated that the infection was spread through the blood since in all three cases the descending branch of the left coronary artery was occluded. Heart involvement resulting from fungal infection should be suspected when chest symptoms of unknown origin occur in this patient population.

Topics: Adult; Amphotericin B; Aspergillosis; Autopsy; Coronary Disease; Female; Humans; Leukemia; Male; Middle Aged; Myocardial Infarction

Serum total iron-binding capacity (TIBC) was measured serially on 70 patients with acute leukemia throughout the period of chemotherapy-induced granulocytopenia. Fungal infections were documented in 13 of these patients (18.6%), while 41 patients (58.6%) had clinically suspected fungal infections and 16 (22.9%) had no evidence of fungal infections during the granulocytopenia. Documented fungal infection occurred in patients with the greatest reduction in TIBC (P less than .015). Early reduction in TIBC also correlated with a greater risk for occurrence of fungal infection, and the earliest institution of amphotericin B (Amp-B) (P less than .004). Effective antifungal therapy was further associated with a return of TIBC levels toward normal. These data demonstrate that altered iron metabolism during granulocytopenia is associated with the development of fungal infections in compromised patients. Serial monitoring of TIBC, along with other clinical and mycologic findings, may prove useful in developing strategies for predicting patients at risk for developing a fungal infection and directing the appropriate use of empiric therapy with Amp-B.

Topics: Acute Disease; Adult; Aged; Agranulocytosis; Amphotericin B; Blood Transfusion; Disease Susceptibility; Erythrocyte Transfusion; Humans; Iron; Leukemia; Middle Aged; Mycoses; Platelet Transfusion; Protein Binding; Risk; Transferrin

Disseminated fungal disease, predominantly involving liver and spleen, developed in eight patients with hematologic malignancies. Because the patients failed to respond to standard antifungal drugs, they were treated with liposomal amphotericin B (L AmpB). Before therapy began, the diagnosis was confirmed histologically and the patients underwent abdominal computed tomography (CT), which indicated hepatosplenomegaly with or without multiple microabscesses in the liver and spleen. After each course of treatment with L AmpB, patients underwent CT, followed by either open or CT-guided percutaneous aspiration biopsy of the liver. Post-treatment CT showed partial regression of lesions in six patients and persistence in two. In all patients a liver biopsy confirmed that the lesions noted after treatment were due to granulomas or focal areas of fibrosis compatible with healing. Thus, the persistence of multiple defects on enhanced scans in two patients was not an indication of persistent abscesses. Clinical response was an additional important factor. Close clinical and pathologic correlation in addition to CT scanning are required in the follow-up of hepatosplenic fungal infections.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Biopsy; Candidiasis; Child; Female; Humans; Leukemia; Liposomes; Liver; Liver Diseases; Lymphoma; Male; Middle Aged; Splenic Diseases; Tomography, X-Ray Computed

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Digestive System; Drug Combinations; Humans; Leukemia; Leukocyte Count; Neomycin; Polymyxin B; Polymyxins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Candidiasis; Female; Histoplasmosis; Humans; Leukemia; Liposomes; Lymphoma; Male; Middle Aged; Mucormycosis; Mycoses; Neoplasms; Sarcoma, Kaposi

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.

Topics: Acute Disease; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Diagnosis, Differential; Diagnostic Errors; Humans; Leukemia; Lung Diseases, Fungal

Topics: Amphotericin B; Humans; Ketoconazole; Leukemia; Mycoses

Disseminated candidiasis is likely to become an increasing problem in cancer patients. It has occurred in patients undergoing intensive chemotherapy, thermotherapy, and bone marrow transplant. The availability of broad-spectrum cephalosporins with biliary excretion is likely to increase the problem. Although localized candidiasis responds to both topical and parenteral therapy, systemic candidiasis is often fatal, especially in neutropenic patients. A major obstacle to control of this infection is inadequate diagnostic techniques. It is to be hoped that continuing research will yield more effective diagnostic and therapeutic measures.

Topics: Amphotericin B; Antibodies, Fungal; Candidiasis; Cephalosporins; Humans; Ketoconazole; Leukemia; Miconazole; Neoplasms; Pneumonia

Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period. One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein. The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution. Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common. Blood cultures were positive in only 35 percent of patients with disseminated candidiasis. Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered. Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients. Only six (4.5 percent) of 133 patients with proved deep organ infections recovered. Respiratory failure was the clinical cause of death in 62 percent of patients. Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Bacteriological Techniques; Candida; Candidiasis; Cytomegalovirus Infections; Humans; Ketoconazole; Leukemia; Lymphoma; Miconazole; Mycoses; Neoplasms; Neutropenia

Topics: Acute Disease; Amphotericin B; Humans; Ketoconazole; Leukemia; Mycoses

The recovery of an adequate granulocyte count after chemotherapy is the most important prognostic factor in neutropenic patients. In granulocytopenic patients, the risk of infection is very high and its course usually severe. Empiric antibiotic treatment must be started as soon as fever rises and blood cultures have been taken. The combination of an anti-pseudomonas penicillin with an aminoglycoside is presently the standard empiric therapy for febrile granulocytopenic patients. If the clinical response is inadequate, antimicrobial therapy should be adjusted to a bactericidal activity of greater than 1:16 in the serum. If antibiotic therapy fails, a fungal infection should be considered and amphotericin B added empirically. Patients must be closely supervised for superinfections. Therapeutic transfusions of granulocytes have proven useful in severe granulocytopenia and when antibiotic therapy has failed.

Topics: Amphotericin B; Anti-Bacterial Agents; Drug Antagonism; Drug Therapy, Combination; Humans; Klebsiella Infections; Leukemia; Leukocyte Count; Leukopenia; Mycoses; Pseudomonas Infections

Between July 1973 and June 1981 systemic fungal infections were found in 27 of 270 autopsies of patients with hematologic malignancies: in 16 aspergillosis, in 6 candidiasis, in one aspergillosis and candidiasis, and in 4 mucormycosis. The frequency increased from 6% during the first 6 years to 25% during the last 2 years (p = 0.025). Fever despite antibiotics and new pulmonary infiltrates were the major symptoms. In only 6 of 16 patients did microbiological findings support the clinically suspected diagnosis. Systemic fungal infections were the principal cause of death in 12 patients. Because of the difficulty of establishing the diagnosis, empiric antimycotic therapy should be started promptly on clinical suspicion in patients with neutropenia and fever despite antibiotics.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Humans; Leukemia; Lymphoma; Mucormycosis; Mycoses; Myeloproliferative Disorders; Retrospective Studies

Of 78 patients with blastomycosis, 3 patients had received glucocorticoid therapy prior to diagnosis and 3 others had an underlying hematologic malignancy (chronic lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma). The clinical picture in these 6 patients was similar to blastomycosis in nonimmunosuppressed patients (in contrast to histoplasmosis or coccidioidomycosis in immunosuppressed patients in whom a distinct clinical syndrome is often seen). The patients presented with chronic pulmonary infiltrates or with isolated skin ulcers. The response to therapy was good if the diagnosis was made early. Blastomycosis can occur in immunosuppressed patients. However, the spectrum of underlying illness is not that seen in opportunistic histoplasmosis or coccidioidomycosis, where patients with T-cell defects predominate. Possible explanations for the rarity of blastomycosis in more classically T-cell-immunosuppressed patients are discussed.

Topics: Adult; Aged; Amphotericin B; Blastomycosis; Female; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Myeloid; Male; Middle Aged; Multiple Myeloma; Prednisone

Phycomycosis is the preferred terminology to define a fungal disease which may be devastating and fatal. It is caused by a nonseptate hyphae, class phycomycetes and genus (Rhizopus, Mucor, Absidia). Phycomycosis in man is usually associated with debilitating diseases such as: diabetes mellitus, leukemia and immunosuppressive conditions. The cephalic phycomycosis has two forms: 1. rhino-orbital cerebral which may be fatal, and 2. rhino-paranasal sinuses form which usually has a benign clinical course. From 1943 to 1967, only 45 cases of the cephalic form were described with a mortality rate of 50%. Since then several series have been added to the literature with improved survival, probably due to the addition of amphotericin B to the therapy. Even with modern therapy, the mortality rate is still about 30%. Modern technology C.T. scan is very helpful to establish orbital and intracranial extension. When intracranial involvement is present, the prognosis is dismal. Our series of 8 patients is reported.

Topics: Adult; Aged; Amphotericin B; Brain Diseases; Diabetes Complications; Female; Humans; Leukemia; Male; Middle Aged; Mucormycosis; Nose Diseases; Orbital Diseases; Paranasal Sinus Diseases; Tomography, X-Ray Computed

We reviewed the records of 32 patients with acute leukemia and proved invasive fungal infections to determine the clinical and pathologic characteristics of systemic mycosis in patients undergoing intensive induction chemotherapy. The incidence of invasive fungal infections among our patients was at least 27 percent, and Candida and Aspergillus accounted for the majority of these infections. Patients with systemic candidiasis generally had prolonged severe neutropenia, fever refractory to antibiotics, and evidence of mucosal colonization by fungi. At autopsy, Candida was always widely disseminated. Patients with aspergillosis generally had neutropenia, fever, and pulmonary infiltrates at the time of admission to the hospital and, at autopsy, their infections were primarily confined to the lungs. Patients infected with both Candida and Aspergillus had clinical and pathologic findings that were a combination of the features of each type of infection. A diagnosis of invasive fungal infection was established before death in only nine of the patients, all of whom had systemic candidiasis. Four of these patients were successfully treated and survived their hospitalization. The reasons for frequently misdiagnosing and unsuccessfully treating systemic mycosis in patients with acute leukemia are examined, and suggestions are made for improved management of patients at high risk for these infections. These suggestions are based upon recognition of the clinical settings in which fungal infections occur, the aggressive use of invasive diagnostic procedures, and the early empiric use of amphotericin B.

Topics: Acute Disease; Amphotericin B; Aspergillosis; Candidiasis; Humans; Leukemia; Lung; Lung Diseases, Fungal; Nausea; Retrospective Studies; Vomiting

Rhinocerebral mucormycosis is, with few exceptions, only reported in patients with severe metabolic or immunologic imbalances. Factors which may predispose to the development of mucormycosis are reviewed. These factors include ketoacidosis and immunologic deficiency states due either to the primary disease or to the treatment for other diseases. An appreciation for these predisposing factors is very important in order that aggressive diagnosis and therapy be undertaken without delay.

Topics: Acidosis; Adrenal Cortex Hormones; Aged; Amphotericin B; Anemia; Brain Diseases; Diabetes Complications; Humans; Immunologic Deficiency Syndromes; Keto Acids; Leukemia; Male; Mucormycosis; Neutropenia; Nose Diseases; Turbinates; Uremia

Two patients with acute leukemia were found to have candidal splenic abscesses. Both patients were in remission and had normal granulocyte counts at the time the abscesses became evident. Both patients were treated with splenectomy and antifungal therapy with a definite response. The incidence and treatment of fungal splenic abscesses in leukemia patients is discussed with emphasis on the role of splenectomy.

Topics: Abscess; Acute Disease; Amphotericin B; Candidiasis; Humans; Infant; Leukemia; Leukemia, Lymphoid; Male; Splenectomy; Splenic Diseases

Topics: Amphotericin B; Humans; Leukemia; Leukocyte Transfusion; Lung Diseases; Sepsis; Transfusion Reaction

A case of disseminated infection with Trichosporon cutaneum, a fungus that causes white piedra, is described. The patient, a 58-year-old barber with acute leukemia, had fever, myalgias and skin lesions. He was receiving cytotoxic drug therapy and prednisone, was severely neutropenic and was being treated with broad spectrum antibiotics. Blood cultures and a biopsy of the skin lesion grew T. cutaneum. He died despite amphotericin B therapy. At autopsy, widespread infection with T. cutaneum was present. T. cutaneum is another fungus capable of causing widespread systemic disease in the immunocompromised host.

Topics: Amphotericin B; Epithelium; Humans; Leukemia; Male; Middle Aged; Mouth; Mycoses; Pharynx; Skin

Lymphadenitis caused by Candida developed in a patient with acute leukemia but there was no other evidence of disseminated infection. He was successfully treated intravenously with only 800 mg of amphotericin B. The presentation of disseminated candidiasis in immunocompromised hosts is discussed. The unusual finding in this case of Candida infection apparently confined to a lymph node was interpreted as a stage of fungal invasion more limited than the widely disseminated disease. The concept of a locally invasive but nondisseminated Candida infection was the basis for giving this patient a low dose of amphotericin B.

Topics: Acute Disease; Adult; Amphotericin B; Candidiasis; Humans; Leukemia; Lymph Nodes; Lymphadenitis; Male; Neck

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

The development of resistance to amphotericin B and nystatin in yeast isolates was determined. Organisms recovered from patients on the oncology service, undergoing extensive chemotherapy for acute leukemia and bone marrow transplantation, were compared with yeasts recovered from patients on other services in the same hospital over a 7-month period. An agar dilution method was used to assay the susceptibility for each antibiotic; resistance was defined as a minimal inhibitory concentration of greater than or equal to 2 micrograms/ml for amphotericin B and greater than or equal to 16 micrograms/ml for nystatin. None of 625 isolates from 238 patients on non-oncology services demonstrated polyene resistance. Resistance only occurred in a subpopulation of oncology patients, in which 55 isolates (7.4%) from six patients (8.6%) exhibited polyene resistance. Resistance yeasts included Candida albicans (three strains), Candida tropicalis (one strain), and Torulopsis glabrata (two strains). All of the patients from whom resistant yeasts were recovered had experienced extensive chemotherapy with cytotoxic agents, granulocytopenia, and long-term treatment with both antibacterial and polyene antibiotics. Resistance to 2 micrograms of amphotericin B per ml and to 16 micrograms of nystatin per ml was associated with loss or marked depression of ergosterol in the cell membrane as measured by ultraviolet spectra. A significant incidence of polyene resistance in an oncology subpopulation was documented, suggesting a need for susceptibility testing in patients who are at high risk for development of drug-resistant fungal pathogens.

Topics: Amphotericin B; Anemia, Aplastic; Anti-Bacterial Agents; Drug Resistance, Microbial; Ergosterol; Humans; Leukemia; Mycoses; Polyenes; Yeasts

Between January 1974 and July 1976, three adult patients with leukemia, therapy-associated granulocytopenia and febrile courses unresponsive to broad spectrum antibiotic therapy were operated upon for a preoperative diagnosis of candidal abscess of the spleen. The diagnosis was based upon a high index of suspicion of invasive candidiasis in this immunosuppressed group of patients; the failure of the patients to respond to the empiric administration of broad spectrum antibiotics, salicylates and steroids, and the presence of discrete scintiscan defects on liver-spleen scan with both 99Tc sulfur colloid and 67Ga citrate. Multiple splenic abscesses containing candidal organisms were confirmed in all three patients, and two of the three also had multiple small abscesses of the liver. The fourth patient, whose liver-spleen scintiscans were abnormal only in showing splenomegaly and whose febrile course responded to aspirin, did not have a candidal abscess of the spleen at the time of celiotomy which was undertaken for fever of unknown cause. The antemortem diagnosis and treatment of candidal splenic abscess in patients with leukemia is dependent upon a high index of suspicion and appropriate clinical correlation with diagnostic tests. Although the prophylactic oral administration of mycostatin to patients at high risk may prevent this once fatal complication, only prompt and aggressive treatment can cure it.

Topics: Abscess; Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Candidiasis; Female; Humans; Leukemia; Male; Middle Aged; Splenic Diseases

The clinical triad of fever, erythematous papular rash, and diffuse muscle tenderness has recently been reported to be presumptive evidence for disseminated candidiasis in the immunocompromised host who is receiving broad-spectrum antibiotics. This case report further explores this clinical association and demonstrates that the immediate institution of antifungal therapy before laboratory test results are known may favorably alter the outcome of this frequently fatal condition. In view of the low positive yield of blood cultures, skin biopsy may represent an effective method for achieving rapid laboratory confirmation of the diagnosis.

Topics: Adult; Amphotericin B; Candidiasis; Humans; Leukemia; Male

The diagnosis of rhinocerebral mucormycosis is most often made at autopsy. We report a series of nine patients in whom the diagnosis was established premortem. Six of the patients had underlying diabetes mellitus and three had acute leukemia. Facial or ocular pain was the complaint found in all patients, and frequently was the initial symptom. The diagnosis was established by examination and culture of infected tissue obtained by biopsy. In seven patients, identification of hyphal elements in smears of biopsy material allowed the immediate institution of amphotericin B therapy. Four of the seven patients treated with amphotericin B survived. All surviving patients had underlying diabetes mellitus and had undergone surgical debridement. Early diagnosis leading to immediate institution of appropriate therapy is most important for survival of patients with mucormycosis.

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Brain Diseases; Diabetes Complications; Female; Humans; Leukemia; Male; Middle Aged; Mucormycosis; Nose Diseases

Topics: Acute Disease; Amphotericin B; Aspergillosis, Allergic Bronchopulmonary; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leukemia; Middle Aged; Rifampin

Invasive pulmonary aspergillosis is a common fungal infection in the compromised host. The outcome has been generally poor and, until recently, most reports are derived from autopsy series. We report nine patients with leukemia and the characteristic clinical presentation of pulmonary infarction. There is histological evidence that infarction is due to fungal invasion of the pulmonary arterial system with distal hemorrhagic infarction, cavitation, and mycetoma formation. This complete evolution was detected in six patients, none of whom had previous cavitary pulmonary disease. Therapy included amphotericin B (9 patients), aerosolized nystatin (6 patients), and 5-fluorocytosine (5 patients). Complete resolution of the pulmonary lesions occurred in six patients with a subsequent median survival of 13.5 months (range: 5-32+ months). Three patients died with continuing pulmonary infiltrate. Despite the antifungal chemotherapy, resolution seemed to correlate best with recovery of circulating neutrophils.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Female; Flucytosine; Humans; Leukemia; Lung Diseases, Fungal; Male; Middle Aged; Nystatin; Sputum

Fungal infections are increasing in frequency, especially among patients with haematological malignancies. The fungi which cause most of the infections in cancer patients are Candida spp. and Aspergillus spp. These fungi seldom infect individuals with normal host defence mechanisms. Many factors predispose patients to fungal infection, including neutropenia, lymphopenia, gastro-intestinal ulceration, intravenous catheters and adrenal corticosteroid therapy. Candida spp. cause 5 major types of infection: dermatitis, thrush, gastro-intestinal, primary organ and disseminated infection. Aspergillus spp. and Phycomycetes cause pulmonary, disseminated or rhino-cerebral infection. Cryptococcus neoformans usually causes meningitis but may cause pneumonia or disseminated infection. The diagnosis of fungal infection is often made only at postmortem examination, because it is difficult to isolate the aetiological agent from sites of infection. Amphotericin B remains the mainstay of antifungal therapy, but is seldom effective in the patient with compromised host defences. Successful management of these infections in the future will depend upon improvement in diagnostic capabilities as well as the introduction of more effective and less toxic antifungal agents.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Humans; Leukemia; Lymphoma; Mycoses; Neoplasms; Nocardia Infections

Pulmonary aspergillosis in patients with leukemia or lymphoma is usually a fatal infection. However, difficulty in obtaining a premortem diagnosis has often prevented an adequate trial of anti-fungal chemotherapy. In this report, nine cases of aspergillus pneumonia in patients with hematologic malignancy were diagnosed during a one-year period. Five of nine patients had a premortem diagnosis (56%) and eight of nine (89%) received a premortem trial of amphotericin B. Two of nine patients survived infection, including one patient with prolonged neutropenia. Better diagnostic methods and wider use of antifungal chemotherapy may improve prognosis for aspergillus infection in patients with hematologic malignancy.

Topics: Amphotericin B; Aspergillosis; Humans; Immunosuppression Therapy; Leukemia; Lymphoma; Pneumonia

An Aspergillus fumigatus immunodiffusion test was performed biweekly for one year on 80 hospitalized patients with acute leukemia to determine if serologic conversion accompanied clinical aspergillosis. A micro-ouchterlony technique with agarose was used. The antigens were prepared from concentrated A. fumigatus culture filtrates and the sera were concentrated 3-fold before testing. Of 80 patients, 10 were proved at autopsy, lung biopsy, or closed space culture to have invasive aspergillosis. Six of 10 patients converted from a negative to a positive immunodiffusion test, whereas a seventh patient's weakly positive test became strongly positive. Three patients with documented aspergillosis did not develop a positive immunodiffusion test. Four of the patients who converted from a negative to a positive test were treated early and successfully with amphotericin B. A fifth patient developed immunodiffusion test antibody late in the course and died despite therapy. A sixth patient died of concomitant mucormycosis despite early therapy. Six additional patients who converted from a negative to a positive immunodiffusion test could not be evaluated because of inadequate documentation of aspergillosis. In severely immunosuppressed patients, our immunodiffusion test proved to be a specific but not always a sensitive test for aspergillosis. In 4 patients, biweekly tests showed conversion associated with invasive aspergillosis, which was diagnosed early and treated successfully.

Topics: Acute Disease; Amphotericin B; Antibodies, Fungal; Humans; Immunodiffusion; Immunosuppression Therapy; Leukemia; Lung Diseases, Fungal

The diagnosis and successful control of systemic Aspergillus niger infection in 2 adult patients with acute leukemia is reported. During induction therapy, the first patient developed pulmonary infiltrates, skin lesions and abnormal liver function tests. Aspergillus niger was found on skin and liver biopsy. This patient was successfully treated with Amphotericin B and granulocyte transfusions and he remains in remission. The second patient developed a pneumonitis and adynamic ileus with positive sputum and stool cultures for Aspergillus niger. The infection only responded to Amphotericin B and granulocyte transfusions and the leukemia to cytoreductive chemotherapy. The patient later relapsed and died after a febrile illness. Fungi morpholocially consistent with Aspergillus were found in the liver at autopsy. Infection with A. niger is rare even in this patient population; however fungal infections have become an increasing problem. The need for a high index of suspicion, especially when an infection is unresponsive to antibacterial antibiotics, the various diagnostic tools, and the need for aggressive therapy are stressed. Amphotericin B is the chemotherapy of choice but may be insufficient in a severely neutropenic host where the simultaneous use of granulocyte transfusions might be lifesaving.

Topics: Acute Disease; Adult; Amphotericin B; Antineoplastic Agents; Aspergillosis; Aspergillus; Aspergillus niger; Blood Transfusion; Female; Granulocytes; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Myeloid, Acute; Leukocytes; Male; Sputum

Groups of AKR mice bearing spontaneous leukemia-lymphoma were treated with five different combinations of chemotherapy or chemoradiotherapy. Each treatment combination was given in two sequences--high dose first and low dose last, or low dose first and high dose last--administered over 6-7 days. When the initial treatment was a high dose of chemotherapy, radiotherapy, or chemoradiotherapy, mortality in the first 24 hours exceeded 40%, and at least 70% of the mice in each group were dead within 2 weeks. When low-dose chemotherapy was given first, mortality in the first 24 hours was minimal but, most significantly, no deaths occurred in the 24 hours after subsequent high-dose treatment. In the most successful group (100 mg cyclophosphamide/kg on day 0, and 250 mg cyclophosphamide/kg and 400 R total-body X-irradiation on day 7), the median survival time increased significantly as compared with the median survival time among mice given the same regimen in reverse sequence (p less than 0.001) or among untreated control mice (p less than 0.01). With this regimen, survival 60 days after the last treatment was 47%. No mouse survived 30 days when the sequence of treatments was reversed. From these results, we conclude that chemotherapeutic and chemoradiotherapeutic regimens for AKR spontaneous leukemia-lymphoma should be designed so that low, minimally lethal doses precede higher doses.

Topics: Amphotericin B; Animals; Cyclophosphamide; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Leukemia; Lymphoma; Mice; Mice, Inbred AKR; Nitrosourea Compounds

Topics: Aged; Amphotericin B; Biopsy; Candida; Candidiasis; Candidiasis, Cutaneous; Child, Preschool; Female; Flucytosine; Humans; Leukemia; Male; Skin

Topics: Amphotericin B; Animals; Carmustine; Cell Division; Cell Survival; Clone Cells; Drug Synergism; L Cells; Leukemia; Mice; Mice, Inbred AKR; RNA; Spleen

Topics: Amphotericin B; Catheterization; Cerebral Ventricles; Cerebrospinal Fluid; Humans; Injections, Spinal; Leukemia; Meningitis; Methods; Subarachnoid Space

Topics: Adolescent; Adult; Amphotericin B; Bacterial Infections; Drug Therapy, Combination; Gentamicins; Humans; Intestines; Kanamycin; Leukemia; Middle Aged

Topics: Acute Disease; Adolescent; Adult; Aged; Amphotericin B; Aspergillosis; Autopsy; Biopsy; Candidiasis; Candidiasis, Oral; Child, Preschool; Female; Fever of Unknown Origin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lung Diseases, Fungal; Male; Middle Aged; Mucor; Mycoses; Retrospective Studies

Topics: Adult; Amphotericin B; Candidiasis; Candidiasis, Oral; Esophageal Diseases; Fluoroscopy; Humans; Leukemia; Leukemia, Myeloid; Male; Middle Aged; Nystatin

Topics: Acute Disease; Adult; Amphotericin B; Blood Cell Count; Blood Platelets; Candida; Candidiasis; Cytarabine; Feces; Fever; Humans; Hypersplenism; Leukemia; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Nose; Pharynx; Prednisone; Skin; Spleen

Topics: Acetazolamide; Adolescent; Amphotericin B; Candidiasis; Humans; Infectious Mononucleosis; Kidney Diseases; Leukemia; Male; Mercaptopurine; Methotrexate; Nystatin; Penicillins; Peripheral Nervous System Diseases; Prednisone; Rolitetracycline; Sepsis; Uric Acid

Topics: Amphotericin B; Cryptococcosis; Drug Therapy; Fistula; Geriatrics; Humans; Leukemia; Male; Pathology; Postoperative Complications; Prostate; Prostatectomy

Topics: Adolescent; Adult; Agranulocytosis; Amphotericin B; Blood Transfusion; Child; Colistin; Humans; In Vitro Techniques; Infection Control; Infections; Leukemia; Male; Methicillin; Oxacillin; Polymyxins; Prednisone

Topics: Amphotericin B; Anemia; Anemia, Aplastic; Bone Marrow Examination; Diagnosis, Differential; Histoplasmosis; Humans; Leukemia; Pancytopenia; Prednisolone

Topics: Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Candidiasis; Drug Therapy; Esophagoscopy; Esophagus; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Sarcoma

Topics: Amphotericin B; Arizona; Coccidioidomycosis; Humans; Leukemia; Leukemia, Lymphoid; Lung Diseases; Lung Diseases, Fungal; Prednisone; Sarcoidosis; Toxicology

Topics: Amphotericin B; Child; Clinical Laboratory Techniques; Cryptococcosis; Cryptococcus; Diagnosis, Differential; Drug Therapy; Fever; Humans; Leukemia; Leukemia, Lymphoid; Lung Diseases; Lung Diseases, Fungal; Lymphadenitis; Meningitis; Radiography; Sulfadiazine

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

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