Chronic Disseminated Candidiasis Research Articles

Diffuse disseminated Candidiasis in a patient with Felty’s syndrome: a case report

Severe granulocytopenia predispose patients with Felty's syndrome to severe infectious diseases. The following report deals with an occurrence of chronic disseminated candidiasis in a patient with Felty's syndrome who presented with prolonged and severe granulocytopenia. To the best of our knowledge this coexistence has never been described before.

Caspofungin for the treatment of less common forms of invasive candidiasis

Caspofungin has demonstrated efficacy in invasive candidiasis. However, in a comparative study, most patients (>83%) had candidaemia. Therefore, we performed a study in patients with non-fungaemic invasive candidiasis. Adults with proven non-fungaemic invasive candidiasis or probable chronic disseminated candidiasis (CDC) received caspofungin primary or salvage monotherapy. Most patients received 50 mg daily following a 70 mg loading dose. Patients with endocarditis, osteomyelitis or septic arthritis received caspofungin at 100 mg daily and were allowed dose escalation up to 150 mg. Primary efficacy endpoint was the overall response at end of caspofungin therapy. A favourable overall response required complete resolution of symptoms and either eradication of Candida or radiographic resolution. All 48 patients enrolled had confirmed infection and received>or=1 dose of caspofungin. At study entry, 8% were neutropenic. The mean APACHE II score was 14.3. Most infections were due to Candida albicans (60%) or Candida glabrata (14%). The overall success at end of caspofungin therapy was 81%. Success by site of infection was as follows: peritonitis 77% (10/13), abdominal abscess 89% (8/9), CDC 88% (7/8), osteomyelitis/septic arthritis 100% (4/4), endocarditis 33% (1/3) and multiple sites 75% (6/8). Outcomes were similar across Candida spp. None of the patients had a serious drug-related adverse event or discontinued caspofungin due to toxicity. Overall mortality until 12 week follow-up was 23%. In deep-seated invasive candidiasis, including peritonitis, abdominal abscesses, CDC and arthritis, caspofungin was effective and safe at regular doses and up to 100 mg daily.

Salvage Therapy of Refractory Chronic Disseminated Candidiasis in a Patient with Acute Myeloid Leukaemia and Secondary Prophylaxis During Allogeneic Stem Cell Transplantation

We report on the treatment course of a 27-year-old male patient with acute myeloid leukaemia M1 and chronic disseminated candidiasis. After induction chemotherapy, the patient developed oesophageal candidiasis while participating in a voriconazole vs. placebo prophylaxis trial. He was then switched to oral fluconazole 400 mg q.i.d. After 6 days of futile fluconazole therapy he was switched to caspofungin 50 mg q.i.d. Caspofungin dose was later increased to 100 mg q.i.d after disseminated candidiasis with involvement of lung, spleen and liver was diagnosed. Following 63 days of caspofungin without resolution of symptoms, i.e. being persistently febrile, and emergence of soft tissue Candida abscesses, he was included into a trial allowing compassionate use of posaconazole as salvage therapy for refractory invasive fungal infections. Symptoms rapidly resolved under posaconazole 200 mg q.i.d. treatment and the patient was able to undergo allogeneic haematopoietic stem cell transplantation on secondary prophylaxis with posaconazole.

Successful treatment of refractory chronic disseminated candidiasis after prolonged administration of caspofungin in a child with acute myeloid leukemia

This report documents the clinical activity of caspofungin in a 13-year-old girl with acute myeloid leukemia (AML) and chronic disseminated candidiasis (CDC), refractory to amphotericin B and fluconazole. Caspofungin was started at 50 mg/d resulting in a temporary response. With no further clinical improvement and radiological progress after 2 months of therapy, the dose of caspofungin was increased to 100 mg/d, leading to a sustained clinical response. Therapy was given for a total of 12 months and had no attributable adverse effects. This approach resulted in successful treatment of refractory CDC with caspofungin.

Candidaemia in Patients with Haematological Disorders and Stem Cell Transplant

The incidence of non-albicans species of Candida has recently increased, especially in patients with malignant haematological disorders receiving fluconazole prophylaxis. A retrospective study of patients who developed candidaemia at Riyadh Armed Forces Hospital between January 1992 and December 2002 was carried out. Thirty one episodes of candidaemia occurred in 27 patients with a variety of haematological disorders. Twenty-four episodes were caused by non-albicans species of Candida and only 7 episodes were caused by C.albicans. The most frequent underlying haematological disorders were acute myeloid leukaemia (AML) followed by acute lymphoblastic leukaemia (ALL). The main predisposing factors for the development of candidaemia were: broad spectrum antibiotics, central venous catheters, neutropenia, cytotoxic chemotherapy, coexisting bacterial infections, steroid therapy, relapsing or untreated primary disease and fluconazole prophylaxis.Eight episodes were complicated by chronic disseminated candidiasis. Amphotericin-B and amBisome were used in the treatment of Candida infections. The treatment was successful in 86% of the episodes of C. albicans and 50% of the episodes due to nonalbicans species of Candida. The highest mortality rate was encountered with C.tropicalis infections.Candidaemia is an important cause of mortality and morbidity in patients with malignant haematological disorders and stem cell transplant. The predominance of non-albicans species of Candida especially C.krusei and C.tropicalis is alarming. The early administration of appropriate antifungal therapy and the removal of infected intravascular catheters improve the outcome considerably.

The usefulness of the PlateliaCandidaantigen in a patient with acute lymphocytic leukemia and chronic disseminated candidiasis

We report a protracted course of disseminated candidiasis due to Candida tropicalis in a 17-year-old man with acute lymphocytic leukemia. Despite adequate antifungal therapy (amphotericin B), C. tropicalis was recovered from biopsy specimens 25 days (skin) and 109 days (kidney) after the first positive blood cultures. While blood cultures became negative for C. tropicalis 11 days after the initiation of treatment, mannanemia persisted and became negative only after 130 days of antifungal therapy. Thus, antigen assays provided indicators of antifungal response. Differential diagnosis was difficult for this patient with the observation of persistent lesions in image studies. With positive results of antigen assays, an invasive procedure might be avoided and preemptive antifungal treatment could be initiated in a timely manner. Anti-mannan antibody remained undetectable up to 164 days after first positive blood culture despite the patient's recovery from neutropenia and recruitment of neutrophils in the tissue (skin).

Hepatic candidiasis in a kidney transplant recipient treated successfully with amphotericin B and itraconazole

Keywords: Candida; hepatic candidiasis; kidney;liver; mycosis; transplantationThe incidence of hepatic candidiasis is difficultto estimate because of diagnostic difficulties. Itsfrequency was 7% in a study of 562 adult patientswith leukaemia [1]. Hepatic candidiasis (HC), alsoreferred to as chronic disseminated candidiasis,hepatosplenic candidiasis and granulomatous hepaticcandidiasis, affects almost exclusively patients under-going remission induction chemotherapy or bonemarrow transplantation for acute leukaemia [2].It occurs on recovery following prolonged episodesof bone marrow dysfunction and neutropenia [1].Theliver,spleenandsometimesthekidneysareinfectedwith Candida. Occasionally, patients with other typesof immunosuppression (aplastic anaemia, lymphoma,sarcoma or liver transplantation) may develophepatosplenic candidiasis [3]. This is the first reportedcase of HC in a kidney transplant recipient.

Common polymorphisms in critical genes of innate immunity do not contribute to the risk for chronic disseminated candidiasis in adult leukemia patients

Chronic disseminated candidiasis is a serious fungal infection in immunocompromised patients, particularly those undergoing therapy for acute leukemia. Coordination between innate and adaptive immune system is critical to resistance or susceptibility to Candida infection. In order to investigate possible genetic contribution to chronic disseminated candidiasis of key molecules in the innate immune pathway, we performed a case control study using the candidate gene approach. Forty subjects with chronic disseminated candidiasis and 50 controls without chronic disseminated candidiasis but an underlying diagnosis of leukemia were enrolled in the Helsinki University Central Hospital during the period 1980-1998. Candidate genes were selected for analysis based upon the following criteria: a common polymorphism (>5% frequency) and existence a priori of clinical and biological data suggesting a role for the variant in the pathogenesis of chronic disseminated candidiasis. Six genes were selected from critical microbicidal and innate immune pathways, including three low-affinity Fcgamma receptors (FCGR2A, FCGR3A and FCGR3B), chitotriosidase (CHIT1), p22-phox NADPH oxidase (CYBA), and mannose binding lectin (MBL2). There was no statistically significant association of susceptibility to chronic disseminated candidiasis with the polymorphisms in this study. Common variants in the six studied genes most likely do not contribute to the risk for chronic disseminated candidiasis in patients with acute leukemia.

Hepatosplenic Candidiasis in Patients with Acute Leukemia

Hepatosplenic candidiasis (HSC) or chronic disseminated candidiasis (CDC) is an invasive fungal infection that affects neutropenic patients. The Invasive Fungal Infectious Group of the European Organization for Research and Treatment of Cancer (EORTC-IFIG) and the Mycoses Study Group of the National Institute for Allergy and Infectious Diseases (MSG-NIAID) require peripheral, target-like abscesses on liver and/or spleen imaging in addition to elevated serum alkaline phosphatase levels for diagnosis of HSC [1]. Despite this standardized definition, consistent data yielding an estimated incidence is not yet available.

Chronic disseminated candidiasis in patients with acute leukemia: emphasis on diagnostic definition and treatment

Background: Chronic disseminated candidiasis (CDC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy. Recent studies have provided evidence for diagnostic alternatives to invasive procedures and more therapeutic options for the management of this complication. In order to put diagnostic criteria and methodological approach to the disease into the perspective of developing strategies for therapy, all relevant studies published in the English literature over the last 30 years were examined. Materials and methods: The English-language articles located through MEDLINE (1966 to present) and from selected bibliographies. Results: There is increased recognition of CDC as complication of treatment with chemotherapy in patients with acute leukemia. Liver biopsy may not always be revealing or feasible to perform in some patients. Among the imaging modalities, magnetic resonance imaging has obtained preeminence as a non-invasive tool for the diagnosis of hepatosplenic fungal infections. Administration of amphotericin B (Amp B) in relatively large cumulative doses is needed to ensure appropriate control of the infection and prevention of future relapse. Patients intolerant of, or refractory to conventional Amp B have been successfully salvaged using fluconazole or lipid formulations of Amp B. A constellation of clinical, laboratory and radiologic parameters should be used to determine response and efficacy of therapy. There is sufficient evidence to support the safety and feasibility of continuing chemotherapy for acute leukemia in conjunction with antifungal treatment in patients diagnosed with CDC. Conclusion: The development of CDC in patients with acute leukemia does not preclude further chemotherapy or constitute contraindication for bone marrow transplantation. Knowledge of the course and pattern of evolution of the disease and adopting aggressive therapeutic approach will likely reduce the morbidity and mortality from this complication.

Ojo de buey en tomografía hepática.

Invasive fungal infections are more commonly found in patients who develop neutropenia after chemotherapy. A 4-year-old girl with diagnosis of acute lymphoid leukemia developed febrile neutropenia after chemotherapy. Broad spectrum antibiotics and antimycotic therapy were initiated. Candida albicans was isolated and Entamoeba histolytica was observed in stool examination. Chronic disseminated candidiasis had developed and was treated with amphotericin B, initially, and fluconazol. Computed tomography images were obtained that demonstrated a classic 'bull's eye' pattern; a concurrent histological study confirmed the diagnosis. Candida spp. is the major cause of opportunistic mycosis in immunosuppresed patients receiving chemotherapy for haematologic malignancies. An initial infection results in disseminated candidiasis, which persists and becomes chronic. In the 4-year-old patient, the identified risk factors consisted of a previous therapy with broad spectrum antibiotics, the gastrointestinal tract colonization with Candida albicans and prolonged neutropenia. Imaging diagnoses are made by ultrasonography, computed tomography and magnetic resonance. With ultrasound and tomography, 4 distinct patterns have been described. Pattern 1 ('wheels within wheels') and 2 ('bull's eye') are important, since they are characteristic of chronic disseminated candidiasis. The third pattern (hypoechoic image) is the most common finding with both techniques. In the current patient, patterns 2 and 3 were seen and the diagnosis was confirmed by histological study.

好中球減少患者における診療指針

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in neutropenic patients with leukemia and those undergoing hematopoietic stem cell transplant (HSCT). Two major IFIs are systemic candidiasis (including candidemia, chronic disseminated candidiasis and pneumonia) and invasive pulmonary aspergillosis. Recently, the incidence of the latter has been increasing. Three levels of diagnosis are specified in the Japanese guidelines for the diagnosis and treatment of IFIs. Proven fungal infections are diagnosed by histological/microbiological evidence of fungi at the site of infection or positive blood culture (fungemia). Clinically documented fungal infections are diagnosed by typical radiological findings such as halo sign on chest CT plus positive serological/molecular evidence of fungi such as Aspergillus galactomannan, beta-glucan or fungal DNA. Possible fungal infections are diagnosed by typical radiological findings or positive serological/molecular evidence of fungi. For patients with high risk such as those undergoing HSCT, antifungal prophylaxis using oral antifungal agents is recommended. For possible fungal infections, empiric therapy with fluconazole (FLCZ) or amphotericin B (AMPH) is recommended. For patients with proven fungal infections or clinically documented fungal infections, targeted therapy is warranted. In case of candidemia, the best choice is FLCZ (400 mg/day) or AMPH (0.5-0.7 mg/kg/day), and for invasive pulmonary aspergillosis, a higher dose of AMPH (1.0-1.5 mg/kg/day) is indicated. Micafungin (MCFG), recently licensed in Japan, is an active agent for both Candida and Aspergillus. This drug seems useful for empiric and targeted therapy of IFIs.

Systemic Candidiasis

HomeRadioGraphicsVol. 23, No. 5 PreviousNext AFIP ARCHIVESSystemic CandidiasisNicholas J. E. Moore, Johnsey L. Leef, III, Yijun PangNicholas J. E. Moore, Johnsey L. Leef, III, Yijun PangAuthor Affiliations1From the Departments of Radiology and Pathology, University of Vermont School of Medicine, 111 Colchester Ave, Burlington, VT 05401. Received November 13, 2002; revision requested January 15, 2003 and received February 28; accepted March 5. Address correspondence to N.J.E.M. (e-mail: [email protected]).Nicholas J. E. MooreJohnsey L. Leef, IIIYijun PangPublished Online:Sep 1 2003https://doi.org/10.1148/rg.235025162MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References 1 Lee GR, Foerster J, Lukens J, et al. eds. Wintrobe’s clinical hematology 10th ed. Baltimore, Md: Williams & Wilkins, 1999. Google Scholar2 Anttila VJ, Elonen E, Nordling S, Sivonen A, Ruutu T, Ruutu P. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis 1997; 24:375-380. Crossref, Medline, Google Scholar3 Rossetti F, Brawner DL, Bowden R, et al. Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features. Clin Infect Dis 1995; 20:801-811. Crossref, Medline, Google Scholar4 van Burik JH, Leisenring W, Myerson D, et al. The effect of prophylactic fluconazole on the clinical spectrum of fungal diseases in bone marrow transplant recipients with special attention to hepatic candidiasis: an autopsy study of 355 patients. Medicine (Baltimore) 1998; 77:246-254. Crossref, Medline, Google Scholar5 Schwartz RS, Mackintosh FR, Schrier SL, et al. Multivariate analysis of factors associated with invasive fungal disease during remission induction therapy for acute myelogenous leukemia. Cancer 1984; 53:411-419. Crossref, Medline, Google Scholar6 Kontoyiannis DP, Luna MA, Samuels BI, Bodey GP. Hepatosplenic candidiasis: a manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am 2000; 14:721-739. Crossref, Medline, Google Scholar7 Sallah S, Semelka RC, Wehbie R, Sallah W, Nguyen NP, Vos P. Hepatosplenic candidiasis in patients with acute leukaemia. Br J Haematol 1999; 106:697-701. Crossref, Medline, Google Scholar8 Lamminen AE, Anttila VJ, Bondestam S, Ruutu T, Ruutu PJ. Infectious liver foci in leukemia: comparison of short-inversion-time inversion-recovery, T1-weighted spin-echo, and dynamic gadolinium-enhanced MR imaging. Radiology 1994; 191:539-543. Link, Google Scholar9 Semelka RC, Kelekis NL, Sallah S, Worawattanakul S, Ascher SM. Hepatosplenic fungal disease: diagnostic accuracy and spectrum of appearances on MR imaging. AJR Am J Roentgenol 1997; 169:1311-1316. Crossref, Medline, Google Scholar10 Sallah S, Semelka R, Kelekis N, Worawattanakul S, Sallah W. Diagnosis and monitoring response to treatment of hepatosplenic candidiasis in patients with acute leukemia using magnetic resonance imaging. Acta Haematol 1998; 100:77-81. Crossref, Medline, Google ScholarArticle HistoryPublished in print: Sept 2003 FiguresReferencesRelatedDetailsCited ByCurrent Problems in Diagnostic Radiology, Vol. 51, No. 1Abdominal Radiology, Vol. 46, No. 6Journal of the American Academy of Dermatology, Vol. 80, No. 4Seminars in Roentgenology, Vol. 52, No. 2Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential PitfallsPablo Bächler, María José Baladron, Christine Menias, Ignacio Beddings, Ron Loch, Eugenio Zalaquett, Matías Vargas, Sarah Connolly, Sanjeev Bhalla, Álvaro Huete, 27 May 2016 | RadioGraphics, Vol. 36, No. 4Current Radiology Reports, Vol. 4, No. 1Clinical Imaging, Vol. 40, No. 4Seminars in Roentgenology, Vol. 50, No. 4Ultrasound Quarterly, Vol. 24, No. 4Radiología, Vol. 49, No. 6Fungal Liver Infection in Immunocompromised Patients: Depiction with Multiphasic Contrast-enhanced Helical CT1Ur Metser, , Masoom A. Haider, , Marcus Dill-Macky, , Mostafa Atri, , Gina Lockwood, , and Mark Minden, 1 April 2005 | Radiology, Vol. 235, No. 1Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 23, No. 5 Metrics Downloaded 8,670 times Altmetric Score PDF download

Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes.

Chronic disseminated candidiasis (CDC) is a form of Candida species infection observed primarily in patients with acute leukemia. To investigate possible genetic factors associated with CDC, we conducted a pilot study of 40 patients with both leukemia and CDC and 50 control patients with leukemia only. A common haplotype of the IL4 promoter (-1098T/-589C/-33C) was overrepresented in patients with CDC (P= .01; odds ratio [OR], 2.16), whereas another common haplotype (-1098T/-589T/-33T) appeared to be protective against CDC (P= .018; OR, 0.47). Genetic variants of IL4 could contribute to the development of CDC in patients with acute leukemia.

Echinocandins — An Advance in the Primary Treatment of Invasive Candidiasis

Candida species are now the fourth leading cause of nosocomial bloodstream infection in the United States, exceeded in some series only by Staphylococcus aureus, coagulase-negative staphylococcus, and enterococcus species.1,2 Wey and colleagues estimate the attributable mortality of candidemia at 38 percent.3 Candidemia is a surrogate marker for the presence of deeply invasive candidiasis, particularly in immunocompromised hosts.4 In patients with untreated or inadequately treated candidemia, the rate of clinically overt complications, including endophthalmitis, endocarditis, septic arthritis, and renal candidiasis, may be as high as 15 percent. Candidemia may be complicated by chronic disseminated candidiasis in neutropenic hosts and by . . .

Clinical microbiological case: chronic disseminated candidiasis unresponsive to treatment

Clinical microbiological case: chronic disseminated candidiasis unresponsive to treatment

Clinical microbiological case: chronic disseminated candidiasis unresponsive to treatment

A 24-year-old male patient with acute myeloid leukemia (AML), who had been in remission for 18 months following the completion of chemotherapy, presented with fatigue and nasal bleeding. He was found to have pancytopenia, and bone marrow aspiration showed relapsed AML. He was given high-dose sequential chemotherapy consisting of cytosine arabinoside, 500 mg/m per day as a 24-h continuous infusion, idarubicin, 12 mg/m per day on days 1–3, etoposide, 200 mg/m per day as a 24-h continuous infusion on days 8–10, and granulocyte colony-stimulating factor (GCSF), 5 mg/kg per day subcutaneously, starting from day 12 until absolute neutrophil recovery above 1000/mL. The patient became neutropenic, with a count below 100/mL, on the 5th day of chemotherapy. He was pyrexial on the next day, with a temperature of 39 8C, without any localizing symptoms or signs of infection. Blood cultures were taken, and chest X-ray was normal. Empirical antibiotic therapy with piperacillin–tazobactam was commenced, and vancomycin was added 48 h later, when no response was obtained. Examination revealed widespread oral mucositis on the fourth day of the febrile neutropenic episode. Blood cultures, which had been taken every other febrile day, revealed extended-spectrum b-lactamase-producing Escherichia coli on the seventh day of pyrexia, and meropenem and amikacin were substituted for piperacillin–tazobactam. Total parenteral nutrition was also commenced on the same date, as the patient now suffered from severe dysphagia and could not tolerate any oral intake. Fever and dysphagia continued, and an endoscopy was performed, revealing esophageal candidiasis on the 12th day of pyrexia. Fluconazole, 6 mg/kg per day, was commenced intravenously. A non-albicans Candida sp. was grown in both esophageal and blood cultures on the 14th day of pyrexia, and fluconazole was changed to amphotericin B deoxycholate, 0.7 mg/kg per day, due to continuing pyrexia and the possibility of a fluconazole-resistant Candida sp. Surprisingly, two different non-albicans Candida species were identified later, with esophageal cultures revealing C. krusei, whereas blood cultures yielded C. kefyr with a fluconazole MIC of 4 mg/L and an amphotericin B deoxycholate MIC of 0.25 mg/L. Fundoscopic examination was negative for candida retinitis. The patient’s neutrophil count rose above 500/ mL on the 19th day of pyrexia (25th day following chemotherapy). Mucositis and dysphagia gradually resolved with a subsequent increase in the oral intake, and parenteral nutrition was terminated. However, pyrexia reaching 39 8C continued. Amphotericin B deoxycholate was replaced with liposomal amphotericin B, 100 mg, daily due to hypokalemia refractory to intravenous replacement therapy, and meropenem, amikacin and vancomycin treatment was terminated on the 26th day of pyrexia. The patient remained febrile, and liver transaminase levels were found to be elevated. Abdominal CT on the 33rd day of pyrexia demonstrated numerous, prominent hypodense lesions within the spleen, and few lesions in the liver and kidneys, consistent with abscesses. A diagnosis of chronic disseminated candidiasis (CDC) was made. A bone marrow aspirate at this stage confirmed that the patient’s AML was still

Analysis of factors related to the occurrence of chronic disseminated candidiasis in patients with acute leukemia in a non-bone marrow transplant setting: a follow-up study.

Chronic disseminated candidiasis (CDC) is a serious complication of treatment in patients with acute leukemia. Although some general risk factors are known to predispose to systemic fungal infections, few studies have addressed the relevance of certain clinical and laboratory features in patients with CDC. To define a subset of patients at high risk for CDC, the authors evaluated the demographics and clinical and laboratory characteristics of 423 patients with acute leukemia. Patients who had bone marrow transplant before the diagnosis of CDC were excluded from the analysis. The diagnosis of CDC was based on blood cultures, liver biopsy, and imaging studies. The authors conducted 2 separate regression analyses on 3 subsets of patients: patients without documented candidiasis (n = 374), patients with CDC (n = 23), and patients with candidemia (n = 26). According to multivariate analysis, younger age (P = 0.009; odds ratio [OR], 1.96; 95% confidence interval [CI], 1.72-2.99), duration of neutropenia of 15 days or longer (P = 0.0003; OR, 11.7; 95% CI, 3.04-45.1), and use of prophylactic quinolone antibiotics (P = 0.039; OR, 3.85; 95% CI, 1.11-13.4) emerged as independent factors related to the development of CDC in patients with acute leukemia. The presence of severe mucositis, colonization with Candida, and administration of high-dose ara-C were statistically significant parameters in univariate analysis only (P = 0.0001, P = 0.003, and P = 0.058, respectively). On the basis of the results of this investigation, it is possible to define a subset of patients with acute leukemia at very high risk for CDC. Because of the morbidity and mortality of this infection, a targeted prophylactic approach may be more effective and less costly than the random administration of antifungal agents.

Invasive candidiasis stimulates hepatocyte and monocyte production of active transforming growth factor beta.

Candida albicans is an opportunistic fungal pathogen and a major cause of morbidity and mortality in patients with compromised immune function. The cytokine response to tissue invasion by C. albicans can influence the differentiation and function of lymphocytes and other mononuclear cells that are critical components of the host response. While the production of transforming growth factor beta (TGF-beta) has been documented in mice infected with C. albicans and is known to suppress phagocyte function, the cellular source and role of this cytokine in the pathogenesis of systemic candidiasis are not well understood. We have investigated the source of production of TGF-beta by immunohistochemical studies in tissue samples from patients with an uncommon complication of lymphoreticular malignancy, chronic disseminated candidiasis (CDC), and from a neutropenic-rabbit model of CDC. Liver biopsy specimens from patients with documented CDC demonstrated intense staining for extracellular matrix-associated TGF-beta1 within inflammatory granulomas, as well as staining for TGF-beta1 and TGF-beta3 within adjacent hepatocytes. These results correlate with the immunolocalization of TGF-beta observed in livers of infected neutropenic rabbits, using a neutralizing antibody that recognizes the mature TGF-beta protein. Human peripheral blood monocytes incubated with C. albicans in vitro release large amounts of biologically active TGF-beta1. The data demonstrate that local production of active TGF-betas by hepatocytes and by infected mononuclear cells is a component of the response to C. albicans infection that most probably contributes to disease progression in the immunocompromised host.

Successful Treatment of Chronic Disseminated Candidiasis with Fluconazole and a Granulocyte?Macrophage Colony-stimulating Factor Combination

We report a case of chronic disseminated candidiasis in a patient with acute non-lymphoid leukaemia. After 12 months of combined therapy with fluconazole and granulocyte-macrophage colony-stimulating factor, lesions in the liver and spleen resolved completely. The patient has given birth to a healthy baby and has been in complete hematological remission for 3 years.