Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.
(33/1200)
AIMS: To compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies. PATIENTS: 213 consecutive, afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies. METHODS: A randomised, double blind, single centre study. Patients were randomly assigned to receive fluconazole 50 mg or itraconazole 100 mg, both twice daily in identical capsules. An intention to treat analysis was performed on 202 patients, 101 in each group. RESULTS: Microbiologically documented systemic fungal infections occurred in four patients in each group. Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole. In all 202 patients, 29 proceeded to intravenous amphotericin (amphotericin B), 16 in the fluconazole group and 13 in the itraconazole group. Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group. All these infections were oral. No major differences were noted in the isolates of fungi in mouth washes and fecal samples. Overall mortality was 8.9% (18 deaths; seven in the fluconazole group, 11 in the itraconazole group). Mortality from microbiologically and clinically documented fungal infection was 4.5% (nine deaths; three in the fluconazole group, six in the itraconazole group). Median time to suspected or proven fungal infection was 16 days in both groups. None of these comparisons reached statistical significance (p < 0.05). No major clinical toxicity was noted and compliance was excellent. CONCLUSIONS: In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation, fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease. Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals. (+info)
Typhlitis.
(34/1200)
OBJECTIVE: To provide an overview of the pathophysiological features and management of the clinical entity typhlitis. DATA SOURCES AND STUDY SELECTION: The data presented are derived from a review of the English-language literature on typhlitis. The majority of papers analysed were small clinical series. DATA EXTRACTION AND SYNTHESIS: Data derived from the literature review were collated. The major finding was that typhlitis comprises a number of different diseases characterized by the presence of right lower quadrant pain, an immunocompromised host and altered function of the mucosal barrier of the right colon. CONCLUSIONS: Typhlitis should be suspected in any immunocompromised patient presenting with right lower quadrant pain with compatible radiographic findings. Most patients can be treated conservatively with intravenously administered fluids and antibiotics, although surgery may be necessary if complications arise. (+info)
Invasion and intracellular survival of Burkholderia cepacia.
(35/1200)
Burkholderia cepacia has emerged as an important pulmonary pathogen in immunocompromised patients and in patients with cystic fibrosis (CF). Little is known about the virulence factors and pathogenesis of B. cepacia, although the persistent and sometimes invasive infections caused by B. cepacia suggest that the organism possesses mechanisms for both cellular invasion and evasion of the host immune response. In this study, cultured human cells were used to analyze the invasion and intracellular survival of B. cepacia J2315, a highly transmissible clinical isolate responsible for morbidity and mortality in CF patients. Quantitative invasion and intracellular growth assays demonstrated that B. cepacia J2315 was able to enter, survive, and replicate intracellularly in U937-derived macrophages and A549 pulmonary epithelial cells. Transmission electron microscopy of infected macrophages confirmed the presence of intracellular B. cepacia and showed that intracellular bacteria were contained within membrane-bound vacuoles. An environmental isolate of B. cepacia, strain J2540, was also examined for its ability to invade and survive intracellularly in cultured human cells. J2540 entered cultured macrophages with an invasion frequency similar to that of the clinical strain, but it was less invasive than the clinical strain in epithelial cells. In marked contrast to the clinical strain, the environmental isolate was unable to survive or replicate intracellularly in either cultured macrophages or epithelial cells. Invasion and intracellular survival may play important roles in the ability of virulent strains of B. cepacia to evade the host immune response and cause persistent infections in CF patients. (+info)
Invasive aspergillosis as an opportunistic infection in nonallografted patients with multiple myeloma: a European Organization for Research and Treatment of Cancer/ Invasive Fungal Infections Cooperative Group and the Intergroupe Francais du Myelome.
(36/1200)
We report the occurrence of invasive aspergillosis (IA) in nonallografted patients with multiple myeloma (MM) who were treated at hematology or oncology centers in Europe during 1984-1996. Thirty-one cases met the criteria for definitive (21 [68%]) or probable (10 [32%]) IA. Of these cases, 23 (74%) were reported during 1992-1996. Twenty-nine cases (94%) occurred in patients with Durie-Salmon stage 3 MM, and 2 (6%) occurred in patients with Durie-Salmon stage 2 MM. The median time between MM and IA diagnoses was 8 months (range, 1-75 months). Sixteen patients (51%) had a neutrophil count +info)
Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency.
(37/1200)
BACKGROUND: Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise. OBJECTIVES: To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome. SETTING: The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital. METHODS: Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998. RESULTS: Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP. CONCLUSIONS: PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful. (+info)
Cryptococcal meningitis in an HIV negative patient with systemic sarcoidosis.
(38/1200)
A case of Cryptococcus neoformans meningitis is described in an HIV negative patient with undiagnosed systemic sarcoidosis. The patient presented with signs of meningitis together with generalised lymphadenopathy and hepatosplenomegaly. Cryptococcal meningitis was diagnosed on lumbar puncture. She was treated with intravenous amphotericin B but died within two weeks of admission. Necropsy revealed lesions in the lungs, liver, spleen, lymph nodes, small intestine, and bone marrow consistent with sarcoidosis. Microscopically the lesions contained non-caseating epithelioid cell granulomas typical of sarcoidosis. No Schaumann or Hamazaki-Wesenberg bodies were identified. Cryptococcus neoformans meningitis is generally associated with immunosuppressive disorders. As T cell abnormalities have been described in sarcoidosis, this could have been a case of opportunistic infection. Although rare, sarcoidosis merits consideration in patients with cryptococcal disease in the absence of HIV infection. (+info)
Management and outcome of brain abscess in renal transplant recipients.
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Although infection is the commonest central nervous system complication following renal transplantation, brain abscess is uncommon. Over the last 11 years, five renal transplant recipients who had brain abscesses were treated by computed tomography (CT)-guided stereotactic aspiration. Three patients had a fungal abscess, one a tuberculous abscess and the other had a methicillin-resistant Staphylococcus aureus abscess. One patient required a craniotomy for the excision of a fungal abscess which was persistent after two CT-guided stereotactic aspirations. The survivors in this group are the patient with a tuberculous abscess who is alive and well 5 years after diagnosis, and another with a dematiaceous fungal abscess (phaeohyphomycosis). CT-guided stereotactic surgery is minimally invasive, and can safely be performed in these patients. It often leads to an aetiological diagnosis in renal transplant recipients with brain abscesses. Specific antibiotic management directed towards the causative organism rather than empirical treatment can be instituted following the procedure. Although the ultimate prognosis in these patients is bleak even with specific antibiotic therapy, an occasional patient might have a good outcome with prompt and appropriate therapy. (+info)
Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.
(40/1200)
To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels. (+info)