Fluconazole-resistant Candida parapsilosis fungemia in a patient with AIDS.
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Biomedical subjects
Publications and source records attributed to R Cauda.
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The objective of this case-control study, conducted in a large Italian university hospital over a 12-month period, was to evaluate the risk factors associated with the emergence of azole resistant oral candidosis in 64 Human Immunodeficiency Virus (HIV) infected patients. A swab was obtained from each patient by brushing candidal lesions. Candida albicans was isolated in 41 patients (64%), Candida glabrata in ten (16%), Candida krusei in five (8%), Candida kefyr in two (3%), Candida tropicalis in two (3%), and Candida lipolytica and Candida guilliermondii in one case, respectively. Two patients suffered a double infection i.e. C. albicans+C. krusei and C. albicans+C. glabrata, respectively. Candida species were tested in vitro for their susceptibility to ketoconazole, fluconazole, itraconazole and amphotericin B. MICs of the four antifungal drugs were obtained for each yeast using a microdilution broth method developed in our laboratory. Twenty four (37%) of the isolated strains were resistant both to itraconazole and fluconazole, five (8%) to fluconazole alone, and two (3%) to ketoconazole alone, while none of the isolated strains was resistant to amphotericin B. Patients with oral candidosis caused by a strain resistant to one or more azole drug were compared to control patients with azole-susceptible oral candidosis. On univariate analysis, more than five episodes of oral candidosis in the last year (P = 0.01), previous use of azole therapy (P = 0.001), C2-3 category of HIV infection (P = 0.01) and low number of circulating CD4+ T-cells (P = 0.03) were significantly associated with an increased risk for the development of azole resistance. However, previous use of azole therapy was the only factor selected by a stepwise logistic regression analysis which was independently associated with the isolation of azole resistant strains (P = 0.003). Our findings indicate that, in view of the potential risk for the emergence and selection of azole resistant strains of Candida in patients with AIDS, it is important to carefully choose the antifungal drug for the therapy of mild fungal infections after evaluation of the in-vitro susceptibility of the isolated strains.
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Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was assessed in HIV seropositive patients and healthy heterosexual controls. A selective depletion of lymphocytes with the CD16+ NK phenotype was found among the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were significantly decreased. Analysis of activation antigens revealed a large proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8 and CD56 antigens among the NK population with an increase in activation status may be due to differential loss of the NK cell subsets or, alternatively, to the loss of immunoregulatory cytokines, which have been shown to be important in maintaining NK activity. Whether these changes in the NK compartment may influence the outcome of individuals with HIV disease still remains an open question but is an important issue when performing phenotypic analysis of HIV+ subjects.
In the present study we analyze peripheral blood lymphocytes (PBL) from patients with human immunodeficiency virus (HIV) infection for both phenotypic expression and function of P-glycoprotein (P-170). This transmembrane efflux pump is known to be one of the mechanisms responsible for the multidrug resistance (MDR) in cancer therapy and it is also constitutively expressed in normal PBL. P-170 function, evaluated as Rhodamine 123 (Rh123) efflux in flow cytometry, was found to be significantly reduced in CD16+ natural killer (NK) cells from patients with HIV infection. Interestingly, this reduced efflux significantly correlates with the decreased NK cytotoxicity observed in HIV+ patients, as evaluated against the NK-specific K562 target cell line. These results support a possible role of the P-170-related pump in specific immunological lymphocyte function such as NK cell-mediated cytotoxicity.
The object of this case control study was to evaluate the frequency, the risk factors, the microbiological spectrum and the outcome of 249 cases of bacteraemia observed in 209 HIV-infected patients, most them affected by AIDS. The rate of bacteraemia in the total yearly HIV-related admissions increased from 4% in 1985 to 13% in 1993. The more common aetiological agents of bacteraemia were: Staphylococcus aureus (29.7%), non-typhoidal species of Salmonella (14.1%), Staphylococcus epidermidis (10.9%), Streptococcus pneumoniae (8.4%) and Pseudomonas aeruginosa (7.6%). A mixed flora was found in 14% of the episodes. Multivariate analysis of predisposing factors indicated that a low CD4+T-cell count (<0.2 x 10(9)/l) (P=0.01), use of central venous catheters (CVC) (P=0.01) and neutropenia (polymorphonuclear neutrophils <1.0 x 10(9)/l) (P=0.04) were independent risk factors for the development of bacteraemia. Logistic regression did not reveal any association of bacteraemia with intravenous drug abuse (on univariate analysis P=0.04). The response (31.8%). Recurrences to specific therapy was favourable in 170 episodes (68.2%); death occurred in 79 (31.8%). Recurrences arose in 40 patients, 17 (42.5%) of them died. The outcome of bacteraemia was influenced by a low number of CD4+T-cells (P<0.001) but not of polymorphonuclear cells. Our findings suggest that bacteraemia is a relatively common event in HIV-infected patients, especially under particular conditions (e.g. intravenous drug abuse, use of CVC, neutropenia and a low CD4-T-cell count). It requires special attention from physicians who must recognise and treat the condition promptly at an early stage.
P-glycoprotein (P-gp/P-170), a transmembrane efflux pump known to be one of the mechanisms responsible for multidrug resistance in cancer therapy, is constitutively expressed in several solid human tissues as well as in normal peripheral blood lymphocytes and bone marrow cells. In particular, this molecule has been associated with the transport of perforin and other cytolysins in natural killer (NK) and T cytotoxic lymphocytes. In the present study, we analyzed peripheral blood lymphocytes (PBLs) from controls and HIV+ patients for phenotypic expression and function of the P-gp/P-170 molecule. We found that 90% of all PBL subsets (i.e., CD4+, CD8+, CD56+, and CD19+ cells) expressed surface P-gp/P-170 both in controls and HIV+ patients. However, a significant decrease in CD4+/P-170+ and CD19+/P-170+ cells was observed in HIV+ individuals with respect to controls. PHA and IL-2 stimulation of PBLs was unable to increase the expression of P-gp/P-170 both in controls and HIV+ patients, despite the increased detection of the CD25 molecule. On the other hand, stimulation with anti-CD3 determined a significant increase in lymphocyte P-gp/P-170. The function of P-gp/P-170, assessed by a flow cytometric assay for rhodamine-123 (Rh123) efflux, was significantly reduced in CD16+ NK cells and CD19+ B cells from HIV+ patients. The Rh123 efflux by NK cells correlated (p < 0.01) with the NK cytotoxicity against the 51Cr-labeled K562 cell line. Last, the effect of the antiretroviral drugs AZT, ddI, and ddC on P-gp expression and function was evaluated. The dideoxynucleoside compounds did not inhibit P-gp/P-170 function of normal mononuclear cells in vitro, and did not increase P-gp/P-170 expression in vivo, in patients undergoing antiretroviral therapy with AZT. These findings provide further evidence of a possible involvement of the P-gp/P-170 system in specific immunological lymphocyte functions, and especially in cytotoxic-type functions. In addition, it is possible to suggest, on the basis of our experimental data, that the dideoxynucleoside class of antiretroviral agents does not contribute to the phenotypic and functional alterations related to P-glycoprotein during HIV infection.
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OBJECTIVE: To evaluate the prevalence of, risk factors for, treatment and outcome of Clostridium difficile-associated diarrhoea (CDAD) in patients with human immunodeficiency virus (HIV) infection. DESIGN: A prospective case-control study, conducted between January 1992 and April 1994. SETTING: Department of Infectious Diseases in a large university hospital with HIV in- and out-patient units. PATIENTS AND METHODS: The study included 124 patients grouped as follows: 31 HIV-infected patients with CDAD (group A); 31 HIV-seronegative patients with CDAD (group B) and 62 HIV-infected patients without CDAD (group C). The patients in group B and C were selected randomly during the study period. RESULTS: The prevalence of CDAD in HIV-infected patients was 3.1% compared with 1.6% in HIV-seronegative patients (P = 0.02). On univariate analysis, the predisposing factors in group A were antibiotic use in the 4 weeks prior to the onset of CDAD (P = 0.03 versus group C), prolonged hospitalization (over 20 days; P = 0.04), low levels of circulating CD4+ cells (P = 0.03) and use of antacids (P = 0.04). The antibiotics significantly associated with CDAD were trimethoprim-sulfamethoxazole (P = 0.02 versus group C), third generation cephalosporins (P = 0.03) and clindamycin (P = 0.03). On multivariate analysis of the risk factors, the use of antibiotics was the sole independent risk factor for CDAD (P = 0.03). The clinical symptoms of CDAD were more severe in HIV-infected patients than in controls. Three patients in group A (9.7%) had one relapse and one patient (3.2%) experienced chronic diarrhoea. The outcome of CDAD was not influenced by the number of circulating polymorphonuclear cells and CD4+ cells. No difference in the survival curves of AIDS patients with or without CDAD, stratified according to age, sex and CD4+ cell count was observed. CONCLUSIONS: Our data suggest that CDAD is more common in HIV-infected patients, particularly those receiving antibiotic therapy, than in HIV-seronegative patients. Since C. difficile can cause severe and recurrent or chronic infections in HIV-infected patients, CDAD must be always considered in the differential diagnosis of diarrhoea in patients with AIDS and AIDS-related conditions.
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In this study we analyzed the expression of EB6 and GL183, which are part of P58 molecular family that represents the putative NK receptor for MHC class I molecules, in peripheral blood lymphocytes of 60 patients with HIV infection (20 asymptomatic HIV-seropositive individuals, 20 patients with constitutional symptoms, and 20 AIDS patients) and correlated it with the level of CD4+, CD56+ cells, and the NK cell activity in order to determine a possible relation with disease progression. The absolute number (but not the percentage) of CD56+, EB6+, and GL183+ cells was significantly reduced only in AIDS patients but not in the other AIDS-related clinical conditions. On the contrary, NK cell activity was reduced in all HIV-infected patients. In a 6-month follow-up, patients with constant clinical conditions and stable CD4+ cells level showed no significant difference, either in the percentage or absolute number of EB6+ and GL183+ cells. Interestingly, dual-color fluorescence indicates that GL183 and EB6 molecules (that in normal individuals are virtually absent on CD3- NK cells) are expressed in HIV-infected individuals not only in CD56+ cells but also in CD3+ cells. This may reflect a depletion of other T cell subsets or alternatively (less likely) a specific immune response. Our data indicate that the expression of EB6 and GL183 in T and NK cells from HIV-infected patients might be relevant in the course of the disease and for the disease-associated functional defect of NK cell activity.
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Invasive pulmonary aspergillosis usually occurs in patients with severe granulocytopenia or defects of cell-mediated immunity secondary to cytotoxic chemotherapy or high-dose corticosteroids, but it is an unusual opportunistic infection in patients with AIDS. Eleven cases of Aspergillus pulmonary disease were diagnosed in HIV-infected patients from January 1985 to December 1992, in the Department of Infectious Diseases of the Catholic University. Four patients had invasive pulmonary aspergillosis, six probable pulmonary invasive aspergillosis and one allergic bronchopulmonary aspergillosis. Fiberoptic bronchoscopy with bronchoalveolar lavage was confirmed to be an useful tool for the diagnosis of pulmonary aspergillosis in AIDS patients. The response of aspergillosis to therapy, either amphotericin B or itraconazole, has usually been poor. It is possible to speculate that the longer survival of AIDS patients and the latter development of other functional immunological abnormalities related to HIV infection may allow the appearance of opportunistic infection, such as pulmonary aspergillosis, different from those more often observed.
In Italy three epidemic peaks of meningococcal meningitis have occurred reflecting pandemic recrudescence of the disease. The seasonal distribution of the disease is similar in the epidemic or non-epidemic periods. There is no significant difference in the regional distribution of the disease. The disease is more prevalent among young males. The prevalent serogroup of Neisseria meningitidis is C. There has been a decrease in resistance to sulphonamides and an increase to rifampin among the isolated strains.
Patients with human immunodeficiency virus (HIV) infections have aberrant production of a number of lymphokines and monokines. Envelope glycoproteins are believed to be important in HIV pathogenesis and may influence the production of these cytokines. Therefore, synthetic peptides corresponding to amino acid sequences 735-752 and 846-860 of glycoprotein gp41 and to amino acid sequence 304-328 of gp120 were investigated for their abilities to affect the production of the following cytokines by normal peripheral blood mononuclear cells in the presence of appropriate inducers: interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF). In contrast to cells and inducers alone (or in the presence of a control peptide), gp41 or gp120 synthetic peptides were able to depress the production of IFN-alpha, IFN-gamma and IL-2. In contrast, these peptides produced an elevation of the production of IL-1 and TNF. The effect of the gp41 peptides was more marked than that of gp120 peptides in most cases. These studies indicate that these HIV envelope glycoproteins may be directly responsible for aberrant lymphokine and monokine production in patients infected with this virus and therefore may be at least partially responsible for the pathogenesis of AIDS.
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