[Mortality risk factors for bloodstream infections caused by extended-spectrum beta-lactamase-producing microorganisms]. / Factores de riesgo de mortalidad en pacientes con bacteriemia por cepas productoras de betalactamasas de espectro extendido.

OBJECTIVE: To identify risk factors for mortality in patients with bloodstream infection by extended-spectrum beta-lactamase (ESBL)-producing microorganisms. MATERIAL AND METHODS: A retrospective study in patients with bloodstream infection by ESBL-producing microorganisms from January 2000 to December 2006 was carried out. RESULTS: A total of 4,172 bloodstream infections were identified, 1,218 (29.2%) and 226 (5.4%) of which were caused by Escherichia coli and Klebsiella pneumoniae, respectively. The overall mortality rate was 50.9% in patients with bacteriema due to ESBL-producing strains. The binomial logistic regression model, adjusted for age and severity, identified admission to an intensive care unit (OR 38,631; 95%CI:3,375-424,618; P=.002) and a SAPS II severity index score >30 in the 24-48 h before obtaining blood culture (OR 17,980; 95% CI:2,193-170,439; P=.010) as factors associated to mortality, while the urinary tract as primary site of infection was an independent determinant for non-mortality (OR 0.184; 95% CI:0.034-0.975; P=.047). CONCLUSIONS: Patients with suspicion of bacteriema who have been admitted to the ICU with a score of elevated severity should be candidates for early empirical treatments as they have a greater risk of mortality. However, the benefit of this strategy may be limited due to the baseline severity of the patient.

Long-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicin.

INTRODUCTION: Incidence of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected persons has dramatically decreased in the highly active antiretroviral therapy era. However, this tumor still represents the most common cancer in this population. OBJECTIVES: The objectives of this study were to evaluate long-term prognosis of HIV-infected patients with KS who had received pegylated liposomal doxorubicin (PLD) and, more specifically, to assess tumor relapse rate, mortality, and cause of death in these subjects. DESIGN: This study was a retrospective review of all patients with KS who had received PLD in centers belonging to the Caelyx/KS Spanish Group. Kaplan-Meier analysis and univariate and multivariate Cox-regression analysis were used to assess the rate of and factors associated with relapse and death through January 2006. RESULTS: A total of 98 patients received PLD from September 1997 through June 2002. Median follow-up after initiation of treatment was 28.7 months (interquartile range, 6.6-73.2 months); during follow-up, 29 patients died (a mortality rate of 14.6% per year). In 9 patients (31%), the cause of death was related to the appearance of other tumors (including 7 lymphomas, 1 gastrointestinal adenocarcinoma, and 1 tongue epidermoid cancer). Death caused by progression of KS occurred in 3 cases. Death risk was inversely related to CD4(+) cell counts at the end of follow-up (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.5-0.9). A relapse study was performed for 61 patients who had complete or partial response to PLD and who attended a control visit after treatment completion. After a median follow-up of 50 months (interquartile range, 17.2-76 months), 8 patients (13%) had experienced relapse; 5 of these patient experienced relapse within the first year after stopping PLD. The only factor that was independently related to risk of relapse was having a CD4(+) cell count >200 cells/microL at baseline (hazard ratio, 6.2; 95% confidence interval, 1.2-30). Lower CD4(+) cell count at the end of follow-up was marginally associated with relapse (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.6-1.01). CONCLUSIONS: Treatment of KS with PLD in HIV-infected patients is followed by a low relapse rate, with most relapses occurring during the first year after stopping chemotherapy. However, the mortality rate in this population was high, in part because of an unexpectedly high incidence of other tumors, mainly lymphomas.

Impact of early central venous catheter removal on outcome in patients with candidaemia.

Removal of central venous catheters (CVCs) from candidaemic patients is considered the reference standard of care, although this practice is not always possible. The impact of prompt catheter removal on outcome was investigated by analysing data from an active population-based surveillance study in Barcelona, Spain. Patients with candidaemia and a CVC were identified between January 2002 and December 2003. Cases with CVC removal within 2 days were classified as having early CVC removal. Outcome, defined as in-hospital mortality 2-30 days after diagnosis of candidaemia, was determined among hospitalised adults using univariate, Kaplan-Meier and multivariate logistic regression analysis. Outpatients, paediatric patients and those who died or were discharged within 2 days were excluded. The study identified 265 patients with candidaemia and a CVC. Median time from diagnosis of candidaemia to catheter removal was 1 day (range 0-29 days). Overall, 172 patients met the criteria for inclusion in the outcome study. Patients with early CVC removal differed significantly from those with delayed CVC removal. According to univariate, Kaplan-Meier and multivariate analysis, the marker most predictive of in-hospital mortality among candidaemic patients with CVCs was severity of illness. These data suggest that timing of CVC removal may best be determined after carefully considering the risks and benefits to individual patients.

Recurrent and self-healing cutaneous monoclonal plasmablastic infiltrates in a patient with AIDS and Kaposi sarcoma.

Infection with human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin lymphoma. Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell lymphoma that often involves the oral cavity of HIV+ patients. It is characterized by immunoblastic morphology and plasma cell phenotype. Cutaneous involvement in PBL appears to be rare. We report a 44-year-old man with AIDS and Kaposi sarcoma (KS) previously treated with doxorubicin who, following treatment with highly active antiretroviral therapy, developed an erythematous infiltrated nodule on the right arm. Histology showed subcutaneous fat necrosis and clusters of atypical large plasma cells (plasmablastic cells). Immunohistochemistry revealed lambda light chain restriction. Epstein-Barr virus (EBV) mRNA was detected by in situ hybridization within the plasmablastic cells. Polymerase chain reaction amplification with specific primers for human herpesvirus 8 (HHV-8) performed on the skin biopsy specimen detected a specific band. A complete screening (bone marrow biopsy, computed tomographic scan, radiological survey) disclosed no abnormalities. The lesion resolved spontaneously after 3 months. Two years later an infiltrated plaque developed on the abdominal wall. The clinical and histopathological features of this new lesion were similar to those observed 2 years previously. No evidence of extracutaneous involvement was detected. The lesion again resolved spontaneously after 25 days. PBL may be seen in patients with transplants or receiving chemotherapy, but is usually observed in patients with advanced AIDS. The observation of recurrent self-healing EBV- and HHV-8-associated cutaneous monoclonal plasmablastic infiltrates, in a patient with AIDS and KS, expands the clinical spectrum of AIDS-associated plasmablastic lymphoproliferative disorders.

Response to liposomal doxorubicin and clinical outcome of HIV-1-infected patients with Kaposi's sarcoma receiving highly active antiretroviral therapy.

PURPOSE: HIV-associated Kaposi's sarcoma (KS) may not resolve despite highly active antiretroviral therapy (HAART). Moreover, the therapeutic goal has shifted from palliative care to long-term durable complete remission. The objective of the study was to assess the impact of liposomal doxorubicin in the treatment of HIV-associated KS in the HAART era. METHOD: In this prospective, noncomparative, multicenter study, patients with more than 10 cutaneous lesions or visceral disease were treated with 20 mg/m(2) of liposomal doxorubicin (Caelyx) every 3 weeks in addition to their antiretroviral therapy. In addition to tumor measurements and laboratory tests, human herpes virus 8 (HHV-8) polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC) was performed. RESULTS: Out of 79 participants enrolled in the study, 47 (59%) had stage T(1), 41 (52%) I(1), and 32 (40%) S(1). Nine individuals were not evaluable for response, 32 (40%) had complete response, 30 (38%) partial response, 5 (6%) stable disease, and 3 (4%) progression. Regression analysis did not find any statistically significant factor predicting response. HHV-8 PCR was positive in 37/53 (70%) patients with available PBMC samples, and HHV-8 viremia cleared in 14/27 (52%) without correlation with clinical response. Eleven (14%) participants experienced a relapse of KS, while at the last update of data, 49 (62%) remained stable. The only risk factor for recurrence identified was the follow-up time (odds ratio [OR] 1.21, 95% CI 1.07-1.36; p =.002). CONCLUSION: The response rate of AIDS-associated KS to liposomal doxorubicin administered with HAART was high, and most often the response was durable. HHV-8 viremia did not correlate well with clinical outcome.

Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors.

In this observational single-center cohort study outside the clinical trial setting, outcome and predictors of virologic failure of highly active antiretroviral therapy (HAART) containing a protease inhibitor were evaluated in human immunodeficiency (HIV)-infected persons. The study population consisted of 807 protease inhibitor-naive HIV-seropositive patients who initiated antiretroviral therapy with reverse transcriptase inhibitors and protease inhibitors (indinavir, nelfinavir, ritonavir) between January 1997 and January 1999. Demographic variable, plasma HIV-1 RNA levels, CD4+ T-cell count, adverse drug reactions, and adherence to HAART were assessed. Virologic treatment response was defined as a decrease in plasma HIV-1 RNA load from baseline to below 500 copies per milliliter after 12 months of therapy. Levels of HIV-1 RNA were undetectable in 43% of patients at 12 months. Factors associated with failure to suppress viral load included age 40 years or younger, baseline CD4+ T cell count less than 200 x 10(6) per liter baseline viral load greater than 4.3 log(10) per milliliter, and non-adherence to HAART. After adjustment by logistic regression, non-adherence was the only statistically significant variable associated with virologic failure (odds ratio 0.38, 95% confidence interval 0.21 to 0.67). Unselected patients in whom protease inhibitor is started in a usual clinical setting achieve viral suppression less frequently than do patients in controlled clinical trials. Failure to adherence to HAART was the strongest predictor of virologic failure.

[Adherence to very active antiretroviral treatment: impact of individualized assessment]. / Adherencia al tratamiento antirretroviral de gran actividad: impacto de una intervención de asesoramiento individualizado.

BACKGROUND: To determine if the intervention of individual advice improves adherence and effectiveness to highly active antiretroviral therapy. METHODS: Randomized open trial. Patients treated with zidovudine + lamivudine + indinavir were assigned (2/1) to conventional care or individual advise. Individual advise consists in adaptation to treatment to patient style of live and detailed information of therapy. Adherence were estimated with structured interview and pillo counts and were considered correct when more than 90% of prescribed drugs were taken. RESULTS: Patients 170, conventional care: 110 and IA: 60. FOLLOW-UP: 24 weeks. Baseline characteristics were similar in both groups. Correct adherence were estimated in 52.7% of conventional care and in 76.7% of individual advise (p = 0.002, relative risk: 1.45; CI 95%: 1.16-1.82). Undetectable viral load (NASBA < 50 copies/ml) in 54.5% of conventional care and in 65% of individual advise (p = 0.18, relative risk: 1.19; CI 95%: 0.93-1.53). Reduction of viral load in the conventional care group 1.02 +/- 0.5 log10/ml, and in the individual advise group 1.98 +/- 0.7 log10/ml. CONCLUSION: The individual advice improve adherence with a tendency to improve effectiveness of highly active antiretroviral therapy.

[Minimal inhibitory concentrations of Candida species to five antifungals by using the reference dilution micromethod and the E-test.]. / Concentraciones mínimas inhibitorias de levaduras a cinco antifúngicos utilizando un micrométodo de dilución estandarizado y el E-test.

It is accepted that the frequency of candidosis has increased during the last decade, specially in hospitalized patients. The more frequent use of azole antifungals and the recognition of isolates of Candida sp resistant to these and other drugs such as 5-fluorocytosine constitute a great need for a reproducible and useful C. albicans in vitro susceptibility testing method for monitoring antifungal therapy in clinical mycological laboratories. The E-test is a novel agar diffussion technique for testing the susceptibility of yeasts against a defined continous gradient of drug and could be used by most clinical laboratories. In this study the E-test and the NCCLS reference microbroth method (M27-P guidelines) were used to determine the MICs of amphotericin B, 5-flucytosine, itraconazole, fluconazole and ketoconazole for 50 clinical isolates of Candida albicans, Torulopsis glabrata, C. tropicalis and Hansenula anomala and five reference ATCC strains. The main purpose of the study was to compare the results obtained by the two methods. In general good agreement (+/- 1 dilution) was otained between both methods, despite differences observed for some species-antifungal combinations in which the MICs were lower by the E-test than by the microbroth method. MICs for C. albicans and T. glabrata to amphotericin B were < 0.50 microg/mL. Two isolates of C. albicans and two others of H. anomala, showed MIC < 8 microg/mL for 5- flucytosine. All isolates of T. glabrata and 40% of C. albicans showed MICs > 16 microg/mL for fluconazole. The results of this study indicate that E-test is an alternative for susceptibility testing to the NCCLS reference method. Because its simplicity it seems to be an easier test for routine clinical laboratories.

Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group.

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

[Fever of unknown origin in patients with human immunodeficiency virus infection. Study of 100 cases]. / Fiebre de origen desconocido en pacientes con infección por el virus de la inmunodeficiencia humana. Estudio de 100 casos.

BACKGROUND: Fever of unknown origin (FUO) has been insufficiently studied in patients infected with HIV. The aim of this study was to determine the incidence, mean hospital stay, etiology, diagnostic methods and clinical course in patients infected with HIV and FUO. METHODS: Descriptive prospective study of patients infected with HIV and with FUO for a period of 24 months (February 1993-February 1995). Out of a total of 1,202 admissions, 100 were prompted by FUO in 95 patients (61 males, 34 women). Sixty-six per cent were parenteral drug abusers or had been so and the mean T CD4+ lymphocyte count was 0.061 x 10(9)/1 +/- 0.075 x 10(9)/1. RESULTS: The incidence of FUO was 8.3 every 100 patients/year. The mean hospital stay was 31.3 +/- 17.8 days, compared with an overall mean stay for HIV-positive patients of 14.6 +/- 8 days (p < 0.001). An etiologic diagnosis was achieved in 90% of cases. Pulmonary or extrapulmonary tuberculosis accounted for approximately 50% of cases, whereas non tuberculous mycobacteria (MAI and M. kansasii) for 20%. The other etiologies (CMV, visceral leishmaniasis, PCP, toxoplasmosis, cryptococcosis, lymphoma) accounted each for less than 5% of diagnoses. In 14 occasions there were two concomitant diagnoses. Mortality rate was 22%, which was higher when two simultaneous diagnosis were present [RR: 3.17 (1.5-6.6)]. In 45% of fatal cases one of the diagnoses went undiagnosed premortem. The highest diagnostic yield was obtained with sputum culture (34.2% of diagnosis) and blood culture (21.5%). CONCLUSIONS: FUO in common in patients infected with HIV, with important health resources consumption associated. The obtention of diagnosis was possible in a high percentage of patients. It is associated with a high hospital mortality rate. The most common diagnoses were tuberculosis and infections by other mycobacteria. It is possible to obtain the diagnosis with non-invasive procedures in 75% of cases.

[Clinico-radiologic characteristics of 8 cases of brain tuberculoma]. / Características clinico-radiológicas de ocho casos de tuberculomas cerebrales.

Several problems are presented in differential diagnosis between cerebral tuberculomas and other brain lesions. Eight cases of cerebral tuberculomas diagnosed in our hospital between 1962 and 1992 were studied. Data about age, sex, HIV antibodies, clinical manifestation, tomographic images, non cerebral locations, diagnostic method, evolution and treatment resolution were collected. Eight cases were diagnosed, seven men and one woman, age 40.75 +/- 10 HIV antibodies in three patients were positive. Meningitis (4 cases) and weight loss (4 cases) were the first clinical features. Confusional state, fever and seizures were presented in three cases one (37.5%), ataxia in two cases (25%) and headache in one (12.5%). Lesions were sole in 62.5% of cases, and several in 37.5%. Were high density in 25.9% and low density in 75%. All patients presented a other localization of tuberculosis. Mycobacterium tuberculosis was isolated in sputum in 75% of cases. After six month, most of the lesions improved.

Renal infection due to Absidia corymbifera in an AIDS patient.

A case of renal zygomycosis due to Absidia corymbifera in an heroin addict suffering from AIDS (phase IV C2) is described. Diagnosis was by histopathology after nephrectomy, but A. corymbifera was isolated several times from urine and from the exudate from a fistula in the surgical wound. After amphotericin B treatment (1.5 g overall dose) clinical cure and negative cultures were obtained. No relapses were observed until death 1 year later from Pneumocystis carinii pneumonia.

[Salmonella typhimurium as the causal agent of pulmonary cavitations]. / Salmonella typhimurium como agente productor de cavidades pulmonares.

BACKGROUND: Relation between patients with immunosuppression (malignancy, renal transplant) and bacteremia by Salmonella non-typhi, specially by Salmonella typhimurium, is known. This relation has been published for patients who suffer from AIDS, and so Salmonella bacteremia could even begin the clinical disease. But even though the relation between the infection by Salmonella and AIDS is well known, and the pulmonary involvement in them has been told, this etiology as a producing agent of lung cavitation has not much documentation. METHODS: We examined three patients (two women and one man) suffering from fever of one week of duration, cough, expectoration and thoracic pain in two of them. The third patient had fever and cachexia without clinical symptoms. The man and the two women had a blood count with neutrophilia and leucocytosis in two cases and leucopenia in the other one. All of them suffered a very important depression of cell immunity (CD4 of 140, 70 and 4, respectively) and positive blood cultures for Salmonella typhimurium. RESULTS: Chest X-Ray showed, in all the cases, pulmonary cavities. CONCLUSIONS: Salmonella typhimurium must be included among the agents that can produce pulmonary cavities like Staphylococcus aureus, mycobacteria, fungus and other gram-negative bacilli.

Extensive dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patient with AIDS.

Retrospective studies have shown the occurrence of episodes of deep or superficial fungal infections in 58 to 81% of HIV/AIDS patients as a result of impairment of cell immunity. We describe a case of disseminated cutaneous dermatophytoses caused by Trichophyton mentagrophytes and Microsporum canis in a patients with AIDS. Diagnostic and therapeutic problems in relation to this unusual presentation are emphasized as well as the importance of an early mycologic diagnosis to prescribe antifungal therapy.