Milagro Montero

Influence of HAART on the Clinical Course of HIV-1-Infected Patients With Progressive Multifocal Leukoencephalopathy : Results of an Observational Multicenter Study

Background:The aim of this study was to analyze the incidence of new cases, survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy (PML), and the characteristics of PML-associated immune reconstitution inflammatory syndrome (IRIS). Methods:Multicenter observational cohort study of all HIV-1-infected patients newly diagnosed of PML in 7 hospitals in Barcelona (Spain) from 2002 to 2006. The annual incidence of PML was calculated. Survival was estimated using the Kaplan-Meier method. IRIS was defined as new onset or rapid worsening of PML shortly after initiation of highly active antiretroviral therapy together with a decline in HIV-1 viral load and rising of CD4 lymphocytes. Results:Sixty-one new cases of PML were diagnosed. The mean survival time was 15 months [95% confidence interval (CI), 11 to 19]. The Kaplan-Meier estimates of the probability of survival were 47.7% (95% CI, 35 to 59) at 6 months, 38.6% (95% CI, 25 to 51) at 12 months, 35.1% (95% CI, 22 to 48) at 24 months, and 25.1% (95% CI, 10 to 40) at 36 months. IRIS was diagnosed in 14 (23%) cases. Mortality was similar in patients with and without IRIS. Conclusions:PML continues to be one of the deadliest opportunistic infections in acquired immunodeficiency syndrome patients. The development of PML-associated IRIS has no influence on prognosis.

Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial.

Background:Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. Objectives:To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1–infected patients with virologic suppression. Methods:A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1–infected patients with viral load of <20 copies per milliliter for at least 2 years. Patients were randomized to oral supplementation with probiotics or placebo during 12 weeks. Markers of microbial translocation (lipopolysaccharide-binding protein [LBP] and soluble CD14), inflammation (interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, high-sensitivity C-reactive protein), and immunological and clinical data were determined before and after the intervention and 3 months after treatment discontinuation. Quantitative variables were compared using the Mann–Whitney U test, and categorical variables were compared using the Fisher exact test. Results:After 12 weeks of treatment, differences between the probiotic arm and the placebo arm were observed in LBP values (−0.30 vs +0.70 pg/mL) and IL-6 (−0.60 vs +0.78 pg/mL). These differences were also noted at 3 months after treatment withdrawal. Qualitative analysis was performed, defining a variable as “decreased” or “increased” from baseline LBP. A significant decrease of LBP at 12 weeks of treatment was observed (57.9% patients in the probiotic group vs 6.2% in the placebo group, P = 0.002). Conclusions:Treatment with S. boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1–infected patients with long-term virologic suppression.

Community-onset healthcare-related urinary tract infections: Comparison with community and hospital-acquired urinary tract infections

OBJECTIVES To analyze the characteristics of infection, adequacy of empirical treatment and outcome of patients with community-onset healthcare-associated (HCA) urinary tract infections (UTI) and compare them with hospital (HA) and community-acquired (CA) UTI. METHODS Prospective observational cohort study performed at a university 600-bed hospital between July 2009 and February 2010. Patients with UTI requiring hospital admission were included. Epidemiological, clinical and outcome data were recorded. RESULTS 251 patients were included. Patients with community-onset HCA UTI were older, had more co-morbidities and had received previous antimicrobial treatment more frequently than CA UTI (p = 0.02, p = 0.01 and p < 0.01). ESBL-Escherichia coli and Pseudomonas aeruginosa infections were more frequent in HCA than in CA UTI (p = 0.03 and p < 0.01). Inadequate empirical treatment was not significantly different between community-onset HCA and CA. Factors related to mortality were P. aeruginosa infection (OR 6.51; 95%CI: 1.01-41.73), diabetes mellitus (OR 22.66; 95%CI: 3.61-142.21), solid neoplasia (OR 22.48; 95%CI: 3.38-149.49) and age (OR 1.15; 95%CI 1.03-1.28). CONCLUSIONS Epidemiological, clinical and microbiological features suggest that community-onset HCA UTI is different from CA and similar to HA UTI. However, in our series inadequate empirical antimicrobial therapy and mortality were not significantly higher in community-onset HCA than in CA UTI.

Chronic Kidney Disease Prevalence and Risk Factors Among Hiv-infected Patients

To the Editors: Chronic kidney disease (CKD) in its different stages is independently related to higher risk of death, development of cardiovascular diseases, and higher hospitalization rates. It is currently considered a relevant and growing public health problem. Therefore, early diagnosis is crucial for the implementation of preventive measures. The regular use of combined antiretroviral therapy (CART) has had a substantial impact on the survival rate of human immunodeficiency virus (HIV)– infected patients, resulting in the aging of this population in which chronic pathologies can appear. The deterioration of renal function is clinically silent. Only through specific analyses it is possible to diagnose and evaluate the presence of CKD in the early stages. For all these, there is an increasing concern about renal dysfunction in HIV-infected patients. A cross-sectional study was carried out onHIV-infected patients at a university hospital in Barcelona, Spain. All patients were 20 years or older. Exclusion criteria included evidence of clinical signs of active acquired immunodeficiency syndrome or no related acquired immunodeficiency syndrome infections in the 3 months before inclusion due to their possible impact on the anthropometric and biochemical parameters. A control group, adjusted by age, was recruited during the same period from the outpatient clinic of the hospital. These patients should have had a minimum follow-up of 3 consecutive visits during 1 year. Estimated glomerular filtration rate (GFR) was ascertained according to the Modification of Diet in Renal Disease (MDRD-4) formula. CKD was defined as GFR <60 mL/min/1.73 m on at least 2 occasions separated by at least 3months. In the control group, only age, sex, and GFR were recorded. For each HIV-infected patient, cardiovascular risk factors were evaluated according to the recommendations of Panel III of the National Cholesterol Education Program. We also recorded HIV exposure (mutually exclusive in the following order: intravenous drug use, homosexual or heterosexual activity), length of time from diagnosis, nadir lymphocyte CD4 cell count and the viral load before starting CART, HIV disease status according to the 1993 Centers for Disease Control and Prevention classification, exposure to antiretroviral treatment, classified as ‘‘naive’’ or ‘‘currently in treatment,’’ and hepatitis C coinfection. For those receiving CART, duration of exposure was also considered. The physical examination included height and weight measurements and arterial pressure readings. Lipodystrophy was defined through the patient’s own perception of changes in distribution of body fat and an evaluation by a single investigator. We studied 854 patients. Seven hundred forty-seven (87.5%) received antiretroviral treatment, and of these, 156 (18.3%) were exposed to tenofovir (TDF). Average exposure to CART was 80 months. In the control group (2134 HIVnegative patients), a prevalence of CKD was 5.6% [95% confidence interval (CI): 4.7 to 6.7], whereas in the HIV infected was 7.6% (95% CI: 6.0 to 9.6). In naive patients, CKD prevalence was 4.7% and in CARTexposed was 8% (P: 0.3). Thus, in comparison to the control group, HIV-infected patients showed a greater prevalence of CKD (Odds ratio (OR): 1.40; 95% CI: 1.02 to 1.91; P: 0.04). Whenwe analyzed the factors potentially associated to CKD, TDF exposure was related to a high proportion of patients with CKD (9.3%); however, it did not reach statistical significance compared neither with naives nor patients exposed to other antiretroviral drugs (7.6%). In the univariate analysis, the factors associated with CKD were older age, female gender, hypertension, and diabetes mellitus. Other risk factors associated with CKD were being exposed to CART for more than 5 years, to have a symptomatic HIV infection (B+C category), and the presence of lipoatrophy. In the multivariate logistic regression model, classic risk factors, such as the presence of hypertension and diabetes mellitus, lost statistical significance. Only age (AOR: 3.19 per 10-year increment; 95% CI: 2.42 to 4.21), being female (AOR: 4.55; 95% CI: 2.46 to 8.40), the presence of lipoatrophy (AOR: 1.84; 95% CI: 1.03 to 3.27), and the symptomatic HIV infection (Adjusted odds ratio (AOR): 1.77; 95% CI: 1 to 3.14) appeared as factors independently associated with CKD (Table 1). The prevalence of CKD among HIV-infected patients was higher than in the HIV-negative patients. However, when datawere adjusted by age and gender, HIV infection did not result as an independent risk factor for CKD. The Third National Health and Nutrition Examination Survey III conducted in the United States included 15,626 adults from the general population estimating a prevalence of CKD of 4.6% for GFR <60 mL/min. In Spain, the prevalence of CKD defined as GFR <60 mL/min is 5.7% in a population whose average age is 49.5 years. It must be stated that the HIV-negative population of the present study does not constitute the general population but rather individuals seeking outpatient care at our hospital. Moreover, this population has an average age nearly 10 years older than the population sample discussed in other studies, and for this reason, it could be possible that they have an increased burden of CKD risk factors. However, our results were very similar to those reported in the above mentioned studies carried out in the general population. Data concerning the prevalence of CKD in the HIV-infected population are scarce. The study, which included the greatest number of patients, found a prevalence of 3.5% when using the Cockcroft–Gault equation or 4.7% using MDRD formula. A study that included a high proportion of black race patients found a prevalence of CKD of 15.5%. Our study group is representative of the Spanish population; the relatively low prevalence of CKD may be explained by the low proportion of black race patients. In the logistic regression analysis, factors such as hypertension and diabetes

Prevalencia de factores de riesgo cardiovascular en pacientes con infección por el VIH

Introduccion Determinar la prevalencia de los factores de riesgo cardiovascular en pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH). Pacientes y metodo Estudio transversal en pacientes de 20 anos o mayores con infeccion por el VIH durante el ano 2003 en la consulta externa del Servicio de Medicina Interna y Enfermedades Infecciosas del Hospital del Mar de Barcelona. Se evaluaron las caracteristicas clinico-epidemiologicas de la infeccion por el VIH y los factores de riesgo cardiovascular. Resultados Los 760 pacientes incluidos en el estudio presentaban una media de 1,5 factores de riesgo cardiovascular, siendo el consumo de cigarrillos el mas prevalente (66,8%; intervalo de confianza [IC] 95%: 63,4-70,2). La edad y el sexo como factor de riesgo cardiovascular estuvo presente en el 26,4% (IC 95%: 23,3-29,7) de los pacientes y los antecedentes familiares de cardiopatia isquemica precoz en el 14,3% (IC 95%: 11,8-16,9). La prevalencia de hipertension y de diabetes mellitus fue del 13,2% (IC 95%: 10,8-15,8) y 4,3% (IC 95%: 3,0-6,0), respectivamente. En el 29,3% (IC 95%: 26,1-32,7) se detecto una concentracion de colesterol de las lipoproteinas de alta densidad (c-HDL) inferior a 40 mg/dl y superior a 60 mg/dl en el 16,3% (IC 95%:13,8-19,1). Veinticinco pacientes (3,3%; IC 95%: 2,1-4,8) habian presentado enfermedad cardiovascular sintomatica. Conclusion El tabaquismo y el c-HDL destacan como los principales factores de riesgo cardiovascular en esta cohorte de pacientes con infeccion por el VIH.

Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection

IntroductionInherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains.MethodsWe studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection.ResultsMultivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A0 were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A1 was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A1 haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A0 (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A1 was associated with a higher PaO2/FiO2 ratio (P = 0.001).ConclusionsOur data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A1) SP-A2 for future IAV pandemics.

Globally Expanding Carbapenemase Finally Appears in Spain: Nosocomial Outbreak of Acinetobacter baumannii Producing Plasmid-Encoded OXA-23 in Barcelona, Spain

ABSTRACT Resistance of Acinetobacter baumannii clinical isolates to carbapenems is on the rise worldwide mainly in association with the production of OXA-23. Until recently, however, OXA-23 was absent in Spain. In this work, we report the molecular characterization of a hospital outbreak of OXA-23-producing A. baumannii in Barcelona caused by a multidrug-resistant (MDR) clone belonging to international clone IC-II/sequence type ST85 between October 2010 and May 2011. blaOXA-23 was carried in a plasmid of 90 kb and located within the composite transposon Tn2006.

Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: A matched cohort study.

OBJECTIVE To analyze the clinical and economic impact of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli requiring hospitalization. METHODS Matched cohort study including adults with UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between August 2010 and July 2013. Demographic, clinical and economic data were analyzed. RESULTS One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 due to non-ESBL-producing E. coli. Bivariate analysis showed that prior antimicrobial treatment (p = 0.007) and ESBL production (p < 0.001) were related to clinical failure during the first 7 days. Multivariate analysis selected ESBL as the sole risk factor for clinical failure (p = 0.002). Regarding the economic impact of infections caused by ESBL-producing E. coli, an ESBL-producing infection cost more than a non-ESBL-producing E. coli infection (mean €4980 vs. €2612). Looking at hospital expenses separately, the total pharmacy costs and antibiotic costs of ESBL infections were considerably higher than for non-ESBL infections (p < 0.001), as was the need for outpatient parenteral antibiotic therapy (OPAT) and its related costs. Multivariate analysis performed for the higher costs of UTI episodes found statistically significant differences for males (p = 0.004), chronic renal failure (p = 0.025), ESBL production (p = 0.008) and OPAT (p = 0.009). CONCLUSION UTIs caused by EBSL-producing E. coli requiring hospital admission are associated with worse clinical and economic outcomes.

Prevalence and Factors Associated with Vitamin D Deficiency and Hyperparathyroidism in HIV-Infected Patients Treated in Barcelona

Vitamin D deficiency is an important problem in patients with chronic conditions including those with human immunodeficiency virus (HIV) infection. The aim of this cross-sectional study was to identify the prevalence and factors associated with vitamin D deficiency and hyperparathyroidism in HIV patients attended in Barcelona. Cholecalciferol (25OH vitamin D3) and PTH levels were measured. Vitamin D insufficiency was defined as 25(OH) D < 20 ng/mL and deficiency as <12 ng/mL. Hyperparathyroidism was defined as PTH levels >65 pg/mL. Cases with chronic kidney failure, liver disease, treatments or conditions potentially affecting bone metabolism were excluded. Among the 566 patients included, 56.4% were exposed to tenofovir. Vitamin D insufficiency was found in 71.2% and 39.6% of those had deficiency. PTH was measured in 228 subjects, and 86 of them (37.7%) showed high levels. Adjusted predictors of vitamin D deficiency were nonwhite race and psychiatric comorbidity, while lipoatrophy was a protective factor. Independent risk factors of hyperparathyroidism were vitamin D < 12 ng/mL (OR: 2.14, CI 95%: 1.19–3.82, P: 0.01) and tenofovir exposure (OR: 3.55, CI 95%: 1.62–7.7, P: 0.002). High prevalence of vitamin deficiency and hyperparathyroidism was found in an area with high annual solar exposure.

Urinary micafungin levels are sufficient to treat urinary tract infections caused by Candida spp.

Six cases of patients diagnosed with urinary tract infection (UTI) successfully treated with micafungin are reported. Four were infected with fluconazole-resistant Candida spp. and two (with hepatic injury) were infected with fluconazole-sensitive Candida spp. Traditionally, echinocandins have not been considered for the treatment of UTIs. However, despite its low urinary excretion rate, therapeutic drug monitoring of micafungin urinary levels could be helpful in order to achieve optimal pharmacokinetic/pharmacodynamic (PK/PD) indices for treating UTIs caused by Candida spp. resistant to fluconazole.