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Biomedical subjects

Pilar Martín-Dávila

Publications and source records attributed to Pilar Martín-Dávila.

14 recordsLinked to original sources

HCV clearance and treatment outcome in genotype 1 HCV-monoinfected, HIV-coinfected and liver transplanted patients on peg-IFN-alpha-2b/ribavirin.

BACKGROUND/AIMS: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients. METHODS: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-alpha-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%). RESULTS: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P<0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95% CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95% CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95% CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not. CONCLUSIONS: HIV-coinfection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.

Adult↗

Linezolid for the treatment of multidrug-resistant tuberculosis.

OBJECTIVES: In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce. METHODS: We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. RESULTS: Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and <50 CD4 cells/mm(3)). The other three patients were infected by multidrug-resistant M. tuberculosis strains, with resistance to all first-line drugs and other second-line drugs. All patients received linezolid in combination with thiacetazone, clofazimine or amoxicillin/clavulanate. Susceptibility tests showed linezolid MIC values < or =0.5 mg/L against all tuberculosis strains tested (standard proportion method, Middlebrook agar 7H10). In all cases, tuberculosis cultures from respiratory samples were sterile after 6 weeks of therapy. Three patients have clinical and microbiological cure of tuberculosis with a combination regimen with linezolid (range: 5-24 months). One patient was lost to follow-up at month 5. The remaining patient has completed 11 months of therapy and is still on treatment. Four patients developed anaemia and needed blood transfusions. In two of these patients, the linezolid daily-dose (600 mg twice a day) was successfully reduced to 50% (300 mg twice a day) to decrease toxicity while maintaining efficacy. Peripheral neuropathy (two patients) and pancreatitis (one patient) were other adverse events observed during linezolid treatment. CONCLUSIONS: In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.

Acetamides↗

Liver transplantation in HIV-infected recipients.

Liver transplantation is being evaluated as a therapeutic option for human immunodeficiency virus (HIV)-infected patients with end-stage liver disease, but experience is still scarce. We describe the outcome of 4 HIV-infected patients who underwent liver transplantation in our hospital between July 2002 and April 2003. HIV-infected liver transplant recipients meet the same standard criteria for transplantation as do HIV-negative candidates. In addition, HIV infected persons are required to have a CD4 T-cell count greater than 100/mL (CD4 T-cells are targets for HIV infection). Immunosuppressive regimens, perioperative surgical prophylaxis, and prophylaxis for opportunistic infections are standard in the Liver Transplantation Unit in our hospital. Four patients, including 3 former intravenous drug users, received a liver transplant (2 from deceased donors and 2 from living donors), with a median follow-up of 510 days. Three patients (75%) are alive, with 1 death occurring 17 months posttransplantation in a patient who developed fibrosing cholestatic hepatitis. Rejection occurred in 1 patient, and was managed with no complications. Hepatitis C virus (HCV) recurrence occurred in 3 patients. HIV-infection has remained under control with antiretroviral treatment. A combination of 3 nucleoside analogs was used in 3 patients, with no need for drug adjustments. No opportunistic infections or other significant infectious complications developed. In conclusion, orthotopic liver transplantation seems a safe therapeutic option in the short term for HIV-infected persons with end stage liver disease, including patients with a history of drug abuse. If indicated, an antiretroviral regimen consisting of 3 nucleosides could be used to avoid interactions with immunosuppressive drugs.

Adult↗

Analysis of mortality and risk factors associated with native valve endocarditis in drug users: the importance of vegetation size.

BACKGROUND: Native valve endocarditis in drug-user patients had a microbiology, a frequency of involvement of different cardiac valves, and a prognosis that differ from those in non-drug users. A retrospective study of native valve endocarditis cases in intravenous drug users diagnosed from 1985 to 1999 in our institution was performed to analyze the inhospital mortality of drug users with native valve endocarditis and to identify factors predictive of mortality. METHODS: All patients fulfilled the Duke's criteria for definite or probable endocarditis. Analysis of predictors of inhospital mortality was restricted to right-sided infective endocarditis (IE) with definite diagnosis and echocardiographic data. The following variables were analyzed: sex, HIV serostatus, CD4 cell count < 200/mm3, time of IE diagnosis (before 1993 or after 1993), previous valvulopathy, polymicrobial IE, fungal etiology (mixed or alone), neurological complication, arterial emboli, pulmonary emboli, congestive heart failure, vegetation size (VS) > 2 cm, and inhospital cardiac surgery. Logistic regression was used in a multivariate model to identify factors independently associated with mortality. Adjusted odds ratios (OR) and 95% CIs were examined. RESULTS: Four hundred ninety-three cases of IE were diagnosed in this period. Two hundred twenty cases of native valve endocarditis in intravenous drug users were identified. Fourteen cases in this group died (6%). Mean time from diagnosis to death was 18.5 +/- 15 days (range, 3-52). Vegetation size was available in 111 cases. Univariate analysis identified the following variables associated with inhospital mortality in right-sided cases: VS > 2 cm and fungal etiology. In multivariate analysis, the variables associated with mortality that achieved statistical significance were size of vegetation > 2 cm (P = .014, OR 10.2, 95% CI 1.6-78.0) and fungal etiology (P = .009, OR 46.2, 95% CI 2.4-1100.9). CONCLUSIONS: The main prognostic factors of inhospital mortality in right-sided IE in drug users in our series were VS > 2 cm and fungal etiology. The role of early surgery in these patients should be reevaluated.

Adult↗

Nosocomial endocarditis in a tertiary hospital: an increasing trend in native valve cases.

INTRODUCTION: Changes in the etiology, epidemiology, and outcome of infective endocarditis (IE) have been observed in recent years. Newer invasive therapeutic interventions have increased the risk of bacteremia and nosocomial endocarditis in the population at risk. A retrospective analysis of hospital-acquired IE cases was performed in a tertiary hospital during 1985 to 1999. MATERIAL AND METHODS: Cases included were those classified as "probable" or "definite" by the IE diagnostic criteria of Durack. Nosocomial acquisition was considered if diagnosis was made > 72 h after hospital admission and there was no evidence that IE was present at the time of admission. Patients receiving a diagnosis within 60 days of a previous hospital admission were also classified as nosocomial, when a risk procedure for bacteremia was performed, or when any predisposing factor for IE was present during hospitalization. Early prosthetic valve endocarditis (PVE) cases (< 1 year) were excluded from the analysis. Clinical characteristics, etiology, predisposing cardiac condition, source of infection, and outcome were analyzed. Results were compared with those obtained in community-acquired cases. RESULTS: Of 493 cases of IE diagnosed over 15 years, 38 were considered to be hospital acquired. Twenty-eight cases were native valve endocarditis (NVE) in non-IV drug user patients, and 10 cases were late PVE. Overall, the most frequent microorganisms involved were staphylococci (58%). The main sources of infection were intravascular procedures or catheter-related infections (55%). When nosocomial NVE cases were compared with community-acquired cases, mortality was greater (29% vs 9.7%) in hospital-acquired endocarditis. Analysis of time trends showed an increased rate of nosocomial cases in NVE throughout the years of the study. CONCLUSIONS: In NVE, the number of cases that are hospital acquired has been increasing during the last 15 years. These cases are frequently associated with invasive intravascular procedures or IV catheter-related infections. Most patients have a previous valvulopathy that predisposes to IE. The spectrum of microorganisms involved is different from the community-acquired cases. Also, the outcome of endocarditis is worse in nosocomial NVE patients.

Adolescent↗

High genetic diversity among Stenotrophomonas maltophilia strains despite their originating at a single hospital.

The levels of genetic relatedness of 139 Stenotrophomonas maltophilia strains recovered from 105 hospitalized non-cystic fibrosis patients (51% from medical wards, 35% from intensive care units, and 14% from surgical wards) and 7 environmental sources in the same hospital setting during a 4-year period were typed by the pulsed-field gel electrophoresis (PFGE) technique. A total of 99 well-defined distinct XbaI PFGE patterns were identified (Simpson's discrimination index, 0.996). The dendrogram showed a Dice similarity coefficient ranging from 28 to 80%. Two major clusters (I and II), three minor clusters (III, IV, and V), and two independent branches were observed when using a 36% Dice coefficient, indicating a high diversity of genetic relatedness. It is of note that 84% of strains were grouped within two major clonal lineages. No special cluster gathering was found among strains belonging to the same sample type specimen, patients' infection or colonization status, and ward of precedence. Despite this fact, three different clones (A, B, and C) recovered from respiratory samples from six, three, and two patients, respectively, and two clones, D and E, in two bacteremic patients each, were identified. Isolation of an S. maltophilia strain belonging to the clone A profile in a bronchoscope demonstrated a common source from this clone. This study revealed a high genetic diversity of S. maltophilia isolates despite their origin from a single hospital, which may be related to the wide environmental distribution of this pathogen. However, few clones could be transmitted among different patients, yielding outbreak situations.

Bacteremia↗

Neurological complications of varicella-zoster virus in human immunodeficiency virus-infected patients: changes in prevalence and diagnostic utility of polymerase chain reaction in cerebrospinal fluid.

Neurological complications caused by varicella-zoster virus (VZV) were diagnosed in 13 human immunodeficiency virus (HIV)-infected patients in our hospital. There was a favorable influence of highly active antiretroviral therapy (HAART) in the prevalence of these disorders among acquired immunodeficiency syndrome (AIDS) patients: Since 1996, only 1 of 961 AIDS patients had VZV neurological disease, compared to 9 of 1088 patients before that year (P =.02). Polymerase chain reaction (PCR) detected VZV DNA in cerebrospinal from 4 of 5 patients with VZV neurological disease, and from 2 of 130 HIV-infected patients with other neurological diseases (sensitivity 0.8, specificity 0.98 [95% confidence intervals 0.45-1 and 0.96-1, respectively], positive predictive value 0.94).

Adolescent↗

Risk factors for invasive aspergillosis in liver transplant recipients.

Aspergillosis is a potential, severe, and usually early complication of liver transplantation. New promising strategies, such as detecting Aspergillus antigenemia, have been used for the diagnosis of aspergillosis in immunosuppressed patients, but the impact in solid organ transplantation is not well known. A case-control study in 260 adults who underwent liver transplantation from January 1994 to June 2000 was performed. A case was defined as any liver transplant recipient with a proven or probable diagnosis of invasive aspergillosis. Controls were defined as a liver transplant recipient without aspergillosis infection with a survival longer than two months after transplantation. Clinical and analytical variables, including Aspergillus antigenemia, were compared. A special analysis was performed in patients in whom late aspergillosis developed (after day 100 posttransplantation). Among 260 patients, invasive aspergillosis developed in 15 (5.6%). Median time from transplantation to aspergillosis in 13 patients with sufficient data for analysis was 126 days (range, 22 to 1117). Seven (54%) developed the infection after day 100 posttransplantation. Thirty-eight patients were used as controls. Antigenemia was available in nine of 13 cases and in 33 of 38 controls. By multivariate analysis, retransplantation (OR, 29.9 [95% CI, 2.1 to 425.1]), dialysis requirements after transplantation (OR, 24.5 [95% CI, 1.25 to 354]), and the presence of Aspergillus antigenemia in serum at any time point after transplantation (OR, 50.0 [95% CI, 3.56 to 650]) were independently associated to aspergillosis. In the subgroup of patients that developed late aspergillosis, cytomegalovirus infection (OR, 6.7 [95% CI, 1.0 to 42.5]) was the only independent factor associated. Hepatic and renal dysfunction predispose to Aspergillus infection in liver transplant recipients. Cytomegalovirus infection and increased immunosuppression favor invasive aspergillosis during the late posttransplantation period. Aspergillus antigenemia seems to be a good predictor of invasive aspergillosis.

Adult↗

Risk factors associated with ampicillin resistance in patients with bacteraemia caused by Enterococcus faecium.

Epidemiological characteristics of ampicillin-resistant, vancomycin-susceptible Enterococcus faecium are not well known. Recently, these strains have been proposed as the substratum for the later appearance of vancomycin-resistant E. faecium. To analyse this problem, the medical charts of patients with bacteraemia caused by E. faecium diagnosed in our institution during a 6 year period (1994-1999) were reviewed. Demographic data, clinical characteristics, antibiotic exposure and outcome were compared among patients with ampicillin-resistant (MIC > 16 mg/L, NCCLS criteria) and ampicillin-susceptible strains. Clonality between different strains was analysed by pulsed-field gel electrophoresis (PFGE). We evaluated 49 cases of E. faecium bacteraemia; 29 patients with ampicillin-resistant strains and 20 patients with -susceptible strains were identified. By logistic regression analysis, only previous administration of beta-lactams (OR: 6.3; 95% CI: 1.12-20.0) and urinary catheterization (OR:4.2; 95% CI: 1.3-30.0) were identified as predictors of ampicillin resistance in enterococcal bacteraemic patients. An elevated APACHE II score was the only independent factor associated with mortality in enterococcal bacteraemia (OR:13.5; 95% CI: 1.04-175.4). PFGE analysis revealed a strong association between specific ampicillin-resistant clones and the location of patients during hospitalization, suggesting nosocomial transmission. Bacteraemia caused by ampicillin-resistant enterococci was not associated with increased mortality when compared with bacteraemias caused by ampicillin-susceptible strains.

Ampicillin Resistance↗

[Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus infection in transplanted patients].

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.

Antiviral Agents↗