Belén Padilla

Treatment of Aids-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy

Objectives:To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). Patients and methods:The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. Results:With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74 × 106/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P < 0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. Conclusions:This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.

Inflammatory reactions in progressive multifocal leukoencephalopathy after highly active antiretroviral therapy.

Three patients with progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) worsened clinically and radiologically. At the time of deterioration all three had reduced HIV viraemia and increased CD4 cell counts. Brain biopsy in all three disclosed PML and marked perivascular lymphoplasmacytic infiltration. We reviewed the slides of 28 brain biopsies diagnostic of PML. Inflammatory changes were observed in four out of nine patients on HAART and in one out of 19 patients not on HAART.

Visceral leishmaniasis (Kala-Azar) in transplant recipients : Case report and review

BACKGROUND In endemic areas, visceral leishmaniasis has been identified as an opportunistic infection in patients with derangements in their cellular immune system. METHODS We report a renal transplant patient with visceral leishmaniasis. We also reviewed the previously published cases of 17 organ transplant recipients with this parasitic disease. RESULTS Visceral leishmaniasis occurred a median time of 8 months after transplantation, and the clinical picture was characterized by fever, splenomegaly, and blood cytopenias. Leishmaniae were detected in bone marrow in 16 of 18 patients and diagnostic serology results were found in 8 of 10 tested patients. Pentavalent antimonials were used to treat 16 patients, five of which developed pancreatitis. Five of 18 patients died, including two untreated patients. Relapses of visceral leishmaniasis occurred in 4 of 13 survivors. CONCLUSIONS In endemic areas, visceral leishmaniasis may complicate the clinical course of organ transplantation and can have fatal consequences, particularly when untreated.

Community-acquired methicillin-resistant Staphylococcus aureus in Madrid, Spain: transcontinental importation and polyclonal emergence of Panton–Valentine leukocidin-positive isolates

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates producing the Panton-Valentine leukocidin (PVL) have been reported worldwide. We describe the molecular characteristics of PVL-positive CA-MRSA strains isolated in Madrid, Spain, and analyze the clinical features of patients infected with these isolates. From 2004 to 2007, we collected 13 PVL-positive MRSA isolates from patients attending to the emergency department. The isolates were genotyped by pulsed-field gel electrophoresis, SCCmec typing, agr polymorphism, and multilocus sequence typing. Susceptibility to 29 antimicrobials was determined by the broth microdilution and by the E-test methods. The isolates belonged to 3 genotypes: ST8-SCCmec IVc (n = 11), ST5-SCCmec IVa (n = 1), and ST80-SCCmec IVc (n = 1). The corresponding agr types were I, II, and III, respectively. Five isolates were resistant to tetracycline and doxycycline, and 1 was resistant to fusidic acid (ST80). The isolates were from children (n = 9) and adults (n = 4), and were associated with skin and soft tissue infections (n = 9), otitis (n = 1), and bacteremia (n = 1). Nine patients were from South America. Our results indicate the transcontinental importation and recent emergence in Spain of PVL-positive CA-MRSA strains belonging to 3 distinct lineages, including 1 predominant (ST8-SCCmec IVc).

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance

The clinical and microbiological characteristics of community-onset healthcare-associated (HCA) bacteraemia of urinary source are not well defined. We conducted a prospective cohort study at eight tertiary-care hospitals in Spain, from October 2010 to June 2011. All consecutive adult patients hospitalized with bacteraemic urinary tract infection (BUTI) were included. HCA-BUTI episodes were compared with community-acquired (CA) and hospital-acquired (HA) BUTI. A logistic regression analysis was performed to identify 30-day mortality risk factors. We included 667 episodes of BUTI (246 HCA, 279 CA and 142 HA). Differences between HCA-BUTI and CA-BUTI were female gender (40% vs 69%, p <0.001), McCabe score II-III (48% vs 14%, p <0.001), Pitt score ≥2 (40% vs 31%, p 0.03), isolation of extended spectrum β-lactamase-producing Enterobacteriaciae (13% vs 5%, p <0.001), median hospital stay (9 vs 7 days, p 0.03), inappropriate empirical antimicrobial therapy (21% vs 13%, p 0.02) and mortality (11.4% vs 3.9%, p 0.001). Pseudomonas aeruginosa was more frequently isolated in HA-BUTI (16%) than in HCA-BUTI (4%, p <0.001). Independent factors for mortality were age (OR 1.04; 95% CI 1.01-1.07), McCabe score II-III (OR 3.2; 95% CI 1.8-5.5), Pitt score ≥2 (OR 3.2 (1.8-5.5) and HA-BUTI OR 3.4 (1.2-9.0)). Patients with HCA-BUTI are a specific group with significant clinical and microbiological differences from patients with CA-BUTI, and some similarities with patients with HA-BUTI. Mortality was associated with patient condition, the severity of infection and hospital acquisition.

Prolonged viral shedding in pandemic influenza A(H1N1): clinical significance and viral load analysis in hospitalized patients

The clinical significance of prolonged viral shedding (PVS) and viral load (VL) dynamics has not been sufficiently assessed in hospitalized patients with pandemic 2009 influenza A(H1N1). We performed a prospective study of adults with confirmed influenza A(H1N1) virus infection admitted to our hospital from 20 September 2009 to 31 December 2009. Consecutive nasopharyngeal swabs were collected every 2 days during the first week after diagnosis, and then every week or until viral detection was negative. Relative VL was measured on the basis of haemagglutinin and RNaseP gene analysis. PVS was defined as positive detection of influenza A(H1N1) virus by real-time RT-PCR at day 7 after diagnosis. We studied 64 patients: 16 (25%) presented PVS. The factors associated with PVS were admission to the intensive-care unit (69% vs. 33%, p 0.02), purulent expectoration (75% vs. 44%, p 0.04), higher dosage of oseltamivir (62.5% vs. 27%, p 0.016), corticosteroid treatment (50% vs. 21%, p 0.05), mechanical ventilation (MV) (50% vs. 12.5%, p 0.004), and longer stay (34 vs. 7 median days, p 0.003). Multivariate analysis revealed the factors independently associated with PVS to be immunosuppression (OR 5.15; 95% CI 1.2-22.2; p 0.03) and the need for MV (OR 11.7; 95% CI 2.5-54.4; p 0.002). VL at diagnosis correlated negatively with age and septic shock. VL dynamics of patients with acute respiratory distress syndrome and/or mortality were very different from those of other patients. PVS was detected in 25% of hospitalized patients with pandemic 2009 influenza A(H1N1) and was strongly associated with immunosuppression and the need for MV. Diagnostic VL and viral clearance varied with the clinical course.

Impact of inappropriate empirical therapy for sepsis due to health care-associated methicillin-resistant Staphylococcus aureus

OBJECTIVES We investigated the influence of empirical therapy on the mortality of patients with health care-associated (HCA) sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA) infections in a multicenter cohort, and the variables associated with inappropriate empirical therapy. METHODS All new cases of infection caused by HCA-MRSA presenting with sepsis syndrome in 59 Spanish hospitals during June 2003 were prospectively followed. The main outcome variable was mortality at day 30. Predictors of mortality and of inappropriate empirical therapy were studied using multivariate logistic regression. RESULTS We included 209 cases. Crude mortality was 23%. After controlling for severity of the underlying condition, ICU stay, presentation with severe sepsis or shock, and site of infection, inappropriate empirical therapy was associated with an increased odds of mortality (OR=3.0; 95% CI: 1.01-9.0; p=0.04). Only 21.1% of the patients received appropriate empirical therapy. Variables independently associated with appropriate therapy were recent surgery, central venous catheter and certain sites of infection (primary bacteraemia, intraabdominal infections, and respiratory tract infections). Cancer patients were at an increased risk of receiving inappropriate therapy. CONCLUSIONS Inappropriate empirical therapy was independently associated with increased mortality in this multicenter cohort. Clinicians should be aware of the need to consider coverage against MRSA more frequently.

Clinical and molecular epidemiology of community-acquired, healthcare-associated and nosocomial methicillin-resistant Staphylococcus aureus in Spain

A prospective cohort study including all new cases of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in 64 Spanish hospitals during June 2003 was performed to investigate the epidemiology of MRSA in Spain. Only patients who yielded clinical MRSA-positive samples were included. Epidemiological and clinical data for a total of 370 cases were collected. Genotyping was performed using pulsed-field gel electrophoresis and multilocus sequence typing. Panton-Valentine leukocidin genes and the staphylococcal chromosomal cassette mec (SCCmec) were identified in representative isolates. MRSA was considered to be nosocomially acquired in 202 cases (55%), healthcare-associated (HCA) in 139 cases (38%), community-acquired (CA) in three cases, and of uncertain mode of acquisition in 26 (7%) cases. The pooled population-based rate was 2.31 cases/100,000 population/month, and the pooled nosocomial rate was 0.21 cases/1000 hospital stays (20.2% of S. aureus). Peripheral vascular disease, respiratory tract infections, catheter infections, bloodstream infections and crude mortality were more frequent among HCA cases, whereas neoplasia and urinary tract infections were more frequent among nosocomially acquired cases. Two clones related to the paediatric clone ST5-IV accounted for 71% of the isolates; EMRSA-16 has emerged in two different geographical areas. Only one isolate belonged to the formerly predominant Iberian clone. The three CA isolates were related to the USA300 clone. SCCmec type IV was the most frequent type in nosocomial and HCA isolates. The epidemiology of MRSA has changed in Spain; outpatients with previous healthcare contact represent a very important reservoir of MRSA, and community isolates are emerging.

Evaluation of MycAssay™ Aspergillus for diagnosis of invasive pulmonary aspergillosis in patients without hematological cancer.

Methods based on real-time polymerase chain reaction (PCR) can speed up the diagnosis of invasive aspergillosis but are limited by a lack of standardization. We evaluated the commercially available MycAssay™ Aspergillus test for the diagnosis of invasive aspergillosis in patients without hematological cancer. We prospectively collected 322 lower respiratory tract samples (November 2009–January 2011) from 175 patients with lower respiratory tract infection and the following predisposing conditions: solid cancer (16.8%), cirrhosis (16.8%), corticosteroid therapy (71.7%), HIV infection (15.6%), chronic obstructive pulmonary disease (COPD, 52.6%), solid organ transplantation (kidney [1.2%], heart [3%], liver [4.6%]), or none (3.5%). Specimens were obtained when clinically indicated and analyzed in the microbiology laboratory. Aspergillus DNA was extracted and amplified by means of MycXtra® and MycAssay™ Aspergillus. Aspergillus spp. was isolated from 65 samples (31 patients). According to the European Organization for Research and Treatment of Cancer and Bulpas criteria (for patients with COPD), 15 had probable invasive aspergillosis. MycAssay™ Aspergillus results were negative (n = 254), positive (n = 54), or indeterminate (n = 14). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio of the MycAssay™ (first sample/any sample) were 86.7/93, 87.6/82.4, 34.1/34.1, 92.2/100, and 48/68.75. The differences between the proportion of samples with positive PCR determinations (63%) and the proportion of samples with Aspergillus spp. isolation (75%) did not reach statistical significance (P = 0.112). The median time from sample culture to visualization of fungal growth was 3 days, compared with ∼4 hours for MycAssay™ Aspergillus PCR. MycAssay™ Aspergillus showed high sensitivity for the diagnosis of invasive aspergillosis in patients without hematological cancer. Sensitivity increased when multiple samples were used. Compared with fungal culture, PCR significantly reduced the time to diagnosis.