Mireia Puig

Current and Potential Usefulness of Pneumococcal Urinary Antigen Detection in Hospitalized Patients With Community-Acquired Pneumonia to Guide Antimicrobial Therapy

BACKGROUND The role of pneumococcal urinary antigen detection in the treatment of adults with community-acquired pneumonia (CAP) is not well defined. We assessed the usefulness of pneumococcal urinary antigen detection in the diagnosis and antimicrobial guidance in patients hospitalized with CAP. METHODS A prospective study of all adults hospitalized with CAP was performed from February 2007 through January 2008. To evaluate the accuracy of the test, we calculated its sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. The gold standard used for diagnosis of pneumococcal pneumonia was isolation in blood or pleural fluid (definite diagnosis) and isolation in sputum (probable diagnosis). Antibiotic modifications, complications, and mortality were analyzed. RESULTS A total of 474 episodes of CAP were included. Streptococcus pneumoniae was the causative pathogen in 171 cases (36.1%). It was detected exclusively by urinary antigen test in 75 cases (43.8%). Sixty-nine patients had CAP caused by a pathogen other than S pneumoniae. Specificity was 96%, positive predictive value ranged from 88.8% to 96.5%, and the positive likelihood ratio ranged from 14.6 to 19.9. The results of the test led the clinicians to reduce the spectrum of antibiotics in 41 patients. Pneumonia was cured in all of them. Potentially, this optimization would be possible in the 75 patients diagnosed exclusively by the test. CONCLUSION When its findings are positive, the pneumococcal urinary antigen test is a useful tool in the treatment of hospitalized adult patients with CAP because it may allow the clinician to optimize antimicrobial therapy with good clinical outcomes.

Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts

BACKGROUND Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. METHODS We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with alpha-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. RESULTS Mature cardiomyocytes from the host (1-2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic alpha-actin were also identified (1-21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. CONCLUSIONS Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.

The Spectrum of Pneumococcal Empyema in Adults in the Early 21st Century

BACKGROUND Increased rates of empyema have been reported in children after the introduction of the pneumococcal conjugate vaccine (PCV7). Our objective was to describe the risk factors for pneumococcal empyema in adults and to analyze the differences in the incidence, disease characteristics, and serotype distribution between the pre- and post-PCV7 eras. METHODS An observational study of all adults hospitalized with invasive pneumococcal disease (IPD) who presented with empyema in 2 Spanish hospitals was conducted during the periods 1996-2001 (prevaccine period) and 2005-2009 (postvaccine period). Incidences of empyema were calculated. A multivariate analysis was performed to identify variables associated with pneumococcal empyema. RESULTS Empyema was diagnosed in 128 of 1080 patients with invasive pneumococcal disease. Among patients aged 18-50 years, the rates of pneumococcal pneumonia with empyema increased from 7.6% to 14.9% (P = .04) and the incidence of pneumococcal empyema increased from 0.5 to 1.6 cases per 100,000 person-years (198% [95% confidence interval {CI}, 49%-494%]). The incidence of empyema due to serotype 1 increased significantly from 0.2 to 0.8 cases per 100,000 person-years (253% [95% CI, 67%-646%]). Serotype 1 caused 43.3% of cases of empyema during the postvaccine period. Serotypes 1 (odds ratio [OR], 5.88; [95% CI, 2.66-13]) and 3 (OR, 5.49 [95% CI, 1.93-15.62]) were independently associated with development of empyema. CONCLUSIONS The incidence of pneumococcal empyema in young adults has increased during the postvaccine period, mainly as a result of the emergence of serotype 1. Serotypes 1 and 3 are the main determinants of development of this suppurative complication.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation

OBJECTIVES The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Frequency and predictors of symptomatic intracerebral hemorrhage in patients with ischemic stroke treated with recombinant tissue plasminogen activator outside clinical trials.

Background: To determine the frequency and predictors of symptomatic intracerebral hemorrhage (SICH) in patients treated with recombinant tissue plasminogen activator (rt-PA). Methods: We reviewed the databases of 7 tertiary hospitals that treated ischemic stroke patients with intravenous rt-PA. We recorded demographic data, vascular risk factors, time between onset and treatment, dose, the NIHSS score, body temperature, blood pressure, platelet count, blood glucose, antiplatelet treatment, and CT data. We also registered the study protocol used for treatment and deviations from the accepted protocol. A control CT was performed on all patients. SICH was diagnosed if a parenchymal hematoma was detected within the 36 h after rt-PA and was associated with an increase of ≧4 in the NIHSS score. Bivariate analyses were performed followed by a logistic regression analysis. Results: A total of 347 patients were studied, whose mean age was 68 ± 10.9 years; 56% were men. Thirty-two patients (9.2%) exhibited a parenchymal hematoma, and 8 patients (2.3%) suffered a SICH. Patients with SICH had a higher frequency of previous transient ischemic attack (p = 0.04), early signs of ischemia (p = 0.003), hyperdense arterial sign (p = 0.008), and deviations (p = 0.002). Early signs of ischemia (OR 8.5, 95% CI 1.6–45.4, p = 0.01) and deviation from the protocol (OR 11.1, 95% CI 2.4–50, p = 0.002) were independent predictors of SICH. Conclusions: SICH is infrequent in patients with ischemic stroke treated with rt-PA outside of a clinical trial. Its frequency increases in the presence of early signs of ischemia on the noncontrast CT scan and deviations from the recommended protocol.

Burden of myocardial damage in cardiac allograft rejection: Scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis

BackgroundBecause myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens.Methods and ResultsForty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage.ConclusionsApoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Risk factors for respiratory failure in pneumococcal pneumonia. The importance of pneumococcal serotypes

Pneumococcal serotypes are one of the main determinants of pneumococcal disease severity; however, data about their implication in respiratory failure are scarce. We conducted an observational study of adults hospitalised with invasive pneumococcal pneumonia to describe the host- and pathogen-related factors associated with respiratory failure. Of 1258 adults with invasive pneumococcal disease, 615 (48.9%) had respiratory failure at presentation. Patients with respiratory failure were older (62.1 years versus 55.4 years, p<0.001) and had a greater proportion of comorbid conditions. They also had a greater proportion of septic shock (41.7% versus 6.1%, p<0.001), required admission to the intensive care unit more often (38.4% versus 4.2%, p<0.001) and had a higher mortality (25.5% versus 3.5%, p<0.001). After adjustment, independent risk factors for respiratory failure were: age >50 years (OR 1.63, 95% CI 1.15–2.3), chronic lung disease (OR 1.54, 95% CI 1.1–2.15), chronic heart disease (OR 1.49, 95% CI 1.01–2.22) and infection caused by serotypes 3 (OR 1.97, 95% CI 1.23–3.16), 19A (OR 2.34, 95% CI 1.14–4.42) and 19F (OR 3.55, 95% CI 1.22–10.28). In conclusion, respiratory failure is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Pneumococcal serotypes 3, 19A and 19F are the main risk factors for this complication. Respiratory failure in invasive pneumonia is determined by older age, comorbidities and serotypes 3, 19A and 19F http://ow.ly/qHN6D

Cerebrovascular Disease as a Complication of Cardiac Transplantation

Background and Objectives: To characterize the frequency, risk factors, clinical presentation and etiological subtypes of cerebrovascular diseases (CVD) following cardiac transplantation (CTX). Methods: In a retrospective review of our CTX database (period 1984–2002), we assessed demographic data, vascular risk factors, surgery and donor details. We classified ischemic stroke (IS) using the clinical criteria of the Oxfordshire Community Stroke Project and the etiological criteria of the TOAST study. Logistic regression analysis and survival curves were carried out. Results: CTX was performed in a total of 314 patients (age 46 ± 14 years, 78% male) and mean follow-up was 54 ± 57 months. Twenty-two patients (7%) presented CVD: hemorrhagic stroke in 12%, transient ischemic attack in 28% and IS in 60%. CVD were early postoperative (less than 2 weeks) in 20% of patients and late in 80%. The clinical presentation in patients with IS was total anterior circulation (23.1%), partial anterior (38.4%), lacunar (15.4%) and posterior circulation (23.1%), and the etiological classification was large artery atherosclerosis (15.4%), cardioembolism (14.4%), small vessel disease (15.4%), unusual causes (15.4%) and undetermined cause (38.4%). The only independent predictor of CVD was a prior CVD event with an odds ratio of 8.2 (95% CI, 2.2–30.2, p < 0.02). The estimated risk of CVD at 5 years was greater (p < 0.02) in patients with prior CVD (4.1%) than in those without (1.1%). Conclusions: CVD are a relatively frequent complication after CTX (7%) and usually occur in the late postoperative phase. CVD prior to transplantation increase the risk of CVD after this procedure.

Health care associated hematogenous pyogenic vertebral osteomyelitis: a severe and potentially preventable infectious disease.

AbstractAlthough hematogenous pyogenic spinal infections have been related to hemodialysis (HD), catheter-related sepsis, and sporadically, to other nosocomial infections or procedures, in most recent studies and reviews the impact of nosocomial infection as a risk factor for vertebral osteomyelitis (VO) is not well established. The aim of our study was to describe the risk factors, infectious source, etiology, clinical features, therapy, and outcome of health care associated VO (HCAVO), and compare them with community-acquired VO (CAVO) cases.A retrospective cohort study of consecutive patients with hematogenous VO was conducted in our third-level hospital between 1987 and 2011. HCAVO was defined as onset of symptoms after 1 month of hospitalization or within 6 months after hospital discharge, or ambulatory manipulations in the 6 months before the diagnosis.Over the 25-year study period, among 163 hematogenous pyogenic VO, 41 (25%) were health care associated, a percentage that increased from 15% (9/61) in the 1987–1999 period to 31% (32/102) in the 2000–2011 period (P < 0.01). The presumed source of infection was an intravenous catheter in 14 (34%), cutaneous foci in 8 (20%), urinary tract in 7 (17%), gastrointestinal in 3 (7%), other foci in 3 (7%), and unknown in 6 (15%). Staphylococcus aureus was the most frequently isolated microorganism (14 cases, 34%), followed by coagulase-negative Staphylococci (CoNS) in 6 (15%), and Enterobacteriaceae in 6 (15%) cases.Compared with CAVO cases, patients with HCAVO were older (mean 66.0 SD 13.0 years vs 60.5 SD 15.5 years), had more underlying conditions (73% vs 50%, P < 0.05), neoplasm/immunosuppression (39% vs 7%, P < 0.005), chronic renal failure (19% vs 4%, P < 0.001), a known source of infection (85% vs 54% P < 0.05), Candida spp (7% vs 0%, P < 0.01) or CoNS infections (15% vs 2%, P < 0.05), higher mortality (15% vs 6%, P = 0.069), and a higher relapse rate in survivors (9% vs 1%, P < 0.05).Presently, in our setting, one-third of hematogenous pyogenic VO infections are health care associated, and a third of these are potentially preventable catheter-related infections. Compared with CAVO, in health care associated hematogenous VO, mortality and relapse rates are higher; hence, further prevention measures should be assessed.

Disseminated Cytomegalovirus Infection in an Immunocompetent Adult Successfully Treated with Ganciclovir

We report the case of a previously healthy man who suffered a disseminated cytomegalovirus infection. He presented with prolonged fever, weight loss of 8 kg, anicteric hepatitis, upper digestive tract bleeding from gastric ulcers, acute polyneuritis and bilateral retinitis. Immunodeficiency was not detected either during admission or during a 3-year follow-up period. The patient was treated with ganciclovir (5 mg/kg BID) during 4 weeks with a favourable clinical outcome. To our knowledge, this is the first reported case with such characteristics.