Joaquin Burgos

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.

Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy.

Objective:To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients continuing with PI/r. Design:Substudy of the prospective, randomized, open-label, multicenter SPIRAL study. Methods:Patients were randomized (1 : 1) to continue with the PI/r-based regimen or switch to RAL, maintaining the rest of the treatment unchanged. Dual-energy X-ray absorptiometry and computed tomography scans were performed at baseline and after 48 weeks to measure body fat and bone composition, analyzing intragroup and intergroup differences. Results:Eighty-six patients were included and 74 patients (39 RAL, 35 PI/r) completed the substudy. Significant increases in median [interquartile range (IQR)] visceral adipose tissue (VAT) [20.7 (−2.4 to 45.6) cm2, P = 0.002] and total adipose tissue (TAT) [21.4 (−1.3 to 55.4) cm2, P = 0.013] were seen within the PI/r group. No significant changes in body fat were seen with RAL or between treatment groups. Regarding bone composition, total BMD [0.01 (0 to 0.02) g/cm2, P = 0.002], total hip BMD [0.01 (0 to 0.03) g/cm2, P = 0.015] and total hip T score [0.12 (−0.05 to 0.21) SD, P = 0.004] significantly increased with RAL, with no significant changes within the PI/r group. Differences between treatment groups were significant in femoral neck BMD [0.01 (−0.02 to 0.02) g/cm2, P = 0.032] and T score [0.01 (−0.18 to 0.18) SD, P = 0.016]. Conclusion:Although there were no significant changes in body fat between groups, maintaining a PI/r-based regimen was associated with a significant increase in VAT and TAT. Switching to RAL led to a significant increase in femoral neck BMD when comparing between groups.

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.

The increasing incidence of empyema.

Purpose of review The aim of this review is to highlight recent changes concerning the incidence of empyema. In this article we have focused on community-acquired empyema Recent findings The incidence of empyema seems to have been increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. The bacteriology of pleural infection is changing as well. In children, the most common microorganism that causes empyema continues to be Streptococcus pneumoniae. Interestingly, the widespread use of the seven valent conjugate vaccine has produced a replacement phenomenon with the emergence of some pneumococcal serotypes such as serotypes 1, 3 and 19A, which have a higher propensity to cause empyema. Moreover increases in the incidence of empyema due to Staphylococcus aureus have also been observed. In adults, increases in the rate of empyema due to Streptococcus milleri group and S. aureus have been reported. Summary Continued surveillance in the epidemiology of empyema is needed. Progress in new strategies of prevention, such as a new generation of conjugate pneumococcal vaccines and protein-based vaccines, could become an important step in the control of this important complication.

Effects of Immunocompromise and Comorbidities on Pneumococcal Serotypes Causing Invasive Respiratory Infection in Adults: Implications for Vaccine Strategies

BACKGROUND The 13-valent pneumococcal conjugate vaccine (PCV13) has recently been approved for use in immunocompromised adults. However, it is unclear whether there is an association between specific underlying conditions and infection by individual serotypes. The objective was to determine the prevalence of serotypes covered by PCV13 in a cohort of patients with invasive pneumococcal disease of respiratory origin and to determine whether there are specific risk factors for each serotype. METHODS An observational study of adults hospitalized with invasive pneumococcal disease in 2 Spanish hospitals was conducted during the period 1996-2011. A multinomial regression analysis was performed to identify conditions associated with infection by specific serotypes (grouped according their formulation in vaccines and individually). RESULTS A total of 1094 patients were enrolled; the infecting serotype was determined in 993. In immunocompromised patients, 64% of infecting serotypes were covered by PCV13. After adjusting for age, smoking, alcohol abuse, and nonimmunocompromising comorbidities, the group of serotypes not included in either PCV13 or PPV23 were more frequently isolated in patients with immunocompromising conditions and cardiopulmonary comorbidities. Regarding individual serotypes, 6A, 23F, 11A, and 33F were isolated more frequently in patients with immunocompromise and specifically in some of their subgroups. The subgroup analysis showed that serotype10A was also associated with HIV infection. CONCLUSIONS Specific factors related to immunocompromise seem to determine the appearance of invasive infection by specific pneumococcal serotypes. Although the coverage of serotypes in the 13-valent conjugate pneumococcal vaccine (PCV13) was high, some non-PCV13-emergent serotypes are more prevalent in immunocompromised patients.

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

Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected MSM.

Objective:To assess the value of several factors to predict the risk of progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-infected MSM. Design:Longitudinal study of 556 HIV-infected MSM who underwent screening for anal dysplasia (include anal cytology and high-resolution anoscopy at each visit). Methods:Progression rate to HGAIN was estimated by Kaplan–Meier analysis. Predictors of progression were assessed by Cox-proportional hazards regression. Results:Sixty-eight incidents HGAIN cases over 649 person-years of follow-up were diagnosed, resulting in a progression rate of 10.5 cases/100 person-years [95% confidence interval (CI), 8.1–13.3). The cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3–10.1) and 16.2% at 24 months (95% CI, 11.7–20.7). Independent risk factors for progression were as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2–4.9) if low-grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4–5.3) if atypical squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3–25.4) if high-grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR 3.57; 95% CI, 2–6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95% CI, 1–2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2–0.7) and have stable sexual couple (HR 0.62; 95% CI, 0.4–0.9) were protective factors. Patients with favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI, 3.5–10.3). Conclusion:The rate of progression to HGAIN varies according to different predictors that should be considered when assessing the particular risk of each patient. Patients with low risk of progression could be screened at longer intervals. Brief summary:We describe the risk of progression to HGAIN in a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely according to different predictors. These factors should be considered when assessing the particular risk of each patient.

Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial

OBJECTIVES Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. METHODS This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). RESULTS Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US

Invasive pneumococcal disease in HIV-infected adults: clinical changes after the introduction of the pneumococcal conjugate vaccine in children.

7273. CONCLUSIONS The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.

Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital.

BackgroundFew data exist on the implications of widespread use of 7-valent pneumococcal conjugate vaccine in children in the invasive pneumococcal disease (IPD) in HIV-infected adults. We conducted a multicenter study to analyze differences in clinical presentation of IPD between HIV-infected and non–HIV-infected adults in the prevaccine and postvaccine era. MethodsStudy of all cases of IPD in HIV-infected adults diagnosed since 1996 to 2010. Episodes were classified into prevaccine (1996–2001), early postvaccine (2002–2004), and late postvaccine period (2005–2010). For each case, we identified an HIV-negative control patient with IPD matched by hospital, age, and vaccine period. ResultsTwo hundred twenty-one episodes of IPD in HIV-infected patients were diagnosed. The incidence of IPD decreased from 7.81 to 3.69 episodes per 1000 patient-years (−53%; 95% confidence interval: −65% to −36%, P < 0.001) between prevaccine and late postvaccine period. There was an 81% (95% confidence interval: −88% to −69%, P < 0.001) decrease of IPD caused by vaccine serotypes. In late postvaccine period IPD in HIV-infected patients was associated to higher rates of respiratory failure (28.4% vs. 48.4%, P = 0.011), greater intensive care unit admission (8.2% vs. 21.7%, P = 0.02) and a higher need for mechanical ventilation (5.9% vs. 16.3%, P = 0.033). In the prevaccine period, non–HIV-infected patients had a more severe illness than in those with HIV infection; however, these differences disappeared in the late postvaccine period. ConclusionsIn the late postvaccine era, the incidence of IPD in HIV-infected patients has decreased, however, clinical presentation seems to have changed to a more severe illness. The widespread use of highly active antiretroviral therapy, polyssacharide vaccine, and 7-valent pneumococcal conjugate vaccine has contributed to these changes.