Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

PURPOSE: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. METHODS: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. RESULTS: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. CONCLUSION: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. CLINICAL TRIAL: ClinicalTrial. Gov identification number: NCT01730690.

Burden of pneumococcal pneumonia requiring ICU admission in France: 1-year prognosis, resources use, and costs.

BACKGROUND: Community-acquired pneumonia (CAP), especially pneumococcal CAP (P-CAP), is associated with a heavy burden of illness as evidenced by high rates of intensive care unit (ICU) admission, mortality, and costs. Although well-defined acutely, determinants influencing long-term burden are less known. This study assessed determinants of 28-day and 1-year mortality and costs among P-CAP patients admitted in ICUs. METHODS: Data regarding all hospital and ICU stays in France in 2014 were extracted from the French healthcare administrative database. All patients admitted in the ICU with a pneumonia diagnosis were included, except those hospitalized for pneumonia within the previous 3 months. The pneumococcal etiology and comorbidities were captured. All hospital stays were included in the cost analysis. Comorbidities and other factors effect on the 28-day and 1-year mortality were assessed using a Cox regression model. Factors associated with increased costs were identified using log-linear regression models. RESULTS: Among 182,858 patients hospitalized for CAP in France for 1 year, 10,587 (5.8%) had a P-CAP, among whom 1665 (15.7%) required ICU admission. The in-hospital mortality reached 22.8% at day 28 and 32.3% at 1 year. The mortality risk increased with age > 54 years, malignancies (hazard ratio (HR) 1.54, 95% CI [1.23-1.94], p = 0.0002), liver diseases (HR 2.08, 95% CI [1.61-2.69], p < 0.0001), and the illness severity at ICU admission. Compared with non-ICU-admitted patients, ICU survivors remained at higher risk of 1-year mortality. Within the following year, 38.2% (516/1350) of the 28-day survivors required at least another hospital stay, mostly for respiratory diseases. The mean cost of the initial stay was €19,008 for all patients and €11,637 for subsequent hospital stays within 1 year. One-year costs were influenced by age (lower in patients > 75 years old, p = 0.008), chronic cardiac (+ 11% [0.02-0.19], p = 0.019), and respiratory diseases (+ 11% [0.03-0.18], p = 0.006). CONCLUSIONS: P-CAP in ICU-admitted patients was associated with a heavy burden of mortality and costs at one year. Older age was associated with both early and 1-year increased mortality. Malignant and chronic liver diseases were associated with increased mortality, whereas chronic cardiac failure and chronic respiratory disease with increased costs. TRIAL REGISTRATION: N/A (study on existing database).

Antibiothérapie du sujet âgé : On peut toujours mieux faire.

Antimicrobials are among the most prescribed drugs and their prescription increases with age, due to frailty and accrued risk factors for acquiring infections. Antimicrobial prescription in elderly patients must not only account for the risk of toxicity due to drug overexposure, but also of treatment failure or promotion of antimicrobial resistance due to under-dosage. This paper reviews the main antimicrobial, pharmacokinetic and pharmacodynamic variations induced by aging, comorbidities and polypharmacy, and how to take them into account to optimize antimicrobial prescription in elders.

Is herpes zoster an additional complication in old age alongside comorbidity and multiple medications? Results of the post hoc analysis of the 12-month longitudinal prospective observational ARIZONA cohort study.

OBJECTIVES: To examine the burden of comorbidity, polypharmacy and herpes zoster (HZ), an infectious disease, and its main complication post-herpetic neuralgia (PHN) in young (50-70 years of age: 70-) and old (≥ 70 years of age: 70+) patients. DESIGN: Post hoc analysis of the results of the 12-month longitudinal prospective multicentre observational ARIZONA cohort study. SETTINGS AND PARTICIPANTS: The study took place in primary care in France from 20 November 2006 to 12 September 2008. Overall, 644 general practitioners (GPs) collected data from 1358 patients aged 50 years or more with acute eruptive HZ. OUTCOME MEASURES: Presence of HZ-related pain or PHN (pain persisting >3 months) was documented at day 0 and at months 3, 6, and 12. To investigate HZ and PHN burden, pain, quality of life (QoL) and mood were self-assessed using validated questionnaires (Zoster Brief Pain Inventory, 12-item Short-Form health survey and Hospital Anxiety and Depression Scale, respectively). RESULTS: As compared with younger patients, older patients more frequently presented with comorbidities, more frequently took analgesics and had poorer response on all questionnaires, indicating greater burden, at inclusion. Analgesics were more frequently prescribed to relieve acute pain or PHN in 70+ than 70- patients. Despite higher levels of medication prescription, poorer pain relief and poorer response to all questionnaires were reported in 70+ than 70- patients. CONCLUSIONS: Occurrence of HZ and progression to PHN adds extra burden on top of pharmacological treatment and impaired quality of life, especially in older patients who already have health problems to cope with in everyday life.

Involvement of the same TNFR1 residue in mendelian and multifactorial inflammatory disorders.

OBJECTIVES: TNFRSF1A is involved in an autosomal dominant autoinflammatory disorder called TNFR-associated periodic syndrome (TRAPS). Most TNFRSF1A mutations are missense changes and, apart from those affecting conserved cysteines, their deleterious effect remains often questionable. This is especially true for the frequent R92Q mutation, which might not be responsible for TRAPS per se but represents a susceptibility factor to multifactorial inflammatory disorders. This study investigates TRAPS pathophysiology in a family exceptional by its size (13 members) and compares the consequences of several mutations affecting arginine 92. METHODS: TNFRSF1A screening was performed by PCR-sequencing. Comparison of the 3-dimensional structure and electrostatic properties of wild-type and mutated TNFR1 proteins was performed by in silico homology modeling. TNFR1 expression was assessed by FACS analysis, western blotting and ELISA in lysates and supernatants of HEK293T cells transiently expressing wild-type and mutated TNFR1. RESULTS: A TNFRSF1A heterozygous missense mutation, R92W (c.361C>T), was shown to perfectly segregate with typical TRAPS manifestations within the family investigated (p<5.10(-4)). It was associated with very high disease penetrance (0.9). Prediction of its impact on the protein structure revealed local conformational changes and alterations of the receptor electrostatic properties. R92W also impairs the TNFR1 expression at the cell surface and the levels of soluble receptor. Similar results were obtained with R92P, another mutation previously identified in a very small familial form with incomplete penetrance and variable expressivity. In contrast, TNFR1-R92Q behaves like the wild-type receptor. CONCLUSIONS: These data demonstrate the pathogenicity of a mutation affecting arginine 92, a residue whose involvement in inflammatory disorders is deeply debated. Combined with previous reports on arginine 92 mutations, this study discloses an unusual situation in which different amino acid substitutions at the same position in the protein are associated with a clinical spectrum bridging Mendelian to multifactorial conditions.

[Adequacy to the recommendations in urinary tract infections: a multicenter transversal survey in hospitalized patients aged over 75 years]. / Suivi des recommandations dans l'infection urinaire : étude transversale multicentrique chez le sujet âgé hospitalisé de plus de 75 ans.

UNLABELLED: French diagnostic and therapeutic recommendations about UI were built-up in 2008. We studied clinician's practices and evaluated the adequacy to the recommendations in hospitalized patients aged over 75 years. METHOD: Multicenter survey in acute care of geriatric, internal medicine and infectious disease wards. During one week, all positive urine cultures of patients over 75 were reported to the local investigator who had to fill out a questionnaire. The data specified the final diagnosis: cystitis, pyelonephritis, prostatitis, or colonization, the antibiotic treatment, the re-evaluation after 72 hours of treatment, the association with another infectious diagnosis and the radiological examinations performed. RESULTS: 241 questionnaires were collected from 48 wards. Colonization, cystitis, pyelonephritis and prostatitis were diagnosed respectively in 42, 27, 20 and 11% of urine cultures. In 48% of cystitis cases, the duration of treatment was inadequate. In 77% cases of pyelonephritis, the antibiotic was adapted to the recommendations, but 44% of patients had no further radiological examination. In cases of prostatitis antibiotic therapy was adequate in 74% of cases but often with a non-conform duration of treatment (56%) and absence of further radiographic examination (70%). The reassessment of the treatment at day 3 ranged from 63 to 88%. In 26% of UI diagnosis, another associated infection was described, mainly bronchopneumonia (56%). CONCLUSION: Progress is needed to optimize treatment revaluation at 72 hours and adequate duration of treatment. The association of UI and bronchopneumonia is questionable. More specific recommendations would probably be useful to optimize the management of UI in the elderly.

Acute respiratory illness as a trigger for detecting chronic bronchitis in adults at risk of COPD: a primary care survey.

AIM: To evaluate the impact of chronic bronchitis in patients identified among subjects at risk of chronic obstructive pulmonary disease (COPD) but currently free from any known chronic respiratory disorder, visiting a general practitioner for an acute respiratory episode. METHOD: A multicentre, cross-sectional survey carried out in primary care. RESULTS: Primary care practitioners (n = 772) examined 14,030 patients with acute cough (male: 56.9%, age 50.6 ± 16.5 years). Of these, 3,615 were at risk of COPD (> 40 years and tobacco use > 10 pack-years) and constituted the study population: 79.8% reported current symptoms of chronic bronchitis. Compared to patients without chronic bronchitis, they were older, more frequently exposed to occupational pollutants or to passive smoking, had more tobacco use (p < 0.001), reported dyspnoea > Grade 2 more frequently, and had poorer quality of life as assessed by the EuroQOL-5D questionnaire. CONCLUSIONS: In this survey, previously unrecognised chronic bronchitis was diagnosed in a high proportion of at-risk patients with acute respiratory episodes. Chronic bronchitis was associated with significantly poorer health status. Acute respiratory illness could be an appropriate opportunity for screening those patients at risk of COPD with lung function testing.