Dataset Information

Considerable variation of trough ?-lactam concentrations in older adults hospitalized with infection-a prospective observational study.

ABSTRACT: In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous ?-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of ?-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

SUBMITTER: Hatti M

PROVIDER: S-EPMC5816762 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Considerable variation of trough β-lactam concentrations in older adults hospitalized with infection-a prospective observational study.

Hatti Malini M Solomonidi Nikolitsa N Odenholt Inga I Tham Johan J Resman Fredrik F

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20180129 3

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characterist ...[more]

PMID: 29380225

Similar Datasets

Project description:OBJECTIVE:Mycophenolate mofetil (MMF) is an established therapy for systemic sclerosis (SSc), but its pharmacokinetics in this disease remains unexplored. We have investigated drug exposure in MMF-treated patients with SSc in relation to clinical features of the disease and common concomitant drugs. METHODS:This study was predefined to include 35 MMF-treated SSc patients who were using MMF at a fixed dose of 0.5, 1.0 or 1.5?g twice daily since at least 3?months. The 12-h drug exposure of the active MMF metabolite mycophenolic acid (MPA) was estimated by repeated analysis of plasma MPA over a 6-h period. This 12-h drug exposure was dose normalised to a daily intake of 3?g MMF (MPA_AUC3g) in order to compare subjects using MMF at different doses. Drug exposure was analysed in reference to the clinical characteristics including body weight, renal function, autoantibodies, intestinal dysbiosis, intestinal inflammation assessed by faecal (F)-calprotectin, intestinal symptoms assessed by the University of California Los Angeles Scleroderma Trial Consortium Gastrointestinal Tract Instrument 2.0 and concomitant drug usage including proton-pump inhibitors (PPI). RESULTS:Thirty-four out of 35 study participants completed the study. The mean daily MMF dose was 2.1?g. Drug exposure expressed as MPA_AUC3g varied up to 8-fold between patients (median 115, range 27-226?mg h/L). MPA_AUC3g was inversely related to body weight (rs?=?-?0.58, p?<?0.001) and renal function (rs?=?-?0.34, p?=?0.054). Anti-topoisomerase-1 antibodies and male sex were associated with lower MPA_AUC3g (87 vs 123 and 71 vs 141; p?=?0.008 and p?=?0.015, respectively). MPA_AUC3g was inversely related to the intestinal abundance of lactobacilli and to F-calprotectin (rs?=?-?0.54, p?=?0.004; rs?=?-?0.36, p?=?0.034), but not to gastrointestinal symptoms. MPA_AUC3g was inversely related to PPI usage (rs?=?-?0.45, p?=?0.007). We found no association between MPA_AUC3g and disease subtype, disease duration or disease activity. CONCLUSION:MMF-treated SSc patients exhibit considerable inter-individual variation in drug exposure, and lower MPA levels were primarily found in PPI users with poor prognostic factors. Body weight, renal function, sex, serology, gastrointestinal manifestations and/or measuring individual MPA exposure should be considered when using MMF for SSc.

Project description:Background In a hospital setting and among older patients, inactivity and bedrest are associated with a wide range of negative outcomes such as functional decline, increased risk of falls, longer hospitalization and institutionalization. Our aim was to assess the distribution, determinants and predictors of physical activity (PA) levels using wrist-worn accelerometers in older patients hospitalized with acute medical illness. Methods Observational study conducted from February to November 2018 at an acute internal medicine unit in the University hospital of Lausanne, Switzerland. We enrolled 177 patients aged ?65?years, able to walk prior to admission. PA during acute hospital stay was continuously recorded via a 3D wrist accelerometer. Clinical data was collected from medical records or by interview. Autonomy level prior to inclusion was assessed using Barthel Index score. PA levels were defined as <?30?mg for inactivity, 30–99?mg for light and???100 for moderate PA. Physically active patients were defined as 1) being in the highest quartile of time spent in light and moderate PA or 2) spending ?20?min/day in moderate PA. Results Median [interquartile range - IQR] age was 83 [74–87] years and 60% of participants were male. The median [IQR] time spent inactive and in light PA was 613 [518–663] and 63 [30–97] minutes/day, respectively. PA peaked between 8 and 10?am, at 12?am and at 6?pm. Less than 10% of patients were considered physically active according to definition 2. For both definitions, active patients had a lower prevalence of walking aids and a lower dependency level according to Barthel Index score. For definition 1, use of medical equipment was associated with a 70% reduction in the likelihood of being active: odds ratio (OR) 0.30 [0.10–0.92] p =?0.034; for definition 2, use of walking aids was associated with a 75% reduction in the likelihood of being active: OR?=?0.24 [0.06–0.89], p =?0.032. Conclusion Older hospitalized patients are physically active only 10% of daily time and concentrate their PA around eating periods. Whether a Barthel Index below 95 prior to admission may be used to identify patients at risk of inactivity during hospital stay remains to be proven.

Project description:ObjectivesTo investigate the association between delirium motor subtypes and hospital mortality and 12-month mortality in hospitalized older adults.DesignProspective cohort study conducted from 2009 to 2015.SettingGeriatric ward of a university hospital in Sao Paulo, Brazil.ParticipantsWe included 1,409 consecutive admissions of acutely ill patients aged 60 years and over. We excluded admissions for end-of-life care, with missing data on the main variables, length of stay shorter than 48 hours, or when consent to participate was not given.Main outcomes and measuresDelirium was detected using the Confusion Assessment Method and categorized in hypoactive, hyperactive, or mixed delirium. Primary outcomes were time to death in the hospital, and time to death in 12 months (for the discharged sample). Comprehensive geriatric assessment was performed at admission and included socio-demographic, clinical, functional, cognitive, and laboratory variables. Further clinical data were documented upon death or discharge. Multivariate analyses used Cox proportional hazards models adjusted for possible confounders.ResultsWe included 1,409 admissions, with a mean age of 80 years. The proportion of in-hospital deaths was 19%, with a cumulative mortality of 38% in 12 months. Delirium occurred in 47% of the admissions. Hypoactive delirium was the predominant motor subtype (53%), followed by mixed delirium (30%) and hyperactive delirium (17%). Hospital mortality rates were respectively 33%, 34% and 15%. We verified that hypoactive and mixed delirium were independently associated with hospital mortality, with respective hazard ratios of 2.43 (95%CI = 1.64-3.59) and 2.31 (95%CI = 1.53-3.50). Delirium motor subtypes were not independently predictive of 12-month mortality.ConclusionsOne in three acutely ill hospitalized older adults who suffered hypoactive or mixed delirium died in the hospital. Clinicians should be aware that hypoactive symptoms of delirium, whether shown exclusively or in alternation with hyperactive symptoms, are indicative of a worse prognosis in this population.

Project description:BackgroundHospitalized older adults with preexisting dementia have increased risk of having delirium, but little is known regarding the effect of delirium superimposed on dementia (DSD) on the outcomes of these patients. Our aim was to investigate the association between DSD and hospital mortality and 12-mo mortality in hospitalized older adults.Methods and findingsThis was a prospective cohort study completed in the geriatric ward of a university hospital in São Paulo, Brazil. We included 1,409 hospitalizations of acutely ill patients aged 60 y and over from January 2009 to June 2015. Main variables and measures included dementia and dementia severity (Informant Questionnaire on Cognitive Decline in the Elderly, Clinical Dementia Rating) and delirium (Confusion Assessment Method). Primary outcomes were time to death in the hospital and time to death in 12 mo (for the discharged sample). Comprehensive geriatric assessment was performed at admission, and additional clinical data were documented upon death or discharge. Cases were categorized into four groups (no delirium or dementia, dementia alone, delirium alone, and DSD). The no delirium/dementia group was defined as the referent category for comparisons, and multivariate analyses were performed using Cox proportional hazards models adjusted for possible confounders (sociodemographic information, medical history and physical examination data, functional and nutritional status, polypharmacy, and laboratory covariates). Overall, 61% were women and 39% had dementia, with a mean age of 80 y. Dementia alone was observed in 13% of the cases, with delirium alone in 21% and DSD in 26% of the cases. In-hospital mortality was 8% for patients without delirium or dementia, 12% for patients with dementia alone, 29% for patients with delirium alone, and 32% for DSD patients (Pearson Chi-square = 112, p < 0.001). DSD and delirium alone were independently associated with in-hospital mortality, with respective hazard ratios (HRs) of 2.14 (95% CI = 1.33-3.45, p = 0.002) and 2.72 (95% CI = 1.77-4.18, p < 0.001). Dementia alone did not have a significant statistical association with in-hospital mortality (HR = 1.69, 95% CI = 0.72-2.30, p = 0.385). Finally, while 24% of the patients died after discharge, 12-mo mortality was not associated with dementia or delirium in any of the diagnostic groups (DSD: HR = 1.15, 95% CI = 0.79-1.68, p = 0.463; delirium alone: HR = 1.05, 95% CI = 0.71-1.54, p = 0.810; dementia alone: HR = 1.19, 95% CI = 0.79-1.78, p = 0.399). Limitations to this study include not exploring the effects of the duration and severity of delirium on the outcomes.ConclusionsDSD and delirium alone were independently associated with a worse prognosis in hospitalized older adults. Health care professionals should recognize the importance of delirium as a predictor of hospital mortality regardless of the coexistence with dementia.

Project description:BackgroundCommunity acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.MethodsPROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.DiscussionWith the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.Trial registrationThe PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Dataset Information

Considerable variation of trough ?-lactam concentrations in older adults hospitalized with infection-a prospective observational study.

Publications

Considerable variation of trough β-lactam concentrations in older adults hospitalized with infection-a prospective observational study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets