An agent-based model on antimicrobial de-escalation in intensive care units: Implications on clinical trial design
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ABSTRACT:
SUBMITTER: Huo X
PROVIDER: S-EPMC11020418 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesConcern for late detection of bacterial pathogens is a barrier to early de-escalation efforts. The purpose of this study was to assess blood, respiratory and urine culture results at 72 h to test the hypothesis that early negative culture results have a clinically meaningful negative predictive value.MethodsWe retrospectively reviewed all patients admitted to the medical intensive care unit between March 2012 and July 2018 with blood cultures obtained. Blood, respiratory and urine culture results were assessed for time to positivity, defined as the time between culture collection and preliminary species identification. The primary outcome was the negative predictive value of negative blood culture results at 72 h. Secondary outcomes included sensitivity, specificity, positive predictive value and negative predictive value of blood, respiratory and urine culture results.ResultsThe analysis included 1567 blood, 514 respiratory and 1059 urine cultures. Of the blood, respiratory and urine cultures ultimately positive, 90.3%, 76.2% and 90.4% were positive at 72 h. The negative predictive value of negative 72-h blood, respiratory and urine cultures were 0.99, 0.82 and 0.97, respectively. Antibiotic de-escalation had good specificity, positive predictive value and negative predictive value for finalized negative cultures.ConclusionNegative blood and urine culture results at 72 h had a high negative predictive value. These findings have important ramifications for antimicrobial stewardship efforts and support protocolized re-evaluation of empiric antibiotic therapy at 72 h. Caution should be used in patients with clinically suspected pneumonia, since negative respiratory culture results at 72 h were weakly predictive of finalized negative cultures.
| S-EPMC8381457 | biostudies-literature
Project description:Sequential antimicrobial de-escalation aims to minimize resistance to high-value broad-spectrum empiric antimicrobials by switching to alternative drugs when testing confirms susceptibility. Though widely practiced, the effects de-escalation are not well understood. Definitions of interventions and outcomes differ among studies. We use mathematical models of the transmission and evolution of Pseudomonas aeruginosa in an intensive care unit to assess the effect of de-escalation on a broad range of outcomes, and clarify expectations. In these models, de-escalation reduces the use of high-value drugs and preserves the effectiveness of empiric therapy, while also selecting for multidrug-resistant strains and leaving patients vulnerable to colonization and superinfection. The net effect of de-escalation in our models is to increase infection prevalence while also increasing the probability of effective treatment. Changes in mortality are small, and can be either positive or negative. The clinical significance of small changes in outcomes such as infection prevalence and death may exceed more easily detectable changes in drug use and resistance. Integrating harms and benefits into ranked outcomes for each patient may provide a way forward in the analysis of these tradeoffs. Our models provide a conceptual framework for the collection and interpretation of evidence needed to inform antimicrobial stewardship.
| S-EPMC5300270 | biostudies-literature
Project description:Long-term outcomes in breast cancer patients differ based on the molecular subtype, with HER2-E being the most aggressive one. Advances in clinical practice have dramatically shifted HER2+ breast cancer prognosis. Risk adapted strategies to individualize therapies are necessary. De-escalation approaches have been encouraged based on the risks of clinical-pathological factors. Molecular gene subtyping could further accurately define HER2 addicted tumours that are sensitive to anti-HER2 therapies, thus sparing unnecessary treatments. The transition from immunochemistry to molecular profiling in HER2+ breast cancer is discussed.
| S-EPMC8833556 | biostudies-literature
Project description:BackgroundIntensive care units (ICUs) experienced a surge in patient cases during the COVID-19 pandemic. Demand was managed by redeploying healthcare workers (HCWs) and restructuring facilities. The rate of ICU admissions has subsided in many regions, with the redeployed workforce and facilities returning to usual functions. Previous literature has focused on the escalation of ICUs, limited research exists on de-escalation. This study aimed to identify the supportive and operational strategies used for the flexible de-escalation of ICUs in the context of COVID-19.MethodsThe systematic review was developed by searching eight databases in April and November 2021. Papers discussing the return of redeployed staff and facilities and the training, wellbeing, and operational strategies were included. Excluded papers were non-English and unrelated to ICU de-escalation. Quality was assessed using the mixed methods appraisal tool (MMAT) and authority, accuracy, coverage, objectivity, date, and significance (AACODS) checklist, findings were developed using narrative synthesis and thematic analysis.FindingsFifteen papers were included from six countries covering wellbeing and training themes encompassing; time off, psychological follow-up, gratitude, identification of training needs, missed training catch-up, and continuation of ICU and disaster management training. Operational themes included management of rotas, retainment of staff, division of ICU facilities, leadership changes, traffic light systems, and preparation for re-expansion.InterpretationThe review provided an overview of the landscape of de-escalation strategies that have taken place in six countries. Limited empirical evidence was available that evaluated the effectiveness of such strategies. Empirical and evaluative research from a larger array of countries is needed to be able to make global recommendations on ICU de-escalation practices.
| S-EPMC8820730 | biostudies-literature
Project description:Objectives: We aimed to summarize the current state of antimicrobial stewardship (ASP) and diagnostic stewardship programs (DSPs) implemented in pediatric intensive care units (PICUs). Methods: Embase, MEDLINE, Scopus and the Cochrane Library were searched, including studies from 1 January 2007 to 20 February 2024. Studies were included in the review if they assessed the implementation of an ASP or a DSP in a PICU. Identified references were downloaded into Rayyan software, and data were extracted using a standardized data collection form. Results: 18 studies were included; 13 described an ASP intervention, and 5 described a diagnostic stewardship intervention. Most studies were retrospective and adopted a persuasive strategy for ASP, reporting positive effects on antimicrobial consumption. However, studies were dramatically heterogeneous in terms of intervention type, outcomes and metrics used, limiting the possibility of a broader comparison. Diagnostic stewardship studies included mainly the impact of biomarkers and pathogen testing panels without significant impact on antibiotic prescription patterns. Antimicrobial resistance changes were not described by the majority of studies. Conclusions: the implementation of ASP in PICUs is still limited, with significant variability in the metrics used to evaluate outcomes. To enhance the effectiveness of these programs, it is crucial to harmonize reporting metrics to allow an adequate comparison of results and to find the best strategies to inform ASP in PICUs.
| S-EPMC11852047 | biostudies-literature
Project description:BackgroundIntensive care units (ICU) constitute a high-risk setting for antimicrobial resistance (AMR).AimWe aimed to describe secular AMR trends including meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci (GRE), extended-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) and Klebsiella pneumoniae (ESCR-KP), carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) from Swiss ICU. We assessed time trends of antibiotic consumption and identified factors associated with CRE and CRPA.MethodsWe analysed patient isolate and antibiotic consumption data of Swiss ICU sent to the Swiss Centre for Antibiotic Resistance (2009-2018). Time trends were assessed using linear logistic regression; a mixed-effects logistic regression was used to identify factors associated with CRE and CRPA.ResultsAmong 52 ICU, MRSA decreased from 14% to 6% (p = 0.005; n = 6,465); GRE increased from 1% to 3% (p = 0.011; n = 4,776). ESCR-EC and ESCR-KP increased from 7% to 15% (p < 0.001, n = 10,648) and 5% to 11% (p = 0.002; n = 4,052), respectively. CRE, mostly Enterobacter spp., increased from 1% to 5% (p = 0.008; n = 17,987); CRPA remained stable at 27% (p = 0.759; n = 4,185). Antibiotic consumption in 58 ICU increased from 2009 to 2013 (82.5 to 97.4 defined daily doses (DDD)/100 bed-days) and declined until 2018 (78.3 DDD/100 bed-days). Total institutional antibiotic consumption was associated with detection of CRE in multivariable analysis (odds ratio per DDD: 1.01; 95% confidence interval: 1.0-1.02; p = 0.004).DiscussionIn Swiss ICU, antibiotic-resistant Enterobacterales have been steadily increasing over the last decade. The emergence of CRE, associated with institutional antibiotic consumption, is of particular concern and calls for reinforced surveillance and antibiotic stewardship in this setting.
| S-EPMC8603405 | biostudies-literature
Project description:BackgroundVietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam.MethodsMonthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included.ResultsAmong 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively).ConclusionA high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.
| S-EPMC4732823 | biostudies-literature
Project description:IntroductionThe number of older adults who receive life support in an intensive care unit (ICU), now 2 million per year, is increasing while survival remains unchanged. Because the quality of ICU-based palliative care is highly variable, we developed a mobile app intervention that integrates into the electronic health records (EHR) system called PCplanner (Palliative Care planner) with the goal of improving collaborative primary and specialist palliative care delivery in ICU settings.ObjectiveTo describe the methods of a randomized clinical trial (RCT) being conducted to compare PCplanner vs. usual care.Methods and analysisThe goal of this two-arm, parallel group mixed methods RCT is to determine the clinical impact of the PCplanner intervention on outcomes of interest to patients, family members, clinicians, and policymakers over a 3-month follow up period. The primary outcome is change in unmet palliative care needs measured by the NEST instrument between baseline and 1 week post-randomization. Secondary outcomes include goal concordance of care, patient-centeredness of care, and quality of communication at 1 week post-randomization; length of stay; as well as symptoms of depression, anxiety, and post-traumatic stress disorder at 3 months post-randomization. We will use general linear models for repeated measures to compare outcomes across the main effects and interactions of the factors. We hypothesize that compared to usual care, PCplanner will have a greater impact on the quality of ICU-based palliative care delivery across domains of core palliative care needs, psychological distress, patient-centeredness, and healthcare resource utilization.
| S-EPMC7686302 | biostudies-literature
Project description:BackgroundInitiating parenteral nutrition (PN) within 24 h in critically ill children is inferior to withholding PN during the first week, as was found in the PEPaNIC study. The aims of this study were to investigate de-implementation of early initiation of PN at PICUs worldwide, and to identify factors influencing de-implementation.MethodsA cross-sectional online survey was conducted (May - October 2017), consisting of 41 questions addressing current PN practices, the degree of de-implementation, and factors affecting de-implementation.ResultsWe analysed 81 responses from 39 countries. Of these 81 respondents, 53 (65%) were aware of the findings of the PEPaNIC study, and 43 (53%) have read the article. In these 43 PICUs, PN was completely withheld during the first week in 10 PICUs, of which 5 already withheld PN (12%), and 5 de-implemented early initiation of PN (12%). Partial de-implementation was reported by 17 (40%) and no de-implementation by 16 (37%). Higher de-implementation rates were observed when the interpreted level of evidence and grade of recommendation of PEPaNIC was high. Predominant reasons for retaining early initiation of PN were concerns on withholding amino acids, the safety in undernourished children and neonates, and the long-term consequences. Furthermore, the respondents were waiting for updated guidelines.ConclusionsOne year after the publication of the PEPaNIC trial, only two-thirds of the respondents was aware of the study results. Within this group, early initiation of PN was de-implemented completely in 12% of the PICUs, while 40% asserted partial de-implementation. Increasing the awareness, addressing the intervention-specific questions and more frequently revising international guidelines might help to accelerate de-implementation of ineffective, unproven or harmful healthcare.
| S-EPMC6567488 | biostudies-literature
Project description:BackgroundInformation about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs).MethodsAs part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials.ResultsA total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%).ConclusionsThe recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis.
| S-EPMC5985371 | biostudies-literature