Dataset Information

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II.

ABSTRACT: Rapid molecular diagnostic (RMD) platforms may lead to better antibiotic use. Our objective was to develop analytical strategies to enhance the interpretation of RMDs for clinicians.We compared the performance characteristics of 4 RMD platforms for detecting resistance against ?-lactams in 72 highly resistant isolates of Escherichia coli and Klebsiella pneumoniae (PRIMERS I). Subsequently, 2 platforms were used in a blinded study in which a heterogeneous collection of 196 isolates of E. coli and K. pneumoniae (PRIMERS II) were examined. We evaluated the genotypic results as predictors of resistance or susceptibility against ?-lactam antibiotics. We designed analytical strategies and graphical representations of platform performance, including discrimination summary plots and susceptibility and resistance predictive values, that are readily interpretable by practitioners to inform decision-making.In PRIMERS I, the 4 RMD platforms detected ?-lactamase (bla) genes and identified susceptibility or resistance in >95% of cases. In PRIMERS II, the 2 platforms identified susceptibility against extended-spectrum cephalosporins and carbapenems in >90% of cases; however, against piperacillin/tazobactam, susceptibility was identified in <80% of cases. Applying the analytical strategies to a population with 15% prevalence of ceftazidime-resistance and 5% imipenem-resistance, RMD platforms predicted susceptibility in >95% of cases, while prediction of resistance was 69%-73% for ceftazidime and 41%-50% for imipenem.RMD platforms can help inform empiric ?-lactam therapy in cases where bla genes are not detected and the prevalence of resistance is known. Our analysis is a first step in bridging the gap between RMDs and empiric treatment decisions.

SUBMITTER: Evans SR

PROVIDER: S-EPMC4690483 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II.

Evans Scott R SR Hujer Andrea M AM Jiang Hongyu H Hujer Kristine M KM Hall Thomas T Marzan Christine C Jacobs Michael R MR Sampath Rangarajan R Ecker David J DJ Manca Claudia C Chavda Kalyan K Zhang Pan P Fernandez Helen H Chen Liang L Mediavilla Jose R JR Hill Carol B CB Perez Federico F Caliendo Angela M AM Fowler Vance G VG Chambers Henry F HF Kreiswirth Barry N BN Bonomo Robert A RA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20150925 2

<h4>Background</h4>Rapid molecular diagnostic (RMD) platforms may lead to better antibiotic use. Our objective was to develop analytical strategies to enhance the interpretation of RMDs for clinicians.<h4>Methods</h4>We compared the performance characteristics of 4 RMD platforms for detecting resistance against β-lactams in 72 highly resistant isolates of Escherichia coli and Klebsiella pneumoniae (PRIMERS I). Subsequently, 2 platforms were used in a blinded study in which a heterogeneous collec ...[more]

PMID: 26409063

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Project description:BackgroundEmpiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19.MethodsThis was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics.ResultsA total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes.ConclusionFollowing the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.

Project description:Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses (I(2) > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval = 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval = 8 to 15]; I(2) = 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.

Project description:BackgroundFew educational resources have been developed to inform patients' renal replacement therapy (RRT) selection decisions. Patients progressing toward end stage renal disease (ESRD) must decide among multiple treatment options with varying characteristics. Complex information about treatments must be adequately conveyed to patients with different educational backgrounds and informational needs. Decisions about treatment options also require family input, as families often participate in patients' treatment and support patients' decisions. We describe the development, design, and preliminary evaluation of an informational, evidence-based, and patient-and family-centered decision aid for patients with ESRD and varying levels of health literacy, health numeracy, and cognitive function.MethodsWe designed a decision aid comprising a complementary video and informational handbook. We based our development process on data previously obtained from qualitative focus groups and systematic literature reviews. We simultaneously developed the video and handbook in "stages." For the video, stages included (1) directed interviews with culturally appropriate patients and families and preliminary script development, (2) video production, and (3) screening the video with patients and their families. For the handbook, stages comprised (1) preliminary content design, (2) a mixed-methods pilot study among diverse patients to assess comprehension of handbook material, and (3) screening the handbook with patients and their families.ResultsThe video and handbook both addressed potential benefits and trade-offs of treatment selections. The 50-minute video consisted of demographically diverse patients and their families describing their positive and negative experiences with selecting a treatment option. The video also incorporated health professionals' testimonials regarding various considerations that might influence patients' and families' treatment selections. The handbook was comprised of written words, pictures of patients and health care providers, and diagrams describing the findings and quality of scientific studies comparing treatments. The handbook text was written at a 4th to 6th grade reading level. Pilot study results demonstrated that a majority of patients could understand information presented in the handbook. Patient and families screening the nearly completed video and handbook reviewed the materials favorably.ConclusionsThis rigorously designed decision aid may help patients and families make informed decisions about their treatment options for RRT that are well aligned with their values.

Project description:Background: Antibiotics are often prescribed empirically to treat infection syndromes before causative bacteria and their susceptibility to antibiotics are identified. Guidelines on empiric antibiotic prescribing are key to effective treatment of infection syndromes, and need to be informed by likely bacterial aetiology and antibiotic resistance patterns. We aimed to create a clinically-relevant composite index of antibiotic resistance for common infection syndromes to inform recommendations at the national level. Methods: To create our index, we used open-access antimicrobial resistance (AMR) surveillance datasets, including the ECDC Surveillance Atlas, CDDEP ResistanceMap, WHO GLASS and the newly-available Pfizer ATLAS dataset. We integrated these with data on aetiology of common infection syndromes, existing empiric prescribing guidelines, and pricing and availability of antibiotics. Results: The ATLAS dataset covered many more bacterial species (287) and antibiotics (52) than other datasets (ranges = 8-11 and 16-32 respectively), but had a similar number of samples per country per year. Using these data, we were able to make empiric prescribing recommendations for bloodstream infection, pneumonia and cellulitis/skin abscess in up to 44 countries. There was insufficient data to make national-level recommendations for the other six syndromes investigated. Results are presented in an interactive web app, where users can visualise underlying resistance proportions to first-line empiric antibiotics for infection syndromes and countries of interest. Conclusions: We found that whilst the creation of a composite resistance index for empiric antibiotic therapy was technically feasible, the ATLAS dataset in its current form can only inform on a limited number of infection syndromes. Other open-access AMR surveillance datasets are largely limited to bloodstream infection specimens and cannot directly inform treatment of other syndromes. With improving availability of international AMR data and better understanding of infection aetiology, this approach may prove useful for informing empiric prescribing decisions in settings with limited local AMR surveillance data.

Dataset Information

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II.

Publications

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II.

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