Project description:Antimicrobial susceptibility test and report guidelines are an important tool for antimicrobial stewardship programs. Since 1972, Tables 1 within the Clinical and Laboratory Standards Institute (CLSI) M100 document have provided a general framework upon which clinical microbiologists and antimicrobial stewardship teams can build algorithms for susceptibility testing and reporting that meet the specific needs of their institution. Many changes were made to Tables 1 in M100-Ed33 to modernize the content to reflect the landscape of current clinical practice, including the growing armamentarium of antimicrobial agents, the emergence of new mechanisms of antimicrobial resistance, the increasing prevalence of infections caused by multidrug-resistant organisms, and updated consensus recommendations for first-choice and alternative agents for treatment. With these items in mind, the CLSI Table 1 ad hoc working group revised Tables 1 with the ultimate goal of supporting institutions in the creation of individualized test and report strategies that support local antimicrobial stewardship program initiatives. These strategies are built on the concepts of selective and cascade reporting. This minireview introduces the concept of CLSI M100-Ed33 Tables 1, describes the changes to Tables 1 introduced in 2023, and provides clinical vignettes that demonstrate how Tables 1 can be used in various scenarios to devise antimicrobial susceptibility test and report strategies.
Project description:The need for optimized as well as standardized test systems of novel antimicrobial peptides (AMPs) was discussed by experts in the field at the International Meeting on Antimicrobial Peptides (IMAP) 2017 and the 2019 Gordon Research Conference (GRC) on Antimicrobial Peptides, and a survey related to this topic was circulated to participants to collate opinions. The survey included questions ranging from the relevance of susceptibility testing for understanding the mode of action of AMPs, to the importance of optimization and a degree of standardization of test methods and their clinical relevance. Based on the survey results, suggestions for future improvements in the research field are made.
Project description:Rapid antibiotic susceptibility testing is in high demand in health care fields as antimicrobial-resistant bacterial strains emerge and spread. Here, we describe an optical screening system (oCelloScope) which, based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time, introduces real-time detection of bacterial growth and antimicrobial susceptibility with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effects within 6 min and within 30 min in complex samples from pigs suffering from catheter-associated urinary tract infections. The oCelloScope system provides a fast high-throughput screening method for detecting bacterial susceptibility that might entail an earlier diagnosis and introduction of appropriate targeted therapy and thus combat the threat from multidrug-resistant pathogenic bacteria. The oCelloScope system can be employed for a broad range of applications within bacteriology and might present new vistas as a point-of-care instrument in clinical and veterinary settings.
Project description:During the development of antimicrobial peptides (AMP) as potential therapeutics, antimicrobial susceptibility testing (AST) stands as an essential part of the process in identification and optimisation of candidate AMP. Standard methods for AST, developed almost 60 years ago for testing conventional antibiotics, are not necessarily fit for purpose when it comes to determining the susceptibility of microorganisms to AMP. Without careful consideration of the parameters comprising AST there is a risk of failing to identify novel antimicrobials at a time when antimicrobial resistance (AMR) is leading the planet toward a post-antibiotic era. More physiologically/clinically relevant AST will allow better determination of the preclinical activity of drug candidates and allow the identification of lead compounds. An important consideration is the efficacy of AMP in biological matrices replicating sites of infection, e.g., blood/plasma/serum, lung bronchiolar lavage fluid/sputum, urine, biofilms, etc., as this will likely be more predictive of clinical efficacy. Additionally, specific AST for different target microorganisms may help to better predict efficacy of AMP in specific infections. In this manuscript, we describe what we believe are the key considerations for AST of AMP and hope that this information can better guide the preclinical development of AMP toward becoming a new generation of urgently needed antimicrobials.
Project description:BackgroundSelf-reported penicillin allergy infrequently reflects an inability to tolerate penicillins. Inpatients reporting penicillin allergy receive alternative antibiotics that might be broader spectrum, more toxic, or less effective.ObjectiveTo develop and assess a clinical guideline for the general inpatient provider that directs taking a history and prescribing antibiotics for patients with penicillin or cephalosporin allergy.MethodsA guideline was implemented to assist providers with assessing allergy history and prescribing antibiotics for patients with reported penicillin or cephalosporin allergy. The guideline used a standard 2-step graded challenge or test dose. A quasi-experimental study was performed to assess safety, feasibility, and impact on antibiotic use by comparing treatment 21 months before guideline implementation with 12 months after guideline implementation.ResultsSignificantly more test doses to β-lactam antibiotics were performed monthly after vs before guideline implementation (median 14.5, interquartile range 13-16.25, vs 2, interquartile range 1-3.25, P < .001). Seven adverse drug reactions occurred during guideline-driven test doses, with no significant difference in rate (3.9% vs 6.1%, P = .44) or severity (P > .5) between periods. Guideline-driven test doses decreased alternative antimicrobial therapy after the test dose, including vancomycin (68.3% vs 37.2%, P < .001), aztreonam (11.5% vs 0.5%, P < .001), aminoglycosides (6.0% vs 1.1%, P = .004), and fluoro quinolones (15.3% vs 3.3%, P < .001).ConclusionThe implementation of an inpatient antibiotic prescribing guideline for patients with penicillin or cephalosporin allergy was associated with an almost 7-fold increase in the number of test doses to β-lactams without increased adverse drug reactions. Patients assessed with guideline-driven test doses were observed to have significantly decreased alternative antibiotic exposure.
Project description:Antimicrobial resistance is increasingly recognized as a major threat to global health. To combat this emerging threat, accessible antimicrobial susceptibility testing should be prioritized as a key component of stewardship efforts. In this work, we developed a user-friendly paper-based test that provides visual readout of bacterial antibiotic susceptibility in a semiquantitative format. We leveraged on-chip paper microfluidics to enable multiplexed testing of multiple antibiotic dilutions with a single sample addition step, replicating the functionality of traditional broth-dilution-based susceptibility testing in a simplified format. Our paper-based test offers several advantages including low sample volume requirement and lack of need for humidity control during incubation, an innovation that addresses a key limitation of conventional paper-microfluidic devices. Using several clinically relevant bacterial organisms and antimicrobial agents, we demonstrate that our colorimetric readout approach provides a strong predictor of susceptibility category.
Project description:Antimicrobial susceptibility testing (AST) technologies help to accelerate the initiation of targeted antimicrobial therapy for patients with infections and could potentially extend the lifespan of current narrow-spectrum antimicrobials. Although conceptually new and rapid AST technologies have been described, including new phenotyping methods, digital imaging and genomic approaches, there is no single major, or broadly accepted, technological breakthrough that leads the field of rapid AST platform development. This might be owing to several barriers that prevent the timely development and implementation of novel and rapid AST platforms in health-care settings. In this Consensus Statement, we explore such barriers, which include the utility of new methods, the complex process of validating new technology against reference methods beyond the proof-of-concept phase, the legal and regulatory landscapes, costs, the uptake of new tools, reagent stability, optimization of target product profiles, difficulties conducting clinical trials and issues relating to quality and quality control, and present possible solutions.
Project description:Slow progress towards implementation of conventional clinical bacteriology in low resource settings and strong interest in greater speed for antimicrobial susceptibility testing (AST) more generally has focused attention on next-generation rapid AST technologies. In this Review, we systematically synthesize publications and submissions to regulatory agencies describing technologies that provide phenotypic AST faster than conventional methods. We characterize over ninety technologies in terms of underlying technical innovations, technology readiness level, extent of clinical validation, and time-to-results. This work provides a guide for technology developers and clinical microbiologists to understand the rapid phenotypic AST technology landscape, current development pipeline, and AST-specific validation milestones.
Project description:Tuberculosis drug susceptibility, treatment and outcomes for Belarusian HIV-patients with tuberculosis: results from a national and international laboratory
Project description:BackgroundPromoting appropriate pharmacotherapy requires understanding the factors that influence how clinicians prescribe medications. While prior work has focused on patient and clinician factors, features of the organizational setting have received less attention, though identifying sources of variation in prescribing may help identify opportunities to improve patient safety and outcomes.ObjectiveTo evaluate the relationship between the number of clinicians who prescribe medications in a facility and facility prescribing intensity of six individual medication classes by clinician specialty: benzodiazepines, antipsychotics, antiepileptics, and antidepressants by psychiatrists and antibiotics, opioids, antiepileptics, and antidepressants by primary care clinicians (PCPs).DesignWe used 2017 Veterans Health Administration (VHA) administrative data.SubjectsWe included patient-clinician dyads of older patients (> 55 years) with an outpatient encounter with a clinician in 2017. Patient-clinician data from 140 VHA facilities were included (n = 13,347,658). Analysis was repeated for years 2014 to 2016.Main measuresFor each medication, facility prescribing intensity measures were calculated as clinician prescribing intensity averaged over all clinicians at each facility. Clinician prescribing intensity measures included percentage of each clinician's patients prescribed the medication and mean number of days supply per patient among all patients of each clinician.Key resultsAs the number of prescribing clinicians in a facility increased, the intensity of prescribing decreased. Every increase of 10 facility clinicians was associated with a significant decline in prescribing intensity for both specialties for different medication classes: for psychiatrists, declines ranged from 6 to 11%, and for PCPs, from 2 to 3%. The pattern of more clinicians less prescribing was significant across all years.ConclusionFuture work should explore the mechanisms that link the number of facility clinicians with prescribing intensity for benzodiazepines, antipsychotics, antiepileptics, antidepressants, antibiotics, and opioids. Facilities with fewer clinicians may need additional resources to avoid unwanted prescribing of potentially harmful or unnecessary medications.