Breakpoint Changes Research Articles

Amikacin treatment in patients with Enterobacterales bacteraemia: impact of MIC on mortality.

Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin. This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality. We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality. We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin.

Impact of MIC Breakpoint Changes for Enterobacterales on Trends of Antibiotic Susceptibilities in An Academic Medical Center

Background: The Clinical & Laboratory Standards Institute (CLSI) recommends use of annual antibiograms to help guide empiric antibiotic therapy. Because CLSI periodically updates minimum inhibitory concentration (MIC) breakpoints, we assessed the impact of these updates on longitudinal trends in antibiotic susceptibility rates for Escherichia coli and Klebsiella pneumoniae at a single academic medical center in Atlanta, GA. Methods: Susceptibilities for cefepime, ceftazidime, and levofloxacin in E. coli and K. pneumoniae were extracted from hospital antibiograms from 1988 to 2022. Starting in 1995, intensive care units (ICUs) and wards had separate annual antibiograms, which we combined using weighted averages to create annual overall hospital antibiograms. After summarizing the frequency of isolates tested and susceptibilities using medians and interquartile ranges (IQR), we conducted an interrupted time series analysis using linear segmented regression models, to evaluate the level changes and trends in susceptibility, before and after CLSI MIC breakpoints were updated for ceftazidime (2010 and 2017), cefepime (2014 and 2017), and levofloxacin (2013). Results: Among 21,214 E. coli, there was a median of 291 [IQR: 104, 555] isolates tested annually. Similarly, among 8,686 K. pneumoniae isolates, the median was 125 per year (IQR: 76, 178). Prior to the MIC breakpoint changes, baseline susceptibility trends of both organisms to all 3 antibiotics significantly declined at a rate between 0.2% to 2.4% per year (Table 1). For cefepime (Figure 1), susceptibility decreased annually during 1988 – 2013 for both E. coli (-0.5%) and K. pneumoniae (-1.2%). There were no significant level changes but there were trend changes after 2018, for E. coli (+2.1%) and K. pneumoniae (– 5.5%). For ceftazidime (Figure 2), significant level changes occurred after 2010 for both organisms (E. coli: -5.7%; K. pneumoniae: -5.2%). For levofloxacin (Figure 3), the breakpoint update in 2013 lead to significant level change in susceptibility (E. coli: +8.4%; K. pneumoniae: +11.4%). Conclusion: Overall, we observed a consistent decrease in antibiotic susceptibility in E. coli and K. pneumoniae over three decades, with immediate increases in the level change of susceptibility when MIC breakpoints were changed, followed by a decreasing trend. These findings highlight the importance of longitudinal surveillance and MIC breakpoint changes to inform antimicrobial stewardship strategies.

Possible impact of revisions in disc diffusion breakpoints for aminoglycosides and piperacillin/tazobactam in the 33rd edition of CLSI M100 document on clinical reporting and use in Indian settings with low susceptibility

PurposeThe study explores the impact of significant interpretative breakpoint changes for aminoglycosides and piperacillin-tazobactam in Enterobacterales and Pseudomonas aeruginosa, considering PK/PD, clinical data, and susceptibility on clinical reporting and use. ProcedureBetween January 2021 and June 2023, a total of 189,583 samples were processed for bacterial pathogens and antimicrobial susceptibility testing was performed using disc diffusion method/VITEK® 2 Compact system/broth microdilution. WHONET software was utilised to capture and analyse the changes in the interpretation of disc diffusion method, following updates to CLSI M100 documents in comparison to previous editions. Antimicrobial consumption data was collected and interpreted as DDD/100 bed days using AMC tool software. Here, we present data for 13,615 members of Order Enterobacterales and 1793 Pseudomonas aeruginosa isolates. FindingEnterobacterales exhibited a significant susceptibility drop of 14.7% for gentamicin and 21.7% for amikacin. Pseudomonas aeruginosa showed an increase in isolates with intermediate tobramycin susceptibility, from 0.6% to 29.7%, with relatively minor changes in piperacillin-tazobactam interpretation. ConclusionThe changes indicate a shift toward increased 'resistance' and 'intermediate susceptibility' for these antibiotics, emphasizing the need for cautious use and leveraging PK/PD knowledge for improved antibiotic utilization, patient outcomes, and antimicrobial stewardship.

356. Impact of CLSI Breakpoint Changes on Unit-Specific Combination Antibiograms for Gram-Negative Respiratory Isolates

Abstract Background In 2023, the CLSI updated aminoglycoside breakpoints for P. aeruginosa and Enterobacterales. The anticipated decrease in aminoglycoside susceptibility rates resulting from these revised breakpoints will impact empiric antibiotic selection for nosocomial pneumonia. This study aims to evaluate the impact of the new breakpoints on the susceptibility rates of various combination antibiotic regimens for Gram-negative pneumonia at Michigan Medicine. Methods The susceptibility rates of single and combination antibiotic regimens were determined by applying the CLSI breakpoints to 221 non-duplicated, first Gram-negative respiratory isolates obtained from patients in the MICU and SICU of Michigan Medicine in 2021. Combination antibiograms were developed to compare susceptibility rates of various potential empiric regimens based on the 2022 vs. 2023 aminoglycoside breakpoints. Subgroup analyses for P. aeruginosa vs. non-P. aeruginosa were performed. Results Comparisons of unit-specific combination antibiograms against all Gram-negative respiratory isolates using 2022 vs. 2023 breakpoints are shown in Table 1. Based on the 2022 breakpoints, overall susceptibility rates for aminoglycosides were higher than those of anti-pseudomonal β-lactams. The addition of an aminoglycoside improved the susceptibility percentages of a β-lactam up to 23%, allowing similar activity with amikacin-based combination therapy to levofloxacin-based. In contrast, based on 2023 breakpoints, the susceptibility rates of amikacin and gentamicin dropped significantly (85.1 to 58.8% and 81.0 to 56.6%, respectively) and combination with these two agents did not provide additional benefit to the β-lactam backbone. The tobramycin susceptibility rate was minimally affected by the breakpoint changes (82.8% vs. 79.2%). Subgroup analyses demonstrated that the decrease in susceptibility percentages for aminoglycosides was largely driven by the breakpoint changes for P. aeruginosa (Table 1). Conclusion The updated 2023 CLSI breakpoints resulted in a substantial decrease in the susceptibility percentages of amikacin and gentamicin which clinicians need to be aware of when choosing empiric antibiotic treatment. Disclosures Virginia M. Pierce, MD, FIDSA, UpToDate, Inc.: Authorship royalties jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant

How Robust are Empirical Factor Models to the Choice of Breakpoints?

We comprehensively investigate the robustness of well-known factor models to altered factor formation breakpoints. Deviating from the standard 30th and 70th percentile selection, we use an extensive set of anomaly test portfolios to uncover two main findings: First, there is a trade-off between specification and diversification. More centered breakpoints tend to result in less (idiosyncratic) risk. More extreme sorts lead to greater exposure to the underlying anomalies and thus to higher average returns. Second, the models are robust to varying degrees. Hou et al.’s model [2015, Digesting Anomalies: An Investment Approach, Review of Financial Studies 28, 650–705] is much more sensitive to changes in breakpoints than the Fama–French models.

Updating breakpoints in the United States: a summary from the ASM Clinical Microbiology Open 2022.

Accurate antimicrobial susceptibility testing (AST) and reporting are essential for guiding appropriate therapy for patients and direction for public health prevention and control actions. A critical feature of AST reporting is the interpretation of AST results using clinical breakpoints for reporting as susceptible, susceptible-dose dependent, intermediate, or resistant. Breakpoints are subject to continuous adjustment and updating to best reflect current clinical data. These breakpoint changes can benefit patients and public health only if adopted in a timely manner. A recent survey identified that up to 70% of College of American Pathologists (CAP)-accredited U.S. laboratories and 45% of CAP-accredited laboratories outside the U.S. use various obsolete clinical breakpoints to interpret AST results to guide patient care. The reason for the ongoing use of obsolete breakpoints is multifactorial, including barriers encountered by laboratories, commercial AST device manufacturers, standards development organizations, and regulatory bodies alike. To begin to address this important patient safety issue, CAP implemented checklist requirements for CAP-accredited laboratories to ensure up-to-date clinical breakpoint use. Furthermore, the topic was discussed at the June 2022 American Society for Microbiology Clinical Microbiology Open (CMO) with various stakeholders to identify potential solutions. This minireview summarizes the breakpoint setting process in the U.S. and highlights solutions to close the gap between breakpoint revisions and implementation in clinical and public health laboratories. Solutions discussed include clarification of data requirements and minimum inhibitory concentration only reporting for regulatory clearance of AST devices, clinical data generation to close breakpoints gaps, advocacy, education, and greater dialogue between stakeholders.

A-280 Impact of 2022 CLSI Revised Piperacillin/Tazobactam Clinical Breakpoints on Enterobacterales Isolates Identified at a Tertiary Medical Center in Southern Taiwan

Abstract Background Piperacillin-tazobactam (TZP) is one of the most common antibiotics administered to hospitalized patients. Its broad activity against gram-negative, gram-positive, and anaerobic pathogens. The Clinical and Laboratory Standards Institute (CLSI) publishes revised TZP breakpoints in 2022. The purpose of this study was to evaluate the impact of changing the TZP breakpoint in a regional teaching hospital in southern Taiwan. Methods We retrospectively evaluated TZP for 1347 Enterobacterales isolates identified by MALDI-TOF (Bruker Daltonik, Bremen, Germany) between September 1, 2022, through December 31, 2022, at Chang Gung Memorial Hospital in Chiayi. Blood antimicrobial susceptibility testing was performed using an NMIC-411 panel on the BD Phoenix™ M50. The antibiotic susceptibility test of Enterobacterales from other sources of infection used the Disk diffusion method (Kirby-Bauer Method). Susceptibilities were assessed based on historic CLSI breakpoints in 2021 as well as the current CLSI breakpoints from the most recent CLSI MIC breakpoints, the 32th edition of document M100, published in 2022. Results We evaluated 1347 Enterobacterales isolates. Most isolates identified were Escherichia coli [n = 768 (57%)] and Klebsiella pneumoniae [n = 286(21.2%)]. The new TZP breakpoints reduced the percentage of strains that were previously judged to be susceptible by CLSI M100-S31 from 80.9%(1090/1347) to 50%(674/1347). The majority of isolates 674(50%) were susceptible; 416 (30.9%) isolates were susceptible-dose dependent and 257 (19.1%) were resistant to piperacillin/tazobactam using the new CLSI breakpoints. The results of the analysis of the source of infection found that the bacteria that had the greatest impact on the respiratory tract decreased from 43.6% to 12.7%, followed by the genitourinary tract infection decreased from 80.4% to 27%, bodily fluid infection decreased from 69.8% to 24.5%, and abscesses,wounds,pus decreased from 72.7% to 28.1%; The most insignificant are blood infection strains, from 83.1% to 81.3%. Conclusion Our results indicate an increase in resistance to Enterobacterales isolates tested. Non- susceptible to piperacillin/tazobactam from 19.1% to 50% using the revised CLSI breakpoints. The decreased susceptibilities make it clear that microbiology laboratories should accept new MIC breakpoints. Although our study has demonstrated decreased susceptibilities, there is no correlation with clinical outcomes. In conclusion, changes in breakpoints had a significant impact on the susceptibility of TZP for Enterobacterales isolates in our study. Understanding and evaluating the impact of the breakpoint changes is of paramount importance. Institutions should ensure that their breakpoints are up to date to allow for the most optimized treatment.

Introduction to the revised international guidelines on breakpoints for antimicrobial susceptibility testing

Clinical and Laboratory Standards Institute (CLSI) M100 ‘Performance Standards for Antimicrobial Susceptibility Testing (AST)’ and the European Committee on AST (EUCAST) ‘Breakpoint tables for interpretation of MICs and zone diameters’ guidelines for conducting and interpreting AST are revised yearly. The 2023 CLSI guideline introduces selective and cascade reporting methods for antibacterial agents as a part of strengthening antibiotic stewardship and changes in breakpoints for aminoglycoside (AG) in Enterobacterales and AG and piperacillin in Pseudomonas aeruginosa. Main changes in EUCAST include revised breakpoints for aminopenicillins in Enterobacterales, and detailed criteria reflecting the clinical situation and antibacterial agent administration method.

Impact of the Recent Clinical and Laboratory Standards Institute Breakpoint Changes on the Antimicrobial Spectrum of Aminoglycosides and the Activity of Plazomicin Against Multidrug-Resistant and Carbapenem-Resistant Enterobacterales From United States Medical Centers.

The Clinical and Laboratory Standards Institute (CLSI) lowered the Enterobacterales-susceptible/-resistant breakpoints for amikacin in 2023 from ≤16/≥64 mg/L to ≤4/≥16 mg/L and the breakpoints for gentamicin and tobramycin from ≤4/≥16 mg/L to ≤2/≥8 mg/L. Because aminoglycosides are frequently used to treat infections caused by multidrug-resistant (MDR) and carbapenem-resistant Enterobacterales (CRE), we evaluated the impact of these changes on the susceptibility rates (%S) of Enterobacterales collected from US medical centers. A total of 9809 Enterobacterales isolates were consecutively collected (1/patient) from 37 US medical centers in 2017-2021 and susceptibility was tested by broth microdilution. Susceptibility rates were calculated using CLSI 2022, CLSI 2023, and US Food and Drug Administration 2022 criteria. Aminoglycoside-nonsusceptible isolates were screened for genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases (16RMT). The CLSI breakpoint changes mostly affected amikacin, especially against MDR (94.0%S to 71.0%S), extended-spectrum β-lactamase (ESBL)-producing (96.9%S to 79.7%S), and CRE (75.2%S to 59.0%S) isolates. Plazomicin was active against 96.4% of isolates and retained potent activity against CRE (94.0%S), ESBL-producing (98.9%S), and MDR (94.8%S) isolates. Gentamicin and tobramycin showed limited activity against resistant subsets of Enterobacterales. The AME-encoding genes and 16RMT were observed in 801 (8.2%) and 11 (0.1%) isolates, respectively. Plazomicin was active against 97.3% of the AME producers. The spectrum of activity of amikacin against resistant subsets of Enterobacterales was drastically reduced when interpretative criteria based on pharmacokinetic/pharmacodynamic parameters that are currently used to establish breakpoints for other antimicrobials were applied. Plazomicin was markedly more active than amikacin, gentamicin, or tobramycin against antimicrobial-resistant Enterobacterales.

Dopamine D1 receptor and effort-based decision making in rats: The moderating effect of sex

Dopamine is a modulating factor in effort-based decision-making, and emerging evidence from pharmacological research suggests that the dopamine D1 receptor is the primary regulator. Given the limited selectivity of pharmacological tools, we further explored this hypothesis using dopamine D1 mutant (DAD1−/−) rats which have a specific genetic reduction in functional D1 receptors. Moreover, given the strong focus on males in neuroscience research in general and in the role of D1 receptors in effort-based learning, we compared both sexes in the present study.Adult male and female DAD1−/− mutant rats and wild type controls were trained to press a lever for a reinforcer. Once trained, subjects completed multiple fixed ratio, progressive ratio, and operant effort-choice (concurrent progressive ratio/chow feeding task [PROG/chow]) experiments. We predicted that DAD1−/− mutant rats would press the lever significantly less than controls across all experiments, have lower breakpoints, and consume more freely available food. As predicted, DAD1−/− mutant rats (regardless of sex) pressed the lever significantly less than controls and had lower breakpoints. Interestingly, there was a sex * genotype interaction for acquisition rates of lever pressing and change in breakpoints with free food available. Only 31% of DAD1−/− mutant males acquired lever pressing while 73% of DAD1−/− mutant females acquired lever pressing. Additionally, DAD1−/− mutant males had significantly larger decreases in breakpoints when free food was available. These findings extend the pharmacological research suggesting that the dopamine D1 receptor modulates decisions based on effort, which has implications for the development of treatment targeting amotivation in neuropsychiatric disorders. The sex * genotype interaction highlights the importance of including both sexes in future research, especially when there are sex differences in incidences and severity of neuropsychiatric disorders.

It's Not You, It's SOSA: A Case Study on Breaking Up With an FDA-Cleared Susceptibility Testing System's Oxacillin Results for Staphylococcus spp. Other Than S. aureus and S. lugdunensis.

BackgroundIn 2021, the Clinical and Laboratory Standards Institute revised its susceptible oxacillin minimum inhibitory concentration (MIC) breakpoint for Staphylococcus spp. other than S. aureus and S. lugdunensis (SOSA) from ≤0.25 to ≤0.5 µg/mL. Here, we describe the response to this breakpoint change, which at the time of this study was not yet recognized by the US Food and Drug Administration (FDA), in our laboratory, where the primary method for antimicrobial susceptibility testing (AST) of SOSA is VITEK 2. VITEK 2 uses the Automated Expert System (AES) to integrate the results of oxacillin MIC and cefoxitin screen tests into a final interpretation; our laboratory also adjudicates discordant oxacillin and cefoxitin results using a PBP2a test.MethodsWe retrospectively reviewed and assessed the yield of PBP2a testing for 189 SOSA isolates with discordant (when applying the FDA susceptible oxacillin breakpoint of ≤0.25 µg/mL) VITEK 2 oxacillin and cefoxitin results, and then prospectively incorporated PBP2a testing for isolates with oxacillin MICs of 0.5 µg/mL and positive cefoxitin screens into our algorithm.ResultsCompared with accepting the VITEK 2 AES interpretation, PBP2a testing substantially improved the accuracy of mecA-mediated resistance classification in both scenarios, especially for the ∼4.7% of isolates with oxacillin MICs ≤0.5 µg/mL and positive cefoxitin screens.ConclusionsAlthough detection of mecA or PBP2a is the gold standard for assessment of β-lactam resistance in staphylococci, targeting a subset of isolates for mecA or PBP2a testing based on phenotypic AST results that predict an increased risk of misclassification may be a pragmatic, labor- and cost-saving approach.

Focused Commentary; About Revision of CLSI Antimicrobial Breakpoints, 2018-2021

In recent years, antimicrobial resistance has been on the rise and infectious disease specialists and other clinicians face several challenges when treating patients with antimicrobial resistant infections. Clinical and Laboratory Standards Institute (CLSI) annually publishes guidelines for antimicrobial resistance tests, including revised antimicrobial breakpoints, because of the rise in antimicrobial resistance and changes to nomenclature owing to advances in whole genome sequencing technology. However, many laboratories use historical guidelines and do not follow the revised breakpoints. Moreover, the current breakpoints have limitations. This study evaluated the changes in antimicrobial breakpoints over the last 4 years, from 2018 to 2021. Here, I describe the microbiological and clinical background of the CLSI breakpoint revision and evaluate the advantages and limitations of new breakpoints with a review of large study data. In addition, I reviewed problems associated with each antimicrobial breakpoint and made suggestions for how they might be improved, for example, increasing or decreasing the minimum inhibitory concentration (MIC) or zone diameter, deleting or adding an S, I, or R category, introducing new concepts (such as susceptible-dose dependent (SDD)), and requesting more evaluation methods. Conclusions; CLSI annually publishes guidelines for antimicrobial resistance tests. I reviewed problems associated with each antimicrobial breakpoint for last 4 years, and made suggestions for how they might be improved.

Unravelling seasonal trends in coastal marine heatwave metrics across global biogeographical realms

Marine heatwaves (MHWs) can cause dramatic changes to ecologically, culturally, and economically important coastal ecosystems. To date, MHW studies have focused on geographically isolated regions or broad-scale global oceanic analyses, without considering coastal biogeographical regions and seasons. However, to understand impacts from MHWs on diverse coastal communities, a combined biogeographical-seasonal approach is necessary, because (1) bioregions reflect community-wide temperature tolerances and (2) summer or winter heatwaves likely affect communities differently. We therefore carried out season-specific Theil–Sen robust linear regressions and Pettitt change point analyses from 1982 to 2021 on the number of events, number of MHW days, mean intensity, maximum intensity, and cumulative intensity of MHWs, for each of the world’s 12 major coastal biogeographical realms. We found that 70% of 240 trend analyses increased significantly, 5% decreased and 25% were unaffected. There were clear differences between trends in metrics within biogeographical regions, and among seasons. For the significant increases, most change points occurred between 1998 and 2006. Regression slopes were generally positive across MHW metrics, seasons, and biogeographical realms as well as being highest after change point detection. Trends were highest for the Arctic, Northern Pacific, and Northern Atlantic realms in summer, and lowest for the Southern Ocean and several equatorial realms in other seasons. Our analysis highlights that future case studies should incorporate break point changes and seasonality in MHW analysis, to increase our understanding of how future, more frequent, and stronger MHWs will affect coastal ecosystems.

Raising the Bar: Improving Antimicrobial Resistance Detection by Clinical Laboratories by Ensuring Use of Current Breakpoints.

BackgroundAntimicrobial resistance (AMR) is a pressing global challenge detected by antimicrobial susceptibility testing (AST) performed by clinical laboratories. AST results are interpreted using clinical breakpoints, which are updated to enable accurate detection of new and emerging AMR. Laboratories that do not apply up-to-date breakpoints impede global efforts to address the AMR crisis, but the extent of this practice is poorly understood.MethodsA total of 1490 clinical laboratories participating in a College of American Pathologists proficiency testing survey for bacterial cultures were queried to determine use of obsolete breakpoints.ResultsBetween 37.9% and 70.5% of US laboratories reported using obsolete breakpoints for the antimicrobials that were queried. In contrast, only 17.7%–43.7% of international laboratories reported using obsolete breakpoints (P < .001 for all comparisons). Use of current breakpoints varied by AST system, with more laboratories reporting use of current breakpoints in the US if the system had achieved US Food and Drug Administration clearance with current breakpoints. Among laboratories that indicated use of obsolete breakpoints, 55.9% had no plans to update to current standards. The most common reason cited was manufacturer-related issues (51.3%) and lack of internal resources to perform analytical validation studies to make the update (23.4%). Thirteen percent of laboratories indicated they were unaware of breakpoint changes or the need to update breakpoints.ConclusionsThese data demonstrate a significant gap in the ability to detect AMR in the US, and to a lesser extent internationally. Improved application of current breakpoints by clinical laboratories will require combined action from regulatory agencies, laboratory accreditation groups, and device manufacturers.

Changing times: The impact of gram-negative breakpoint changes over the previous decade.

We assessed breakpoint changes of 13,101 Enterobacterales and Pseudomonas aeruginosa isolates from the past decade. All β-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. Enterobacter cloacae experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.3% and P. aeruginosa experienced an average decrease in susceptibility of 9.3%.

Use of LSTM for Sinkhole-Related Anomaly Detection and Classification of InSAR Deformation Time Series

Sinkholes exhibit precursory deformation patterns. Such deformation patterns can be studied using InSAR time-series analysis over constantly coherent scatterrers (CCS). In the past we identified Heaviside and Breakpoint changes as two important forms of anomalous behaviour. It is challenging to efficiently detect and classify these sudden step and sudden velocity changes in deformation time series, especially in the presence of tens of thousands CCS. To address this challenge, we propose to classify these forms of anomalous behaviour with a deep learning-based supervised time series classification. In this study, we used a two-layered Bidirectional Long Short Term Memory (LSTM) classification model for this purpose. The classified deformation classes were analyzed as well in the context of scattering mechanisms. We implemented this model on a sinkhole affected region spanning <inline-formula><tex-math notation="LaTeX"><?TeX ${\sim }63\times 44$?></tex-math></inline-formula> km<inline-formula><tex-math notation="LaTeX"><?TeX $^{2}$?></tex-math></inline-formula> in Ireland, using 104 Sentinel-1&#x00A0;A SAR images acquired between 2015 and 2018. Our results show that the CCS with a linear trend can be correctly classified with a maximum accuracy of <inline-formula><tex-math notation="LaTeX"><?TeX ${\sim }99 \%$?></tex-math></inline-formula> whereas for the CCS categorized as anomalous Heaviside and Breakpoint changes the accuracy drops to a maximum of 62&#x0025;. Multi-threshold-based filtering of samples increased the classification accuracy by as much as 50&#x0025;. We conclude that the method that we propose is effective in detecting anomalous deformation changes. Future research should investigate how it can be applied to other hazard-related detection and classification problems.

Impact of CLSI Break Point Changes Over the Past Decade on Antimicrobial Susceptibility in Gram-Negative Bacteria

Background: Over the past decade, the CLSI has updated susceptibility break points for several antimicrobial agents. The purpose of this study was to evaluate the impact of these changes against gram-negative bacteria at our academic medical center. Methods: In this retrospective, IRB-approved study, we collected consecutive, nonduplicate clinical isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, and Pseudomonas aeruginosa for the past decade (2010–2019) at our academic medical center and 3 adult ICUs. Susceptibility testing was performed using the BD Phoenix automated system. For these isolates, susceptibilities for 7 β-lactams (aztreonam, ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, ertapenem, and meropenem) and 2 fluoroquinolones (levofloxacin, ciprofloxacin) were calculated based upon CLSI break points in 2010 and current CLSI break points in 2020. Any change &gt;5% in susceptibility was deemed significant for this analysis. Results: In 17.5% of Enterobacteriales isolates tested, at least 1 antimicrobial demonstrated significant decline. Ertapenem was the most commonly affected antimicrobial (45% of the isolates) followed by ceftriaxone (35%) and cefepime (25%). Susceptibilities of aztreonam, ceftazidime, and meropenem were not affected for any of the Enterobacteriales. The most common organism demonstrating a significant impact on change in susceptibility among the Enterobacteriales was E. cloacae (41.7% of the time) followed by E. aerogenes (20.8%), K. oxytoca (12.5%), K. pneumoniae (8.3%) and E. coli (4.2%). Most of the impact was observed hospital-wide (33.3%), followed closely by the MICU (28.6%), the NSICU (23.8%) and the CVICU (14.3%). For P. aeruginosa, the impact of the antimicrobial break-point changes on susceptibility was more pronounced than the Enterobacteriales. Overall, 93.8% of the time there was a significant decline in antimicrobial susceptibility. Each antimicrobial (ciprofloxacin, levofloxacin, meropenem, and piperacillin/tazobactam) demonstrated a significant decline in susceptibility hospital-wide and in each ICU except for the susceptibility of meropenem in the NSICU. Conclusions: Changes in break points had a significant impact on the susceptibility of all antimicrobials for P. aeruginosa at our institution, both hospital-wide and in the adult ICUs. Although the impact was less for the Enterobacteriales, ertapenem, ceftriaxone, and cefepime demonstrated significant susceptibility changes, especially with E. cloacae. Understanding and evaluating the impact of the break-point changes may lead to changes in empiric therapy in other institutions.Funding: NoDisclosures: None

Impact of Tigecycline's MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy-Validation of 2019's EUCAST Proposed Breakpoint Changes.

Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline’s minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy. Methods: Patients with monomicrobial bacteraemia due to CP-Kp that received appropriate targeted monotherapy or no appropriate treatment were included. Primary outcome was 30-day mortality. MICs of meropenem, tigecycline, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. PCR for blaKPC, blaVIM, blaNDM, and blaOXA genes was applied. Results: Among 302 CP-Kp bacteraemias, 32 isolates (10.6%) showed MICs of tigecycline ≤ 0.5 mg/L, whereas 177 (58.6%) showed MICs that were 0.75–2 mg/L. Colistin and aminoglycoside susceptibility was observed in 43.0% and 23.8% of isolates, respectively. The majority of isolates carried blaKPC (249; 82.5%), followed by blaVIM (26; 8.6%), both blaKPC and blaVIM (16; 5.3%), and blaNDM (11; 3.6%). Fifteen patients with tigecycline MIC ≤ 0.5 mg/L and 55 with MIC 0.75–2 mg/L were treated with tigecycline monotherapy; 30-day mortality was 20.0% and 50.9%, respectively (p = 0.042). Mortality of 150 patients that received other antimicrobials was 24.7%; among 82 patients that received no appropriate treatment, mortality was 39.0%. No difference in 30-day mortality was observed between patients that received tigecycline (MIC ≤ 0.5 mg/L) or other antimicrobials. Conclusion: Tigecycline monotherapy was as efficacious as other antimicrobials in the treatment of bloodstream infections due to CP-Kp isolates with a tigecycline’s MIC ≤ 0.5 mg/L.

Carnivores and Communities: A Case Study of Human-Carnivore Conflict Mitigation in Southwestern Alberta

Facilitating long-term coexistence between people and large carnivores is a persistent, global conservation challenge. Evidence-based decisions to help design and implement programs that promote coexistence between people and carnivores are required. Using a case study approach, we evaluated the effectiveness of conflict mitigation efforts of a community-based program in southwestern Alberta, Canada: the Waterton Biosphere Reserve’s (WBR) Carnivores and Communities Program (CACP). The CACP’s overall goal is to support coexistence of people and large carnivores through initiatives including reducing livestock loss, damage to stored crops, and safety risks from carnivores by engaging residents in hands-on programming. We used an online survey to assess program participants’ general awareness of and motivation to engage in the CACP, safety risks associated with living with large carnivores, and attractant management and deadstock removal programming. We received 116 completed surveys. Survey results indicated that participants felt the CACP effectively reduced conflicts with large carnivores, increased their sense of safety when living with large carnivores, and enabled them to learn skills and gain confidence in using mitigation tools (e.g., bear spray). We also evaluated temporal trends in large carnivore conflicts using occurrence records (i.e., complaint data) from 1999 through 2016. We classified these data into incidents (e.g., situations where carnivores caused property damage, obtained anthropogenic food, killed or attempted to kill livestock or pets) and focussed on incidents related to attractants, including deadstock. We focus our incident review on grizzly bears because most agricultural attractant incidents in the study area are caused by grizzly bears. We used a Chow test to evaluate if the 2009 CACP commencement represented a break point or structural change in the data. Although total reported incidents increased from 1999 through 2016, we show both reported attractant and deadstock-based incidents changed from increasing to decreasing after the CACP implementation in 2009. Our results demonstrate the effectiveness of a contextually specific, community-based approach to addressing human-carnivore conflicts. More broadly, our evaluation and lessons learned provide other conservation organizations with a useful framework for addressing human-carnivore or other wildlife conflicts.

Phenotypic and Genotypic Correlates of Penicillin Susceptibility in Nontoxigenic Corynebacterium diphtheriae, British Columbia, Canada, 2015-2018.

In 2015, the Clinical and Laboratory Standards Institute (CLSI) updated its breakpoints for penicillin susceptibility in Corynebacterium species from <1 mg/L to <0.12 mg/L. We assessed the effect of this change on C. diphtheriae susceptibility reported at an inner city, tertiary care center in Vancouver, British Columbia, Canada, during 2015–2018 and performed whole-genome sequencing to investigate phenotypic and genotypic resistance to penicillin. We identified 44/45 isolates that were intermediately susceptible to penicillin by the 2015 breakpoint, despite meeting previous CLSI criteria for susceptibility. Sequencing did not reveal β-lactam resistance genes. Multilocus sequence typing revealed a notable predominance of sequence type 76. Overall, we saw no evidence of penicillin nonsusceptibility at the phenotypic or genotypic level in C. diphtheriae isolates from our institution. The 2015 CLSI breakpoint change could cause misclassification of penicillin susceptibility in C. diphtheriae isolates, potentially leading to suboptimal antimicrobial treatment selection.