bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time Above All Else: Pharmacodynamic Analysis of Β-Lactams in Critically Ill Patients
Authors: Landmesser Katherine , Burgess David , Clark Justin 
Published: November 2021

Background: Despite the development of new β-lactam agents, gram-negative resistance continues to be an increasing concern in the healthcare setting. The understanding and optimizing antimicrobial pharmacokinetics and pharmacodynamics are essential to enhance activity of appropriate therapy, improve clinical outcomes, and reduce the development of resistance. Methods: A pharmacodynamic analysis was performed for 4 β-lactams (aztreonam, cefepime, piperacillin/tazobactam, and meropenem) and 14 dosage regimens as either intermittent bolus (IB) or prolonged infusion (PI) against 7 gram-negative pathogens: Klebsiella pneumoniae, K. oxytoca, Escherichia coli, Enterobacter cloacae, E. aerogenes, Acinetobacter baumannii, and Pseudomonas aeruginosa. Unit-specific minimum inhibitory concentration (MIC) distribution data were generated using antibiogram data over a decade for 4 intensive care units within our institution: medical ICU, cardiovascular ICU, surgical ICU, and neurosurgical ICU. Published pharmacokinetic parameter estimates in critically ill patients, combined with this MIC distribution data, were utilized to perform Monte Carlo simulations for each antimicrobial regimen. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (ƒT>MIC) was utilized as the pharmacodynamic target for each agent: 40% ƒT>MIC for meropenem, 50% ƒT>MIC for piperacillin/tazobactam, 60% ƒT>MIC for aztreonam, and 70% ƒT>MIC for cefepime. Regimens were modeled using Oracle Crystal Ball software to determine the likelihood of achieving >90% probability of target attainment (PTA). Because resistance rates were significantly higher for P. aeruginosa and A. baumannii, cumulative PTAs for K. pneumoniae, K. oxytoca, E. coli, E. cloacae, and E. aerogenes were analyzed separately to determine the relative PTA for Enterobacterales in each ICU. Results: No intermittent infusion regimens of piperacillin/tazobactam, aztreonam, or cefepime achieved >90% PTA for any organism. Piperacillin/tazobactam 4.5 g infused over 4 hours (PI q6h) and aztreonam 2 g PI q6h failed to achieve adequate PTA for Enterobacterales with only 84% and 85% PTA, respectively. For Enterobacterales, the only regimens to achieve >90% PTA included cefepime 2 g infused over 3 hours (PI q8h) and meropenem 1g IB q8h with 95% and 99% PTA, respectively. Meropenem 2 g PI q8h was the only regimen capable of achieving >90% PTA for both A. baumannii and P. aeruginosa with 97% and 92% PTA, respectively. Conclusions: Although utilization of high doses and prolonged infusions dramatically improve the pharmacodynamics of β-lactam therapy, the only regimen capable of achieving adequate PTA for all organisms analyzed was meropenem 2g PI q8h. To reduce carbapenem use, combination therapy may be considered for critically ill patients receiving aztreonam, cefepime, or piperacillin/tazobactam for empiric treatment of gram-negative infections.Funding: NoDisclosures: None
Working with Respiratory Illness: Presenteeism Among Healthcare Personnel at Tertiary-Care Hospitals in Bangladesh, 2008–2016
Authors: Mah-E-Muneer Syeda , Hassan Md. Zakiul , Uddin Bhuiyan Mejbah , Hussain Kamal , Akhtar Zubair , Rahman Mustafizur , Iuliano A. Danielle , Azziz-Baumgartner Eduardo , Chowdhury Fahmida 
Published: November 2021

Background: Healthcare personnel (HCP) in crowded and resource-poor countries (eg Bangladesh), might be at risk of exposure to and transmission of respiratory illnesses to coworkers, patients, and caregivers. The infection control practices in public hospitals are inadequate in Bangladesh. We estimated the incidence of respiratory illness episodes among HCP, and proportion of HCP who worked during respiratory illnesses, including influenza virus infection, at 2 tertiary-care public hospitals in Bangladesh. Methods: From May 2008 to February 2016, HCP (defined as physicians, nurses, interns, patient care assistant, cleaners, and administrative staff working in adult and pediatric medicine wards) were asked to self-report to study physicians when they experienced new onset of cough, rhinorrhea, difficulty breathing, or fever during the April–September influenza epidemic period each year. Study physicians followed HCP throughout their respiratory illness episodes and recorded respiratory symptoms, onset dates, duration of illness, and days of presenteeism and absenteeism during illness. Nasopharyngeal and oropharyngeal swabs were collected after informed written consent and were tested for influenza by rRT-PCR. We used hospital records to enumerate total HCP working in the study wards during influenza season and multiplied by 6-months follow-up per year to calculate person-time contribution for estimating respiratory illness incidence. Results: HCP self-reported 107 episodes of respiratory illness during 656 person years of follow-up, for an estimated incidence of 16.3 per 100 person years (95% CI, 13–20). Of 107 episodes, 33 (31%) included fever and cough. The mean illness length was 3.9 days (SD, ±1.8). HCP worked an average of 3.4 days (SD, ±1.4) while ill. HCP missed work for a median of 1 day (IQR, 1–2) during 29 (27%) of 107 illness episodes. HCP consented to collect swabs during 56 (52%) episodes, and among them 8 (14%) of 56 tested positive for influenza (flu-A, n = 5; flu-B, n = 3). Also, 63% of HCP with influenza reported fever and cough. HCP experiencing either respiratory illness or influenza worked for similar periods of days while ill: mean, 4 (SD, ±2.2) versus mean, 3.3 (SD, ±1.4) (P = .257). HCP worked during 105 (98%) of 107 respiratory illness and 7 (88%) of 8 influenza episodes. Conclusions: Most HCP in Bangladesh, including those with influenza, worked during respiratory illnesses. The potential value of stay-at-home policies, compensation for sick days, and influenza vaccination in reducing HCP-associated respiratory pathogen transmission could be assessed in Bangladesh and similar settings.Funding: NoDisclosures: None
Knobmanship: Dialing Up Understanding of VAE Triggers
Authors: Cawcutt Kelly , Rupp Mark , Musil Lauren 
Published: November 2021

Background: Mechanical ventilation is a lifesaving therapy for critically ill patients. Hospitals perform surveillance for the NHSN for ventilator-associated events (VAE) by monitoring mechanically ventilated patients for metrics that are generally thought to be objective and preventable and that lead to poor patient outcomes. The VAE definition is met in a stepwise manner; initially, a ventilator-associated condition (VAC) is triggered with an increase in positive end-expiratory pressure (PEEP, >3 cm H2O) or fraction of inspired oxygen (FIO2, 0.20 or 20 points) after a period of stability or improvement on the ventilator. We believe that many reported VAEs could be avoided by provider and respiratory therapy attention to “knobmanship.” We define knobmanship as knowledge of the VAE definition and trigger points combined with appropriate clinical care for mechanically ventilated patients while avoiding unnecessary triggering of the VAE definition by avoiding small unneeded changes in PEEP or FIO2. Methods: We performed a chart review of 283 patients who had a reported VAE to the NHSN between January 1, 2019, and December 31, 2020. We collected data including type of VAE, VAE triggering criteria, and clinical course. Results: Of the 283 VAEs, 59 were triggered by a PEEP increase from 5 to 8 with stable or decreasing FIO2. Of the 59 VAEs, 33 were VACs, 18 were infection-related ventilator- associated complications (IVACs), and 8 were possible ventilator-associated pneumonia (PVAP). Most of these transient changes in PEEP were deemed clinically unnecessary. A 21% reduction of VAEs reported to the NSHN over the 2-year review period could have been avoided by knobmanship. Conclusions: The VAE definition may often be triggered by provider bias to the ventilator settings rather than what the patient’s clinical-condition requires. Attention to knobmanship may result in substantial decrease in reported VAE.Funding: NoDisclosures: None
Model Input and Optimization: Improving the Speed and Accuracy of Our COVID-19 Hospitalization Forecasts
Authors: Rhea Sarah , Hadley Emily , Jones Kasey , Preiss Alexander , Stoner Marie , Kery Caroline , Baumgartner Peter , Giarrocco Alex 
Published: November 2021

Background: During the COVID-19 pandemic, public-health decision makers have increasingly relied on hospitalization forecasts that are routinely provided, accurate, and based on timely input data to inform pandemic planning. In North Carolina, we adapted an existing agent-based model (ABM) to produce 30-day hospitalization forecasts of COVID-19 and non–COVID-19 hospitalizations for use by public-health decision makers. We sought to continually improve model speed and accuracy during forecasting. Methods: The geospatially explicit ABM included movement of agents (ie, patients) among 104 short-term acute-care hospitals, 10 long-term acute-care hospitals, 421 licensed nursing homes, and the community in North Carolina. Agents were based on a synthetic population of North Carolina residents (ie, >10.4 million agents). We assigned SARS-CoV-2 infections to agents according to county-level susceptible, exposed, infectious, recovered (SEIR) models informed by reported COVID-19 cases by county. Agents’ COVID-19 severity and probability of hospitalization were determined using agent-specific characteristics (eg, age, comorbidities). During May 2020–December 2020, we produced weekly 30-day forecasts of intensive care unit (ICU) and non-ICU bed occupancy for COVID-19 agents and non–COVID-19 agents statewide and by region under a range of SARS-CoV-2 effective reproduction numbers. During the reporting period, we identified optimizations for faster results turnaround. We evaluated the incorporation of real-time hospital-level occupancy data at model initialization on forecast accuracy using mean absolute percent error (MAPE). Results: During May 2020–December 2020, we provided 31 weekly reports of 30-day hospitalization forecasts with a 1-day turnaround time. Reports included (1) raw and smoothed 7-day average values for 42 model output variables; (2) static visuals of ICU and non-ICU bed demand and capacity; and (3) an interactive Tableau workbook of hospital demand variables. Identifying code efficiencies reduced a single model runtime from ~100 seconds to 28 seconds. The use of cloud computing reduced simulation runtime from ~20 hours to 15 minutes. Across forecasts, the average MAPEs were 21.6% and 7.1% for ICU and non-ICU bed demand, respectively. By incorporating hospital-level occupancy data, we reduced the average MAPE to 6.5% for ICU bed demand and 3.9% for non-ICU bed demand, indicating improved accuracy. Conclusions: We adapted an ABM and continually improved it during COVID-19 forecasting by optimizing code and computing resources and including real-time hospital-level occupancy data. Planned SEIR model updates for enhanced forecasts include the addition of compartments for undocumented infections and recoveries as well as permission of reinfection from recovered compartments.Funding: NoDisclosures: None
Retrospective Study on Personal Protective Equipment During Pandemic Link to Outbreak of Carbpenem-Resistant Enterobacteriace
Authors: Evans Kenisha , LeRose Jennifer , Beatriz Cruz Angela , Jabbo Lavina , Chopra Teena 
Published: November 2021

Background: In 2019, according to the Centers for Disease Control and Prevention, carbapenem-resistant Enterobacteriaceae (CRE), had cost the lives of >35,000 patients, particularly the most virulent plasmid-mediated New Delhi metallo-β-lactamase (NDM). Although healthcare systems normally have strict surveillance and infection control measures for CRE, the rapid emergence of novel SAR-CoV-2 and COVID-19 led to a shortage of personal protective equipment (PPE) and medical supplies. As a result, routine infection practices, such as contact precautions, were violated. Studies have shown this depletion and shift in resources compromised the control of infections such CRE leading to rising horizontal transmission. Method: A retrospective study was conducted at a tertiary healthcare system in Detroit, Michigan, to determine the impact of PPE shortages during the COVID-19 pandemic on NDM infection rates. The following periods were established during 2020 based on PPE availability: (1) pre-PPE shortage (January–June), (2) PPE shortage (July–October), and (3) post-PPE shortage (November–December). Rates of NDM per 10,000 patient days were compared between periods using the Wilcoxon signed rank-sum test. Isolates were confirmed resistant by NDM by molecular typing performed by the Michigan State Health Department. Patient characteristics were gathered by medical chart review and patient interviews by telephone. Results: Overall, the average rate of NDM infections was 1.82 ±1.5 per 10,000 patient days. Rates during the PPE shortage were significantly higher, averaging 3.6 ±1.1 cases per 10,000 patient days (P = .02). During this time, several infections occurred within patients on the same unit and/or patients with same treating team, suggesting possible horizontal transmission. Once PPE stock was replenished and isolation practices were reinstated, NDM infection rates decreased to 0.77 ±1.1 per 10,000 patient days. Conclusion: Control of CRE requires strategic planning with active surveillance, antimicrobial constructs, and infection control measures. The study illustrates that in times of crisis, such as the COVID-19 pandemic, the burden of effective infection control requires much more multidisciplinary efforts to prevent unintentional lapses in patient safety. A swift response by the state and local health departments at a tertiary-care healthcare center conveyed a positive mitigation of the highest clinical threats and decreased horizontal transmission of disease.Funding: NoDisclosures: None
Assessing Robustness of Antimicrobial Stewardship in Colorado Hospitals and Barriers to Improvement
Authors: Dodson Daniel , Kronman Matthew , Parker Sarah , Czaja Christopher 
Published: November 2021

Background: Adherence to core elements of antimicrobial stewardship programs (ASPs) is increasing nationally but the robustness of programs and inclusion of pediatrics is poorly understood. We describe the details of ASP in Colorado hospitals and identify steps by which academic centers and public health departments can assist community ASPs. Methods: We invited ASP leaders at the 102 acute-care hospitals (ACHs) and critical-access hospitals (CAHs) in Colorado to participate in a web-based survey regarding their ASPs. Questions related to adherence to Centers for Disease Control and Prevention (CDC) core elements, barriers to improvement, desired resources, and extension to pediatrics. Enrollment began in August 2020. Hospital types were compared using the Fisher exact test. Results: As of January 1, 2021, 31 hospitals (30% of targeted hospitals) completed the web-based survey including 19 ACH and 12 CAH. Hospitals were distributed across the state. Median number of beds was 52 (range, 11–680). Of the responding hospitals, 87% were adherent to all CDC core elements. However, if action was defined as prospective audit and feedback or prior authorization, tracking was defined as measuring antibiotic use in days of therapy (DOT) or defined daily dose (DDD) quarterly, and reporting was defined as providing unit- or provider-specific antibiotic use reports annually. Overall adherence fell to 35% including 81% for action, 58% for tracking, and 58% for reporting. CAHs were less likely to adhere to these strict criteria than ACHs (Figure 1). In the 27 hospitals (87% of hospitals) caring for pediatric patients, adherence to a strict action for at least 1 pediatric population was 59%. Reported barriers to improved ASP were available time and personnel, information technology support, perceived concerns about provider attitudes, and education gaps (Figure 2). CAHs were less likely to use the NHSN antibiotic use or resistance modules or have a data analyst than ACHs (Figure 3). Pediatric pharmacy expertise and guidelines were often not available in hospitals caring for pediatric patients. Desired ASP resources included assistance with data analysis, access to stewardship expertise and education, and treatment guidelines, including for pediatrics. Conclusions: Adherence to CDC core elements of an ASP was excellent but fell dramatically when stricter criteria were used and was worse in pediatric patients. Academic centers and public health departments can assist community hospitals by providing educational resources, assistance in analyzing data including using the NHSN ED: /AR modules, and ASP expertise and clinical care guidelines including those for pediatrics.Funding: NoDisclosures: None
Interrupted Time-Series Analysis to Evaluate the Impact of a Behavioral Change Outpatient Antibiotic Stewardship Intervention
Authors: Morgan Brittany , May Larissa , Bettencourt Haylee 
Published: November 2021

Background: The Centers for Disease Control and Prevention (CDC) estimates that outpatient settings account for 85%–90% of antibiotic prescriptions in the United States, and ~30% of those prescriptions are unnecessary. One of the most common examples of inappropriate prescribing is for viral upper respiratory infections (URIs). Up to 50% of prescriptions written for URIs are deemed inappropriate, making it an important focus for Antibiotic Stewardship programs. In this study, we evaluated the effect of a behaviorally enhanced quality improvement intervention in reducing inappropriate antibiotic prescribing for viral URIs. Methods: A quasi-experimental study assessed the effects of an Antibiotic Stewardship intervention on antibiotic prescribing for viral URIs. The outcome of interest was a change in the number of antibiotics prescribed at each participating clinic over a 1-year preimplementation period and a 2-year postimplementation period. Time trends were analyzed using segmented regression analysis, and a stepped wedge design was used to account for intervention roll-out across clinics. Results: From 2017 to 2020, there were 63,028 patient visits in 21 clinic locations. Antibiotics were prescribed an average of 11.5% and 5.8% of visits during the pre- and postimplementation periods, respectively. The most frequently prescribed antibiotic over the study period was azithromycin (n = 3,551), followed by amoxicillin (n = 924). Overall, the intervention was associated with a 46% reduction in antibiotic prescriptions or 0.54 times (P = .001) as many inappropriate antibiotics prescribed as before the intervention. There was no significant change in the month-to-month trend in inappropriate prescriptions after the intervention was implemented (P = .87). Conclusions: Our study demonstrates that a behaviorally enhanced quality improvement intervention to reduce inappropriate prescribing for URI in ambulatory care encounters was successful in reducing potentially inappropriate prescriptions for presumed viral respiratory infections.Funding: NoDisclosures: None
Suspected COVID-19 Reinfections at a Tertiary Care Center, Iowa 2020
Authors: Kobayashi Takaaki , Alsuhaibani Mohammed , Ortiz Miguel , Imborek Katherine , Holley Stephanie , Trannel Alexandra , Marra Alexandre , Etienne William , Jenn Kyle , Abosi Oluchi , Meacham Holly , Sheeler Lorinda , Dains Angie , Kukla Mary , McCray Paul , Perlman Stanley , Ford Bradley , Diekema Daniel , Wellington Melanie , Pezzulo Alejandro , Salinas Jorge 
Published: November 2021

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 RNA can be detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) for several weeks after infection. Discerning persistent RT-PCR positivity versus reinfection is challenging and the frequency of COVID-19 reinfections is unknown. We aimed to determine the frequency of clinically suspected reinfection in our center and confirm reinfection using viral whole-genome sequencing (WGS). Methods: The University of Iowa Hospitals and Clinics (UIHC) is an 811-bed academic medical center. Patients with respiratory complaints undergo COVID-19 RT-PCR using nasopharyngeal swabs. The RT-PCR (TaqPath COVID-19 Combo kit) uses 3 targets (ORF1ab, S gene, and N gene). We identified patients with previous laboratory-confirmed COVID-19 who sought care for new respiratory complaints and underwent a repeated SARS-CoV-2 test at least 45 days from their first positive test. We then identified patients with median RT-PCR cycle threshold (Ct) values. Results: During the study period, 13,603 patients had a SARS-CoV-2– positive RT-PCR. Of these, 296 (2.2%) had a clinical visit for new onset of symptoms and a repeated RT-PCR assay >45 days from the first test. Moreover, 29 patients (9.8%) had a positive RT-PCR assay in the repeated testing. Ct values were available for samples from 25 patients; 7 (28%) had Ct values. Conclusions: In patients with a recent history of COVID-19 infection, repeated testing for respiratory symptoms was infrequent. Some had a SARS-CoV-2–positive RT-PCR assay on repeated testing, but only 1 in 4 had Ct values suggestive of a reinfection. We confirmed 1 case of reinfection using WGS.Funding: NoDisclosures: None