bluuebunny/crossref_metadata_2025 huggingface dataset:
612. Pharmacokinetics of Piperacillin-Tazobactam in Patients with Severe Infections
Authors: Rodríguez-Báez Ana S , Ortiz-Álvarez Arturo , Romano-Aguilar Melissa , Martínez-Gutiérrez Fidel , Romano-Moreno Silvia , Milán-Segovia Rosa C , Medellín-Garibay Susanna
Published: December 2022

Background

Piperacillin-Tazobactam (PIP/TAZ) is a combination of a β-lactam antibiotic with a β-lactamase inhibitor, used to treat moderate to severe infections due to its broad-spectrum antibacterial activity. Its bactericidal effect is time-dependent. Therefore, the free-drug concentration should remain above the minimum inhibitory concentration during at least 50% of the dosing interval. Patients with severe infections develop pathophysiological changes that alter drugs pharmacokinetics (PK), leading to only 30% of probability of target attainment in clinical setting.

Methods

A prospective observational study was performed in patients with severe infections from Hospital Central “Dr. Ignacio Morones Prieto”. The protocol was approved by the Research and Ethics Committee (register 05-20) and patients signed written informed consent. Samples were collected at steady-state and plasma concentrations were quantified by liquid chromatography coupled to mass spectrometry. Data were analyzed by a population approach using NONMEM® software.

Results

A total of 52 patients were included (52% male) with a mean age of 46 ± 17 years and a body mass index of 25 ± 5 Kg/m2. According to the Akaike information criterion and visual inspection, a one-compartment open model was chosen to describe the concentration vs time data (n=156) for both drugs. Typical values (relative standard error) of PK parameters obtained were Clearance [CLPIP (L/h)] = 8.79 (12%) and Volume of distribution [VPIP (L)] = 17.6 (13%); and CLTAZ (L/h) = 12.6 (14%), VTAZ (L) = 32.8 (13%). Interindividual variability (IIV) of each parameter was modeled by exponential error and reported as coefficient of variation as follows: 75.3% and 88.7% for CL; 67.2% and 68.8% for V of PIP and TAZ, respectively. Finally, residual error was modeled as additive and presented a standard deviation (SD) of 7.28 µg/mL for PIP, and for TAZ was modeled as a combined with a SD of 0.22 µg/mL and a coefficient of variation of 17.32%.

Conclusion

Individualization and optimization of β-lactam dosing are essential in drugs with wide IIV as PIP/TAZ; hence, development of a population PK model will provide a valuable aid in explaining and quantifying some of this variability to allow a priori predictions to design initial regimens to reach pharmacotherapeutic targets.

Disclosures

All Authors: No reported disclosures.
620. Pharmacokinetic-Pharmacodynamic Analysis of Oral Vancomycin and Gut Microbiome Changes in Healthy Volunteers: an Exploratory Study
Authors: Jo Jinhee , McPherson Jacob , Gonzales-Luna Anne J , Lancaster Chris , Garey Kevin W
Published: December 2022

Background

Oral vancomycin causes profound changes to the gut microbiome due to high intra-colonic vancomycin concentrations. However, pharmacokinetics of oral vancomycin causing pharmacodynamic changes have not been explored, especially during the early dosing period. The purpose of this study was to investigate fecal vancomycin concentrations in healthy individuals in relation to gut microbiome diversity changes.

Methods

Healthy subjects 18-45 years with no antibiotic use for at least 28 days were given oral vancomycin 125 mg was given every 6 hours for 10 days. Stool samples were collected at baseline and during antibiotic therapy. Vancomycin concentrations were obtained through high-performance liquid chromatography (HPLC) assay. For this early pharmacokinetics analysis, stool samples from day 0 (baseline) to day 4 were included. Shotgun metagenomics sequencing was used for microbiome analysis. Descriptive analysis was performed to identify gut-microbiome phyla changes in correlation with detectable oral vancomycin fecal concentrations.

Results

A total of 6 healthy volunteers aged 32±5 years (Male: 100%; Caucasian: 50%; mean BMI: 26.8±4.5 kg/m2) were included. In the early dosing period (day 0-4), the mean fecal vancomycin concentrations increased daily with the highest concentration of 1,586 μg/g of stool occurring on day 4. Three of 9 subjects (50%) had undetectable oral vancomycin levels one days 1 and 2 of dosing. Within 24-48 hour of detectable vancomycin levels, subject-specific changes of gut microbiome phylum-level proportions were observable. Overall, an increase in Actinobacteria and Proteobacteria phyla and decrease in Firmicute phylum was observed within 24 hours that vancomycin was detected in the feces.

Conclusion

High concentrations of vancomycin are achieved in the stool by day four of dosing for all subjects; however, low concentrations are observed early in the dosing period for some subjects. Proportional, subject specific differences in gut microbiome phyla were observed within 24 hours of detectable vancomycin levels in the feces.

Disclosures

Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.
660. In vitro activity of cefiderocol against difficult-to-treat resistance European Gram-negative bacterial pathogens from the multi-national sentinel surveillance study, SENTRY in 2020 and 2021
Authors: Santerre Henriksen Anne Laurence , Longshaw Christopher M , Shortridge Dee , Streit Jennifer M , Takemura Miki , Yamano Yoshinori
Published: December 2022

Background

Difficult-to-treat resistance (DTR) organisms are defined as non-susceptible to all first-line high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems and fluoroquinolones), leaving physicians with limited treatment options. Cefiderocol is a parenteral siderophore cephalosporin with potent activity against aerobic Gram-negative pathogens, including carbapenem-resistant strains. We evaluated the in vitro activity of cefiderocol and comparators against DTR pathogens collected in Europe by the SENTRY surveillance study in 2020 and 2021.

Methods

A total of 11434 clinical isolates of Gram-negative bacilli were systematically collected from 16 EU countries, Israel and Turkey in 2020 and 2021. Minimum inhibitory concentrations (MICs) were determined by broth microdilution for a panel of twenty-two antibiotics according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller-Hinton broth (CAMHB) except for cefiderocol, for which iron-depleted CAMHB was used. Susceptibility was determined according to CLSI breakpoints, and DTR pathogens were defined as being resistant to cefepime, ceftazidime ceftriaxone, imipenem, meropenem, ciprofloxacin and levofloxacin according to CLSI breakpoints.

Results

Among 11434 Gram-negative isolates collected in 2020 and 2021, 792 (7.0%) were resistant to all 1st line therapy including cephalosporins, carbapenems and fluoroquinolone and could be defined as DTR. DTR was most frequently observed in Acinetobacter spp. (530/931, 56.9%), Enterobacterales (201/7739, 2.6%) and Pseudomonas aeruginosa (61/2440, 2.5. Based on CLSI breakpoints, cefiderocol was the most active antibiotic tested against DTR-Acinetobacter spp. (MIC90= 2mg/L, 97.4% susceptibility). Ampicillin/sulbactam was active in less than 1% of the DTR-Acinetobacter spp isolates. None of the drugs recommended by the IDSA for the treatment of resistant Gram-negative infections were as potent as cefiderocol (Table 1).

Conclusion

Cefiderocol was the only treatment option with demonstrated in vitro activity against more than 95% of all the tested DTR Gram-negative pathogens with limited treatment options.

Disclosures

Anne Laurence Santerre Henriksen, PhD, Shionogi: Contractor|UTILITY therapeutics Ltd: Advisor/Consultant Christopher M. Longshaw, PhD, Shionogi: Employee Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Miki Takemura, n/a, Shionogi: Employee Yoshinori Yamano, PhD, Shionogi: Employee.
898. Development of Risk Score to Guide Therapy for Carbapenem-resistant Pathogens
Authors: Vogler Andrew J , Fairman Kathleen A , Mai Nikki , VanDenBerg Chad M , Huang Vanthida
Published: December 2022

Background

Carbapenem resistance is a major concern of the World Health Organization (WHO) and Centers for Disease Control (CDC). The mortality in carbapenem-resistant infection ranges from 26-44%. Delays in appropriate antibiotic therapy can lead to increased mortality and longer hospital stay. Studies have identified several risk factors associated with carbapenem resistance including mechanical ventilation, indwelling devices, recent invasive surgery, severity of illness, recent hospitalization, and prior antibiotic exposure. However, most of these studies include Enterobacterales and not Acinetobacter baumannii or Psuedomonas aeruginosa. Therefore, we aimed to identify risk factors associated with carbapenem resistance to all pathogen types and develop a risk scoring tool.

Methods

This was an observational nested case-control study of hospitalized patients from January 2016-2022. Risk factors were compared for patients with culture-confirmed carbapenem-resistant gram-negative (GN) organisms (CRO) vs culture-confirmed carbapenem-susceptible GN organisms (CSO). Using accumulated data and logistic regression backwards-stepwise analysis, a scoring tool was created with c-statistic validation performed on a 75% subsample.

Results

There were 1,020 CRO and 51,157 CSO patients identified. Patients were primarily female (70.6%) with a mean age of 61 years. The most common CRO site of infection was respiratory (47.1%) followed by urine (29.0%). CRO pathogens included Pseudomonas (66.6%), Acinetobacter (18.9%), and Enterobacterales (14.5%). Included risk factors in the final tool were age 46-79 years, male sex, prior admission, prior invasive procedure, prior antibiotic use, admission unit, APACHE II score, chronic diseases (cardiovascular, liver, renal, respiratory), infection site, and nosocomial infection (c-statistic, 0.879). A separate scoring tool was created to include pathogen type, once identified, improving the accuracy of the scoring tool (c-statistic, 0.941).

Conclusion

Utilizing obtainable risk factors, a straightforward scoring tool can be used to predict carbapenem resistance to, provide guidance for treatment decisions. Further validation of scoring tool is warranted.

Disclosures

All Authors: No reported disclosures.
903. Formulary Edits and Consistent Messaging for Unproven COVID-19 Therapeutics
Authors: Stephen Tyler , Tutino Alyssa , Bender Justin , Sageer Michelle , Chitre Mona , Louie Ted
Published: December 2022

Background

A challenge the healthcare system faced during the COVID-19 pandemic was ensuring appropriate use of therapeutics. Hydroxychloroquine (HCQ), azithromycin, and ivermectin are FDA-approved for rheumatic, antibacterial, and antiparasitic conditions, respectively. During the pandemic, these drugs were used for COVID-19 treatment, despite unproven benefit and lack of clinical guideline support. Payer-based formulary edits of these agents during the COVID-19 pandemic were reviewed to determine effectiveness in supporting appropriate use.

Methods

After local discovery of COVID-19 the University of Rochester Medical Center and a local payor in the upstate New York area, Excellus BlueCross BlueShield, disseminated education about the unproven role of these agents in treatment or prevention of COVID-19. In March 2020, May 2020 and February 2021, respectively, Excellus BCBS placed a quantity limit (QL) on prescriptions for HCQ, azithromycin and ivermectin and prior authorization (PA) for ivermectin in October 2021 for all formularies except Medicare. The QL for HCQ and azithromycin were in effect until December 2020. An exception process was available for individuals who required a higher quantity. Data was gathered retrospectively for claims and total drug utilization amongst Excellus BCBS members through February 2022.

Results

Use of HCQ increased by 56.5% prior to QL implementation. After HCQ QL was implemented, HCQ use returned to near pre-pandemic baseline, and most (88%) claims were processed. For azithromycin, after the QL limit was implemented, while overall usage dropped, most claims (77%) were processed. Prior to QL and PA, ivermectin usage quadrupled. Following implementation of the ivermectin QL, usage was stable and a minority (41%) of ivermectin claims were processed. The month that PA was implemented, usage dropped by 81%, and 9% of claims were processed.

Conclusion

Formulary edits resulted in returning use of HCQ to pre-pandemic levels despite an initial rise in use. The edits may have curtailed azithromycin use as well. A QL was associated with stabilization in ivermectin use but ultimately usage did not decrease until PA was required. Formulary edits consistent with local messaging appeared to help control use of unproven therapeutics for COVID-19.

Disclosures

Alyssa Tutino, PharmD, BCGP, Excellus BlueCross BlueShield: Salary Justin Bender, BS, Excellus BlueCross BlueShield: Salary Michelle Sageer, Pharm D, BCACP, Excellus BlueCross BlueShield: Salary Mona Chitre, PharmD, Excellus BlueCross BlueShield: Salary.
906. Impact of Accelerate Rapid Diagnostic Technology on Time to Optimal Antimicrobial Therapy in Gram Negative Bloodstream Infection
Authors: Jung Hye Lim , Jozefczyk Caroline , Faulkner-Fennell Carmen M , Shirley Rhett , Schrank John
Published: December 2022

Background

Previous studies at our institution evaluating rapid diagnostic testing (RDT) for blood culture identification (BCID) did not show significant differences in time to optimal antimicrobial therapy for Gram negative bloodstream infections (GNBSI). Recent studies of Accelerate Pheno® system (Accelerate-PS) for blood culture identification and susceptibility have shown significant reduction in time to optimal antimicrobial therapy. This study evaluated the impact of Accelerate-PS compared to BCID RDT on time to optimal antimicrobial therapy for GNBSI.

Methods

A single center, retrospective, cohort study included adult patients with GNBSI from February 2017 to January 2018 (pre-implementation) and February 2020 to January 2021 (post-implementation). The primary outcome was time to optimal antimicrobial therapy for GNBSI, defined as time from positive blood cultures to time patient received optimal antimicrobial therapy. Secondary outcomes include duration of therapy, rate of antimicrobial-related adverse effects, hospital length of stay, in-hospital mortality, and infection-related readmission.

Results

The final cohort included 190 patients in pre-implementation group and 179 patients in post-implementation group. Escherichia coli and Klebsiella species were the most common pathogens and urinary tract was the most common source of bacteremia in both groups. More patients in the pre-implementation group had congestive heart failure while more patients in the post-implementation group had peripheral vascular disease. Patients in the post-implementation group had higher Pitt bacteremia scores (1.05 vs. 1.37, P=0.017). Patients in the post-implementation group had significantly shorter time to optimal therapy (mean 60.62 hours vs. 20.17 hours, P< 0.001) and shorter duration of therapy (mean 366.56 vs 310.24 hours, P < 0.001) than in the pre-implementation group. There were no differences in mortality or readmission at 30-days.

Conclusion

The results of this study indicate that incorporation of Accelerate-PS into microbiology lab workflow significantly reduces time to optimal antimicrobial therapy for GNBSI. Rapid diagnostic testing is a vital component of a robust antimicrobial stewardship program.

Disclosures

John Schrank, MD, Gilead: Speaker's Bureau.
964. Physicians' acceptable treatment failure rates and interpretation of antibiogram for Gram-negative infections: A pilot survey study of infectious diseases specialists
Authors: Hasegawa Shinya , Perencevich Eli N , Dukes Kimberly , Goto Michihiko
Published: December 2022

Background

The recommendations of many clinical guidelines include an antibiogram as a key component when making empiric therapy decisions. However, little is known about how clinicians interpret antibiograms. We aim to characterize the threshold of the acceptable risk of selecting inappropriate antibiotics among clinicians through clinical case-based questionnaires.

Methods

We conducted an online survey of infectious diseases (ID) specialists at the University of Iowa, as an internal pilot study. We created realistic clinical case scenarios and asked clinicians to provide the desired minimum percentage of susceptible isolates on an antibiogram for them to feel comfortable with selecting that agent for empiric therapy. We included four scenarios in the questionnaire: i) a patient with urinary tract infection (UTI) in an outpatient setting, ii) a patient with UTI in an inpatient setting, iii) a patient with Gram-negative rod bloodstream infection (GNR-BSI) in an intensive care unit (ICU) setting, iv) a patient with GNR-BSI in a non-ICU setting.

Results

Of the 16 of 26 providers (62%) who responded, 15 were considered effective responses. ID Physicians reported wide ranges in thresholds of minimum percentage to feel comfortable with prescribing a hypothetical antibiotic and higher thresholds for patients with more severe illnesses (outpatient with UTI: 85% [range: 75-100%]; inpatient with UTI: 95% [range: 50-99%]; inpatient with GNR-BSI in non-ICU settings: 90% [range: 80-95%]; inpatient with GNR-BSI in ICU: 95% [range: 88-100%]) (Figure 1). Figure 1.The distribution of physicians’ acceptable likelihood of susceptibility in four realistic clinical case-scenarios.

Abbreviations: GNR-BSI, Gram-negative rod bloodstream infection; ICU, intensive care unit; UTI, urinary tract infection.

Conclusion

There were wide ranges in thresholds for interpretation of antibiogram among frontline clinicians, especially for less severe infections. Understanding physicians’ antibiogram usage can be helpful to determine how and if antibiogram guides clinicians toward more appropriate empiric therapy decisions. As this was a preliminary study, we plan to conduct a study with a larger sample size to better characterize the use of antibiogram among clinicians from diverse practice settings.

Disclosures

Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.
985. Practice Patterns of Antimicrobial Suppression Therapy in Total Knee Arthroplasty Infections
Authors: Lastinger Allison , Scribner Jacob
Published: December 2022

Background

There are no current established guidelines for the role of antimicrobial suppression therapy in management of prosthetic joint infection (PJI). In 2013, the IDSA provided initial treatment guidelines for PJI but did not address suppressive therapy. The guidelines do not address suppressive therapy beyond the initial 4-6 weeks for non-staphylococcal infections nor do they address suppressive therapy after 3-6 months of treatment for Staphylococcal infections. Practitioners must delicately balance the risk of PJI recurrence and the negative effects of continued antibiotic therapy including toxicity and resistance. In this study, we surveyed Infectious Disease providers to better understand their antimicrobial suppression practice patterns in different clinical scenarios.

Methods

We surveyed Infectious Disease providers across the United States from April 2022 to May 2022. We received 78 unique response from 31 different states. Basic demographic data was obtained. Providers presented six multiple choice clinical scenarios and were asked if they would start suppressive therapy and the duration of suppressive therapy.

Results

The preliminary data revealed that practice patterns vary greatly amongst providers in the management of antibiotic suppressive therapy in PJI. Of the 6 scenarios, only half had greater than 50% consensus (50.6%, 51.3% and 70.1%). Scenario 1 involved a patient who underwent a single stage revision. It was of particular interest as 51.3% of providers indicated they would stop antimicrobial therapy and 48.7% indicated they would extend antimicrobial therapy with 25.6% electing for lifelong suppressive therapy.

Conclusion

Practice patterns for antimicrobial suppression therapy in knee PJI varies significantly among providers. Even with IDSA guidelines addressing Staphylococcal PJI, the practice patterns among infectious diseases providers still varied greatly especially with regards to single stage revisions. Additional randomized controlled trials examining the best way to manage antimicrobial suppression in PJI would be helpful, and would allow for development of evidence-based guidelines. We also plan to survey orthopedic surgeons using the same clinical scenarios to see if there is a difference in management styles.

Disclosures

All Authors: No reported disclosures.
998. Clinical Outcomes and Cost Savings of Dalbavancin Use in OPAT: Focus on Complicated Staphylococcus aureus Infections
Authors: Alexander Bryan T , Miller Molly M , LeMaster Melissa , Bergman Scott J , Van Schooneveld Trevor C , Cortes-Penfield Nicolas W
Published: December 2022

Background

The practical and financial benefits of long-acting glycopeptides are increasingly recognized, and their efficacy is becoming better established for a variety of indications. Dalbavancin use as primary therapy for complicated Staphylococcus aureus (cSA) infections, however, has only been described in small case series to this point.

Methods

This retrospective review identified patients prescribed dalbavancin for any indication and followed by the Nebraska Medicine OPAT team since program implementation (4/1/19 - 4/30/22). Patients in the cSA infection subgroup were defined by need for >2 weeks of treatment for a Staphylococcus aureus infection involving bacteremia. Dalbavancin as primary therapy for cSA was defined as initiation of dalbavancin within the first 10 days of antibiotic therapy and continued through the end of treatment. The primary clinical outcome was 30-day readmission rate (both infection-related and not infection-related).

Results

A total of 66 patients were prescribed dalbavancin for treatment of any infection (Table 1), with an all-cause 30-day readmission rate of 13.6% (9 of 66); only two of these were infection-related (3%). Updating a prior institutional analysis, use of dalbavancin led to the avoidance of 506 planned inpatient days per year on average and $1,113,000 in yearly inpatient costs. Dalbavancin was utilized for primary therapy of cSA in 16 patients, of whom only one (6.3%) had a 30-day readmission, due to progression of cSA vertebral osteomyelitis-discitis. Table 1:Characteristics of the Dalbavancin Cohort

Conclusion

In both overall and cSA subgroup analysis, OPAT use of dalbavancin was associated with low readmission rates. This study is the largest to date suggesting favorable clinical outcomes with dalbavancin as primary therapy for cSA infections; others have reported few of these patients or utilized dalbavancin exclusively as consolidation therapy following significant lead-in with other antimicrobials. The enrolling Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia study (DOTS; NCT04775953) is anticipated to provide randomized controlled data evaluating this approach. Discharge facilitation utilizing dalbavancin contributed significantly to OPAT program cost justification and resources to support team expansion.

Disclosures

Bryan T. Alexander, PharmD, BCIDP, AAHIVP, Astellas Pharma: Advisor/Consultant Scott J. Bergman, PharmD, BCIDP, FCCP, FIDSA, Merck & Co., Inc: Advisor/Consultant|Merck & Co., Inc: Grant/Research Support|Merck & Co., Inc: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Trevor C. Van Schooneveld, MD, bioMerieux: Advisor/Consultant|bioMerieux: Grant/Research Support|Insmed: Grant/Research Support|Merck: Grant/Research Support|Thermo-Fischer: Advisor/Consultant.
1020. The Impact of COVID-19 on Outpatient Intravenous Antimicrobial Therapy (OPAT) at an Academic Medical Center
Authors: Goteti Ravitej , Monday Lea M , Weinmann Allison J
Published: December 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic dramatically affected the delivery of healthcare. Patients discharged on outpatient parenteral antibiotic therapy (OPAT) require clinic follow-up and laboratory monitoring which is a logistical challenge to standardize across discharge locations. We sought to investigate how COVID-19 impacted patients discharged with OPAT at an academic medical center. Primary objectives included 30-day readmission rates and ID clinic follow-up before and during COVID-19. Secondary outcomes included whether suspected infection type, antimicrobial selection and discharge location differed between the two cohorts.

Baseline Patient Characteristics & Outcomes between pre-COVID-19 and COVID-19 cohorts

Methods

Patients discharged on OPAT were evaluated in two 3-month cohorts from Oct-Dec 2019 (pre-COVID-19) and compared to Oct-Dec 2020 (COVID)-19. Demographics, infection type, discharge location, therapy characteristics, and outcomes were compared retrospectively (Fig 1). Statistical analysis was performed using Chi-square and Wilcoxon rank-Sum test with p< 0.05 considered statistically significant.

Suspected Infectious Source among the two cohorts

Results

A total of 316 pre-COVID patients were discharged with OPAT compared to 263 COVID-19 patients. Table 1 shows the comparison of OPAT characteristics between 2019 and 2020. There were significantly more patients discharged home and fewer patients discharged to facilities in COVID-19 group(p=0.001 and p=0.011, respectively). LOS, ID clinic follow-up, and 30-day readmission did not differ between groups. Reasons for readmission were similar (Fig 1). Antimicrobial prescribing was generally similar except for more vancomycin prescribed in the COVID-19 group (12.5% versus 7.3%, p=0.033). Suspected source of infection did not differ between groups (Fig 2), nor did isolation of pseudomonas, MRSA, or drug resistant organisms (Table 2).

Conclusion

Sources of infection and antimicrobial classes were generally similar despite decrease in elective procedures during a COVID-19 related winter surge. Rates of readmission and clinic follow did not differ, however, patients discharged with OPAT post-COVID were more likely to go home versus a facility. Further analysis of this difference may help determine best practices to facilitate improved monitoring and clinic follow-up among OPAT patients.

Disclosures

All Authors: No reported disclosures.
1022. The Role of Baseline Body Temperature in Neutropenic Fever
Authors: Corsi Anthony J , Searles Madison , Lupone Christina , Geneva Ivayla I
Published: December 2022

Background

The management of neutropenic fever patients is challenging – from identification to diagnosis to treatment. We hypothesize that patients’ individual baseline body temperature provides diagnostic and prognostic value.

Methods

This is an analysis of 92 adult patients admitted for neutropenic fever to a tertiary medical center over 1 year period. We modelled the length of stay and the ability to find a definitive diagnosis using the change in body temperature from each patient’s outpatient baseline, the neutropenia level and overall patient acuity on admission, persistence of fever over 48-72 hours, and age. All temperatures were standardized to oral. Refer to Table 1 for the inclusion and exclusion criteria and statistical methods. Table 1.Inclusion and exclusion criteria and statistical methods.

Results

Refer to Tables 2 and 3 for demographics and descriptive statistics of temperature readings, to Table 4 for advanced statistical analyses. Importantly, the average baseline body temperature was at 36.7C; the average fever on admission was at 38.1C; based on the ≥ 38C cutoff, only 24% of patients had persistent fever over 48-72 hours but based on personalized cutoffs at > 2 standard deviations (SDs) or > 3 SDs above their outpatient baseline, 54% and 34% had persistent fever, respectively; the etiology of fever was identified in 48% of patients, all of which constituted infections; our multiple regression model demonstrated that a longer length of stay (LOS) of ≥ 4 days was predicted by larger deviation from baseline body temperature at admission and independently by fever persistence, after correcting for age, neutropenia level, and need for ICU level of care on admission. A similar model could not predict the ability to identify a fever-explaining diagnosis.

Conclusion

Given the average outpatient baseline body temperature of 36.7 +/- 0.3C, at 2 standard deviations (SDs) above this baseline, only 3% of patients would be at the 38C cutoff for fever, at 3 SDs, it would be 20%, thus rendering the standard 38C cutoff too high to be useful in identifying many neutropenic fever cases and supporting the use of personalized cutoffs based on patient’s baseline temperature. Further, consideration of the specific deviation from patients’ baseline body temperature could serve as a predictor for hospital LOS in patients admitted with neutropenic fever.

Disclosures

All Authors: No reported disclosures.
1027. Cerebrospinal Fluid Findings of Solid Organ Transplant Recipients with West Nile Virus Infections
Authors: Abbas Anum , Sikyta Adia , Florescu Diana F
Published: December 2022

Background

In the solid organ transplant (SOT) population, West Nile virus (WNV) neuroinvasive disease can have significant morbidity and mortality. We evaluated cerebrospinal fluid (CSF) findings in neuroinvasive WNv infections among SOT recipients.

Methods

We retrospectively reviewed medical records of all SOT recipients at our institution with WNv neuroinvasive disease (meningitis, encephalitis, meningo-encephalitis) from 2010 to 2018. Descriptive statistics were examined on key variables.

Results

Eight transplant patients with mean age 54.47 years (12.79) were included: 5 kidney transplants, 1 in each kidney-pancreas, liver and lung transplants. Median time from transplant to infection was 49.8 months (2.7-175.4) and mean time-to-diagnosis 2 days (1.31) . On admission, mean total CSF WBC count was 134.57 cells/mm3 (150.82), mean lymphocyte count 56.29 cells/mm3 (32.32), mean neutrophil count 27.14 cells/mm3 (34.34), and mean CSF protein 95.4 mg/dL (40.52mg/dL). West Nile virus CSF IgG at the time of diagnosis was negative in 7 patients, and not performed on 1 patient. WNv diagnosis is depicted below.

Serum and CSF WNV Antibodies in Neuroinvasive Disease in SOT Recipients

WNV CSF and serum IgG was negative at the time of diagnosis in 7/8 patients. Initial CSF IgM was positive in 3 out of 7 patients.

Conclusion

WNv infection produces a CSF pleocytosis with neutrophilic predominance, though we noted more lymphocytic predominance among SOT recipients. CSF IgM and IgG are important diagnostics in neuroinvasive WNv.

Disclosures

Diana F. Florescu, MD, AlloVir: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|NobelPharma: Grant/Research Support|Novavax: Grant/Research Support|Regeneron: Grant/Research Support|SymBio: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support.
1087. COVID-19 in Solid Organ Transplant Recipients: A Single Transplant Center Experience
Authors: Sabunwala Suhel A , Cornelius Tuhina , Aslam Sadaf , Alrabaa Sally
Published: December 2022

Background

COVID-19 disease became a global health care crisis and was declared pandemic by WHO in March 2020. Some studies have indicated that Solid Organ Transplant (SOT) patients may have increased morbidity and mortality while others showed no difference. Our study aims to investigate patients’ characteristics, disease course, management of COVID-19 and outcomes in our SOT patient population.

Methods

We conducted a retrospective cohort study of all consecutive SOT recipients who were admitted to our transplant center from March 2020 to April 2021 with COVID-19 infection. Data was collected from the electronic medical records after receiving Institutional Review Board approval. Table 1Study Population Demographics

Figure 1 Age and Gender distribution of the study population

Results

A total of 135 patients met inclusion criteria. Average age at the time of COVID-19 diagnosis was 56.38±12.93 years. Majority of the patients (54%) were kidney transplant recipients. Out of the total, 28% of the patients required supplemental oxygen and 14% required intensive care unit (ICU) care. A total of 12 patients (9%) required intubation and mechanical ventilation. 21% of the patients were treated with Remdesivir and 30% met criteria for the use of corticosteroids. Unfortunately, 11 patients (8%) of the patients died from COVID-19 infection and its complications. Of those 11 patients 5 were treated with Remdesivir and 10 were treated Corticosteroids. None of the patients met the criteria for ECMO (Extra Corporeal Membrane Oxygenation). Figure 2Study Population Distribution of the Types of Transplants at time of COVID-19 infection

Figure 3 Outcomes - Admission to ICU and Mortality

Figure 4 COVID-19 Therapies and Outcomes in the SOT Recipients

Conclusion

Our study showed a higher mortality rate in SOT patients compared to general population. Treatment with Remdesivir and Corticosteroids improved the overall mortality rate but had no benefit in patients with critical illness requiring ICU level care. COVID vaccination significantly improved the outcome, and the major limitation of the study was COVID vaccination information was not included since the study was initiated prior to introduction of vaccines. More studies with larger sample size and vaccine data need to be conducted to accurately determine the outcome of COVID-19 infection in this patient population.

Disclosures

All Authors: No reported disclosures.
Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients
Authors: Dhakal Santosh , Yu Tong , Yin Anna , Pisanic Nora , Demko Zoe O , Antar Annukka A R , Cox Andrea L , Heaney Christopher D , Manabe Yukari C , Klein Sabra L
Published: December 2022

Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance.
Against Realism
Authors: Panaccio Claude
Published: December 2022

Chapter 2 first spells out Ockham’s main arguments against realism with respect to universals, that is, arguments from numerical unity, from ontological separability, from mereology (the theory of part-whole relations), and from the principle of the indiscernibility of identicals. Within these arguments, specific advantages and concerns are addressed, including the theological and philosophical aspects of separability and the adherence to Aristotelian notions of individual entities in opposition to Platonic notions of participation and Forms. It then presents Ockham’s critique of realism with respect to relations and his arguments from infinite regress and from the famous Razor principle. The chapter finally discusses Ockham’s critique of realism with respect to quantities, that is, extension and numbers.
Induction, Objects, and the Uniformity of Nature
Authors: Boyle Deborah
Published: December 2022

This chapter examines the final two points that Shepherd makes in her rebuttal of Humean causation: that nature is uniform and cannot change its course and that when we make causal inferences, reason rather than custom or habit is our guide. The chapter begins with an explanation of Shepherd’s account of objects and qualities, as well as of the way names and definitions apply to objects, and then examines how her account of effects as qualities that are necessarily connected with the objects that cause them grounds her claim that nature is uniform. The chapter also explores how Shepherd thinks we can make good causal inferences in ordinary life. It ends with discussions of Shepherd’s appeal to Locke (to show that Hume incorrectly appropriated Locke’s views to bolster his own position) and of her objections to views espoused by Scottish philosopher Thomas Brown.
Mind and Body
Authors: Boyle Deborah
Published: December 2022

This chapter examines Shepherd’s account of the connection between the mind—which she takes to be immaterial—and the material, external world and, more specifically, how she conceives of the relationship between mind and body in a human being. It explicates her terms ‘mind,’ ‘soul,’ and ‘self,’ arguing that Shepherd works with a narrower and a broader sense of all three terms. After exploring her argument for how each person knows that their own mind exists, the chapter considers her accounts of one’s knowledge of other minds, her claims about personal identity over time, how she might individuate minds, and how she accounts for the relationship of mind to the human body.
My Own Backyard
Authors: Bunch Ryan
Published: December 2022

The MGM film The Wizard of Oz (1939) adapts L. Frank Baum’s book to the conventions of the classical Hollywood musical. As collaborative art, its middle-American values are in dialogue with its subcultural sensibilities, contributed by queer, Jewish, and other minority collaborators. Its aesthetics involve an interplay of child-like make-believe, vaudeville, and the integrated musical. “Over the Rainbow” is a model of the musical theater “I want” song, expressing an American utopian dream that appeals to mainstream and marginal audiences. In their journey through Oz, Dorothy and her traveling companions practice the gestures of musical theater in the conscious performance of American identities. Audiences receive the film earnestly or as camp, decoding its cultural meanings about home and Oz while rewatching and reenacting the film.
The Intimate State
Authors: Chettiar Teri
Published: December 2022

The Intimate State tells the story of how intimate relationships acquired political and cultural resonance in Britain during the transformative decades following WWII. Long before the late-1960s feminist proclamation, “the personal is political,” private family life attained profound political importance through the work of prominent psychiatrists, psychologists, social scientists, politicians, and social reformers in Britain. During the early decades of the Cold War, a new generation of self-styled relationship experts made the compelling case that emotional “health” was forged within the intimate space of the loving, nuclear family and formed the bedrock of responsible democratic citizenship. The new emphasis on emotional relationships transformed British politics as the emerging welfare state assumed responsibility for protecting citizens’ emotional wellbeing. But many groups either oppressed by or excluded from this ideal intimate heteronormative family mobilized against this new emotional vision of the modern political order. Movements advocating for the rights of women, queer people, and adolescents seeking a greater range of political rights focused on the serious emotional harms caused by being either excessively trapped within or excluded from the idealized nuclear family. By the 1970s, such efforts to claim a more inclusive model of intimacy that provided space for transformed gender roles, non-monogamous romance, non-traditional families, and friendship-based political activism, became the basis for both socio-political reform and new models of healthy emotional life. This book traces both the emergence of a new vision of social modernity, focused on emotion, in Britain after 1945 and the exclusions and resistance that repeatedly threatened to upend it.
Introduction
Authors: Arban Erika
Published: December 2022

The aim of the Introduction is to present the purpose and main themes discussed in the edited volume Cities in Federal Constitutional Theory. The book takes as its point of departure the importance of cities and urbanization in recent decades. Because of their unique features, cities have become sites of conflict and innovation, solidarity and cohabitation of diverse people, thus expressing tensions between diversity and social cohesion. While in the past decades an important body of scholarship has blossomed in the social sciences exploring the multifaceted reality of cities through different epistemological lenses, this intellectual production has not been matched by an equally vibrant scholarship in (comparative) constitutional law and federalism theory, where the city as an independent subject of scholarly theorization and investigation has remained largely neglected. There is thus a need to develop a thicker theoretical framework in which the debate on the role and place of cities in constitutional law and federalism can be situated. As explained in the Introduction, the volume thus offers a fresh theoretical account of cities as federalism subjects. All chapters introduce the city as a constitutional unit of analysis in federalism, and directly address the relationship between cities, federalism, and localism (or subsidiarity).
Cities in Federal Systems
Authors: Hirschl Ran
Published: December 2022

This chapter considers two questions concerning the constitutional status of cities in federal systems. First, what is the significance of the federal/unitary distinction in determining the constitutional status of cities? It is suggested, in a nutshell, that the evidence is mixed and inconclusive, and that ultimately the Global North/Global South distinction, and in particular the tendency towards stagnation in the former versus a tendency towards innovation in the latter appears more significant than the federal/unitary dimension in assessing the constitutional status of cities. Second, what do national constitutions say about the urban/rural divide—one of the most significant factors in contemporary politics—and how significant is the federal/unitary dimension in addressing that challenge? Here too, the data suggest that despite the central place of subsidiarity and local autonomy in federalism theory, the constitutions of federal countries are no more likely than the constitutions of unitary states to commit to addressing the urban/rural divide. This in turn raises the possibility that federal constitutional theory’s preoccupation with traditional subnational unit boundaries may in fact lead to conceptual rigidity and institutional path dependence when it comes to addressing new spatial challenges such as urban agglomeration, the rise of megacities, or the increasing salience of the urban/rural divide. It may also suggest that whether federalism is favourable or unfavourable to cities is merely an auxiliary question to other more pertinent factors such as the North/South distinction, constitutional ‘newness’ or malleability, and concerted political will to constitutionally strengthen cities.
Constitutional Theory, Federalism, and Cities
Authors: Kong Hoi L
Published: December 2022

This chapter will argue that cities should be understood in light of a specific constitutional theory of federalism. Section I argues for a particular version of republican theory that justifies constitutionally entrenching a division of powers between territorially defined jurisdictions. Section II argues that cities and their residents have interests and characteristics that can be described and understood in the terms of this republican theory. Section III argues that according to a general theory of constitutional change, the Canadian Constitution should be amended to entrench the status of cities. The chapter concludes by showing how entrenchment in the Canadian context serves republican ends and by offering policy prescriptions for achieving entrenchment. This chapter contributes to an emerging theoretical debate about whether federations should constitutionally entrench the jurisdictional status of their cities. In the context of this debate, conceptual and normative arguments are advanced. Some arguments are conceptual, in that they aim to show how the reasons supporting entrenchment in this context are consistent with the reasons supporting entrenchment in federations, generally. Other arguments are normative, in that they advance republican claims that are available to individual city dwellers, as well as to cities that have distinct cultural identities.
The Self-legitimation of Global Governance Institutions
Authors: Stappert Nora , Gregoratti Catia
Published: December 2022

This chapter compares the normative justifications that global governance institutions (GGIs) provide in their public statements in order to legitimate themselves and through which they give reasons for their right to rule. Drawing on a comprehensive content analysis of annual reports published by nine GGIs between 1985 and 2017, the chapter analyzes the normative underpinnings of legitimation regarding the core purpose, procedures, and performance of GGIs. Moreover, it explores whether these justifications have been subject to change. The chapter shows that the main purpose that GGIs communicated has stayed remarkably stable over time. It emphasizes the central, but at times overlooked, role of legality in purpose-based normative justifications. Justifications concerning GGI procedures and performance, in turn, were more amenable to change. The chapter demonstrates that economic and regional GGIs more frequently relied on technocratic norms, while multistakeholder institutions were more likely to refer to democratic norms. In the case of GGIs with a comparatively high level of authority, such self-legitimation invoking democratic norms increased following periods of contestation of the institution’s authority. Such an increase, however, was typically only temporary.
Justifying Delegitimation
Authors: Gregoratti Catia , Stappert Nora , Söderbaum Fredrik
Published: December 2022

This chapter focuses on delegitimation and asks how far the institutional set-up of global governance institutions determines which normative justifications are raised to challenge their legitimacy. Specifically, it compares the normative justifications used by African states and civil society organizations to delegitimate the African Union (AU), the International Criminal Court (ICC), and the Kimberley Process. Such a focus not only responds to calls for Global International Relations, but also explores regional dynamics in delegitimation practices that are often overlooked in extant literature on legitimacy in global governance. The chapter draws on a range of statements made by African states and civil society organizations, additional documents, and qualitative interviews, enabling the comparative case studies to probe key institutionalist and structuralist theoretical expectations. It asks whether differing institutional set-ups or a shared history of colonialism results in continuing power hierarchies that shape normative justifications of delegitimation practices. The chapter highlights the importance of underlying power hierarchies for delegitimation practices, as it finds support for structuralist expectations across the three cases. However, it also outlines important synergies between institutionalist and structuralist expectations.