bluuebunny/crossref_metadata_2025_split huggingface dataset:
444. Effect of multidisciplinary management of CKD on proteinuria in people with HIV
Authors: Bennani Yussef , Richey Lauren , Hasan Hira , Perez Annalisa 
Published: December 2022

Abstract

Background
Optimizing management of chronic kidney disease in people with HIV has become a more pressing priority both to minimize morbidity and preserve HIV antiretroviral options. Part of standard care is employing the beneficial effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) in patients with clinically significant proteinuria. Our analysis looks at the proteinuria outcomes of PWH with CKD co-managed by a multidisciplinary team of infectious disease and nephrology physicians nested in a Ryan White-funded clinic in New Orleans.

Methods
Patients with HIV and at least grade 3 CKD or with significant proteinuria were referred to the multidisciplinary clinic. Patients were evaluated by an HIV specialist and nephrologist at the initial visit for a jointly developed management plan. Renal function and proteinuria were measured at baseline and longitudinally per standard of care. Change in proteinuria and GFR over time were calculated. Patients were also assessed for whether they were prescribed ACE/ARB therapy, if appropriate. Patients included in this analysis were evaluated between January 1, 2021 and March 31, 2022.

Results
During the analysis period, 46 patients with at least CKD 3 or proteinuria were evaluated. 35 patients were Black non-Hispanic, 9 were White non-Hispanic, and 2 were Hispanic. 39 were male, and 7 were female. 35 had a previous diagnosis of hypertension, and 10 had diabetes mellitus. Of the 42 with a recorded baseline urine protein measurement, 24 were found to have clinically significant proteinuria. Of those with proteinuria, 16 were on an ACE or ARB at their baseline evaluation. 20 were on ACE/ARB’s the end of the analysis period (p=0.058). Average baseline proteinuria was 1,158 mg/g, while average final was 938 mg/g, which was less but not significantly different (p=0.54). Mean baseline GFR was not significantly different from final GFR (50.8 mL/min vs 50.5 mL/min, p=0.67).

Conclusion
A multidisciplinary model of managing CKD among people with HIV may improve adherence with management guidelines and limit progression of proteinuria and decrease in GFR. In general, the natural history of kidney disease with proteinuria is to worsen over time, so while not significant, proteinuria in this cohort did decrease over time

Disclosures
All Authors: No reported disclosures.
539. Impact of a Rapid Diagnostic Assay for the Detection of Bacterial and Viral Agents on Antimicrobial use in Critically Ill Patients with Pneumonia
Authors: Sielatchom Noubissie Lionel K , Ciochetto Zachary , Willey Emily , Olexia Deanna , Wrzesinski Magdalena , Buchan Blake W , Njeri Wainaina J , Gibble Allison 
Published: December 2022

Abstract

Background
Conventional diagnostic methods for pneumonia have a long turnaround time, and a pathogen is isolated in only 33% of cases. As a result, empiric therapy with broad-spectrum antimicrobials often becomes definitive therapy. Rapid molecular diagnostics paired with antimicrobial stewardship intervention have the potential to improve outcomes for patients with lower respiratory tract infections (LRTIs). However, data to support this hypothesis are scarce. This study examined the influence of a rapid multiplex polymerase-chain-reaction (PCR) test on antimicrobial use in critically ill patients with LRTIs.

Methods
This single-center study consisted of pre-implementation (PrIP, December 1, 2018, to February 28, 2019) and post-implementation periods (PoIP, December 1, 2021, to February 28, 2022). Both groups included intensive-care unit (ICU) patients with respiratory cultures from bronchoalveolar lavage (BAL), mini-BAL, or tracheal aspirates. Interventions during the PoIP included concurrent testing of specimens with the BioFire® Pneumonia Panel and clinical decision support tools to streamline treatment recommendations from ICU pharmacists. The primary outcome was the difference in time to optimal therapy (TTOT). Secondary outcomes included time to effective therapy (TTET) and duration of therapy (DOT) for antipseudomonal and anti-MRSA agents.

Results
A total of 163 patients were included (n = 80, PrIP; n = 83, PoIP). The mean age was 57 + 16 years, and medical ICU patients accounted for 60% (n = 97) of cases. The median APACHE II score was the only significant baseline difference between the two arms (22 vs. 18, interquartile range [IQR] 16, 28 vs. 12, 25, p = 0.01). The median TTOT was 38 hours in the PrIP and 21 hours in the PoIP (p &lt; 0.001). TTET was 5.7 hours in the PrIP and 4.9 hours in the PoIP (p = 0.106). The median DOT for antipseudomonal agents decreased by 52% (4.4 days in the PrIP and 2.1 days in the PoIP, p &lt; 0.001), and anti-MRSA agent DOT was 53% shorter in the PoIP (1.9 days vs. 0.9 days, p &lt; 0.001).

Conclusion
Implementation of a rapid multiplex PCR panel for lower respiratory-tract pathogens significantly reduced the time to optimal therapy in critically ill patients with pneumonia. Clinically meaningful reductions in anti-MRSA and anti-pseudomonal agent duration were also noted.

Disclosures
Blake W. Buchan, PhD, Accelerate: Advisor/Consultant|Accelerate: Honoraria|BioFire: Honoraria|ChromaCode: Advisor/Consultant|ChromaCode: Honoraria|Pattern: Advisor/Consultant|Pattern: Honoraria.
600. Cefiderocol is Not Sequestered in an Ex vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit
Authors: Berry Angela V , Conelius Allison M , Gluck Jason A , Nicolau David P , Kuti Joseph L 
Published: December 2022

Abstract

Background
ECMO is widely used in critically-ill patients that require respiratory and/or cardiac support, but may affect drug exposure by altering pharmacokinetics within patients or sequestering drugs in the circuit. Cefiderocol, a siderophore antibiotic with activity against multi-drug resistant gram-negative bacteria, may be used to treat serious infections in critically-ill patients supported by ECMO. Limited data are available to guide dosing in this population. Herein, we determined the loss of cefiderocol through an ex vivo ECMO circuit.

Methods
A closed-loop ECMO circuit prepared with a Quadrox-i adult oxygenator and primed with Isolyte S was used during all experiments. Fresh whole blood collected from healthy volunteers was pooled, injected to replace priming fluid, and circulated at 4.5 L/min at 37° C. Cefiderocol was administered into the circuit at 0h to obtain peak plasma concentrations of ∼89.7 mg/L. A pre-oxygenator blood sample was taken at 0h to confirm baseline concentration. Post-oxygenator blood samples were collected between 0-24h to determine loss of cefiderocol in the circuit. A control jar of the same pooled matrix spiked with cefiderocol was maintained at 37° C for comparison. Each ECMO/control experiment was performed in triplicate. A general linear model was constructed to compare the rate of loss between the ECMO circuit and controls.

Results
Baseline cefiderocol concentrations in the ECMO circuit and control jar ranged from 51.7-91.8 mg/L and 67.7-100.5 mg/L, respectively. At 0h, the difference in pre- vs post-oxygenator concentration was -4 ± 4% (range: 0-7%). After 24h, cefiderocol % reduction was similar between the ECMO circuits and controls (50% ± 13 vs 50% ± 9, p=1.0). The degradation rate of cefiderocol followed a zero order process and did not differ significantly between the circuit and control (slope: -0.0186 ± 0.0052 vs -0.0201 ± 0.0039, p=0.786).

Conclusion
Cefiderocol was not sequestered in an ex vivo ECMO circuit studied with an adult oxygenator, suggesting insignificant removal from the circuit can be expected. Pharmacokinetic studies in critically ill patients supported by ECMO are warranted to determine final dosing recommendations in this population.

Disclosures
David P. Nicolau, PharmD, Shionogi: Grant/Research Support Joseph L. Kuti, PharmD, Abbvie: Honoraria|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Contrafect: Grant/Research Support|Entasis: Grant/Research Support|Merck and Co: Grant/Research Support|Roche Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Summit: Grant/Research Support.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.