bluuebunny/crossref_metadata_2025_split huggingface dataset:
118. Rapid Uptake of 2014 ACIP Pneumococcal Vaccination Recommendations among Adults Aged 65 or Higher at the Veterans Health Administration
Authors: Kakiuchi Satoshi , Hasegawa Shinya , Suzuki Hiroyuki , Goto Michihiko 
Published: December 2022

Abstract

Background
Vaccination of the 13-valent pneumococcal conjugate vaccine (PCV13) for adults 65 years and older was recommended by the Advisory Committee on Immunization Practices (ACIP) in 2014 until it was withdrawn in 2019. While estimated overall vaccination coverage rates with both vaccines at ∼30% were previously reported using data from surveys or Medicare claims, it is unclear how rapidly the uptake of this ACIP recommendation occurred. We aimed to describe the uptake of the ACIP among the Veterans Health Administration (VHA) population.

Methods
We conducted a retrospective cohort study of patients who were at 65 years or older in October 2014 who were registered in primary care of VHA. The study period was from October 2014 to November 2019. We obtained data on the first PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination and dropout from primary care follow-up due to death and termination of primary care relationship from the VHA Corporate Data Warehouse. We calculated the monthly proportion of PCV13 and PPSV23 vaccination among primary care follow-up patients in VHA.

Results
We enrolled 2,166,173 patients at the beginning of the study period (median age: 73 (interquartile range: 68–81)), and at the end of the study period, 30% (645,975) were dropout due to death. The numbers of patients who had at least one PCV13 and PPSV23 vaccination at the beginning of the study period were 17,718 (0.8%) and 934,836 (43.2%), respectively. Of the PCV13 used during the study period, 78.4% were administered in the first two years (Figure 1). At the end of the study period, 50.3% of the follow-up patients had been vaccinated with PCV13 and 53.3% with PPSV23 (Figure 2). 55.3% of patients received at least one dose of any vaccine, and 48.2% received both. Figure 1.Administered dose of first PCV13 and PPSV23 among the study populationFigure 2.The proportion of vaccination coverage among the study population

Conclusion
At the VHA, there was a very rapid uptake of 2014 ACIP pneumococcal vaccination recommendations in the first two years, followed by a steady increase. At the end of the study period, the VHA achieved comparable or higher vaccination coverage in this population with both PCV13 and PPSV23 than the previously reported Medicare population. Further studies are needed to elucidate factors contributing to this rapid uptake and improve the implementation of future vaccine recommendations.

Disclosures
Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.
139. Development of cefiderocol resistance in an Enterobacter hormaechei strain following prolonged antibiotic exposure
Authors: Medernach Rachel , Moore William J , Nozick Sophia , Alamri Maha M , Kling Kendall , Ison Michael G , Chao Qi , Bachta Kelly E R , Rhodes Nathaniel J , Ozer Egon A , Hauser Alan R 
Published: December 2022

Abstract

Background
Cefiderocol (FDC) is a novel antimicrobial agent used for multi-drug resistant Gram-negative pathogens. To date, reports of mutations in β-lactamase and siderophore complex genes have been described and may contribute to FDC resistance. This case describes a New Dehli metallo-β-lactamase (NDM)-producing strain of Enterobacter hormaechei that developed FDC resistance following antibiotic exposure.

Methods
Serial respiratory and blood cultures were collected from a lung transplant recipient throughout 72 days of hospitalization. Confirmatory susceptibility and combination minimal inhibitory concentration (MIC) testing were performed using broth dilution and E-test assays. Short-read sequencing libraries were prepared using a seqWell plexWell 96 kit, and whole-genome sequencing was performed using the Illumina NovaSeq platform. Reads from the sample genomes were aligned to the chromosome and three plasmid sequences of reference genome ENCL48880.

Results
Four serial respiratory E. hormaechei isolates and one blood isolate were evaluated. Although initial isolates were susceptible to FDC (MICs 1-2 µg/mL), two respiratory isolates cultured after 41 days of FDC therapy had MICs of 128 µg/mL. The blood isolate remained FDC susceptible despite respiratory resistance. The combination of ceftazidime/avibactam and aztreonam was determined to be active via synergy MIC testing in all isolates, and aztreonam therapeutic drug monitoring confirmed an adequate dosing strategy. Whole-genome sequencing revealed no nonsynonymous single nucleotide variants (SNVs) within the chromosomes but identified a deletion of a large urease island in the resistant isolates. In four of the five isolates, a plasmid (p48880_mcr) was identified and analyzed for possible contributions to FDC resistance.
Enterobacter Isolate Assemblies
This figure demonstrates genomic assemblies from the five Enterobacter clinical isolates, noting an absence of sequence from ECResp2.

Conclusion
This case demonstrates development of FDC resistance in E. hormaechei isolates during a 41 day course of FDC therapy. Possible causes of resistance include a large chromosomal deletion and plasmid alleles, demonstrating a potential novel mechanism for FDC resistance. Partnering molecular testing and enhanced antimicrobial stewardship should be encouraged to optimize selection of regimens and durations to prevent resistance to FDC.

Disclosures
Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant Nathaniel J. Rhodes, PharmD, MSc, American Academy of Colleges of Pharmacy: Grant/Research Support|Paratek: Grant/Research Support|Third Pole Therapeutics: Advisor/Consultant.
141. Evaluating Cefepime And Alternative Beta-lactams For The Treatment Of Serratia marcescens Blood Stream Infections
Authors: Vicente-Lopez Natcha , Patel Radha , Stock Kent J 
Published: December 2022

Abstract

Background
AmpC β-lactamase enzymes can be produced by a number of Enterobacterales. Due to its inducible chromosomal resistance, cefepime is often preferred. In vitro analysis and clinical reports have shown AmpC expression can occur less than 5% among S. marcescens. Locally, there has been a rise in beta-lactam resistant S. marcescens, however guidelines and small clinical trials have suggested treatment according to susceptibility testing. This study aimed to evaluate the use of cefepime vs. alternative beta-lactams like third generation cephalosporins or piperacillin-tazobactam as treatment of S. marcescens.
Overall treatment Failure

Methods
This is a single-center, retrospective review of adult hospitalized patients with S. marcescens BSIs over a five-year period. Patients who received more than 24 hours of susceptible antibiotics were included. Patients who received at least 72 hours of antibiotics from index blood culture were divided into definitive cefepime (DCEF) or definitive alternative beta-lactams (DBLA) groups. Composite outcome of 30-day re-admission, 90-day reinfection rates, and mortality was used to evaluate treatment failure.

Results
A total of 53 patients were enrolled. Common sources of infection include genitourinary (12), bone and joint (6), and skin and soft tissue (6). DCEF and DBLA groups included 35 and 18 patients, respectively. Most DBLA patients received piperacillin-tazobactam (9/18). Median Charlson Comorbidity Index (CCI) was 6 for DCEF and 4.5 for DBLA. 11 patients in the DCEF group were readmitted, vs 2 patients in the DBLA group. One patient in each group had reinfection within 90 days. In-hospital mortality occurred in 4 and 1 patients in the DCEF and DBLA groups, respectively. Overall treatment failure was observed in 15 patients in the DCEF group and 3 patients in the DBLA group. Median hospital length of stay was 10.1 days for DCEF and 9.5 days for DBLA.

Conclusion
More patients received DCEF compared to DBLA, potentially related to acuity evidenced by higher CCI and ICU admissions. Results showed a higher rate of overall treatment failure among DCEF group. Due to the retrospective design and small sample size, it is difficult to infer clinical significance. These findings prompt further investigation into the difference in treatment failure between these groups.

Disclosures
All Authors: No reported disclosures.
145. Harnessing the Inoculum Effect to Diagnose Molecular Mechanisms of Carbapenem Resistance
Authors: Cartagena Alexis Jaramillo , Taylor Kyra , Bhattacharyya Roby P 
Published: December 2022

Abstract

Background
The global spread of carbapenem-resistant Enterobacterales (CRE) presents a major threat to public health. CRE employ two molecular mechanisms to evade carbapenems: 1) expression carbapenemases (CPases), which efficiently hydrolyze carbapenems or 2) disruption of porins, which reduces carbapenem influx to levels that can be hydrolyzed by certain beta-lactamases. Diagnosing mechanisms underlying carbapenem resistance is important for infection control and to administer appropriate treatments.

Methods
We measured Meropenem and Ertapenem minimum inhibitory concentrations (MICs) for 103 clinical Enterobacterales isolated from hospitals in Massachusetts and California using broth microdilution assays at 14 inocula spanning four orders of magnitude. They represented 30 isolates encoding CPases and intact porins, 46 isolates with disruptions in one or both of the porins responsible for carbapenem influx (OmpC and OmpF), 25 encoding CPases with disrupted porins, and two controls encoding intact porins and no CPases.

Results
We observed that the two mechanisms result in distinct profiles; first the carbapenem MICs of CPase-encoding strains show a strong inoculum dependence (Fig 1.A), whereas the MICs of porin deficient strains remain largely constant at all inocula (Fig 1.B). The synergistic action of these two mechanisms leads to high-level resistance that we termed “hyper-CRE” (Fig 1.C). Together these factors explain the level of resistance in nearly all our CRE isolates. To validate the hyper-CRE phenotype, we successfully employed CRISPR-based gene editing to show that knocking out the major porin in CPase-producing strains elevates their carbapenem resistance to hyper-CRE levels.
We also determined 18% of our isolates changed susceptibility classification within the Clinical Laboratory and Standards Institute (CLSI) recommended inoculum range. This is worrisome for the treatment of infections with strains that are deemed susceptible via in vitro AST assays but are truly resistant in vivo.

Conclusion
Overall, our approach has demonstrated that measuring MICs at different inoculum can yield crucial diagnostic information about mechanisms of resistance which has important implications for patient care, infection control, and surveillance of emerging CPases.

Disclosures
All Authors: No reported disclosures.
158. Adherence to use of blood cultures according to current national guidelines and their impact in patients with community acquired pneumonia: A retrospective cohort
Authors: Ruiz Gaviria Rafael E , Rivera Arturo Marroquin , Pardi Maria D , Ross Robert W 
Published: December 2022

Abstract

Background
Community acquired pneumonia(CAP) is one of the highest infectious causes of mortality. Recommendations about the use of blood cultures in the diagnosis and treatment of CAP has been a continuous topic of debate. Current guidelines specify the situations when blood cultures should be ordered.

Methods
A retrospective cohort in a teaching hospital in Baltimore USA was conducted that include all the patients that were admitted with diagnosis of CAP as per the International Disease Classification 10 ( ICD 10) between January 1, 2019, and December 31, 2019. Socio demographic and clinical characteristics were obtained, as well as length of hospital stay and mortality. Blood cultures were classified as positive or negative and at the same time it was evaluated if they were done in compliance with current recommendations of Infectious Disease Society of America ( IDSA)

Results
721 patients had CAP and were included in the study. Median age was 68 years and almost 50% of the patients were male (n= 293). Most of the patients were from home (84%) and the most common comorbidities were hypertension and diabetes ( 68% and 31 % respectively). 96 patients had positive blood culture and 34% (n= 247) of all the blood cultures were adequately ordered as per current IDSA guidelines. 80 patients died or went to hospice and the median length of stay in our cohort was of 7 days. The multivariate model showed that mortality was associated with positive blood cultures ( OR= 3.1 95%CI 1.63- 5.87)and appropriateness of blood cultures ( OR=2.96 95% CI 1.25.7). Length of hospital stay did not show any association with positive blood cultures, but it was associated with blood culture appropriateness (OR= 1.63 95% CI 1-2.65).
Relation bewteen BC and LOS
Relationship between appropriateness of BC and length of stay according to the positivity of the BC
Multivariate with final disposition
Multivariate logistic regression to assess the association with mortality
Multivariate length of stay
Multivariate logistic regression to assess the association with extended length of stay

Conclusion
Adequate use of blood cultures in patients with CAP might have some association in the outcomes of patients suffering from this condition. However, a prospective study evaluating the utility of this test following current IDSA recommendations is needed to understand their impact in mortality and morbidity of CAP

Disclosures
All Authors: No reported disclosures.
160. Antimicrobial Prescribing Patterns in Bloodstream Infections Caused by Cefepime-Susceptible Extended Spectrum β-lactamase Enterobacterales
Authors: O’Rourke Emerald , Binkley Amanda , Talati Naasha J , Patel Sonal , Maguire Christina 
Published: December 2022

Abstract

Background
The reliability of piperacillin-tazobactam (TZP) and cefepime (FEP) breakpoints for extended spectrum β-lactamase Enterobacterales (ESBL-E) isolates remains controversial. The Infectious Diseases Society of America recommends against the use of TZP and FEP for the treatment of bloodstream infections (BSIs) caused by ESBL-E, even when in-vitro susceptibility is demonstrated. The University of Pennsylvania Health System microbiology laboratory suppresses TZP susceptibilities on Escherichia coli and Klebsiella pneumoniae blood isolates nonsusceptible to ceftriaxone (CRO) or ceftazidime (CAZ) and specifies the presence of a multidrug resistant organism. However, FEP susceptibilities are reported. The objective of this study was to assess appropriate antimicrobial prescribing for the treatment of FEP-susceptible ESBL-E BSIs with our institution’s current susceptibility reporting practices.

Methods
This multicenter retrospective observational study included patients with blood cultures positive for E. coli, K. oxytoca, K. pneumoniae, and Proteus mirabilis nonsusceptible to CRO or CAZ but susceptible to FEP from August 1, 2018 through August 1, 2021. Patients with a concominant gram-negative infection or true beta-lactam allergy were excluded. Patients were assessed for appropriate therapy (demonstrated susceptibility to and administration of carbapenems fluoroquinolones, novel beta-lactam/beta-lactamase inhibitors, or sulfamethoxazole-trimethoprim) within 24 h following the availability of susceptibility results.

Results
During the study period 38 patients were included. Of the 38 patients, 52.6% (n=20) received appropriate therapy with an average time to appropriate therapy of 3.7 (SD 2.1) h. Among patients receiving inappropriate therapy (n=18), 50% (n=9) were changed to appropriate therapy &gt;24 h after susceptibility results, with an average time to appropriate therapy of 46.5 (SD 44.4) h. The remaining 9 patients (23.7%) did not receive appropriate therapy beyond 24 h.

Conclusion
Reporting FEP susceptibility results on ESBL-E blood isolates may contribute to the prescribing of FEP for the treatment of ESBL-E BSIs and delay appropriate antimicrobial therapy. Given these findings, cefepime will now be suppressed on ESBL-E blood isolates.

Disclosures
All Authors: No reported disclosures.
168. Closing Time: A Quasi-experiment Comparing Time to Optimal Therapy using Traditional Identification and Susceptibility Methods, Rapid Identification, or Rapid Identification with Phenotype for Gram-negative Bloodstream Infections
Authors: Perry Rachel , Mercuro Nicholas J , Mercuro Nicholas J , Connolly Kristina Rokas , Dollard Eliza W , Stogsdill Patricia , Wungwattana Minkey 
Published: December 2022

Abstract

Background
Bloodstream infections (BSI) are a major cause of morbidity and mortality. Compared to traditional microbiology methods, rapid diagnostic testing (RDT) provides prompt organism identification and antibiotic susceptibility results. This leads to earlier opportunities to optimize therapy, which may improve patient outcomes.

Methods
This was a single center quasi-experimental study of hospitalized adults with Gram-negative (GN) BSI, comparing the management and outcomes across three periods: pre-RDT (traditional identification and susceptibilities with BD Phoenix®, December 2014 to September 2016), RDT1 (Nanosphere Verigene®, December 2016 to December 2019), and RDT2 (Accelerate Pheno™, February 2020 to September 2021). The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to oral antibiotic step-down, hospital length of stay (LOS), incidence of Clostridioides difficile infection, and 30-day inpatient mortality. Chi-squared and Kruskal-Wallis tests were used to compare categorical and continuous variables. Significance values for the primary endpoint were adjusted with Bonferroni correction to account for multiple pairwise comparisons.

Results
Of 296 included patients, 100 were in the pre-RDT, 98 in the RDT1, and 98 in the RDT2 arms. The most common organisms were Escherichia coli (64.5%) and Klebsiella species (20.3%). The TTOT (median, interquartile range) in the pre-RDT, RDT1, and RDT2 groups were 46 (7-61), 30 (0-53), and 12 (0-28) hours (P&lt; 0.001), respectively. The time to oral antibiotic step-down and hospital LOS was similar between groups. There was no difference in C. difficile infection or 30-day inpatient mortality (Table 1). Table 1.Comparison of Outcomes

Conclusion
In patients with GN BSI the TTOT in RDT1 was shorter when compared to traditional susceptibility methods. Compared to both rapid identification alone and traditional identification and susceptibility methods, RDT2 improved time to optimal therapy. Larger, controlled studies are needed to examine the clinical impact of different RDT methods for Gram negative bloodstream infections.

Disclosures
Rachel Perry, PharmD, Accelerate Diagnostics: Investigator initiated funding for research presentation; no funding for study design or data analysis Minkey Wungwattana, PharmD, BCIDP, Accelerate Diagnostics: Investigator initiated funding for research presentation; no funding for study design or data analysis.
171. Diagnostic stewardship to limit repeat plasma cytomegalovirus viral load testing
Authors: Trirattanapikul Akeatit , Pasomsub Ekawat , Siriyotha Sukanya , Pattanaprateep Oraluck , Phuphuakrat Angsana 
Published: December 2022

Abstract

Background
Serial monitoring of plasma cytomegalovirus (CMV) viral load monitoring with intervals of less than five days or using different assays for monitoring may cause unnecessary budgets for laboratory testing without changes in treatment, morbidity, and mortality.

Methods
The pre-intervention retrospective study and post-intervention prospective cohort study were performed. In 2021, the inpatient electronic pop-up and telephone interview and feedback were used to limit unnecessary plasma CMV viral load testing. The rate of plasma CMV viral load testing being performed with intervals of less than five days was compared before and after protocol implementation using the Poisson regression model. The cost-effectiveness of plasma CMV viral load testing after protocol implementation was also studied.

Results
After protocol implementation, there was a significant decrease in the rate of plasma CMV viral load test requests with intervals of less than five days from 11.8% to 6.2% [Incident rate ratio (IRR) 0.50, p-value &lt; 0.001]. Of these, 38.9% was due to unintentional requests. After telephone interviews the rate of plasma CMV viral load test requests with intervals of less than five days decreased further to 4.7% (IRR 0.37, p-value &lt; 0.001). The costs of plasma CMV viral load testing performed with intervals of less than five days and anti-CMV drugs were reduced significantly. (822,500 to 345,000 Thai Baht, p &lt; 0.001 and 12,327,436 to 7,860,187 Thai Baht, p = 0.001)
Incidence of plasma CMV viral load testing performed with intervals of less than five days
Costs of plasma CMV viral load testing, anti-CMV drug, bronchoscopy, and gastrointestinal endoscopy

Conclusion
The diagnostic stewardship program is helpful to reduce unnecessary plasma CMV viral load testing and costs without increasing CMV viremia and CMV diseases. This program should be maintained, and an electronic hard stop alert program should be developed.

Disclosures
All Authors: No reported disclosures.
172. Does Passive Reporting of Streptococcus spp Identified by Rapid Molecular Assay Change Antibacterial Prescribing Compared to Gram Stain (GS) Alone?
Authors: Archer Adam W , Cox Heather L , Donohue Lindsay E , Mathers Amy J 
Published: December 2022

Abstract

Background
At University of Virginia Health, the detection of Streptococcus spp via rapid molecular assay from blood cultures (BCx) was not historically reported in the EMR until the isolate was further identified. However this was reconsidered following anecdotal observation of inappropriate vancomycin (VAN) prescribing with GS alone. The purpose of this study was to investigate the impact of implementing passive reporting of Streptococcus spp on antibacterial prescribing patterns with a focus on VAN.

Methods
This was a single-center, pre-post quasi-experimental study of adult inpatients with non-duplicate Streptococcus spp identified via rapid molecular assay (ePlex®; GenMark Diagnostics) from BCx before (pre-intervention, Jul 2020 – Sep 2021) and after (post-intervention, Oct 2021 - Apr 2022) implementing passive reporting of Streptococcus spp. The primary outcome was any antibacterial switch within 24 hours of GS. VAN days of therapy (DOT) within 7 days and rates of Streptococcus spp deemed contamination by the primary team were also assessed.

Results
A total of 83 patients were included (58 pre- and 25 post-intervention). Baseline characteristics were similar including immunocompromised status (45% vs 52%), febrile neutropenia (28% vs 28%), and admission to a medical service (90% vs 96%). An antibacterial switch occurred within 24 hours of GS in 59% and 64% of the pre- and post-intervention groups, respectively, and was most commonly the addition of VAN (66% [25/38] vs 40% [8/20]; p=0.09). Fewer post-intervention patients continued VAN beyond 24 hours (66% vs 48%; p=0.15), but this was not statistically significant. The median VAN DOT remained unchanged at 2 days. A non-significant decrease in Streptococcus spp deemed contaminants was noted in the post-intervention arm (28% vs 16%; p=0.16). Finally, a non-streptococcal organism was isolated from concomitant BCx in approximately one-third of patients in each arm.

Conclusion
Passively reporting Streptococcus spp identified by rapid molecular assay without paired stewardship intervention did not impact antibacterial prescribing. The identification of Streptococcus spp may be characterized by heterogeneous circumstances requiring nuanced real-time stewardship intervention.

Disclosures
All Authors: No reported disclosures.