bluuebunny/crossref_metadata_2025_split huggingface dataset:
556. Evaluation of Antimicrobial Susceptibility Patterns Following Implementation of Levofloxacin Prophylaxis in those with Cancer and Blood Disorders
Authors: MacBrayne Christine , Dowell Elaine , Weber Matthew J , Janelle Sarah J , Parker Sarah K 
Published: December 2022

Abstract

Background
Prophylaxis with levofloxacin to prevent bacteremia in certain high-risk oncologic populations has been standard of care since the 2018 publication from the Children’s Oncology Group (JAMA 2018; 320(10)). This study only had susceptibility data for a minority of isolates and did not assess unit-wide impact on development of resistance, an important outcome given fluoroquinolones (FLQs) lead to resistance not only to FLQs but other drug classes, and not only for patients receiving fluoroquinolones rather unit wide. Our objective was to evaluate the development of resistance unit wide after implementing FLQ prophylaxis in our high-risk oncology patients, in addition to evaluating the overall impact on bacteremia.

Methods
A 6-year (1/2016-12/2021) single-center, retrospective review rates of bacteremia and susceptibility data from the Children’s Hospital Colorado Center for Cancer and Blood Disorders, encompassing the FLQ prophylaxis initiation date of 11/2018. All positive blood cultures were extracted from Meditech® or EPIC Beaker®, and susceptibility data from Microscan® or Sensititer®, with Institutional review board approval. Repeat cultures were not included. All data was analyzed using descriptive statistics performed in Excel®.

Results
Within the defined study period, there were 199 total blood cultures. These data were normalized per 1000 central line days, and analysis suggests there has been no significant change in bacteremia rates after implementing levofloxacin prophylaxis. Organisms reported nonsusceptible to levofloxacin or ciprofloxacin rose from over 11% in 2016 to almost 46% in 2021. Comparison of trends before and after the 2018 change reveals a significant difference in percent nonsusceptibility for those antibiotics (p = 0.02). Ceftriaxone or cefotaxime and cefepime were also analyzed and while not statistically significant there was a trend toward increasing resistance for ceftriaxone or cefotaxime (Figures).

Conclusion
Bacteremia on the oncology unit did not decrease after the implementation FLQ prophylaxis in November 2018. Additionally, resistance to FLQ and other antimicrobial classes is increasing, calling into question the benefit of this practice.

Disclosures
All Authors: No reported disclosures.
560. Meningitis/encephalitis PCR panel result and antimicrobial use in children
Authors: Olson Jared , Valentine Marilyn E , Thorell Emily A , Stallsmith Jena , Blaschke Anne J 
Published: December 2022

Abstract

Background
The meningitis/encephalitis multiplex polymerase chain reaction panel (ME PCR) detects common pathogens associated with community acquired CNS infections. The impact of this test on antimicrobial use in children is not well characterized.

Methods
We performed a retrospective, observational study in children &lt; 18 years of age who had ME PCR performed on CSF collected within 24 hours of admission to the hospital, presentation to the ED, or outpatient encounter from January 2018 to April 2022. Decision to order ME PCR was determined by the treating team. There are no restrictions on ordering ME PCR at our institution. The total calendar days of antimicrobial use from 24 hours prior to CSF collection to 7 days after CSF collection was evaluated. Our primary objective was to compare antimicrobial duration between subgroups based on ME PCR results: negative, virus positive, bacteria positive, and positive for both.

Results
Of 1282 ME PCR tests performed, 806 were done within the first 24 hours of the encounter. 190 (23.6%) patients never received antimicrobials for empiric treatment of meningitis/encephalitis and were excluded from subsequent analyses. Demographics and antimicrobial use are summarized for patients receiving at least one dose of an antimicrobial in Tables 1 and 2. CSF WBC was highest in bacteria positive CSF (p&lt; 0.001) followed by viral positive (p=0.0066). A positive bacterial result was associated with a longer duration of ceftriaxone, vancomycin and penicillin G and a shorter duration of acyclovir compared to viral and negative results (Table 2). A positive viral result was associated with a shorter length of total antimicrobial treatment (LOT) than negative (p=0.041) and bacterial positive (p&lt; 0.001).

Conclusion
Positive ME PCR results for bacteria may promote faster initiation of targeted therapy. Positive viral tests were associated with shorter LOT than both negative and bacteria positive ME PCR. Median LOT for negative testing was still 2 days suggesting rapid negative testing does not impact LOT. Prioritizing ME PCR for use in CSF samples with high pretest probability of a positive test may increase its effect on antimicrobial use.

Disclosures
Anne J. Blaschke, MD, PhD, BioFire Diagnostics/Biomerieux: Advisor/Consultant|BioFire Diagnostics/Biomerieux: Grant/Research Support|BioFire Diagnostics/Biomerieux: IP licensed to BioFire Diagnostics through the University of Utah and royalties received through the University of Utah related to the FilmArray|Merck: Advisor/Consultant.
576. Burden of Pneumococcal Disease Due to Serotypes Covered by the 13-Valent and New Higher-Valent Pneumococcal Conjugate Vaccines in All Children and Children at Risk in the United States
Authors: Huang Liping , Cane Alejandro D , Perdrizet Johnna , Arguedas Adriano 
Published: December 2022

Abstract

Background
Routine vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) in infants along with a catch-up option with PCV13/PPSV23 in children with underlying medical conditions (UMC) have considerably reduced invasive pneumococcal disease (IPD) and non-invasive pneumococcal disease (PD), including community acquired pneumonia (CAP) and acute otitis media (AOM), in the United State (US). However, a rise in IPD and non-invasive PD caused by non-PCV13 serotypes has been observed. A 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, are anticipated for children soon. The objective of the study was to estimate the annual cases, deaths, and economic burden of disease attributable to PCV13, PCV15, and PCV20 serotypes in children &lt; 18 years old overall and those with UMC in the US.

Methods
Estimated annual cases, deaths and direct medical costs associated with PD caused by PCV13, PCV15 and PCV20 serotypes were calculated based on published incidence rates of IPD, CAP, and AOM, along with age-group specific serotype coverage, case fatality rates, and disease-related costs (Table 1). The PD burden in those with UMC were extrapolated based on incidence rate ratios of those with UMC vs. those without UMC. The results were reported for 0-17 years and were further stratified into 2 age groups: 0-4 and 5-17 years. Table 1:Source Data for the Calculation

Results
The estimated annual PD cases attributable to PCV13, PCV15, and PCV20 serotypes in those 0-17 years were 768,301, 1,275,187, and 1,656,716 and in those with UMC were 23,209, 43,579, 63,949 (Table 2.1), respectively. The estimated direct medical costs were $494, $833, $1,103 million in those 0-17 years, and $76, $127, and $186 million in those with UMC, respectively (Table 3.1). The total estimated IPD cases in children with UMC were 18% (PCV13), 20% (PCV15) and 23% (PCV20) of all estimated IPD cases in all children.

Conclusion
This study demonstrates that the clinical and economic burden associated with new serotypes included in higher valent PCVs are substantial and higher in children with UMCs. The result shows that PCV20 will offer broader PCV coverage in the prevention of PD in ages &lt; 18 years overall and those specifically with UMC.

Disclosures
Alejandro D. Cane, MD, PhD, Pfizer: Full time employee|Pfizer: Stocks/Bonds Johnna Perdrizet, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Stocks/Bonds.
577. Cord Blood Protective Antibodies Seroprevalence against Diphtheria, Pertussis, Measles, Mumps and Rubella at Birth among Healthy Term Indian Neonates
Authors: Verma Sanjay , James Deepak , Lavanya Jula , Rawat Amit , Venkataseshan Sundaram , Aggarwal Neelam 
Published: December 2022

Abstract

Background
The resurgence of vaccine preventable diseases in young infants is a matter of concern worldwide. Cord blood antibodies seroprevalence against various vaccine preventable diseases could reflect protection rates among adults, which could be important in providing protection in early infancy of newborn baby. Tdap vaccination is not yet part of immunization program for pregnant women in India.

Methods
Apparently healthy term newborns, delivered at a tertiary care hospital in Northern India, over two-year period were enrolled after taking informed written consent from their parents, and their cord blood sample was collected at birth. Ethical clearance was obtained from Institute Ethics Committee before starting enrollment.

Results
A total of 160 newborns (M:F=86:74) were enrolled. In our study, antibodies (IgG) against diphtheria toxin (DT) were &gt;0.1 IU/ml in 44.4% (71/160), 0.01 to 0.1 IU/ml in 53.1% (85/160) and &lt; 0.01 IU/ml in 2.5% (4/160). Only 44.4% of them were fully protected at birth against diphtheria.
Antibodies (IgG) against pertussis toxin (PT) &gt;40 U/ml were seen in 41.2% (66/160). Out of these 66 children, 23 had titers &gt;100 U/ml. Total of 58.8% (94/160) children had antibodies &lt; 40 U/ml. Out of these 94 children, 48 had titers &lt; 20 U/ml. Since correlates of protection in pertussis are not defined; those having titers &gt;100 U/ml i.e. 14.3% were most protected; while those having titers &lt; 20 U/ml were least protected.
Antibodies (IgG) against measles antigen were &gt;12 IU/ml in 88.8% (142/160). Antibodies (IgG) against mumps antigen were &gt;12 IU/ml in 83.1% (133/160). Antibodies (IgG) against rubella antigen were &gt;12 IU/ml in 83.7% (134/160).

Conclusion
Protective antibodies against diphtheria and pertussis toxins were less in the studied newborns at birth making them susceptible to these diseases in early infancy, before primary vaccination commences. Tdap vaccination for pregnant mothers in India could help in improving these titers and protection in early infancy. Protective antibodies against measles, mumps and rubella in studied newborns at birth were satisfactory. For further enhancing protection, especially against rubella, one dose of MMR vaccine may be advised for women in child bearing age.
Acknowledgement: PGI Intramural Research Grant

Disclosures
All Authors: No reported disclosures.
582. Pediatric vaccine completion and compliance in the Military Health System, 2006–2016
Authors: Romano Celeste , Bukowinski Anna , Hall Clinton , Burrell Monica , Gumbs Gia , Conlin Ava Marie , Ramchandar Nanda 
Published: December 2022

Abstract

Background
Few studies have reported on pediatric vaccination trends among military beneficiaries, though some evidence suggests military dependents have lower vaccination rates than their civilian counterparts. No prior work has examined timeliness of vaccinations in this population. Here, we assessed completion of and compliance with rotavirus; inactivated polio virus (IPV); and diphtheria, tetanus, and acellular-pertussis (DTaP) vaccination among military beneficiaries.

Methods
Department of Defense Birth and Infant Health Research program data were used to identify infants born at military treatment facilities (MTFs), 2006–2016. Infants were required to be enrolled in TRICARE within the first year of life, continuously enrolled through 2 years of age thereafter, and have at least 1 immunization at an MTF and 1 well-child visit annually by age 2. Immunization status was assessed using vaccine administered and Current Procedural Terminology codes from MTF immunization records and outpatient health care records, respectively. Completion of rotavirus (2 doses), IPV (3 doses), and DTaP (4 doses) vaccination was assessed by 2 years of age. Vaccine compliance was assessed by additionally applying the Advisory Committee on Immunization Practices childhood immunization schedule.

Results
A total of 317,348 infants were identified for vaccination assessment. Completion and compliance for all vaccines increased between 2006 and 2016, though there were wide disparities between the two measures, particularly for the DTaP series. While 89.8% of infants born between 2009 and 2016 (n=228,641) received 2 doses of rotavirus, 3 doses of IPV, and 3 doses of DTaP by 2 years of age, only 80.5% received a fourth dose of DTaP. More than 40.0% of infants were undervaccinated for at least 1 day before age 2, 2014–2016.
Percent of infants born to military beneficiaries who complete and are compliant with vaccine recommendations, by vaccine series and overall, Department of Defense Birth and Infant Health Research program data, 2006–2016 (n=317,348).

Conclusion
Rotavirus, IPV, and DTaP vaccine coverage appeared higher in this population of military children than what has been reported nationally, but gaps remain. Providers serving military beneficiaries should ensure infants return for a care visit during the 15- to 18-month age window in order to remain compliant with the DTaP series and limit periods of undervaccination.

Disclosures
All Authors: No reported disclosures.
616. Pharmacodynamics (PD) of the lipopeptide QPX9003 Against Acinetobacter baumannii and Pseudomonas aeruginosa in the Neutropenic Mouse Thigh Infection Model
Authors: Tarazi Ziad , Roos Niki , Page Ted , Li Jian , Wang Jiping , Roberts Kade , Griffith David 
Published: December 2022

Abstract

Background
Acinetobacter baumannii and Pseudomonas aeruginosa are important pathogens in hospital-acquired infections and can be resistant to multiple classes of antibiotics. QPX9003 is a novel synthetic lipopeptide that is highly active in vitro against MDR Acinetobacter sp. and P. aeruginosa. The purpose of these studies was to determine the pharmacodynamic parameter that best described the bacterial killing of QPX9003 in vivo.
PK-PD of QPX9003 against A. baumannii
PK-PD of QPX9003 against P. aeruginosa

Methods
Seven A. baumannii and six P. aeruginosa isolates were used in these studies. Swiss-Webster mice were rendered neutropenic by 150 mg/kg IP injections of cyclophosphamide 4 and 1 days prior to infection. The bacterial inoculum was prepared from an overnight culture adjusted to 108 CFU/mL then further diluted for inoculation into the thighs. Various dose and dose regimens of QPX9003 were administered by the IP route starting 2 hours post infection and continuing for 24 hours. Untreated control groups were sacrificed at the start of treatment. Treated and untreated control groups were sacrificed 24 hours after the start of treatment, thighs harvested, homogenized and plated to determine colony counts. PK was conducted in neutropenic, infected mice at doses ranging from 3 to 50 mg/kg administered by the IP route. The relationship between PK-PD parameters and the reduction in the log number of CFU per thigh between time zero and 24 h after the start of treatment were analyzed by using the sigmoid maximum reduction (Emax) PD model.

Results
The activity of QPX9003 was best described by the 24h free AUC/MIC ratio, with stasis and 1 log kill targets of 47.1 and 67.1 for A. baumannii and 96.1 and 117 for P. aeruginosa, respectively.

Conclusion
The PD of QPX9003 was best described by the 24h free AUC/MIC ratio. Based on the QPX9003 MIC90 for P. aeruginosa (0.25 mg/L) and A. baumannii (1 mg/L), 24h free AUCs between 30 and 67 mg*h/L will produce 1-log of bacterial killing for ∼90% of P. aeruginosa and A. baumannii strains, respectively. QPX9003 is a potentially useful treatment for infections due to P. aeruginosa and A. baumannii, including MDR isolates, that is advancing in clinical studies.

Disclosures
Ziad Tarazi, Qpex Biopharma: Employee Niki Roos, n/a, Qpex Biopharma: Employee Ted Page, n/a, Qpex Biopharma: Employee David Griffith, n/a, Qpex Biopharma: Employee.
647. Cefepime Versus Carbapenems for the Treatment of ESBL-producing Enterobacterales among Non-blood Isolates
Authors: Garcia Brandon , King Madeline , Kludjian Geena , Hanretty Alexandra 
Published: December 2022

Abstract

Background
The incidence of organisms with extended-spectrum beta-lactamases (ESBLs) is increasing. The data for using cefepime in ESBL-producing Enterobacterales infections is conflicting. More favorable outcomes are likely if minimum inhibitory concentrations (MICs) &lt; 2 mcg/mL. The aim of this study is to compare the efficacy of cefepime versus carbapenems for ESBL-producing, non-bloodstream Enterobacterales infections.

Methods
This study was a single-center retrospective cohort study of patients who received cefepime or a carbapenem for at least 72 hours for the definitive treatment of an ESBL-producing Enterobacterales non-bloodstream infection between Jan. 1, 2011 and Sept. 30, 2021. ESBL production was identified if the isolate either had a positive confirmatory ESBL test from VITEK 2 (bioMérieux) or phenotypic resistance to ceftriaxone. Isolates had to have a MIC &lt; 2 mcg/mL to cefepime or be susceptible to carbapenems. Isolates with a cefepime MIC 4-8 mcg/mL were not included due to likely higher rates of treatment failure. The primary endpoint was clinical failure, defined as persistence of symptoms requiring escalation of therapy or death. Descriptive statistics were used to compare groups. A univariate analysis and odds ratio was calculated for clinical outcomes.

Results
One hundred patients were included. Twenty-two patients received cefepime and 78 received a carbapenem. Table 1 describes patient characteristics and clinical outcomes. Most patients had a urinary tract infection (UTI) (94%). More patients receiving cefepime were admitted to the intensive care unit (40.9% versus 15.4%). Treatment with cefepime displayed higher rates of clinical failure when compared to treatment with carbapenems (13.6% versus 6.4%). Cohen’s d-test for clinical failure was 0.46, indicating a medium effect.

Conclusion
Based on our analysis, cefepime may have higher rates of clinical failure when compared to carbapenem treatment for ESBL-producing Enterobacterales. Most of our patients were treated for UTIs and the sample size for both arms were limited, particularly for the cefepime arm. Further research is needed to confirm the role of cefepime as a carbapenem-sparing option in the treatment of these drug-resistant infections.

Disclosures
Madeline King, PharmD, Shionogi: Honoraria|Tetraphase: speakers' bureau.
662. In vitro antibacterial activity of contezolid compared to linezolid and vancomycin in clinical isolates from China
Authors: Wang Shanmei , Li Hao , Cheng Jianjian 
Published: December 2022

Abstract

Background
Linezolid and vancomycin are insufficient in the treatment of drug-resistant Gram-positive bacteria due to adverse drug reactions and drug resistance, and new antibiotics are needed, especially for patients with myelosuppression and vancomycin-resistant Enteroccocus (VRE) infection. Contezolid (CZD) is a novel oral oxazolidinone with potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and VRE. We evaluate the in vitro antibacterial activity of contezolid compared to linezolid and vancomycin in Gram-positive clinical isolates.

Methods
176 clinical isolates were obtained from 176 sterile body fluids from patients at 3 tertiary care hospitals in China, and the minimal inhibitory concentrations (MICs) of contezolid, linezolid and vancomycin determined by broth microdilution assay.

Results
Contezolid exhibits excellent antibacterial activity against prevalent Gram-positive bacteria, Staphylococcus spp. and Enterococcus spp., including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant and coagulase-negative Staphylococcus (MRCNS), and vancomycin-resistant Enterococcus (VRE). MIC90 values of contezolid were 2 mg/L for all MRSA and VRE isolates and 1 mg/L for MRCNS isolates. The antibacterial activity of contezolid against Staphylococcus spp., including S. aureus, was essentially similar to linezolid, and slightly higher than or similar to vancomycin. Antibacterial activity of contezolid against Enterococcus, including VRE, was similar to linezolid, while being slightly lower than for vancomycin in vancomycin-susceptible isolates. Consistent with the shared antibacterial mode of action, bacterial strains resistant to linezolid were cross-resistant to contezolid. Table 1.Antimicrobial susceptibility testing results of clinical bacterial strains (MICs, mg/L)

Conclusion
Contezolid, a novel oxazolidinone drug, exhibits potent in vitro antibacterial activity against clinical isolates of common Gram-positive pathogens, including multidrug-resistant (MDR) Gram-positive bacteria, MRSA, MRCNS, and VRE. Contezolid has antibacterial activity similar to standard-of-care antibiotics linezolid and vancomycin. Results suggest that contezolid can play an important role in treatment of MDR Gram-positive bacterial infections. Figure 1.Distribution of MICs of CZD or LZD against 48 strains of MRSAFigure 2.Distribution of MICs of CZD or LZD against 29 strains of MRCNSFigure 3.Distribution of MICs of CZD or LZD against 17 strains of VRE

Disclosures
All Authors: No reported disclosures.
671. Relevance of Levofloxacin-Resistant MRSA and hVISA when utilizing directed antibiotic locks to treat stage 4 biofilm bone and joint infections
Authors: Vicent Martie , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , LaPlante Kerry L 
Published: December 2022

Abstract

Background
Directed antibiotic locks have the potential to treat orthopedic infections due to the ability to bypass specific systemic absorption allowing for higher antimicrobial concentrations. With limiting antimicrobial options to treat biofilm commonly associated with bone and joint infections, our aim is to understand and further test the relevance of utilizing standard systemic MIC values to direct therapy.

Methods
Using our previously described biofilm assay with six unique spa-type (t004, t018, t062, t064, t1340, t008) MRSA isolates, biofilm was grown for 4, 6, and 24hrs at 6 log10 CFU/mL in TSB per CLSI guidance adding dextrose 1.25% for biofilm promotion. MIC were run using CLSI guidance. Planktonic cells were removed by irrigation, simulating debridement. 24hr treatment assays, simulating antibiotic locks included levofloxacin (5 mg/mL) in d5W solution and vancomycin (5 mg/mL) in NS.

Results
Levofloxacin by definition of standard MIC values was found to be resistant in five out of the six MRSA isolates (MIC ranging from 1 – 312mcg.mL). However, at 16-25,000 times the MIC, levofloxacin demonstrated a decrease in biofilm growth on mature 24-hr established biofilm by 9-130%. Similarly, vancomycin heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), at 3000-6000 the MIC demonstrated a decrease of 53-190% mature biofilm growth.

Conclusion
All isolates produced consistent biofilm as previously tested as a low or high biofilm-producer when there was no antibiotic present. Levofloxacin and vancomycin at least 1000X the MIC nearly eradicated all established MRSA biofilm. Our next steps will be to evaluate if the MIC values have any effect on additional antibiotics in a lock solution.

Disclosures
Kerry L. LaPlante, Pharm.D., FCCP, FIDSA, FIDP, AbbVie Inc.: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.,: Grant/Research Support|Merck & Co., Inc.: Advisor/Consultant|Merck & Co., Inc.: Grant/Research Support|Nabriva Therapeutics US, Inc.,: Grant/Research Support|Ocean Spray Cranberries, Inc.: Grant/Research Support|Pfizer Pharmaceuticals: Grant/Research Support|Shionogi, Inc.: Grant/Research Support|Tetraphase Pharmaceuticals.: Grant/Research Support.