bluuebunny/crossref_metadata_2025 huggingface dataset:
1296. Efficacy of Human-Simulated Exposures of Meropenem/Vaborbactam (MVB) and Meropenem (MEM) against OXA-48 β-lactamase-producing Enterobacterales in the Neutropenic Murine Thigh Infection Model
Authors: Gill Christian M , Asempa Tomefa E , Nicolau David P
Published: January 2021

Background

OXA-48 exhibits variable hydrolytic activity toward carbapenems, with imipenem and meropenem MICs, though increased, often reporting within the ‘susceptible’ or ‘intermediate’ ranges defined by CLSI and EUCAST. Although vaborbactam (VAB) does not enhance MEM activity against OXA-48, ~ 1/3 of OXA-48-producing Enterobacterales will test susceptible to MVB due to its higher breakpoint. Clinical implications of this discordance warrant investigation.

Methods

26 isolates harboring OXA-48 (n=24) and KPC (n=2) were evaluated in the neutropenic murine thigh model. MICs were determined in triplicate per CLSI. Human-simulated regimens of MVB (simulating doses of 2-2 g IV q 8 hours (h) over 3 h) and MEM (2 g IV q 8 h over 3 h) were administered resulting in similar f%T >MIC and fAUC as humans for MEM and VAB, respectively. Mice received MVB, MEM, or sham control for 24 h. Efficacy was assessed on the resulting overall change in mean± SD log10 CFU/thigh as well as the achievement of ≥ 1 log10 reduction as an established surrogate marker predictive of success for serious infections.

Results

MVB and MEM MICs ranged from 1- 64 and 2 - > 64 mg/L, respectively. Relative to 0 h control, the mean bacterial growth (mean ± SD, CFU/thigh) at 24 h in the untreated control mice was 2.69 ± 1.31. As anticipated for KPCs, MVB resulted in a mean bacterial reduction ≥ 1 log10 (-1.10 ± 0.26), whereas growth was observed on MEM (+1.45 ± 0.88). For all OXA-48 isolates, MVB resulted in variable bacterial densities ranging from -2.54 to +2.68, similarly MEM resulted in -2.18 to +2.66. Addition of vaborbactam did not enhance MEM activity for any isolate. For isolates with MVB MICs ≥ 16 (n=5), 8 (n=5, EUCAST breakpoint), 4 (n=9, CLSI breakpoint), and ≤ 2 (n=5) mg/L, 0%, 0%, 44%, and 60% of isolates treated with MVB or MEM achieved the target reduction of ≥ 1 log10 kill, respectively.

Conclusion

Across the range of MICs evaluated, MVB and MEM humanized exposures in vivo resulted in similar reductions and growth in bacterial density for OXA-48-producing Enterobacterales. Moreover, these data highlight the poor efficacy of MVB for OXA-48 defined as susceptible using the current EUCAST and CLSI susceptibility criterion. Caution is therefore warranted when treating Enterobacterales testing susceptible to MVB without the genotypic profile.

Disclosures

David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)
1300. ACOG Committee Opinion #797 and the Dose of Intrapartum Vancomycin: a Potential Danger to Mother and Newborn Alike
Authors: Farkas Andras , Feldman Kristina M , Woods Krystina L , Yassin Arsheena
Published: January 2021

Background

Intra-partum (IP) IV vancomycin (VAN) 20 mg/kg every 8 hours is proposed by #797 for the prevention of early onset neonatal group B streptococcal disease (GBS), a recommendation for which the basis of scientific merit is poor. The goal of our study was to analyze the sparsely sampled published data and raise awareness about the underlying risk of VAN toxicity with this dosing approach.

Methods

Plasma and cord-blood concentration-time data of IV VAN given to mothers in the IP period was analyzed. 5000 Monte Carlo runs were conducted to simulate maternal/fetal exposure (AUC0-24; 24-48) for doses of 1500, 1750 and 2000 mgs q8h and for possible birth times at two-hour intervals. Neonatal VAN clearance was not possible to determine; hence, we used a validated PK model to calculate exposure for the first 24h of life for gestational ages (GA) of 33 to 40 weeks. The AUC range of 400 – 600, and > 600 mg*h/L were considered for indices of efficacy and toxicity, respectively.

Results

Estimates from 30 pairs of serum and cord-blood concentrations analyzed with a 2-compartment model are shown in Table 1. Maternal VAN exposures seem acceptable up to 2 IP doses given with mean (SD) AUC0-24 of 394 (140), 474 (167), and 540 (193) mg*h/L for the 1500, 1750 and 2000 mg regimens. Most mothers (up to 83%) who receive three or more doses will be subjected to nephrotoxic exposures (Figure 1.). Neonatal evaluations indicate similarly low PTAs for the three dosing regimens when the efficacy target is considered (Figure 2. A). On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA of 33 to 35 weeks and birth times beyond 20 hours after the initiation of intra-partum prophylaxis (Figure 2. B).

Figure 1.

Figure 2.A

Figure 2.B

Conclusion

Current recommendations by #797 for dosing of vancomycin pose significant risk to mother and newborn alike, especially in cases with lengthy duration of labor. Based on our results, maternal therapeutic drug monitoring for all cases requiring more than two doses should be considered. With the proposed dosing regimen going un-adjusted, 1 out of 4 newborns and 4 out of 5 mothers may be subjected to nephrotoxic exposures in prolonged labor.

Table 1.

Disclosures

All Authors: No reported disclosures
1306. Comparison of the Use of Extended and Intermittent Infusion Cefepime and Piperacillin/tazobactam in Non-critically Ill, Obese Patients
Authors: Marg Carolyn , DeLanoit Zach , Boeser Kimberly D
Published: January 2021

Background

Obesity rates have dramatically increased over the last several decades, however, there is limited data to guide how antibiotics should be adjusted in obese patients. Physiologic differences including an increased volume of distribution and increased renal clearance may alter their pharmacokinetics and pharmacodynamics and subsequently, their efficacy. For beta-lactams like piperacillin/tazobactam (pip/tazo) and cefepime, extended infusion (EI) maximizes the time above the minimum inhibitory concentration (MIC) for optimal bactericidal activity. This dosing strategy may help decrease variability in achieving the target time above MIC in this patient population and lead to more favorable outcomes.

Methods

This single-center, retrospective, pre-/post- analysis included patients with a body mass index (BMI) > 30 that received EI (infused over 4 hours) or intermittent infusion (II) (infused over 30 minutes) pip/tazo or cefepime between 2/1/2020-4/30/2020 and 2/1/2019-4/30/2019, respectively. The primary outcome was in-hospital, all-cause mortality. Secondary outcomes included clinical success rate and hospital length of stay (LOS).

Results

During the evaluation periods, 98 patients met inclusion criteria (EI, N=53; II, N=45). Mean BMI was not statistically different between groups (EI, 36.0 kg/m2 [30.1-46.3]; II, 36.5 kg/m2 [30-48]). There were no cases of mortality in either group. The mean LOS in the II group was 13 days compared to 11.5 days in the EI group [95% CI -4.14-7.04; p=0.606]. After excluding one outlier of 104 days in the EI group, the average LOS was 9.5 days [95% CI: -0.87-7.33; p=0.121]. Markers of clinical success including time to resolution of fever (II: 47 hours; EI: 34 hours; p=0.216) and time to resolution of leukocytosis (II: 2 days; EI: 3.8 days; p=0.089) were not significantly different between groups.

Conclusion

The use of EI pip/tazo and cefepime was not associated with any differences in in-hospital, all-cause mortality, hospital LOS, or clinical success when compared to the use of II pip/tazo and cefepime. The lack of significant differences between groups may be attributable to the small sample size limiting the ability to detect a difference, especially regarding hospital LOS.

Disclosures

All Authors: No reported disclosures
1308. Ex vivo Impact of Autologous Blood Transfusion (ABT) on Concentrations of Antibiotics used for Surgical Prophylaxis
Authors: Lasko Maxwell J , Conelius Allison , Serrano Oscar , Nicolau David P , Kuti Joseph L
Published: January 2021

Background

ABT is widely employed during surgical procedures involving high blood loss, such as liver transplantation and open heart surgery. While ABT mitigates the need for allogeneic blood transfusions, an unintended consequence may be removal of drugs, including antimicrobials. Herein, we determined the ex vivo loss of antimicrobials utilized for surgical prophylaxis through an ABT system.

Methods

Experiments were conducted in duplicate to simulate processing of ABT blood during surgery. Packed red blood cells and fresh frozen plasma (300ml) were acquired from banked blood and inoculated to achieve clinically-relevant plasma concentrations of vancomycin (VAN), the piperacillin (PIP) component of piperacillin/tazobactam, and the ampicillin (AMP) component of ampicillin/sulbactam. Inoculated blood was processed through a Cell Saver® Elite™ ABT system to fill a 125mL Latham bowl and washed with 500mL of normal saline. Processed fluid was directed to a reinfusion or waste bag; additional blood samples were collected from each. Drug concentrations were measured in all samples. The amount of VAN, PIP, and AMP infused through the Cell Saver (initial), and resulting in the reinfusion and waste bags was calculated.

Results

A range of 193-265mL of combined blood containing drug were processed in each experiment through the ABT system. Initial average plasma concentrations were 61, 107, and 172 mg/L for VAN, PIP, and AMP, respectively. When corrected for volume and hematocrit, plasma concentrations translated to a mean ± SD of 3 ± 1% of VAN in the reinfusion bag and 93 ± 2% in the waste bag. For PIP, plasma concentrations translated to 2 ± 1% of PIP in the reinfusion bag and 84 ± 13% in waste, while 2 ± 1% and 120 ± 5% of AMP was found in the reinfusion and waste bags, respectively. Unaccounted drug (0-14%) was considered sequestered in the device.

Conclusion

These ex vivo assessments of antibiotic removal during ABT are the first to demonstrate significant loss of antibiotics (>95%) when processed through the ABT system. Further studies measuring impact of ABT on drug concentrations in patients undergoing surgery are warranted.

Disclosures

David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))
1313. MIC Profiling of Ceftazidime-Avibactam (CAZ/AVI) Against Two Carbapenemase producing Klebsiella pneumoniae Isolates
Authors: Zidaru Andrei , Eales Brianna M , Wang Weiqun , Merlau Paul , Lasco Todd , Sofjan Amelia K , H Tam Vincent
Published: January 2021

Background

Carbapenemases confer resistance against a broad range of beta-lactams with a prevalence of 40-60% among CRE (carbapenem-resistant Enterobacteriaceae). CAZ-AVI is commonly used to treat infections due to CPE (carbapenemase-producing Enterobacteriaceae), typically guided by susceptibility testing with a single AVI concentration. This methodology does not take into consideration varying AVI concentration observed in vivo, and may not reliably predict positive clinical outcomes. Our objective was to investigate a novel susceptibility testing method to guide CAZ-AVI therapy.

Methods

Two bloodstream K. pneumoniae isolates (CAZ/AVI susceptible) from an abdominal source were recovered from 2 unrelated patients. Both patients were treated with CAZ/AVI, but had discordant outcomes: KP118 (eradication within 24h) and KP286 (persistent bacteremia for over 30 days). Carbapenemase production in the 2 isolates was confirmed via Carba NP test, and CAZ susceptibility was determined in a clinically relevant range of AVI concentration (0 - 16 mg/L). The concentration-response was characterized by the sigmoid inhibitory maximum effect (Emax) model. The best-fit parameter values were used to predict %T > MICi associated with CAZ/AVI exposures expected in peritoneal fluid after standard dosing (2.5g q8h). These CAZ/AVI exposures were simulated in the hollow-fiber infection model (HFIM), and the bacterial responses were correlated to observed clinical outcomes.

Results

The AVI-dependent reduction in CAZ MIC was well characterized in both strains (R2 > 0.98). In HFIM, sustained suppression of KP118 (T > MICi = 100%) was observed over 5 days, but not with KP286 (T > MICi < 100%). These observations are consistent with the clinical courses of the patients.

Conclusion

The discordant patient outcomes could be explained by MIC profiling of CAZ/AVI. This method appears to be more robust than conventional susceptibility testing, and the clinical utility of this approach should be further investigated.

Disclosures

All Authors: No reported disclosures
1315. No Dose Adjustment of Metformin with Fostemsavir Coadministration Based on Mechanistic Static and Physiologically Based Pharmacokinetic Models
Authors: Nguyen Dung N , Miao Xiusheng , Magee Mindy , Tai Guoying , Gorycki Peter D , Moore Katy P
Published: January 2021

Background

Fostemsavir (FTR) is an oral prodrug of the first-in-class attachment inhibitor temsavir (TMR) which is being evaluated in patients with multidrug resistant HIV-1 infection. In vitro studies indicated that TMR and its 2 major metabolites are inhibitors of organic cation transporters (OCT)1, OCT2, and multidrug and toxin extrusion transporters (MATEs). To assess the clinical relevance, of OCT and MATE inhibition, mechanistic static DDI prediction with calculated Imax,u/IC50 ratios was below the cut-off limits for a DDI flag based on FDA guidelines and above the cut-off limits for MATEs based on EMA guidelines.

Methods

Metformin is a commonly used probe substrate for OCT1, OCT2 and MATEs. To predict the potential for a drug interaction between TMR and metformin, a physiologically based pharmacokinetic (PBPK) model for TMR was developed based on its physicochemical properties, in vitro and in vivo data. The model was verified and validated through comparison with clinical data. The TMR PBPK model accurately described AUC and Cmax within 30% of the observed data for single and repeat dose studies with or without food. The SimCYP models for metformin and ritonavir were qualified using literature data before applications of DDI prediction for TMR

Results

TMR was simulated at steady state concentrations after repeated oral doses of FTR 600 mg twice daily which allowed assessment of the potential OCT1, OCT2, and MATEs inhibition by TMR and metabolites. No significant increase in metformin systemic exposure (AUC or Cmax) was predicted with FTR co-administration. In addition, a sensitivity analysis was conducted for either hepatic OCT1 Ki, or renal OCT2 and MATEs Ki values. The model output indicated that, a 10-fold more potent Ki value for TMR would be required to have a ~15% increase in metformin exposure

Conclusion

Based on mechanistic static models and PBPK modeling and simulation, the OCT1/2 and MATEs inhibition potential of TMR and its metabolites on metformin pharmacokinetics is not clinically significant. No dose adjustment of metformin is necessary when co-administered with FTR

Disclosures

Xiusheng Miao, PhD, GlaxoSmithKline (Employee) Mindy Magee, Doctor of Pharmacy, GlaxoSmithKline (Employee, Shareholder) Peter D. Gorycki, BEChe, MSc, PhD, GSK (Employee, Shareholder) Katy P. Moore, PharmD, RPh, ViiV Healthcare (Employee)
1322. Quantifying the Effects of Frequently Prescribed Antimicrobials with Perceived Potential for QT Interval Prolongation during the COVID-19 Era
Authors: Sy Hendrik , Woods Krystina L , Yassin Arsheena , Ciummo Francesco , Shah Ami , Freites Christian Olivo , Farkas Andras
Published: January 2021

Background

Countless diseases and medications have been implicated in the past as causing prolongation of the QT interval. Their unique role through the means of quantifying the definite magnitude of relative risk they contribute during hospitalization still requires further investigation. The aim of this study was to describe the impact of commonly used anti-infectives on the QT interval in hospitalized patients during the COVID-19 era.

Methods

Demographic information, medical history, laboratory data, medication administration history and ECG recording data was collected from the electronic records of adult patients admitted to two urban hospitals. A mixed effects approach with four sub-models for the QT interval comprised of: heart rate, circadian rhythm, gender, and the drug (regressed as the cumulative mg dose administered over time) and disease effects was used. Fixed and random effects with between occasion variability were estimated for the parameters with a Bayesian approach using the STAN software.

Results

Data from 2180 patients were used with baseline characteristics shown in Table 1. Observed vs. predicted plots based on the training (Figure 1.A) and validation data set (Figure 1.B) showed excellent fit. The parameters for QTc0, α, gender, and circadian rhythm were identified within the range previously described (Table 2.). Similarly, the model correctly identified the impact of acute or chronic diseases on the QT interval. Model coefficient estimates [mean (95% CI) of 0.010 (0.006, 0.15) and 0.0045 (0.0013, 0.01100) msec/mg cumulative dose, respectively] suggest that patients treated with conventional regimens of fluconazole and levofloxacin are most likely to present with a QT interval increase > 5 msec, the cutoff threshold of regulatory concern.

Figure 1. A-B

Table 1.

Table 2.

Conclusion

The model developed accurately identified the impact baseline risk factors and concomitant medications have on the QT interval. When adjusted for these confounding variables, estimates of QT interval prolongation show that treatment with fluconazole and levofloxacin pose a considerable risk; while treatment with azithromycin or hydroxychloroquine is of moderate risk for QT interval prolongation.

Disclosures

All Authors: No reported disclosures
1335. Accuracy of Outpatient Antibiotic Prescriptions for Urinary Tract Infection in Pediatric Ambulatory Care
Authors: Polischuk Emily , Mannix Mary Kathryn , Islam Shamim
Published: January 2021

Background

Antimicrobial stewardship programs have typically focused on inpatient care, but antibiotics are frequently prescribed at pediatric ambulatory care centers. Ensuring accurate pediatric antibiotic dosing is important to optimize outcomes while minimizing adverse drug effects. Outpatient pharmacists often lack the resources to recommend optimal antibiotic dosing for pediatric infections. The primary objective was to evaluate the accuracy of antibiotic dose, frequency and formulation prescribed. The secondary objective was to describe the most commonly prescribed treatment durations.

Methods

A retrospective review of electronic medical records was conducted at two suburban pediatric practices. Patients diagnosed with uncomplicated UTI over a two year period were identified using ICD-10 codes N39, R30 and R35. Patients 2 months-18 years were included if prescribed an oral antibiotic for the treatment of UTI. Data collected included baseline demographics, antibiotic, dose (mg and mg/kg), frequency, formulation, and duration. Antibiotic dose, frequency and formulation were considered accurate if they were consistent with clinical guidelines and tertiary dosing references, allowing for 10% rounding in weight-based doses.

Results

A total of 472 outpatient prescriptions met inclusion criteria. Overall, 24% of dosing regimens were found to be inaccurate. Patients were most commonly prescribed doses that were too low (54/118, 45%) or too high (41/118, 35%). Less frequently, doses exceeded the maximum total dose (9/118, 8%), were given at the wrong frequency (8/118, 7%), or the wrong dosage form was selected (6/118, 5%). Of the commonly prescribed antibiotics, dosing errors were most likely to occur with ciprofloxacin (24/27, 89%) and amoxicillin (33/64; 55%). The majority of patients completed a 10 day course of antibiotics (381, 80%), followed by 7 days (66, 13.9%). Durations of 3 days (20, 4.2%), 5 days (7, 1.5%) and 14 days (2, 0.4%) occurred less frequently.

Conclusion

Errors in antibiotic dosing occurred with nearly one in four prescriptions written for outpatient UTI from pediatric primary care centers. Durations were most commonly 10 days. Education and resources should be provided to outpatient pediatric providers to optimize antibiotic dosing.

Disclosures

All Authors: No reported disclosures
1355. Resistance in Gram-Negative Bacteria in the Pediatric Patient Population by Age and Sex
Authors: Malamet Benjamin J , Sims Matthew
Published: January 2021

Background

Previous research within the Beaumont Infectious Diseases Research Program found an overall increase in antibiotic resistance in adult males versus females. Furthermore, there is a peak in resistance in 18-29-year-old males, not seen in females. The origin of this early peak of antibiotic resistance in adults is unclear. This study examines these trends in the pediatric patient population.

Methods

Resistance data for all Gram-negative bacterial clinical isolates from Beaumont Health System’s clinical microbiology lab between October 1st, 2010, and December 31st, 2014 was analyzed. The pediatric isolates were categorized into sextiles (0-2, 3-5, 6-8, 9-11, 12-14, 15-17) and the sensitivities for each antibiotic were compared based on gender and age and separated by urine isolates vs. non-urine isolates to account for potential bias based on an abundance of urine samples in females.

Results

There were 7878 pediatric Gram-negative bacterial isolates in the database, and 96 duplicate samples were removed, leaving 7782 isolates to be analyzed. There were more female isolates (n=6888) than male isolates (n=890) due to the preponderance of urine cultures in females. At most age ranges, antibiotic resistance was significantly higher in males than females. In males, antibiotic resistance was highest between 12-14 and 15-17 years old. When analyzing the cultures based on sample type, the peak in resistance in males is seen in urine isolates, but the patterns of resistance are chaotic in non-urine isolates. This is likely attributable to a low number of isolates.

Conclusion

Sex is an important factor in determining antibiotic resistance in the pediatric patient population, as males exhibit higher resistance. The peak in antibiotic resistance initially noted in 18-29-year-old males in previous research originates in the pediatric age group and appears to develop between 12-17 years old. Further research is needed to determine the cause of the observed gender bias, to ascertain if it is modifiable in order to reduce antibiotic resistance.

Disclosures

All Authors: No reported disclosures
1364. Effect of Cefepime Prophylaxis on Bacterial Bloodstream Infections in Neutropenic Patients with Acute Myelogenous Leukemia
Authors: Dassner Aimee , Almatrafi Mohammed , Slone Tamra , Aquino Victor M , Sebert Michael
Published: January 2021

Background

Bacteremia is a major cause of morbidity and mortality among children with acute myelogenous leukemia (AML) and chemotherapy-induced neutropenia. Data evaluating the utility of bacterial prophylaxis in this pediatric population are limited. In April 2014, Children’s Health (CH) implemented the use of cefepime bacterial prophylaxis for AML patients undergoing induction and intensification chemotherapy. The objective of this study was to evaluate the impact of this practice on the frequency of documented bacterial bloodstream infections (BSIs).

Methods

This was an observational, retrospective cohort study of patients < 21 years of age with AML admitted at CH from January 2010 through December 2018. The primary outcome was frequency of documented BSIs before (PRE; Jan 2010 to Mar 2014) and after (POST; Apr 2014 to Dec 2018) implementation of routine bacterial prophylaxis. Secondary outcomes included differences in total antibiotic days per neutropenia days and the occurrence of neutropenia-associated C. difficile infection between groups.

Results

Of 90 patients with AML who met the cohort inclusion criteria, 38 and 52 were treated during the PRE and POST prophylaxis periods, respectively. The incidence rate of documented BSIs per 1000 neutropenia days decreased from 15.5 to 2.8 after the implementation of routine cefepime prophylaxis (incidence rate ratio 0.18, Poisson regression 95% CI 0.09 to 0.33, P< 0.001). Patients were more likely to have febrile neutropenia in the PRE group (OR 11.9, 95% CI 6.6 to 20.8). The POST group had more antibiotic days per total neutropenia days (0.76 PRE vs 0.97 POST, P< 0.0001), but the frequency of first-episode C. difficile infection was not significantly different between groups (OR 0.36, 95% CI 0.1 to 1.4).

Conclusion

Universal cefepime prophylaxis for children with AML and chemotherapy-induced neutropenia was associated with a significant reduction in the incidence of febrile neutropenia and neutropenia-associated BSIs without increasing the incidence of C. difficile infection.

Disclosures

All Authors: No reported disclosures
1373. Vaccine Effectiveness and Pneumococcal Serotypes in Pediatric Otitis Media in the Era of Routine 13-valent Pneumococcal Vaccination in the United States
Authors: Hulten Kristina G , Barson William , Lin P Ling , Bradley John S , Peters Timothy R , Tan Tina Q , Romero Jose R , Pannaraj Pia S , Kaplan Sheldon L
Published: January 2021

Background

Pneumococcal acute otitis media (AOM) in children due to vaccine related serotypes (St) declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).

Methods

Patients < 18 years with pneumococcal OM isolates from 2014-2019 from the U S Pediatric Multicenter Pneumococcal Surveillance Group were analyzed for demographics, immunization status, antimicrobial susceptibility and St distribution. p< 0.05 was considered statistically significant. Vaccine effectiveness (VE) was calculated using a standard formula: 1-([PCV13St vaccinated (≥3 PCV13 doses) x Non-PCV13St unvaccinated (0-1 PCV13 doses)]/[PCV13St unvaccinated x Non-PCV13St vaccinated])

Results

646 patients were identified. Patients with PCV13 St were older compared to patients with non-PCV13 serotypes (3.3 vs 1.5 median years, p< 0.0001). Most isolates were from spontaneous drainage (71.4 %) and PE tube placements (26.9%). 36 different Sts were identified; 83.4% of isolates were non-PCV13 Sts; 35B represented 18.3% of all isolates. St 19A decreased over time (p=0.0003). 14% of isolates had penicillin MIC ≥2 µg/ml and 2.4% had ceftriaxone MIC >1 µg/ml. (Figure) 633 patients had known vaccine status. VE was 86.4% (Table).

Table.

Conclusion

Non-PCV13 Sts caused most pneumococcal OM. St35B was the most common St. St 19A decreased as a cause of otitis. In this study the VE of≥3 PCV13 doses was 86% for pneumococcal OM.

Disclosures

Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support)
1377. Perinatal Transmission Dynamics of Antimicrobial Resistance
Authors: Styczynski Ashley , Amin Md Badrul , Parveen Shahana , Pervez Md Abu , Zeba Dilruba , Akhter Akhi , Gurley Emily S , Luby Stephen
Published: January 2021

Background

Antimicrobial resistance (AMR) is a global health threat that disproportionately affects low- and middle-income countries. An ongoing study of childhood mortality in Bangladesh revealed a common cause of death among neonates is sepsis from Gram-negative multi-drug-resistant organisms.

Methods

To ascertain factors leading to neonatal exposure, we enrolled 100 women presenting for delivery to Faridpur Hospital during February-March 2020. We collected vaginal and rectal swabs from mothers on presentation and at least 24 hours after delivery as well as rectal swabs from newborns. Swabs were plated on chromogenic agars selective for extended-spectrum-beta-lactamase-(ESBL) producing organisms and carbapenem-resistant Enterobacteriaceae (CRE).

Results

Eight-five percent of women underwent C-section. Prior to delivery, ESBL organisms were isolated from 15% of vaginal and 63% of rectal swabs. CRE was detected in 2% of vaginal and 8% of rectal swabs. Following delivery, colonization exceeded 90% (ESBL) and 70% (CRE) in both swab sets. Similarly, among newborns, 85% were colonized with ESBL and 67% with CRE. Maternal AMR colonization on admission did not correlate with income, education, parity, prenatal care, or prior antibiotic use, but was associated with hospitalization during pregnancy (rectal CRE OR 11.9, p< 0.01). Maternal colonization at discharge was positively associated with membrane stripping (vaginal ESBL OR 9.0, p< 0.01; rectal CRE OR 5.0, p=0.03), C-section (OR 4.0-15.4, p< 0.05), and administration of third-generation cephalosporins (OR 5.0-10.1, p< 0.05). Newborn colonization correlated with maternal colonization on discharge (p< 0.005) but not on admission. Among newborns delivered by C-section, there was an 8-9-fold increased risk of ESBL and CRE colonization (p< 0.01).

Conclusion

These results demonstrate that AMR is driven by nosocomial factors in the perinatal setting, and invasive procedures and perinatal antibiotic use increase risk of AMR colonization. These findings emphasize the urgent need for enhanced antibiotic stewardship and infection prevention and control practices to preserve the benefits of hospital-based deliveries.

Disclosures

All Authors: No reported disclosures
1384. Conceptual Economic Model Methodology for Infant Pneumococcal Conjugate Vaccine Program and its Impact on Antimicrobial Resistance
Authors: Farkouh Raymond , Nevo Arianna , Uyei Jennifer , Althouse Benjamin , Hall-Murray Cassandra , Lewnard Joseph , Wasserman Matthew
Published: January 2021

Background

Antimicrobial resistance (AMR) is a global threat to effective prevention and treatment of an ever-increasing range of infections. Pneumococcal conjugate vaccines (PCV) used in infant national immunization programs have been shown to decrease AMR pneumococci. Cost-effectiveness models evaluating the value for money of PCV programs have not considered the economic impact of reducing antimicrobial prescribing or prolonged infections due to treatment failures. Standardized frameworks are needed for models to address outcomes and impact on health resource utilization related to AMR.

Methods

We developed a conceptual modeling methodology suitable for a health economic evaluation of an infant PCV program. We considered impact of PCVs on pneumococcal disease (PD) specifically related to clinical management of AMR-PD, including AMR epidemiology, antibiotic prescribing patterns, and healthcare resource utilization. Model inputs were evaluated regarding optimal and available data sources considering the complex nature of AMR at the national, regional, and global level.

Results

The proposed framework considers impact of PCVs on antimicrobial prescribing due to invasive pneumococcal disease (IPD), community acquired pneumonia (CAP), and acute otitis media (AOM) across 3 pathways (Figure 1). The population and pathogen-level pathway describe epidemiology and vaccine impact. The care level pathway describes clinical disease management. The health outcomes pathway characterizes resistant or successfully treated PD costs and quality of life.

Conceptual Economic Model Methodology

Conclusion

We present a generalizable methodology to quantify impact of PCVs on cases and outcomes of PD related to AMR. Modelling vaccine-preventable burden of AMR-PD requires data extrapolations and assumptions due to the myriad of interconnected pathways (i.e. microbiology, epidemiology, environment, health systems). Further work is needed to validate assumptions and linkages across incomplete data sources.

Disclosures

Raymond Farkouh, PhD, Pfizer (Employee) Arianna Nevo, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Jennifer Uyei, PhD, MPH, Pfizer, Inc. (Other Financial or Material Support, I am an employee of IQVIA. IQVIA received funding from Pfizer to carry out the project.) Cassandra Hall-Murray, PharmD, Pfizer, Inc. (Employee) Joseph Lewnard, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Advisor or Review Panel member) Matthew Wasserman, MSc., Pfizer Inc. (Employee)
1397. Long term impact of the 13-valent pneumococcal conjugate vaccine use in infant immunization program on all-cause pneumonia hospitalizations in British Columbia, Canada: a time series analysis
Authors: Vadlamudi Nirma Khatri , Patrick David M , Hoang Linda , Rose Caren , Sadatsafavi Mohsen , Marra Fawziah
Published: January 2021

Background

Pneumonia is a leading cause of hospitalization and in-patient mortality globally. We determined the impact of 13-valent pneumococcal conjugate vaccine (PCV13) use on all-cause pneumonia hospitalization rates eight years after the vaccine was introduced in British Columbia, Canada.

Methods

Routine administrative databases, such as, hospital discharge abstract databases, registry and demographics were used to build the cohort. Overall and age-specific all-cause pneumonia hospital admissions per month (Jan 2000 to Dec 2018) for those aged < 2 years, 2-5 years, 6-17 years, 18-64 years and ≥ 65 years were obtained using International Classification of Diseases 9 and 10 codes (480-486, J12-J18). Changes in the all-cause pneumonia hospitalization incidence rates before and after the PCV13 vaccine program introduction were evaluated using a negative binomial regression and time-series modelling while adjusting for seasonality, influenza-likeness illnesses, 7-valent pneumococcal conjugate vaccine (PCV7) program and pre-PCV13 vaccine secular trends.

Results

Long term use of the PCV13 vaccine in the infant immunization program was associated with significant declines in all-cause pneumonia hospitalization rates among all children, < 2 years (IRR: 0.63; 95% Confidence Interval (CI): 0.59-0.67), 2-5 years (IRR: 0.82; 95%CI: 0.77-0.87) and 6-17 years (IRR: 0.73; 95%CI: 0.69-0.78). All-cause pneumonia rates did not change significantly in those aged 18-64 years (IRR: 0.98; 95%CI: 0.96-1), whereas a modest increase was observed in those 65 years and over (IRR: 1.05; 95%CI: 1.02-1.07). Consequently, we did not observe significant change in the overall rate (IRR: 1.02; 95%CI: 1-1.02).

Conclusion

Significant reduction in all-cause pneumonia hospitalization rates in children demonstrates long term beneficial effect of PCV13 use. A modest increase in all-cause pneumonia hospitalization rates in adults aged 65 years and over indicates a need for further microbial investigation.

Disclosures

Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support) Fawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support)
1402. Smart Technology and Education for Smart Protection against the Flu: Impact of a Multifaceted Quality Improvement (QI) Intervention on Influenza Vaccination Rates in Children
Authors: Kaushik Ashlesha , Beal Kristen , Gupta Sandeep , Malley Richard
Published: January 2021

Background

Low pediatric influenza vaccination rates are a public health challenge. It is imperative that innovative measures to promote influenza immunization are studied.

Methods

Aim: To study impact of a multifaceted QI intervention on influenza vaccination rates in children evaluated at outpatient clinics, urgent care (UC) and emergency departments (ED) at UnityPoint Health tertiary care centers (UPH) across Northwestern (NW) and Northcentral (NC) Iowa (IA). Patients aged 6 months-18 years evaluated at UPH in NW and NC IA (encompassing 5 outpatient clinics, 2 UC, 2 ED) were included. A multifaceted QI intervention was implemented on 9/1/2018 consisting of all of the following concomitantly: 1. Patient/family education: Posters about flu vaccination displayed at entrance, in waiting rooms and patient rooms throughout the clinics, UC, ED as well as patient/family handouts emphasizing importance of influenza immunization. 2. Information Technology: “Health maintenance” reminder in outpatient electronic medical record (EMR- EPIC) that appears as soon as a patient’s chart is accessed to remind nurses/providers that influenza vaccine is due. 3. Provider Education flyers at study sites about debunking flu myths. We compared pre-intervention period (P1, 09/01/2017– 05/31/2018) with intervention period (P2, 09/01/2018 – 05/31/2019) for influenza vaccination rates.

Results

A total of 10050 and 9889 patients were evaluated during P1 and P2 respectively. Influenza vaccination rate increased significantly from 56.1% (5642) in P1 to 73.3% (7252) in P2 (p< 0.0001). Patients were 1.43 times more likely to get vaccinated during P2 than P1 (95% CI= 1.32-1.46). Regionally during P2, influenza vaccination rate was higher than the national (62.6%; p< 0.0001) and Iowa state averages (65.8%; p< 0.0001) respectively. Proportion of children aged < 9 years receiving second dose of influenza vaccine increased from 43% to 69% (p< 0.001). Influenza vaccination rates among children aged 6-36 months increased significantly [40% (1078/2671) in P1 to 47.2% (1287/2723) in P2; p< 0.01].

Conclusion

With the combined educational and technologic intervention, pediatric influenza vaccination rates increased significantly across NW and NC IA, including proportion of patients receiving second dose of the vaccine.

Disclosures

Richard Malley, MD, Merck (Consultant)
1413. Trends in Risk of Respiratory Syncytial Virus Hospitalizations in Preterm Infants Over a 10-Year Period
Authors: Kong Amanda M , Winer Isabelle H , diakun david , Bloomfield Adam , Gonzales Tara
Published: January 2021

Background

The American Academy of Pediatrics (AAP) recommended respiratory syncytial virus (RSV) immunoprophylaxis (RSV-IP) to reduce the risk of severe RSV hospitalization (RSVH) for certain infants < 35 weeks gestational age (wGA) until 2014, when the AAP no longer recommended use among infants born >29 wGA without other medical conditions. Studies have shown that RSV-IP utilization subsequently decreased among these infants, as well as infants born < 29 wGA from whom RSV-IP is still currently recommended. We described RSVH rates among preterm (PT) infants < 35 wGA compared to term infants from 2008-2019.

Methods

We identified infants born between 7/1/2008 and 7/30/2019 in the MarketScan® Commercial and Multi-State Medicaid claims databases. Infants with a code for birth at < 35 wGA were classified by wGA. Those with a code for full-term without major health problems were classified as term. Infants contributed follow-up time during the RSV season (November to March) while < 6 months old, summarized as infant-seasons (days of follow-up during the RSV season divided by 151 [number of days in an RSV season]) (Table 1). Using diagnoses codes, we identified RSVH during each RSV season for infants < 6 months. Unadjusted rate ratios comparing PT infants to term infants were calculated to account for seasonal variation in virus circulation.

Number of Infants and Follow-up Time

Results

The number of infants contributing time at < 6 months old during the RSV season and their follow-up time are shown in Table 1. There were 796 RSVH among Commercial PT infants, 6,486 RSVH among Commercial term infants, 2,501 RSVH among Medicaid PT infants, and 13,962 RSVH among Medicaid term infants during the 10 seasons in the database. RSVH rates for PT infants tended to increase over time, with the exception of the 2009-2010 season for Medicaid infants (Table 2). Rate ratios comparing PT to term infants also increased after the 2014 guidance change (Figure 1 and 2). The risk of 29-34 wGA infants compared to term infants approximately doubled in the 5 years after the guidance change (Table 2).

Comparisons of RSV Hospitalization Rates for Preterm vs. Term Infants < 6 Months Old

Rate Ratios for RSV Hospitalization Rates for Commercial Infants < 6 Months Old

Rate Ratios for RSV Hospitalization Rates for Medicaid Infants < 6 Months Old

Conclusion

After the change in AAP recommendations for RSV-IP, increases in RSVH rates for infants born at 29-34 wGA compared to term were found. This was also true for < 29 wGA infants for whom RSV-IP is recommended, although the effect sizes were smaller.

Disclosures

Amanda M. Kong, DrPH, Sobi (Other Financial or Material Support, I am an employee of IBM Watson Health which received funding from Sobi to conduct this analysis.) david diakun, BS, Sobi (Grant/Research Support) Adam Bloomfield, MD, Sobi NA (Employee) Tara Gonzales, MD, Sobi, Inc. (Employee)
1416. Assessing the potential for interspecies transmission of Clostridioides difficile on dairy farms
Authors: Redding Laurel , Webb Terry , Barnhart Denise , Baker Linda , Bender Joseph , Kristula Michaela , Kelly Donna
Published: January 2021

Background

Clostridioides difficile (CD) can cause severe colitis in humans and many species of animals. It is thought that farm animals could be a reservoir for CD and that farm workers could therefore be at increased risk of colonization and infection with CD. While pigs and swine farm workers have been shown to be colonized with identical clones of CD, the zoonotic transmission of CD from animals to people has not been definitively demonstrated, and no studies have examined whether dairy farm workers, who are generally in closer contact with animals than swine farmers, are at increased risk of being colonized or infected with CD. The aim of this study was to assess whether dairy calves and farm workers harbored genetically similar isolates of CD.

Methods

First, we validated a glove-juice protocol to detect CD spores on the hands of farm workers. Volunteers’ hands were inoculated with serially diluted suspensions of non-toxigenic CD organisms, and hand rinsates underwent broth enrichment and anaerobic culture. Second, we collected fecal samples from 5 randomly selected dairy calves (< 7 d of age) from each of 23 farms in southeastern Pennsylvania, northern Maryland, and Delaware. We focused specifically on dairy calves, as the prevalence of CD is highest in this age group. Third, using the glove-juice protocol, we collected hand rinsates from 38 dairy farm workers who work closely with calves. Only 4 of these workers were willing to submit fecal samples along with their hand rinsates. All fecal samples and hand rinsates underwent broth enrichment and anaerobic culture for CD.

Results

Validation of the glove juice protocol showed that CD could be recovered successfully from all hand rinsate dilutions (up to 10-6). When applied to farm workers, this method yielded CD in none of the hand rinsates (0%, 95% CI 0.0-92.2%). CD was also not detected in any of the human fecal samples. However, CD was detected from calf fecal samples on 10 farms (43.5%, 95% CI 20.8%-80.0%).

Conclusion

While the zoonotic transmission of CD cannot be ruled out, our results suggest that contact with dairy animals is not likely to be associated with an increased risk of acquiring CD via the fecal-oral route. The glove-juice protocol appears to be a useful tool for studying the epidemiology of CD in populations where obtaining fecal samples is difficult.

Disclosures

All Authors: No reported disclosures
1429. Meningococcal Disease Outbreak in a Refugee Reception Identification Center in Greece and Administration of Mass Antibiotic Prophylaxis
Authors: Magaziotou Ioanna , Tsiodras Sotirios , Xirogianni Athanasia , Tseroni Maria , Syrigonaki Katerina , Stoli Artemis , Tsekou Aikaterini , Papandreou Anastasia , Sapounas Spyros , Panagiotakopoulos George , Theodoridou Maria , Tzanakaki Georgina , Georgakopoulou Theano
Published: January 2021

Background

An increased likelihood of transmission of communicable diseases such as invasive meningococcal disease (IMD) exists in refugee camps. Herein, we describe an outbreak investigation of 5 IMD cases among immigrants in Greece.

Methods

Epidemiological, clinical and laboratory data (culture and molecular identification) as well as the public health management concerning an outbreak of meningococcal disease in a refugee Reception Identification Center (RIC), are described.

Results

During the period 17th January - 17th February 2020, five cases of IMD in refugees were reported to the National Public Health Organization (NPHO). Four cases were from Afghanistan and resided in the RIC of Lesvos Island; two females aged 2 yo and 21 yo and two males 13 yo and 6 yo. The fifth case, a 4 month old male of Syrian nationality, exhibited symptoms after moving to an inland accommodation center (AC) from Lesvos RIC, on December 2019. Four of the cases presented with meningitis and septicaemia. All cases recovered and had no common exposure other than shared geographic space. Neisseria meningitidis was identified by molecular typing (mPCR, PorA, MLST, WGS) in all cases at the National Meningitis Reference Laboratory; 3/5 cases were identified as MenB, porA 7-2,4, and ST-3129 (new clone) while 2/5 (21 yo female, 13 yo male) as MenY, porA: 5.2, ST-22cc. To prevent secondary cases, antimicrobial chemoprophylaxis via Directly Observed Therapy (DOT) was administered to 4.024 Afgan close contacts (26.7% of the total Afgan population). MenACWY and MenB vaccination was recommended in response to outbreak among persons aged < 20 years old. No new IMD case occurred in the RIC during a follow-up period of 4 months.

Conclusion

The detection of a new clone in Greece of Chinese and Taiwanese origin through migrants, further underlines the need of enhanced surveillance for early detection, molecular typing, immediate intervention with antibiotic prophylaxis and/or supplemental vaccination in order to prevent IMD in refugee camps.

Disclosures

All Authors: No reported disclosures