bluuebunny/crossref_metadata_2025_split huggingface dataset:
1080. Relebactam Increases Imipenem Activity Against Imipenem-Nonsusceptible and -Susceptible Pseudomonas aeruginosa and Enterobacterales: Assessment of Isolates from RESTORE-IMI 2
Authors: Hilbert David W , Andrew DeRyke C , Losada Maria C , Moise Pamela , Chen Luke F , Young Katherine 
Published: December 2021

Abstract

Background
Relebactam (REL) inhibits class A and C β-lactamases (BLs) and is approved in the US in the combination imipenem/cilastatin/REL (IMI/REL) for hospital acquired bacterial pneumonia (HABP) and ventilator associated bacterial pneumonia (VABP), and also in patients with limited treatment options for complicated urinary tract infections and complicated intraabdominal infections. The objective of this study was to evaluate the potentiation of imipenem (IMI) by REL in baseline respiratory isolates from the recently completed Phase 3 RESTORE-IMI 2 study that demonstrated efficacy and safety of IMI/REL in the treatment of patients with HABP/VABP.

Methods
Baseline lower respiratory tract (LRT) isolates were evaluated for IMI MICs in the presence and absence of REL using broth microdilution and CLSI interpretive criteria. All Pseudomonas aeruginosa and Enterobacterales for which IMI/REL is either indicated or the MIC90 is less than or equal to the susceptibility breakpoint were evaluated.

Results
Summary statistics and the MIC distribution for P. aeruginosa are shown in the figure. For P. aeruginosa, REL reduces the IMI mode MIC of IMI-nonsusceptible (IMI-NS) (MIC &gt;2) isolates ≥8-fold (from 16-32 to 2 µg/mL) and that of IMI-susceptible (IMI-S) (MIC ≤2) isolates ≥2-fold (from 1 to ≤0.5 µg/mL). Among Enterobacterales, the IMI mode MIC of IMI-NS (MIC &gt;1) isolates was reduced ≥4-fold (from 2 to ≤0.5 µg/mL). REL enhanced the activity of IMI among IMI-S isolates (MIC ≤1), most notably observed in Enterobacterales species that produce a chromosomal AmpC, increasing the proportion with MIC ≤0.5 µg/mL from 76% to 98%.
MIC Distribution and Summary Statistics of RESTORE IMI-2 Isolates

Conclusion
Among baseline LRT isolates from RESTORE-IMI 2 the potentiation of IMI by REL results in the restoration of susceptibility among IMI-NS P. aeruginosa and Enterobacterales and enhanced IMI activity among IMI-S isolates. This enhanced activity among IMI-S Enterobacterales is most notable among species with reported chromosomal expression of AmpC. This lowering of IMI MICs upon addition of REL contributes to the high probability of target attainment (≥90%) observed following administration of IMI/REL 1.25g every 6 hours, further supporting the IMI/REL efficacy data observed in RESTORE-IMI 2.

Disclosures
David W. Hilbert, PhD, Merck (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck (Employee) Pamela Moise, PharmD, Merck (Employee) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck (Employee) Katherine Young, MS, Merck (Employee)
1100. A Prospective Evaluation of Neurotoxicity Among Patients Receiving Dose-Optimized Cefepime or Meropenem With Concomitant Therapeutic Drug Monitoring
Authors: Smith Brandon , Kline Ellen G , Shutter Lori , Fong-Isariyawongse Joanna , Urban Alexandra , Murray Holt , Byers Karin , Shields Ryan K 
Published: December 2021

Abstract

Background
Cefepime (FEP) induced neurotoxicity (NT) may have serious implications for patients (pts). Retrospective studies have employed variable definitions of NT, finding renal impairment and FEP trough concentrations (Cmin) &gt; 20 mg/L as risk factors. Prospective studies comparing antibiotics have not been performed.

Methods
We conducted a prospective study of pts receiving FEP or meropenem (MEM) with neurologic evaluation and therapeutic drug monitoring (TDM). A NT advisory board (NTAB) was established to develop standardized definitions of possible, probable and definitive NT (Fig 1). Cases of potential NT were adjudicated by the NTAB who were blinded to study treatment. FEP and MEM midpoint and Cmin concentrations were measured at steady-state by validated methods.

Results
127 patients were included (70 FEP, 57 MEM). Demographics and treatment characteristics were similar between groups (Fig 2); 63% were in the ICU. FEP and MEM Cmin varied from 1.9 – 140.5 and 0.6 – 31.3 mg/L, respectively. Median FEP Cmin and total exposures (AUC) were 23.1 mg/L and 347.6 hr*mg/L, respectively. Corresponding MEM values were 5.9 mg/L and 124.8 hr*mg/L, respectively. Cmin values were inversely correlated with renal function for both FEP and MEM (P&lt; 0.001). Rates of possible, probable, or definitive NT were 10% and 5% for FEP and MEM, respectively (P=0.51; Fig 3). 16% and 3% of pts with FEP Cmin &gt; or &lt; 20 mg/L had NT, respectively (P=0.11; Fig 4). Median MEM Cmin were 12.3 and 5.4 mg/L among pts with and without NT, respectively (P=0.09; Fig 4). Rates of NT did not vary by infusion length or dose. FEP and MEM exposures were similar between patients with (17%) or without (83%) microbiologic recurrence due to the same pathogen. FEP was discontinued in 4 pts due to NT; no pts stopped MEM due to NT.

Conclusion
Our study is the first to evaluate FEP NT prospectively and compare rates of NT to pts receiving MEM. We established criteria that were applied by a blinded NTAB. In doing so we found rates of NT to be lower than previously reported and not statistically different between FEP and MEM. Cmin values were highly variable and associated with numerically, but not statistically higher rates of NT for both agents. These findings serve as the basis for larger, multicenter studies and justify use of routine TDM to limit NT among high-risk pts.

Disclosures
Brandon Smith, MD, PharmD, Shionogi (Consultant, Advisor or Review Panel member) Alexandra Urban, MD, Neuropace (Consultant) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support)
1125. Decreasing Concomitant Vancomycin and Piperacillin-Tazobactam Use in Children to Reduce Incidence of Acute Kidney Injury
Authors: Lamb Gabriella S , Lamb Gabriella S , Traum Avram , Khoury Zana , Yim Ramy , Jones Sarah , Nakamura Mari M 
Published: December 2021

Abstract

Background
Concomitant use of vancomycin (V) and piperacillin-tazobactam (PT) is associated with increased incidence of acute kidney injury (AKI). AKI develops 3 times faster on this combination compared to alternative vancomycin combinations. We sought to reduce AKI in our patients by reducing concomitant use of V/PT using a QI framework.

Methods
We implemented several PDSA cycles to reduce concomitant V/PT use at a 415-bed quaternary children’s hospital in Boston, MA. Interventions included substitution of PT with other agents in surgical prophylaxis guidelines and order sets starting in February 2020 and in the hospital-wide sepsis order set in March 2021. The Antimicrobial Stewardship Program reinforced these changes during daily audit-and-feedback reviews. In November 2020, we implemented an electronic alert that apprises clinicians of the AKI risk when V/PT are ordered and recommends an alternative regimen. We measured the monthly number of patients on combination V/PT, new exposures to nephrotoxic medications, AKI events, and the percentage of days with serum creatinine monitoring for patients on ≥2 nephrotoxic medications.

Results
From 02/01/20 to 05/31/21, the number of patients exposed to combination V/PT decreased from 23 to 6 per month (Figure 1). New nephrotoxic medication exposures declined from 17.1 to 7.7 per 1,000 patient days, and AKI events dropped from 2.8 to 0.6 per 1,000 patient days (Figures 2 and 3). The percentage of days with serum creatinine monitoring increased from 60% to 66%.

Rate of New Exposures to Nephrotoxic Medications per 1000 Patient Days

Conclusion
Revising guidelines and electronic order sets and implementing an order alert led to marked decreases in exposures to V/PT and nephrotoxic medications overall and was associated with reduced AKI events. Use of electronic health record tools is an effective way to drive safer antimicrobial use.

Disclosures
Gabriella S. Lamb, MD, MPH, Nothing to disclose
1157. Determining the Clinical Utility of 16S rRNA in the Management of Pediatric Infections
Authors: Lim Peter Paul , Desai Ankita P , Cherian Sree Sarah , Malay Sindhoosha 
Published: December 2021

Abstract

Background
Conventional culture remains the gold standard to facilitate a targeted antimicrobial regimen in the treatment of bacterial infections. However, certain pediatric infections are caused by fastidious organisms and treatment with antibiotics prior to specimen collection may hamper growth of pathogens in routine culture. The use of 16S rRNA in culture negative infections has improved identification of bacterial pathogens in select scenarios. However, the specific impact of 16S rRNA on clinical decision making, especially in pediatric infections, is not well-defined. This study aims to elucidate the utility of 16S rRNA on clinical management of pediatric infections.

Methods
A retrospective analysis was done on different clinical specimens which had 16S rRNA performed from August 2016 – March 2020 in our institution. Detailed chart review was performed to determine how the 16S rRNA result impacted clinical decision making. Clinical utility was defined as change in patient’s overall antimicrobial regimen, pathogen confirmation, and treatment duration.

Results
Seventy-four samples from 71 pediatric patients were included in the analysis: 32 (43%) were fluid specimens and 42 (57%) were tissue specimens. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p &lt; 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n=9, 30%) followed equally by joint fluid (n=6, 20%) and bone (n=6, 20%). There was no significant difference in clinical utility between fluid and tissue specimens (p= 0.346). In 64 patients whose antimicrobial spectrum coverage was analyzed, patients with broad spectrum coverage was decreased from 48 to 21 and narrow spectrum coverage increased from 16 to 43 using 16S rRNA result, though not significant (p= 0.4111). Of all patients included in the analysis, the median number of antibiotics used before 16S rRNA result, 2, was significantly decreased to 1 (p &lt; 0.0001).

Conclusion
16S rRNA has a significant impact in terms of decreasing number of antibiotics used in treatment of pediatric infections. Pulmonary specimens have the highest clinical utility among all samples. Additional cost benefit analysis needs to be completed to further determine clinical benefit.

Disclosures
All Authors: No reported disclosures
1164. Acquisition of Methicillin-Susceptible Staphylococcus aureus in the Neonatal Intensive Care Unit: Molecular Comparison of Relatedness of Isolates
Authors: Eid Dalia F , Gomez-Simmonds Angela , Boyar Vitaliya , Uhlemann Anne-Catrin , Rubin Lorry G 
Published: December 2021

Abstract

Background
In the NICU MSSA infections occur frequently and cause morbidity and mortality. Colonization is a risk factor for infection. Optimal infection prevention strategies await a more complete understanding of acquisition and transmission. To investigate possible transmission, we studied whether newly MSSA colonized infants share a strain with another contemporaneously colonized infant.

Methods
This is a prospective observational study in a level IV NICU from April through November 2019. Infants had weekly MSSA nasal surveillance cultures. Isolates from newly MSSA colonized infants and other infants colonized with MSSA during the same/previous week were subjected to staphylococcal protein A (spa) typing; most pairs with a concordant (CC) spa type were analyzed by whole genome sequencing (WGS; Illumina MiSeq). Pairs of isolates with a CC spa type and &lt; 25 single nucleotide polymorphism differences on WGS were considered closely related (CC pairs). A control group consisted of pairs of isolates from a newly colonized infant with one randomly chosen colonized infant with a discordant (DC) spa type during the same/previous week. The medical records were reviewed for staff member (SM) and room assignment. Fischer’s exact test was used to compare proportions.

Results
Isolates from 60/68 consecutive newly MSSA colonized infants and 111/133 comparison infants were available for spa typing. Of these 60 infants, 23 (38 %) had a CC spa type with another infant colonized during the same/previous week. Of 18 isolate pairs from infants with a CC spa type that were subjected to WGS, 12 (67%) pairs of isolates were closely related. 7/12 (58 %) of CC pairs had a SM in common compared to 2/13 (15 %) in the DC pair groups, p=0.04. 2/12 (17 %) of CC pairs shared a room compared to 2/13 (15 %) pairs in the DC group, p=1.0.

Conclusion
Among newly MSSA colonized infants at least 25% are colonized with an isolate closely related to that of another colonized infant indicating likely infant to infant transmission. WGS is more discriminatory than spa typing for MSSA. Given the lack of commonality of room assignment and the commonality of SM assignment, a possible role of healthcare personnel in MSSA transmission should be further investigated.

Disclosures
Anne-Catrin Uhlemann, MD, PhD, Merck (Grant/Research Support)
1165. Seroprevalence of Chagas Disease among Latin American Children Living in New York
Authors: Handel Andrew S , Hellman Harriet , Flores Egar , Beneri Christy 
Published: December 2021

Abstract

Background
Approximately 300,00 individuals in the United States are estimated to have Chagas disease. To date, only one seroprevalence study in the US has included children. Diagnosis during childhood prevents irreversible sequelae and is better tolerated than during adulthood. Seropositive children may be difficult to identify, as those infected vertically may have never visited an endemic region. We sought to identify children with Chagas disease through a pilot study of serology and risk factors.

Methods
Participants were recruited from Stony Brook University Hospital (SBUH) or an ambulatory pediatric office, both in Suffolk County, New York (population: 1,476,000; 20.2% Hispanic or Latino). Study participants were 1 - 25 years old, resided in Suffolk County, and either the child and/or the child’s mother was born in or had long-term residence (≥ 3 years) in Latin America. T. cruzi serum IgG was determined with a Chagatest ELISA (Weiner Lab) or a Chagas Detect Plus Rapid Test (InBios). Positive screens were confirmed with a second serologic test at the CDC. Participants completed a survey of demographics and Chagas disease knowledge and risk factors, in English or Spanish. Descriptive statistics were applied. SBUH IRB provided study approval.

Results
We enrolled 93 children (Table 1). Three (3.2%) had a positive IgG screen, of which only one had a confirmed infection (1.1%). This was a 17-year-old who had lived in a rural adobe home and moved to the US at 8 years old. No children or their mothers recalled being bitten by or seeing triatomine insects in their Latin American homes. Of 27 children whose mothers had been screened for infection, 13 were born to 3 mothers with confirmed Chagas disease; all 13 children were seronegative. Of 8 participants reporting other family members with Chagas disease, all were seronegative.
Demographics of 93 participants screened for Chagas disease

SD
standard deviation; US: United States

Conclusion
Without reliable tools for identifying those at greatest risk of Chagas disease, universal screening of children born in high-risk Latin American regions remains a reasonable strategy. In addition, screening mothers born in Latin America is likely a more cost-efficient means to evaluate second-generation children. A tremendous knowledge gap of pediatric Chagas disease in the US remains.

Disclosures
All Authors: No reported disclosures
1168. Are the Staphylococcus aureus Isolates that Recolonize Infants in a NICU Following Successful Decolonization the Same or Different from the Initial Colonizing Isolate?
Authors: Rubin Lorry G , Balamohan Archana , Gomez-Simmonds Angela , Boyar Vitaliya , Chong Alexander , Uhlemann Anne-Catrin 
Published: December 2021

Abstract

Background
Staphylococcus aureus is an important pathogen of infants in a neonatal intensive care unit (NICU). Colonization precedes infection and decolonization may prevent infection. The origin of colonizing organisms may be the NICU environment or personnel or visitors. We have observed infants who became recolonized after successful decolonization. The purpose of this study was to determine the proportion of infants who become recolonized with the same strain or a different strain.

Methods
Eligible infants were consecutive infants who 1. were colonized with methicillin-susceptible S. aureus and were successfully decolonized with topical mupirocin ointment (nares and umbilicus) as evidenced by 2 or more consecutive negative weekly surveillance cultures (in the absence of a course of systemic antibiotics with activity against MSSA), 2. subsequently became recolonized, and 3. the pair of isolates was available for analysis. Isolates were analyzed by staphylococcal protein A (spa) typing and pairs with concordant spa types were subjected to whole genome sequencing (WGS; Illumina MiSeq) and phylogenetic analyses. Pairs of isolates with fewer than 25 single nucleotide polymorphism differences were considered closely related.

Results
There were 19 occurrences of MSSA recolonization in 17 infants following 2-6 (median, 2) negative weekly intervening surveillance cultures. Based upon spa typing (that identified 19 spa types), in 11 (58%) there was a concordant spa type and in 8 (42%) there was a discordant spa type. Of the 11 pairs of isolates with concordant spa types that were compared after WGS, 10 were closely related resulting overall in recolonization with a closely related strain in 53% of episodes.

Conclusion
Among MSSA colonized infants who become recolonized after successful decolonization, the recolonizing strain is the same as the original strain in over half of cases. In such cases the source is more likely to be a visitor than the NICU environment or staff. The possibility that some cases classified as recolonization were in fact persistent low level colonization or carriage in another body site not detected by surveillance cultures cannot be excluded.

Disclosures
Anne-Catrin Uhlemann, MD, PhD, Merck (Grant/Research Support)
137. Risk Factors of B-lactams Associated Cytopenias during Outpatient Parenteral Antimicrobial Therapy: Results from a Large National Sample
Authors: Hamad Yasir , Nickel Katelin B , George Ige , Burnett Yvonne J , Olsen Margaret A 
Published: December 2021

Abstract

Background
Cytopenias are rare complications of prolonged beta-lactam use; however, incidence and associated risk factors are not well described.

Methods
Patients aged 18-64 years in the 2010-2016 IBM MarketScan Commercial Database discharged from the hospital on cephalosporin, penicillin, or carbapenem outpatient Parenteral Antimicrobial Therapy (OPAT) were included. The primary endpoint was hospital admission coded for neutropenia, leukopenia, or thrombocytopenia within the first 6 weeks post index discharge and within 7 days of beta-lactam discontinuation. Patients with history of malignancy and those who are on chemotherapy were excluded. Significant factors in univariate analysis were incorporated into a multivariable logistic regression model with sequential exclusion of variables with p &gt; 0.1.

Results
A total of 35,102 patients received beta-lactam OPAT; median age was 52 years and 53.6% were male. The primary outcome occurred in 150 (0.43%) patients at a median of 19 days (IQR 10-28 days after index discharge), which included 63 (0.18%) neutropenia, 85 (0.24%) thrombocytopenia, and 23 (0.07%) leukopenia admissions. Factors independently associated with readmission cytopenias included chronic liver disease (OR 4.61 [CI 2.93-7.25]), valvular heart disease (2.69 [1.71-4.24]), receipt of vancomycin (2.10 [1.42-3.12]), or antifungal therapy (4.42 [2.01-9.68]); lower risk was associated with carbapenem therapy (0.49 [0.32-0.75]) and diabetes (0.48 [0.31-0.74]) (Table 1).

Conclusion
Readmissions with cytopenias during beta-lactam OPAT were rare and carbapenem use was associated with lower risk compared to other classes of beta-lactams. Combination of beta-lactam with vancomycin was associated with an increased risk of cytopenias, and those patients might benefit from closer monitoring.
Table 1. Factors Associated with Cytopenias during Beta-Lactams Outpatient Parenteral Antimicrobial Therapy (OPAT)

Disclosures
Margaret A. Olsen, PhD, MPH, Pfizer (Consultant, Research Grant or Support)
1185. Oseltamivir Prescribing Patterns for Infants with Influenza and Factors Associated with Guideline Adherence
Authors: Zaheer Haniah A , Chamseddine Sarah , Liu Hui , Williams John V , Martin Judith M , Rick Anne-Marie 
Published: December 2021

Abstract

Background
The Centers for Disease Control and Prevention (CDC) recommends oseltamivir be given to children &lt; 2 years old with confirmed or suspected influenza as they are at high risk for complications. We sought to analyze oseltamivir prescribing patterns and to describe factors associated with adherence and non-adherence to CDC guidelines.

Methods
We used a retrospective cohort of infants ≤ 12 months old born from January 1, 2011 to December 31, 2019 within the University of Pittsburgh Medical Center health system in Southwestern Pennsylvania and who had ≥ 2 well-child visits during their first year. Infants with laboratory-confirmed influenza from January 1, 2011 to April 30, 2020 were included. Electronic health records were reviewed to describe oseltamivir prescriptions and influenza-related characteristics. Factors associated with adherence and non-adherence to CDC influenza treatment guidelines were assessed with univariate logistic regression.

Results
Of 422 infants with laboratory-confirmed influenza, 86% were prescribed oseltamivir. The proportion of infants prescribed oseltamivir increased from an average of 63% during 2011-2016 to 90% during 2016-2020 (OR:5.2; 95%CI: 2.9-9.5). 96% of prescriptions instructed twice daily dosing, 2% had once daily, and 2% were unknown frequency. 91% of prescriptions were for 5 days, 7% had no duration, and 2% were for &gt; 5 days. Infants ≥ 6 months of age compared to &lt; 6 months were less likely to be prescribed oseltamivir (83.3% vs. 100%; p&lt; 0.001); tested for influenza in the emergency room/urgent care (OR: 0.3; 95%CI: 0.2-0.6), or admitted to the hospital (OR:0.5; 95%CI:0.2-0.9). Infants were more likely to be treated with oseltamivir if they had a known influenza positive contact (OR:2.3; 95%CI:1.0-5.2) or had fever ≥ 38.0C (OR:2.0; 95%CI:1.2-3.5). There was no difference in prescribing practices based on history of prematurity or chronic medical conditions.

Conclusion
Adherence to CDC influenza treatment guidelines for infants is high and has improved over time. However, targeted education at high-risk contact points may further improve guideline adherence.

Disclosures
John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)