bluuebunny/crossref_metadata_2025 huggingface dataset:
1432. Population-based Surveillance of Carbapenem-Resistant Enterobacteriaceae (CRE) in Alameda County, 2017-2020
Authors: Horwich-Scholefield Sam , Lloyd Tyler , Varghese Vici , Yette Emily , Huang Sandra , Pandori Mark
Published: January 2021

Background

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially those that are carbapenemase-producing (CP), are difficult to treat and result in high mortality— the Centers for Disease Control and Prevention (CDC) designates CRE an urgent level threat to public health. Alameda, a northern California county with 1.67 million residents, mandates submission of all carbapenem-resistant isolates Escherichia coli, Klebsiella spp., and Enterobacter spp. We assessed the genetic profiles of CRE isolates and compared to aggregate US data from the same time period.

Methods

Isolates are submitted to the Alameda County Public Health Laboratory (ACPHL), where antimicrobial resistance genetic markers are identified by whole genome sequencing (WGS) using single-end, 150-cycle reactions in a MiSeq (Illumina). Resistance genes were identified using pipelines built in Geneious and confirmed with Resfinder. All epidemiological analyses were conducted using R (Version 4.0).

Results

ACPHL performed WGS on 226 CRE isolates submitted between June 2017 and February 2020. A total of 34/95 (36%) Klebsiella spp., 17/60 (28%) E. coli, and 10/71 (14%) Enterobacter spp. a carbapenemase enzyme. Among all Enterobacteriaceae, 21/226 (9%) produced the New Delhi-metallo-β-lactamase (NDM) carbapenemase (Table 1). Among all CRE, 17/226 (8%) were Klebsiella pneumoniae with the multilocus sequence type (MLST) of ST-258. All six Klebsiella pneumoniae ST-35 and ST-11 isolates produced a carbapenemase (Table 2).

Table 1: Carbapenemases, Extended Spectrum β-Lactamases (ESBL) and Other β-Lactamases by Organism

Table 2: Organism, Multilocus Sequence Type (MLST) and Carbapenemases Present

Conclusion

Compared to US data, Alameda County Klebsiella spp. were nearly half as likely to produce any carbapenemase, and E. coli were three times more likely to produce an NDM carbapenemase. CP-CRE represented a wide array of MLST, with the globally distributed KPC-producing outbreak strain ST-258 being the most frequently identified. Two strains that have been associated with hypervirulent and multidrug resistant infections in Asia, K. pneumoniae ST-35 and ST-11, were also reported.

Disclosures

Sam Horwich-Scholefield, MPH CIC, Merck (Research Grant or Support)
1436. Use of Whole Genome Sequencing to Characterize Antimicrobial-resistant Salmonella Berta Isolates from Clinical and Retail Meat Sources
Authors: M’ikanatha Nkuchia M , Jacques Rachael , Faucette David , Lisa Dettinger , Libuit Kevin , Tate Heather
Published: January 2021

Background

Antimicrobial resistance (AMR) in foodborne pathogens of animal origin, including non-typhoidal Salmonella (NTS) are a public health concern. Pennsylvania conducts integrated surveillance for AMR in NTS isolates from human and animal sources in collaboration with the National Antimicrobial Resistance Monitoring System (NARMS).

Methods

During 2009-2014, Salmonella enterica isolates from various types of meat purchased from randomly selected retail outlets in southeastern Pennsylvania were analyzed by pulsed-field gel electrophoresis (PFGE). We compared PFGE patterns from meat with clinical isolates in the Pennsylvania surveillance database. All meat isolates and a subset of matched clinical isolates were tested for susceptibility to antimicrobial agents. Eleven isolates with indistinguishable PFGE patterns were analyzed by whole genome sequencing (WGS). Sequence data were uploaded to the FDA’s GalaxyTrakr platform for quality assessment, genome assembly, AMR gene detection, and phylogenetic inference via single-nucleotide polymorphism (SNP) analysis.

Results

PFGE patterns of 86 (48.6%) of 177 meat isolates had PFGE matches to 1,665 clinical isolates; 40 distinct PFGE patterns were represented among the shared patterns. Seventeen (43%) of the 40 shared PFGE patterns (with ≥1 isolate(s) from both sources) were considered multi-drug resistant (MDR). Among the 48 S. Berta pattern JAXX01.0001 isolates, 5 (10.9%) and 2 (100%) from human and meat sources respectively were MDR including resistance to amoxicillin and ceftriaxone. WGS analysis of one isolate from ground turkey meat (PNUSAS061602) was genetically related to clinical isolates including two within 9 and 11 SNPs [Figure]. Presence of genes that hydrolyze extended spectrum cephalosporins (ESC), [blaCMY, blaHERA, or blaTEM], was identified in eight (two meat and six clinical) isolates. One meat isolate was resistant to six antibiotics including ceftriaxone.

Figure 2. Single nucleotide polymorphism (SNP) distance matrix showing relatedness in non-typhoidal Salmonella isolates from retail meat (n=2) and human (n=9) sources — Pennsylvania, 2010-2014. One S Berta from retail meat was separated from two clinical two clinical isolates by 9 and 11 SNPs. Second isolate from meat was separated from those associated with human infections by 14 (n=1), 17 (n=1) and ≥20 (n=7).

Conclusion

WGS analysis revealed clinically relevant ESCs genes in closely related S. Berta isolates from human and animal sources. Presence of these genes in NTS highlights the need for enhanced One-Health surveillance and judicious use of antibiotics in humans and food-animal production.

Disclosures

All Authors: No reported disclosures
1440. The Genetic Basis for a Neisseria gonorrhoeae Clinical Isolate That Contains mtrR-79 Mutation But Is Highly Susceptible to Antibiotics Effluxed by the Mtr Pump System
Authors: Huang Jianzhong , Ingraham Karen
Published: January 2021

Background

Neisseria gonorrhoeae (NG) possesses multiple drug efflux systems that play an important role in evading antibiotics in the treatment for gonorrhea and in helping this pathogen to evade innate antimicrobial defenses during infection. The mtrR-79 and mtr120 mutations in the promoter region between mtrR and mtrCDE are common mutations contributing to overexpression of the MtrCDE efflux pump resulting in increased efflux to multiple antibiotics including macrolides, β-lactams and tetracycline. However, we found a NG clinical isolate that contains the mtrR-79 mutation but is highly susceptible to antibiotics effluxed by the MtrCDE pump system.

Methods

PCR amplification, DNA sequencing and natural transformation were used to investigate the genetic basis responsible for the increased susceptibility by this isolate.

Results

We amplified by PCR the individual genes of mtrCDE, respectively, from this susceptible isolate as well as a NG isolate that contains the mtrR-79 mutation with increased efflux; there was no difference in the size of PCR products between the susceptible isolate and the isolate with increased efflux, indicating there was no large deletion/insertion in these genes. DNA sequence analysis of mtrCDE revealed the susceptible isolate also contained a loss-of-function mutation ΔGC from a 6 GC repeat GCGCGCGCGCGC in mtrC resulting in MtrC A117 frameshift predicted to produce a truncated MtrC protein that results in a low efflux phenotype. Natural transformation of the susceptible isolate with a wild type mtrC and selection with ciprofloxacin generated transformants that corrected the ΔGC mutation and restored the increased efflux phenotype.

Conclusion

Our results indicate that genotyping of mtrR and the promoter region between mtrR and mtrCDE is insufficient to predict increased efflux phenotype and provide direct evidence that NG isolates with elevated efflux is able to genetically revert to low efflux via loss-of-function mutations in the coding region of the efflux pump genes.

Disclosures

Jianzhong Huang, PhD, GlaxoSmithKline (Employee, Shareholder) Karen Ingraham, MS, GlaxoSmithKline (Employee, Shareholder)
119. Procalcitonin to Guide Antibiotic Therapy for Respiratory Infection: A Systematic Review of Systematic Reviews
Authors: York Joshua A , Varadarajan Maithili , Yates Joseph R , Barlow Gavin
Published: January 2021

Background

Antimicrobial resistance is an international calamity; closely linked to antibiotic use. Safely reducing antibiotic course length and overall use are imperative. Procalcitonin (PCT) is a biomarker expressed in serum in response to bacterial infection. Systematic reviews (SRs) evaluating PCT as an adjunct to guide antibiotic therapy have been performed but its use remains contentious. The aim of this SR of SRs was to evaluate the extent to which PCT impacts the likelihood of antibiotic initiation and antibiotic duration in cases of respiratory infection.

Methods

A systematic search of databases using an a priori strategy was conducted. SRs which reported an outcome related to antibiotic initiation and/or duration in the context of respiratory infection were included. Data extraction was performed by the first author and checked independently by a second author. The quality of SRs was assessed by two authors independently using ROBIS criteria. Disagreements were resolved by consensus with a third author. Results are presented narratively and in tabular format (Table 1 and Table 2).

Results

13 SRs were included (see PRISMA diagram). The number of respiratory patients included in these SRs ranged from 308 to 6708 (median = 3457). There was a consistent finding of a statistically significant reduction in antibiotic initiation in the PCT study group compared to the control group (Table 1). SRs that meta-analysed antibiotic duration (n = 9) as a difference in days showed a median reduction of 2.15 days (reduction range 0.80 to 3.83 days) with PCT use.

PRISMA Diagram

Table 1: Summary of odds ratios/ risk ratios in antibiotic initiation with the use of PCT

Conclusion

PCT use leads to a reduction in antibiotic initiation for respiratory diseases. It also results in a decrease in antibiotic duration, but this finding was not consistently statistically significant. There are no data presented in the SRs about the impact of this on antimicrobial resistance.

Disclosures

All Authors: No reported disclosures
1467. Association between Pathogen Load in the Upper Respiratory Tract and Severe Acute Respiratory Infections in Guatemalan Adults: Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pneumoniae, Klebsiella pneumoniae
Authors: Hamid Sarah , Milucky Jennifer , Shang Nong , Wolff Bernard , Van Beneden Chris , Winchell Jonas , López María Reneé , Clasen Thomas , McCracken John P
Published: January 2021

Background

The causal attribution of bacterial pathogens to severe acute respiratory infections (SARI) is challenging because many bacteria are frequently detected in the upper respiratory tract of asymptomatic persons. Quantification of pathogen load may help differentiate asymptomatic pathogen carriage from clinically significant infection. We aimed to determine whether real-time PCR (rt-PCR) cycle threshold (Ct) values, as a proxy for bacterial load, differ between adults with SARI and asymptomatic adults.

Methods

Adults with SARI (acute onset of fever and cough, requiring hospitalization) were frequency matched to asymptomatic adults (enrolled from trauma and orthopedic inpatient wards) by age group, catchment area, and enrollment date at three surveillance sites in Guatemala. Nasopharyngeal and oropharyngeal specimens were collected from all participants and tested for pathogens using rt-PCR. Using the Wilcoxon rank sum test, we compared the distributions and median Ct values between ill and asymptomatic adults in whom Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pneumoniae, and Klebsiella pneumoniae were detected.

Results

Between October 2013 and October 2015, 304 adults with SARI and 174 asymptomatic adults were enrolled (Table). M. catarrhalis, S. aureus, and S. pneumoniae were detected with similar frequency in both groups. H. influenzae and K. pneumoniae were detected more frequently in asymptomatic adults. We found the greatest difference in Ct value distributions between ill (median Ct=30.8) and asymptomatic adults (median Ct=35.6) with S. pneumoniae detections (p< 0.01) (Figure). Median Ct values of H. influenzae (29.3 vs 31.1, p=0.04) and M. catarrhalis (29.2 vs 31.5, p=0.05) were also lower among adults with SARI.

Frequency of select bacterial pathogen detection among adults with SARI and among asymptomatic adults, Guatemala, 2013-2015

Distributions of Ct values among adults with SARI and asymptomatic adults in whom a given bacterial pathogen was detected

Conclusion

Pathogen loads of S. pneumoniae, H. influenzae, and M. catarrhalis were higher among adults with SARI than among asymptomatic adults, suggesting that Ct values may provide insight into SARI etiology for some pathogens, despite the similar frequency of detection among both ill and asymptomatic adults. Future work will normalize Ct values to account for variation in testing and analysis and explore the use of Ct values to estimate population attributable fractions of respiratory infections.

Disclosures

All Authors: No reported disclosures
1474. Impact of 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Non-bacteremic Pneumococcal Pneumonia (NBPP) among Adults in the United States, 2013-2017
Authors: Gierke Ryan , Matanock Almea , Shang Nong , Farley Monica M , Schaffner William , Thomas Ann , Reingold Art , Harrison Lee , Schleiss Katherine , Burzlaff Kari , Petit Susan , Alden Nisha B , Pilishvili Tamara
Published: January 2021

Background

PCV13 was recommended for U.S. children in 2010 and for adults ≥ 65 years in 2014. Vaccine coverage among adults ≥ 65 years was 43% in 2017. We evaluated PCV13 impact on NBPP among adults.

Methods

NBPP cases (clinically or radiographically confirmed pneumonia and a positive pneumococcal urine antigen test (PUAT) in a hospitalized adult aged ≥ 18 years) were identified at select hospitals in 10 sites within CDC’s Active Bacterial Core surveillance during 2013-2017. NBPP rates (per 100,000) were estimated using U.S. Census Bureau population denominators and adjusted for the proportion of pneumonia patients tested by PUAT and the number of pneumonia admissions in the catchment area.

Results

Between 2013 and 2017, 4,430 NBPP cases were identified. Adults aged ≥ 65 years accounted for 49% of cases. Case fatality rate was 6%. From 2013 to 2014, rates of NBPP declined from 153 to 90 (41% reduction, 95%CI 28%, 51%) in ≥ 65 year-olds; 60 to 40 (34% reduction, 95%CI 22%, 45%) in 50-64 year-olds; and 15 to 10 (36% reduction, 95%CI 25%, 47%) in 18-49 year-olds. From 2014 to 2017, rates of NBPP increased in all ages, but remained below 2013 rates (Figure).

Figure. Estimated Annual Non-Bacteremic Pneumococcal Pneumonia Incidence by Age Group, 2013–2017

Conclusion

Reductions in NBPP among adults were primarily due to indirect effects of PCV13 use in children, with no additional declines following PCV13 introduction for adults aged ≥ 65 years.

Disclosures

Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant) Nisha B. Alden, MPH, CDC (Grant/Research Support)
1476. Impact of an Educational Campaign on Rates of Sputum Culture Acquisition as an Opportunity for Antibiotic De-escalation
Authors: Snawerdt Jessica , Bremmer Derek N , Carr Dustin R , Walsh Thomas L , Trienski Tamara , Buchanan Carley
Published: January 2021

Background

The 2019 community-acquired pneumonia (CAP) guidelines recommend obtaining a sputum culture in patients who are empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa to assist clinicians in optimizing antimicrobial therapy. A previous study at our institution found respiratory cultures were rarely obtained in patients with CAP. As a result of these findings, an educational campaign was implemented to promote the use of an induced sputum protocol.

Methods

This was a multicenter, retrospective cohort study that included patients who were ≥18 years of age, had a diagnosis of CAP, and received ≥48 hours of anti-pseudomonal antibiotics. Patients were excluded if mechanically ventilated within 48 hours of admission or diagnosed with hospital-acquired or ventilator-associated pneumonia. Patients were grouped into pre- and post-intervention time periods. The intervention involved education on obtaining respiratory cultures including technique on induced sputums and updates to CAP order sets. The primary outcome was the rate of sputum culture acquisition. Secondary outcomes included duration of anti-pseudomonal and anti-MRSA therapy, in-hospital mortality, and length of stay.

Results

A total of 143 patients met inclusion criteria, 72 in the pre-implementation group and 71 in the post-implementation group. Baseline characteristics were similar between the two groups. More patients in the post-implementation group had a sputum culture obtained but the difference was not statistically significant (38.9% vs 53.5%; p=0.08). Anti-pseudomonal therapy was continued for an average of 5.6 days pre-implementation and 5.2 days post-implementation (p=0.499). There was also not a significant difference in anti-MRSA duration between the two groups (3.4 days vs 3.2 days; p=0.606). In-hospital mortality and length of stay were similar between the two groups.

Conclusion

An educational campaign focusing on the acquisition of induced sputums led to an increase in rates of sputum cultures collected. However, this did not correlate with a decrease in duration of anti-MRSA or anti-pseudomonal therapy. Further interventions should be made to optimize de-escalation of broad spectrum antibiotics based on sputum culture results.

Disclosures

All Authors: No reported disclosures
1477. Impact Of Resistance Thresholds On Mortality In Hospital-Acquired And Ventilator-Associated Pneumonia
Authors: Mazi Patrick B , Guillamet M Cristina Vazquez , Micek Scott , Kollef Marin
Published: January 2021

Background

Hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) represent a significant source of morbidity and mortality in hospitalized patients. Numerous studies demonstrate mortality benefit with appropriate empiric therapy. Choosing the right empiric coverage is paramount; however, this decision becomes more challenging as rates of antibiotic resistance rise. Most recent HAP/VAP guidelines use an arbitrary population resistance rate of 20% to recommended methicillin-resistant Staphylococcus aureus (MRSA) coverage and double-coverage of resistant gram negative bacilli (GNB). Using this threshold has led to overuse of broad spectrum antimicrobials. The goal of this study is to mathematically explore the impact of this threshold on patient outcomes and link population resistance rates to individual mortality risk.

Methods

We used the concept of excess morality risk (EMR) to develop a theoretical simulation model based for HAP/VAP caused by GNB and MRSA empirically treated with piperacillin-tazobactam and vancomycin. EMR is the product of the proportion of HAP/VAP caused by GNB/MRSA, the rate of antibiotic (piperacillin-tazobactam/ methicillin) resistance in GNB and Staphylococcus aureus isolates and the difference in mortality between discordant and appropriate antibiotic therapy. Model parameters were obtained from large surveillance networks and published clinical trials.

Results

At the HAP/VAP guideline threshold of 20% methicillin resistance in SA isolates, the EMR was 0.3%; when the model included only culture positive patients, EMR was 0.6%. At a threshold of 20% resistance to piperacillin-tazobactam in GNB isolates, EMR was 1.9% and 3.1% when culture-negative patients were excluded. EMR increased as baseline risk of failure with discordant therapy increased (e.g. critically ill patients, ventilated HAP).

Risk Difference of Death for Staphylococcus aureus Isolates

Risk Difference of Death for Gram Negative Bacilli

Conclusion

This model offers a mathematical exploration of the individual excess risk for death in patients with HAP/VAP caused by GNB/MRSA because of discordant therapy. The objectivity of the model would better allow clinicians, guideline authors, and health policy makers to weigh excess risk versus possible harms of broad-spectrum therapy when developing population resistance thresholds cutoffs for empiric therapy recommendations.

Disclosures

All Authors: No reported disclosures
121. Temporal Trends in Urine Culture Rates in the U.S. Acute Care Hospitals During 2012–2017
Authors: Kazakova Sophia , McCarthy Natalie , Baggs James , Hatfield Kelly M , Wolford Hannah , Olubajo Babatunde , Jernigan John A , Reddy Sujan
Published: January 2021

Background

Decreasing inappropriate urine cultures in hospitalized patients has been a target of diagnostic stewardship to improve infection surveillance and antimicrobial use. The impact of such efforts has been largely unstudied. This study assessed temporal trends in urine culture rates in a cohort of acute care hospitals (ACHs) between 2012 and 2017.

Hospital Level Variation in Admission Urine Culture Rates

Hospital Level Variation in Post-admission Urine Culture Rates

Methods

We used microbiology data from ACHs participating in the Premier Healthcare Database and Cerner Health Facts to measure monthly urine culture rates. All cultures from the urinary tract collected on or before day 3 were defined as admission cultures (AC) and those collected on day 4 or later as post-admission cultures (PAC). Temporal trends in AC and PAC rates were estimated using general estimating equation models adjusting for hospital-level clustering, hospital size, teaching status, urban/rural designation, discharge month, and region.

Results

During the study period, ACHs had 20.8 million discharges and performed 4,946,717 urine cultures, of which 21% were PAC. In 2012 and 2017, the unadjusted AC rates were 18.7 and 18.4 per 100 discharges; the unadjusted PAC rates were 11.5 and 8.5 per 1,000 patient days (PD) respectively. The median annual hospital-level AC rate was 17.2 with inter-hospital variation ranging from 12.7 (quartile 1) to 24.1 (quartile 3) per 100 discharges, Figure 1. Similarly, the PAC rates varied among the ACHs with a median of 7.1 and inter-hospital variation ranging from 4.6 (quartile 1) to 10.5 (quartile 3) per 1,000 PDs, Figure 2. In multivariable analysis, no temporal trends in AC rates were detected (rate ratio (RR) 1.01; 95% confidence interval (CI): 0.99–1.02). However, PAC rates decreased 6.3% annually (RR 0.937; 95% CI: 0.93–0.95). Factors significantly associated (p< 0.02) with PAC rates were discharge month, teaching status, bed size, and region. For AC, significant associations (p< 0.0001) were discharge month and region.

Conclusion

Between 2012 and 2017, the rate of AC remained unchanged, but PAC rates decreased significantly. Factors driving this trend are unknown, but potential explanations include changes in culturing practices and/or decreases in hospital-onset urinary tract infections. Understanding factors related to the decrease and the impact on patient outcomes warrants further study.

Disclosures

All Authors: No reported disclosures
1482. Local validation of the drug resistance in pneumonia clinical prediction score at a large academic medical center and a community hospital
Authors: Reinhard Jennifer L , Elshaboury Ramy H , Hayes Bryan D , Mallada Jason , Paras Molly L , Bidell Monique R , Adamsick Meagan L , Gandhi Ronak G
Published: January 2021

Background

Community-acquired pneumonia (CAP) is responsible for ~1 million emergency department (ED) visits yearly and the leading cause of infection-related deaths. Given that increasing antibiotic resistance rates complicate appropriate empiric antibiotic selection, clinicians may benefit from tools to help identify patients at risk for drug-resistant pathogens (DRPs). Limitations of traditional tools, such as healthcare-associated pneumonia criteria (HCAP), have led to development of novel scoring tools such as the drug resistance in pneumonia (DRIP) score. Webb et al. showed the DRIP score was more predictive of CAP caused by DRPs than HCAP criteria. The objective of this study was to validate the DRIP score in a local population of hospitalized patients at an academic and a community medical center.

Methods

Patients who presented to the ED between May 2017 and May 2019 were included in this retrospective review. Patients were included if they were ≥ 18 years diagnosed with CAP by radiographic evidence with respiratory culture positivity and susceptibility results. Exclusion criteria were: presence of non-bacterial non-respiratory pathogens, patients with cystic fibrosis, lung transplant or systemic co-infections. The primary outcome was validation of the DRIP score by comparing the sensitivity, specificity, negative and positive predictive values (NPV/PPV) to the derivation and validation study by Webb et al. Secondary outcomes were the percentage of CAP cases with DRPs and the predictability of DRP using the DRIP score versus HCAP criteria.

Results

A total of 164 patients were included; 60.4% were male with a median age of 70 years. The primary outcome shown in Table 1 demonstrated similar sensitivity, specificity, NPV, and PPV of the DRIP score to those in the study by Webb et al. Staphylococcus aureus (32.9%) and Streptococcus pneumoniae (27.4%) were the most commonly isolated pathogens and CAP due to DRPs occurred in 30.5% of patients. The DRIP score also demonstrated improved performance in predicting DRPs in CAP compared to the HCAP Criteria as shown in Table 2.

Table 1. DRIP Score Validation

Table 2. Predictability of the DRIP score vs. HCAP criteria

Conclusion

Our results further validate the DRIP score derived by Webb et al. in predicting DRPs in CAP. These results encourage a local prospective evaluation of the DRIP score as an antimicrobial stewardship tool.

Disclosures

All Authors: No reported disclosures
1492. Targeted Substitution of Omadacycline in Place of Standard of Care for CABP Treatment is Associated with a Risk Reduction of Clostridioides difficile Infection and Financial Cost Savings in the Acute Care Setting
Authors: Rodriguez Mauricio , Chitra Surya , Wright Kelly , Lodise Thomas
Published: January 2021

Background

Real-world evidence studies indicate that around 3% of hospitalized patients with community-acquired pneumonia (CAP) develop Clostridioides difficile infection (CDI; Chalmers et al, J Infect 2016;73:45–53). Factors associated with increased CDI risk include Davis risk score (DRS) ≥ 6, and treatment with high-risk antibiotics such as fluroquinolones (FQ) and ceftriaxone (CTX). Omadacycline (OMC) is indicated for the treatment of community-acquired bacterial pneumonia (CABP) and has demonstrated a low propensity to induce CDI in preclinical and clinical studies. In the phase 3 OPTIC study, 2% of CABP patients who received moxifloxacin (MOX) developed CDI vs 0% for OMC (Stets et al, N Engl J Med 2019;380:517–27); 14% of MOX patients with DRS ≥ 6 developed CDI vs 0% in the OMC group (Table 1; Figure 1). We assessed the economic impact of substituting current CABP treatment (FQ and CTX) with OMC for hospitalized CABP patients with DRS ≥ 6.

Table 1

Figure 1

Methods

A deterministic healthcare-decision analytic model was performed. Only excess costs associated with each treatment were considered. Base-case model inputs were: yearly CAP admission in US, prevalence of CAP patients with DRS ≥ 6, CDI risk for CAP patients with DRS ≥ 6 with current CABP treatments, CDI costs (initial and recurrent), and OMC cost (Table 2). Efficacy and safety of treatments were assumed to be equal. CDI risk of 0% was assumed for OMC. Costs are reported as USD.

Table 2

Results

For patients with CABP, total CDI costs were $738M, with first-episode costs of $489M plus recurrence costs of $249M. The cost of 5 days (mean hospital length of stay for CABP) of OMC was $207M. Use of OMC for the estimated 100,000 CABP patients with DRS ≥ 6 would result in a potential cost saving of up to $531M for this patient population, assuming CDI risk of 0% with OMC. As CDI is a risk from any antibiotic use, cost savings can be achieved when OMC is used in place of high-risk antibiotics patients when CDI risk rates exceed 3.9%.

Conclusion

Our findings suggest prioritizing use of omadacycline over current CABP treatments in hospitalized CABP with a DRS ≥ 6 may substantially reduce attributable CDI costs. These results can serve as a basis for stewardship interventions to reduce hospital CDI rates and associated costs.

Disclosures

Mauricio Rodriguez, PharmD, BCPS, BCCCP, BCIDP, Paratek Pharmaceuticals, Inc. (Employee) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Thomas Lodise, PharmD, PhD, Paratek Pharmaceuticals, Inc. (Consultant)
1493. The Incremental Burden of Nontuberculous Mycobacterial Lung Disease (NTMLD) among Patients with chronic obstructive pulmonary disease (COPD): Hospitalizations and ER Visits among US Medicare Beneficiaries
Authors: Wang Ping , Hassan Mariam , Chatterjee Anjan
Published: January 2021

Background

NTMLD is a rare mycobacterial infection characterized by worsening lung function and increased healthcare resource burden. Many patients with NTMLD have comorbid respiratory diseases such as COPD. Management of NTMLD in patients with COPD may not get adequate attention as clinical management of COPD is often prioritized. There is a lack of data quantifying the incremental burden of NTMLD among patients with COPD. We assessed the incremental burden of NTMLD in patients with comorbid COPD by comparing their healthcare resource utilization (HCRU), in terms of hospitalizations and emergency room (ER) visits, to matched COPD patients without NTMLD.

Methods

A retrospective cohort study was conducted using the US Medicare claims database (2010-2017). COPD patients with NTMLD were matched 1:3 to COPD patients without NTMLD (controls) by age and gender. HCRU was assessed in terms of hospitalizations (all-cause, respiratory related and COPD related) as well as ER visits (with and without subsequent hospitalization) over a 12-month follow-up period. Incremental burden of NTMLD was assessed by comparing the HCRU between COPD patients with NTMLD and controls using univariate and multivariate analyses adjusting for baseline comorbidities.

Results

A total of 4,010 COPD patients with NTMLD were matched to 12,030 controls. In univariate analyses, a significantly higher proportion of COPD patients with NTMLD had hospitalizations and ER visits compared to controls (Fig 1(A)); the number of hospitalizations and ER visits were also higher among patients with NTMLD (Fig 2(A)). This incremental burden was also reflected in subsequent multivariate analyses after adjusting for baseline comorbidities. As an example, respiratory-related hospitalizations in COPD patients with NTMLD had Odds Ratio of 2.5 (95%CI 2.2-2.7) and Incident Rate Ratio (IRR) of 2.3 (95%CI 2.1-2.4) compared to controls (Fig 1(B), 2(B)).

Figure 1: Proportion of Patients (A) and Odds Ratio (B) of Hospitalizations and ER Visits over a 12-month follow-up period among COPD patients with NTMLD vs. matched COPD patients without NTMLD.

Figure 2: Per Patient Rate (A) and Incidence Rate Ratio (B) of Hospitalization and ER Visits over a 12-month follow-up period among COPD patients with NTMLD vs. matched COPD patients without NTMLD.

Conclusion

COPD patients with NTMLD have a significantly higher disease burden due to hospitalizations and ER visits compared to COPD patients without NTMLD. These findings suggest the substantial incremental burden that NTMLD adds to existing COPD in patients and highlight the urgent need for attention and appropriate management.

Disclosures

Ping Wang, PhD, Insmed Incorporated (Employee) Mariam Hassan, PhD, B. Pharm, Insmed Incorporated (Employee) Anjan Chatterjee, MD, MPH, Insmed Incorporated (Employee)
1494. Validation of Methicillin-Resistant Staphylococcus aureus (MRSA) Risk Factors in Predicting MRSA Community-Acquired Pneumonia at an Academic Medical Center
Authors: Arieno Joelle , Seabury Robert , Steele Jeffrey , Darko William , Miller Christopher , Probst Luke A , Riddell Scott W , Kufel Wesley D
Published: January 2021

Background

The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution.

Methods

This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and a respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vassar Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Microsoft Excel 2019.

Results

Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3 – 74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74 – 4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0 – 12.1), negative LR 0.28 (95% CI 0.08 – 0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%.

Conclusion

Our study utilized institutional data to validate guideline-recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

Disclosures

Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member) Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)
1496. Aspergillosis Complicating Severe Respiratory Syncytial Virus (RSV) in ICU Patients: A Retrospective Cohort Study
Authors: Nam Hannah , Ison Michael G
Published: January 2021

Background

There are recent reports that identify severe influenza pneumonia as an independent risk factor for the development of invasive pulmonary aspergillosis (IPA), even in patients without immunocompromise. We aimed to understand the incidence of IPA as well as other coinfections over multiple seasons in patients with RSV pneumonia in the intensive care unit (ICU).

Methods

A retrospective cohort study was conducted in a single center in Chicago. Data was collected over 9 seasons (January 2009-March 2018) from adult patients admitted to the ICU at a large urban tertiary care center with severe RSV pneumonia. Patients were included if they had a positive RSV PCR test, older than 18 years, admitted to the ICU with acute respiratory failure, and had pulmonary infiltrates on imaging. IPA was defined per both the EORTC/MSG criteria as well as the revised AspICU criteria (Schauwvlieghe et al). Descriptive statistics were calculated. In univariable analysis, we compared categorical variables by Fisher’s exact test and Chi-square test, continuous variables by Wilcoxon Rank Sum where appropriate.

Results

Of 224 patients admitted to the ICU with RSV (median ICU LoS 10.5 d), IPA was diagnosed in 8 (3.5%). Patients diagnosed with IPA had an increased LoS in the hospital (23.7 days vs. 11.6 days, p=0.01). Although the mortality was numerically higher (3, 37.5% vs 26, 17.9%) this was statistically not significant). History of hematological malignancy, stem cell transplant, and neutropenia were significant factors in the development of IPA. Those with lung disease had significantly lower rates of IPA. All patients with IPA were treated with voriconazole. Other coinfections among RSV-infected ICU patients included bacterial (21, 13.7%), viral (10, 6.5%), and non-IPA fungal (13, 8.5%) pathogens.

Baseline Characteristics and Mortality/Morbidity

Patient Characteristics in Invasive Pulmonary Aspergillosis

Conclusion

Although IPA is relatively uncommon in patients admitted to the ICU with severe RSV pneumonia, patients with IPA had significant increased LOS and tended to have underlying host factors. Other coinfections with bacterial, viral, and non-IPA fungal pathogens are common in those with severe RSV pneumonia.

Disclosures

Michael G. Ison, MD MS, AlloVir (Consultant)
123. Utilization of the BioFire® FilmArray® Pneumonia Panel in Critically Ill Patients with Influenza Pneumonia
Authors: Ereshefsky Benjamin , Raju Mina
Published: January 2021

Background

Severe influenza pneumonia is associated with poor clinical outcomes and may be complicated by bacterial co-infections. Traditional culture techniques may fail to identify organisms, especially if antibiotics were administered prior to culture collection. In critically ill patients, negative cultures may lead to prolonged use of empiric, broad-spectrum antibiotics.

Methods

This is a single-center descriptive study on the use of the BioFire® FilmArray® Pneumonia (PNA) panel in critically ill patients with influenza. All intubated patients diagnosed with influenza pneumonia admitted to an ICU between December 1, 2019 and March 31, 2020 were included for analysis. The purpose of this study was to compare the results from rapid diagnostic testing with traditional culture results, and to describe the impact on time to results and the time to de-escalation of antibiotics.

Results

A total of 21 patients with 22 PNA panels were included. The mean age was 64 years, and 43% were female. Diabetes and COPD were present in 29% and 33%, respectively. A majority of patients (91%) had influenza A. Bacterial co-infection was found in 82% of cases, with all having bacteria identified on the PNA panel. Polymicrobial results from the PNA panel occurred 32% of the time. The most frequently identified bacterial pathogens by PNA panel were S. pneumoniae (41%), MSSA (27%), H. influenzae (14%), and P. aeruginosa (9%). Respiratory cultures had no growth 50% of the time, with MSSA most commonly identified at 23%. P. aeruginosa and MRSA were the only organisms that were detected by both PNA panel and respiratory culture with 100% agreement. PNA panel results were available 5.1 (2.7–11.3) hours after respiratory culture collection, compared to 45.8 (31.5–55.6) hours for culture results. De-escalation of empiric antibiotics occurred 13.2 (1.7–24.0) hours after PNA panel results in the 18 evaluable patients.

Table 1: Pathogens Identified by BioFire Pneumonia Panel and Respiratory Culture

Conclusion

The PNA panel identified a high rate of bacterial pathogens in this cohort of critically ill patients with influenza. It also provided actionable results much quicker than traditional respiratory cultures. Further study is needed to evaluate the significance of positive molecular tests when cultures are negative.

Disclosures

All Authors: No reported disclosures
1518. Real-World Comparative Effectiveness of Baloxavir Marboxil versus Oseltamivir on Influenza-Related Complication and Resource Utilization
Authors: Neuberger Eddie , Wallick Chris , Chawla Devika , Castro Rita de Cassia
Published: January 2021

Background

In the 2018-19 season, there were an estimated 490,500 hospitalizations and 24,000 deaths from influenza in the US. Understanding how antiviral use affects rates and severity of complications is crucial to inform clinical practice. The objective of this study was to compare the frequency and costs of complications in influenza patients treated with baloxavir compared with oseltamivir-treated patients. This is one of the first analyses to examine comparative effectiveness of baloxavir in a real-world setting.

Methods

This retrospective cohort study used IBM MarketScan US administrative claims data from the 2018–19 influenza season. Patients were required to have an outpatient visit for influenza followed by a prescription for baloxavir or oseltamivir within 2 days. Baloxavir- and oseltamivir-treated patients were propensity score matched based on key baseline clinical and demographic characteristics. All-cause, all respiratory-related, and select respiratory-related (infection, asthma, and COPD) HRU in the 15 and 30 days following prescription fill were assessed using chi-square and Fisher’s exact tests for categorical measures and Wilcoxon signed-rank tests for counts and costs.

Results

We included 5,080 baloxavir-treated patients and 10,160 matched oseltamivir-treated patients in the analysis. Statistically significantly lower HRU was associated with baloxavir compared with oseltamivir therapy (15-day: respiratory-related ED visits, select respiratory-related ED visits and outpatient visits; 30-day: all-cause hospitalization, respiratory-related ED visits, select respiratory-related ED visits and outpatient visits (Table 1). Similarly, associated costs were generally lower in the baloxavir-treated group. Baloxavir-treated patients had lower mean per-patient all-cause 15-day costs (ED visits: $30 [95% CI: $21–$39] vs $42 [95% CI: $32–$51]; hospitalizations: $31 [95% CI: $6–$55] vs $74 [95% CI: $43–$104]) and 30-day costs (ED visits: $46 [95% CI: $35–$57] vs $67 [95% CI: $55–$79]; hospitalizations: $47 [95% CI: $15–$80] vs $119 [95% CI: $78–$161]).

Table 1. Proportion of patients with at least one event

Conclusion

These findings suggest that treatment of influenza with baloxavir may improve outcomes and lower HRU costs compared with oseltamivir treatment.

Disclosures

Eddie Neuberger, PharmD, Genentech, Inc. (Employee) Chris Wallick, PharmD, MS, Genentech, Inc. (Employee) Devika Chawla, PhD MSPH, Genentech, Inc. (Employee) Rita de Cassia Castro, MD, Genentech, Inc. (Employee)
1521. Risk factors associated with complications of influenza A or B infection, southern Puerto Rico, 2016-2019
Authors: Perez-Caro Angel L , Toro Frances Quiñones-Del , García-Burgos Marilyn , Rivera-Amill Vanessa , Alvarado-Domenech Luisa I
Published: January 2021

Background

Influenza is one of the most common viral respiratory diseases in the United States with 9–45 million cases per year. In Puerto Rico, more than 18,000 cases of influenza were reported during the 2019/20 season. The Sentinel Enhanced Dengue Surveillance System (SEDSS) conducts acute febrile illness surveillance for inpatient and outpatients at a southern Puerto Rico tertiary care hospital.

Methods

We performed a retrospective analysis of disease severity among laboratory-confirmed influenza cases enrolled in SEDSS. Cases with complications such as pneumonia or bronchitis evidenced by chest x-ray or clinical diagnosis were classified as severe.

Results

Between January 2016 and December 2019, there were 2,835 laboratory-confirmed influenza cases. More than half (1,662, 59%) were aged 0–20 years, 51% (n=1,447)were female, and 4% (n=124)required hospital admission. Among all influenza cases, influenza A virus was most common (n = 1,963, 69%) followed by influenza B virus (n = 872, 31%). Odds of having influenza A were higher among adults (OR=1.62; 95% CI:1.38-1.92). Chronic disease history among influenza cases included: asthma (n= 507, 18%), hypertension (n = 337, 12%), hypercholesterolemia (n = 157, 6%), coronary heart disease (n = 79, 3%), immunodeficiency (n = 11, 1%), and kidney disease (n = 10, 1%). Overall, 61(2%) influenza cases developed complications, 21 developed pneumonia of which 85% had chest x-ray performed. One-third of influenza cases with pneumonia or bronchitis had preexisting conditions like asthma (33%) and hypertension (34%). Seventy five percent of Influenza A cases with asthma developed bronchitis or pneumonia. The odds of having severe Influenza were higher among patients with underlying hypertension compared to those without hypertension (OR= 3.8; 95% CI:2.0–7.1). Moreover, influenza cases with asthma had a higher odd of developing pneumonia or bronchitis as compared to those without asthma (OR=2.3; 95% CI: 1.3–4.0). While asthma is a recognized risk factor for influenza complications, isolated hypertension is not.

Conclusion

Identifying people at risk for influenza complications provides a guide for clinicians and public health officials to implement preventive measures and improve clinical outcomes.

Disclosures

All Authors: No reported disclosures
1522. Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model
Authors: Han Alison , Czajkowski Lindsay , Rosas Luz Angela , Cervantes-Medina Adriana , Xiao Yongli , Gouzoulis Monica , Lumbard Keith , Hunsberger Sally , Reed Susan , Athota Rani , Baus Holly , Lwin Amy , Sadoff Jerald , Taubenberger Jeffery , Memoli Matthew J
Published: January 2021

Background

Influenza virus infections cause significant morbidity and mortality during yearly seasonal epidemics and during sporadic pandemics. It is imperative to identify new targets for vaccines and therapeutics. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein.

Methods

We conducted a randomized, double-blind, Phase II placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. CR6261 was infused 24 hours after challenge with H1N1pdm09 and the primary efficacy outcome was area under the curve (AUC) of viral shedding.

Results

Between March 2015-May 2018, 104 healthy volunteers were enrolled and randomized with 91 undergoing influenza challenge, of which 49 participants (54%) received treatment with CR6261 and 42 participants (46%) received placebo. A mean of 1x106 ng/mL of serum CR6261 was detected by 24 hours after infusion. Nasal CR6261 levels reached a peak mean of 5.97x102 ng/ml 2 days after infusion. There was no statistically significant difference in the primary outcome measure between the CR6261 group and placebo (median AUC 48.56 and 25.53 respectively, P=0.31). The severity of illness was compared between the two groups, and no significant difference was observed in number of symptoms, duration of symptoms, or FLU-PRO scores.

Conclusion

CR6261 had no statistically significant effect on AUC of viral shedding, and no clinically significant effect on overall influenza disease. Preexisting anti-neuraminidase (NA) antibody titers were most predictive of reduced influenza disease. Nasal CR6261 levels were much lower compared to serum, which may be a factor in the limited effect of CR6261 on this upper respiratory infection. These results suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may have limited efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multi-faceted strategy rather than as a standalone therapeutic or vaccine strategy.

Funding

This study was funded in part by the intramural program of NIAID, NIH, by the NCI Contract No. 75N910D00024, Task Order No. 75N91019F00130, and through a CRADA with Janssen Infectious Diseases and Vaccines.

Disclosures

Amy Lwin, RN, BSN, Janssen Pharmaceutical Company of J&J (Employee) Jerald Sadoff, MD, Janssen Pharmaceutical Company of J&J (Employee)