bluuebunny/crossref_metadata_2025_split huggingface dataset:
1279. Risk Factors for Colistin Resistance Among Carbapenem-Resistant Klebsiella pneumoniae (CRKP) in a Network of Long-term Acute Care Hospitals (LTACHs)
Authors: Zhang Helen L , Han Jennifer , Lapp Zena , Snitkin Evan , Goldstein Ellie J C , Muldoon Sean R , Tolomeo Pam C , Lautenbach Ebbing 
Published: December 2021

Abstract

Background
Colistin resistance in CRKP presents a serious clinical challenge for patients of LTACHs. However, risk factors for colistin-resistant CRKP have not been previously characterized in this population. Here, we determined risk factors for colistin resistance among CRKP isolates from a network of LTACHs.

Methods
CRKP clinical cultures were collected from 21 Kindred Healthcare LTACHs in 4 US states (California, Texas, Florida, Kentucky) from 8/1/14-7/25/15. Cultures collected within 30 days of a prior CRKP culture from the same patient were excluded. Colistin resistance (minimum inhibitory concentration ≥4) was determined using a custom SensititreTM broth microdilution assay (ThermoFisher Scientific, Waltham, MA). Multivariate logistic regression was performed to evaluate candidate risk factors of age, sex, cirrhosis, chronic kidney disease, culture source, length of stay, indwelling line or tracheostomy, and antibiotic exposure (colistin, fluoroquinolones, 3rd-5th generation cephalosporins, piperacillin-tazobactam, carbapenems, and aminoglycosides) for ≥48 hours in the prior 30 days.

Results
Among 430 CRKP cultures (237 respiratory, 145 urine, 38 blood, 10 wound) from 375 patients, 144 (33.5%) were colistin-resistant. In multivariate analysis, colistin resistance was associated with prior colistin exposure (odds ratio [OR] = 5.9, 95% CI = 2.5-14.0) and culture source (Wald test for joint significance, p=0.03), with higher odds of colistin resistance among respiratory (OR = 2.9, 95% CI = 1.2-7.2), urine (OR = 1.6, 95% CI = 0.7-4.1), or wound (OR = 2.2, 95% CI = 0.4-11.5) compared to blood cultures.

Conclusion
In this sample of CRKP from LTACHs, colistin resistance was associated with prior colistin exposure and respiratory culture source. Other patient factors such as co-morbidities, indwelling devices or tracheostomy, or exposure to other antibiotics/antibiotic classes were not associated with colistin resistance in CRKP. These findings will help inform strategies to reduce colistin resistance and identify LTACH patients at risk of colistin-resistant CRKP.

Disclosures
Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))
1289. The Challenge of Treating Community-Associated Enterobacterales Infections in a Middle-Income Country: Data from SMART 2018-2019
Authors: Telles João Paulo , Arend Lavinia , Bail Larissa , Ito Carmen , Tuon Felipe 
Published: December 2021

Abstract

Background
Antimicrobial stewardship programs have been used widely in hospital settings due to the rise of resistant bacteria, antibiotic toxicities, and costs. Nevertheless, few efforts are done to prevent the rising antimicrobial resistance in community settings. The aim of our study was to evaluate the antimicrobial resistance from Enterobacterales community- and hospital-acquired infections in Southern Brazil.

Methods
A total of 272 Enterobacterales isolates (i.e., Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Serratia spp., Proteus spp., and Providencia) were collected from 2018 and 2019. Broth microdilution method was used to determine minimum inhibitory concentrations for ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem. Molecular evaluation of beta-lactamases (ESBLs, AmpC, and KPC) was also performed.

Results
Ninety-three, and a hundred and seventy-nine isolates were from community- and hospital-acquired infections, respectively. Similar MIC distribution was found between community and hospital settings (Table 1). Levofloxacin MIC of 8mg/L occurred in 38.7% (n=36) and 30.7% (n=55) of isolates from community- and hospital-acquired infections, respectively (Figure 1). Ceftriaxone MIC of 16mg/L occurred in 39.7%(n=37) and 39.1% (n=70) of isolates from community- and hospital-acquired infections, respectively (Figure 1). At last, cefepime MIC of 32mg/L occurred in 22% (n=21) and 25% (n=46) of isolates from community- and hospital-acquired infections, respectively. The following beta-lactamases were found in isolates from community-acquired group, ACT-MIR, CTX-M, SHV and TEM; while beta-lactamases from the hospital-acquired group were ACT-MIR, CMY II, KPC-2, CTX-M, SHV and TEM.

Table 1. Enterobacterales ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings.

Figure 1. Enterobacterales ceftriaxone and levofloxacin minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings.

Conclusion
Similar antimicrobials resistances were found in Enterobacterales from community- and hospital-acquired infections. New anti-infective agents are needed urgently to treat pathogens from the community-acquired infections and hospitals that have resistance to the first line regimen. Additionally, community antimicrobial stewardship programs are required.

Disclosures
All Authors: No reported disclosures
1299. Epidemiology of Invasive Pneumococcal Disease (IPD) in the United States 2011-2019
Authors: Gierke Ryan , Farley Monica M , Schaffner William , Thomas Ann , Reingold Art , Harrison Lee , Holtzman Corinne , Burzlaff Kari , Petit Susan , Barnes Meghan , Torres Salina , Beall Bernard , Pilishvili Tamara 
Published: December 2021

Abstract

Background
Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for U.S. children aged &lt; 5 years in February 2010 and recommended in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥ 65 years in 2014. PCV13 has led to dramatic reductions in invasive pneumococcal disease (IPD) burden. New, higher valency PCVs (PCV15, PCV20) are expected to be licensed for adults in late 2021. We examined remaining PCV13-type IPD among children and adults and assessed IPD burden potentially preventable through PCV15 and PCV20 use.

Methods
IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998–2019. Isolates were serotyped by Quellung or whole genome sequencing. Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators.

Results
After introduction of PCV13 in children, by 2013–2014, PCV13-type IPD declined 89% (from 15 to 2 cases/100,000) in children age &lt; 5 years and 67% (from 19 to 7 cases/100,000) in adults age ≥ 65 years. During 2014–2019, rates of PCV13-type IPD in children and adults remained stable. In 2018–2019, among children age &lt; 5 years, serotypes 3, 19F, 19A, and 6C accounted for most of the remaining PCV13-type IPD (46%, 32%, 14% and 4% respectively) (Figure 1). Among adults age ≥ 65 years, serotypes 3, 6C, 19A, and 19F accounted for most of the remaining PCV13-type IPD (62%, 12%, 10%, and 9% respectively) (Figure 1). During 2015–2019, rates of PCV15 and PCV20-type IPD have remained stable. In 2018–2019, among adults age ≥ 65 years, PCV15 non-PCV13-type IPD rates were 3.6 cases per 100,000 and accounted for 15% of all IPD. PCV20 non-PCV13-type IPD rates were 6.8 cases per 100,000 and accounted for 29% of all IPD (Figure 2). Among children age &lt; 5 years, PCV15 non-PCV13-type IPD rates were 1.6 cases per 100,000 and accounted for 17% of all IPD. PCV20 non-PCV13-type IPD rates were 2.8 cases per 100,000 and accounted for 39% of all IPD (Figure 2).
Figure 1. Incidence rates of IPD among children &lt; 5 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019

Figure 2. Incidence rates of IPD among adults ≥ 65 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019

Conclusion
Following the dramatic reductions after PCV13 introduction, PCV13-type IPD has remained stable during the past five years. There are opportunities to prevent an additional 30% IPD burden among adults through new PCV use.

Disclosures
William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)
1300. Comparison of Narrow vs. Broad Spectrum Antibiotics for Treatment of Community-acquired Aspiration Pneumonia
Authors: Box Maggie , Sophonsri Anthony , Bagsic Samantha 
Published: December 2021

Abstract

Background
Aspiration pneumonia (aspPNA) accounts for 5-15% of pneumonia admissions. Despite the absence of risk factors for organisms such as methicillin-resistant S. aureus (MRSA) or Pseudomonas aeruginosa (PsA), broad-spectrum (BS) antibiotics active against these pathogens are frequently prescribed. We compared outcomes of patients receiving narrow-spectrum (NS) versus BS antibiotics for aspPNA.

Methods
This is a retrospective cohort study of hospitalized patients started on antibiotics for aspPNA upon admission from 1/1/2019 to 12/31/2019. The BS cohort included patients prescribed antibiotics with activity against PsA or MRSA and were on BS antibiotics for &gt; 50% duration of therapy regardless of de-escalation. The primary endpoint was clinical response, defined as resolved, improved, no change, or worsened. Secondary endpoints included 30-day all-cause mortality, duration of therapy, 30-day C. difficile infection, and length of stay. Outcomes were assessed using logistic regression with antibiotic group as a fixed effect, and all analyses were conducted using R v. 4.0.3.

Results
A total of N=95 patients were included in the study, 35 in the NS and 60 in the BS groups. Clinical response was similar in distribution between groups (p &gt; 0.3). 30-day all-cause mortality was lower in the NS (11.4%) as compared to the BS group (33.3%) (OR 0.26; 95% CI 0.09- 0.81; p &lt; 0.04). There were no differences for the secondary endpoints including median duration of therapy (4 [IQR 2.5] days vs. 6 [IQR 6] days, p&gt; 0.2), 30-day C. difficile infection (0% vs 6.7%, p &gt; 0.3), and median length of stay (6 [IQR 5] days vs. 7 [IQR 8.5] days, p &gt; 0.2) in NS vs. BS groups, respectively. A positive blood or respiratory culture was isolated in 37% (35/95) patients. Enteric organisms were the most prevalent bacteria isolated (20%), followed by methicillin susceptible S. aureus (8%), and Streptococcus spp (7%). MRSA and PsA were detected in 2% and 3% of patients, respectively.

Conclusion
There is no difference in efficacy between NS and BS antibiotics for aspPNA. Microbiologic data confirm the low incidence of PsA or MRSA causing aspPNA despite high empiric prescribing of antibiotics active against these pathogens. These results support the ongoing need for targeted antibiotic stewardship initiatives for aspPNA.

Disclosures
All Authors: No reported disclosures
1313. Disease Burden and Real-world Clinical Practice for the Treatment of Hospital-Acquired Bacterial Pneumonia Using a Japanese Large-scale Claims Database: A Retrospective Cohort Study
Authors: Kimata Masahiro , Aoki Yosuke , Noriaki Adachi , Akiyama Takeshi , Harada Akiko 
Published: December 2021

Abstract

Background
With an aging population and increasing healthcare utilization, the frequency of hospital-acquired pneumonia (HAP) is expected to increase. Since HAP is life threatening, appropriate diagnosis and treatment are required; however, large-scale Japanese data focusing on patient profiles and treatment patterns is lacking.

Methods
The demographics and treatment patterns of HAP were examined using a large-scale Japanese claims database from Jan. 2016 to Apr. 2018. The HAP population included patients who received injection antibiotics ≧3 consecutive days after admission, but not within 2 days after admission, and those whose reason for hospitalization was not pneumonia but had a diagnosis of pneumonia after hospitalization (based on ICD-10 codes).

Results
2,968 HAP patients (mean age 77 years, 64.9% male) contributing 2,979 total HAP episodes were included. The 12-month pre-index mean Charlson Comorbidity Index (CCI) score was 4.0±3.1 (mean±SD), CCI scores ≧4 comprised 44.0%. Most HAP episodes (77.6%) occurred ≧5 days after hospitalization. During the 12month pre-index period including outpatients, 84.9% of patients had some type of pneumonia record, 9.1% had VAP (ventilator associated pneumonia) records, and 7.4% had anti-MRSA prescription records. For post-index HAP treatment, ampicillin/sulbactam (36.4%, 8.2±3.8 days) and piperacillin/tazobactam (22.0%, 8.8±4.4 days) were frequently prescribed as the first antibiotic prescription. Ceftriaxone (19.4%) and meropenem (9.8%) were also frequently prescribed. Examinations prescribed during HAP: 30.5% blood culture tests, 28.2% sputum examinations and 29.2% urine antigen tests. The overall mortality rate of HAP in overall hospitalization post-index was 22.0%, in which 14.4% of deaths occurred within 30 days. The mean (±SD) length of overall hospital stay was 49.9 (±34.2) days (11.3 days for HAP period), with 12.4% ICU use and 17.6% ventilator use. The median total cost during hospitalization was ¥1,924,848.18 (&19,248).

Conclusion
The data revealed patient characteristics, treatment patterns, mortality rates and healthcare costs in Japanese HAP patients. This database approach should prove useful for discussing antibiotics usage trends in highly aging Japan.

Disclosures
Masahiro Kimata, PhD, MSD K.K., Tokyo, Japan (Employee) Yosuke Aoki, MD, PhD, MSD K.K., Tokyo, Japan (Other Financial or Material Support, Honorarium for Lecturing)SHIONOGI & Co., Ltd (Grant/Research Support, Other Financial or Material Support, Honorarium for Lecturing) Adachi Noriaki, n/a, MSD K.K., Tokyo, Japan (Employee) Takeshi Akiyama, MSc, MSD K.K., Tokyo, Japan (Independent Contractor) Akiko Harada, n/a, MSD K.K., Tokyo, Japan (Employee)
151. Simplifying Empiric Antimicrobial Therapy Selection for Lower Respiratory Tract Infections in Intensive Care Unit Patients: Using Resistance Frequency to Guide Decision Making
Authors: Klinker Kenneth , Hidayat Levita K , Andrew DeRyke C , Motyl Mary , Bauer Karri A 
Published: December 2021

Abstract

Background
In the US, the burden of multidrug resistant bacterial infections, including carbapenem-resistant P. aeruginosa (CRPA) and ESBL-producing Enterobacterales (ESBL-E), is substantial. These resistant pathogens may affect the delivery of timely effective therapy. The aim of this study is to evaluate beta-lactam (BL) susceptibility trends based on the aggregate frequency of CRPA and a combined ESBL-E phenotype (K. pneumoniae (KPn) + E. coli (EC)) observed in critically ill patients with lower respiratory tract infections (LRTI).

Methods
In 2016-2019, ~20 US institutions per year submitted up to 250 gram-negative pathogens as part of the Study for Monitoring Antimicrobial Resistance Trends. A total of 871 PA, 380 KPn, and 336 EC isolates were collected from ICU patients with LRTI. MICs were determined using broth microdilution and interpreted using 2021 CLSI breakpoints. ESBL-E phenotype was defined as: ceftriaxone MIC ≥ 2 mcg/mL. Institutions were stratified into two groups based on frequency of CRPA and combined ESBL-E phenotype: Group 1: CRPA ≤ 15% and ESBL-E ≤ 15%; Group 2: CRPA &gt; 15% and ESBL-E &gt; 15%. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥90% was deemed optimal.

Results
Overall, CRPA and ESBL-E phenotypes were identified in 28.4% and 21.2% of isolates, respectively. Aggregate BL susceptibility in group 1 was above the 90% threshold for cefepime (FEP), piperacillin/tazobactam (TZP), meropenem (MEM), ceftolozane/tazobactam (C/T), and imipenem/relebactam (I/R) (Table 1). However, as frequency of CRPA and ESBL-E exceeded 15%, aggregate BL susceptibility declined to 77.3%, 79.3%, and 86.2% for FEP, TZP, and MEM, respectively. In contrast, C/T and I/R maintain susceptibility above the empiric susceptibility threshold.
Table 1. Aggregate susceptibility of P. aeruginosa, E. coli, and K. pneumoniae ICU LRTI isolates stratified by resistance frequency: Best- (Group 1) and worst-case (Group 2) scenarios

Conclusion
In ICU patients, exceeding CRPA and combined ESBL-E phenotype frequency of 15% for both classifications, impacts susceptibility to 1st line BL’s resulting in a failure to achieve empiric susceptibility thresholds. This stratification could serve as a decision point for triggering earlier susceptibility testing or modifying empiric therapy recommendations for LRTI to include newer agents pending microbiology results.

Disclosures
Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder)
1319. Assessment of Spectrum Score-Based Antibiotic De-Escalation in Patients with Nosocomial Pneumonia
Authors: Ilges Daniel T , Neuner Elizabeth , Krekel Tamara , Ritchie David J , Hampton Nicholas B , Micek Scott 
Published: December 2021

Abstract

Background
Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant morbidity and mortality. Guidelines recommend broad-spectrum empiric antibiotic therapy, including treatment for Pseudomonas aeruginosa (PSAR) and methicillin-resistant Staphylococcus aureus (MRSA), followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods
This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016–2019. Patients were enrolled if they met pre-defined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). Data were compared using chi-square, Mann-Whitney U, or T-tests. The primary outcome was composite treatment failure, defined as all-cause mortality or re-admission for pneumonia within 30 days of diagnosis, analyzed using a Cox proportional hazards analysis to control for confounding variables.
Figure 1. Study Schematic

Table 1. Spectrum Score Assignment

Results
Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs. 1026 NDE). Groups were well-matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs. 50.6%, P=0.011). Patients receiving DE experienced a 65% and 44% reduction in anti-MRSA and anti-PSAR therapies by day 3, respectively. There was no difference in composite treatment failure (35.0% DE vs. 33.8% NDE, P=0.604). DE was not associated with treatment failure on Cox multivariate regression analysis (HR 1.13, 95% CI 0.97-1.33, P=0.149). Patients receiving DE had fewer antimicrobial days (median 9 vs. 11, P&lt; 0.0001), episodes of Clostridioides difficile (2.2% vs. 3.8%, P=0.046), and days of hospitalization (median 20 vs. 22 days, P=0.006).
Figure 2: Median Spectrum Scores (SS) Days 0 to 28

Table 2: Cox Regression Analysis

Conclusion
DE and NDE resulted in similar rates of composite treatment failure at 30 days; however, DE was associated with fewer antimicrobial days, episodes of C. difficile, and days of hospitalization. Spectrum scores can objectively identify DE, but further studies are needed to fully understand their utility in this context.

Disclosures
Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) David J. Ritchie, PharmD, BCPS (AQ-ID), AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)
1324. Identification of Local Risk Factors for P. aeruginosa in Community-acquired Pneumonia in a Veteran Population
Authors: Gibbons Emily A , Hopkins Teri L , Yang Linda , Frei Christopher R , Restrepo Marcos I , Walter Elizabeth , Cadena-Zuluaga Jose 
Published: December 2021

Abstract

Background
The 2019 ATS/IDSA community-acquired pneumonia (CAP) guidelines recommend empiric P. aeruginosa (PSA) coverage if locally validated risk factors are present. They further recommend obtaining local data on CAP pathogens to quantify risk factors and help guide clinical decision-making. To comply with the current guideline recommendations and to determine which patients may benefit from empiric anti-pseudomonal therapy, we aimed to characterize our institution’s local risk factors for CAP caused by PSA.

Methods
This is a retrospective single-center matched cohort study of patients admitted to our institution with a CAP diagnosis and a positive respiratory culture who received antibiotic treatment in the past 19 years. Multivariate logistic regression was performed to assess the relationship between PSA and the following risk factors: severe or very severe COPD (FEV1 &lt; 50% predicted), requiring invasive mechanical ventilation or vasopressor support in the first 24 hours of admission, history of PSA infection/colonization in the previous year, tracheostomy, bronchiectasis, long-term care facility residence and admission with receipt of IV antibiotics in the previous 90 days.

Results
A total of 343 patients were screened and 213 were included. Patients were mostly male (99%) with a median (IQR) age of 70 (63-76) years. Long-term care facility residence was removed from the model to prevent it from being over fit as it was related tracheostomy. In the multivariate analysis the only independently associated risk factor for PSA CAP was evidence during the prior year of PSA infection or colonization (OR 3.66; 95% CI 1.26 – 10.56; p = 0.018). Other risk factors that did not reach statistical significance but may be clinically significant included severe or very severe COPD (OR 2.52; 95% CI 2.52 – 6.38; p = 0.055) and tracheostomy (OR 5.28; 95% CI 0.74 – 38.85; p = 0.098).

Conclusion
The results of this study provide valuable data to help guide empiric CAP treatment at our institution. Based on these results, patients with PSA infection or colonization in the past year are appropriate to provide empiric anti-pseudomonal therapy for CAP. Further evaluation of severe or very severe COPD and tracheostomy would be beneficial to better characterize their role in PSA CAP.

Disclosures
All Authors: No reported disclosures