bluuebunny/crossref_metadata_2025_split huggingface dataset:
1214. Household Transmission of Febrile Illness Measured by Smartphone-Connected Thermometers, United States, 2016-2021
Authors: Bloch Danielle , Zicker John , Somhegyi Hannah , Philips Patrick , Singh Inder , Daitch Amy 
Published: December 2021

Abstract

Background
Understanding household transmission dynamics of infectious diseases can help develop mitigation strategies. Traditional methods of population-level disease surveillance do not capture household transmission. Data collected from smartphone-connected thermometers that can differentiate among individuals in a household can be used to study these characteristics. Using this technology, we estimated the household secondary attack rate (SAR) of febrile illness, assessed its correlation with CDC-reported influenza-like illness (ILI) and COVID-19 case incidence, and identified risk factors for secondary transmission.

Methods
We conducted a retrospective cohort study among 596,096 febrile illness index cases recorded from August 1, 2016 to January 20, 2021 in households with two or more individuals in all 50 states. Fevers were measured using the Kinsa Smart Thermometer and mobile device app. Secondary cases were defined as household members who recorded a fever 1–10 days after an index case. We calculated SAR prior to and during the COVID-19 pandemic within the study period, and assessed correlation to ILI and COVID-19 case incidence using Spearman’s rank correlation coefficient. Bivariate and multivariable mixed logistic regression models were used to identify risk factors for secondary transmission.

Results
SAR in the pre-COVID-19 period was 5.9% (95% CI: 5.8%–6.0%) during flu season (November to April), and 3.7% (95% CI: 3.6%–3.7%) in flu off-season, and weekly SAR was significantly correlated with ILI reported from CDC (ρ=0.84, p&lt; 0.001). Secondary transmission was 40% more likely to occur in households where the index case’s initial temperature was ≥ 39.1°C. During the COVID-19 period, SAR was 3.3% (95% CI: 3.3%–3.4%), and daily SAR was significantly correlated with national daily COVID-19 incidence rates (ρ=0.86, p&lt; 0.001). Households in census tracts with &gt;50% essential workforce were 50% more likely to experience secondary transmission.

Conclusion
Household SAR was highly correlated with ILI and COVID-19 cases. Capturing household transmission of febrile illness through routine public health surveillance may identify risk factors for infectious disease transmission, allowing for more targeted interventions.

Disclosures
Danielle Bloch, MPH, Kinsa Health (Employee, Shareholder) John Zicker, MS, Kinsa Health (Employee, Shareholder) Hannah Somhegyi, PhD, Kinsa Health (Employee, Shareholder) Patrick Philips, n/a, Kinsa Health (Employee, Shareholder) Inder Singh, n/a, Kinsa Health (Board Member, Employee, Shareholder) Amy Daitch, PhD, Kinsa Health (Employee, Shareholder)
1216. Presence of the Narrow-Spectrum OXA-1 Beta-lactamase Enzyme Is Associated with Elevated Piperacillin-Tazobactam MIC Values Among ESBL-producing Escherichia coli Clinical Isolates (CANWARD, 2007-2018)
Authors: Walkty Andrew , Karlowsky James , Lagace-Wiens Philippe , Golden Alyssa , Baxter Melanie , Denisuik Andrew , McCracken Melissa , Mulvey Michael , Adam Heather , Zhanel George 
Published: December 2021

Abstract

Background
The clinical outcome of patients with bacteremia due to an extended-spectrum beta-lactamase (ESBL)-producing member of the family Enterobacteriaceae who are treated with piperacillin-tazobactam appears to depend, at least in part, on the piperacillin-tazobactam MIC. The purpose of this study was to determine whether there is any association between the MIC of piperacillin-tazobactam and presence of the narrow spectrum OXA-1 beta-lactamase enzyme among ESBL-producing Escherichia coli.

Methods
E. coli clinical isolates were obtained from patients evaluated at hospitals across Canada (January 2007 to December 2018) as part of an ongoing national surveillance study (CANWARD). ESBL production was confirmed using the Clinical and Laboratory Standards Institute phenotypic method. Susceptibility testing was carried out using custom broth microdilution panels, and all isolates underwent whole genome sequencing for beta-lactamase gene detection.

Results
In total, 671 ESBL-producing E. coli were identified as part of the CANWARD study. The majority of isolates (92.0%; 617/671) harbored a CTX-M ESBL enzyme. CTX-M-15 (62.3%; 418/671), CTX-M-27 (13.9%; 93/671), and CTX-M-14 (13.4%; 90/671) were the most common variants identified. The narrow spectrum OXA-1 beta-lactamase enzyme was present in 42.6% (286/671) of isolates. OXA-1 was detected in 66.3% (277/418) of isolates with a CTX-M-15 ESBL enzyme versus only 3.6% (9/253) of isolates with other ESBL enzyme types. The piperacillin-tazobactam MIC50 and MIC90 values were 8 µg/mL and 32 µg/mL for isolates that possessed the OXA-1 enzyme versus 2 μg/mL and 8 µg/mL for those that did not. The percentage of ESBL-producing E. coli isolates that were inhibited by a piperacillin-tazobactam MIC of ≤8 μg/mL was 68.5% for isolates that were OXA-1 positive and 93.8% for isolates that were OXA-1 negative.

Conclusion
The MIC50 and MIC90 values of piperacillin-tazobactam among ESBL-producing E. coli were higher for the subset of isolates that harbored a narrow spectrum OXA-1 beta-lactamase enzyme relative to the subset that did not. This association was primarily observed among ESBL-producers with the CTX-M-15 enzyme variant. OXA-1 was infrequently detected among isolates with other ESBL enzyme types.

Disclosures
George Zhanel, PhD, AVIR (Grant/Research Support)Iterum (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Sandoz (Grant/Research Support)Sunovion (Grant/Research Support)Venatorx (Grant/Research Support)Verity (Grant/Research Support)
141. Effectiveness of a Multipronged Approach to Improve Prophylactic Antibiotic Prescribing in Patients Undergoing Trans-Arterial Chemoembolization
Authors: Hung Kai Chee , Chua Nathalie Grace Sy , Lee Winnie , Kwa Lay Hoon Andrea , Chung Shimin Jasmine , Sum Leong 
Published: December 2021

Abstract

Background
In our institution, the significant use of broad-spectrum antibiotics for antibiotic prophylaxis (AP) in trans-arterial chemoembolization (TACE) was operator dependent and not evidence based. Hence, an AP guideline was developed with the Department of Vascular and Interventional Radiology and launched in May 2019, following department roadshows and creation of user-friendly electronic AP order sets. We analyzed the effectiveness and outcomes of our multipronged approach towards improving the standardization of AP prescribing.

Methods
This was a retrospective study of TACE procedures from November 2018 to March 2020, pre and post guideline implementation (Figure 1). Single IV cefazolin 2g dose (or IV clindamycin 600mg in the setting of β-lactam allergy) before TACE in patients with an uncompromised sphincter of Oddi was recommended. Patients with active infections prior to TACE were excluded. AP was deemed inappropriate if it deviated from guidelines (antibiotic choice and/or duration). Primary outcome was AP appropriateness and 30-day TACE related infections.
Figure 1. Timeline of our multipronged approach

Results
Seventy patients were included. There were no differences in baseline demographics pre and post implementation (Table 1). Following guideline implementation, there was a significant improvement in AP used for TACE. AP appropriateness pre-implementation and post-implementation was 14/31 (45.2%) and 37/39 (94.9%) respectively (p&lt; 0.001). Guideline compliant antibiotics were selected more frequently (14 [45.2%] vs 38 [97.4%], p&lt; 0.001), and more patients received single dose AP (22 [71.0%] vs 38 [97.4%], p=0.004). Of the 18 patients who did not receive guideline recommended AP, 16 (88.9%) received IV ceftriaxone and metronidazole, 1 (5.6%) IV amoxicillin/clavulanic acid, and 1 (5.6%) IV ciprofloxacin. Ten patients received a prolonged course of AP with a median duration of 6 days (IQR 4.3, 6.5). There were no significant differences in 30-day TACE related infections (1 [3.2%] vs 2 [5.1%], p=1.000) and 30-day mortality (1 [3.2%] vs 1 [2.6%], p=1.000). No patient had surgical site skin infection.

Conclusion
Our multipronged approach improved AP prescribing in patients undergoing TACE. Single dose IV cefazolin prophylaxis for TACE did not compromise safety outcomes in the post implementation review.

Disclosures
All Authors: No reported disclosures
1220. Is MIC all that matters? MIC Distributions of Ceftazidime and Cefepime in Ceftriaxone-Resistant E. coli and Klebsiella spp
Authors: Heil Emily , Heil Emily , Claeys Kimberly C , Luethy Paul 
Published: December 2021

Abstract

Background
The Clinical and Laboratory Standards Institute (CLSI) lowered MIC breakpoints for many beta-lactam antibiotics to enhance detection of resistance among Enterobacterales. This shift was also meant to eliminate the need for routine testing for extended-spectrum beta-lactamases (ESBLs). The recommended treatment for ESBL-producing Enterobacterales is carbapenems. The IDSA guidelines for MDR-GN organisms recommend using ceftriaxone (CRO) resistance as a proxy for ESBL production and thus carbapenem treatment. Under CLSI guidelines, alternative beta-lactams such as ceftazidime (CAZ) and cefepime (FEP) may still be reported as susceptible and thus used by clinicians even in light of IDSA recommendations. The aim of this project was to characterize the MIC distributions of CAZ and FEP stratified by CRO susceptibility.

Methods
Clinical E. coli, K. pneumoniae, and K. oxytoca isolates from blood cultures in adult patients from Nov 2016-Dec 2018 that had MICs tested by the Vitek-2 automated susceptibility testing system for CRO, FEP and CAZ were identified. Descriptive statistics were used to compare MIC distributions across the antibiotics of interest (SPSS).

Results
573 isolates were included, of these, 17.3% were CRO resistant. Most (53%) CRO-R isolates had FEP MICs ≤2 which is considered susceptible per CLSI; 19% had FEP MICs of 4-8 which would be considered S-DD by CLSI (Figure 1A; breakpoints noted by dashed lines). Using the EUCAST breakpoint of ≤1, only 11% of CRO-R isolates would be reported as FEP-S. For CAZ, 40% of CRO-R isolates had CAZ MICs ≤4, which is considered S by CLSI. Using the EUCAST breakpoint of ≤1, only 12% of CRO-R isolates would be reported as CAZ-S (Figure 1B).
Cefepime MIC Distribution for Ceftriaxone Resistant Isolates

Distribution of MICs for cefepime for ceftriaxone resistant isolates with the breakpoints for EUCAST and CLSI noted with a dashed line
Ceftazidime MIC Distribution for Ceftriaxone Resistant Isolates

Distribution of MICs for ceftazidime for ceftriaxone resistant isolates with the breakpoints for EUCAST and CLSI noted with a dashed line

Conclusion
Half of CRO-R E. coli, K. pneumoniae and K. oxytoca have FEP and CAZ MICs at or below the current CLSI breakpoints. This may lead to their use for serious ESBL infections where a carbapenem is preferred. To prevent unnecessary use, laboratories should consider suppressing FEP and CAZ susceptibilities when CRO-R or adopting more the aggressive EUCAST breakpoints for these agents.

Disclosures
Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)
1222. Ceftolozane-Tazobactam Heteroresistance in Cystic Fibrosis Related Pseudomonas aeruginosa Infections
Authors: Sanders James , Monogue Marguerite , Greenberg David E , Pybus Christine A , Clark Andrew E 
Published: December 2021

Abstract

Background
Cystic fibrosis (CF) patients are often colonized with Pseudomonas aeruginosa (PSA). During treatment, PSA can develop subpopulations exhibiting variable in vitro antimicrobial susceptibility patterns. Heteroresistance may underlie the reported discordant in vitro results and clinical responses to various antimicrobials. Here, we sought to examine the presence and nature of PSA heteroresistance to ceftolozane-tazobactam (C-T) in isolates originating from CF pulmonary exacerbations.

Methods
Respiratory cultures from 26 adult CF patients were collected. From each sample, 5-10 PSA colonies were selected. Susceptibility testing was conducted via E-test for C-T, ceftazidime-avibactam (CZA), and imipenem-relebactam (I-R). Polyclonal-heteroresistance (PHR) was defined as the presence of different susceptibility profiles among the colonies that originated from a single patient specimen. Population analysis profile (PAPs) were performed to assess the presence of monoclonal-heteroresistance (MHR), defined as ≥ 4 fold change in the C-T MIC from a single colony over 24-48 hours.

Results
246 PSA isolates from 26 adult CF patients were included. The C-T MIC50 and MIC90 were 1/4 and ≥ 256/4 µg/mL, respectively (Figure 1). Sixteen of the 26 patients (62%) demonstrated ≥ 2 fold change in C-T MIC between isolates from the same culture. Of these 16 isolates, the fold change in C-T MIC was &gt;2 fold for 7 isolates (27%) and resulted in a susceptibility interpretation change in 6 of the isolates (23%). Of the 32 isolates that underwent PAP testing, 7 grew on MH plates at 2-fold the C-T MIC concentration. One isolate, PSA 1311, demonstrated growth on PAPs up to 4 fold the MIC (16/4 µg/mL) (Figure 2).
Figure 1. Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam MIC distributions against PSA isolates from 26 adult CF patients

Figure 2. Monoclonal heteroresistance to C-T (PSA 1311 [C-T MIC 1/4 µg/mL] PAPs at 2, 4, 6, and 8-fold the C-T MIC).

Conclusion
Susceptibilities to C-T and CZA were similar across our CF PSA isolates. Comparatively, I-R retained better in vitro potency. C-T PHR exists among PSA isolates in the majority of our CF patients. Approximately 25% of these PHR isolates resulted in susceptibility interpretation changes supporting concerns surrounding the utility of traditional susceptibility testing methodology for CF isolates. These data suggest MHR also exists, albeit rare in this small subset. Additional data are needed to better understand these results in clinical context.

Disclosures
David E. Greenberg, MD, Shionogi (Grant/Research Support)Solenic Medical (Shareholder)
1223. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2019
Authors: Lob Sibylle , Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: December 2021

Abstract

Background
Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards.

Methods
Non-duplicate clinical isolates were collected in 2017-2019 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC &gt;1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC &gt;1 µg/ml.

Results
The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited &gt;96% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 62.3% and 65.6% of ICU and non-ICU isolates, respectively, and 36.3% and 33.2%, respectively, carried metallo-β-lactamases (MBLs). CAZ-AVI inhibited &gt;97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI was &gt;10 percentage points higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (24.4% and 22.0% in ICU and non-ICUs, respectively). CAZ-AVI inhibited &gt;98% of MEM-NS MBL-negative isolates from LA.
Results Table

Conclusion
CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those from patients in ICU wards, where antimicrobial resistance is typically higher.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1224. In vitro Activities of Ceftaroline and Comparator Agents against Gram-positive Bacterial Pathogens Causing Blood Stream Infections in a Global Population: ATLAS Surveillance Program 2012-2019
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: December 2021

Abstract

Background
Typical gram-positive organisms causing bloodstream infections (BSI) include Staphylococcus aureus (methicillin-susceptible [MSSA] and -nonsusceptible [MRSA]), coagulase negative staphylococci, Streptococcus pneumoniae and beta hemolytic streptococci. The parenteral cephem ceftaroline fosamil is approved for treatment of patients with community-acquired bacterial pneumonia caused by S. pneumoniae (including cases with concurrent bacteremia), MSSA, Haemophilus influenzae, and some species of Enterobacterales. Limited data have been published on the in vitro activity of ceftaroline against recent gram-positive clinical isolates known to be frequent bacterial causes of blood stream infections.

Methods
Standard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 2021 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2019 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 21,967 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2019 were tested. Isolates came from (n/%): Asia/South Pacific (2,970/13.5%), Europe (13,691/62.3%), Latin America (2,824/12.9%), MidEast/Africa (1,498/6.8%), and North America (Canada only) (984/4.5%).

Results
Ceftaroline and comparator agent activities are summarized in the following table.
Results Table

Conclusion
Greater than 99% of S. pneumoniae, beta-hemolytic streptococci and MSSA isolates included in a 2012-2019 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 90.8% of MRSA were susceptible, and 9.1% isolates categorized as susceptible-dose dependent (MIC, 2-4 µg/mL); four isolates (two from Thailand and one each from China and S. Korea) were resistant to ceftaroline (MIC &gt;4 µg/mL). The ceftaroline MIC90 for S. epidermidis was 0.5 µg/mL, with 97.7% of MICs ≤1 µg/mL. Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI.

Disclosures
Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
1225. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales Collected from Geriatric Patients in ICU and non-ICU wards, ATLAS Surveillance Program 2016-2019
Authors: Lob Sibylle , Kazmierczak Krystyna , Arhin Francis , Sahm Daniel F 
Published: December 2021

Abstract

Background
Elevated resistance rates have been reported in ICUs. Aztreonam (ATM) combined with avibactam (AVI) is being developed for use against drug-resistant Enterobacterales (Ebact), including metallo-β-lactamase (MBL)-positive isolates. We examined the activity of ATM-AVI and comparators against Ebact isolates collected from geriatric patients in ICU and non-ICU wards as part of the ATLAS surveillance program.

Methods
23754 non-duplicate Ebact isolates were collected in 53 countries in Asia/Pacific (excluding mainland China and India), Europe, Latin America, and Middle East/Africa from patients ≥65 years with lower respiratory tract (LRTI), urinary tract (UTI), skin and soft tissue (SSTI), intra-abdominal (IAI), and bloodstream (BSI) infections. Susceptibility testing was performed by CLSI broth microdilution and values interpreted using CLSI 2021 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in isolates with meropenem MIC &gt;1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC &gt;1 µg/mL.

Results
Susceptibility of the studied comparator agents was generally slightly lower among Ebact from BSI than other infection types (Table). Susceptibility was also generally lower among Ebact from ICU than non-ICU wards by up to 10 percentage points, and MIC90 values were up to 32-fold higher. ATM-AVI MIC90 values were within one doubling-dilution across all studied strata (0.12-0.25 µg/mL), were comparable to or lower than for meropenem in all strata, and were 2 to ≥9 dilutions lower than all other tested comparators. MBL-positive Ebact were found in 1.5% of LRTI (n=91), 1.2% of UTI (n=70), 1.1% of SSTI (n=52), 1.3% of BSI (n=49), and 0.7% of IAI isolates (n=22). MBL-positive rates were higher among ICU (1.7%, n=101) than non-ICU isolates (1.0%, n=183). ATM-AVI MIC90 values were 0.5 µg/mL against MBL-positive isolates from all ward and infection types except SSTI (MIC90 0.25 µg/mL) and BSI (MIC90 1 µg/mL), 2-4 dilutions lower than tigecycline and at least 5-10 dilutions lower than the other comparators.
Results Table

Conclusion
ATM-AVI could provide a valuable therapeutic option for treatment of infections caused by Ebact in patients ≥65 years old in both ICU and non-ICU wards.

Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)