bluuebunny/crossref_metadata_2025 huggingface dataset:
1206. Effects of Climatic Variability on Lyme Disease Outbreaks in California
Authors: Kangath Raghesh Varot , Ramachandra Rajasree Pai , Madurapperuma Buddhika , Scaroni Luke
Published: December 2021

Background

Climate change has increased the risk of tick borne infections. The life cycle and prevalence of deer ticks are strongly influenced by temperature. Warmer temperatures associated with climate change are projected to increase the range of suitable tick habitats driving the spread of Lyme disease (LD). Short winters could also increase tick activity increasing the risk of exposure. This study examines the relationship between LD incidence and temperature-precipitation and their anomalies in CA counties.

Methods

Trends and relationships of Lyme Disease (LD) cases and climatic factors were analyzed among the California counties from 2000 to 2019. Lyme disease tabulate data and climatic data were obtained from Centers for Disease Control, and NOAA, and Climate Data Guide respectively. Canonical correspondence analysis (CCA) was performed using variables: (i) LD cases, (ii) precipitation & anomaly, and temperature & anomaly. The CCA ordination explained the variability between LD cases and climatic variables. Biplots were used to visualize the associations between LD cases and climatic anomalies.

Results

We compared the countywide LD cases in relation to climatic factors in California from 2000 to 2019. A total of 96 cases in 2000, 117 cases in 2009, and 144 cases in 2019 were reported in the 55 counties of California. Santa Clara reported the highest LD cases in 2003 (23 cases; 16%), followed by Los Angeles in 2013 (20 cases; 18%) and Santa Cruz in 2017 (19 cases; 13%). CCA ordination showed distinguishable clustering patterns between southern California counties (Santa Clara, Santa Cruz, Alameda, and San Diego) and northern coast and Klamath mountains range (Humboldt, Trinity, Shasta, and Siskiyou) regions (Fig. 1). Moderate mean annual temperature (56.5 °F - 62.5 °F) and temperature anomaly (3.8 °F - 5.5 °F) were the most important variable predictor for high LD outbreak.

The CCA ordination shows the relationships between Lyme Disease and climatic variables for the 55 Counties of California. The bottom right circle represents Lyme cases positively correlated with temperature anomaly (3.8 °F - 5.5 °F) and moderate annual mean temperature (56.5 °F - 62.5 °F). The upper left circle represents Lyme cases negatively correlated with mean annual precipitation.

Conclusion

Moderate temperature with low moist spell anomalies in the south neighboring CA counties showed a positive influence on LD outbreak. The climatic conditions in those areas suitable for Oak trees and masting acorn resulting in the establishment of tick and host (deer) populations. We recommend robust surveillance and lab testing for patients with a history of tick bites in these regions.

Disclosures

All Authors: No reported disclosures
1207. Coronavirus Disease, 2019 (COVID-19) in Long-Term Care Facilities (LTCF): One Large County’s Response, California 2020-2021
Authors: Chinn Raymond Y , Thihalolipavan Sayone , Wheeler Jennifer , Kang Grace , Malone John D , McDonald Eric
Published: December 2021

Background

The coronavirus-19 disease (COVID-19) outbreak has had a particularly devasting effect on skilled nursing facility (SNF) residents and healthcare workers (HCWs). While representing only 11% of COVID-19 cases, the residents accounted for 43% of deaths in the United States.

Methods

We report a retrospective review of the support provided by our local health department (LHD) to long-term care facilities in response to the COVID-19 pandemic. This group comprised of staff from healthcare-associated infections (HAI); the Medical Operations Center (MOC); Testing, Tracing, and Treatment (T3); and the Healthcare Provider Status Taskforce (Table 1 outlines their functions). The HAI team with the State Public Health Department provided infection prevention and control (IPC) outbreak investigation, education, recommendations, and ongoing access to technical assistance. The T3 team focused on rapid response testing and tracing; the HPSTF team collected data and issued questionnaires; the MOC responded to staffing and PPE requests; and the Long-Term Care Facility sector presented routine telebriefings to update the facilities on public health guidance, share resources, and answer questions during and in between briefings.

Table 1. Sectors and Function of Response Teams to COVID-19

Results

From March 2020 through May 2021, there were 504 outbreaks in LTCFs; the HAI team performed 281 outbreak investigations (Figure 1). In the same period, 308,264 molecular tests were performed using various platforms; laboratory services were outsourced during peak testing requests (Figure 2); “strike teams were deployed to facilitate testing on 404 occasions. Self-reported fully vaccination rate for SNF staff was 73% (March 2021) and 76% for residents (April 2021). There were 568 staff requested; total orders for PPE were 4,839 and 16,892,823 PPE items were fulfilled (Figure 3). In addition to knowledge gaps in IPC, other challenges included shifting IPC guidance, PPE shortages, timeliness of test results that impacted cohorting, community acquisition of disease with transmission to residents, interfacility spread among staff, staffing shortages, and vaccine hesitancy issues.

Figure 1. Number of Outbreaks and Number of Outbreak Investigations

Figure 2. Number of Tests Performed by the Public Health Laboratory and the Number of Visits by “Strike Teams”

Figure 3. Personal Protective Equipment Fulfillment during COVID-19 Pandemic

Conclusion

The management of the recent COVID-19 outbreaks required a multi-pronged approach. Lessons learned are applicable to other highly transmissible infectious diseases.

Disclosures

All Authors: No reported disclosures
1208. Omadacycline In Vitro Activity Against Bacillus Anthracis
Authors: Serio Alisa W , Carl Gelhaus H , Eichelberger Noah , Heine Henry S , Anastasiou Diane M , Eichhorst Kristina
Published: December 2021

Background

Bacillus anthracis, the etiological agent of anthrax, is one of the agents most likely to be used in a biologic attack. Omadacycline previously has demonstrated potent in vitro and in vivo activity against B. anthracis. This project evaluated the in vitro activity of omadacycline against a larger set of B. anthracis strains across two laboratories.

Methods

Methods: Antibiotic susceptibility testing followed Clinical Laboratory Standard Institute methods against a collection of 53 B. anthracis strains at the University of Florida (UF) and 50 B. anthracis strains at MRIGlobal, representing human and animal isolates from North America, Africa, Europe, Asia, and Australia. Minimum inhibitory concentrations (MICs) for omadacycline and comparators at both sites (doxycycline, ciprofloxacin, levofloxacin, moxifloxacin) were determined by broth microdilution.

Results

Results: In the UF study, omadacycline demonstrated an MIC50 of 0.015 mg/L and an MIC90 of 0.03 mg/L against B. anthracis. Omadacycline MIC values were equal to or lower than doxycycline. In the MRIGlobal study, omadacycline demonstrated an MIC50 of 0.06 mg/L and an MIC90 of 0.06 mg/L (Table 1). All comparator MIC values were within ranges previously observed against these strains. Against a ciprofloxacin-resistant strain (MIC = 2 mg/L), omadacycline had an MIC value of 0.015 mg/L; against a doxycycline-resistant strain (MIC = 4 mg/L), omadacycline had an MIC value of 0.06 mg/L. Reproducibility was observed between the 2 laboratories for omadacycline in vitro activity against B. anthracis (Table 2).

Table 1. MIC Concentration Summary for Omadacycline and Comparators Against B. anthracis Strains

Table 2. Reproducibility of Omadacycline in Vitro Activity Against B. anthracis Strains

Conclusion

Based on the in vitro activity in both studies, omadacycline has the potential to be effective in treating anthrax infection. Reproducibility of omadacycline in vitro activity against B. anthracis was observed at 2 independent study sites.

Disclosures

Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Diane M. Anastasiou, BA, Paratek Pharmaceuticals, Inc. (Consultant)
1209. The Evolving Nature of Syndromic Surveillance During the COVID-19 Pandemic in Massachusetts
Authors: Willis Sarah J , Eberhardt Karen , Randall Liisa , DeMaria Alfred , Brown Catherine M , Madoff Lawrence C , Zambarano Bob , Ochoa Aileen , Klompas Michael , Cocoros Noelle
Published: December 2021

Background

We developed a syndromic algorithm for COVID-19 like illness (CLI) to provide supplementary surveillance data on COVID-19 activity.

Methods

The CLI algorithm was developed using the Electronic Medical Record Support for Public Health platform (esphealth.org) and data from five clinical practice groups in Massachusetts that collectively care for 25% of the state’s population. Signs and symptoms of CLI were identified using ICD-10 diagnosis codes and measured temperature.

The algorithm originally included three categories: Category 1 required codes for coronavirus infection and lower respiratory tract infections (LRTI); Category 2 required an LRTI-related diagnosis and fever; Category 3 required an upper or lower RTI and fever.

The three categories mirrored statewide laboratory-confirmed case trends during spring and summer 2020 but did not detect the increase in late fall. We hypothesized this was due to the requirements for fever and LRTI. Therefore, we added three new categories defined by milder symptoms without fever: Category 4 requires LRTI-related diagnoses only; Category 5 requires upper or lower RTI or olfactory/taste disorders; and Category 6 requires at least one sign of CLI not identified by another category.

Results

The six-category algorithm detected the initial surge in April 2020, the summer lull, and the second surge in late fall (see figure). Category 1 cases were not identified until mid-March, which coincides with the first laboratory-confirmed cases in Massachusetts. Categories 2 and 3, which required fever, were prominent during the initial surge but declined over time. Category 5, the broadest category, declined during February and March 2020, likely capturing the end of the influenza season, and successfully detected the spring surge and fall resurgence. Weekly number of COVID-19 like illnesses by category, February 2, 2020 through May 8, 2021

Conclusion

A syndromic definition that included mild upper RTI and olfactory/taste disorders, with or without fever or LRTI, mirrored changes in laboratory-confirmed COVID-19 cases better than definitions that required fever and LRTI. This suggests a shift in medically attended care and/or coding practices during initial vs subsequent surges of COVID-19, and the importance of using a broad definition of CLI for ongoing surveillance.

Disclosures

Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)
1212. COVID-19 and the Importance of Institutional Trust to Public Health
Authors: Kricorian Karin , Kricorian Katherine
Published: December 2021

Background

Institutional trust is a key component of the public health system’s effectiveness. However, the COVID-19 pandemic highlighted gaps in institutional trust and hesitation. Analysis was conducted to understand correlates of institutional trust to inform communication strategies for the ongoing pandemic and future public health crises.

Methods

The Roper Center for Public Opinion/ America’s Voice Project Coronavirus Index conducted a US online survey February 22-April 5, 2021 and included questions about COVID-19 experiences, attitudes and behaviors. Respondents also indicated trust in each of four institutions to provide accurate information about COVID-19: federal government, state government, CDC and national public health officials. Scores were summed to create an Institutional Trust (IT) index: the top third was classified as “High IT,” the middle third “Moderate IT” and the bottom third “Low IT.” Data were analyzed using χ2 tests, with z-tests for more granular between-group comparisons.

Results

Those with Low IT were significantly more likely than those with Moderate or High IT to be white, male, rural, politically conservative, married, and live with children under age 18. Low IT individuals were less likely to have been tested for COVID-19 themselves and less likely to know someone who had tested positive for COVID-19. However, Low IT respondents were more likely to have tested positive for COVID-19, even when controlling for their lower propensity to be tested. Low IT individuals were significantly more likely to have visited restaurants and stores in the past week and feel these activities posed no health risk; they also wore masks less often. Despite greater risk-taking, Low IT respondents were over five times more likely than High IT respondents to refuse the COVID-19 vaccine.

Conclusion

Low IT was associated with higher COVID-19 vaccine hesitancy as well as behavior that, at the time data was collected, put people at higher risk of contracting COVID-19. Public health officials should prioritize the development of more effective communications towards Low IT populations. Traditional methods of establishing message credibility may require modification in order to encourage Low IT individuals to participate in behaviors that enhance public health.

Disclosures

All Authors: No reported disclosures
1213. Vaccine Uptake Amongst Participants in the North Carolina COVID-19 Community Research Partnership Who Were Initially Receptive or Hesitant to Receive a COVID-19 Vaccine
Authors: Munawar Iqra , Seals Austin L , Sanders John W , Herrington David M , Wierzba Thomas F
Published: December 2021

Background

Public health officials are concerned that adults may refuse to be vaccinated with an approved COVID-19 vaccine thereby limiting the community health benefit. Here, we studied the self-reported intent to be vaccinated of persons in North Carolina (NC) and then measured whether they did or did not get vaccinated.

Methods

The Community COVID-19 Research Partnership (CCRP) is a large prospective study exploring COVID-19 epidemiology and sequelae in participants of several mid-Atlantic and Southern States. All participants complete an online daily survey where they are asked questions about COVID-like symptoms, infections, and their vaccination status. In addition to the daily survey, in December 2020, we implemented a short online cross-sectional survey questioning NC participants on whether they intended to be vaccinated. After completing the cross-sectional survey, we used daily survey data through 15 May 2021 to see if participants reported receiving vaccine. Unvaccinated participants who did not complete the daily survey 30 days or more prior to 15 May 2021 were excluded.

Results

18,874 participants completed the cross-sectional survey and reported vaccination status. Of these participants, 90% were white, 68% were female, 26% were healthcare workers, and 2% self-reported COVID-19 diagnosis The median age was 54 years (IQR: 41 – 65). 79%, 13%, 9%, and 2% answered yes, unsure, no, and prefer not to answer, respectively, about intention to be vaccinated (Table). 99% of the participants who intended to receive the COVID-19 vaccine reporting being vaccinated. Those who were unsure or intended not to get vaccinated had vaccination rates of 80% and 53%, respectively. 78% of the participants who preferred not to answer were vaccinated.

Table

Vaccine intent versus vaccine status – COVID-19 Community Research Partnership, North Carolina, December 2020 – May 2021

Conclusion

More than three-quarters of NC participants intended to get vaccinated and by mid-May 2021, the vast majority had received at least one dose. Similarly, those who were unsure or preferred not to say were mostly vaccinated. Even among those who reported they would not get vaccine in January, more than half had received vaccine by May. The nature of our sample makes it difficult to generalize results to the population of NC; nevertheless, further investigation as to the causes of the shift in attitudes is warranted.

Disclosures

All Authors: No reported disclosures
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

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< 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< 0.001). Households in census tracts with >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

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

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< 0.001). Guideline compliant antibiotics were selected more frequently (14 [45.2%] vs 38 [97.4%], p< 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

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

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 >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

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 >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >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 >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 >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 >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 >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

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 >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

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 >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >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)
1228. Outcomes Associated with Empiric Cefepime or Meropenem for Bloodstream Infections Caused by Ceftriaxone-Resistant, Cefepime-Susceptible Escherichia coli and Klebsiella pneumoniae
Authors: Frescas Brian E , McCoy Christopher , Kirby James , Bowden Robert , Mercuro Nicholas J
Published: December 2021

Background

Cefepime is a 4th generation cephalosporin frequently used for empiric sepsis therapy. Dose- and MIC-dependent efficacy of cefepime is supported by the Clinical & Laboratory Standards Institute, however its use in infections due to extended-spectrum beta-lactamase-producing Enterobacterales is controversial. This study aims to compare outcomes in patients given empiric meropenem or cefepime for bloodstream infections (BSI) caused by ceftriaxone-resistant E. coli and K. pneumoniae.

Methods

This single-center retrospective cohort included adults hospitalized from 2010 - 2020 and received empiric cefepime or meropenem for BSI caused by ceftriaxone-resistant E. coli or K. pneumoniae. In the cefepime group, only organisms with MIC ≤ 2 mg/L were included. Patients who received the empiric agent for < 48 hours, or received an additional active agent within 48 hours were excluded. The primary outcome was 30-day mortality; secondary outcomes were recurrent infection, readmission, and time to clinical stability. Chi-squared or Fisher’s exact was used for categorical variables and Mann-Whitney-U for continuous variables. Inverse probability treatment weighing was used to determine the impact of empirical therapy on clinical stability at 48 hours.

Results

Fifty-four patients were included: 36 received empiric meropenem, 18 received cefepime. There were no significant differences in baseline severity of illness or comorbid conditions. Urinary source was less common in the meropenem group compared to cefepime (52.8 vs 83.8%, p=0.028) (Table 1). There was no difference in 30-day mortality between meropenem and cefepime (2.8 vs 11.1%, p = 0.255). More patients achieved clinical stability at 48 hours on empiric meropenem compared to cefepime (75 vs 44.4%, p = 0.027), and time to clinical stability was significantly shorter (median 21.3 vs 38.5 hours, p = 0.016). Most patients in the meropenem and cefepime groups completed definitive treatment with a carbapenem (88.9 vs 72.2%, p=0.142).

Table 1: Results

Summary of primary and secondary outcomes

Conclusion

There was no difference in mortality between patients receiving empiric cefepime for BSI due to ceftriaxone-resistant Enterobacterales, with cefepime MIC ≤ 2 mg/L, compared to meropenem; however, time to clinical stability was significantly delayed.

Disclosures

James Kirby, MD, D(ABMM), First Light Biosciences (Board Member)TECAN, Inc. (Research Grant or Support)
1230. Evaluation of the Interplay Between β-lactamases and Porin Production on β-Lactam MICs in Klebsiella pneumoniae
Authors: Whitney Alyssa K , Hanson Nancy D
Published: December 2021

Background

K. pneumoniae can emerge resistant to β-lactam antibiotics through the production of β-lactamase enzymes and/or loss of the outer membrane porins, OmpK35, OmpK36, and/or PhoE. While both mechanisms are hypothesized to work synergistically, β-lactamases have been the focus of previous studies. As a result, the contribution of outer membrane porin loss to the β-lactam minimum inhibitory concentration (MIC) is unknown. The objective of this study was to evaluate the contribution of specific β-lactamases and porin production to β-lactam susceptibility. We hypothesize that production of a β-lactamase in a clinical isolate deficient in 3 major porins will result in higher β-lactam MICs but not always a resistant phenotype.

Methods

The structural gene and promoter of CTX-M-14, CTX-M-15, and CMY-2 were cloned into a low copy number vector and transformed into Kp 23, a wild-type clinical isolate, and KPM 20, a clinical isolate deficient in OmpK35/36 and PhoE. MICs to ceftolozane/tazobactam, cefotaxime, ceftazidime, cefepime, and meropenem were determined by E-test. Kp 23 and KPM 20 were characterized by Western blot and whole genome sequencing.

Results

Production of CMY-2 alone led to a resistant phenotype for ceftolozane/tazobactam, cefotaxime, and ceftazidime regardless of porin production (Figure 1). CMY-2 production in KPM 20 resulted in non-susceptibility to meropenem. Both clones were susceptible to cefepime. Production of CTX-M-14 and CTX-M-15 in Kp 23 resulted in only cefotaxime resistance. Production of CTX-M-14 and CTX-M-15 in KPM 20 resulted in isolates non-susceptible to all antibiotics tested.

Figure 1. MICs of K. pneumoniae clones against panel of β-lactam antibiotics.

Conclusion

When evaluating clinical isolates, it is impossible to determine the contribution of individual resistance mechanisms in the susceptibility pattern. This study demonstrated that resistance is not solely dependent on the β-lactamase produced and that the impact of porin deficiency varies with the antibiotic being evaluated. These data suggest that antibiotic selection may be more nuanced and that a broader range of therapeutics may be available given the appropriate diagnostic tools. Understanding the contributions of all resistance mechanisms is necessary to inform selection of the most appropriate antibiotic therapy.

Disclosures

Nancy D. Hanson, PhD, Merck (Grant/Research Support)
1231. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Lower Respiratory Tract Infections Collected During the ATLAS Global Surveillance Program, 2017-2019
Authors: Lob Sibylle , Kazmierczak Krystyna , Arhin Francis , Sahm Daniel F
Published: December 2021

Background

β-lactamase-producing Enterobacterales (Ebact) frequently co-carry resistance to antimicrobials from other classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Ebact, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Ebact collected in 2017-2019 from patients with lower respiratory tract infections (LRTI) as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program.

Methods

Non-duplicate clinical isolates were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL.

Results

ATM-AVI was active in vitro against Ebact isolates from LRTI (MIC90, 0.25 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Ebact (Table). The tested β-lactam comparators showed susceptibility of < 78% against these subsets of resistant isolates.

Results Table

Conclusion

Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Ebact collected from LRTI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of LRTI caused by drug-resistant Ebact.

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)