bluuebunny/crossref_metadata_2025 huggingface dataset:
1433. Impact of 2019 US Food and Drug Administration (FDA) Guidance on Developing Drugs for Urinary Tract Infection (UTI) on the Perceived Efficacy of Antibiotics for the Treatment of Uncomplicated UTI (uUTI)
Authors: Henriksen Anne Santerre , Nicolle Lindsay , Das Anita F
Published: December 2021

Background

In 2019, the FDA issued guidance on drug development for treatment of UTIs. To explore the impact of this guidance, we compared clinical and microbiological outcomes of the fluoroquinolones norfloxacin and ciprofloxacin and the β-lactams pivmecillinam and sulopenem for treatment of uUTIs from original publications versus recent analyses conducted in accordance with the FDA guidance.

Methods

The efficacy of pivmecillinam 400 mg twice daily (BID), 3 days (3d) versus norfloxacin 400 mg BID, 3d was reported in a 2002 publication. Patient-level data were used to re-analyze clinical and microbiological outcomes in the microbiological intent-to-treat population in accordance with the 2019 FDA guidance. For descriptive comparison, we present the efficacy of ciprofloxacin 250 mg BID, 3d vs sulopenem 500 mg BID, 5d in the 2020 SURE-1 trial (also conducted in accordance with FDA guidance) alongside historical efficacy data for ciprofloxacin.

Results

Re-analysis of data from the trial of pivmecillinam and norfloxacin showed microbiological responses for pivmecillinam and norfloxacin of 64% and 79%, respectively. Microbiological responses were higher, 75% for pivmecillinam and 91% for norfloxacin, in the original analysis. For clinical response, re-analysis showed 75% for pivmecillinam and 88% for norfloxacin, while historical data were 82% and 88%, respectively. In the SURE-1 trial, the microbiological response of patients assessed at Day 12 was 76.6% for sulopenem and 79.1% for ciprofloxacin. In a 2002 publication, bacterial eradication at 4 to 11 days after treatment was 93.7% for ciprofloxacin 250 mg, a higher response rate than that reported in SURE-1. For clinical response, rates were 78.7% for ciprofloxacin in SURE-1 and 92.7% for the historical ciprofloxacin data.

Conclusion

When assessed in accordance with the 2019 FDA guidance, clinical and microbiological efficacy of both fluoroquinolones and β-lactam antibiotics appears lower than has been published in the past. Healthcare providers should be aware that newer antibiotics may appear to have a lower efficacy than older antibiotics due to the application of more stringent definitions in the FDA guidance.

Disclosures

Anne Santerre Henriksen, MS, Advanz (Consultant)Shionogi BV (Consultant)UTILITY Therapeutics (Consultant) Lindsay Nicolle, MD, Entos (Consultant)GSK (Consultant)Iterum (Consultant)Utility Therapeutics (Consultant) Anita F. Das, PhD, Adagio Therapeutics, Inc. (Consultant)
1437. Short Versus Long-Course Intravenous Antibiotics for Young Infants with Urinary Tract Infection
Authors: Lawrence Jolie , Pittet Laure F , Hikmat Samar , Silvester Eloise J , Clifford Vanessa , Hunt Rodney , Gwee Amanda
Published: December 2021

Background

Shorter courses of intravenous (IV) antibiotics for young infants with urinary tract infection (UTI) have myriad advantages. As practice shifts toward shorter IV treatment course, this study aimed to determine the safety of early IV-to-oral antibiotic switch, and identify risk factors for bacteraemia with UTI.

Methods

Retrospective audit of infants aged ≤90 days with a positive urine culture at a quaternary paediatric hospital over four years (2016-2020). Data were collected from the hospital electronic medical record and laboratory information system. Short-course IV antibiotic duration was defined as < 48 hours for nonbacteraemic UTI and < 7 days for bacteraemic UTI. Multivariate analysis was used to determine patient factors predicting bacteraemia.

Results

Among 427 infants with nonbacteraemic UTI, 257 (60.2%) were treated for < 48 hours. Clinicians prescribed shorter IV courses to infants who were female, aged >30 days, afebrile, and those without bacteraemia or cerebrospinal fluid pleocytosis. Treatment failure (30-day UTI recurrence) occurred in 6/451 (1.3%) infants. All had nonbacteraemic UTI and only one received < 48 hours of IV antibiotics. None had serious complications (bacteraemia, meningitis, death). Follow-up audiology was performed in 21/31 (68%) infants with cerebrospinal fluid pleocytosis, and one had sensorineural hearing loss. Bacteraemia occurred in 24/451 (5.3%) infants, with 10 receiving < 7 days IV antibiotics with no treatment failure, meningitis or death. Fever and pyelonephritis were independent predictors of bacteraemia.

Conclusion

Short course IV antibiotics for < 48 hours for young infants with nonbacteraemic UTI are safe provided bacterial meningitis has been excluded. Treatment failure and serious complications were rare in young infants with UTI.

Disclosures

All Authors: No reported disclosures
1438. Prevalence and Risk Factors for Extended Spectrum Betalactamases Among Hospitalized Patients with Community Acquired Pyelonephritis in Colombia
Authors: Rodríguez Mariana Franco , Cortes Jorge
Published: December 2021

Background

Urinary tract infections (UTI) are the most frequent bacterial infection in hospitalized patients. Extented spectrum betalactamases (ESBL) producing bacteria causing UTI have become more prevalent. Escherichia coli (E. coli) is the most frequent ESBL producing bacteria isolated in UTI. This drug resistant organisms are associated with poorer outcomes for patients. In low income countries, approaching to and treating ESBL E. coli, represent a major challenge for health care centers.

Methods

A retrospective cohort of adult patients with community acquired pyelonephritis caused by Escherichia coli was identified in a tertiary hospital in Colombia. Susceptibility was performed with Vitek (BioMerieux, France); extended spectrum beta lactamase (ESBL) production was defined phenotypically. Inclusion criteria were adult patients hospitalized with a positive urine culture for E. coli. Demographic and clinical characteristics were searched in electronic records. Risk factors associated with ESBL production were identified by using a multivariate logistic regression analysis.

Results

During 7 years 817 patients with pyelonephritis caused by E. coli were identified. 79 (9.7%) of them were caused by ESBL producers. Women were 66% and 408 (74.8% of them) had menopause. Mean age was 64.2 years (standard deviation of 19.1). Of the cohort, 481 (561.1%) had at least some comorbidity and was frequent to find diabetes (18.5%), immunosuppression due to oncologic disease or medications (18.4%), urolithiasis or previous surgical procedures (17%). After logistic regression, risk factors identified to predict ESBL production, were: being a man (aOR 5.4, 2.1-18.2), a woman with menopause (aOR 2.9, 1.3 -9.9), and the Charlson score (aOR 0.83, 0.73 – 0.96). Previous antibiotic use was not related to ESBL infection.

Conclusion

In this relatively large cohort of patients with pyelonephritis caused by E. coli, ESBL production risk factors were not clearly identified other than sex and menopause. Curiously, Charlson score predicted a lower risk of resistance. Other factors (food consumptions and others) might be driving the resistance in the community in E. coli.

Disclosures

Jorge Cortes, MD, Pfizer (Research Grant or Support)
1442. Spatiotemporal Clusters of Varicella and the Regional Risks through Bayesian Approach: A National Five-year Cohort Analysis
Authors: Hong Kwan , Kim Jeehyun , Yum Sujin , Gómez Gómez Raquel Elizabeth , Chun Byung Chul
Published: December 2021

Background

Since varicella epidemics repeatedly occurred in Korea, it is essential to control varicella outbreaks preemptively in the targeted region. Therefore, we aimed to reveal spatiotemporal clusters of varicella and the regional risk factor of varicella incidence at the national level.

Methods

All varicella cases (defined as ICD-10 codes, B01-B09) from 2013 to 2017 in Korea were extracted from National Health Insurance Service. Of the total, 566,978 cases were realigned spatially by 250 administrative districts of Korea and temporally by a week. Spatial autocorrelation was tested using the global Moran’s I statistics using Monte Carlo simulation. Kulldorff’s prospective space-time scan statistics were used to reveal space-time clusters of varicella. Possible risk factors were extracted from the Korean Statistical Information Service and Community Health Survey of Korea, including hand hygiene perceptions, alcohol and smoking status, the proportion of children under 15 years old, the number of households, and household income by regions. After selecting significant risk factors through non-spatial generalized linear models, a conditional autoregressive spatiotempoal model with Bayesian extension was applied to estimate the regional factors affecting varicella incidence.

Results

There was spatial autocorrelation using Global Moran’s I statistics (P< 0.01). When the maximum cluster size was limited to 10% of the population, 17 spatiotemporal clusters were detected in specific regions in Korea (figure 1). Low perception of hand hygiene, the high proportion of alcohol drinking and cigarette smoking, high children proportion, low number of familial member, and low household income were associated with varicella spatiotemporal incidence (odds ratio: 0.97, 1.01, 2.31, 1.10, 0.99, 0.99, respectively; 95% credible intervals of all risk factors did not include 1).

Figure 1. Space-time prospective clusters of varicella in Korea using varicella incidence from 2013 to 2017.

Relative risks ratio of each cluster is described at the point.

Conclusion

Varicella incidence shows spatiotemporal clustering patterns in specific regions. Since regional factors such as the perception rate of hand hygiene, child proportion, alcohol drinking, cigarette smoking, and low household income affect varicella’s spatiotemporal incidence, strategies for targeted control of high-risk regions are strongly recommended.

Disclosures

All Authors: No reported disclosures
1443. Seroprevalence of HTLV-I/II in a Tertiary-Level Hospital in Newark, NJ
Authors: Robledo Jorge , O’Shaughnessy Michael , Varughese Tilly , Finkel Diana
Published: December 2021

Background

Human T-cell lymphotropic virus type I (HTLV-I) remains amongst the most neglected tropical diseases in the medical field due to its low prevalence in developed countries and the low incidence of its associated diseases, Adult T-cell lymphoma/leukemia (ATLL) and tropical spastic paraparesis (TSP). We proposed a higher prevalence of infections with this virus in Newark given its significant percentage of foreign-born residents of HTLV-endemic countries such as Jamaica, the Dominican Republic, Peru, and Brazil.

Methods

Descriptive study from secondary data. We obtained the total number of HTLV-I/II tests performed at University Hospital in the last 2 years (05/2018-10/2020). Subsequently, medical charts were reviewed to obtain epidemiological and clinical data.

Results

A total of 89 patients underwent screening for HTLV-I/II, of whom 4 (4%) were positive. The test was more frequently ordered in male (61%) and foreign-born (84%) individuals. The main reasons for testing were positive Strongyloides antibody in transplant candidates (20%), neurological symptoms (20%) and hematological symptoms (20%). In most cases, the test was ordered by Infectious Diseases (58%) and Neurology (18%). Being foreign-born was significantly associated with being tested in the case of non-transplant candidates (93% vs 56%, p< 0.001). Amongst the patients with positive serology, there were 2 cases of ATLL and 2 of TSP. Three of them had their country of origin registered (Ecuador, Barbados and Ghana). Family testing was only offered to one of the positive HTLV-I/II participants. Interestingly, this was the only case referred to Infectious Diseases.

Conclusion

There is low but significant seroprevalence of HTLV-I/II in our screened population. Most of the seropositive patients were lost to follow up and their relatives were not offered testing, demonstrating the need to raise awareness for this disease in health care workers.

Disclosures

All Authors: No reported disclosures
164. Antimicrobial Susceptibility of Urogenital and Extragenital Neisseria gonorrhoeae Isolates Among Men Who Have Sex with Men – SURRG and eGISP, 2018–2019
Authors: Quilter Laura , Cyr Sancta St , Hong Jaeyoung , Asbel Lenore , Bautista Ilene , Carter Bonnie , Casimir Yanick , Denny Michael , Ervin Melissa , Gomez Raquel , Harvey Alesia , Holderman Justin , Johnson Kimberly , Kohn Robert , Learner Emily , Mauk Kerry , Menza Timothy William , Mettenbrink Christie , Nettleton William , Nicosia Karen , Pham Cau D , Ried Christopher , Schlanger Karen , Schneider Annah , Soge Olusegun O , Tabidze Irina , Taylor Stephanie N , Tilghman Winston , Toler Cindy , Weinstock Hillard , Torrone Elizabeth
Published: December 2021

Background

Extragenital gonococcal infections are common among men who have sex with men (MSM); however, data comparing antimicrobial susceptibilities of urogenital and extragenital Neisseria gonorrhoeae isolates are limited. We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender MSM using specimens collected through CDC’s enhanced Gonococcal Isolate Surveillance Project (eGISP) and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG).

Methods

During January 1, 2018–December 31, 2019, 12 eGISP and 8 SURRG sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in STD clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs) and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites.

Results

Participating clinics collected 3,974 urethral, 1,553 rectal, and 1,049 pharyngeal isolates from 5,456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared to anogenital isolates (p< 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥ 0.125 µg/ml) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (p< 0.05).

Conclusion

Based on data collected from multi-jurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of N. gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

Disclosures

Olusegun O. Soge, PhD, Hologic Inc. (Grant/Research Support)SpeeDx Inc. (Grant/Research Support) Stephanie N. Taylor, MD, GARDP - GC Antibiotic Development (Scientific Research Study Investigator, To my institution.)GlaxoSmithKline (Grant/Research Support, Funds to my institution.)
LB10. Impact of SARS-CoV-2 Delta Variant on the Spectrum of Pediatric COVID-19 Disease in Arkansas
Authors: Romero Jose R , Warden Donald E , Cima Michael
Published: December 2021

Background

Pediatric SARS-CoV-2 infection is generally thought to be asymptomatic or result in mild COVID-19 disease, with a paucity of severe outcomes. However, SARS-CoV-2 variants, notably B.1.617.2 (WHO Delta), have changed the clinical landscape of COVID-19 in the United States. Delta became the dominant variant in Arkansas (AR) the 1st week of July 2021. Schools contributed to pediatric infections during the January 2021 surge in COVID-19 infections even with physical mitigation measures (PMM) that were removed in March 2021. We present preliminary data suggesting a shift in the clinical presentation of children with Delta variant infection.

Methods

Pediatric (ages ≤ 18 years) case records for the 3 months representing key inflection points of the COVID-19 Pandemic in AR were reviewed. Outcomes (hospitalizations, ICU admission, mechanical ventilation, death) were recorded by the Arkansas Department of Health (ADH) in a statewide database. Fisher’s Exact Test was used with p-values < 0.05 indicating statistical significance.

Results

During July 2020, 3,268 pediatric cases were reported to ADH with 55 hospitalizations, 6 ICU admissions, 2 mechanical ventilations, and no deaths. A second peak in January 2021 included 11,735 pediatric cases, a 259.1% increase. Increases were also seen in hospitalizations (n=74), ICU admissions (n= 11), and mechanical ventilations (n=2). No deaths reported. The beginning of an exponential growth in cases during July 2021, before the opening of schools, included 8,031 pediatric cases. Despite 31.6% fewer cases than the previous peak, hospitalizations increased 41.9% (n=105) (p < 0.0001) and included increases in ICU and ventilator use of 68.6% (n=18) (p 0.0016) and 300% (n=8) (p 0.0034), respectively. One pediatric death was reported. (Tbl 1)

Conclusion

In the absence of PMM and despite the summer closure of schools, pediatric COVID-19 cases and severe outcomes increased significantly. Initial analysis of the AR July 2021 Delta variant surge indicates a statistically significant increase in pediatric COVID-19 disease and severity as indicated by a proportional increase in hospitalizations, ICU, and ventilator use. Further studies are warranted to better define Delta related childhood disease. Our findings also have implications for school PMM efforts.

Disclosures

All Authors: No reported disclosures
LB11. Preliminary Findings from a HIV Self-Testing Program among People Who Use Drugs
Authors: Rose Michelle , Guy Laura , Shamblen Steve , Guest Greg , Gilbertson Adam , Peiper Nicholas
Published: December 2021

Background

People who use drugs (PWUD) remain at significantly high risk for HIV infection. It is estimated that the majority of all new HIV infections are through injection drug use, with an estimated 2,500 new infections occurring annually among people who inject drugs. Although new HIV infections have been quickly rising over the past year, the Center for Disease Control and Prevention (CDC) preliminarily reported a 50% to 70% intra-pandemic decline in HIV testing. Within Kentucky, an ultra-high-risk state, multiple health departments reported all HIV testing stopped during the early stages of the COVID-19 pandemic (March-July 2020). Once testing resumed, appointments were sparse.

Methods

To address low rates of HIV testing among PWUD, we evaluated the acceptability of a HIV self-testing program (OraQuick In-Home HIV Test by OraSure Technologies, Inc.) implemented at a health department in Louisville, Kentucky that services PWUD. Descriptive statistics were calculated for testing location, testing self-efficacy, reasons and motivations, ease of use, and preferences for future services.

Results

From May to June 2021, a total of 230 PWUD engaged with the program (average of 18 per day). Most participants (87.8%) self-tested at the health department with the help of study staff, while the other 12.2% tested at home and returned at a later time. Approximately 77% of participants reported the self-test kit made them feel better able to keep track of their HIV status compared to standard testing methods. The most common reasons for testing were wanting to know their status (85%), the test was free (37%), fast results (31%), more privacy (23%), and recent high-risk drug use and sexual behaviors (17%). Virtually all (97%) reported the test kits were very easy to use. For future availability of self-test kits through the health department, 33% reported they would use them monthly, 28% every three months, 22% every six months, and 17% annually. In terms of preference for future testing modality, 72% indicated a preference for taking the kits home, while the other 28% indicated a desire to test at the health department with help from staff.

Conclusion

Program participants found the self-test kits to be acceptable and easy to use. Implications for program implementation and future research will be discussed.

Disclosures

Michelle Rose, MBA, Gilead Sciences Inc. (Grant/Research Support) Laura Guy, BS, CCRC, GILEAD Sciences (Grant/Research Support, Research Grant or Support)
LB12. Exebacase Shows Rapid Symptom Resolution in a Phase 2 Study in Adult Patients with Staphylococcus aureus bacteremia
Authors: Cassino Cara , Das Anita F , Lipka Joy
Published: December 2021

Background

Exebacase (EXB), a recombinantly-produced lysin (cell wall hydrolase), is the first direct lytic agent to advance into Phase 3 of clinical development for the treatment of bacteremia including infective endocarditis due to Staphylococcus aureus. The microbiologic attributes of EXB, including pathogen-targeted rapid bacteriolysis, and biofilm eradication are distinct from and synergistic with those of traditional antibiotics and underpin the therapeutic potential for EXB.

Methods

The Phase 2 trial was a randomized, double-blind, placebo-controlled multinational study. Patients were randomized (2:1) to receive a single 2-hour infusion of EXB or placebo (PBO) in addition to standard of care antibiotics. Time to resolution of symptoms (shortness of breath, sweating, fatigue and confusion) attributable to the bacteremia was analyzed using Kaplan-Meier methods. Time to resolution was defined as the number of days until all attributable symptoms were absent. If a new (not present at baseline) attributable symptom was present before the baseline symptoms resolved, this new symptom also had to be absent for symptoms to be considered resolved.

Results

A total of 86 patients (53 EXB and 33 PBO) had at least one attributable symptom present at baseline. Of these, symptoms resolved in 94.3% and 87.9% of EXB and PBO patients, respectively. The median time to resolution was 3 days for EXB and 6 days for PBO patients. Median days to symptom resolution in the MRSA group was 3 and 7 days for EXB and PBO patients, respectively, and 3 and 5 days for EXB and PBO patients in the MSSA group, respectively. Time to symptom resolution in MRSA patients in presented in Figure 1.

Figure 1. Time to Resolution of Symptoms in Patients with MRSA Bacteremia including Infective Endocarditis

Conclusion

The majority of EXB and PBO patients had symptom resolution. However, EXE patients achieved symptom resolution in 3 days compared with 6 days for PBO patients overall, and 7 days for PBO patients with MRSA. These data suggest that rapid bacteriolysis may translate to a clinical benefit for patients receiving EXB and aligns with a median length of hospital stay of 6 and 10 days among US MRSA patients that received EXE and PBO patients, respectively. (Fowler, et al, 2020).

Disclosures

Cara Cassino, MD, ContraFect Corporation (Employee) Anita F. Das, PhD, Adagio (Consultant)AN2 (Consultant)Cidara (Consultant)ContraFect (Consultant)Iterum (Consultant)MicuRx (Consultant)Paratek (Consultant)Union (Consultant) Joy Lipka, MS, ContraFect Corporation (Consultant)
165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020
Authors: Medalla Felicita , Watkins Louise Francois , Hughes Michael , Birhane Meseret , Dorough Layne , Griffin Chelsey , Reynolds Jared , Caidi Hayat , Webb Hattie E , Mintz Eric , Gutelius Bruce , Langley Gayle
Published: December 2021

Background

Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions.

Methods

Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin.

Results

During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states.

Conclusion

Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq.

Disclosures

All Authors: No reported disclosures
LB16. Surveillance Rates of Cefiderocol Heteroresistance Correlate With All-cause Mortality in the APEKS-NP and CREDIBLE-CR Trials
Authors: Choby Jacob E , Ozturk Tugba , Satola Sarah W , Jacob Jesse T , Weiss David
Published: December 2021

Background

Cefiderocol is a recently FDA approved, novel siderophore beta-lactam antibiotic. Conventional antimicrobial susceptibility testing (AST) suggests that a variety of Gram-negative pathogens, including carbapenem-resistant (CR) isolates, are overwhelmingly susceptible to cefiderocol.. This antibiotic performed well in the APEKS-NP trial for the treatment of nosocomial pneumonia caused largely by carbapenem susceptible isolates. However, in the CREDIBLE-CR trial involving exclusively CR Gram-negative bacteria, cefiderocol was associated with a higher rate of all-cause mortality. We hypothesized one explanation for these discrepant data might be undetected cefiderocol heteroresistance (HR).

HR is a form of antibiotic resistance in which an isolate harbors a minority resistant subpopulation of cells co-existing with a majority susceptible population, and is often undetected by standard AST. Isolates exhibiting undetected HR, with as low as 1 in 1 million resistant cells, can cause treatment failure in in vivo models.

Methods

We quantified HR to cefiderocol by population analysis profile (PAP) of 161 Acinetobacter, 180 Klebsiella, and 108 Pseudomonas isolates collected in Georgia, USA.

Results

We observed CR isolates exhibited a high frequency of HR, which was largely undetected by standard AST, and correlated with all-cause mortality in the CREDIBLE-CR study (Table). Carbapenem-susceptible isolates exhibited no or low rates of cefiderocol HR (Table). Cephalosporin-resistant bacteria mostly exhibited increased rates of cefiderocol HR, but below those of CR strains. These differences in rates of cefiderocol HR correlated with the mortality data from the APEKS-NP and CREDIBLE-CR trials, across the bacterial species tested (Table).

Table: Surveillance rates of cefiderocol heteroresistance correlate with all-cause mortality in the APEKS-NP and CREDIBLE-CR trials

Conclusion

These data suggest that the lower rates of cefiderocol HR in carbapenem-susceptible isolates that predominated the APEKS-NP trial may explain the enhanced efficacy of the drug in that study as compared to the CREDIBLE-CR trial. Importantly, the widespread, undetected cefiderocol HR observed among CR pathogens may explain the discordance between this drug’s excellent in vitro susceptibility profile and increased patient mortality in the CREDIBLE-CR trial.

Disclosures

All Authors: No reported disclosures
LB18. Healthcare Utilization for Acute Respiratory Illness by Race/Ethnicity across Ambulatory, Emergency, and Hospital Settings
Authors: Mellis Alexandra M , Gilmer Matthew , Reed Carrie
Published: December 2021

Background

Given the disproportionate impact of COVID-19 among racial/ethnic minority groups across the United States on emergency visits, hospitalizations, and deaths, we examined healthcare utilization more broadly for acute respiratory illness (ARI across healthcare settings by racial/ethnic group.

Methods

Using data on 33,992,254 unique nonpharmacy healthcare encounters from the IBM Explorys Electronic Health Record database from January 1, 2020–May 1, 2021, across healthcare settings (ambulatory care or telehealth, emergency department, and hospitalizations) with nonmissing bridged racial/ethnic data. Encounters were classified as ARI based on ICD-10 and SNOMED codes and aggregated by month and US Census region. We estimated the population denominator as the total number of persons by bridged racial/ethnic group with encounters recorded during 2019. We both estimated the rate of ARI visits per 100,000 persons across healthcare settings and the rate ratio of ARI visits to non-ARI visits. We performed comparisons of these values by race/ethnicity, taking White persons as referent, using Poisson generalized estimating equations clustered within geographic regions.

Results

A total of 244,137 (6.5% of 3,745,135) hospitalizations, 237,873 (18% of 1,305,474) emergency visits, and 1,636,383 (5.7% of 28,941,645) ambulatory visits were associated with ARIs. We observed similar rates of ARI visits across race/ethnicity groups in all settings combined and in ambulatory settings, but higher rates of ARI hospitalization among Hispanic persons (IRR [95% CI]: 2.5 [1.7–3.7]) and higher rates of ARI emergency department visits among Black persons (2.5 [1.9–3.2]) (Figure). We also observed differences in the relative proportion of care received for ARI vs. other visits types by setting, for example with Black persons utilizing higher rates of hospital visits for ARI vs non-ARI care (2.2 [1.7–2.7]) but lower rates of ambulatory care for ARI (0.9 [0.7–0.96]).

ARI Visits Per 100k Persons

Conclusion

Population rates of ARI visits and relative proportions of ARI vs. non ARI visits differed between racial/ethnic groups by setting. Understanding how utilization of care varies for ARI across settings can inform future monitoring efforts for health equity.

Disclosures

All Authors: No reported disclosures
LB19. Intramuscular therapeutic immunization targeting RelMtb/MIP-3 induces immune signatures associated with better TB control in vivo compared to
Authors: Karanika Styliani , Gordy James , Neupane Pranita , Markham Richard , Karakousis Petros
Published: December 2021

Background

Tuberculosis (TB) is one of the leading causes of death from a single infectious agent worldwide. The lengthy treatment regimen reflects the unique ability of a subpopulation of “persister” bacteria to remain in a nonreplicating state in the infected host through various adaptive strategies, including induction of the stringent response. The key stringent response enzyme, RelMtb, is essential for long-term Mycobacterium tuberculosis (Mtb) survival under physiologically relevant stresses in vitro and in animal lungs. Recently, our group has generated a therapeutic, parenteral, relMtb DNA vaccine, which induces RelMtb-specific cellular immunity and augments the activity of the first-line drug isoniazid against active TB in mice and guinea pigs. Our group also has applied a novel vaccination strategy involving the fusion of an antigen of interest with the immature dendritic cell (iDC)-targeting chemokine MIP-3α/CCL20, which significantly enhances antigen-specific T-cell responses. We sought to determine if this iDC-targeting strategy improves the immunogenicity of the therapeutic relMtb DNA vaccine.

Methods

We cloned the relMtb and chemokine MIP-3α genes into the eukaryotic expression plasmid pSectag2b. We conducted an immunogenicity study using C57BL/6J mice, comparing the T-cell responses between the relMtbvs. MIP-3α/relMtb DNA intramuscular vaccination groups.

Results

Intramuscular administration of the DNA vaccine expressing the MIP-3α/relMtb gene fusion induced increased production of various Mtb-protective cytokines (IL-17α, IL-2, TNF-α, IFN-γ) in various mouse tissues, including the spleen, draining lymph nodes and peripheral blood mononuclear cells, relative to the vaccine expressing relMtb alone.

Conclusion

Intramuscular immunization with a DNA vaccine expressing relMtb/MIP-3α induces robust in vivo Mtb-protective immune signatures, suggesting this may be a promising adjunctive approach in combination with standard anti-TB therapy.

Disclosures

All Authors: No reported disclosures
170. Reduction in Bloodborne Pathogen Splash Exposures After Implementation of Universal Masking and Eye Protection for COVID-19
Authors: Drees Marci , Mase Tabe , Garvin Jennifer , Miller Kimberly
Published: December 2021

Background

While splashes to the eyes, nose and mouth can often be prevented through appropriate personal protective equipment (PPE) use, they continue to occur frequently when PPE is not used consistently. Due to the COVID-19 pandemic, we implemented universal masking and eye protection for all healthcare personnel (HCP) performing direct patient care and observed a subsequent decline in bloodborne pathogen (BBP) splash exposures.

Methods

Our healthcare system, employing >12,000 healthcare personnel (HCP), implemented universal masking in April 2020 and eye protection in June 2020. We required HCP to mask at all times, and use a face shield, safety glasses or goggles when providing direct patient care. Occupational Safety tracked all BBP exposures due to splashes to the eyes, nose, mouth and/or face, and compared exposures during 2020 to those in 2019. We estimated costs, including patient and HCP testing, related to splash exposures, as well as the additional cost of PPE incurred.

Results

In 2019, HCP reported 90 splashes, of which 57 (63%) were to the eyes. In 2020, splashes decreased by 54% to 47 (36 [77%] to eyes). In both years, nurses were the most commonly affected HCP type (62% and 72%, respectively, of all exposures). Physicians (including residents) had the greatest decrease in 2020 (10 vs. 1 splash exposures [90%]), while nurses had a 39% decrease (56 vs. 34 exposures). Nearly all of the most common scenarios leading to splash exposures declined in 2020 (Table). We estimated the cost of each BBP exposure as &2,940; this equates to a savings of &123,228. During 2020, we purchased 65,650 face shields, safety glasses and goggles (compared to 5303 similar items in 2019), for an additional cost of &238,440.

Specific activities identified as leading to bloodborne pathogen splash exposures, 2019 vs. 2020.

Conclusion

We observed a significant decline in splash-related BBP exposures after implementing universal masking and eye protection for the COVID-19 pandemic. While cost savings were not observed, we were unable to incorporate the avoided pain and emotional trauma for the patient, exposed HCP, and coworkers. This unintended but positive consequence of the COVID-19 pandemic exemplifies the need for broader use of PPE, particularly masks and eyewear, for all patient care scenarios where splashes may occur.

Disclosures

All Authors: No reported disclosures
174. Increase in Candida auris cases in New Jersey healthcare facilities during the COVID-19 pandemic — 2017–2020
Authors: Magleby Reed , Innes Gabriel , Cherian Diya , Arias Jessica , Mehr Jason , Forsberg Kaitlin , Lyman Meghan , Greeley Rebecca
Published: December 2021

Background

Candida auris is a fungal pathogen associated with multidrug resistance, high mortality, and healthcare transmission. Since its U.S. emergence in 2017, to March 19, 2021, 1708 clinical infections were reported nationwide, of which 235 (13.8%) were reported in New Jersey. The New Jersey Department of Health (NJDOH) maintains C. auris surveillance in healthcare facilities (HCF) such as acute care hospitals, long-term acute care hospitals (LTACHs), and skilled nursing facilities, to monitor clinical infections and patient colonization. We aimed to characterize the epidemiology of C. auris infection and colonization among HCF patients during 2017–2020.

Methods

HCFs report C. auris cases identified from clinical specimens and surveillance activities such as admission screenings and point prevalence surveys (PPS) to NJDOH. Cases are classified as either infection or colonization using National Notifiable Diseases Surveillance System case definitions. We analyzed cases reported during 2017–2020 to describe types of cases, facilities reporting cases, and demographics of affected patients. We analyzed PPS results to calculate percent positivity of tests from patients without previously identified infection and compared percent positivity between types of facilities. We examined quarterly trends for all variables before and after the COVID-19 pandemic peak in the second quarter of 2020.

Results

During 2017–2020, 614 C. auris cases identified from clinical specimens were reported to NJDOH [243 (39.6%) infection, 371 (60.4%) colonization]; of these, 139 (57.2%) and 301 (81.1%) , respectively, were identified at long-term acute care hospitals (LTACHs). PPS percent positivity was higher at LTACHs (mean 7.6%) compared with all other facility types (mean 3.6%) for 13 of 16 quarters during 2017–2020. Case reports increased 2.6-fold from the Q2 2020 peak of the COVID-19 pandemic to Q3 2020.From Q1 to Q4 2020, PPS percent positivity increased from 4.8% to 10.5%.

Figure 1. Candida auris cases reported to New Jersey Department of Health, 2017–2020

Figure 2. Candida auris test percent positivity among healthcare facility patients sampled for point prevalence surveys* and total number of C. auris point prevalence tests performed, New Jersey, 2017–2020. *Excluding individuals already known to be cases

Conclusion

The COVID-19 pandemic may have exacerbated C. auris transmission in HCF and potential causes should be further explored. LTACHs carry a disproportionate burden of patients colonized with C. auris and should be prioritized for surveillance and containment efforts.

Disclosures

All Authors: No reported disclosures
180. Alterations to the Gut Microbiomes and Acquisition of Bacteria Resistance Elements among US International Travelers
Authors: Sridhar Sushmita , Worby Colin , Bronson Ryan , Turbett Sarah , Harris Jason , Ryan Edward T , Earl Ashlee , LaRocque Regina C
Published: December 2021

Background

This study investigated the impact of international travel on the acquisition and carriage of antimicrobial resistance (AMR). We prospectively assessed U.S. international travelers for the acquisition of resistant Enterobacterales species and evaluated changes in travelers’ gut microbiomes.

Methods

Metagenomic sequencing was performed on DNA extracted from pre- and post-travel stool samples of 273 U.S. international travelers. We used Kraken2 to assess microbial gut composition and analyzed antibiotic resistance gene (ARG) content using the Resistance Gene Identifier (RGI) and ResFinder, and read mapping to ARG databases. We assessed the change in gut profile and resistome associated with (i) all international travel; (ii) travel to specific geographic regions; and (iii) traveler’s diarrhea.

Results

International travel resulted in a perturbation of the gut microbiome, which was greater in travelers receiving treatment for diarrhea during travel (p = 4E-5). There was an overall loss in microbial diversity following travel, regardless of health outcome (p = 0.011); this was most consistently observed in travelers to South East Asia (SEA) (loss of gut diversity in 81% of SEA travelers). 78% of all travelers had a higher relative abundance of E. coli after travel, including 85% of travelers who acquired AMR bacteria during travel. Travel to South Asia was also associated with a significantly greater increase of E. coli relative to other destinations (p = 0.04). Additionally, the relative abundance of Pasteurellales was higher in the pre-travel samples of those who subsequently acquired AMR bacteria (FDR = 0.08). Furthermore, there was a significant increase in ARG content among the post-travel samples, with regional differences in the magnitude of acquisition (Figure 1). 72% of all travelers had a greater resistance burden post-travel. SEA was associated with the greatest increase in resistome diversity, while South America was associated with the greatest increase in overall ARG content.

Resistance genes present in the gut microbiome.

Genes mapping to the Comprehensive Antibiotic Resistance Database were measured pre- (x-axis) and post-travel (y-axis) to assess the acquisition of resistance genes in association with travel, distinguished by geographic region. Colors indicate geographic regions visited by travelers: South America (red), South East Asia (blue), South Asia (green), Eastern Africa (purple), Southern Africa (orange), Other (grey).

Conclusion

International travel is associated with a perturbation in the gut microbial community, with the acquisition of AMR bacteria and genes, and an increase in the relative abundance of E. coli. These perturbations following travel may be important factors in the global spread of AMR.

Disclosures

All Authors: No reported disclosures
184. Inducible Clindamycin Resistance Testing on Pediatric Streptococcus pneumoniae Isolates
Authors: Olarte Liset , Swanson Douglas S , Tabakh Jennifer E , Banerjee Dithi , Selvarangan Rangaraj
Published: December 2021

Background

In 2013, the Clinical and Laboratory Standards Institute recommended inducible clindamycin resistance (ICR) testing on macrolide-resistant Streptococcus pneumoniae isolates, which arises due to the ermB gene. Ribosomal methylation by ermB confers resistance to macrolides (high-level resistance), lincosamides and streptogramin B. The goal of our study is to characterize the prevalence of ICR among pediatric pneumococcal isolates.

Methods

We identified erythromycin-resistant(R) (minimum inhibitory concentration [MIC] ≥ 1 µg/mL) and clindamycin-susceptible(S) (MIC ≤ 0.25 µg/mL) pneumococcal isolates from pediatric patients seen at Children’s Mercy Hospital from 2007 to 2017. Determination of ICR was achieved via disk approximation (D-zone test) with standard erythromycin (15 µg) and clindamycin (2 µg) disks. Isolates with high-level erythromycin resistance (MIC ≥ 32µg/mL) were also tested for ermB gene by PCR. Positive and negative controls were used for D-zone test and ermB PCR.

Results

We identified 289 erythromycin-R pneumococcal isolates; of those 194 (67.1%) were clindamycin-S (Figure 1). One-hundred and sixty-nine isolates were available for ICR testing, 166 (98%) isolates represented non-invasive disease samples. Median age of patients with erythromycin-R and clindamycin-S isolates was 19 (range 0.1 – 180) months. None of the isolates expressed ICR based on the D-zone test. Thirteen of those isolates (7.7%) expressed high-level erythromycin-R (MIC range 32-128 µg/mL); all were negative for ermB. The most common serotypes/serogroups among erythromycin-R and clindamycin-S isolates were: 15 (n=22), 35B (n=19), 11 (n=16), 6 (n=16), 19A (n=14) and 33 (n=12).

Conclusion

Erythromycin-R and clindamycin-S pneumococcal isolates did not express ICR and isolates with high-level erythromycin-R did not carry ermB. Multicenter studies are needed to determine if ICR testing is required for macrolide-resistant pneumococcal isolates in the PCV13 era.

Disclosures

Liset Olarte, MD, MSc, GSK (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)Sanofi (Research Grant or Support) Douglas S. Swanson, MD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Sanofi (Research Grant or Support)
186. Characteristics of COVID-19 Vaccine Breakthrough Cases in Minnesota, 2021
Authors: Meyer Stephanie , Saupe Amy , Bieringer Aaron , Holtzman Corinne , Magnuson Luke , Bye Erica , Muscoplat Miriam , Wang Xiong , Lorentz Alexandra , Como-Sabetti Kathryn , Lynfield Ruth , Lynfield Ruth
Published: December 2021

Background

Over 600,000 COVID-19 cases, including >7000 deaths reported to MN Dept of Health (MDH) by June 1, 2021. Clinical trials demonstrated high effectiveness of COVID vaccines. We assessed COVID-19 cases among fully vaccinated residents [vaccine breakthrough (VB) cases].

Methods

COVID-19 VB cases were MN residents with completed COVID-19 vaccination series ≥14 days prior to symptom onset or positive for SARS-CoV-2 by nucleic acid amplification or antigen test. COVID-19 cases were reported to MDH and COVID-19 vaccinations reported to the MN Immunization Information Connection (MIIC). COVID-19 cases were matched to MIIC to identify VB and interviewed; medical records of hospitalized cases were reviewed. Available VB case specimens underwent whole genome sequencing (WGS) at MDH or collaborating lab.

Results

Jan 19 – June 1, 2021, 2765 VB cases were reported among >2.45 million fully vaccinated residents and 147,445 COVID-19 cases. VB case median (MED) age was 52 y (IQR 38, 68), 83% white, 65% female; MED age of fully vaccinated was 55 y (IQR 30, 68), 77% white, 54% female. Of VB cases, 273 (10%) were hospitalized and 32 (1%) died (MED age 74 y; IQR 66, 85). 2212 (80%) VB cases were interviewed; 60% reported symptoms; most common were fatigue (53%), rhinorrhea (49%), cough (42%), headache (41%). 35% reported a comorbidity.

Of hospitalized VB cases, 120 had completed record reviews. 64 were admitted for COVID-19 related illness (MED age 74 y, IQR:65, 83) including 27 admitted to ICU (MED age 71 y, IQR: 65, 83). 90% (108) reported a comorbidity, most common being chronic metabolic conditions (46%), obesity (45%), renal disease (31%) and chronic lung disease (26%); 27 were immunocompromised (not mutually exclusive), including immunosuppressive therapy (15), hematological malignancy (9), other cancer (11), and organ transplant recipients (8).

Of 604 VB case specimens, 79% were B.1.1.7, 9% B.1.427/429, 3% P.1, and 2% B.1.351; lineage distribution was similar to overall 24,157 MN SARS-CoV2 WGS data.

Conclusion

Identified VB cases were 0.1% of those vaccinated and < 2% of total cases reported in the time period. COVID-19 vaccines are an important tool in preventing COVID-19. Additional surveillance, including WGS and case characteristics will be useful to monitor VB.

Disclosures

Ruth Lynfield, MD, Nothing to disclose