bluuebunny/crossref_metadata_2025 huggingface dataset:
1528. Prevalence of Human Papillomavirus Infection and Cervical Intra-Epithelial Lesions in A Subset of Arab American Women in Southeast Michigan
Authors: Shallal Anita , Trak Joseph , Kamatham Saivaishnavi , Fehmi Omar , Farooqi Sarah , Fehmi Ziad , Zervos Marcus , Ali Rouba
Published: January 2021

Background

The Pap smear is a screening examination that detects abnormal cervical cells and may be paired with human papillomavirus (HPV) testing in order to detect high-risk, oncogenic HPV strains. The incidence of cervical cancer varies among groups due to racial and ethnic disparities, and 80% of cases occur in developing countries. Mortality rates for cervical cancer in the Middle East are disproportionately higher when compared to developed countries. Our study aims to assess the prevalence of HPV and cervical cancer among a subset of Arab-American women in southeast Michigan.

Methods

The study is a retrospective chart review of women who presented for routine cancer screening as part of the Breast and Cervical Cancer Control Program (BCCCP), at the Arab-American Center for Economic and Social Services Clinic in southeast Michigan between 2003-2019. Paper charts were reviewed for information such as age, date of birth, monthly income, tobacco use, cervix-related gynecological examination performance, cervical cytology results, and HPV testing results. Women between the ages of 21 and 65 were included. In instances where cytology was performed, results and details of high-risk HPV testing were documented. In instances where high-risk HPV testing was performed, negative results were documented as such, and positive results were documented as either positive for HPV 16, 18, or other high-risk strains, or unknown if serotype testing was not available.

Results

A total of 464 charts from the BCCCP program were reviewed. All women included were uninsured and had immigrated from Middle Eastern countries, including Yemen and Lebanon. The average age of the women was 48.3 years. Of 464 women, 6% (n=28) of women declined to have a Pap smear. 85 women reported they had never had a Pap smear. Of the 436 women who did undergo Pap smear, 42 women (9.6%) had an abnormal pap smear. The remaining results are summarized in Table 1.

Table 1

Conclusion

Our study results show a trend toward HPV serotype 16 and other serotypes compared to HPV serotype 18 in Arab-American women who recently immigrated to the United States. However, this needs to be studied on a larger cohort of patients to determine if these serotypes are more common among this ethnicity compared to the general population.

Disclosures

Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support)
126. Implementation of the core elements of an outpatient antimicrobial stewardship program in pediatric emergency departments and urgent care clinics
Authors: El Feghaly Rana E , Burns Alaina , Goldman Jennifer , Myers Angela , Purandare Amol , Monsees Elizabeth , Hiskey Lisa M , Lee Brian R
Published: January 2021

Background

We used the Center for Disease Control and Prevention’s 4 core elements (commitment, action for policy and practice, tracking and reporting, education and expertise) to establish an outpatient antibiotic stewardship program (ASP) in 2 pediatric emergency departments (EDs) and 3 urgent care clinics (UCCs) of a healthcare system.

Methods

The outpatient ASP team consists of infectious diseases (ID) physicians, a pharmacist, and data analyst collaborating with ED and UCC providers. We placed a commitment letter in every exam room. We coach and support frontline providers to lead and sustain quality improvement (QI) projects. A monthly report evaluates rates of antibiotic use for viral infections and first-line antibiotic use for bacterial infections. We also compare rates of respiratory diagnoses and overall antibiotic use for all respiratory infections among the different sites. We developed an outpatient antibiotic handbook summarizing diagnosis and treatment recommendations for commonly encountered infections. Progress on prescribing trends and positive reinforcement are shared with providers during cookie rounds at bi-annual division meetings. We provide lectures, workshops, and newsletter articles on wise use of antibiotics.

Results

Pre-implementation data showed < 5% antibiotic use for common pediatric viral infections and >85% use of first-line antibiotics for common bacterial infections. Trends in the report help us identify site-specific improvement opportunities we are working with frontline providers on addressing. In 2 years, our QI efforts have resulted in an increase in safety-net antibiotic prescriptions for acute otitis media in the EDs from 0.4% to over 7.5%, and a decrease in the percentage of rapid streptococcal testing performed in children < 3years old from 13% to 5% in one UCC (Figure 1). We have completed 15 cookie rounds attended by all ED/UCC core providers. In a survey completed by 61 providers, 85% found the handbook to be very beneficial, and 97% report it impacts their daily practice (Table 1).

Figure 1: Annotated control charts of 2 quality improvement projects. A. Increase in safety-net antibiotic prescriptions offered to children diagnosed with acute otitis media in the emergency department. B. decrease in the percentage of streptococcal rapid antigen detection tests performed on children younger than 3 years of age in one urgent care clinic

Conclusion

Seeking leadership support and most importantly engaging frontline providers allowed us to be successful in implementing the suggested core elements of an outpatient ASP and maximize existing resources.

Disclosures

Brian R. Lee, MPH, PhD, Merck (Grant/Research Support)
1543. Risk Reduction service delivery during the COVID Pandemic to a marginalized urban population in Newark, NJ
Authors: Rosmarin-DeStefano Corey L , Scarinci Eileen , Finkel Diana , Escabi Erika
Published: January 2021

Background

North Jersey Community Research Initiative (NJCRI) is a non- profit organization in Newark, NJ that provides medical care and support services for highly vulnerable and hard to reach patient populations (e.g. homeless, HIV/AIDS, transgender, MSM, injection drug users, sex workers), 83% of whom are people of color. We are in a unique position to identify critical vulnerabilities and continued risk factors in our communities and patients during pandemics especially identifying HIV, HCV and other STIs and providing support services to this population.

Methods

We assessed the impact of COVID on HIV, HCV, STI Clinical care, testing, prevention, treatment, mental health and substance abuse services and patent retention. We used our EMR data to track patient visits, prevention visits and testing pre and post covid. Post Covid we utilized Telemedicine and mobile units to continue to provide services as well as self collection kits for the patients for testing. We staggered schedules on site in our outdoor triage center for support services like syringe exchange and food pantry and made an outdoor triage center for all services. Our phone system was routed to providers who assessed provided medical care through telemedicine and remote lab orders and Medication orders were sent via EMR to pharmacies who delivered the medications.

Results

Pre Covid Jan-Feb 2020: 855 clinical visits including testing Behavioral visits 191. Syringe exchange 38,653 needles to 73 clients, Food 189 clients received food. LGBTQ service Clients Reached 779

Post Covid

March 2020 333 clinical visits including testing behavioral visits 154

April 2020 360 clinical visits including testing behavioral visits 208

May 2020 447 clinical visits including testing behavioral visits 282

Syringe exchange March- May 27,367 needles to 53 clients

Food received March-may 118 clients

LGBTQ clients reached 2035

Conclusion

Assess and implement best practices post COVID to plan for services in the event that we have another wave of COVID. STI, HIV and HCV services and testing can be successfully delivered remotely and through an outdoor triage facility in an underserved urban setting. Point of Service testing for both home and outdoor settings will be added to treatment paradigms to better serve the needs of the community.

Disclosures

All Authors: No reported disclosures
1544. Sexually Transmitted Infection Laboratory Testing and Education Trends Among Physician Office Visits in the United States, 2009-2016
Authors: Zeidan Amina R , Reveles Kelly R
Published: January 2021

Background

Rates of sexually transmitted infections (STIs) have been rising in the United States (US). Physician offices play an important role in providing both STI prevention and education, as well as STI laboratory testing options for patients who present at risk. However, few studies have documented the extent to which physician’s offices have contributed to prevention and testing efforts. We address this gap by evaluating STI testing and education provided in US physician offices from 2009 to 2016.

Methods

This was a cross-sectional study of the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016. Data weights were applied to extrapolate sample data to national estimates. Testing for HIV, HPV, Chlamydia (2009 – 2016) and Hepatitis and Gonorrhea (2014 – 2016) were presented as testing visits per 1,000 total visits. Subgroup analyses were performed for age group, sex, and geographical region by individual STI test and receipt of STI prevention education.

Results

A total of 7.6 billion visits were included for analysis, of which 0.6% included an STI test. Testing rates increased over the study period for Chlamydia (R2=0.27), HPV (R2=0.28), and HIV (R2=0.51). Peak testing occurred in 2015 for all tests. STI prevention education was provided to 0.5% of patients. Females were tested at a higher rate for all STIs (4.2%) compared to males (0.4%). Females also received more STI prevention education overall (0.6% versus 0.4%, respectively). While the age group 25 – 24 accounted for highest Hepatitis (15.9%) and HPV (11.3%) testing rates, the 15 – 24 age group had the highest overall testing rate (9.4%). STI testing was highest in the South region (Figure 1).

Conclusion

STI testing in US physician offices increased in recent years. Females accounted for the majority of STI testing and STI prevention education. Testing was more frequent among patients 15 – 24 years old and those seen in the South region. Further research should be conducted to determine reasons for differences in testing and education amongst sex, age group, and geographic region.

Disclosures

All Authors: No reported disclosures
1560. Microbiology of Necrotizing Fasciitis and Implications on Antimicrobial Stewardship
Authors: Huang Glen , Kim Brian , Jeng Arthur
Published: January 2021

Background

Necrotizing fasciitis (NF) is a rare but deadly soft tissue infection. Early diagnosis, antibiotics, and surgical management are critical in treatment. Current IDSA guidelines recommend broad empiric antibiotics (eg, vancomycin + piperacillin-tazobactam or a carbapenem). At our institution, this invariably consists of empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative organisms (eg, Pseudomonas aeruginosa), usually with piperacillin-tazobactam. Clindamycin is the common third agent used empirically; however, the literature supports use of clindamycin only in confirmed cases of Group A Streptococcus (GAS). With the increasing dangers of antibiotic resistance, use of such broad agents may not be necessary for NF. We evaluated the microbiology of NF and the implications on empiric antibiotic treatment.

Methods

Retrospective chart review of adults (≥18 years) with a diagnosis of NF from January 2016 to May 2020.

Results

Twenty-five cases of NF in 22 patients were recorded. The median age was 54.5 (IQR 37-59.8) and 15 (60%) were male. On presentation, 24 (96%) met systemic inflammatory response syndrome criteria with a median laboratory risk indicator for necrotizing fasciitis score of 15 (IQR 9-31.3, n = 20). The median presenting white blood cell count was 17.5 x 103 cells/uL (IQR 13.5-25.2), median C-reactive protein was 321.6 mg/L (IQR 25.9-37.6) and median creatinine was 1.2 mg/dL (IQR 0.7-1.6). The most frequently isolated organisms were anaerobes (n=9, 36%) and Streptococci other than GAS (n = 9, 36%). GAS was isolated in 6 patients (24%) and S. aureus in 2 patients (8%). All cases of S. aureus were methicillin-susceptible. No Pseudomonas species (PsA) or extended-spectrum beta-lactamase (ESBL) gram negative organisms were isolated. Three patients (12%) had no organisms isolated from surgical cultures. Seven patients (28%) had positive blood cultures. Of the empiric antibiotics used, 24 (96%) patients were exposed to clindamycin and an anti-pseudomonal antibiotic.

Conclusion

Empiric treatment of PsA and ESBL organisms is not necessary in NF. This infection should be considered a priority target for antimicrobial stewardship to reduce prescribing of broad-spectrum antibiotics to empirically treat these organisms.

Disclosures

All Authors: No reported disclosures
1561. Recurrent Bilateral Culture Negative Abscesses Mimicking a Diabetic Foot Infection
Authors: Liette Michael D , Johnson Lance , Crisologo Peter A , Zheng Shuling , Masadeh Suhail , Smulian Alan
Published: January 2021

Background

The aim of this study is to present a novel case of recurrent bilateral culture negative pedal abscesses, mimicking a diabetic foot infection, as an extra-intestinal manifestation of previously undiagnosed ulcerative colitis. Culture negative abscesses may develop as a rare sequela of ulcerative colitis, with less than 40 cases documented within current literature. They often demonstrate a large neutrophilic predominance, negative cultures, and negative serology testing. The diagnosis was achieved utilizing a multi-specialty team approach with podiatry serving as the primary service coordinating the patient care.

Methods

Multiple incision and drainage procedures were performed with copious purulence expressed from the plantar medial pedal compartment. The patient was initiated on broad spectrum antibiotics post-operatively without a clinical response. Advanced microbiological and rheumatologic testing was performed.

Results

Serial aerobic, anaerobic, acid fast, and fungal cultures as well as 16s rDNA testing remained negative for infection throughout the admission. Rheumatologic work-up consisted of broad autoimmune serologic testing (Table 1). Greatly elevated levels of calprotectin were identified, resulting in a colonoscopy for confirmation of the diagnosis of ulcerative colitis. The patient was then placed on infliximab and has remained free of recurrent abscesses for the 15 months of follow up.

Table 1: Workup Results

Conclusion

The differential diagnosis of a culture negative abscess is broad and a multi-specialty team approach must be considered. Criteria for the diagnosis has previously been proposed and includes: deep abscess with neutrophilic features, negative serologic testing, failure of broad-spectrum antibiotic therapy, and rapid improvement on steroids or other DMARDs with subsequent radiologic evidence of abscess resolution. To our knowledge no bilateral cases have been documented within the foot.

Disclosures

All Authors: No reported disclosures
1563. Variations in the clinical spectrum of the Streptococcus anginosus group: a report of two rare presentations
Authors: Zapata Carlos M , Matos-Casano Harold A M , Shah Jilan M , Bhatt Utpal M
Published: January 2021

Background

The Streptococcus Anginosus Group (SAG) formerly Streptococcus Milleri Group is a subgroup of viridans streptococci including S. anginosus, intermedius, and constellatus. SAG are microaerophilic digestive tract commensals. They are associated with empyema and deep organ abscesses. We present 2 unusual cases: necrotizing fasciitis and aortic valve endocarditis with aortic root abscess, resulting in septic emboli causing renal infarction.

Methods

Review of the literature and reported cases of SAG.

Results

Case1) 48 year-old-male with history of HTN, T2DM, presented with swelling and erythema of the right arm of 2-day evolution. Exam: tender, erythematous indurated right deltoid. Significant labs: WBC 25k/uL and lactate of 2.5. CT of the RUE showed an extensive fluid collection. Vancomycin, levofloxacin and clindamycin were initiated, surgical debridement revealed extensive necrotizing fasciitis Wound cultures grew S. constellatus. Required multiple debridement and prolonged course of penicillin G. Case 2) 53-year-old male with history of COPD, Prior Splenectomy for a large splenic infarct, heterozygous factor V Leiden mutation, HCV infection, cirrhosis, presented with right flank pain, hematuria over 5 days. Labs: WBC 16.8 k/uL, CT abdomen with contrast: right renal infarct. Heparin drip, Vancomycin and Ceftriaxone were initiated. Blood cultures grew S. anginosus. TEE revealed new aortic valve vegetations with severe aortic regurgitation. His condition deteriorated, requiring aortic valve surgery, found to have aortic root abscess requiring aortic root replacement.

Necrotizing Fascitis - Soft Tissue Air

Post-Surgical Debridement

Right Renal Infarct

Conclusion

SAG infections infections are unique from other S viridans, causing severe deep organ abscesses requiring combined surgical and antibiotic therapy. Isolation in clinical specimens should alert the possibility of severe life threatening infections. Here we highlight 2 unusual manifestations of necrotizing fasciitis and aortic valve endocarditis with aortic root abscess and possible large septic renal embolism. One patient had a splenectomy. We are not sure if this contributed to a severe SAG infection

Disclosures

All Authors: No reported disclosures
1564. Activity of bacteriophage against multidrug resistant Klebsiella pneumoniae
Authors: Puttagunta Sailaja , Kahan-Haanum Maya , Kredo-Russo Sharon , Weinstock Eyal , Khabra Efrat , Edgar Rotem , Weiner Iddo , Ben-Ishay Noa , Eyal Stav , Inbar Dana , Puri Doron , Kaikov Dana , Barzily Uriel , Zelcbuch Lior , Gidron Eliya , Gahali-Sass Inbar , Zak Naomi , Bassan Merav
Published: January 2021

Background

The prevalence of extended-spectrum beta-lactamase (ESBL) producing and carbapenem resistant (CR) Klebsiella pneumoniae (KP) has significantly risen in all geographic regions. Infections due to these bacteria are associated with high mortality across different infection types. Even with newer options, there remains an unmet need for safe and effective therapeutic options to treat infections caused by ESBL and CR KP. Phage therapy offers a novel approach with an unprecedented and orthogonal mechanism of action for treatment of diseases caused by pathogenic bacterial strains that are insufficiently addressed by available antibiotics. Phage-based therapies confer a high strain-level specificity and have a strong intrinsic safety profile. Here we describe the identification of novel phages that can effectively target antibiotic resistant KP strains.

Host range of the 21 phages on 33 strain KP panel via solid culture infectivity assays. Red marks resistance to infection while sensitivity to phage is marked in green

Methods

KP clinical strains were isolated from human stool specimens preserved in glycerol. Selective culturing was carried, followed by testing of individual colonies for motility, indole and urease production, sequenced and analyzed by Kleborate tool to determine antibiotic resistant genes. Natural phages were isolated from plaques that developed on susceptible bacterial targets, sequenced and characterized.

Results

Antibiotic-resistant KP strains encoding beta lactamase genes or a carbapenemase (n=33) were isolated from healthy individuals (n=3), and patients with inflammatory bowel disease (n=26) or primary sclerosing cholangitis (n=3). Isolates sequencing revealed bla CTX-M15 and/or bla SHV encoding strains and carbapenamase KPC-2. A panel of 21 phages targeting the beta-lactamase- and carbapenemase-producing KP strains were identified. Phage sequencing revealed that all phages belong to the Caudovirales order and include 6 Siphoviridae, 14 Myoviridae, and 1 Podoviridae. In vitro lytic activity of the phages was tested on the isolated bacteria and revealed a coverage of 70% of the 33 isolated antibiotic resistant strains, >50% of which were targeted by multiple phages.

Conclusion

Collectively, these results demonstrate the feasibility of identifying phage with potent activity against antibiotic resistant KP strains, and may provide a novel therapeutic approach for treatment of ESBL and CR KP infections.

Disclosures

All Authors: No reported disclosures
1565. In Vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2018
Authors: Hackel Meredith , Stone Greg , Sahm Daniel F
Published: January 2021

Background

Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, Streptococcus agalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs.

Methods

From 2012 to 2018 the ATLAS program received 90,119 bacterial isolates that had been cultured by 370 clinical laboratories in 56 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, Inc., (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2020 CLSI MIC breakpoints. Phenotypic ESBL screening and confirmatory testing were performed using the CLSI M100 method.

Results

The in vitro activity of ceftaroline is summarized in the following table. Overall, 100% of MSSA and 93.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 6.2% of MRSA isolates were ceftaroline -susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (57.1% of 1,669 isolates), Thailand (36.5% of 2,318 isolates), and S. Korea (29.3% of 1,231 isolates). No ceftaroline-resistant MRSA were observed. All S. pyogenes and 88.5% of ESBL-negative Enterobacterales were also susceptible to ceftaroline.

Table

Conclusion

Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs.

Disclosures

Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1566. In vitro Activities of Ceftaroline and Comparator Agents against Gram-positive Bacterial Pathogens Causing Blood Stream Infections in a Global Population: ATLAS Surveillance Program 2012-2018
Authors: Hackel Meredith , Stone Greg , Sahm Daniel F
Published: January 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 2020 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2018 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 10,998 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2018 were tested. Isolates came from (n/%): Asia/South Pacific (1,739/15.8%), Europe (5,448/49.5%), Latin America (1,805/16.4%), MidEast/Africa (861/7.8%), and North America (1,145/10.4%).

Results

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

Table

Conclusion

Greater than 98% of S. pneumoniae, S. epidermidis, beta-hemolytic streptococci and MSSA isolates included in a 2012-2018 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 91.4% of MRSA were susceptible, and 8.6% isolates categorized as susceptible-dose dependent (MIC, 2-4 ug/mL); two isolates (one each from Thailand and S. Korea) were resistant to ceftaroline (MIC >4 ug/mL). Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI.

Disclosures

Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1575. Predictors of Negative Clinical Outcomes among Patients treated with Meropenem-Vaborbactam for Serious Gram-Negative Bacterial Infections: Impact of Delayed Appropriate Antibiotic Selection
Authors: Alosaimy Sara , Lagnf Abdalhamid M , Jorgensen Sarah , Carlson Travis J , Jo Jinhee , Garey Kevin W , Allen David , Abbo Lilian M , Abbo Lilian M , DeRonde Kailynn , Vega Ana , Venugopalan Veena , Saw Steven , Athans Vasilios , Claeys Kimberly C , Kufel Wesley , Miller Matthew , Veve Michael , Yost Chritsine , Amaya Lee , Ortwine Jessica , Morrisette Taylor , Davis Susan L , Davis Susan L , Rybak Michael J
Published: January 2021

Background

Numerous number of studies have found a positive correlation between delayed appropriate antibiotic therapy and negative clinical outcomes (NCO) in Gram-negative bacterial infections (GNBI). The combination of meropenem with vaborbactam (MVB) received Food and Drug Administration approval for the treatment of complicated urinary tract infections and acute pyelonephritis caused by susceptible organisms in August 2017. We sought to determine the impact of delayed appropriate therapy with MVB on NCO among patients with GNBI.

Methods

Multi-center, retrospective cohort study from October 2017 to March 2020. We included adult patients treated with MVB for >72 hours. We excluded patients who received alternative appropriate antibiotics for GNB prior to MVB and patients with unknown dates for index culture. NCO were defined as 30-day mortality and/or microbiological recurrence. All outcomes were measured from MVB start date. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineates the risk of NCO. Multivariable logistic regression analysis (MLR) was used to examine the independent association between the CART-derived-BP and NCO. Variables were retained in the model if P< 0.2 and removed in a backward stepwise approach.

Results

A total of 86 patients were included from 13 institutions in the United States: median(IQR) age 55 (37-67) years, 67% male, and 48% Caucasian. Median(IQR) APACHE II and Charlson Comorbidity index scores were 18(11-26) and 4(2-6), respectively. Common sources of infection were respiratory (37%) and intra-abdominal (21%). The most common pathogens were carbapenem-resistant Enterobacterales (83%). CART-derived BP between early and delayed treatment was 48 hours, where NCO was increased (36% vs.7%; P=0.04). Delayed MVB initiation was independently associated with NCO in the MLR (aOR=7.4, P=0.02).

Results of Regression Analysis of Variables Associated With Negative Clinical Outcomes and Delayed Appropriate Therapy with Meropenem-vaborbactam

Conclusion

Our results suggest that delaying appropriate antibiotic therapy with MVB for >48 hours significantly increases the risk of NCO in patients with GNBI. Clinicians must ensure timely administration of MVB to assure best outcomes in patients with GNBI.

Disclosures

Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)
132. Assessment of the Long-Term Effects of Training Consultant Pharmacists to Promote Antimicrobial Stewardship in Long-Term Care Facilities
Authors: Ferguson Claire , Chung Philip , Lodhi Hanan , Bergman Scott , Cavalieri R Jennifer , Neukirch Alex , Ortmeier Rebecca J , Rupp Mark E , Rupp Mark E , Van Schooneveld Trevor C , Ashraf Muhammad Salman
Published: January 2021

Background

We implemented a one-year antimicrobial stewardship training program that lasted through 2018 where we assisted 9 long-term care facility (LTCF) consultant pharmacists in promoting antibiotic stewardship programs (ASP) in 32 LTCF (Figure 1). Surveys were conducted during and after the training program to assess performance.

Methods

Infection Preventionists (IP), Directors of Nursing (DON) and Medical Directors (MD) of the LTCF received mail surveys in 2018 and online surveys in 2019. It included questions assessing the respondents’ perceptions of their ASP, barriers to ASP implementation and stewardship related knowledge, and the skills and contributions of their consultant pharmacists. Qualitative analyses categorized reported barriers into common themes. Fisher exact test compared perceptions of consultant pharmacists’ performance and frequently reported barriers during training and after the intervention was completed.

Results

Representatives (IP, DON and/or MD) of 18 facilities responded to the surveys at both time points of the study, with 34 individual surveys in 2018 and 25 in 2019. Most rated their consultant pharmacists as knowledgeable and helpful who regularly provided feedback and suggestions both during and after the training (Table 1). Fifty-six percent of facilities reported that their consultant pharmacists were similarly involved, and 12% felt they were more involved, in ASP implementation in 2019 compared to 2018. Top 3 reported barriers to ASP implementations were the same during 2018 and 2019 (Table 2). Overall, 84% of facilities in 2019 believed that the consultant pharmacists “definitely helped” their ASP efforts, and 80% of facilities desired to continue the partnership into the future.

Table 1. Comparison of Consultant Pharmacists’ Performance Evaluations During (2018) and After (2019) Completion of Training

Figure 3. Barriers to ASP implementation reported during (2018) and after (2019) training.

Conclusion

This study demonstrates that training consultant pharmacists resulted in meaningful actions and prolonged engagement in ASP activities. Efforts should be directed on making similar training programs available nationwide for consultant pharmacists working in LTCF.

Disclosures

Muhammad Salman Ashraf, MBBS, Merck & Co. Inc (Grant/Research Support)
1605. Differences in Clinical Characteristics of Third Generation Cephalosporin Resistance and Treatment Outcomes in Escherichia coli and Klebsiella pneumoniae Bacteremia in Patients with Liver Cirrhosis
Authors: Ham Sin Young , Jung Hyungul , Song Kyung Ho , Moon Song Mi , Kang Chang Kyung , Kim Nak-Hyun , Park Wan Beom , Bang Ji-Hwan , Park Sang Won , Kim Nam-Joong , Oh Myoung-don , Jeong Sook-Hyang , Kim Hong Bin , Kim Eu Suk
Published: January 2021

Background

This study aimed to identify characteristics of third-generation cephalosporin (3GC) resistance in Escherichia coli bateremia (ECB) and Klebsiella pneumoniae bacteremia (KPB) in patients with liver cirrhosis (LC), and to investigate the effects of appropriateness of empirical antibiotic treatment on outcomes.

Methods

We retrospectively collected demographic, clinical and microbiological information on all ECB and KPB episodes in LC patients ≥ 18 years of age hospitalized to a tertiary-care teaching hospital in South Korea from 2007 to 2018. Clinical characteristics associated with 3GC resistance and treatment failure were analyzed using a multivariate logistic regression model. Treatment failure was defined as persistent bacteremia for ≥ 7 days, or relapsed bacteremia ≤ 30 days, or all-cause mortality ≤ 30 days.

Results

3GC resistance rates of E. coli were 30.3% overall and increased significantly during the study period (P=0.001), while the rates of K. pneumoniae were not changed (24.3% overall) (P=0.994). Of total 356 ECB and KPB episodes, 112 were caused by 3GC resistant strains. The factor associated with 3GC resistance was isolation of 3GC resistant strain ≤ 1 year in both ECB (OR, 7.754; 95% CI, 2.094~28.716) and KPB (OR, 2.774; 1.318~5.838). In ECB, beta-lactam or fluoroquinolone treatment ≤ 30 days was another factor associated with 3GC resistance (OR, 2.774; 95% CI, 1.318~5.838), but not in KPB. The factor associated with treatment failure was high MELD score in both ECB (OR, 1.193 at 1 increase; 95% CI, 1.118~1.272) and KPB (OR, 1.163; 95% CI 1.083~1.250). Additionally, in ECB, non-alcoholic LC (OR 3.262; 95% CI 1.058~10.063), high Charlson Comorbidity Index (OR, 1.285; 95% CI 1.066~1.548), and inappropriate empirical antibiotic treatment (OR, 3.194; 95% CI 1.207~8.447) were associated with treatment failure.

Conclusion

During the study period, 3GC resistance increased in ECB, but not in KPB. In ECB, the severity of the underlying disease and the appropriateness of empirical antibiotics were associated with treatment failure, but there was no correlation in KPB. In ECB of LC patients, the appropriateness of empirical antibiotics was a factor associated with treatment outcome, and is the only correctable factor in the clinical setting.

Disclosures

All Authors: No reported disclosures
1606. Distinct Effectiveness of Oritavancin Against Tolerance-Induced Staphylococcus aureus
Authors: Harven Lauren , Bingley Victoria , Berti Andrew David
Published: January 2021

Background

Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. In Staphylococcus aureus this process can be sharply accelerated by multiple factors present during infection including nutrient limitation, host cationic peptide exposure and polymorphonuclear neutrophil internalization. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. Survivors of antibiotic exposure can restart cell division upon cessation of antibiotics and cause relapse or recurrent infection. In this study we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of tolerant Staphylococcus aureus bacteria.

Methods

S. aureus strain ATCC29213 as well as four clinical isolates (two MSSA, two MRSA) were selected for analysis. Overnight cultures were diluted in pre-warmed broth (MHB50) to 1×106 cfu/mL. Tolerance was induced by exposure to mupirocin (low [0.032 µg/mL] or high [3.2 µg/mL]) for 30 min. Tolerant cultures were exposed to vancomycin (35 µg/mL), cefazolin (25 µg/mL), daptomycin (7 µg/mL), telavancin (10 µg/mL), dalbavancin (6 µg/mL) or oritavancin (14 µg/mL) and viability was assessed by dilution plating at pre-defined time points (0, 2, 6, 24, 48 h). The minimum duration for 3-log viability reduction from baseline (MDK99.9) and culture viability at 48h were calculated independently for each of three biological replicates.

Results

The rate of bacterial killing (MDK99.9) was reduced for all study antibiotics by the addition of mupirocin in a dose-dependent manner. In contrast to all other regimens, including lipoglycopeptide comparators, oritavancin was the only antimicrobial agent that maintained a similar extent of bacterial killing against tolerant staphylococci.

Conclusion

Antimicrobial tolerant staphylococci exhibit a decreased rate of killing by antistaphylococcal agents. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of otritavancin against recurrent or relapse staphylococcal infection is warranted.

Disclosures

All Authors: No reported disclosures
134. Derivation of novel phenotypes of outpatient pediatrician prescribing patterns
Authors: Herigon Joshua C , Hatoun Jonathan , Vernacchio Louis
Published: January 2021

Background

Antibiotics are the most commonly prescribed drugs for children with estimates that 30%-50% of outpatient antibiotic prescriptions are inappropriate. Most analyses of outpatient antibiotic prescribing practices do not examine patterns within individual clinicians’ prescribing practices. We sought to derive unique phenotypes of outpatient antibiotic prescribing practices using an unsupervised machine learning clustering algorithm.

Methods

We extracted diagnoses and prescribing data on all problem-focused visits with a physician or nurse practitioner between 6/11/2018 – 12/11/2018 for a state-wide association of pediatric practices across Massachusetts. Clinicians with fewer than 100 encounters were excluded. The proportion of encounters resulting in an antibiotic prescription were calculated. Proportions were stratified by diagnoses: otitis media (OM), pharyngitis, pneumonia (PNA), sinusitis, skin & soft tissue infection (SSTI), and urinary tract infection (UTI). We then applied consensus k-means clustering, a form of unsupervised machine learning, across all included clinicians to create clusters (or phenotypes) based on their prescribing rates for these 6 conditions. A scree plot was used to determine the optimal number of clusters.

Results

A total of 431 clinicians at 77 practices with 234,288 problem-focused visits were included (Table 1). Overall, 42,441 visits (18%) resulted in an antibiotic prescription. Individual clinician prescribing proportions ranged from 5% of visits up to 44%. The optimal number of clusters was determined to be four (designated alpha, beta, gamma, delta). Antibiotic prescribing rates were similar for each phenotype across AOM, pharyngitis, and pneumonia but differed substantially for sinusitis, SSTI, and UTI (Figure 1). The beta phenotype had the highest median rates of prescribing across all conditions while the delta phenotype had the lowest median prescribing rates except for UTI.

Table 1. Patient demographics and clinician characteristics

Figure 1. Novel phenotypes of antibiotic prescribing practices across six common conditions

Conclusion

Antibiotic prescribing varies by both condition and individual clinician. Clustering algorithms can be used to derive phenotypic antibiotic prescribing practices. Antimicrobial stewardship efforts may have a higher impact if tailored by antibiotic prescribing phenotype.

Disclosures

All Authors: No reported disclosures
1616. Mechanism of Thrombocytopenia Induced by Oxazolidinones Antibiotics (Linezolid, Tedizolid): Demonstration of Impairment of Megakaryocyte Differentiation From Human Hematopoietic Stem Cells associated with Mitochondrial Toxicity
Authors: Tulkens Paul M , Milosevic Tamara V , Vertenoeil Gaëlle , Vainchenker William , Constantinescu Stefan N , Van Bambeke Françoise
Published: January 2021

Background

Linezolid causes thrombocytopenia, which limits its use. In cell culture and in tissues from treated patients, linezolid impairs mitochondrial protein synthesis (due to structural similarities and common binding sites between bacterial and mitochondrial ribosomes). Recent studies have shown that mitochondria act as a key relay in the process leading from activation of the thrombopoietin receptor to megakaryocytes differentiation.

Methods

Validated ex-vivo human model of hematopoietic stem cells (HSC) differentiation for (i) measuring megakaryocytes, granulocyte-monocytes, and burst-forming unit-erythroids colony formation; (ii) differentiation into megakaryocytes (conversion of CD34+ into CD41+/CD42+ cells; morphology) and proplatelets formation, (iii) mitochondrial toxicity (electron microscopy; cytochrome c-oxidase activity [partly encoded by the mitochondrial genome]).

Results

We show that linezolid (and the recently approved tedizolid), both at concentrations corresponding to their human serum concentrations) inhibit the maturation of HSC into fully differentiated megakaryocytes (CD41 and CD42-positive cells) and the formation of proplatelets. Optic and Electron microscopy) showed an impairment of the formation of typical megakaryocytes (lack of large polylobulated nuclei and of intracellular demarcation membrane system [required for platelet formation]), together with disappearance of the internal structure of mitochondria. Biochemical studies showed a complete suppression of the activity of cytochrome c-oxidase (a key enzyme of the mitochondrial respiratory chain).

Conclusion

Our study provides for the first time insights in the mechanism of thrombocytopenia induced by linezolid and tedizolid, identifying mitochondria as their target and showing that the drugs will impair the differentiation of hematopoietic stem cells into mature platelets-releasing megakaryocytes. It illustrates how mitochondria dysfunction may play a key role in toxicology and diseases, while paving the way for rational approaches for the design and screening of less toxic derivatives for the benefit of future patients.

Disclosures

Paul M. Tulkens, MD, PhD, Bayer (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Menarini (Speaker’s Bureau)Merck (Advisor or Review Panel member, Speaker’s Bureau)Trius (now part of Merck) (Advisor or Review Panel member, Research Grant or Support) Françoise Van Bambeke, PharmD, PhD, Bayer (Speaker’s Bureau)
1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia
Authors: Zidaru Andrei , Russo Hannah Ryan , Phe Kady
Published: January 2021

Background

Methicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality.

Methods

This was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.

Results

Sixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04).

Conclusion

There were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy.

Disclosures

All Authors: No reported disclosures
1626. Synergistic Effect of Cefiderocol with Other Antibiotics Against PER-Producing Acinetobacter baumannii Isolates from the Multinational SIDERO-WT Studies
Authors: Yamano Yoshinori , Takemura Miki , Anan Naomi , Nakamura Rio , Echols Roger
Published: January 2021

Background

Cefiderocol (CFDC), a novel siderophore cephalosporin, showed potent activity at minimum inhibitory concentrations (MICs) of ≤4 μg/mL against ≥99% of Gram-negative isolates in the multinational SIDERO-WT studies. PER-producing Acinetobacter baumannii, mainly from Russia, showed high CFDC MICs of 8– >64 μg/mL. This study evaluated the synergistic effects of CFDC combined with other antibiotics against PER-producing A. baumannii isolates with high CFDC MICs.

Methods

Two isolates of PER-producing A. baumannii with resistance to CFDC (MIC 16 μg/mL), meropenem (MEM; MIC 64 μg/mL), ceftazidime-avibactam (CZA; MIC 64/4 μg/mL), amikacin (AMK; MIC 32 or 64 μg/mL), and ciprofloxacin (CIP; MIC ≥64 μg/mL) were tested. Against ampicillin-sulbactam (SAM), one isolate was resistant (MIC 32/64 μg/mL) and another was susceptible (MIC 8/16 μg/mL). Effects of CFDC combined with other antibiotics were evaluated by checkerboard assay and chemostat model reproducing humanized antibiotic exposure. The checkerboard assay used a single agent (e.g. ceftazidime [CAZ], avibactam [AVI], ampicillin [AMP] or sulbactam [SUL]). Iron-depleted cation-adjusted Mueller‒Hinton broth was used as the standard medium for CFDC, as recommended by the Clinical Laboratory and Standards Institute.

Results

Against both isolates, synergy with CFDC was seen for two β-lactamase inhibitors, AVI and SUL, with a fractional inhibitory concentration (FIC) index of 0.026–0.033 and 0.26–0.27, respectively. A synergistic to additive effect was seen for MEM and AMK, with an FIC index of 0.53–0.75 and 0.25–0.52, respectively. In the chemostat model, regrowth during 24-h treatment was observed with single agents (CFDC 2 g, q8h, 3-h infusion; MEM 2 g, q8h, 1-h infusion; CZA 2 g, q8h, 2-h infusion; SAM 3 g, q8h, 3-h infusion; AMK 15 mg/kg, q8h, 3-h infusion) for both isolates, including the SAM-susceptible isolate. However, no regrowth was seen when CFDC was combined with CZA, MEM, SAM or AMK.

Conclusion

The most potent synergy was seen between CFDC and AVI against PER-producing A. baumannii with a decreased MIC to ≤1 µg/mL for all isolates, followed by SUL and MEM. Under humanized pharmacokinetic exposure, combination of CFDC and CZA, MEM, SAM or AMK is expected to be effective against PER-producing A. baumannii in spite of high CFDC MICs.

Disclosures

Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Naomi Anan, MSc, Shionogi & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant)