bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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, &gt;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

Abstract

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

Abstract

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

Methods
Standard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 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 &gt;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

Abstract

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 &gt;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&lt; 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 &gt;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

Abstract

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

Abstract

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

Abstract

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