bluuebunny/crossref_metadata_2025 huggingface dataset:
1607. Dual Therapy with Aztreonam & Ceftazidime/Avibactam Against Multi-Drug Resistant Stenotrophomonas maltophilia on Tricuspid Valve Endocarditis
Authors: Alexander Jose , Carr Amy , Minor Sarah B , Navas Daniel
Published: January 2021

Background

Antimicrobial resistance in Stenotrophomonas maltophilia is one of the most complex among Gram-negatives. Presence of regulating non-specific antimicrobial class efflux pumps and chromosomal encoded L1 metallo-betalactamase (Ambler Class B) and L2 betalactamase (Ambler Class A) are responsible for few clinically active antimicrobials and pan-drug resistant strains.

Methods

A 38 year old male with a history of IV drug use, chronic hepatitis C, and recent MSSA endocarditis was admitted with sepsis. Workup revealed tricuspid valve endocarditis with pulmonary septic emboli due to S. maltophilia. Initial antibiotics were levofloxacin (LVX), metronidazole, and piperacillin-tazobactam (TZP) followed by LVX and minocycline (MIN). He had valve replacement on day 6. Repeat blood cultures and valve tissue culture revealed pan-resistant S. maltophilia (resistant: ceftazidime (CAZ), LVX, MIN, TMP/SMX, chloramphenicol; intermediate: MIN; eravacycline MIC 8 μg/mL; tigecycline MIC 16 μg/mL). Microbiology Department was consulted for additional antimicrobial options. In vitro testing for aztreonam (ATM) with ceftazidime/avibactam (CZA) was recommended.

Results

Synergy testing between ATM and CZA was performed by positioning ATM strip over the area where CZA had been previously been placed and removed after 10 minutes of incubation. The interception of the growth with the ATM strip was read. In presence of avibactam, ATM MIC was 4 μg/mL, 6 two-fold dilutions lower than ATM without CZA. MIC for ATM (256 μg/mL), CAZ (256 μg/mL) and CZA (32 μg/mL) were tested individually. ATM with CZA was recommended as a salvage treatment based on in vitro result. Patient completed 6 weeks of ATM with CZA along with MIN. He achieved microbiologic clearance and clinical recovery from infection. At the end of treatment, he experienced episodes of refractory ascites. With complex comorbidities, patient was not a transplant candidate and transitioned to hospice two weeks later.

Conclusion

Although the surgical excision was key, treatment with ATM and CZA provided effective antimicrobial treatment in the setting of persistent positive blood culture. ATM with CZA should be considered for cases of pan-drug resistant S. maltophilia with limited treatment options.

Disclosures

All Authors: No reported disclosures
1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals
Authors: Cabrera Nicolo , Tran Truc T , Carlson Travis J , Alnezary Faris , Miller William R , Dinh An Q , Hanson Blake , Munita Jose , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L , Garey Kevin W , Garey Kevin W , Puzniak Laura A , Arias Cesar A
Published: January 2021

Background

Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited.

Methods

Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed.

Results

210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related.

Conclusion

We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA.

Disclosures

William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)
1609. Epidemiology and Susceptibility to Imipenem/Relebactam of Gram-Negative Pathogens from Patients with Lower Respiratory Tract Infections – SMART United States 2017-2018
Authors: Lob Sibylle , Hackel Meredith , Young Katherine , Motyl Mary , Sahm Daniel F
Published: January 2021

Background

Relebactam (REL) inhibits class A and C β-lactamases and was approved in the US combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. Using isolates collected as part of the global SMART surveillance program in the US, we evaluated the activity of IMI/REL against gram-negative pathogens (GNP) from patients with lower respiratory tract infections (LRTI), including a comparison of isolates from ICU and non-ICU wards.

Methods

In 2017-2018, 27 US hospitals each collected up to 100 consecutive aerobic or facultative GNP from LRTI patients per year. MICs were determined using CLSI broth microdilution and breakpoints.

Results

Among 3878 GNP isolates from LRTI, the most common species collected were P. aeruginosa (Psa, 33.3%), K. pneumoniae (10.9%), E. coli (10.4%), and S. marcescens (6.9%). Susceptibility of GNP is shown in the table.

IMI/REL inhibited 93% of Psa and Enterobacterales, which included 174 isolates of Morganellaceae that are not expected to be susceptible to IMI or IMI/REL. S. marcescens also showed low susceptibility to IMI, with improved but still reduced activity upon addition of REL. IMI/REL inhibited 83% of all GNP combined, 7-18 percentage points higher than the comparator β-lactams. Of the tested comparators, only amikacin exceeded the activity of IMI/REL.

Only Psa showed substantial differences in susceptibility between isolates from ICU (n=486) and non-ICU wards (n=611), with 63.4% and 70.2%, respectively, susceptible to IMI, 71.6/78.7% to cefepime, and 64.2/73.3% to piperacillin/tazobactam (P/T). Susceptibility to IMI/REL was high in both settings (91.4/93.6%). Among Enterobacterales, susceptibility was generally similar in ICU and non-ICU wards (IMI/REL, 92.5% in both settings; IMI, 86.3 and 87.1%, respectively; cefepime, 89.9/89.0%; P/T, 88.7/87.4%).

Table

Conclusion

Although resistance rates have frequently been reported to be higher in ICU than non-ICU wards, this pattern was seen in the current study only among Psa isolates. IMI/REL showed activity >90% against both Enterobacterales and Psa from both ward types. These in vitro data suggest that IMI/REL could provide an important treatment option for patients with LRTI in the US, including those in ICUs.

Disclosures

Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
1613. Global 2018 Surveillance of Eravacycline Against Gram-negative Pathogens, Including Multi-drug Resistant Isolates
Authors: Lijfrock Virgil , Morgan Steven , Hwang Sara , Efimova Ekaterina , Lawrence Kenneth , Hawser Stephen , Morrissey Ian
Published: January 2021

Background

Eravacycline (ERV) is a fully-synthetic, fluorocycline antibacterial approved by the FDA and EMA for treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age. The purpose of this study was to describe the in vitro activity of ERV against Gram-negative pathogens, including multi-drug resistant (MDR) isolates, collected in 2018.

Methods

Isolates were collected during 2018 from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using the most updated CLSI breakpoints, except for ERV and tigecycline (TGC) where FDA breakpoints established in 2018 and 2005 respectively, were used. MDR was defined as resistance to ≥3 antibiotics from aztreonam, a carbapenem (meropenem or ertapenem [ETP]), cefepime/cefotaxime/ceftazidime/ceftriaxone (any one), gentamicin, levofloxacin, piperacillin-tazobactam TZP, tetracycline or TGC.

Results

Summary MIC data for ERV and select comparators are shown in the Table. ERV MIC90 for all-Enterobacteriaceae was 0.5 μg/ml and for MDR-Enterobacteriaceae was 1μg/ml. The susceptibilities for all-Enterobacteriaceae were 93%, 95%, 93% and 82% for ERV, TGC, ETP and TZP, respectively. ERV further demonstrated higher rates of susceptibility than ETP and TZP against MDR-Enterobateriaceae, 81% vs 71% vs 38%. ERV MIC50/90 for carbapenem-resistant Acinetobacter baumannii (CRAB) were 4-fold lower than TGC.

Table

Conclusion

ERV in vitro activity was demonstrated and comparable susceptibility rates were observed for clinically important Gram-negative pathogens, including resistant isolates. Overall, ERV MIC90 values were 2- to 8- fold lower than TGC. this study further highlights the in vitro activity of ERV against Gram-negative pathogens identified in patients with cIAI.

Disclosures

Virgil Lijfrock, PharMD, Tetraphase (Employee) Steven Morgan, PharMD, Tetraphase Pharmaceuticals (Employee) Sara Hwang, PharMD, Tetraphase Pharmaceuticals (Employee) Ekaterina Efimova, PharMD, Tetraphase Pharmaceuticals (Employee) Kenneth Lawrence, PharmD, Tetraphase Pharmaceuticals (Employee) Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Ian Morrissey, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator)
1615. Isolation of Lytic Bacteriophages with Broad Host Range Activity Against Pseudomonas aeruginosa Strains Isolated from Respiratory Samples from Cystic Fibrosis Patients Intended for Therapeutic Application
Authors: Alexander Jose , Navas Daniel , Flowers Marly , Charles Angela , Carr Amy
Published: January 2021

Background

With the rise of the antimicrobial resistance between different genera and species of bacteria, Phage Therapy is becoming a more realistic and accessible option for patients with limited or no antimicrobial options. Being able to have rapid access to a collection of clinical active phages is key for rapid implementation of phage therapy. The Microbiology Department at AdventHealth Orlando is performing routine screening of environmental and patient samples for isolation of phages against non-fermenting Gram negative bacteria to develop a Phage Bank.

Methods

Protocols for phage isolation from environmental sources such as lakes, rivers and sewers and clinical samples were developed. A series of respiratory, throat, stool and urine samples were processed following an internal protocol that includes centrifugation, filtration and enrichment. Clinical samples were centrifugated for 10 minutes, filtered using 0.45µm centrifugation filters, seeded with targeted host bacteria (clinical isolates) and incubated at 35°C for 24 hours. The enriched samples were centrifugated and filtered for a final phage enriched solution. Screening and isolation were performed using the Gracia method over trypticase soybean agar (TSA) for plaque morphology and quantification. Host range screening of other clinical isolates of P. aeruginosa was performed using the new isolated and purified phages.

Results

4 lytic phages against clinical strains of P. aeruginosa from patient with diagnosis of cystic fibrosis (CF), were isolated and purified from 4 different respiratory samples, including sputum and bronchial alveolar lavage. All phages showed phenotypical characteristics of lytic activity. 1 phage was active against 4 strains of P. aeruginosa, 1 phage was active against 2 strains of P. aeruginosa and the remaining 2 phages were active only against the initial host target strain.

Conclusion

With this study we demonstrated the potential use of clinical samples as source for isolating active bacteriophages against clinically significant bacteria strains. Clinical samples from vulnerable population of patients with chronic infections are part of our routine “phage-hunting” process to stock and grow our Phage Bank project for future clinical use.

Disclosures

All Authors: No reported disclosures
1617. Mecillinam susceptibility against Enterobacterales isolated from urinary tract infections from US patients in 2018
Authors: Hawser Stephen , Morrissey Ian , Charrier Cedric , De Piano Cyntia , Alexander Morton , Henriksen Anne Santerre
Published: January 2021

Background

Mecillinam is a unique amidinopenicillin antibiotic, being the first and the only compound in its class. In contrast to other beta-lactams, it has a unique mechanism of action whereby it exerts its antibacterial activity through binding to penicillin binding protein 2. Pivmecillinam is the oral-prodrug of mecillinam and recommended as a first line therapy in the IDSA guidelines for uncomplicated urinary tract infections (uUTI), despite not yet being available in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of both complicated UTI and uUTI this study investigated the activity of mecillinam against Enterobacterales isolates from the USA during 2018.

Methods

A total of 1,090 isolates from urinary tract infections from patients in the USA were tested. Activity of antibiotics was tested by CLSI methodology and susceptibility interpreted according to CLSI guidelines.

Results

Susceptibility and activity of each antibiotic are shown in the Table. Mecillinam MIC50 and MIC90 were 0.25 and 4 µg/mL, respectively and 94.5% of isolates were susceptible. Fosfomycin MIC50 and MIC90 were 2 and 32 µg/mL, respectively and 95.7% of isolates were susceptible. The other four comparator antibiotics showed MIC90 values >8 µg/mL and a 70.5 – 79.9% susceptible isolates. The highest MIC90 against all isolates combined was 64 µg/mL for nitrofurantoin and the highest percentage of resistance was obtained with trimethoprim-sulfamethoxazole with 29.5%. Resistance towards ceftriaxone and ciprofloxacin was 19.6% and 26.1%, respectively.

Table

Conclusion

Overall, mecillinam showed the lowest MIC90 and a comparable susceptibility profile (94.5 % susceptible and 4.0 % resistant) to fosfomycin (i.e. 95.7% and 2.0% resistant) susceptible isolates). Resistance to ceftriaxone, ciprofloxacin and trimethoprim/sulfamethoxazole around or above 20% is concerning for their clinical usage to treat urinary tract infections. These encouraging susceptibility data warrant further studies to support the clinical development of mecillinam/pivmecillinam for the treatment of UTI in the USA.

Disclosures

Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Cedric Charrier, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Cyntia De Piano, PhD, IHMA (Employee)Utility Therapeutics (Independent Contractor) Morton Alexander, PhD, Utility Therapeutics (Employee, Shareholder) Anne Santerre Henriksen, MS, Maxel Consulting ApS (Employee)Utility Therapeutics (Independent Contractor)
1618. Meropenem-vaborbactam vs standard of care for multidrug resistant carbapenem-resistant Enterobacteriaceae
Authors: Misikir Helina , Mulugeta Surafel , Shallal Anita , Zervos Marcus
Published: January 2021

Background

Antimicrobial resistance to gram negative organisms is an increasing issue worldwide, particularly with regards to extended-spectrum B-lactamase (ESBL) and carbapenem-resistant Enterobacteriaeceae (CRE) producing organisms. Meropenem/vaborbactam (M-V) is an approved antimicrobial for treatment of some CRE infections. This study compares the outcomes of patients with CRE who were treated with M-V to standard of care (SoC) therapy.

Table 1. Results

Methods

A retrospective chart analysis was performed which analyzed 25 patients in the M-V group and 25 patients in the SoC group at an 800-bed tertiary care hospital in Southeast Michigan. Patients were matched by type of infection. Variables included basic demographics, infection source, bacterial species, as well as 30-day readmission, ICU admission, and creatinine pre- and post-treatment. The primary outcome of interest was 30-day mortality and clinical outcome (cure/improved/failure). Secondary outcomes included microbiological outcome (eradication/presumed eradication/persistence/presumed persistence) and acute kidney injury (AKI) on therapy. The data was analyzed using SPSS version 14.0.

Results

The most commonly used antibiotics in the SoC group were ceftazidime-avibactam (64%) and cefepime (32%). In both groups, the most common infection source was intra-abdominal (56%). The most commonly isolated pathogen in each group was Klebsiella pneumoniae (52% in M-V and 48% in SoC). Mortality and re-admission at 30 days did not differ statistically between the two groups. However, patients who received M-V were found to be more likely to achieve clinical cure, although this did not achieve statistical significance. Patients who were treated with SoC were significantly more likely to achieve an improved clinical outcome and presumed microbiological eradication (p=0.001 and 0.01 respectively). Of the 50 patients, only 26 patients (52%) met criteria to analyze for AKI. Patients who received M-V were more likely to have AKI (16% compared to 8%) but this did not reach statistical significance.

Conclusion

M-V is an important option for care of patients with infections due to MDR gram-negative bacteria. However, further studies are warranted to determine whether its use is associated with reduced mortality and improved clinical outcomes.

Disclosures

Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support)
135. Designing And Evaluating A Pharmacist-Driven Approach to Outpatient Azithromycin Stewardship
Authors: Tran Christina , Lata Paul , Tindall Kristin , Barnett Susanne , Balasubramanian Prakash
Published: January 2021

Background

After collecting data on diminishing S. pneumoniae susceptibility rates, the Madison VA aimed to optimize azithromycin prescribing practices by enhancing the involvement of outpatient pharmacists. This study aimed to develop effective pharmacy-led stewardship teams in the outpatient setting and assess their collective impact on promoting judicious azithromycin prescribing.

Methods

Madison VA outpatient pharmacists initiated an azithromycin stewardship protocol in 4/2019 to intervene on prescriptions suspected to be discordant with expert guidelines for COPD, pneumonia, sinusitis, or bronchitis. After pharmacist follow-up with providers to discuss potentially inappropriate prescriptions, recommendations and outcomes were subsequently documented in the electronic health record. Given the longitudinal nature of outpatient pharmacist interventions, a post-hoc survey was provided to assess pharmacists’ perceptions of this protocol, barriers to intervention, and areas for improvement.

Results

Between 10/2018 and 4/2020, 18 pharmacists intervened on 42 outpatient azithromycin prescriptions to recommend alternative antibiotics with improved streptococcal coverage or supportive care alone. Indications warranting the most intervention included COPD exacerbations, upper respiratory infections, and bronchitis. Factors most often cited by pharmacists as barriers to intervention included negative impact on workload, provider reluctance, and insufficient time for follow-up. All surveyed pharmacists believed that prescribers, most commonly primary care providers, were fairly or very receptive to their recommendations. Data evaluated from 10/2018 to 12/2019 revealed a 45% decrease in azithromycin prescribing.

Conclusion

Azithromycin prescribing has steadily declined at the Madison VA, reinforced by the implementation of an outpatient pharmacist stewardship team. To more seamlessly integrate recommendation-making into pharmacist workflow, determining solutions to identified barriers is currently underway. It is hoped that continued pharmacist involvement in outpatient antibiotic stewardship can be a sustainable practice and transferrable strategy to other antimicrobial agents in the future.

Disclosures

All Authors: No reported disclosures
1622. Outcomes of Colistin Weight-Based Dosing Versus The Non-Weight-Based Dosing
Authors: Anouassi Zohour , El Lababidi Rania M , Salem Nouran , El Nekidy Wasim S , Mooty Mohamad
Published: January 2021

Background

The use of colistin is currently the mainstay antimicrobial for several multi-drug resistant organisms (MDROs). New guidelines were recently published recommending non-weight-based (NWB) dosing of colistin. There is limited data on outcomes with this new dosing strategy. The purpose of this study was to investigate the outcomes of the new NWB dosing strategy in comparison to the previously used weight-based (WB) dosing strategy.

Methods

A retrospective study was conducted at our quaternary care hospital between January 2016 and April 2020. Adults (≥ 18 years), who received intravenous (IV) colistin for ≥ 72 hours were included. Documented clinical cure was the primary endpoint, which was defined as having at least two of the following: normalization of white blood cell count or ≥ 25% reduction, defervescence, hemodynamic stability, normalization of inflammatory markers (C-reactive protein and procalcitonin values) or ≥ 25% reduction, or the resolution of signs and symptoms of infection by the end of the therapy. Secondary outcomes were microbiological cure, incidence of acute kidney injury (AKI), time to AKI, outcomes of AKI, time to AKI recovery, new infection while on IV colistin, recurrence of infection, and all-cause mortality.

Results

A total of 104 primarily male (57.7%) patients with a mean age of 63 ± 20.23 years and weight of 70.24 ± 19.46 kg met the inclusion criteria. At baseline for both groups, the estimated creatinine clearance was 74.23 ± 70.86 mL/min and renal replacement therapy was observed in 34.62%. There was no statistically significant difference observed in clinical cure rate in the WB was 77.03% while 83.33% in the NWB (p-value 0.48). However, a higher rate of AKI was observed in NWB was 84.21% while 53.33% in WB (p-value 0.02). Amongst those who had AKI, NWB had better AKI recovery status with 60.00% while 17.95% in WB (p-value 0.00). A higher all-cause mortality rate was observed in the WB group with 55.41% while 20.00% in NWB (p-value 0.02).

Conclusion

The study showed no statistical difference in the primary outcome between the two groups, however, higher AKI rates, AKI recovery and all-cause mortality was observed in non-weight-based dosing when compared to the weight-based dosing. Our data needs to be validated in a larger study.

Disclosures

All Authors: No reported disclosures
1625. Real-World Outpatient Utilization of Ceftolozane/Tazobactam in Physician Office Infusion Centers (OICs)
Authors: Van Anglen Lucinda J , Nathan Ramesh V , Nathan Ramesh V , Metzger Brian S , Luu Quyen , Schroeder Claudia P
Published: January 2021

Background

Ceftolozane/tazobactam (C/T) is indicated for the treatment (tx) of complicated Gram-negative infections including urinary tract infection (cUTI), intra-abdominal infection (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonias caused by susceptible bacteria. Real-world data on the use of C/T are limited. We present a multicenter observational review of C/T outpatient utilization in Infectious Disease OICs.

Methods

Medical records of patients (pts) who received C/T for ≥3 doses from May 2015 to Sept 2019 were reviewed. Data included demographics, diagnosis, disease history, pathogens, C/T tx hospitalizations, emergency department (ED) visits and clinical outcomes. Clinical success was defined as complete or partial symptom resolution at completion of C/T with oral antibiotics as needed. Persistent infection and early discontinuation (D/C) of C/T were deemed non-successful. Indeterminant outcomes were deemed non-evaluable. Chi Square, Fisher’s exact, and t-tests were used to identify characteristics associated with clinical outcome.

Results

120 pts (mean age: 59±15 years, 60% male) from 33 OICs were identified. Median Charlson score was 5 (IQR, 3-7), with 43% immunocompromised, and 77% refractory/recurrent disease. Primary infections were bone and joint (25%), cUTI, (24%), respiratory tract (18%), cIAI (18%), complicated skin and skin-structure (12%), and bacteremia/endocarditis (3%). Most pts had multi-drug resistant Gram-negative pathogens (80/108; 74%), predominantly Pseudomonas aeruginosa. Polymicrobial infections were reported in 44%. Median duration of C/T therapy was 21 days (IQR, 14-34). C/T was initiated in the OIC in 59% of pts. Overall clinical success was 86% (100/117), with rates by infection type in Fig 1. Non-success was reported in 17, 10 due to persistent infection and 7 due to adverse events. The adverse events led to early D/C of C/T, all with resolution. Statistically, infection type did not impact success rate. Hospitalizations and ED visits during tx occurred in 5% of pts with successful outcomes and 35% of pts with non-successful outcomes (p < 0.001).

Fig 1. Clinical success rates of C/T by infection type

Conclusion

These real-world results support the effectiveness of C/T in a wide variety of complicated Gram-negative infections treated in the outpatient setting.

Disclosures

Lucinda J. Van Anglen, PharmD, Merck & Co. (Grant/Research Support) Ramesh V. Nathan, MD, FIDSA, Merck & Co. (Other Financial or Material Support, Grant Steering Committee Member) Brian S. Metzger, MD, MPH, Allergan (Speaker’s Bureau)Cumberland (Speaker’s Bureau)Melinta (Speaker’s Bureau)
1628. Treatment Heterogeneity in Pseudomonas aeruginosa Pneumonia
Authors: Caffrey Aisling , Bodo Emily C , Lopes Vrishali , Puzniak Laura A , LaPlante Kerry
Published: January 2021

Background

Serious bacterial infections present a unique challenge for studies of real-world evidence. Often, the causative organism is unknown during the initial period of treatment and clinical symptoms change day-to-day, which lead to multiple changes in therapy. While it is assumed approaches to treating specific infectious diseases are mostly similar, we’ve previously identified substantial treatment heterogeneity, even among organism-specific and site-specific infections.

Methods

Our retrospective cohort study included inpatients with positive P. aeruginosa from sputum and bronchoalveolar lavage cultures collected during VA medical center and community living center stays from 01/15-04/18. We included the first positive culture during the admission per patient. Daily antibiotic exposures were mapped from 3 days prior to the culture collection date until discharge or 30 days for longer stays. Heterogeneity was defined as patterns of antibiotic treatment (drug and duration) not shared by any other patient.

Results

Our study included 5,435 patients and 87.4% of patients had different patterns of antibiotic drug and duration. Among patients with changes in therapy (84.0%), 96.9% had different antibiotic treatment patterns, with a median time to first change of 1 day and median of 3 changes. When restricting the analysis to antibiotic classes (rather than drug), Gram-negative antibiotics, and anti-pseudomonal antibiotic classes, heterogeneity was 81.8%, 52.0%, and 48.7%, with median time to first change of 1, 3, and 3 days, and a median of 3, 2, and 2 changes, respectively.

Conclusion

Among inpatients with positive P. aeruginosa respiratory cultures, substantial heterogeneity was observed in the national VA Healthcare System. Even at the class level, and restricting the analysis to anti-pseudomonal antibiotic classes, approximately 50% of patients had different treatment patterns during their inpatient stay. Current methods to assess treatment do not adequately account for the extensive heterogeneity observed in infectious diseases and it remains unclear how local or national treatment guidelines affect heterogeneity.

Disclosures

Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Emily C. Bodo, Pham.D, VA Office of Academic Affiliations (OAA) (Other Financial or Material Support, Bodo is supported by the VA Office of Academic Affiliations (OAA)) Laura A. Puzniak, PhD, Merck (Employee) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)
136. Don’t Sweat the Small Stuff: Solutions for Large-Scale Stewardship Obstacles
Authors: Huang Joanne , Escobar Zahra Kassamali , Jain Rupali , Chan Jeannie D , Lynch John B , D’Angeli Marisa A , May Larissa , Bryson-Cahn Chloe
Published: January 2021

Background

In an effort to support stewardship endeavors, the MITIGATE (a Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection for Adult and Children in Emergency Department and Urgent Care Settings) Toolkit was published in 2018, aiming to reduce unnecessary antibiotics for viral respiratory tract infections (RTIs). At the University of Washington, we have incorporated strategies from this toolkit at our urgent care clinics. This study aims to address solutions to some of the challenges we experienced.

Challenges and Solutions

Methods

This was a retrospective observational study conducted at Valley Medical Center (Sept 2019-Mar 2020) and the University of Washington (Jan 2019-Feb 2020) urgent care clinics. Patients were identified through ICD-10 diagnosis codes included in the MITIGATE toolkit. The primary outcome was identifying challenges and solutions developed during this process.

Results

We encountered five challenges during our roll-out of MITIGATE. First, using both ICD-9 and ICD-10 codes can lead to inaccurate data collection. Second, technical support for coding a complex data set is essential and should be accounted for prior to beginning stewardship interventions of this scale. Third, unintentional incorrect diagnosis selection was common and may require reeducation of prescribers on proper selection. Fourth, focusing on singular issues rather than multiple outcomes is more feasible and can offer several opportunities for stewardship interventions. Lastly, changing prescribing behavior can cause unintended tension during implementation. Modifying benchmarks measured, allowing for bi-directional feedback, and identifying provider champions can help maintain open communication.

Conclusion

Resources such as the MITIGATE toolkit are helpful to implement standardized data driven stewardship interventions. We have experienced some challenges including a complex data build, errors with diagnostic coding, providing constructive feedback while maintaining positive stewardship relationships, and choosing feasible outcomes to measure. We present solutions to these challenges with the aim to provide guidance to those who are considering using this toolkit for outpatient stewardship interventions.

Disclosures

All Authors: No reported disclosures
1632. Comparing the epidemiology and clinical characteristics of childhood tuberculosis through active and passive case finding
Authors: Ikeda Saki , Cruz Andrea T , Starke Jeffrey R
Published: January 2021

Background

Childhood tuberculosis can be found via passive case finding (PCF), diagnosing a symptomatic child, and active case finding (ACF), discovering a child through contact tracing. Most high prevalence areas perform PCF, but as ACF is introduced, the clinical and radiologic findings may differ. We compare clinical, radiographic, microbiologic and epidemiological characteristics of children diagnosed through PCF and ACF.

Methods

A retrospective cohort study of all patients diagnosed with TB from 01/01/2012-12/31/2019 at Texas Children’s Hospital. ACF is TB in a child who had not previously sought care before identified via contact tracing, immigration screening, or screening for incarceration. Severity of disease was based on location of illness, imaging and bacteriology/histopathology. Associations between PCF/ACF and demographics, disease severity, and microbiology were analyzed.

Results

Of 178 patients, 80 (45%) were diagnosed via ACF. ACF patients were more likely to be US-born (OR: 2.29, [95% Confidence interval (CI): 1.12-4.67]) and younger (mean 6.18 vs 8.84 years, p= 0.016). Only 2.5% of ACF patients had extrapulmonary disease, compared to 45% of the PCF group (p< 0.0001). All 14 severe extrathoracic cases were in the PCF group (10 central nervous system disease, 3 ocular disease, 1 spondylitis). Fewer patients in the ACF group had severe intrathoracic findings (11% vs 39%, p< 0.001): miliary disease (0% vs 10%, p=0.006), cavity (1% vs 9%, p=0.04), and multilobar involvement (7.5% vs 22.4%, p=0.006). ACF patients had more hilar/mediastinal adenopathy (OR: 2.51, [CI: 1.34-3.72], p=0.004). ACF patients were less often cultured (38% vs 89%, p< 0.0001) and had less microbiological confirmation by cultures or PCR (21% vs 52%, p=< 0.0001).

Conclusion

Patients in the ACF group were younger, had less severe clinical manifestations, and had almost no extrathoracic disease. Clinicians need to be aware that the common clinical and radiographic presentations in children differ between PCF and ACF.

Disclosures

Jeffrey R. Starke, MD, Otsuka Pharmaceuticals (Other Financial or Material Support, Member, Data Safety Monitoring Board)
1638. Synchronous Video Observed Therapy for Monitoring Treatment of Tuberculosis: Experience in a Cases Series from Cali, Colombia, 2019
Authors: Tello-Cajiao Maria E , Mosquera Hernandez Juan Camilo C , Ardila-Giraldo Santiago , Romero-Rosas Nelson , Parra-Lara Luis , Niño Yessenia , Luna Lucy , García-Goez Jose
Published: January 2021

Background

In Directly Observed Treatment (DOT) monitoring strategy for the treatment of tuberculosis (TB), the patient has to travel daily to the health institution to take the TB medication. Although has been usefulness, this strategy increases the catastrophic costs of the disease, rising the probability of rejection, abandonment, and failure to treatment. Therefore, a monitoring strategy was implemented through video calls phone known as Synchronous Video Observed Therapy (S-VOT), to document the experience and its results in a series of patients from a low-middle income country.

Methods

A prospective case series study was conducted involving 23 TB patients managed with standard treatment, who were supervised through daily video call phone, during 2019, Cali-Colombia. Adherence to VOT strategy and treatment were evaluated, as well as patient characteristics, adverse drug effects, perception and costs. Categorical variable data were summarized in absolute and relative frequency tables. Quantitative variables were described with median and Interquartile range. Proportional differences were calculated with Z test, risk opportunities and difference of medians with Mann Whitney’s U test were performed. We take p values < 0.05 as significant.

Results

Adherence to S-VOT monitoring strategy was 99.8% in first phase of treatment and 98.2% in second phase. All patients completed treatment, achieving 100% cure criteria in patients with pulmonary TB. Most adverse drug effects were reported on first month (31.6%, p=0.003). Skin changes were the most frequent complaint at the beginning of management (16.4%) and epigastralgia at the end (20%). The likelyhood of adverse effects was significantly reduced when patients started maintenance phase on third month (OR: 0.29, p = 0.0003). The experience of the strategy was generally positive for patients. Time savings was major advantage. Travel costs in S-VOT were lower than DOT for patients, as well as the daily time investment in TB treatment.

Conclusion

S-VOT strategy was well tolerated and accepted by all patients, allowing an excellent level of adherence, with reduction in travel costs and investment of time for treatment. S-VOT is proposed as a viable alternative to DOT in selected patients.

Disclosures

All Authors: No reported disclosures
1641. A Comparative Analysis Of Lymph Node Tuberculosis Between Children And Adults
Authors: Hammami Fatma , Koubaa Makram , Chakroun Amal , Rekik Khaoula , Smaoui Fatma , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben
Published: January 2021

Background

Lymph node tuberculosis (LNTB) represents the most common site of extrapulmonary tuberculosis. Among children, due to non-specific clinical features, the diagnosis is often delayed. We aimed to compare the clinical, therapeutic and evolutionary features of LNTB between adults and children.

Methods

We conducted a retrospective study including patients hospitalized for LNTB in the infectious diseases and pediatric department between 1993 and 2018. Children aged ≤18 years were included.

Results

Overall, we encountered 231 cases of LNTB. There were 40 children (17.3%) with a mean age of 11±4 years and 191 adults (82.7%) with a mean age of 42±16 years. As to gender, females were more affected (adults: 67% vs children: 70%), with no significant difference (p >0.05). A family history of tuberculosis was significantly more frequent among children (20% vs 6.3%; p=0.01). Raw milk consumption (38.2% vs 30%; p >0.05) and close contact with animals (29.8% vs 35%; p >0.05) were noted among both adults and children. Fever (53.4% vs 32.5%; p=0.01), night sweats (35.8% vs 10%; p=0.001), loss of appetite (38.2% vs 17.5%; p=0.01) and weight loss (35.1% vs 15%; p=0.01) were significantly more frequent among adults. Tuberculin skin test was positive in 75.8% of the cases among adults and in 86.2% of the cases among children (p >0.05). Multifocal tuberculosis was significantly more frequent among adults (23.8% vs 5.7%; p=0.01). Antitubercular therapy was prescribed for a mean duration of 10±4 months among adults and for 9±3 months among children, with no significant difference (p >0.05). Side effects of antitubercular drugs were more frequent among adults (33% vs 10.3%), with a significant difference (p=0.004). Comparison of the disease evolution showed no significant difference between adults and children, regarding recovery (94.8% vs 90%), relapse (5.2% vs 5%) and death (0.5% vs 2.5%).

Conclusion

The clinical presentation of LNTB among children was less common and misleading. A family history of tuberculosis and a high index of suspicion might shorten the diagnostic delay.

Disclosures

All Authors: No reported disclosures
1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)
Authors: Dousa Khalid M , Kurz Sebastian G , Bethel Christopher , Miller Alita , Bonomo Robert A
Published: January 2021

Background

Mab is a MDR nontuberculous mycobacterium that causes lung infections in patients with structural lung disease. Mab harbors a chromosomally encoded class A β-lactamase, BlaMab, able to hydrolyze penicillins, cephalosporins and carbapenems. L,D- and D,D-transpeptidases (L,D TP and D,D TP) shape peptidoglycan (PG) synthesis and contribute to cell wall structure. Select combinations of β-lactams that inhibit L,D TP and D,D TPs and BlaMab are desirable as they can potentially improve treatment outcomes. DUR is a novel DBO β-lactamase inhibitor (BLI) with broad-spectrum activity against Ambler class A, C, and D β-lactamases (Fig.). Here, we investigated the mechanism of action and efficacy of DUR alone and combined with select β-lactams in restoring susceptibility of Mab to β-lactam antibiotics

Methods

Minimum inhibitory concentrations (MICs) of cefuroxime (CEF), imipenem (IMI) and amoxicillin (Amox) with or without DUR were determined using microdilution. Approximately 5 x 105 colony-forming units per milliliter were inoculated into Middlebrook 7H9 Broth supplemented with 10% (vol/vol) oleic albumin dextrose catalase and 0.05% (vol/vol) Tween 80. When more than 2 drugs were combined, Amox was added at fixed concentration of 8 µg/ml to serial dilutions of CEF-DUR or IMI-DUR. Mab isolates were incubated with test agents at 30°C for 48 h, and MIC was defined as lowest antibiotic concentration that prevented visible bacterial growth. Reaction intermediates in the inactivation pathway of BlaMab, L,D-TP and D,D-TPs with DUR

Results

One hundred clinically derived and previously characterized isolates were tested in these assays. MIC50 and MIC90 of DUR alone was 4 and 8 µg/ml, demonstrating intrinsic activity. Combinations of DUR-IMI or DUR-CEF plus 8 µg/mL Amox lowered MIC50 to < 0.06 µg/ml in all 100 clinical isolates (Table). Mass spectrometry analyses of BlaMab, L,D-TP and D,D-TPs Mab (2,4) inactivated by DUR showed formation of stable adducts of DUR to BlaMab, L,D-TP and D,D-TPs (Fig.)

Chemical composition of durlobactam (DUR) and mass spectrometry of BlaMab, L,D TP and D,D TPs incubated with DUR

MIC50 and MIC90 of 100 Mab clinical strains against DUR alone and in combination with Amox, CEF and IMI

Conclusion

We demonstrate that a novel DBO BLI, DUR, is an active agent with potent intrinsic activity against BlaMab and Mab L,D-TPs and D,D-TPs. We hypothesize that DUR improves b-lactam activity by protecting against the hydrolytic activity of BlaMab and by targeting multiple steps in PG synthesis

Disclosures

Alita Miller, PhD, Entasis Therapeutics (Employee) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)
1648. CD4 T Lymphocyte and Monocyte Activation within One Year After Treatment Completion for Pulmonary Tuberculosis: A Pilot Study
Authors: Huaman Moises A , Moussa Anissa , Orsborn Kris I , Ticona Eduardo , Sanchez Jorge , Zavaleta Milagros , Sterling Timothy , Chougnet Claire , Deepe George S , Fichtenbaum Carl
Published: January 2021

Background

Persons with active tuberculosis (TB) have increased immune activation, which declines with TB treatment. Whether residual immune activation is present after completion of TB treatment is unknown. We conducted immunophenotyping of T cells and monocytes from individuals who had completed TB treatment, and compared them to controls without history of active TB.

Methods

Cross-sectional study of HIV-uninfected individuals 40 to 70 years old recruited in Lima, Peru. For this analysis, we included 6 individuals who had completed treatment for pulmonary TB within the past year, and 10 healthy controls without history of active TB (6 QuantiFERON®-TB positive; 4 QuantiFERON®-TB negative). Participants provided blood for T cell and monocyte immunophenotyping using multi-parameter flow cytometry, including expression of cell surface activation markers.

Results

There were no significant differences in age, sex, or comorbidities between patients previously treated for TB and controls without history of active TB. Median time since TB treatment completion was 4 months (range, 2 – 9) for the previously treated group. Compared to controls, persons previously treated for TB had increased CD4+ to CD8+ ratio (2.4 vs. 1.3; p=0.03), increased proportion of CD4+ T cells co-expressing HLA-DR and CD38 activation markers (5.8% vs. 3.1%; p=0.02), increased CD4+ T cell ICAM-1 expression (56.3% vs. 33.2%; p=0.03), as well as increased density of HLA-DR in monocytes (HLA-DR MFI; 7572 vs. 3917; p=0.03).

Conclusion

In this pilot study, individuals who recovered from pulmonary TB exhibited increased CD4+ T cell and monocyte activation phenotypes within one year of TB treatment completion. These results suggest residual immune activation after clinical TB cure.

Disclosures

Carl Fichtenbaum, MD, Amgen (Grant/Research Support, outside the submitted work)Clinical Care Options (Other Financial or Material Support, outside the submitted work)Cytodyn (Grant/Research Support, outside the submitted work)Gilead Sciences (Grant/Research Support, outside the submitted work)Janssen (Grant/Research Support, outside the submitted work)Merck (Grant/Research Support, outside the submitted work)ViiV Healthcare (Research Grant or Support, outside the submitted work)
1649. Characterizing Factors Associated with Pediatric Latent Tuberculosis Infection in an Urban Health System to Improve Screening Practices
Authors: Hoekstra Nadia E , Anderson Mark , Gaensbauer James
Published: January 2021

Background

The epidemiology and risk factors informing current American Academy of Pediatrics (AAP) guidelines on screening for pediatric latent tuberculosis infection (LTBI) have evolved over the past decade. To improve pediatric LTBI screening efficiency, we sought to reevaluate characteristics associated with positive QuantiFERON-TB Gold Plus (QFT-Plus) at Denver Health (DH), an urban health system that includes a network of primary care clinics, a refugee clinic and a tuberculosis clinic.

Methods

We retrospectively analyzed all QFT-Plus tests performed on children aged 2-18 years from 1/2019 to 9/2019. To obtain additional variables we conducted chart review on all positive and indeterminate results, and a random 10% sample of negatives. Characteristics (age range, sex, region of birth, clinic setting, primary language) of patients with positive and negative QFT-Plus were compared using Chi2 or Fisher’s exact tests (Table 1). Using the 10% negative controls, we calculated odds ratios for each variable and included important or significant variables in a multivariable logistic regression model.

Results

Of 1063 QFT-Plus tests performed, 29 (2.7%) were positive. 76% of all positive tests and 83% of positive tests in primary care clinics occurred in patients age ≥10. 51.7% of all positive patients were born in the US. Among factors analyzed by logistic regression including birth region, reason for screening, sex, age, ordering location, insurance status, and language, only Spanish language (OR 5.0, CI 1.6-15.8) and non-English, non-Spanish language (OR 6.4, CI 1.4-28.5) were significant risk factors for positive testing.

Characteristics of Denver Health Patients with Positive and Negative QFT-Plus, January-September 2019.

Conclusion

Language was the only predictor of LTBI in this study, and may be a proxy for high risk travel and family exposure. Region of birth was not predictive, as half of positive tests occurred in US-born children. The majority of positive tests occurred in older children, suggesting they should be prioritized in screening programs, though occasional detection among younger children reinforces the importance of LTBI detection in ages where risk of progression to active TB is higher. Further studies are needed to better elucidate the details behind positive testing, including more detailed characterization of travel and potential family exposures.

Disclosures

All Authors: No reported disclosures