bluuebunny/crossref_metadata_2025 huggingface dataset:
1448. Socio-demographic and clinical characteristic of Tuberculosis in Tor Vergata Hospital, Rome: a 9-years analysis
Authors: Benedetta Rossi
Published: December 2022

Background

Tuberculosis (TB) represents one of the major global health problems worldwide. Italy is a low-incidence country for TB with a prevalence of 23% of extrapulmonary forms (EPTB). Migrants coming from high TB incidence country might modify local epidemiology.

Methods

We conducted a retrospective, single-center observational study including data from patients with an active TB diagnosis, admitted to the Infectious Diseases Department of Tor Vergata Hospital, Rome, from 2013 to 2021

Results

The study included 210 patients with a median age of 38 years (IQR 36-46), 77% were male, 74% were not Italians (31% Africans,26% East-Europeans,11% Asian and 6% Latin Americans)

28% of patients were immunocompromised: 5.7% tested positive for HIV, 4.7% were on immunosuppressive treatment with anti-TNF drugs, 4.7% had onco-hematological diseases, 15.7% had severe malnutrition. PPD, performed in 90 patients, resulted positive in 77; QuantiFERON-TB Gold (QTF), performed in 187 patients, resulted positive in 149, indeterminate in 9 and negative in 29 patients. 43% of patients presented with EPTB, of whom 38 had lymph node TB, 24 bone TB, 20 pleural TB, 17 abdominal TB, 9 central nervous system TB and 23 were disseminated TB (≥3 systems involved). EPTB forms, compared to pulmonary TB (PTB), were significantly more common in males (p=0.027), of younger age (p< 0.001), from Africa and Asia (p< 0.01). Immunosuppression was not significantly associated with EPTB. Lymphocytes and monocytes absolute count were significantly lower in patients with EPTB, compared to PTB (Fig. 1). Lymphocyte subpopulations were analyzed in 89 patients, showing a significantly lower CD4 count in patients with EPTB, compared to PTB (p=0.006) (Fig. 2). QTF tube 2 titer was higher in the EPTB forms (p=0.024), no association was found with QTF tube 1 (p=0.069) and QTF mitogen (p=0.118) with TB localization. (Fig.3) QTF negativity rate was higher in patients with EPTB (p=0.063).

Lymphocytes and monocytes in extrapulmonary TB (E) and pulmonary TB (P)

Analysis of lymphocytes subpopulations in extrapulmonary TB (E) and pulmonary TB (P)

Analysis of Quanti-FERON titer in extrapulmonary TB (E) and pulmonary TB (P)

Conclusion

In our cohort, there was a high prevalence of EPTB (43%), mainly diagnosed in young, otherwise healthy men from high-endemic areas, highlighting the connection of EPTB with socio-demographic determinants. Although QFT negativity rate was higher in EPTB patients, a prudent interpretation of QFT might be needed in patients with high suspicion of EPTB.

Disclosures

All Authors: No reported disclosures.
1454. Describing the Epidemiology of Nosocomial Respiratory Viral Infections (RVIs) at an Academic Medical Center
Authors: Rathod Shardul N , Nam Hannah H , Ison Michael G
Published: December 2022

Background

Nosocomial respiratory viral infections (NRVI), transmitted from infected visitors or healthcare providers to patients, lead to significant morbidity and mortality. This study describes the epidemiology of nosocomial Influenza (flu) and Respiratory Syncytial Virus (RSV) at an academic medical center from 2009 to 2018.

Methods

After institutional review board (IRB) approval, data on NRVI was collected from our Enterprise Data Warehouse and primary chart review. A nosocomial infection was defined as a positive result of flu or RSV collected ≥ 72 hours after admission between April 2009 and March 2018.

Results

There were 93/1,317 (7.1%) nosocomial flu cases and 76/617 (12.3%) nosocomial RSV cases detected during the study period (see Table 1). Flu and RSV were first detected at a median of 6.8 and 8.4 days, respectively, after admission. Patients with nosocomial flu and RSV were more likely to have a cancer diagnosis, be a stem cell transplant recipient within one year, and have undergone chemotherapy in the past 30 days (see Table 2).

Few nosocomial transmissions (15%) occurred outside the usual winter respiratory viral season (December through March, see Figure 1). Table 1Distribution of Nosocomial RVIsTable 2Underlying Medical Conditions Among Patients with Nosocomial and Community-Acquired RVIFigure 1Distribution of nosocomial RVIs over time assessing for transmission seasonality

Conclusion

Nosocomial infections account for 7% of hospitalized flu cases and 12% of hospitalized RSV cases. Infection is more common among patients at high risk of complications. Effort needs to be directed at approaches to reduce the risk of nosocomial transmission of RVI. Future studies are needed to assess the impact of interventions, such as universal masking, on the rate of nosocomial infections.

Disclosures

Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant.
1455. Diagnosis and Testing of Travel-Associated Dengue, Alameda County, California – 2019
Authors: Andemel Naissem L , Heaton Dustin T , Shemsu Munira , Marusinec Rachel , Trivedi Kavita K
Published: December 2022

Background

Dengue is an acute febrile infection with one of the four dengue viruses that are transmitted through the bite of mosquitoes. It is a communicable disease reportable to local health departments under Title 17 of the California Code of Regulations via CalREDIE (California Reportable Disease Information Exchange), which receives positive Electronic Lab Reports or Confidential Morbidity Report forms when Dengue infection is strongly suspected. Alameda County is among the top 5 jurisdictions in California for travel-associated Dengue infection reports. In order to inform best practices for diagnosis and treatment, we explored Dengue reports to Alameda County pre-pandemic.

Methods

CalREDIE data for possible Dengue infections from 2019 were categorized according to CSTE’s Dengue Virus Infections 2015 Surveillance Case Definition into cases (probable and confirmed) or non-cases (suspect and not a case). Univariate and bivariate analysis were conducted in R.

Results

In 2019, 83 reports of possible Dengue infections were received; 23 met the case classification criteria for confirmed (n=8) or probable (n=15) cases. Most (61%) of the cases were reported between the months of June and October (Figure 1). All cases were symptomatic after travel to an area where Dengue is endemic, notably India (39%), Mexico (17%) and the Philippines (13%). Of the cases, 70% visited the Emergency Department and 48% were hospitalized due to concerns for severe dengue (Table 1). Cases had > 4 times the odds of being hospitalized (Odds Ratio = 4.89, 95% Confidence Interval = 1.63-14.7, p = 0.01) compared to non-cases. 78% of the cases were tested for Dengue within 1 week from symptom onset, but of those, only 39% had a PCR or antigen test while 83% had an IgM test and 78% had an IgG test (Table 2). Figure 1Table 1:Patient Characteristics by CalREDIE Case Resolution Status of 2019 Dengue ReportsTable 2:Laboratory Testing Practices for 2019 Cases with Labs within 7 days of Symptom Onset

Conclusion

More outreach efforts are needed to educate health care providers on providing timely and adequate testing to travelers and improve diagnosis of travel-associated Dengue. Based on pre-pandemic surveillance in Alameda County, Dengue should be strongly suspected in patients who present with an acute febrile illness and history of travel to Dengue endemic areas such as India, Mexico, and the Philippines. Health care providers suspecting Dengue should test with either PCR or antigen tests within a week of symptom onset.

Disclosures

All Authors: No reported disclosures.
1464. Real-World (RW) Utilization Pattern of Letermovir in Adult Cytomegalovirus Seropositive Allogeneic Hematopoietic Stem Cell Transplant (HCT) Recipients: A Multicenter Retrospective Cohort Study from the European Society for Blood and Marrow Transplantation (EBMT) Registry
Authors: Styczynski Jan , Tridello Gloria , Knelange Nina , Wendel Lotus , Xhaard Alienor , Cutini Ilaria , Chiusolo Patrizia , Franke Georg-Nikolaus , Kraus Sabina , Raval Amit D , Merchant Sanjay , de la Camara Rafael
Published: December 2022

Background

Letermovir (LET) prophylaxis in CMV seropositive (R+) allogeneic (allo) HCT recipients was approved in 2017 based on a Phase 3 randomized clinical trial (RCT) demonstrating lower rates of CMV infection, disease, and all-cause mortality among LET treated participants. While RCTs demonstrate causal effects between treatments and outcomes, RW data answer practical aspects of utilization such as time to initiation of LET and duration of use. The objective of this study was to assess LET RW utilization pattern in adult CMV R+ recipients of allo-HCT in a large cohort of multiple centers in Europe participating in the EBMT registry.

Methods

A retrospective observational cohort design was used to examine the RW utilization patterns of LET among CMV R+ of an allo-HCT in France, Germany & Italy. Inclusion criteria were CMV R+ recipients >18 years who received LET for any reason between Jan 1 2018- Dec 31, 2020 and had data available for at least until 100 days post-HCT.

Results

In this interim analysis, 138 allo-HCT recipients (52% male) with median age 55 years (range 19-72) received LET as primary prophylaxis. Donor/recipient CMV serostatus was D+/R+ 64% D-/R+ 36%. Donor type was 65% unrelated, 20% mismatched relative, 15% sibling. Standard conditioning was used in 56% and reduced-intensity in 44%. Peripheral blood stem cells were the source in 89%. T-cell depletion was performed in 48%. All centers followed WHO standardization guidelines for CMV viral load assay by PCR. Viral load was determined at time of LET initiation in 86% patients. Oral (PO) only LET formulation was used in 98% of patients (median 2 days post HCT; LET was initiated prior to HCT in 3% of the recipients). Centers indicated that intravenous (IV) formulation was administered only if patients could not tolerate PO. The median duration of PO use was 98 days. LET dose was 240 mg (86%) mostly in patients receiving cyclosporine, 480 mg (9%) or sequentially 240/480 mg (5%).

Conclusion

Some differences were observed in this interim RW LET analysis compared to the phase 3 RCT. Notably, patients began LET at a median of D+2 post HCT (compared to D+9 in the trial), and 98% received only PO LET (as compared to 26.5% receiving IV LET in the trial). Further studies are needed to determine drivers of LET utilization in RW settings.

Disclosures

Jan Styczynski, MD, PhD, MSD: Honoraria Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds Rafael de la Camara, MD, MSD: Honoraria.
1671. Activity of Imipenem/Relebactam and Comparators Against Gram-Negative MDR and DTR Pathogens from Patients with Respiratory and Bloodstream Infections – SMART United States 2018-2020
Authors: Lob Sibylle , Hackel Meredith , Siddiqui Fakhar , Bauer Karri A , DeRyke Charles A , Young Katherine , Motyl Mary , Sahm Daniel F
Published: December 2022

Background

Gram-negative pathogens with multidrug resistance (MDR) or difficult-to-treat resistance (DTR) are increasingly common, resulting in limited treatment options. These resistant pathogens are often isolated from the respiratory tract or bloodstream and can result in significant patient morbidity and mortality. Imipenem/relebactam is a combination of imipenem with relebactam, a β-lactamase inhibitor of class A and C β-lactamases. We evaluated the activity of imipenem/relebactam and comparators (imipenem, meropenem, piperacillin/tazobactam, cefepime, ceftazidime, levofloxacin, and amikacin) against gram-negative MDR and DTR isolates that were collected from patients with lower respiratory tract (RTI) or bloodstream infections (BSI) in the United States (US).

Methods

In 2018-2020, 24 clinical labs participated in the global SMART surveillance program in the US, and each collected up to 100 consecutive aerobic or facultative gram-negative pathogens per year from patients with RTI and 50 from BSI. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints.

Results

MDR isolates were found among 13.5% of collected P. aeruginosa (n=2018), 11.9% of E. coli (n=1952), 13.1% of K. pneumoniae (n=1080), 24.1% of E. cloacae complex (n=460), 19.7% of K. aerogenes (n=304), and 6.1% of S. marcescens isolates (n=304); DTR isolates were found among 7.1%, 0.1%, 2.4%, 1.5%, 0%, and 0.8%, respectively. Imipenem/relebactam was active against 61% of MDR P. aeruginosa, 43-53 percentage points higher than the studied comparator β-lactams, and against 49% of DTR P. aeruginosa, which were nonsusceptible to all studied commonly used β-lactams and levofloxacin (Table). Imipenem/relebactam was also active against 87-100% of MDR Enterobacterales, including against 97% of MDR K. pneumoniae, 18-96 percentage points higher than the studied comparator β-lactams, and against 85% of DTR K. pneumoniae.

Conclusion

Based on these in vitro data, imipenem/relebactam represents a promising treatment option in the US for patients with RTI or BSI caused by highly resistant gram-negative pathogens that pose substantial treatment challenges.

Disclosures

Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Karri A Bauer, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.
1678. Activity of mecillinam against urinary tract clinical isolates from the United States during 2017-2020 including isolates resistant to comparator antibiotics and multi-drug resistant isolates
Authors: Hawser Stephen , Kothari Nimmi , Monti Federica , Henriksen Anne Santerre
Published: December 2022

Background

Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated urinary tract infections (uUTIs) and is approved for the treatment of uUTI in Europe and Canada though not yet in the USA. To support the clinical development of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI, this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTI in the US during 2017-2020

Methods

A total of 3303 Enterobacterales clinical isolates from UTIs from hospitals throughout the USA during 2017-2020 were tested. MIC tests were performed by agar dilution in line with CLSI susceptibility testing standards.

Results

Overall, susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against isolates resistant to ceftriaxone, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim/sulfamethoxazole susceptibility to mecillinam was high with 89.6 %, 90.9 %, 82.4 %, 86.7 % and 93.6 %, respectively. Only fosfomycin exhibited similar activity to mecillinam. The most active antibiotics against MDR Enterobacterales were fosfomycin (86% susceptible) and mecillinam (79.2 % susceptible). Of the 288 MDR Enterobacterales, the majority were E. coli (n = 128) and K. pneumoniae (n = 103). The most active agents against MDR E. coli and MDR K. pneumoniae were fosfomycin and mecillinam that had susceptibilities of 93.8 % and 92.2 % and 79.6 % and 72.8 %, respectively.

Conclusion

Mecillinam exhibited promising activity against the majority of Enterobacterales tested. The drug was notably active against isolates resistant to antibiotics in routine clinical use and notably was similarly active against many MDR isolates. The data from our study strongly support the clinical utility of mecillinam and pivmecillinam in the USA for the treatment of cUTI and uUTI.

Disclosures

Anne Santerre Henriksen, PhD, UTILITY therapeutics Ltd: Advisor/Consultant.
1665. Potential underreporting of treated patients using a Clostridioides difficile testing algorithm that screens with a nucleic acid amplification test
Authors: Guh Alice , Winston Lisa Gail , Johnston Helen , Basiliere Elizabeth , Olson Danyel M , Fridkin Scott , Goodenough Dana , Wilson Christopher , Watkins Jasmine , Korhonen Lauren C , Gerding Dale N
Published: December 2022

Background

U.S. laboratories are increasingly using a two-step algorithm to diagnose Clostridioides difficile infection (CDI) that starts with a nucleic acid amplification test (NAAT), and if positive, reflexes to a toxin enzyme immunoassay. Here only a NAAT+/toxin+ result is reported to the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN) as a CDI laboratory-identified (LabID) event, but limited data suggest that NAAT+/toxin- results may also be considered CDI by clinicians. To explore this discrepancy, we compared the characteristics and treatment of NAAT+/toxin- and NAAT+/toxin+ patients.

Methods

CDC’s Emerging Infections Program (EIP) conducts population-based CDI surveillance. A case was defined as a positive C. difficile test in a person aged ≥1 year with no positive tests in the prior 8 weeks. We included cases detected by this two-step algorithm in 5 EIP sites during 2018–2020 that underwent a full chart review. Multivariable logistic regression models adjusting for age, sex, race, comorbidities, epidemiologic classification, and CDI therapy were used to compare CDI-related complications (i.e., toxic megacolon, ileus, colectomy, or intensive-care unit stay) and recurrence between the two groups.

Results

Of 1250 NAAT+ cases, 897 (72%) were toxin- and 353 (28%) were toxin+. Lower percentages of toxin- versus toxin+ cases were aged ≥65 years (42% vs 58%; P< 0.0001), had diarrhea (779/831 [94%] vs 329/338 [97%]; P=0.01), or had white blood cell counts ≥15,000 cells/μL (183/811 [23%] vs 132/321 [42%]; P< 0.0001). CDI therapy was given to 683/882 (77%) toxin- versus 338/349 (97%) toxin+ cases (P< 0.0001). In multivariable analysis, toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.49; 95% confidence interval [CI], 0.32–0.74) but not for CDI-related complications (aOR, 1.00; 95% CI, 0.64–1.56).

Conclusion

NAAT+/toxin- cases were less likely to have recurrence but were as likely to have CDI-related complications as NAAT+/toxin+ cases. More than twice as many potentially unreported NAAT+/toxin- cases were treated than the number of reported NAAT+/toxin+ treated cases. Use of this two-step algorithm likely results in underreporting of treated CDI cases to NHSN.

Disclosures

Scott Fridkin, MD, Pfizer: Grant/Research Support Dale N. Gerding, MD, Destiny Pharma plc.: Advisor/Consultant.
1666. Sources and Preventability of Hospital-onset Bacteremia and Fungemia in the United States: Evaluation of a Potential Healthcare Quality Measure
Authors: Leekha Surbhi , Robinson Gwen , Jacob Jesse T , Fridkin Scott , Shane Andi L , Sick-Samuels Anna , Milstone Aaron , Nair Rajeshwari , Perencevich Eli N , Puig-Asensio Mireia , Kobayashi Takaaki , Mayer Jeanmarie , Lewis Julia , Bleasdale Susan C , Wenzler Eric , Mena Lora Alfredo J , Baghdadi Jonathan , Schrank Gregory M , Nadimpalli Gita , Harris Anthony
Published: December 2022

Background

Hospital-onset bacteremia and fungemia (HOB) is being proposed as a potential healthcare quality measure due to its clinical significance, objectivity, and ease of detection. However, information is lacking on sources of HOB and the proportion and types of cases considered preventable.

Methods

We evaluated sources and potential preventability of HOB cases at 12 hospitals using retrospective chart review. HOB was defined as a positive blood culture >= day 4 (admission date=day 1) for one or more organisms. Stratified sampling of cases by commensal and noncommensal organisms was used. Infectious disease physicians determined the source of HOB and rated preventability from 1-6 (1=definitely preventable to 6=definitely not preventable) using a previously validated guide. Ratings of 1–3 were collectively considered potentially preventable and 4–6 likely not preventable.

Results

We evaluated sources and potential preventability of HOB cases at 12 hospitals using retrospective chart review. HOB was defined as a positive blood culture >= day 4 (admission date=day 1) for one or more organisms. Stratified sampling of cases by commensal and noncommensal organisms was used. Infectious disease physicians determined the source of HOB and rated preventability from 1–6 (1=definitely preventable to 6=definitely not preventable) using a previously validated guide. Ratings of 1–3 were collectively considered potentially preventable and 4–6 likely not preventable.

Conclusion

Gastrointestinal and endovascular sources account for a large majority of noncommensal HOB cases. A high proportion of noncommensal HOB cases are likely not preventable. The presence of non-preventable events should be considered when using HOB as a quality measure. Approaches to identifying the subset of preventable noncommensal HOB events should be explored.

Disclosures

Scott Fridkin, MD, Pfizer: Grant/Research Support Andi L. Shane, MD, MPH, MSc, International Scientific Association for Probiotics and Prebiotics (ISAPP): travel and lodging to attend international meeting to deliver a presentation, June 2022 Aaron Milstone, MD, Merck: Grant/Research Support Rajeshwari Nair, MBBS, PhD, Vertex Pharmaceuticals: Salary.
1692. Ceftibuten-Xeruborbactam: In vitro Potency against Enterobacterales in Comparison with Other Oral Beta-lactams (BL) and Beta-lactamase Inhibitor (BLI) Combinations
Authors: Lomovskaya Olga , Castanheira Mariana , Lindley Jill
Published: December 2022

Background

The broad spectrum BLI xeruborbactam (XER, formerly, QPX7728) can be delivered IV or orally as the isobutyryloxymethyl prodrug. The prodrug form is in clinical development in combination with ceftibuten (BUT) for oral treatment of resistant gram-negative infections. The objective of this study was to compare the in vitro potency of BUT-XER to that of other investigational oral BL/BLI combinations and tebipenem (TBP) in blinded head-to-head testing against extended beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacterales (CRE).

Methods

A total of 980 Enterobacterales including 515 ESBL and 460 CRE, including 195 KPC-, 97 OXA-48-like- and 168 metallo beta-lactamase (MBL) producers, were susceptibility tested by reference broth microdilution against BUT-XER (at fixed 4 mg/L) and comparator BLs or BL/BLI combinations (tested at their recommended BLI concentrations). MIC testing was conducted blinded to drug identity using CLSI reference microdilution methods and controlled using approved quality control bacterial strains and ranges.

Results

BLI inhibitor combinations and TBP had excellent potency against ESBL isolates with MIC90 in the ≤ 0.03-0.06 mg/L range for BUT-avibactam (AVI) and BUT-XER and in 0.125-0.25 mg/L range for TBP, BUT-VNTX-6236 (VNRX) and cefpodoxime (CPD)-ETX1317 (ETX) (Table). Against KPC and OXA-48-producers, BUT-XER and BUT-AVI (MIC90 0.25-0.5 mg/L) were 4-fold more potent than BUT-VNRX and CPD-ETX (MIC90 of 1-2 mg/L); TBP was not active against these strains. BUT-XER and CPD-ETX were the most potent agents against MBL-producing strains; however, anti-MBL activity of CPD-ETX was due to intrinsic antibacterial activity of ETX. TPB, BUT-AVI and BUT-VNTX did not have any relevant activity against MBL-producing strains.

Conclusion

BUT-XER had the broadest antimicrobial profile, with activity against ESBL and all carbapenemase producing isolates. Its potency against ESBL-producing isolates was comparable to the carbapenem TBP. Its in vitro potency and spectrum combined with the potential of once-daily administration based on PK studies warrants further clinical development.

Disclosures

Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jill Lindley, BS, AbbVie: Grant/Research Support.
1703. Efficacy of Selected Metabolic Inhibitors for the Prevention and Resensitization of High-Level Daptomycin Resistance in Streptococcus mitis-oralis In Vitro and in an Ex Vivo Simulated Endocarditis Model
Authors: Kebriaei Razieh , Rybak Michael J , Lapitan Christian K , Somerville Greg A , Bayer Arnold S , Mishra Nagendra N
Published: December 2022

Background

Rapid development of stable, high-level daptomycin-resistance (DAP-R) is frequent among Streptococcus mitis-oralis strains during exposure to DAP in vitro and in vivo. Metabolomic analyses of in vitro-derived daptomycin-resistant (DAP-R) S. mitis-oralis strains (351D10) revealed substantial glycolytic pathway differences vs. its DAP-susceptible (DAP-S) parental strain, 351. To define translatability of such metabolic changes, we assessed combinations of DAP + strategic metabolic inhibitors likely to impact such pathways, including: oxamic acid [OXA], trimetazidine [TMZ) and 6-mercaptopurine [6-MP]. We assessed these combinations vs. our DAP-S/DAP-R isogenic strain pair both in vitro and ex vivo for: bactericidal and synergistic activities; prevention of high-level DAP-R in DAP-S cells; and/or resensitization of DAP-R cells

Methods

MICs. E test and microbroth dilution

In vitro antimicrobial combination assays. Time-kill curves (24 hr) and serial passaging in DAP (10 d).

Ex vivo IE model: SEVs (simulated endocardial vegetation’s) were quantitatively cultured at serial time-points post-exposures to DAP +/- inhibitors (0, 4, 8, 24, 32, 48 hr).

Results

In vitro , combinations of DAP + OXA or DAP + TMZ, as well as OXA or TMZ monotherapy, exerted bactericidal effect against both strains. Moreover, DAP + 6-MP yielded both a bactericidal, as well as synergistic activity against DAP-S 351 (but not against DAP-R 351 D10). None of the combinations prevented the development of DAP-R or resensitized the DAP-R strain to a DAP-S phenotype in vitro. In the ex vivo SEV model, using PK/PD simulations of humanized drug doses, DAP + OXA was the most effective regimen for both the DAP-S 351 and DAP-R 351 D10 strains; both OXA alone and DAP + OXA prevented DAP-R evolution, although not resensitizing the DAP-R strain to a DAP-S phenotype.

Conclusion

Combinations of DAP plus specific metabolic inhibitors represents a promising approach to enhance killing of S. mitis-oralis strains, as well as to potentially forestall DAP-R emergence. Also, they do provide a solid platform upon which to explore other potential metabolic modifiers for their ability to enhance the efficacy of DAP, based on definable metabolic perturbations in DAP-R S. mitis-oralis.

Disclosures

All Authors: No reported disclosures.
1707. In vitro Activities of Ceftazidime-Avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Hospitalized Adult Patients, ATLAS Global Surveillance Program 2017-2020
Authors: Wise Mark , Stone Gregory , Sahm Daniel F
Published: December 2022

Background

Effective treatments for Gram-negative infections have dwindled with the emergence and dissemination of multi-drug resistant Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa). Fortunately, ceftazidime-avibactam (CAZ-AVI) has activity against Ent and Psa isolates that produce Class A, C and some Class D β-lactamases. This study examined the in vitro activity of CAZ-AVI and comparators against Ent and Psa from presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) infections collected from adult patients as part of the ATLAS surveillance program, 2017-2020.

Methods

59,904 non-duplicate Ent and 2,504 Psa isolates from adult patients (≥18 y.o.) were collected from 271 sites in 57 countries as part of ATLAS 2017-2020 (excluding North America) for which the length of hospitalization stay was specified. Antimicrobial susceptibility testing was by broth microdilution according to CLSI guidelines and analyzed using CLSI 2022 breakpoints. Ent isolates testing with meropenem MICs >1 µg/mL and Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs >1 mg/L were genetically screened for β-lactamases. For Psa, meropenem MIC >2 µg/mL triggered β-lactamase screening. In 2020, approximately 25% of the meropenem non-susceptible isolates were screened.

Results

For Ent, CAZ-AVI was the most active agent examined against both the CA- and HA-infection population of isolates. The percentage of Ent isolates susceptible to CAZ-AVI was 2.6% and 5.3% higher compared to meropenem for the CA- and HA-infection sets, respectively. Considering both the CA- and HA- infection Psa isolates, CAZ-AVI was also the most active agent among comparators, showing %S rates 12.8% and 19.3% higher than meropenem, respectively.

Conclusion

Against Ent and Psa from adult patients, CAZ-AVI exhibited excellent in vitro activity regardless of whether the pathogen was isolated < 48 hrs. or ≥48 hrs. post hospital admission. The slightly decreased susceptibility to CAZ-AVI for the HA Psa isolates as compared to the CA isolates, as well as the relatively low %S rates for comparators, reinforces difficult-to-treat nature of nosocomial infections.

Disclosures

All Authors: No reported disclosures.
1713. In Vitro Activities of Epetraborole, a Novel Bacterial Leucyl-tRNA Synthetase Inhibitor, Against Mycobacterium avium Complex Isolates
Authors: DeStefano Michelle S , Shoen Carolyn M , Alley M R K , Cynamon Michael H
Published: December 2022

Background

Epetraborole (EBO) is a boron-containing, oral inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis; EBO demonstrates potent activity against nontuberculous mycobacteria. We evaluated the effects of select culture conditions on MIC determinations of EBO against isolates of M. avium complex (MAC), as well as EBO MIC90 results with Middlebrook 7H9 broth compared to those with cation-adjusted Mueller Hinton Broth (CAMHB) for 51 MAC isolates.

Methods

Six strains of MAC were used to test the in vitro activity of EBO in different conditions in a broth microdilution (BMD) assay. Activity was compared in Middlebrook 7H9 and CAMHB with 5% OADC from different manufacturers. The effects of glycerol, cations, oxyrase, varying pH levels, and increasing inoculum sizes were tested. Finally, EBO in vitro activity was tested for 51 MAC isolates in a BMD assay in both Middlebrook 7H9 and CAMHB with 5% OADC.

Results

In general, manipulation of select culture conditions caused very little variation in EBO MIC values for the 6 MAC strains except for increasing the inoculum from ∼105 to 107 CFU/mL, which caused an approximately 64x increase in the MIC. Since 1 MAC isolate out of 6 was affected by the addition of casitone, we tested 51 MAC isolates in both the minimal media Middlebrook 7H9 and the complex media CAMHB. EBO had a narrow MIC range in both broths, 0.25-8 mg/L for all isolates. The EBO modal MIC, MIC50 and MIC90 for the entire MAC panel of 51 isolates was 2 mg/L, 2 mg/L, and 8 mg/L for CAMHB and 1 mg/L, 1 mg/L, and 4 mg/L for Middlebrook 7H9, respectively (Table 1). Three clarithromycin-resistant isolates had EBO MIC values of 0.5 mg/L, 1 mg/L, and 2 mg/L suggesting that clarithromycin resistance does not affect EBO in vitro activity. In addition, amikacin resistance as determined using the Clinical Laboratory Standards Institute (CLSI) IV amikacin breakpoint (MIC ≥ 64 mg/L) had no noticeable effect on EBO MIC values. Table 1EBO In Vitro Activity Against 51 Isolates of Mycobacterium avium complex

Conclusion

The MIC distribution for the 51 MAC isolates tested was similar in both media types, indicating that CAMHB can be used to test EBO MAC susceptibilities per CLSI guidelines. Clarithromycin- and amikacin-resistant isolates demonstrated no cross-resistance with EBO.

Disclosures

Michelle S. DeStefano, n/a, AN2 Therapeutics: Grant/Research Support Carolyn M. Shoen, PhD, AN2 Therapeutics: Grant/Research Support MRK Alley, PhD, ABBOTT LABS: Stocks/Bonds|ABBVIE: Stocks/Bonds|AN2 Therapeutics: Author on epetraborole patent|AN2 Therapeutics: Salary|AN2 Therapeutics: Ownership Interest|AVANOS MED INC: Stocks/Bonds|NABRIVA THERAPEUTICS PLC: Stocks/Bonds|NOVARTIS AG: Stocks/Bonds Michael H. Cynamon, MD, AN2: Grant/Research Support|AN2: Grant/Research Support.
1724. Murine Efficacy Studies of Sulopenem Against Bacillus anthracis
Authors: Puttagunta Sailaja , Aronin Steven I , Dunne Michael , Halasohoris Stephanie A , Babyak Ashley , Hourihan Mary K , Meinig James M
Published: December 2022

Background

Sulopenem is a thiopenem β-lactam antibiotic being developed for the treatment of infections caused by multi-drug resistant bacteria. Sulopenem is available as intravenous and oral pro-drug formulations, and its activity aligns with the most urgent drug-resistant antimicrobial threats defined by the CDC. Sulopenem possesses potent activity against species of the Enterobacterales that encode ESBLs or AmpC-type β-lactamases that confer resistance to third generation cephalosporins. It has also demonstrated good in vitro microbiological activity against a range of bacterial pathogens including penicillin resistant S. pneumoniae, β-lactamase-producing H. influenza, and M. catarrhalis. Sulopenem is also active in vitro against a number of bio-threat pathogens at concentrations likely to be achieved after oral dosing in humans and meets criteria to be tested in the murine models of Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei. The development of novel medical countermeasures (MCMs) is critical to biodefense preparedness for both military and public health.

Methods

Female BALB/c mice were challenged with B. anthracis Ames spores by whole-body aerosol, with an average challenge of 15 x LD50 and randomly divided into cohorts of 10 mice per group. At 24h post-exposure prophylaxis (PEP), which represents therapy before onset of clinical symptoms, mice were treated q8h for 14 days with vehicle (saline, IP), ciprofloxacin (30mg/kg, IP) or sulopenem etzadroxil (50, 25, or 12.5 mg/kg, PO). Mice were monitored for a total of 30 days and data analyzed to determine the effects of sulopenem etzadroxil on survival as compared to the positive treatment control, ciprofloxacin, using Log-Ranks tests for the pair wise comparisons with SAS software.

Results

Figure 1:

Conclusion

Sulopenem is active in vivo in the murine model of B. anthracis. Survival in the sulopenem treated groups was not statistically inferior to the ciprofloxacin positive control, a standard-of-care for PEP of B. anthracis. These results support further development of sulopenem for treating B. anthracis as a novel broad-spectrum and orally available MCM.

Disclosures

Sailaja Puttagunta, MD, Iterum Therapeutics: Stocks/Bonds Steven I. Aronin, MD, Iterum Therapeutics: Stocks/Bonds Michael Dunne, MD, Iterum Therapeutics: Advisor/Consultant|Iterum Therapeutics: Board Member|Iterum Therapeutics: Stocks/Bonds.
1730. Real-World Use Of Dalbavancin In A US Tertiary Referral Center
Authors: Bhugra Mudita , Chang Aaron , Polega James , Sanctis Jorgelina De , Vanderhorst Derek , Hassouna Habiba
Published: December 2022

Background

Dalbavancin is a lipoglycopeptide with prolonged half-life currently approved for treatment of bacterial skin and soft tissue infections. Off-label uses of dalbavancin include multiple Gram-positive infections requiring long-term antibiotics use. However, clinical data regarding Dalbavancin use in the real-world setting remains limited.

Methods

We conducted a retrospective cohort study of all adult inpatients who were administered ≥1 dose of Dalbavancin between November 2017 and March 2022.

Results

Forty-nine adults were identified. Dalbavancin was used to treat skin/soft tissue infections in 9 patients (18.8%). Off-label uses accommodated for the majority of patients, with diagnoses included: bloodstream infection (24, 50%), osteomyelitis (9,18.8%), native valve infective endocarditis (6,12.5%), native septic arthritis (6,12.5%), epidural abscess (4,8.3%), catheter-related bacteremia (3,6.3%) prosthetic joint infection (3,6.3%), and diabetic foot infection (1,2.1%). No patients with prosthetic valve infective endocarditis were identified. Staphylococcus aureus was the most common treated pathogen: MRSA (15, 35.7%), MSSA (17, 40.5%). Other pathogens included: Streptococcus (2,4.8%), Enterococcus (4,9.5%), coagulase negative Staphylococcus (5,11.9%), other gram positive (4,9.5%), none (2,4.8%). Among patients who completed therapy, overall cure, and clinical response as assessed at day 42 was achieved in 29 (96.7%) of patients,1 patient (3.3%) had relapse due to noncompliance with antimicrobial suppressive regimen. Intravenous drug use was the most common cause among patients who did not complete treatment (10, 58.8%). Adverse events included mild elevation in liver function tests, which were reversible and were not definitively related to the treatment. No rashes or infusion related reaction were reported. There were no adverse events resulting in drug discontinuation.

Conclusion

Real-world, including off-label, use of Dalbavancin appears safe and is associated with favorable treatment responses. Therefore, it should be considered as an alternative treatment approach in certain patient population including at risk population that may otherwise discharge from the hospital with no antimicrobial treatment or suboptimal oral antibiotics.

Disclosures

All Authors: No reported disclosures.
1751. Evaluation of Antimicrobial Stewardship Interventions in Primary Care Clinics
Authors: Zheng Tina , Mayer Suri , Cham Samantha , Niceforo Patrizia , Ghitan Monica
Published: December 2022

Background

The goal of antimicrobial stewardship is to optimize antimicrobial therapy and clinical outcomes while minimizing the unintended consequences of antimicrobial use. With the majority of antibiotics prescribed in the outpatient setting, optimizing antimicrobial prescribing across the care continuum is necessary. We aimed to evaluate the effect of antimicrobial stewardship interventions on the rate of inappropriate antibiotic prescribing in three adult primary care clinics affiliated with a tertiary care hospital.

Methods

Antibiotic prescriptions were identified by filtering common antibiotics prescribed prior to and post intervention. Prescriptions were excluded if they were prescribed pre-procedure or if the patient had a recent hospitalization within 30 days of the outpatient visit. Appropriateness of antibiotics was determined by indication, agent, dose and duration. Institutional guidelines were created for most common infections treated in the pre-intervention period. Education to outpatient providers was completed in two in-person visits.

Results

A total of 258 prescriptions were reviewed between the pre- and post-intervention periods. The majority of patients were female (73-76%) and the median age was similar between both cohorts. The most common infection treated during the pre-intervention period was urinary tract infection, whereas skin and soft tissue infection was most common in the post-intervention period. During the baseline period, the inappropriate prescribing rate was 61%. After intervention, the rate was reduced to 55%.

Conclusion

The use of outpatient antimicrobial stewardship guidelines and provider education to reinforce knowledge demonstrated reductions in inappropriate antibiotic prescribing.

Disclosures

All Authors: No reported disclosures.
1761. A Pre-Post Interventional Study on the Impact of Asynchronous Microlearning of Antimicrobial Stewardship Principles among Nursing Staff at a Large Academic Medical Center
Authors: Bobbitt Laura , Cimino Christo , Garvey Kim , Craft Leanna , Eichenseer Nicole , Nelson George E
Published: December 2022

Background

Nurses perform several functions that are integral for antimicrobial stewardship (AS). However, nurses are underrepresented in research and underutilized in AS interventions and implementation. Additionally, lack of education and training is consistently cited as a barrier to full nurse participation in AS activities. We used a novel approach for nursing AS education by utilizing an asynchronous mobile learning platform which delivered small amounts of information to participants daily via e-mail or text message. The objective of this study was to determine the effect of this innovated AS microlearning pedagogical approach on nursing staff knowledge, attitudes, and practices (KAP) regarding AS principles.

Methods

A course consisting of 9 case-based multiple-choice questions was developed. One question per day was delivered to participants via an institutional web-based application and followed by a brief educational explanation on associated AS principles. A KAP survey with 20 Likert scale questions on a 5-point scale was administered to participants pre-and post-intervention. Survey results were compared using a Wilcoxon signed-rank test.

Results

Of the 46 participants, most (86%) reported they administer antibiotics to >50% of their patients. Of the 20 KAP questions, participant’s mean score post-intervention demonstrated statistically significant improvement for 90% (18/20) of the items. Participant’s confidence improved in key AS activities including differentiating between colonization and infection (P< 0.001), identifying unnecessary urine cultures and inappropriate treatment of urinary tract infections (P< 0.001), recognizing opportunities for intravenous to oral therapy conversion (P< 0.001), and assessing for antibiotic-associated adverse effects (P< 0.001).

Conclusion

Inclusion of nurses in AS is critical. AS nursing education through an asynchronous, brief educational format via a mobile platform resulted in statistically significant improvement in most topics covered. After course completion, participants felt more confident in their ability to participate in key AS activities. This study forms the basis for expanded AS educational efforts for all healthcare professionals.

Disclosures

All Authors: No reported disclosures.
1763. A study on the effectiveness of a pharmacist led Antifungal stewardship program, in immunocompromised patients of a tertiary care teaching hospital in South-India.
Authors: Rupali Priscilla , John Jisha Sara , Jacob Amita , Karthik Rajiv , Alexander Hanna , Selvarajan Sushil , George Biju
Published: December 2022

Background

Anti-fungal stewardship (AFS) is a less explored area of an anti-microbial stewardship (AMS) program as the patients prone to fungal infections are mostly immunocompromised, post-chemotherapy or post-transplant. In a Low-and- Middle income country (LMIC) like India, there is a dearth of Infectious Disease (ID) trained physicians and pharmacists. We aimed to study the effectiveness of a pharmacist led AFS program to ensure rational prescribing of antifungals via a post-prescription review and feedback method.

Methods

In this prospective interrupted time series analysis from June 2021 to November 2021, AFS was done on adult in-patients in the department of Hematology in a tertiary care teaching hospital in South India. The study had a pre-intervention phase and intervention phase of 3 months each. In the pre-intervention phase, patients on anti-fungal therapy > 48 hours were identified and base line data were collected and no recommendations were given. In the intervention phase, in those on antifungals >48 hours, appropriate recommendations were made with regard to modification and discontinuation of the anti-fungals based on patients’ clinical condition under the supervision of an ID physician. Acceptance and impact of the intervention were monitored and recorded.

METHOD OF THE STUDY

The study was a prospective study with 2 phases : pre-intervention and intervention. In the intervention phase, the appropriateness of the Anti-fungal therapy was analyzed and recommendations were given.

Results

A total of 193 patients were analyzed over 6 months, of which 107 patients with a mean age of 42.1 ± 14.2 belonged to the pre-intervention phase and 86 patients aged 40.2 ±12.6 years were in the intervention phase. There was no statistically significant difference in the in-hospital mortality [26.16% vs 23. 25% (p = 0.64)] between the two groups. In the intervention phase, 15 (17.44%) prescriptions were found to be inappropriate. Among these 66% of the recommendations were accepted by the treating physician. The days of therapy per 100 patient days were calculated for each individual anti-fungal drug and there was a significant reduction in consumption of Anidulafungin [29.648 Vs 14.28 (p < 0.0007)], Amphotericin B [42.05 Vs 22.18 (p< 0.0001)] and Voriconazole [56.41 Vs 35.77 (p< 0.00001)] in the intervention phase.

Outcome measurements

Conclusion

A pharmacist led AFS program resulted in statistically significant reduction in the consumption of antifungals, without a significant difference in the in-hospital mortality.

Disclosures

Priscilla Rupali, MD, DTM&H, PFIZER: Grant/Research Support|PFIZER: Grant/Research Support.
1766. Application of Defined Daily Dose to Antibiotic Prescribing in Massachusetts Jails
Authors: Szewczyk Bart , Campion Maureen , Bylsma Tara , Vazquez Gabriela Andujar , Doron Shira , Wurcel Alysse Gail
Published: December 2022

Background

Minoritized populations experience increased risk of antimicrobial resistant infections in the community and are subjected to further risk of infections because of mass incarceration. At highest risk for infections are criminal-legal involved older adults, who experience increased social vulnerability and are often high users of medical care. Antimicrobial stewardship is recommended by the IDSA to reduce unnecessary or suboptimal antibiotic use but is rarely implemented in carceral settings. The defined daily dose (DDD) per 1000 patient days is a frequently used metric of calculating antibiotic prescriptions that can be used to benchmark and track impact of interventions. The goal of this research was to apply the DDD metric as related to 1000 jail inhabitants to 2021 antibiotics prescribing in Massachusetts jails.

Methods

After receiving approval from the Massachusetts Sheriffs Association, we requested de-identified antibiotics prescription records from the State Office of Pharmaceutical Services for 2021. We followed the World Health Organization guidance for DDD calculation. We grouped antibiotics into 7 categories. We estimated the yearly number of people incarcerated by monthly capacity and the average length of incarceration.

Results

We found heterogeneity in antibiotic use patterns at the jails (Figure 1). Certain jails (e.g., Jail 1) were high users of antibiotics, while other jails (e.g., Jail 6) were low users. We also found significant heterogeneity in the classes of antibiotics used across the jails. Certain jails appear to prefer cephalosporins (e.g., Jail 1) while others (e.g., Jail 8) frequently use fluoroquinolones.

Conclusion

Applying the DDD metric is feasible in the novel setting of jails and may be utilized to benchmark antibiotic usage. This proof of concept can inform future antimicrobial stewardship interventions in carceral settings.

Disclosures

Tara Bylsma, MD, Takeda Pharmaceuticals: My husband was employed by Takeda June-Aug 2021 as a summer MBA intern Shira Doron, MD, Sunovion: Advisor/Consultant.