bluuebunny/crossref_metadata_2025_split huggingface dataset:
1610. Epidemiology and Treatment Heterogeneity in Acinetobacter baumanii Infections
Authors: Caffrey Aisling , Appaneal Haley J , Lopes Vrishali , LaPlante Kerry 
Published: January 2021

Abstract

Background
Acinetobacter baumannii is known as a highly resistant organism causing serious infections in intensive care populations. However, the epidemiology of infections caused by Acinetobacter baumannii and approaches to treatment are not well described in a national healthcare system.

Methods
Our retrospective cohort study included patients with positive Acinetobacter baumannii cultures collected from any source during hospitalizations at Veterans Affairs (VA) medical centers nationally from January 2010 to April 2019. We evaluated patient characteristics and utilized exposure mapping to identify treatment patterns, including treatment heterogeneity. Heterogeneity was defined as patterns of antibiotic treatment (drug and duration) not shared by any other patient.

Results
Our study included 7,551 admissions with positive Acinetobacter baumannii cultures. The mean age was 66.7 years (±12.1) and 97.4% were male. Most patients were admitted from other healthcare facilities (59.2%) and 20.8% were in intensive care during the admission. Most patients had their culture collected on the day after admission and the median time to culture completion was 4 days (interquartile range 3-5). Acinetobacter baumannii cultures were most commonly obtained from urine (33.6%), followed by skin and soft tissue (25.3%), lung (21.8%), blood (9.2%), and bone/joint (5.0%). The median length of hospital stay was 11 days, with inpatient mortality and 30-day mortality rates of 11.6% and 12.5%, respectively.
Treatment heterogeneity was high, with 88.5% of admissions having different antibiotic treatment patterns (drug and duration), with a median time to first change of 1 day and median of 3 changes. Only 2% of the admissions were treated with polymyxins and 3.0% with colistin. Carbapenems were used in 18.9% of the admissions and extended-spectrum cephalosporins in 31.7% of the admissions.

Conclusion
In VA hospitals, Acinetobacter baumannii infections are observed in both critical and non-critical patient populations, mostly among patients with healthcare exposures. Acinetobacter baumannii infections were found to have various sources of infection, mostly from urine and skin and soft tissue, and approaches to treatment were highly varied.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, PharmD, Shionogi, Inc. (Research Grant or Support) 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)
1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia
Authors: Irusta Nerea , Vega Ana , Natori Yoichiro , Abbo Lilian M , Abbo Lilian M , DeRonde Kailynn 
Published: January 2021

Abstract

Background
In-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI.

Methods
IRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if &lt; 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach.

Results
A total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075).
Table 1: Patient Characteristics

Table 2. Primary and Secondary Outcomes

Conclusion
We did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings.

Disclosures
All Authors: No reported disclosures
1614. Gwt1 Inhibitor, APX2104, Protects Against Invasive Aspergillosis in Neutropenic Mouse Model
Authors: Shaheen Shareef , Allen John , Cole D Chris , Asfaw Yohannes , Juvvadi Praveen , Shwab E Keats , Kapoor Mili , Shaw Karen , Steinbach William 
Published: January 2021

Abstract

Background
Aspergillus fumigatus is the leading cause of invasive aspergillosis (IA), a lethal infection among immunocompromised patients. Guideline-recommended antifungal therapy against IA is a triazole antifungal, with other secondary options including an echinocandin and amphotericin B. Concerns about drug-host toxicity and antifungal resistance have been globally reported, so new, safe, and effective therapeutics are imperative.

Methods
In vitro, CLSI standards were upheld as we tested APX2041, voriconazole, caspofungin, and amphotericin B against various A. fumigatus strains. In vivo we assessed toxicity and efficacy of APX2104 in immunocompromised mice respectively. Neutropenia was induced with 150 mg/kg of cyclophosphamide on days -2/+3 and 250 mg/kg of cortisone acetate on days -1/+6. Immunocompromised mice were infected in an inhalation chamber via 12 mL of aerosolized spores of A. fumigatus CEA10 at a concentration of 1x109 spores/mL (Day 0). Treatment started day +1 and ended day +7.

Results
In vitro, APX2041, the active-form of APX2104, has over a 16-fold lower minimum effective concentration (MEC) when compared to voriconazole, caspofungin, and amphotericin B against various A. fumigatus strains, including echinocandin- and azole-resistant strains.
In vivo, given preliminary pharmacokinetic data, APX2104 was tested in non-infected immunocompromised mice at 60 mg/kg and 78 mg/kg once per day (QD). Deaths due to toxicity were seen only at a dose of 78 mg/kg, so 60 mg/kg was set as a safe dose for our in vivo efficacy studies. In IA-challenged neutropenic mice, treatment with either posaconazole (20 mg/kg BID) or APX2104 (60 mg/kg QD) equally prolonged survival in 14 of 15 (93%) mice 14 days post-infection (p= 0.985). Untreatment control yielded a survival of 3 of 15 (20%) 14 days post-infection (p= &lt; 0.001). Consistent with our survival studies, H&E and GMS histological samples also demonstrated that APX2104 treatment decreased fungal burden within the lungs of neutropenic mice when compared to the untreated group.

Conclusion
Future studies will test the efficacy of APX2104 and posaconazole against azole antifungal resistant strains in vivo, as our preliminary findings suggest that APX2104 is a plausible solution to cure IA disease and combat antifungal resistance.

Disclosures
All Authors: No reported disclosures
1619. Meta-analysis of Randomized Control Trials Evaluating New Beta-Lactamase Combination Antibiotics
Authors: Wilson Geneva M , Fitzpatrick Margaret A , Walding Kyle , Gonzalez Beverly , Suda Katie J , Evans Charlesnika T 
Published: January 2021

Abstract

Background
Ceftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies.

Methods
PubMed, EMBASE, and Google Scholar were searched from January 1st, 2013 through October 1st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I2 values and funnel plots, respectively.

Results
Literature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions.

Conclusion
Although older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections.

Disclosures
All Authors: No reported disclosures
1621. Novel Beta-lactam Beta-lactamase Inhibitors Against Alternative Antibiotics for the Treatment of Complicated Urinary Tract Infections and Pyelonephritis Caused by Carbapenem-resistant Enterobacterales
Authors: Green Bliss , Meredith Jacqueline , Ackley Renee , McCarter Maggie S , Polk Christopher 
Published: January 2021

Abstract

Background
There is little data on the comparative efficacy or safety of carbapenem-resistant Enterobacterales (CRE)-targeted beta-lactam beta-lactamase inhibitors (BL-BLI), including ceftazidime/avibactam (CZA) and meropenem/vaborbactam (MVB), versus alternative antibiotics for the treatment of CRE complicated urinary tract infections/acute pyelonephritis (cUTI/AP). The objective of this study was to evaluate rates of clinical failure in patients with CRE cUTI/AP treated with CRE-targeted BL-BLI vs. alternative regimens.

Methods
This was a multicenter, retrospective cohort study of adults admitted with a CRE cUTI/AP treated with CRE-active antibiotic(s), including combination therapy, for at least 48 hours between January 2012 and June 2019. Exclusion criteria included CRE colonization, non-urinary source co-infection, non-Enterobacterales cUTI/AP, or mortality within 48 hours of index culture. The primary outcome was clinical failure, defined as continued symptoms or recurrence at 30 days from index culture. Secondary outcomes included 90-day recurrence and 30-day readmission. Safety outcomes included treatment-limiting adverse effects, non-treatment limiting nephrotoxicity, and C. difficile infection.

Results
A total of 47 patients were included (BL-BLI, n=16; alternative, n=31). Alternative regimens contained aminoglycosides, carbapenems, polymyxins, and tigecycline and utilized combination therapy more often (32.3% vs. 6.3%, p=0.046). Clinical failure occurred in 12.5% of patients in the BL-BLI group vs. 38.7% in the alternative group (p=0.063). Higher rates of 90-day recurrence (25.8% vs. 18.8%) and 30-day readmissions (51.6% vs. 31.3%) occurred in the alternative group vs. the BL-BLI group but were not statistically significant (Table 2). There were clinically significant rates of nephrotoxicity in the alternative group (45.2%) compared to the BL-BLI group (18.8%), contributing largely to the difference in treatment-limiting adverse effects (29% vs. 0%, p=0.017).
Table 1: Antibiotic Data

Table 2: Efficacy Outcomes

Table 3: Safety Outcomes

Conclusion
In this retrospective study, no difference in clinical failure resulted among groups; however, there was significantly more treatment-limiting adverse effects in the alternative group compared to the BL-BLI-based regimens, driven by nephrotoxicity.

Disclosures
All Authors: No reported disclosures
1627. Tedizolid is Well-tolerated Among Patients Receiving Prolonged Treatment Courses, Including Those Who are Intolerant of Alternative Agents
Authors: Smith Brandon , Marini Rachel V , Spigelmyer Amy , Clarke Lloyd , Shields Ryan K 
Published: January 2021

Abstract

Background
Tedizolid (TZD) is approved for acute bacterial skin and skin structure infections (ABSSSI), but often used for complicated infections to avoid linezolid (LZD) adverse events (AE), particularly when long-term treatment is indicated. This studied aimed to characterize the tolerability of TZD, including patients (pts) receiving prolonged treatment.

Methods
Retrospective review of pts who received TZD &gt; 72 hours. Thrombocytopenia was defined as a 50% decrease from baseline platelet count. Favorable clinical outcome was defined as completing therapy without an AE or hospital readmission within 30 days.

Results
86 pts accounting for 102 courses were included. Median age of pts was 57 years and 43% were immunocompromised. Median duration of TZD therapy was 8 days (range: 4 – 350) and 32% of courses were &gt;14 days. Common indications were ABSSSI (n=42), bacteremia (n=15), intra-abdominal infection (n=11), and pneumonia (n=10). 47% and 5% of courses were associated with MRSA or VRE and M. abscessus, respectively. 44% of TZD courses were preceded by treatment failure or AE associated with alternative therapies. AEs attributed to LZD were documented in 13 patients: thrombocytopenia (n=11), lactic acidosis (n=1), or both (n=1). Serotonergic agents were administered during 76% of TZD courses; however, no patient developed serotonin syndrome. 8% of TZD courses were stopped prematurely due to AEs that included thrombocytopenia (n=3), gastrointestinal intolerance (n=2), confusion (n=1), eosinophilia (n=1) and thrombocytopenia with lactic acidosis (n=1). All cases of thrombocytopenia occurred in pts with baseline platelets &lt; 100,000 cells/L. 79% of pts receiving &gt; 14 days of TZD completed therapy successfully without AEs. Among pts who failed alternative therapies, 74% were able to tolerate TZD and completed therapy. Overall, 80% of courses were completed with a favorable outcome.
Clinical Outcomes of Extended TZD Therapy

Conclusion
The safety of prolonged TZD treatment is not well-described. In our experience, TZD was well-tolerated, including among pts who failed alternative therapy. No pt receiving concomitant serotonergic agents developed serotonin syndrome and thrombocytopenia occurred exclusively among pts with low baseline platelets. Treatment courses &gt;14 days were not associated with an increase in the rate of AEs.

Disclosures
Rachel V. Marini, PharmD, Merck (Research Grant or Support) Ryan K. Shields, PharmD, MS, Allergan (Advisor or Review Panel member, Research Grant or Support)Entasis (Advisor or Review Panel member)Melinta (Research Grant or Support)Menarini (Consultant)Merck (Advisor or Review Panel member, Research Grant or Support)Shionogi (Advisor or Review Panel member, Research Grant or Support)Summit (Advisor or Review Panel member)Tetraphase (Research Grant or Support)Venatorx (Advisor or Review Panel member, Research Grant or Support)
1630. What is Treatment Time Zero Among Hospitalized Patients with Bacteremia?
Authors: Caffrey Aisling , Lopes Vrishali 
Published: January 2021

Abstract

Background
Common operational definitions of antibiotic exposures in infectious diseases research do not accurately reflect actual treatment, as daily changes in clinical presentation (i.e. improvement, worsening) and clinical information (i.e. causative organism, susceptibilities) lead to frequent changes in treatment, both within empiric and definitive treatment periods. Common definitions create periods of ‘ignored’ exposures, and we’ve previously shown that antibiotic treatments during ‘ignored’ periods vary widely. Therefore, we assessed the distribution of important time points for antibiotic treatments for Staphylococcus aureus bacteremia.

Methods
Our retrospective cohort study included hospital admissions in the national Veterans Affairs (VA) Healthcare System with S. aureus positive blood cultures from 2010 to 2018. Admissions with inappropriate initial antibiotic therapy for S. aureus were excluded. We implemented daily exposure mapping to identify antibiotic exposures and changes in treatment on each day of the admission until discharge, or 30 days post-admission for longer stays, and in relation to the culture final report date.

Results
We identified 21,947 admissions meeting our inclusion criteria. Antibiotic initiation most often occurred on the culture collection date (68.7%) or the day after (22.6%). Median time to the culture final report date from the culture collection date was 4 days (interquartile range [IQR] 3 to 5). Among those with changes in therapy (n=19,392, 88.4%), median time to first change in therapy was 2 days prior to the culture final report date (IQR -3 to -1). The first change in therapy occurred before the culture final report date for 76.3% of admissions and on the culture final report date for 11.9% of admissions. Further changes were common on the culture final report date (49.5%) and the day after the final report date (45.3%).

Conclusion
Changes in antibiotic therapy are common prior to finalization of culture reports. While initial culture results and provider knowledge of these initial results are not date/time-stamped, initial change within a reasonable period from culture collection appears to be more accurate in defining empiric and definitive treatment periods than commonly used operational definitions.

Disclosures
Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support)
1631. Mycobacterium septicum: A 6-year Clinical Experience from a Tertiary Hospital and Reference Laboratory
Authors: Go John Raymond U , Campioli Cristina G Corsini , Saleh Omar Abu , Wilson John , Deml Sharon , Wengenack Nancy 
Published: January 2021

Abstract

Background
Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined.

Methods
We conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory.

Results
There were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline.
Patient Characteristics, Associated M. septicum Illness, and Therapy Provided

Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation

Patient Demographics and Specimen Source of Mycobacerium septicum Isolates

Conclusion
M. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study.

Disclosures
All Authors: No reported disclosures
1633. Improving the diagnosis of extra-pulmonary tuberculosis (EPTB): experience from north India
Authors: Sharma Anchal , Sharma Kusum , Modi Manish , Sharma Aman 
Published: January 2021

Abstract

Background
Rapid and accurate diagnosis of extra-pulmonary tuberculosis (EPTB) is imperative for early treatment and better patient outcome. Loop-mediated Isothermal Amplification (LAMP) is a promising nucleic-acid amplification assay. LAMP assay could be carried out in simple water bath under isothermal conditions in 60 minutes, and can be performed in any laboratory even in rural setting in resource poor endemic countries. We evaluated LAMP assay using two different target regions LAMP primers specific for Mycobacterium tuberculosis complex for the diagnosis of EPTB.

Methods
LAMP assay using 6 primers (each for IS6110 and IS1081) specific for Mycobacterium tuberculosis complex were performed on patients suspected of EPTB on various EPTB samples(CSF, Synovial fluid, Lymaphnode and tissue biopsies and various other samples) of 150 patients (50 confirmed, 100 suspected) Clinically suspected of EPTB and 100 non-TB control subjects.

Results
Overall LAMP test (using any of the two targets) had sensitivity and specificity of 96% and 100% for confirmed (50 culture positive) EPTB cases. In 100 clinically suspected but unconfirmed EPTB cases, LAMP was positive in 87 out of 100 cases (87%). Sensitivity of IS6110 LAMP, 1S1081 LAMP and IS6110 PCR for clinically suspected cases was 78 (78%), 84 (84%) and 70 (70%), respectively. In total 150 EPTB patients, the overall sensitivity of microscopy, culture, IS6110 PCR, IS6110 LAMP, 1081 LAMP and the LAMP test (if any of the two targets were used) were 4%, 33.3%, 74.6%, 82.66%, 87% and 92%, respectively. Specificity of all the tests was 100%. There were 8 cases which were missed by IS6110 LAMP and 2 cases by 1081 LAMP.

Conclusion
LAMP assay using two targets is a promising technique for rapid diagnosis of EPTB in 60 minutes especially in a resource poor setting who are still battling with this deadly disease.

Disclosures
All Authors: No reported disclosures