15. Real-World Changes in Clostridioides difficile infection (CDI) Treatment Utilization and Clinical Outcomes Associated with Updated 2017 IDSA Guidelines among Medicare Beneficiaries in the U.S

Abstract Background The 2017 IDSA CDI guideline update phased out metronidazole (MTZ) and recommended vancomycin (VAN) or fidaxomicin (FDX) for first-line use. This study examined changes in CDI antibiotic use and clinical outcomes among Medicare beneficiaries with CDI pre- vs. post- the guideline update. Methods This retrospective claims analysis used 2016-2018 national Medicare claims data. The two study samples included continuously eligible fee-for-service Medicare beneficiaries aged ≥66 years with a new CDI diagnosis followed by an antibiotic fill in the pre-period (04/01/2017-09/30/2017) and post-period (04/01/2018-09/30/2018), respectively. Outcomes included type of CDI antibiotic received; sustained response and CDI recurrence. Multivariable regressions compared pre- vs. post-period outcomes while controlling for sociodemographic and clinical factors. Results The pre-period (N=7,389) and post-period (N=7,746) samples had similar characteristics (59% > 75 years, 32% male). Post-guideline update, absolute rates of MTZ use declined 27.7% (relative change [RC] -34.1%, p< 0.001) and VAN use increased 26.9% (RC +150.2%, p< 0.001) (Figure 1). While FDX use increased 0.8% (RC +87.8%, p< 0.001), overall use remained low (1.63%). Surprisingly, clinical outcomes did not improve between the pre- and post-period (Table 1). Even after adjustment, overall sustained response rates decreased (Odds Ratio [OR]: 0.93, p=0.0197) and overall CDI recurrence rates increased (OR: 1.13, p=0.0018) slightly in the post- vs. pre-period. Additional analyses by type of antibiotic showed that VAN (55.0% and 35.1%) was similar in outcomes to MTZ (54.2% and 33.0%), whereas FDX (71.4% and 20.9%) had higher sustained response and lower CDI recurrence rates, respectively (Figure 2). Figure 1. First-line use of CDI treatments, pre- vs. post- the guideline update, among Medicare beneficiaries with CDI Table 1. Clinical outcomes, pre- vs. post- the guideline update, among Medicare beneficiaries with CDI Figure 2. Clinical outcomes* by type of index CDI treatment among Medicare beneficiaries with CDI Note Pooled rates among patients on each index CDI treatment across the pre- and post-index periods. Conclusion The 2017 IDSA guideline update was associated with a substantial increase in VAN use and decrease in MTZ use. FDX use rates remained low (< 2%). Overall CDI outcomes did not improve post guideline update despite the shift to guideline-indicated VAN. This may be because VAN was not associated with meaningfully improved outcomes relative to MTZ. However, improved outcomes seen with FDX relative to VAN and MTZ suggest potential benefits from its greater use in Medicare patients. Disclosures Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant) Justin T. Puckett, BA, COVIA Health Solutions (Employee) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Sachin Kamal-Bahl, PhD, AbbVie (Consultant)Arena Pharmaceuticals, Inc. (Consultant)COVIA Health Solutions (Employee)Janssen, Inc. (Consultant)Merck (Consultant, Shareholder)Novartis (Consultant)Pfizer, Inc. (Consultant, Shareholder)PhRMA (Consultant) Kaushal Desai, PhD, AstraZeneca Pharmaceuticals (Shareholder)Merck & Co. Inc. (Employee) Bruce Stuart, PhD, COVIA Health Solutions (Consultant) Jalpa A. Doshi, PhD, Acadia (Consultant, Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Biogen (Grant/Research Support)Boehringer Ingelheim (Other Financial or Material Support, Scientific lecture)Catabasis (Consultant)Humana (Grant/Research Support)Janssen, Inc. (Consultant, Grant/Research Support)MeiraGTX (Consultant)Merck (Grant/Research Support, Advisor or Review Panel member)Novartis (Grant/Research Support)Otsuka (Advisor or Review Panel member)Regeneron (Grant/Research Support)SAGE Therapeutics (Consultant)Sanofi (Grant/Research Support)Shire (Advisor or Review Panel member)The Medicines Company (Advisor or Review Panel member)

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762. Real-World Utilization of C. difficile Drug Treatments and Associated Clinical Outcomes in a US Hospital System

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.959 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S478-S479

Author(s):

Lauren McDaniel ◽

Nathan Everson ◽

Melissa White ◽

Engels N Obi ◽

Yiyun Chen ◽

...

Keyword(s):

Clinical Outcomes ◽

Clinical Cure ◽

Treatment Options ◽

Sustained Response ◽

Oral Vancomycin ◽

Research Support ◽

Recurrence Rates ◽

Hospital System ◽

Drug Treatments ◽

Order Set

Abstract Background IDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes. Methods This was a retrospective, quasi-experimental study evaluating CDI therapies pre- (8/2016-11/2017) and post- (5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1st or 2nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions. Results After screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group. Figure 1. CDI Treatment Utilization Table 1. Clinical Outcomes Conclusion Implementation of the CDI order set increased fidaxomicin use and was associated with a decrease in CDI recurrences and CDI-related readmissions and increase in clinical cure and sustained response. Findings suggest increased first-line use of fidaxomicin results in better clinical outcomes. Disclosures Lauren McDaniel, Pharm.D., BCIDP, Merck Sharp & Dohme Corp (Grant/Research Support) Nathan Everson, Pharm.D., BCIDP, AAHIVE, Merck & Co. (Grant/Research Support) Melissa White, PharmD, Merck Sharpe & Co (Grant/Research Support) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Rose Kohinke, PharmD, Merck Sharpe & Co (Research Grant or Support)

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823. Characteristics, Comorbidities, and Medication Burden among People Living with HIV in the U.S. Medicare Program

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1019 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S504-S504

Author(s):

Pengxiang Li ◽

Vrushabh P Ladage ◽

Jianbin Mao ◽

Girish Prajapati ◽

Dovie L Watson ◽

...

Keyword(s):

Panel Member ◽

Administrative Claims ◽

People Living With Hiv ◽

Medicare Beneficiaries ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Medicare Program ◽

Living With Hiv ◽

The U.S

Abstract Background Among the 1.2 million people living with HIV (PLWH) in the U.S., many are covered by Medicare, a federally funded health insurance program for elderly (≥65 years) and disabled (< 65 years) individuals. Medicare has emerged as a major source of HIV care for PLWH. Given limited research in this population, a better understanding of patient characteristics, comorbidities, and comedication use among PLWH in the Medicare program is needed to help optimize clinical care. Methods A retrospective claims analysis of a national cross-sectional sample of fee-for-service (FFS) Medicare beneficiaries with continuous medical and prescription coverage in 2018 was conducted using 100% Medicare administrative claims. The PLWH group included individuals with ≥1 HIV diagnosis code in medical claims and ≥1 pharmacy claim for an anchor antiretroviral (ARV) drug (i.e., NNRTI, PI or InSTI) in 2018. The comparison group included a random sample of Medicare beneficiaries without HIV (PLWoH). Sociodemographic characteristics, comorbidities, and medication use were compared between PLWH and PLWoH. Results The study sample included 86,856 PLWH and 552,645 PLWoH. PLWH were more likely to be younger (mean age: 57.4 vs 71.1 years and < 65 years: 72% vs 18%), male (75% vs 42%), Black (42% vs 10%), eligible for Medicare due to disability (83% vs 27%) and receiving full low-income subsidies (77% vs 31%); all p< 0.001. Prevalence of >3 comorbidities was high in PLWH (70.2%) and only slightly lower than in PLWoH (71.7% p< 0.001). Prevalence of neuropsychiatric conditions, chronic kidney disease, liver disease, COPD, hepatitis B, and hepatitis C were higher in PLWH (Figure 1). The mean hierarchical condition categories risk score was higher in PLWH vs PLWoH (1.81 vs. 1.32; p< 0.001). On average, polypharmacy was higher among PLWH vs PLWoH (annual number of unique medications: 12.6 vs. 9.4 for all drugs and 10.3 vs. 9.4 for non-ARV drugs, both p< 0.001). Figure 1. Percentage of PLWH and PLWoH with multimorbidity and selected comorbid conditions. Abbreviations: COPD=chronic obstructive pulmonary disease; GI=gastrointestinal; PLWH=people living with HIV; PLWoH=people living without HIV All p-values <0.001 except GI Disorders (p=0.14). Conclusion In the Medicare FFS population, multimorbidity and polypharmacy were highly prevalent in PLWH despite their substantially younger age compared to PLWoH. Our findings highlight the need to consider comorbidities and comedications in HIV management including ARV regimens to minimize medication burden and drug interactions, which might improve clinical outcomes. Disclosures Pengxiang Li, PhD, Avalon Health Economics LLC (Consultant)COVIA Health Solutions (Consultant)Healthstatistics, LLC (Consultant) Jianbin Mao, PhD, Merck (Employee)Merck (Shareholder) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Jalpa A. Doshi, PhD, Acadia (Consultant, Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Biogen (Grant/Research Support)Boehringer Ingelheim (Other Financial or Material Support, Scientific lecture)Catabasis (Consultant)Humana (Grant/Research Support)Janssen, Inc. (Consultant, Grant/Research Support)MeiraGTX (Consultant)Merck (Grant/Research Support, Advisor or Review Panel member)Novartis (Grant/Research Support)Otsuka (Advisor or Review Panel member)Regeneron (Grant/Research Support)SAGE Therapeutics (Consultant)Sanofi (Grant/Research Support)Shire (Advisor or Review Panel member)The Medicines Company (Advisor or Review Panel member)

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1172. Mucormycosis Treated with Isavuconazole: A matched-Pair Analysis from the FungiScope® Registry

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1358 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S611-S612

Author(s):

Danila Seidel ◽

Oliver Cornely ◽

Maria J G T Vehreschild ◽

Philipp Koehler ◽

Jon Salmanton-García ◽

...

Keyword(s):

Research Study ◽

Panel Member ◽

First Line ◽

Research Support ◽

Review Panel ◽

Material Support ◽

First Line Therapy ◽

Line Therapy ◽

Study Investigator ◽

All Cause Mortality

Abstract Background Isavuconazole (ISAV) is a novel, broad-spectrum triazole antifungal, available in both intravenous and oral formulations, for the treatment of adult patients with invasive aspergillosis or mucormycosis. In this retrospective case collection study, we compared outcomes for patients with invasive mucormycosis treated with ISAV versus other systemic antifungal therapies, in order to evaluate the real-world effectiveness of ISAV. Methods Proven and probable invasive mucormycosis cases treated with ISAV for a minimum of four consecutive days between 2016 and 2019 were identified from the FungiScope® registry. Matched controls were defined as patients treated with lipid formulations of amphotericin B (lipid-AMB), posaconazole, or a combination of both, as first-line therapy between 2011 and 2019. Case-matching criteria included disease severity, presence of hematological malignancy or allogeneic stem cell transplantation, and surgery for fungal disease. Baseline patient characteristics and clinical outcomes were compared descriptively. Results Each of 30 ISAV cases was matched to 1–3 controls, including 25 ISAV cases each matched to 2 or 3 controls, which resulted in a total of 69 control cases. In 70.0% of ISAV cases (n=21), ISAV was administered as a treatment for invasive mucormycosis in patients who had received prior lipid-AMB. In the remaining cases, ISAV was administered after prior voriconazole treatment (n=3) or as first-line therapy (n=6). All control patients received either lipid-AMB, posaconazole, or a combination of both. Baseline demographic and clinical characteristics and causative pathogens were similar between ISAV cases and controls (Table). Overall response rates (defined as achieving a complete or partial response) at the final assessment were 50.0% (15/30) for ISAV cases and 50.7% (35/69) for controls. All-cause mortality was 43.3% (13/30) in ISAV cases as compared to 46.4% (32/69) in controls (Figure). Table. Demographic and clinical characteristics of 30 isavuconazole cases and 69 control cases Figure. Clinical response at final assessment and all cause mortality for 30 isavuconazole cases and 69 control cases Conclusion In this retrospective analysis of cases from the FungiScope® registry, patients with invasive mucormycosis showed similar overall treatment response and all-cause mortality rates with ISAV compared to treatment with lipid-AMB and/or posaconazole. These data support the effectiveness of isavuconazole in clinical practice. Disclosures Danila Seidel, PhD, Basilea (Other Financial or Material Support, travel grant) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Philipp Koehler, MD, Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker’s Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker’s Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees) Nikolay Klimko, n/a, Astellas (Speaker’s Bureau)Gilead (Speaker’s Bureau)Merck/MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Farima Barmaki-Rad, n/a, Basilea Pharmaceutica International Ltd. (Employee) Mikael Saulay, n/a, Basilea Pharmaceutica International Ltd. (Employee) Marc Engelhardt, n/a, Basilea Pharmaceutica International Ltd. (Board Member, Consultant, Employee, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Shareholder, Speaker’s Bureau, Independent Contractor, Other Financial or Material Support)Basilea Pharmaceutica International Ltd. (Employee) Kamal Hamed, n/a, Basilea Pharmaceutica International Ltd. (Employee)

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158. Intra- and Inter-hospital Epidemiology of Carbapenem-resistant klebsiella Pneumoniae in US Hospitals

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.468 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S208-S209

Author(s):

Courtney Luterbach ◽

Liang Chen ◽

Blake Hanson ◽

Michelle Earley ◽

Lauren Komarow ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Clinical Outcomes ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Recent Common Ancestor ◽

Research Support ◽

Review Panel ◽

Carbapenem Resistant ◽

Study Investigator

Abstract Background Carbapenem-resistant Enterobacterales (CRE) and specifically Klebsiella pneumoniae (CRKp) are a global threat. CRE rapidly spreading in a healthcare network may infect a distinct patient cohort or have higher virulence. We determined the impact of cluster assignment of CRKp on transmission dynamics and clinical outcomes. Methods CRACKLE-2 is a multi-site, prospective, observational cohort study of hospitalized patients with a clinical CRE culture from any anatomic site. We analyzed 351 patients enrolled 4/30/2016–8/31/2017 in 42 US hospitals with clonal group 258 CRKp. Static clusters were set as ≤ 21 core single nucleotide polymorphisms (SNPs), identified by Snippy, and sharing a recent common ancestor, using a maximum likelihood phylogeny (RAxML v8.2.4). Dynamic clusters were set as > 80% probability of being within 3 transmissions by the R program transcluster (λ = 4, β = 1.6). Clinical outcome was assessed by desirability of outcome ranking with best outcome as alive without events and worst outcome as death. Events were no clinical response, unsuccessful discharge, and adverse events. We compared patients in and out of clusters. For patients in clusters, we also compared intra- vs inter-hospital clusters. Results In total, there were 49 static (median: 5, IQR: 2, 8) and 45 dynamic clusters (median: 5, IQR: 2, 20). For static clusters, 176 patients (50%) were in clusters with 82 (47%) patients in intra-hospital clusters. A higher proportion of patients in clusters, vs not in clusters, had a CRKp culture > 3 days from admission (P = 0.037). More patients in inter-hospital, vs intra-hospital, clusters had diabetes (P = 0.02). For dynamic clusters, 179 patients (51%) were in clusters with 69 (39%) patients in intra-hospital clusters. A lower proportion of patients in clusters, vs not in clusters, had CRKp isolated from urine (P = 0.04). More patients in inter-hospital, vs intra-hospital, clusters had a CRKp culture 3 days from admission (P = 0.04). Clinical outcomes were the same for patients in clusters vs not in clusters for static and dynamic clusters. Conclusion This analysis shows that clinical outcomes are independent of clustering assignment. Static clustering better represented nosocomial spread, based on a higher proportion of patients in clusters having a later CRKp culture. Disclosures Gregory Weston, MD MSCR, Allergan (Grant/Research Support) W. Charles Huskins, MD, MSc, ADMA Biologics (Consultant)Pfizer, Inc (Consultant) Jason C. Gallagher, PharmD, Allergan (Consultant)Astellas (Consultant)Merck (Consultant)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support) David van Duin, MD, PhD, Achaogen (Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Astellas (Advisor or Review Panel member)MedImmune (Advisor or Review Panel member)Merck (Advisor or Review Panel member)NeuMedicine (Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi-Pasteur (Advisor or Review Panel member)Shionogi (Advisor or Review Panel member)T2 Biosystems (Advisor or Review Panel member)Tetraphase (Advisor or Review Panel member)

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1084. Comparative Outcomes Among Patients Receiving Varying Daptomycin Dosing Regimens in Hemodialysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1278 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S633-S634

Author(s):

Tyler Maxwell ◽

James E Orban ◽

Wesley D Kufel ◽

Christopher Destache ◽

Karen S Williams ◽

...

Keyword(s):

Clinical Outcomes ◽

Small Sample Size ◽

Panel Member ◽

The United States ◽

Small Sample ◽

Pharmacokinetic Studies ◽

Research Support ◽

Review Panel ◽

Dosing Regimens ◽

Research Grant

Abstract Background Daptomycin (DAP) has become an appealing treatment option for gram-positive infections, which are common in patients receiving hemodialysis (HD), due to frequent access and manipulation. The approved DAP dosing of 4 to 6 mg/kg every 48 hours (q48h) quickly becomes desynchronized from the patient’s HD schedule and requires the burden of additional IV access. Previous pharmacokinetic studies have suggested that DAP can be dosed three-times weekly following HD, but no studies have evaluated clinical outcomes of this regimen. Methods This was a multi-center, retrospective cohort study across 6 hospitals in the United States. Adult, nonpregnant patients who received HD and DAP between 2015 and 2020 were screened for inclusion. Electronic medical records were reviewed for relevant study data. The primary outcome was clinical and microbiological outcomes among patients who received DAP thrice weekly versus q48h dosing. Microbiological Failure was defined as positive cultures after 7 days and further study definitions are included under Table 3. Results Baseline characteristics are summarized in Table 1. Length of stay was similar between both groups at a median of 25 days and patients had a median QPitt score of 0 on admission. The average DAP dose used was 7 mg/kg and 7mg-7mg-9mg on HD days in the q48h dosing and thrice weekly dosing regimens, respectively. The majority of patients had bacteremia and the most commonly isolated bacteria was methicillin-resistant Staphylococcus aureus. No differences in clinical outcomes were observed (p=0.87). Microbiological failure was higher among patients who received DAP thrice weekly compared to q48h dosing (69.2% vs 34.8%, p=0.047). Conclusion DAP dosed thrice weekly on HD days offers similar clinical resolution compared to q48h dosing. While the thrice weekly dosing regimen did have a significantly higher rate of microbiological failure, the analysis was limited by a small sample size. As this is a retrospective analysis not accounting for confounding variables, additional prospective studies are warranted to confirm these findings. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker's Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)

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1219. Unfavorable Clinical Outcomes with Polymyxins Compared to Ceftolozane/Tazobactam for the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1411 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S699-S700

Author(s):

Jessica Howard-Anderson ◽

Michelle Earley ◽

Toshimitsu Hamasaki ◽

Chris W Bower ◽

Gillian Smith ◽

...

Keyword(s):

Adverse Events ◽

Clinical Outcomes ◽

Panel Member ◽

Partial Credit ◽

Research Support ◽

Review Panel ◽

Inverse Probability ◽

Carbapenem Resistant ◽

Credit Scores ◽

Credit Analysis

Abstract Background Patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) have high in-hospital mortality rates. It is unknown if patients with CRPA treated with ceftolozane/tazobactam (C/T) have improved clinical outcomes compared to those treated with polymyxins. Methods The CDC-funded, Georgia Emerging Infections Program performed active population- and laboratory-based surveillance for CRPA isolated from sterile sites, urine, lower respiratory tract and wounds in metropolitan Atlanta, GA from 8/1/2016–7/31/2018. We reviewed charts of adults without cystic fibrosis who were hospitalized within 1 week of CRPA culture. Using a desirability of outcome ranking (DOOR) analysis which incorporates both benefits and risks into a single outcome, we estimated the probability that a patient treated first with C/T would have a more desirable clinical outcome at 30-days than a patient treated with polymyxins (polymyxin B or colistin). We adjusted for confounding using inverse probability of treatment weighting (IPTW) based on culture source and need for dialysis at baseline. A partial credit analysis allowed for variable weighting of DOOR ranks and calculation of differences in mean partial credit scores. Results Among 710 cases from 18 different hospitals, we identified 73 patients treated for CRPA infections with polymyxins (n=31) or C/T (n=42). Most patients were male (64%) and Black (80%), and those receiving polymyxins were more likely to have required dialysis at baseline (35% vs. 14%, p=0.03) (Table 1). At 30 days after culture, 34 (47%) were alive with no adverse events, 21 (29%) were alive with ≥ 1 adverse event, and 18 (25%) had died. Patients first treated with C/T had a lower 30-day mortality rate than those treated with polymyxins (14% vs 39%, p=0.03). Additionally, those receiving C/T had better overall clinical outcomes, with an adjusted DOOR probability of having an improved outcome of 67% (95% CI 53%–80%) compared to those receiving polymyxins (Figure 1). Partial credit analyses indicated consistent results across different patient values of survival with adverse events (Figure 2). Figure 1: Inverse probability of treatment weighting-adjusted desirability of outcome ranking (DOOR) distributions by treatment group, accounting for adverse events and survival status that occurred up to 30 days after CRPA culture. 1. Percentages are adjusted using inverse probability of treatment weighting, controlling for culture source and need for dialysis at baseline 2. Adverse events measured included: acute kidney injury, discharge to higher acuity location than previous residence, or being hospitalized 30 days after culture Figure 2: Inverse probability of treatment weighting-adjusted partial credit analysis. This displays the difference (ceftolozane/tazobactam minus polymyxin) in mean partial credit scores (black line) and associated 95% confidence bands (gray lines) as a function of the partial credit score assigned to an individual having at least one adverse event (range 0 – 100%). A score of 100% is assigned to patients alive with no adverse events and a score of 0% is assigned to patients who die. A difference in mean partial credit scores of approximately zero suggests there was no difference observed between treatment groups. Conclusion These findings support the recent Infectious Diseases Society of America guidance favoring C/T over polymyxins for treatment of CRPA infections. Disclosures David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Scott R. Evans, PhD, Abbvie (Consultant)Advantagene (Consultant)Alexion (Consultant)Amgen (Consultant)AstraZeneca (Consultant)Atricure (Consultant)Breast International Group (Consultant)Cardinal Health (Consultant)Clover (Consultant)FHI Clinical (Consultant)Genentech (Consultant)Gilead (Consultant)Horizon (Consultant)International Drug Development Institute (Consultant)Lung Biotech (Consultant)Microbiotix (Consultant)Neovasc (Consultant)Nobel Pharma (Consultant)Novartis (Consultant)Nuvelution (Consultant)Pfizer (Consultant)Rakuten (Consultant)Roche (Consultant)Roivant (Consultant)SAB Biopharm (Consultant)Shire (Consultant)Stryker (Consultant)SVB Leerink (Consultant)Takeda (Consultant)Teva (Consultant)Tracon (Consultant)Vir (Consultant)

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1388. Epidemiology and Treatment Outcomes of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1580 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S779-S779

Author(s):

Y Vivian Tsai ◽

Caroline Derrick ◽

Ismaeel Yunusa ◽

Sharon Weissman ◽

Majdi N Al-hasan ◽

...

Keyword(s):

United States ◽

Treatment Outcome ◽

Treatment Outcomes ◽

Species Distribution ◽

Southeastern United States ◽

Panel Member ◽

Positive Culture ◽

First Line ◽

Research Support ◽

Review Panel

Abstract Background Gaps in evidence concerning the epidemiology of nontuberculous mycobacterial (NTM) organisms and their associated treatment outcomes are evident in the literature. The aim of this study was to describe NTM species distribution and susceptibility profile and associated treatment outcomes among adult patients at a tertiary referral hospital in the Southeastern United States. Methods A retrospective cohort study of adult patients with NTM infections from January 1, 2010 to June 30, 2020 was performed. Included patients had a positive culture for NTM species and clinical suspicion of infection. Patients were excluded if they had concurrent positive culture for M. tuberculosis (MTB) or monomicrobial culture for M. gordonae. Study endpoints included predictors for favorable treatment outcome, species distribution, and susceptibility at baseline. Favorable treatment outcome was defined as physician-guided cessation of therapy due to clinical improvement. Univariate followed by multivariate regression analysis was used to analyze favorable predictors. Results A total of 250 and 78 patients were included in microbiologic and outcomes cohorts, respectively. Among treated patients, 47 (60%) had a favorable treatment outcome. The outcomes cohort consisted primarily of non-Hispanic Caucasians (71%) with pulmonary infection (67%). The most common isolates observed were Mycobacterium avium complex (MAC) (67%) and M. abscessus (18%). Being self-pay, underweight, history of MTB treatment, and concurrent asthma were more common in those with unfavorable treatment outcomes. The significant favorable predictors included antibiotic change not due to escalation or de-escalation of therapy and private insurance. Among MAC isolates, clarithromycin and amikacin were highly susceptible; however, M. abscessus has reduced susceptibility to first-line agents such as amikacin, clarithromycin, and cefoxitin (Table 1). Table 1. Baseline Susceptibility Conclusion Considering the long incubation time, knowledge of prevalence, antimicrobial susceptibility patterns, and outcomes could guide empirical antimicrobial selection for NTM infections. This is particularly useful for M. abscessus infections where most isolates carry significant resistance to one or more first-line agents. Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)

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1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1198 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S534-S535

Author(s):

Charlotte-Paige M Rolle ◽

Vu Nguyen ◽

Kiran Patel ◽

Dan Cruz ◽

Federico Hinestrosa ◽

...

Keyword(s):

Older Adults ◽

Drug Interactions ◽

Real World ◽

Research Study ◽

Panel Member ◽

Median Number ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.846 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S384-S384

Author(s):

Jadyn C Anderson ◽

Amanda R Krueger ◽

Elizabeth C Smith ◽

Morgan L Bixby ◽

Hunter V Brigman ◽

...

Keyword(s):

Clinical Efficacy ◽

Inhibitory Concentration ◽

Panel Member ◽

Colony Growth ◽

The United States ◽

Research Support ◽

Review Panel ◽

Agreement Rate ◽

Future Studies ◽

Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

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