1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications

Abstract Background Non-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen. Methods We conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen. Results There were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively). Table 1: Adverse events Conclusion A clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin. Disclosures Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)

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547. A Retrospective Cohort Study of Treatment Patterns and Clinical Outcomes in Patients with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.741 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S339-S340

Author(s):

Haley Pritchard ◽

Jon Hiles ◽

Batteiger Teresa ◽

Armisha Desai ◽

Justin E Wrin ◽

...

Keyword(s):

Cohort Study ◽

Adverse Events ◽

Hospital Mortality ◽

Retrospective Cohort ◽

Research Study ◽

Panel Member ◽

Review Panel ◽

Off Label ◽

Study Investigator ◽

Treatment Trends

Abstract Background The SARS-CoV-2 pandemic has caused over 400,000 deaths worldwide thus far, and poses therapeutic challenges for millions of patients. There is currently no treatment for SARS-CoV-2 infection approved by the United States Food and Drug Administration. Multiple agents have been used off-label to treat SARS-CoV-2 infection based on small observational cohorts and in vitro data. Here we present the experience of a large academic medical center in treating SARS-CoV-2 infection. Methods We performed a retrospective cohort study of patients admitted for greater than 24 hours with a nasopharyngeal, oropharyngeal, and/or bronchoalveolar lavage sample positive for SARS-CoV-2 by polymerase chain reaction (PCR). Demographic data, comorbidities, clinical data, and treatment data were collected from the electronic medical record. Off-label therapies were used at the discretion of the treating providers guided by regularly updated treatment guidelines assembled by infectious diseases physicians and antimicrobial stewardship pharmacists. The primary outcome assessed was in-hospital mortality. Secondary outcomes included admission to the intensive care unit (ICU), endotracheal intubation, initiation of vasopressors, and drug-related adverse events. Results Data collection was completed for 448 patients admitted between March 18, 2020 and May 8, 2020. All-cause in-hospital mortality was 13.4% (60/448) during this time. Mortality rates increased with age, up to 45% for patients over 80 years old. Male sex, hypertension, chronic pulmonary disease, end-stage renal disease, chronic liver disease were also risk factors for increased mortality. QTc interval prolongation occurred significantly more frequently in patients who received hydroxychloroquine (HCQ) with or without azithromycin(AZM) than those who did not (HCQ 6%, HCQ+AZM 7.8% vs all other patients, 0%, p< .0001). Review of treatment trends showed close adherence to the treatment recommendations at that time (Figure 1). Patient Characteristics Admission Laboratory Data by Disease Severity QTc Prolongation Conclusion SARS-CoV-2 infection is associated with significant inpatient mortality, and use of off-label treatments was associated with significant drug-related adverse events. Treatment regimens changed rapidly, and providers adhered closely to institutional guidelines as they evolved. Treatment Trends by Week QTC pre/post Treatment by Hydroxychloroquine Use vs. No Hydroxychloroquine Use Disclosures Samir Gupta, MD, Gilead Sciences (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)

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235. In outpatient clinics serving Veterans, antibiotic prescriptions precede a minority of antibiotic-associated adverse events

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.279 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S118-S118

Author(s):

Brigid Wilson ◽

Taissa A Bej ◽

Richard Banks ◽

Janet Briggs ◽

Sunah Song ◽

...

Keyword(s):

Primary Care ◽

Adverse Events ◽

Antibiotic Prescription ◽

Panel Member ◽

Outpatient Clinics ◽

Drug Resistant ◽

Antibiotic Exposure ◽

Research Support ◽

Review Panel ◽

Research Grant

Abstract Background An estimated 30% of antibiotic prescriptions in outpatient settings may be inappropriate. Antibiotic exposure increases an individual’s risk of Clostridioides difficile infection (CDI) and acquiring drug-resistant pathogens. To quantify the increased risk of CDI and drug-resistant pathogens posed by antibiotics prescribed in outpatient visits, we examined a two-year cohort of patients seen in primary care clinics at VA Community-Based Outpatient Clinics (CBOC) associated with a large VA Medical Center. Methods Among patients with an in-person visit at 13 CBOCs in 2018–2019, we examined rates of antibiotic-associated adverse events (AEs), defined as community-onset CDI or acquisition of resistant Gram-negative bacteria (R-GNB), in the 90 days following those visits. For each visit, we used administrative databases to determine if systemic antibiotics were prescribed, if there was an associated infectious diagnosis, and the subsequent occurrence of AEs. We summarized quarterly rates of prescribed antibiotics and AEs, characterized patients with and without AEs, and estimated the risk ratio of AE for an antibiotic prescription. Results Following 236,665 primary care visits, we observed 62 and 225 AEs due to CDI and R-GNB, respectively (0.12% combined rate) among 278 patients (5 with both). Patients who developed CDI or R-GNB had a higher Charlson Comorbidity Index (3.6 ± SD 3.0 and 2.68 ± SD 2.7, respectively) compared to those without AEs (0.72 ± SD 1.3; Table). The rate of new antibiotic prescriptions was 4% in visits without and 10% in visits with a subsequent AE, yielding a risk ratio of 2.5 (95% CI: 1.7–3.7). The rates of both antibiotic prescribing and AE were steady over the examined two-year period (Figure). Table Figure Conclusion Among all patients with a CBOC visit between 2018–2019, an AE, defined as CDI or R-GNB acquisition, was observed following only 0.1% of primary care visits. Among patients who experienced an AE, only 10% of primary care visits preceding those events included a new antibiotic prescription. While this analysis does not address antibiotics during inpatient stays or prescribed by specialty clinics, these findings suggest that among Veterans, outpatient antibiotic exposure may have only a modest contribution to the risk of AE. Disclosures Robin Jump, MD, PhD, Accelerate (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member) Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

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192. Tolerability Outcomes of Multi-drug Antibiotic Treatment for Pulmonary Nontuberculous Mycobacterial Disease due to Mycobacterium avium Complex in U.S. Medicare Beneficiaries with Bronchiectasis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.192 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S116-S117

Author(s):

Jennifer Ku ◽

Emily Henkle ◽

Kathleen F Carlson ◽

Miguel Marino ◽

Sarah K Brode ◽

...

Keyword(s):

Mycobacterium Avium ◽

Mycobacterium Avium Complex ◽

Cox Regression ◽

Organ Transplant ◽

Panel Member ◽

Drug Regimen ◽

Treatment Change ◽

Review Panel ◽

Treatment Interruptions ◽

Regimen Change

Abstract Background Nontuberculous mycobacteria (NTM), most frequently Mycobacterium avium complex (MAC), cause increasingly common pulmonary infections. Treatment interruptions and early discontinuation are common in MAC therapy, but population-based data on treatment outcomes are severely lacking. We examined tolerability outcomes of guideline-based 3-drug therapies (GBT) targeted for pulmonary MAC infection. Methods Among beneficiaries with bronchiectasis (ICD-9-CM 494.0 or 494.1) in U.S. Medicare data (01/2006 – 12/2014), we identified first-time MAC GBT therapy users, excluding those with cystic fibrosis, HIV, or a history of organ transplant. MAC GBT was defined as an overlapping prescription of ≥ 28-day supply of a macrolide, ethambutol and rifamycin. Using Cox regression methods, we compared time-to-regimen change or discontinuation within 12 months of therapy start in the following groups: 1) azithromycin-ethambutol-rifamycin vs. clarithromycin-ethambutol-rifamycin; 2) macrolide-ethambutol-rifampin vs. macrolide-ethambutol-rifabutin; and 3) azithromycin-ethambutol-rifampin vs. clarithromycin-ethambutol-rifabutin. Results We identified 4,626 GBT therapy users (mean 77.9 years [s.d. 6.1], female [77.7%], and non-Hispanic white [87.2%]). Overall, the rate of regimen change or discontinuation was higher in the clarithromycin-based regimens compared to azithromycin-containing regimens, and in rifabutin-containing regimens compared to rifampin-containing regimens. The rate of drug regimen change or discontinuation was 65% greater in the clarithromycin-ethambutol-rifabutin group compared to the azithromycin-ethambutol-rifampin group (adjusted hazard ratio: 1.64, 95% CI: 1.43, 1.64) (Table 1, Figure 1). Conclusion Azithromycin-based regimens and rifampin-containing regimens were less likely to be changed or discontinued within 12 months of therapy compared to clarithromycin-based regimens and rifabutin-containing regimens, respectively. More research is needed to identify factors associated with early treatment change or discontinuation. Disclosures Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Theodore K. Marras, MD, Astra Zeneca (Speaker’s Bureau)Insmed (Scientific Research Study Investigator)Novartis (Speaker’s Bureau)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)

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900. Switching to DTG/3TC Fixed-Dose Combination (FDC) Is Non-inferior to Continuing a TAF-Based Regimen (TBR) in Maintaining Virologic Suppression Through 144 Weeks (TANGO Study)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1095 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S541-S541

Author(s):

Olayemi Osiyemi ◽

Faïza Ajana ◽

Fiona Bisshop ◽

Stéphane De Wit ◽

Joaquín Portilla ◽

...

Keyword(s):

Virologic Failure ◽

Panel Member ◽

Drug Regimen ◽

Fixed Dose ◽

People Living With Hiv ◽

Virologic Suppression ◽

Research Support ◽

Review Panel ◽

Good Tolerability ◽

Material Support

Abstract Background DTG/3TC is a complete 2-drug regimen (2DR) for the treatment of HIV-1 infection. Non-inferior virologic efficacy has been proven over 3 years in treatment-naive people living with HIV (PLWH) and 2 years in a stable switch setting. Methods TANGO, a randomized, open-label, non-inferiority study, evaluates efficacy and safety of switching to DTG/3TC in PLWH who are virologically suppressed ( > 6 months, no prior virologic failure [VF], no major NRTI/INSTI resistance) vs remaining on a 3- or 4-drug TAF-based regimen (TBR), stratified by baseline 3rd agent class. Week 144 analyses assessed non-inferiority (NI) with a 4% NI margin for Snapshot virologic failure (VF) and 8% for virologic success (VS; FDA Snapshot algorithm, intention-to-treat–exposed [ITT-E] population). Results Of 741 randomized/exposed pts (DTG/3TC: 369; TBR: 372), most pts entered the study on EVG/c (66%). For Week 144 Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR in the ITT-E analysis: 0.3% vs 1.3%; adjusted difference (95% CI): −1.1% (−2.4%, 0.2%) and superior to TBR in the per-protocol analysis: 0% vs 1.1%; adjusted difference: −1.1% (−2.3, −0.0); P=0.044 (2-sided). Snapshot VS was high in both arms and demonstrated non-inferiority (Table). Zero pts on DTG/3TC and 3 (0.8%) on TBR met confirmed virologic withdrawal criteria with no resistance observed. Zero pts on DTG/3TC and 6 (1.6%) on TBR discontinued for lack of efficacy. Overall AE rates were similar between arms (Table). TC, LDL-C, and triglycerides improved with DTG/3TC, HDL-C improved with TBR, with no difference in TC/HDL-C ratio between arms. Changes in eGFR (cystatin C) and proximal tubular function marker were similar across arms. Adjusted mean change from BL in weight was 2.2 and 1.7 kg in the DTG/3TC and TBR arms, respectively, and proportion of pts with > 10% weight increase was similar across arms (13% and 12%, respectively). Table. Efficacy and Key Safety Results for the ITT-E and Safety Population Conclusion Switching to the 2-drug regimen of DTG/3TC from a TAF-based 3- or 4-drug regimen resulted in high, non-inferior efficacy with zero confirmed virologic withdrawals and good tolerability over 3 years of treatment. DTG/3TC 2DR is a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance. Disclosures Olayemi Osiyemi, M.D, Gilead (Advisor or Review Panel member, Speaker’s Bureau)Merck (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Fiona Bisshop, MBBBS, Gilead (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Joaquín Portilla, MD, AbbVie (Other Financial or Material Support)Gilead (Grant/Research Support, Other Financial or Material Support)Janssen (Grant/Research Support, Other Financial or Material Support)Merck Sharpe & Dohme (Other Financial or Material Support)ViiV Healthcare (Grant/Research Support, Other Financial or Material Support) Jean-Pierre Routy, MD, FRCPC, ViiV Healthcare (Grant/Research Support) Mounir Ait-Khaled, PhD, ViiV Healthcare (Employee) Keith Pappa, PharmD, Glaxo Smith Kline (Shareholder)ViiV Healthcare (Employee) Ruolan Wang, Master of Science, ViiV Healthcare (Employee) Peter Leone, MD, viiv healthcare (Employee) Jonathan Wright, MSc, GlaxoSmithKline (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kimberly Smith, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

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1185. Oseltamivir Prescribing Patterns for Infants with Influenza and Factors Associated with Guideline Adherence

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1377 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S684-S684

Author(s):

Haniah A Zaheer ◽

Sarah Chamseddine ◽

Hui Liu ◽

John V Williams ◽

Judith M Martin ◽

...

Keyword(s):

High Risk ◽

Guideline Adherence ◽

Treatment Guidelines ◽

Data Monitoring Committee ◽

Panel Member ◽

Prescribing Patterns ◽

Urgent Care ◽

Review Panel ◽

Factors Associated ◽

Contact Points

Abstract Background The Centers for Disease Control and Prevention (CDC) recommends oseltamivir be given to children < 2 years old with confirmed or suspected influenza as they are at high risk for complications. We sought to analyze oseltamivir prescribing patterns and to describe factors associated with adherence and non-adherence to CDC guidelines. Methods We used a retrospective cohort of infants ≤ 12 months old born from January 1, 2011 to December 31, 2019 within the University of Pittsburgh Medical Center health system in Southwestern Pennsylvania and who had ≥ 2 well-child visits during their first year. Infants with laboratory-confirmed influenza from January 1, 2011 to April 30, 2020 were included. Electronic health records were reviewed to describe oseltamivir prescriptions and influenza-related characteristics. Factors associated with adherence and non-adherence to CDC influenza treatment guidelines were assessed with univariate logistic regression. Results Of 422 infants with laboratory-confirmed influenza, 86% were prescribed oseltamivir. The proportion of infants prescribed oseltamivir increased from an average of 63% during 2011-2016 to 90% during 2016-2020 (OR:5.2; 95%CI: 2.9-9.5). 96% of prescriptions instructed twice daily dosing, 2% had once daily, and 2% were unknown frequency. 91% of prescriptions were for 5 days, 7% had no duration, and 2% were for > 5 days. Infants ≥ 6 months of age compared to < 6 months were less likely to be prescribed oseltamivir (83.3% vs. 100%; p< 0.001); tested for influenza in the emergency room/urgent care (OR: 0.3; 95%CI: 0.2-0.6), or admitted to the hospital (OR:0.5; 95%CI:0.2-0.9). Infants were more likely to be treated with oseltamivir if they had a known influenza positive contact (OR:2.3; 95%CI:1.0-5.2) or had fever ≥ 38.0C (OR:2.0; 95%CI:1.2-3.5). There was no difference in prescribing practices based on history of prematurity or chronic medical conditions. Conclusion Adherence to CDC influenza treatment guidelines for infants is high and has improved over time. However, targeted education at high-risk contact points may further improve guideline adherence. Disclosures John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)

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Adverse Effects, Adherence and Cost–Benefits in Glaucoma Treatment

European Ophthalmic Review ◽

10.17925/eor.2011.05.02.116 ◽

2011 ◽

Vol 05 (02) ◽

pp. 116 ◽

Cited By ~ 4

Author(s):

Philippe Denis ◽

Keyword(s):

Adverse Effects ◽

Adverse Events ◽

Treatment Guidelines ◽

Patient Adherence ◽

Holistic Approach ◽

Current Treatment ◽

Eye Drops ◽

Ongoing Research ◽

Glaucoma Progression

Intraocular pressure (IOP)-lowering eye drops can prevent glaucoma progression and hence preserve vision, but adherence may be inadequate in as many as 59 % of patients. Improving medication adherence is crucial for effective glaucoma control and represents a major challenge for physicians. Poor adherence, adverse events, poor health literacy and dissatisfaction with treatment are interrelated as well as being important risk factors for disease progression. Some adverse events may also reflect irreversible ocular damage with serious long-term consequences, including worsened outcomes following filtration surgery. Current treatment guidelines call for interventions that can maintain visual function and quality of life at a sustainable cost, including non-financial costs such as inconvenience and adverse events. Accumulating evidence suggests that the choice of first-line therapy is a leading determinant of long-term outcomes and economic costs. Effective early treatment that prevents or delays glaucoma progression could halve the long-term costs of disease management. Selecting an effective and well-tolerated IOP-lowering formulation is thus a vital first step to achieving effective disease control for the patient’s lifetime. A holistic approach to patient management should comprise a straightforward regimen including effective and well-tolerated drugs (and excipients), combined with patient-centred communication to optimise disease understanding. Available data suggest that addressing all known causes of non-adherence from the start may prove to be the best strategy for managing glaucoma. Ongoing research offers potential drug delivery technologies that could increase patient adherence while improving efficacy and decreasing adverse effects and, ultimately, maintaining vision for glaucoma patients. Until these innovations are introduced, we can only choose the best options currently available.

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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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889. Early Discontinuations and Adverse Events Among Treatment-Naïve Patients Initiating Integrase Inhibitors in a Real-world Setting

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1084 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S535-S536

Author(s):

Charlotte-Paige M Rolle ◽

Jamie Castano ◽

Vu Nguyen ◽

Kiran Patel ◽

Federico Hinestrosa ◽

...

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Integrase Inhibitors ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Treatment Naïve

Abstract Background Cohort studies suggest higher rates of discontinuations (DCs) and adverse events (AEs) with integrase inhibitors (INSTIs) than is reported in clinical trials. Here, we assess DC of different INSTIs in combination with one of two tenofovir prodrugs in the first year following initiation defined as “early DC” in a real-world cohort of treatment-naïve patients. Methods This analysis evaluated treatment-naïve patients at a single center initiating raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) or bictegravir (BIC) in combination with emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) between 10/2007-1/2020. Eligible patients had a minimum follow-up of 1 year. The primary endpoint was incidence of early INSTI DC. Secondary endpoints included AEs and risk factors for early INSTI DC and treatment-related AEs. Results 331 patients were included. Median age was 32 years, 89% were male, 43% were non-White, 8% started RAL-based therapy, 46% started EVG/c-based therapy, 22% started DTG-based therapy and 24% started BIC/F/TAF. 36 discontinued INSTI-based therapy early yielding an incidence rate of 0.17 DCs per person-years (PPY) among RAL patients, 0.14 DCs PPY among EVG/c patients, 0.22 DCs PPY among DTG patients, and 0 DCs PPY among BIC patients, p=0.006. Treatment-related AEs occurred in 27% of RAL patients, 42% of EVG/c patients, 50% of DTG patients, and 43% of BIC patients p=0.607; and were responsible for early DC rates of 0.022 in 3 EVG/c patients and 0.075 in 5 DTG patients. No treatment-related early DCs occurred among RAL or BIC patients. No evaluated factor was significantly associated with early INSTI DC, however DTG use was significantly associated with treatment-related AEs (aOR 3.46, 95% confidence interval: [1.20; 10.82]). Table 1. Risk factors for early integrase inhibitor discontinuation and treatment-related adverse events Conclusion In this cohort, early DCs occurred in 11% initiating INSTI-based therapy, however of these only 2% were treatment-related. These data support use of INSTI-based regimens as preferred options for treatment-naïve patients living with HIV due to their favorable safety and tolerability profiles. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)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 (Advisor or Review Panel member, Speaker’s Bureau)Theratechonologies (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member)

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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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1612. Evaluation of the Use of Ceftolozane/Tazobactam for the Treatment of ESBL-producing Enterobacterales Infections Using International Data from SPECTRA (Study of Prescribing Patterns and Effectiveness of Ceftolozane/Tazobactam Real World Analysis)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1792 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S800-S800

Author(s):

Alex Soriano ◽

Laura A Puzniak ◽

Matteo Bassetti ◽

Sundeep Kaul ◽

Pamela Moise ◽

...

Keyword(s):

Clinical Success ◽

Panel Member ◽

Empiric Therapy ◽

Prescribing Patterns ◽

Research Support ◽

Review Panel ◽

Patient Database ◽

Severe Infections ◽

Immunocompromised Hosts

Abstract Background There is a paucity of data on outcomes of patients with severe ESBL-producing Enterobacterales infections treated with empiric or directed ceftolozane/tazobactam (C/T). This study looked at the treatment patterns and outcomes associated with C/T use in the treatment of ESBL-producing Enterobacterales. Methods Data were collected from an international cohort of 32 hospitals in 6 countries as part of SPECTRA, a retrospective multicenter database of C/T use globally, from 2016 – 2019. All adult patients with an ESBL positive Enterobacterales sterile site culture and treated with ≥ 48 hours of C/T were eligible. Outcomes assessed were clinical success, 30-day mortality from index event and readmission. Results There were 59 patients with 121 ESBL positive isolates. Blood and urine were the most common sites of infection at 19.8% each, followed by respiratory (18.2%). E. coli (50%) and K. pneumoniae (30%) were the most common pathogens. On average patients had 2 positive ESBL isolates; median 1; range 1-15. Most patients had the same infection site and ESBL pathogen, however 13 had multi-site ESBL pathogens identified and only 2 had polymicrobial ESBL pathogens. Septic shock was observed in 14 (24%) patients; 29 (49%) were in the ICU at the onset of infection. The most common comorbid conditions were immunocompromised hosts (37%) and cardiac disease (32%). 29% of patients were transplant recipients, and 28% had a CrCl < 50 ml/min. In most patients (71%), C/T was given as directed therapy (i.e., once culture results were available). C/T was given prior to culture results (i.e., as empiric therapy) in 17 (29%) patients, of which 77% had clinical success. C/T dose was 1.5 g in 49%. Only 2 of 10 patients with a respiratory source received the currently licensed 3 g dose. Overall, clinical success was observed in 36 (61%) patients. 30-day mortality was 12%. Readmissions occurred in 5%, of which 2 were infection related. Conclusion The role of newer non-carbapenem antibiotics in the treatment of severe ESBL infections is currently undefined. In a multinational patient database, C/T was found to be effective in severe infections caused by ESBL-producing Enterobacterales. Prospective studies are needed to further define the role of C/T in the setting of frequent drug-resistant Gram-negative pathogens. Disclosures Laura A. Puzniak, PhD, Merck (Employee) Matteo Bassetti, MD, Shionogi Inc. (Advisor or Review Panel member) Pamela Moise, PharmD, Merck & Co., Inc. (Employee, Shareholder) David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member)

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