Corticosteroids for COVID-19: the search for an optimum duration of therapy

SummaryForty-one patients with phlebographically proven DVT of the popliteal, femoral or iliac veins were treated with different regimens of urokinase (UK) given by continuous intravenous infusion. The four groups were comparable with respect to localization, extension and estimated age of the thrombi. Another phlebographic picture was taken within 48 hr after the end of UK infusion. Substantial lysis had occurred in 2 of 10 patients treated with 1500 U/kg/h for 2 days, in 4 of 11 treated with 2500/U/kg/h for 3 days, in 2 of 10 treated with 2500 U/kg/h for 7 days and in 4 of 10 treated with 4000 U/kg/h for 4 days. Only thrombi younger than 8 days could be lysed, with 61% (8/13) rate of lysis for thrombi less than 5 days old. Bleeding complications were observed more frequently with the higher doses and longer durations of therapy. The four treatment regimens all induced dose-dependent changes in fibrinogen, fibrin(ogen) degradation products, plasminogen and antiplasmin. Neither pre- nor postinfusion values of these parameters could differentiate patients with lysis from those without lysis. It is concluded that UK can provoke a high rate of thrombolysis of DVT treated early after the appearance of symptoms but that there is no relationship between UK-induced modifications of fibrinolysis and the outcome of therapy.

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1096. Linezolid versus Tedizolid for the Treatment of Nontuberculous Mycobacteria in Solid Organ Transplant Recipients: An Assessment of Safety

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1282 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S577-S578

Author(s):

Yi Kee Poon ◽

Ricardo M La Hoz ◽

James Sanders ◽

Linda S Hynan ◽

Marguerite Monogue

Keyword(s):

Nontuberculous Mycobacteria ◽

Organ Transplant ◽

Drug Regimen ◽

Solid Organ Transplant ◽

Mixed Effects ◽

Solid Organ ◽

Transplant Recipients ◽

Duration Of Therapy ◽

Anova Model ◽

Solid Organ Transplant Recipients

Abstract Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the long-term tolerability of antimicrobials. The oxazolidinones, linezolid and tedizolid, display in vitro activity against many NTM species and demonstrate excellent oral bioavailability. This study compares the hematologic safety profile of linezolid versus tedizolid for the treatment of NTM in solid organ transplant (SOT) recipients. Methods This retrospective cohort study included adult SOT recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat NTM between January 1, 2010 to August 31, 2019. The primary endpoint was the hematologic effects of linezolid versus tedizolid from therapy initiation to week seven. This time frame was chosen based on the median duration of therapy. A mixed-effects ANOVA model was used to assess the effects of linezolid and tedizolid on platelet counts (PLT), absolute neutrophil counts (ANC), and hemoglobin (Hgb) across time. Subjects were treated as a random effect. The secondary analysis described the proportion of adverse effects and discontinuation. Results Twenty-four patients were included in the analysis (9 linezolid, 15 tedizolid). Mycobacterium abscessus abscessus was the most common isolate, and pulmonary was the most common site of infection (Table 1). The median duration of therapy was 24 days (range 3 to 164 days) and 48 days (range 11 to 571 days) for linezolid and tedizolid, respectively. All patients in the linezolid group received 600 mg daily or less for the majority of treatment duration. In the mixed-effects ANOVA, the ANC decreased in both groups after seven weeks of therapy (p=0.04). Otherwise, no significant effects for week, treatment group, or interaction between week and treatment group were found (Figure 1). Thrombocytopenia and neutropenia were common in both groups, and around one-fifth of patients in each group discontinued the medication due to adverse effects (Table 2). Table 1. Baseline characteristics of solid organ transplant recipients who received linezolid or tedizolid as part of a multi-drug regimen to treat nontuberculous mycobacteria infections between January 1, 2010 to August 31, 2019 at UT Southwestern Medical Center. Table 2. Adverse drug events and discontinuation of therapy over seven weeks of therapy. Figure 1. Effects of linezolid versus tedizolid during the initial seven weeks of therapy using a mixed-effects ANOVA model, (a) platelet counts, (b) absolute neutrophil counts, and (c) hemoglobin. Conclusion Non-significant statistical differences were found comparing the effects of linezolid versus tedizolid for PLT, ANC, and Hgb using mixed-effects ANOVA models. Larger cohort studies are required to compare the hematologic adverse effect profile of the oxazolidinones for the treatment of NTM infections in SOT recipients. Disclosures All Authors: No reported disclosures

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1147. Short Course of Voriconazole Therapy as a Risk Factor for Relapse of Invasive Pulmonary Aspergillosis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1333 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S600-S601

Author(s):

Dong Hoon Shin ◽

Seung-Jin Yoo ◽

Jongtak Jung ◽

Kang Il Jun ◽

Hyungjin Kim ◽

...

Keyword(s):

Risk Factors ◽

Cox Regression ◽

Tertiary Care ◽

Invasive Pulmonary Aspergillosis ◽

Care Hospital ◽

Pulmonary Aspergillosis ◽

Treatment Termination ◽

Duration Of Therapy ◽

Short Course ◽

Life Threatening

Abstract Background Invasive pulmonary aspergillosis (IPA) is a life-threatening opportunistic infection which usually occurs in immunocompromised patients. Recommended duration of voriconazole therapy is a minimum of 6-12 weeks for IPA, despite the lack of any firm evidence. In addition, risk factors for relapse of IPA are still unclear. Here, we explored risk factors for IPA relapse after initial treatment. Methods All patients with proven or probable IPA who had finished voriconazole treatment between 2005 and 2019 in a tertiary-care hospital were reviewed. IPA relapse was defined as re-diagnosis of proven or probable IPA at the same site within 1 year after treatment termination. Short course of voriconazole treatment was defined as a treatment less than 9 weeks, which is a median of the recommended minimum duration of therapy from the Infectious Disease Society of America. The radiological response was defined as a reduction in IPA burden by more than 50% on chest computed tomography (CT). Results Of 87 patients who had completed voriconazole treatment, 14 (16.1%) experienced IPA relapse. Multivariable Cox regression identified that short voriconazole treatment duration (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.1–12.3; P=0.033) and radiological non-response (aHR, 4.6; 95% CI, 1.2–17.5; P=0.026) were independently associated with relapse of IPA after adjusting for several clinical risk factors. Conclusion Less improvement in CT, and short duration of voriconazole therapy were the independent risk factors for relapse after treatment of IPA. Longer duration of therapy should be considered for those at higher risk of relapse. Disclosures All Authors: No reported disclosures

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OP0133 THE PREVALENCE AND RISK FACTORS OF RETINAL TOXICITY ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.328 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 77-78

Author(s):

S. Do ◽

J. H. Du ◽

J. X. An ◽

J. Wang ◽

A. Lin

Keyword(s):

Risk Factors ◽

Cumulative Dose ◽

Daily Intake ◽

Retinal Toxicity ◽

Factors Associated ◽

Duration Of Therapy ◽

Increased Risk ◽

Hydroxychloroquine Retinopathy ◽

Risk Of Retinopathy

Background:Hydroxychloroquine (HCQ) is commonly used for the treatment of various autoimmune diseases. The medication is generally well-tolerated. However, long-term use after 5 years may increase the risk of retinopathy. One study in 2014 has demonstrated the risk can be as high as 7.5%. Optical Coherence Tomography (OCT) has become a major modality in screening retinopathy.Objectives:To evaluate the prevalence of retinal toxicity among patients using hydroxychloroquine and to determine various risk factors associated with hydroxychloroquine-associated retinal toxicity.Methods:We performed a retrospective chart review on a cohort of adult patients with long-term use (≥ 5 years cumulative) of HCQ between January 1st, 2011 to December 31st, 2018 from the Kaiser Permanente San Bernardino County and Riverside medical center areas in Southern California, USA. Patients were excluded if they had previously been diagnosed with retinopathy prior to hydroxychloroquine use, were deceased, or had incomplete OCT exam. Our primary endpoint was the prevalence of patients who developed retinal toxicity detected by OCT, and later confirmed by retinal specialist. Potential risk factors (age, duration of therapy, daily consumption per actual body weight, cumulative dose, confounding diseases and medication) for developing retinopathy were also evaluated. Univariable and multivariable logistic regression analyses were used to determine risk factors associated with retinal toxicity.Results:Among 676 patients exposed to more than 5 years of HCQ, the overall prevalence of retinal toxicity was 6.8%, and ranged from 2.5% to 22.2% depending on the age, weight-based dosing, duration of use and cumulative dose. Duration of therapy for 10 years or more increased risk of retinopathy by approximately 5 to 19 folds. Similarly, weight-based dose of 7 mg/kg/day or greater was assciated with increased risk of retinopathy by approximately 5 times. Patients with cumulative dose of 2000 grams or more had greater than 15 times higher risk of developing retinopathy. Duration of use for10 years or more (odd ratio 4.32, 95% CI 1.99 – 12.49), age (odd ratio 1.04; 95% CI 1.01 - 1.08), cumulative dose of more than 1500 g (odd ratio 7.4; 95% CI 1.40 – 39.04) and atherosclerosis of the aorta (odd ratio 2.59; 95% CI, 1.24 – 5.41) correlated with higher risk of retinal toxicity.Conclusion:The overall prevalence of retinopathy was 6.8%. Regular OCT screening, especially in patients with hydroxychloroquine use for more than 10 years, daily intake > 7 mg/kg, or cumulative dose > 1500 grams is important in detecting hydroxychloroquine-associated retinal toxicityReferences:[1]Hobbs HE. Sorsby A, & Freedman A. Retinopathy Following Chloroquine Therapy. The Lancet. 1959; 2(7101): 478-480.[2]Levy, G. D., Munz, S. J., Paschal, J., Cohen, H. B., Pince, K. J., & Peterson, T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: 1997; 40(8): 1482-1486.[3]Ding, H. J., Denniston, A. K., Rao, V. K., & Gordon, C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2016; 55(6): 957-967.[4]Stelton, C. R., Connors, D. B., Walia, S. S., & Walia, H. S. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clinical rheumatology. 2013; 32(6): 895-898.[5]Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B., & Mieler, W. F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123(6): 1386-1394.[6]Melles, R. B., & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014; 132(12): 1453-1460.Disclosure of Interests:None declared

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Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective?

Prostate Cancer and Prostatic Diseases ◽

10.1038/pcan.2012.26 ◽

2012 ◽

Vol 15 (4) ◽

pp. 380-385

Author(s):

S B Stewart ◽

C D Scales ◽

J W Moul ◽

S D Reed

Keyword(s):

Cost Effective ◽

Duration Of Therapy

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2054. Hospital-initiated Antibiotics in Nursing Homes

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1734 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S692-S692

Author(s):

Jon P Furuno ◽

Brie N Noble ◽

Vicki Nordby ◽

Bo Weber ◽

Jessina C McGregor ◽

...

Keyword(s):

Nursing Homes ◽

Hospital Setting ◽

Antibiotic Prescribing ◽

Administration Route ◽

Electronic Health Record Data ◽

For Profit ◽

Duration Of Therapy ◽

Record Data ◽

One Year ◽

The One

Abstract Background Nursing homes (NHs) are required by the Centers for Medicare and Medicaid Services to maintain antimicrobial stewardship programs. Hospital-initiated antibiotics may pose a barrier to optimizing antibiotic prescribing in this setting. Our objective was to characterize hospital-initiated antibiotic prescriptions among NH residents. Methods We collected electronic health record data on antibiotic prescribing events within 60 days of residents’ admission to 17 for-profit NHs in Oregon, California, and Nevada between January 1, and December 31, 2017. We characterized antibiotics prescribed, administration route, and proportion initiated in a hospital setting. Results Over the one-year study period, there were 4350 antibiotic prescribing events among 1633 NH residents. Mean (standard deviation) age was 77 (12) years and 58% were female. Approximately 45% (1,973/4,350) of antibiotics prescribed within 60 days of NH admission were hospital-initiated. The most frequently prescribed hospital-initiated antibiotics were cephalosporins (27%; 1st gen: 54%, 2nd gen: 6%, 3rd gen: 34%, 4th gen: 5%, 5th gen: 1%), fluoroquinolones (20%), and penicillins (14%; natural penicilins: 4%, semisynthetic penicillins: 3%, aminopenicillans: 57%, β-lactam/β-lactamase inhibitors: 21%, and antipseudomonal penicillins: 15%). Additionally, 24% of antibiotics were parenteral and the median (interquartile range) duration of therapy was 6 (3–10) days. Over 15% of residents with hospital-initiated antibiotics were readmitted to the hospital within 30 days. Conclusion Approximately 45% of antibiotic prescribing in a multistate sample of NHs were hospital-initiated, of which roughly 40% was broad-spectrum. Interventions specifically targeting antibiotic prescribing during and following the transition from hospitals to NHs are needed. Disclosures All authors: No reported disclosures.

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