Total Duration Of Therapy Research Articles

Long-Term Effects of Iron Chelating Agents on Ocular Function in Patients with Thalassemia Major.

BackgroundThe aim of this study is to evaluate eye structures and function in patients receiving iron chelating therapy and to assess whether a correlation exists between the onset of ocular alterations and the intake of iron chelating drugs.MethodsA prospective cohort study was performed. Eighty-eight patients, composed of children and adults with thalassemia major (TM) who are taking or had taken iron chelating drugs (deferoxamine, deferiprone or deferasirox), have been initially enrolled in the study. The final sample featured 80 patients, including 18 children and 62 adults. These subjects received an eye examination to evaluate intraocular pressure (IOP), best corrected visual acuity (BCVA), the presence of refractive defects, cornea, anterior chamber, lens, fundus oculi, visual field and mean retinal nerve fiber layer (RNFL) thickness. Logistic regression model analysis was performed in order to assess any correlation. In addition, a literature search regarding the relation between iron chelating drugs and ocular adverse events was carried out to compare the results obtained with the evidence in the literature.ResultsLogistic regression did not report a significant correlation between the intake of iron chelating drugs and the onset of anterior ocular segment alterations, lens opacities, retinal diseases, optical neuropathies, astigmatism, visual field and RNFL thickness defects. Logistic regression returned a statistically significant correlation between myopia and iron chelation therapy (p-value 0.04; OR 1.05) and also between presbyopia and total duration of therapy with deferoxamine (p-value 0.03; OR 1.21). Although intraocular pressure levels remained within the normal range, a significant correlation with the length of deferoxamine therapy has been found (p-value 0.002; association coefficient −0.12). A negative correlation between deferiprone and presbyopia has also been observed.ConclusionIron chelation therapy is not associated with severe visual function alterations. Limitation of deferoxamine treatment can help prevent ocular complications. Deferiprone and/or deferasirox may be preferable, especially in patients over age 40 years.

Timing for Step-Down Therapy of Candidemia in Non-Neutropenic Patients: An International Multi-Center Study.

BackgroundCandida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival.MethodWe performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon, Spain and the United States, to assess the duration of IV therapy and appropriate time to step-down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down.ResultsCandida albicans contributed to 45% of bloodstream infection versus 55% of infection caused by Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU, whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. Forty-five patients were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step-down was 5 days. Patients who had a stepdown had more favorable outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1–4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75).ConclusionOur data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step-down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.

STUDY ON REDUCTION OF MICROALBUMINURIA AMONGST HYPERTENSIVE PATIENTS WITH USE OF TRIPLE COMBINATION THERAPY (TRIPLIXAM)

Objective: Persistent microalbuminuria is earliest indicator of Chronic Kidney Disease amongst hypertensive patients and is also associated with target organ damage resulting in stroke, retinopathy and adverse cardiovascular outcomes. The present study was aimed to evaluate the reduction in microalbuminuria amongst uncontrolled essential hypertensive patients with use of triple combination therapy. Design and method: It was a hospital based cross sectional prospective study done on 50 essential hypertension patients having uncontrolled blood pressure and presence of microalbuminuria in urine. Total duration of therapy was 3 months and triple combination therapy used in study as antihypertensive was Triplixam (Perindopril 4 mg, Amlodipine 5 mg and Indapamide 1.25 mg). Patients having Diabetes and other co morbidities were excluded from the study. Patients were evaluated at baseline and end of study visit for SBP,DBP, Urine for albumin excretion. Ethical clearance was taken prior to inclusion of patients. Results: There was significant reduction in both SBP (18 mm Hg) and DBP (10 mm Hg) with use of triple combination therapy (Triplixam). Microalbuminuria turned to normal albumin excretion in urine that was statistically significant (p &lt; 0.01) was most significant and convincing finding. Conclusions: Triplixam is an excellent triple agent that can reduce blood pressure promptly and bring about reduction in urine albumin excretion thereby decreasing risk of end target organ damage. Early detection of renal dysfunction through microalbuminuria and prompt treatment can confer future protection from end stage renal disease.

Duration of antibiotic therapy in systemic lupus erythematosus patients with hospital-acquired bacterial pneumonia in eastern China.

To investigate the duration of antibiotic therapy and its influencing factors in treating systemic lupus erythematosus (SLE) patients with hospital-acquired bacterial pneumonia (HABP). Clinical data of SLE patients with HABP from January 2015 to December 2019 were collected. Duration of antibiotic treatment and its correlations with the severity of pneumonia, status of SLE and the time to clinical stability (TCS) were analysed. A logistic regression model was performed to screen the risk factors influencing the total antibiotic treatment course >7 days. Three hundred and forty-four patients were finally enrolled in the study and the mean duration of total antibiotic therapy was 9.5 days. The TCS was related to the duration of antibiotic therapy (R2 =0.76, P<0.0001). More patients with multidrug-resistant pathogen infection and Candida colonization were found in the total duration >7 days group. SLE disease activity index (SLEDAI) [odds ratio (OR) =5.52, 95% confidence interval (CI): 3.59-7.28], taking immunosuppressants during HABP treatment (OR =5.29, 95% CI: 3.93-7.09) and multidrug-resistant pathogen infection (OR =4.91, 95% CI: 1.45-6.87) were greatly impacted risk factors (P<0.05, respectively). The duration of antibiotic therapy in SLE patients with HABP was longer than the course recommended by practice guidelines. The severity of the disease and the host's immune status might influence the duration of treatment.

Impact of an Antimicrobial Stewardship Program-bundled initiative utilizing Accelerate Pheno\u2122 system in the management of patients with aerobic Gram-negative bacilli bacteremia

PurposeGram-negative bacteria (GNB) are a leading cause of bloodstream infections (BSI) and management is complicated by antibiotic resistance. The Accelerate Pheno™ system (ACC) can provide rapid organism identification and antimicrobial susceptibility testing (AST).MethodsA retrospective, pre-intervention/post-intervention study was conducted to compare management of non-critically ill patients with GNB BSI before and after implementation of a bundled initiative. This bundled initiative included dissemination of a clinical decision algorithm, ACC testing on all GNB isolated from blood cultures, real-time communication of results to the Antimicrobial Stewardship Program (ASP), and prospective audit with feedback by the ASP. The pre-intervention period was January 2018 through December 2018, and the post-intervention period was May 2019 through February 2020.ResultsSeventy-seven and 129 patients were included in the pre-intervention and post-intervention cohorts, respectively. When compared with the pre-intervention group, the time from Gram stain to AST decreased from 46.1 to 6.9 h (p < 0.001), and the time to definitive therapy (TTDT) improved from 32.6 to 10.5 h (p < 0.001). Implementation led to shorter median total duration of antibiotic therapy (14.2 vs 9.5 days; p < 0.001) and mean hospital length of stay (7.9 vs 5.3 days; p = 0.047) without an increase in 30-day readmissions (22.1% vs 14%; p = 0.13).ConclusionImplementation of an ASP-bundled approach incorporating the ACC aimed at optimizing antibiotic therapy in the management GNB BSI in non-critically ill patients led to reduced TTDT, shorter duration of antibiotic therapy, and shorter hospital length of stay without adversely affecting readmission rates.

Evaluation of intravenous to oral antimicrobial switch at a hospital with a tightly regulated antimicrobial stewardship program.

Timely intravenous (IV) to oral antimicrobial switch (IV-oral-switch) is a key antimicrobial stewardship (AMS) strategy. We aimed to explore concordance with IV-oral-switch guidelines in the context of a long-standing, tightly regulated AMS program. Data was retrospectively collected for 107 adult general medical and surgical patients in an Australian hospital. Median duration of IV antimicrobial courses before switching to oral therapy was 3 days (interquartile range [IQR] 2.25-5.00). Timely IV-oral-switch occurred in 57% (n = 61) of patients. The median delay to switching was 0 days (IQR 0 to 1.25). In most courses (92/106, 86.8%), the choice of oral alternative after switching was appropriate. In 45% (47/105) of courses, total duration of therapy (IV plus oral) exceeded the recommended duration by >1.0 day. Excessive IV antimicrobial duration was uncommon at a hospital with a tightly regulated AMS program. Total duration of therapy was identified as an AMS target for improvement.

Abbreviated (8 hours) versus Traditional (24 hours) Postpartum MgSO4 Prophylaxis in Severe Preeclampsia: A Randomised Control Trial

Introduction: Preeclampsia is a multisystem disorder affecting pregnancy after 20 weeks of gestation featured by hypertension and proteinuria. Magnesium Sulphate (MgSO4) has been used for 24 hours following delivery to prevent eclampsia in patients with severe preeclampsia. Aim: To determine the need to continue magnesium sulphate therapy 8 hours following delivery. Materials and Methods: The double blinded randomised controlled study was performed in the Department of Gynaecology and Obstetrics at R.G. Kar Medical College, Kolkata, West Bengal, India, from 1st July 2015 to 30th June 2016. Total 90 patients with severe preeclampsia were randomised in two group. In group A MgSO4 was discontinued 8 hours following delivery (abbreviated group) and in the group B it was continued for 24 hours following delivery (traditional group). The primary objective of study was to determine the need to continue MgSO4 therapy 8 hours following delivery. Secondary objectives were monitoring time by doctors, nursing care time, postpartum ambulation time, duration of urinary catheterisation, minor complication like urinary tract infection, duration and total dose of MgSO4 therapy. In order to calculate statistical significance of the different variables in between two groups, Student’s independent sample’s t-test was used for normally distributed numerical values and Chi-square test or Fischer’s-exact test was used for unpaired proportion data. Results: In abbreviated group, the number of patients (n=1) who did not need to continue MgSO4 therapy beyond 8 hours following delivery as safety measures were statistically significant (p-value &lt;0.0001) in comparison to traditional group. Total duration and dose of MgSO4 therapy were significantly less (p-value &lt;0.0001) in the abbreviated group. There was statistically significant reduction in time from delivery to postpartum ambulation and duration of indwelling urinary catheter in the abbreviated group. Conclusion: The abbreviated (8 hours) regime of postpartum MgSO4 for seizure prophylaxis is a suitable alternative to the traditional (24 hours) regime.

1461. Impact of the Ampicillin/Sulbactam Shortage on Antibiotic Prescribing and Clinical Outcomes for Adult Inpatients with Aspiration Pneumonia

BackgroundAmpicillin/sulbactam is a recommended first-line agent for the treatment of aspiration pneumonia. Due to the ampicillin/sulbactam shortage, beginning in March 2019, alternative therapies, such as ceftriaxone plus metronidazole, have been utilized more frequently. The objective of this study is to examine clinical outcomes in adult inpatients treated with either ampicillin/sulbactam or ceftriaxone/metronidazole for aspiration pneumonia.MethodsAn electronic health record report identified patients ≥18 years of age that received ampicillin/sulbactam (pre-March 2019) or ceftriaxone/metronidazole (post-March 2019) with the indication of aspiration pneumonia. The primary objective was to describe 30-day all-cause readmission rates for patients that received ampicillin/sulbactam compared to ceftriaxone/metronidazole. The secondary objectives included hospital length of stay (LOS), 30-day all-cause mortality, C.difficile infection (CDI) within 3 months, and total antibiotic costs.ResultsA total of 86 patients (50 received ampicillin/sulbactam and 36 received ceftriaxone/ metronidazole) were included. Demographics were similar between groups. There was no significant difference in 30-day all-cause readmission rates (30% vs 19%, p=0.322). The ampicillin/sulbactam group, however, was found to have a significantly higher rate of 30-day all-cause mortality (12% vs 0%, p=0.038). Additionally, total duration of therapy was found to be significantly shorter in the ampicillin/sulbactam group (5 vs 7 days, p=0.002) with reduced overall cost of therapy($130 vs $235, p< 0.001). No differences were observed in hospital LOS or CDI within 3 months.ConclusionNo difference was observed in 30-day all-cause readmissions in patients receiving ampicillin/sulbactam compared to ceftriaxone/metronidazole for the treatment of aspiration pneumonia. Further analyses are recommended to evaluate the impact on 30-day all-cause mortality.Disclosures All Authors: No reported disclosures

68. Impact of a Pharmacy-Driven Antimicrobial Time-out on Duration of Therapy in Community-Acquired Pneumonia

BackgroundCommunity-Acquired Pneumonia (CAP) is associated with substantial antibiotic use and potential for overprescribing. Previous studies have demonstrated a reduction in antimicrobial exposure following implementation of provider-driven antimicrobial time-outs (ATOs). ATOs prompt assessment of appropriateness of therapy, clinical response, and duration of therapy. In January 2018, OSF Healthcare System implemented a 48-hour pharmacy-driven ATO in the electronic health record. The purpose of this study was to determine if the implementation of the ATO decreased the duration of antibiotic therapy for CAP at a community hospital.MethodsThis was a retrospective chart review of adults hospitalized with CAP at OSF Saint Anthony Medical Center between May 2016 - October 2017 (pre-implementation; PRE) and April 2018 - September 2019 (post-implementation; POST). The primary outcome was total duration of antibiotic therapy between hospitalization and discharge prescriptions. Secondary outcomes included hospital length of stay (LOS), duration of IV therapy, and rates of treatment failure, relapse, and antibiotic-associated adverse events.ResultsA total of 808 patient charts were reviewed with 155 patients meeting inclusion criteria in both study groups. The mean duration of antibiotic therapy was reduced by 2.14 days (PRE 10.51 days vs. POST 8.37 days; P< 0.001). Duration of IV therapy (3.86% vs. 3.21%; P< 0.001) and 30-day emergency department visit rate (16.13% vs. 3.23%; P< 0.001) were also significantly reduced. Differences in LOS (4.60 days vs. 4.45 days; P=0.279) and 30-day readmission rate (9.03% vs. 4.52%; P=0.114) did not meet statistical significance. Antibiotic-associated diarrhea (28.39% vs. 17.42%; P=0.022) and acute kidney injury (17.42% vs. 6.45%; P=0.003) were significantly reduced while C. difficile infection (2.58% vs. 0.65%; P=0.371) and treatment failure (3.22% vs. 1.94%; P=0.723) only trended downward.ConclusionImplementation of the pharmacy-driven ATO was associated with reduced duration of antibiotic therapy in patients hospitalized with CAP, though total durations still exceeded evidence-based recommendations. The ATO maintained the efficacy of treatment and reduced treatment-associated adverse effects, such as diarrhea and AKI.Disclosures All Authors: No reported disclosures

723. Epidemiology, Risk Factors, and Treatment Considerations for Pyogenic Liver Abscess (PLA) in the Calgary Health Zone (CHZ) Revisited: A Population-Based Study

BackgroundPLA is a significant cause of morbidity and mortality. However, its epidemiology and outcomes have not been recently evaluated in the CHZ. Understanding current trends will help guide management.MethodsIn this population-based study, we evaluated epidemiology, risk factors, and treatment of patients with PLA in the CHZ. CHZ residents aged ≥ 20 years diagnosed with PLA in 2015-2017 were included. Charts were reviewed for demographics and clinical outcomes. Multivariate logistic regression was used to determine factors associated with 30-day mortality. Findings were compared to a previous assessment of PLA in the CHZ from 1999-2003 (Kaplan et al., 2004).ResultsA total of 136 patients with PLA were identified, representing an annual incidence rate of 3.7 cases per 100,000 population. Compared to 1999-2003, incidence of PLA was increased (2.3 per 100,000; p< 0.01) but mortality was similar (1999-2003: 0.22 per 100,000 vs. 2015-2017: 0.26 per 100,000; p=0.6). The most common culprit organisms were Streptococcus anginosus group (40%), Klebsiella species (25%), Escherichia coli (18%), and obligate anaerobes (16%). Pathogen prevalence was similar to the prior cohort. Compared to 1999-2003, antibiotic resistant organisms were more frequent (8% vs 1%, p=0.04). In our cohort, liver aspirations were less frequent (p=0.02) but aspirate culture was more often positive (p< 0.01). The median duration of intravenous antibiotic therapy was longer compared to previous (2015-2017: 23 days (IQR 9-38) vs. 1999-2003: 17 days (IQR 10-29); p=0.001). Similarly, the total duration of antibiotic therapy was longer (2015-2017: 42 days (IQR 25-65) vs. 1999-2003: 31 days (IQR 18-45); p< 0.001). Thirty-day mortality from admission was 7% and did not differ amongst cohorts. Risk factors are shown in Table-1.Table-1: Risk factors for 30-day mortality in PLA ConclusionIncidence of PLA in the CHZ is rising with more antimicrobial resistance. Diagnostic liver aspirations are less frequent. Antibiotic durations are longer with no reduction in mortality. Understanding changing trends is valuable in directing future care. Encouraging liver aspirations to obtain a microbiologic diagnosis, especially with increasing resistance, is crucial. Considering shorter antibiotic durations in light of stable mortality warrants further exploration.Disclosures All Authors: No reported disclosures

64. Impact of a Duration Bundle on Antimicrobial Use in a Pediatric Hospital

BackgroundLimiting antibiotic durations to the shortest effective duration is a strong recommendation with moderate-quality evidence in the 2016 IDSA Antimicrobial Stewardship Program (ASP) guidelines. An ASP bundle including a decrease in antimicrobial automatic stop dates from 14 days to 10 days along with a guideline for standard durations for 48 specific indications was implemented at a tertiary pediatric hospital in November 2019. The purpose of this review and was to assess the impact of this ASP initiative on patient outcomes and hospital cost-savings by comparison of pre-intervention and post-intervention data.MethodsA set of antimicrobial duration recommendations for pediatric patients was created by the Antimicrobial Stewardship Program, Pediatric Hospital Medicine providers, and Infectious Disease providers specific to indication, agent, or pathogen. After education of medical care providers and distribution of the recommendations, automatic stop dates in the Electronic Medical Record (EMR) were updated from 14 days to 10 days for all antimicrobials. Concomitant advertising campaigns were shown on all hospital screensavers. Data were collected for a one month pre-intervention period of Nov.15 - Dec.15, 2018 including 133 patients and a one month intervention period of Nov.15 - Dec.15, 2019 including 125 patients.ResultsThe average length of stay decreased from an average of 8.3 days pre-implementation to 6.7 days (p=0.043) post implementation. The ratio of actual to recommended duration also decreased from 1.56 to 1.30 (p< 0.001) when comparing pre vs. post initiative. Balancing measures did not change for restarting treatment within 48 hours of stopping or readmission within 30 days for the same infection. The decrease in inpatient therapy translated to more than $10,000 per year in direct drug cost.ConclusionThis intervention lead to a significant reduction in average length of stay per admission and significantly reduced the secondary outcomes of the total duration of antimicrobial therapy and the ratio of actual duration compared to recommended duration. This lead to cost savings and decreased inappropriate antibiotic exposure.Disclosures All Authors: No reported disclosures

175. Impact of Infectious Diseases Pharmacist Interventions on Appropriateness of Antibiotics Prescribed at Hospital Discharge

BackgroundHospital discharge is an important opportunity for antimicrobial stewardship. Despite inpatient stewardship efforts, antibiotics ordered at discharge are frequently prescribed inappropriately. Discharge antibiotic therapy may be too broad or narrow in spectrum, inappropriately dosed, or for an unnecessarily long duration. The purpose of this study was to assess the inappropriateness of antimicrobial prescribing on discharge and to measure the effect of infectious diseases pharmacist (IDP) intervention on antibiotics prescribed at discharge from the inpatient setting.MethodsAnalyses were completed before and after implementation of an IDP intervention at hospital discharge. IDPs were alerted to patients discharged on antimicrobial therapy for community-acquired pneumonia (CAP), skin and soft tissue infections (SSTIs), and urinary tract infections (UTIs). IDPs reviewed patient and laboratory data and made recommendations for modifications of antibiotics prior to patients leaving the hospital. Prescribing algorithms were created and used to standardize the assessment of discharge antibiotics using local antibiograms and IDSA guidelines. The primary outcome was the composite of appropriateness including antibiotic dose, duration, and spectrum. Secondary outcomes included appropriateness of the individual components of the primary outcome as well as the mean total duration of antibiotic therapy per disease state.ResultsA total of 77 patients were assessed during the study period occurring December 2019 through February 2020. Intervention increased the rate of appropriate prescribing for the composite of antibiotic dose, duration, and spectrum from 48.1% at baseline to 84.4% (P < 0.05). By subset, intervention increased the proportion of patients receiving antibiotics of appropriate duration from 59.7% at baseline to 85.7% (P < 0.001), and proportion of patients receiving antibiotics of appropriate spectrum from 90.9% at baseline to 100% (P < 0.05). The mean duration of therapy for CAP decreased by 0.6 days (6.8 vs 7.4 days, P < 0.05).ConclusionIDP intervention improved appropriateness of prescribing consistent with guideline recommendations and local antibiogram data.Disclosures All Authors: No reported disclosures

1154. Characterizing fungemic outcomes among adult inpatients at a community teaching hospital: a retrospective cohort study

BackgroundFungemia is among the highest causes of mortality and length of stay (LOS) within the inpatient setting. We aim to characterize outcomes in adult inpatients with fungemia at our institution.MethodsAdult inpatients with at least one positive blood culture with yeast between January 1st, 2017 and December 31st, 2018 were retrospectively identified via an electronic health record report. Outcome measurements were stratified into three categories: demographic, infectious, and antifungal-related.ResultsForty-five patients were identified for review. The mean age was 62 years (SD 16.8) while the prevalence of fungemia among men and women was comparable (48.9 versus 51.1%). Diabetes (24.4%) and past malignancy (22.2%) were among the top comorbidities. One in five patients received total parenteral nutrition at the time of positive blood culture results. Central lines were present in 66.7% of patients and were implicated as the source of infection in the majority of cases (31%). Intensive care unit (ICU) admission, 30-day mortality, and 30-day hospital readmission occurred in 66.7%, 24.4%, and 26.7% of patients, respectively. The median time to culture positivity and time to antifungal therapy after positive culture results were 42.5 (IQR 36.5 - 63) and 6.5 hours (IQR 2.75 - 12.5), respectively. Candida albicans was found to be the primary fungal pathogen identified among cases reviewed, isolated in 53.3% of patients. ID consultation occurred in 86.7% of cases. Caspofungin was the predominant empiric antifungal agent prescribed (50.8%). Median total duration of therapy was 14 days (IQR 11.5 - 19).ConclusionThis analysis successfully identified key high-risk areas of attention in the clinical management of adult inpatients with fungemia at our institution. Central lines and ICU admission were predominant characteristics identified, suggesting the complexity of the management of these patients. Although 30-day mortality and readmission rates were found to mirror current national averages for this population, further risk-assessment of these outcomes would be appropriate to evaluate in a larger study cohort.Disclosures All Authors: No reported disclosures

1369. The Spectrum of Chronic Osteomyelitis in Children

BackgroundWhile the majority of pediatric osteomyelitis cases are acute in nature, a significant subset present with prolonged symptoms often associated with substantial morbidity. Little data exist to guide clinicians in the management of these infections. We sought to describe the epidemiology, clinical features and management of chronic osteomyelitis in children.MethodsWe reviewed hospital admissions with an ICD10 code for chronic osteomyelitis from 2011-2018 at Texas Children’s Hospital. Cases were included if symptoms lasted >28 days on presentation. Patients diagnosed with chronic recurrent multifocal osteomyelitis were excluded. Cases were classified as those 1) associated with a contiguous focus (CoF), 2) penetrating or open trauma, 3) orthopedic hardware (OH), 4) post-acute chronic osteomyelitis (PACO, those occurring after >28 days of therapy for acute osteomyelitis) and 5) primary hematogenous chronic osteomyelitis (PHCO, those with 28 days of symptoms without other clear risk factors).Results114 cases met inclusion criteria. The median patient age is 11.8 years and 35.9% patients had underlying comorbidities. 83% of patients underwent a surgical procedure. Cases were diverse in terms of pathogenesis (Figure 1). A microbiologic etiology was identified in 72.8% of cases and was polymicrobial in 20.2% of cases; Staphylococcus aureus was the single most common etiology (Figure 2). CoF infection was more often associated with polymicrobial etiology with or without Pseudomonas (P< 0.001) and disease of the foot. PACO was caused by S. aureus in 95% of cases (p< 0.001, Figure 3). The overall median duration of total therapy was 210 days. 41% were discharged from hospital on OPAT with or without later transition to oral antibiotics. 26.3% of patients had persistent functional limitations at time of last follow-up of which 46% experienced repeat hospital admission/surgery. There was no association between duration of intravenous therapy and persistent functional limitations.Figure 1. Categories of Chronic Osteomyelitis Figure 2. Microbiology of Pediatric Chronic Osteomyelitis Figure 3. Clinical Features of Pediatric Chronic Osteomyelitis ConclusionChildren with chronic osteomyelitis are diverse both in terms of pathogenesis and microbiology. Pathogenesis and clinical presentation can provide clues to microbiologic etiology. Prolonged intravenous therapy does not appear to improve functional outcomes in chronic osteomyelitisDisclosures Jonathon C. McNeil, MD, Allergan (Research Grant or Support, Allergan provided ceftaroline powder for use in studies described in this abstract)

Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM Group report

The purpose of our study was to investigate the efficacy of an acute lymphoblastic leukemia (ALL)-type treatment with moderate-dose, prophylactic cranial irradiation and without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). From April 1990 to March 1995, 105 evaluable patients, 1.1 to 16.4 years of age, with T-LBL were enrolled in study NHL-BFM 90 (non-Hodgkin's lymphoma-Berlin-Frankfurt-Munster 90). They received an 8-drug induction over 9 weeks followed by an 8-week consolidation including methotrexate (MTX) 5 g/m(2) x 4. Patients with stage I (n = 2) and II (n = 2) continued with maintenance therapy (6-mercaptopurine daily and MTX weekly, both orally) until a total therapy duration of 24 months. Patients with stage III (n = 82) and IV (n = 19) received an 8-drug intensification over 7 weeks and cranial radiotherapy (12 Gy for prophylaxis) after consolidation, followed by maintenance. Residual tumor after induction had to be resected. Patients received intensified chemotherapy if tumor regression on day 33 of induction was less than 70% or when vital residual tumor was present after the complete induction phase. With a median follow-up of 4.5 years, the estimated event-free survival at 5 years is 90% (95% confidence interval, 82%-100%). Events were 1 early death, 8 tumor failures, and 1 secondary acute myeloid leukemia. A total of 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to less than 70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. We conclude that, with intensive ALL-type chemotherapy including moderate cumulative doses of anthracyclines 240 mg/m(2) and cyclophosphamide (3 g/m(2)) and moderate-dose prophylactic cranial irradiation but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. (Blood. 2000;95:416-421)

Sequential Intravenous to Oral Proteasome Inhibitor Based Regimens for the Treatment of Newly Diagnosed Multiple Myeloma Patients: A Real-World Study

Objective To assess in-class transition (iCT) from intravenous bortezomib-based induction to all-oral ixazomib-based treatment improving proteasome inhibitor-based continuous therapy with efficiency, safety and convenience in clinical practice. Methods In this real-world retrospective study from Chinese seven hospitals during Oct, 2017-Jul, 2020, we analysed newly diagnosed multiple myeloma (NDMM) patients without transplantation, who achieved at least partial response of bortezomib-based introduction, and then received ixazomib-based regimen for 2 years or until progression/intolerant toxicity. Primary endpoint: progression-free survival (PFS). Key endpoints included response rate, therapy duration and adverse event (AE). Results 96 patients were enrolled in this study (median age 61 years; 25% ≥ 65 years; 7% ≥ 75 years; 61% male; ISS stage I/II/III 10%/35%/55%; IgG/IgA/IgD/IgE/light chain /double clonal /non-secretory 50%/18%/2%/1%/26%/1%/2%). R-ISS stage was estimated in 85 patients (stage I/II/III 6%/78%/16%). 35% high risk(HR) (27/78) and 65% standard risk (SR)(51/78) were tested by metaphase fluorescence in situ hybridization (M-FISH) according to Mayo clinic risk stratification. 96 patients received median 5 cycles (2-12) of bortezomib-based regimen including VD1/VRD1/VTD1/VCD1/PAD1/PD2D1, and median 6 cycles (1-17) of iCT regimen including ID1/IRD1/ITD1/ICD1 (30/96,43/96,10/96,13/96), three-drug ixazomib-based regimens account for the majority (66/96). Median duration of total PI therapy was 11.3 months and of ixazomib-based regimen was 5.3 months. With 13 months median follow-up, 18-month progression free survival (PFS) rate was 87% (95% confidence interval,78-95) from the start of bortezomib-based induction and 82% (95% confidence interval,70-94) from the start of ixazomib-based treatment(Figure 1A), 79% patients remain on therapy at data cutoff. After bortezomib-based induction, overall response(ORR) rate was 100% (strict complete response [sCR], 10/96, 10%; complete response [CR], 31/96, 32%; very good partial response [VGPR], 24/96, 26%; partial response [PR], 31/96, 32%) and 88% (sCR 22/96, 23%; CR, 28/96, 29%; VGPR, 16/96, 17%; PR, 18/96, 19%) at data cutoff. There were 3 PR improved to VGPR, 4 VGPR improved to CR, 1 PR, 4 VGPR and 5 CR improved to sCR (Figure 1B). ORR of HR patients were 100% and 85%(23/27), 1 PR improved to VGPR, 1PR improved to CR, 4CR improved to sCR; ORR of SR patients were 100% and 85% (45/51), 2PR improved to VGPR, 5VGPR improved to CR, 4VGPR and 3CR improved to sCR, before and after ixazomib-based regimen, respectively. Among 66 patients who transited to IRD1/ITD1/ICD1 regimen, medium duration of total PI therapy was 11.0 months and of ixazomib-based regimen was 5.4 months, 77% patients remain on therapy. ORR rate was 100% (sCR, 7/66, 11%; CR, 16/66, 24 %; VGPR, 16/66, 24%; PR, 27/66, 41%) and 91% (sCR 15/66, 23%; CR, 18/66, 27%; VGPR, 9/66, 14%; PR, 18/66, 27%) at data cutoff, 3 PR improved to VGPR, 4PR and 6 VGPR improved to CR, 4 VGPR and 3 CR improved to sCR. ORR of HR (23/52) patients were 100% and 96%, ORR of SR patients (29/52)were 100% and 86% before and after ixazomib-based regimen, respectively. The ixazomib-safety profile was consistent with previous clinical trial data. In our study, 59% (57/96) of patients had any grade adverse events AE. In which, the most frequent grade &amp;lt;=2 AEs were peripheral neuropathy(PN) (31%, 31/96, PN of 23 patients began after bortezomib-based induction), nausea and vomiting (33%), diarrhea (5%), constipation (4%), incomplete intestinal obstruction (3%), fatigue (2%), edema (1%), abdominal distension (1%) , anorexia (1%), rash(1%) , weakness of lower limbs (1%). The most frequent grade 3/4 AEs were agranulocytosis (2%) , rash (2%), PN (2%, occurred after bortezomib-based induction). Treatment discontinued of ixazomib-based regimen are PN (6/96), incomplete intestinal obstruction (1/96), agranulocytosis (1/96), rash (2/96). Conclusion In real-world China MM population, NDMM patients are sensitive to PI-based continuous therapy with satisfied response rate; iCT can permit prolonged PI-based therapy with promising efficacy and tolerated adverse events. Note: VD1, VRD1, VTD1, VCD1, PAD1, PD2D1, IRD1, ITD1, ICD1 : I: ixazomib, R: lenalidomide, T: thalidomide, C: cyclophosphamide, V: bortezomib, D1: dexamethasone P: bortezomib, A: adriamycin D2: liposome doxorubicin Disclosures No relevant conflicts of interest to declare.

Feasibility study on pre or postoperative accelerated radiotherapy (POP-ART) in breast cancer patients

BackgroundIn early-stage breast cancer, the cornerstone of treatment is surgery. After breast-conserving surgery, adjuvant radiotherapy has shown to improve locoregional control and overall survival rates. The use of breast radiotherapy in the preoperative (preop) setting is far less common. Nevertheless, it might improve disease-free survival as compared to postoperative radiotherapy. There is also a possibility of downsizing the tumour which might lead to a lower need for mastectomy. There are some obstacles that complicate its introduction into daily practice. It may complicate surgery or lead to an increase in wound complications or delayed wound healing. Another fear of preop radiotherapy is delaying surgery for too long. At Ghent University Hospital, we have experience with a 5-fraction radiotherapy schedule allowing radiotherapy delivery in a very short time span.MethodsTwenty female breast cancer patients with non-metastatic disease receiving preop chemotherapy will be randomized between preop or postoperative radiotherapy. The feasibility of preop radiotherapy will be evaluated based on overall treatment time. All patients will be treated in 5 fractions of 5.7 Gy to the whole breast with a simultaneous integrated boost to the tumour/tumour bed of 5 × 6.2 Gy. In case of lymph node irradiation, the lymph node regions will receive a dose of 27 Gy in 5 fractions of 5.4 Gy. The total duration of therapy will be 10 to 12 days. In the preop group, overall treatment time is defined as the time between diagnosis and the day of last surgery, in the postop group between diagnosis and last irradiation fraction. Toxicity related to surgery, radio-, and chemotherapy will be evaluated on dedicated case-report forms at predefined time points. Tumour response will be evaluated on the pathology report and on MRI at baseline and in the interval between chemotherapy and surgery.DiscussionThe primary objective of the trial is to investigate the feasibility of preop radiotherapy. Secondary objectives are to search for biomarkers of response and toxicity and identify the involved cell death mechanisms and the effect of preop breast radiotherapy on the in-situ immune micro-environment.

126 Efficacy of Omadacycline in the Treatment of Acute Bacterial Skin and Skin Structure Infections in Patients With Cellulitis or Abscesses

Patients with acute bacterial skin and skin structure infections (ABSSSI) are often admitted for intravenous (IV) antibiotic administration. Omadacycline (OMC) is a novel aminomethylcycline antibiotic, approved for community-acquired bacterial pneumonia and ABSSSI, with activity against key causative pathogens, notably methicillin-susceptible (MSSA) and resistant (MRSA) Staphylococcus aureus. We report pooled results from a post-hoc analysis in patients with cellulitis/erysipelas or major abscesses who were not people who inject drugs (PWID), from the Omadacycline in Acute Skin and Skin Structure Infections (OASIS)-1 and -2 studies. Patients with ABSSSI were randomized to OMC or linezolid (LZD), both IV-to-oral, in OASIS-1 (NCT02378480); and to once-daily oral OMC or twice-daily oral LZD in OASIS-2 (NCT02877927). Total therapy duration was 7-14 days. Populations included modified intent-to-treat (mITT, randomized patients without a sole Gram-negative pathogen); and micro-mITT (mITT patients with ≥1 identified Gram-positive causative pathogen). Primary endpoint: early clinical response (ECR) in the mITT population (survival with ≥20% reduction in lesion size, 48-72 h after first dose, without rescue therapy). Secondary endpoint: survival with infection resolution/improvement at post-treatment evaluation in the mITT population (PTE; 7-14 days after last dose). Baseline characteristics were generally similar between groups. In the mITT population, 294 patients had cellulitis/erysipelas (148 OMC, 146 LZD); 146 patients had major abscesses (77 OMC, 69 LZD). In the micro-mITT population, S. aureus was the primary baseline pathogen, detected in 111 (76%) of patients with cellulitis/erysipelas and in 94 (76%) of patients with major abscesses (Table). MRSA was detected in 46 (41%) patients with cellulitis/erysipelas and in 56 (60%) patients with major abscesses. ECR was achieved in 117 (79%) patients receiving OMC and 115 (79%) receiving LZD with cellulitis/erysipelas, and in 70 (91%) patients receiving OMC and 61 (88%) receiving LZD with major abscesses; these results were similar for patients who presented at baseline with low/high white blood cell counts, fever, and lesion sizes ≤300 cm2 (Table). Success at PTE was comparable between OMC and LZD across groups. When analyzed by baseline pathogen, high clinical success at PTE was observed with both OMC and LZD in patients with S. aureus for both infection types (cellulitis/erysipelas and major abscesses; Table). There were no new safety signals; nausea and vomiting were the most frequent treatment-emergent adverse events across groups. OMC is a once-daily, IV or oral option for inpatient and outpatient treatment of ABSSSI in patients with cellulitis or major abscesses, including those due to MRSA.TableTreatment efficacy at ECR and PTE in patients with cellulitis/erysipelas or major abscesses from the OASIS-1 and OASIS-2 clinical trials (mITT and micro-mITT populations)Cellulitis/erysipelas (N=294)Major abscess (N=146)OmadacyclineLinezolidDifference (95% CI)OmadacyclineLinezolidDifference (95% CI)mITT, n1481467769Success at ECR; n/N (%)117/148 (79)115/146 (79)0.3% (−9.1, 9.7)70/77 (91)61/69 (88)2.5% (−7.8, 13.4)WBC count ≥10,000 cells/mm3 or ≤4000 cells/mm3, n/N (%)44/60 (73.3)43/55 (78.2)−4.8% (−20.4, 11.1)26/29 (89.7)22/27 (81.5)8.2% (−11.3, 28.4)Fever >38.0°C, n/N (%)35/39 (89.7)32/43 (74.4)15.3% (−1.7, 31.9)17/20 (85.0)15/16 (93.8)-8.8% (−31.6, 16.1)Lesion size 75–300 cm2, n/N (%)63/80 (78.8)58/77 (75.3)3.4% (−9.8, 16.7)50/55 (90.9)43/49 (87.8)3.2% (−9.3, 16.5)Success at PTE, n/N (%)135/148 (94)130/146 (90)4.1% (−2.4, 10.9)68/77 (87)58/69 (81)6.6% (−5.3, 18.9)WBC count ≥10,000 cells/mm3 or ≤4000 cells/mm3, n/N (%)57/60 (95.0)46/55 (83.6)11.4% (0.1, 24.1)24/29 (82.8)22/27 (81.5)1.3% (−19.6, 22.6)Fever >38.0°C, n/N (%)38/39 (97.4)40/43 (93.0)4.4% (−7.1, 16.5)19/20 (95.0)15/16 (93.8)1.3% (−18.9, 24.5)Lesion size 75–300 cm2, n/N (%)75/80 (93.8)69/77 (89.6)4.1% (−4.9, 13.8)50/55 (90.9)38/49 (77.6)13.4% (−0.6, 28.2)Micro-mITT, n64826756Success at PTE by S. aureus baseline pathogen*, n/N (%)48/51 (94)53/60 (88)44/52 (85)31/42 (74)*Success at PTE by MRSA baseline pathogen was achieved by 43/46 (93%) patients with cellulitis/erysipelas, and 42/56 (75%) patients with major abscesses; success at PTE by MSSA baseline pathogen was achieved by 59/66 (89%) patients with cellulitis/erysipelas, and 34/40 (85%) patients with major abscesses. Open table in a new tab

Patterns of Oral Antibiotic Use and Excess Duration at Hospital Discharge

Background: Antimicrobial stewardship (AMS) interventions have predominantly involved inpatient antimicrobial therapy. However, for many hospitalized patients, most antibiotic use occurs after discharge, and unnecessarily prolonged courses of therapy are common. Patient transition from hospitalization to discharge represents an important opportunity for AMS intervention. We describe patterns of antibiotic use selection and duration of therapy (DOT) for common infections including discharge antibiotics. Methods: This retrospective cross-sectional analysis was derived from an IRB-approved, multihospital, quasi-experiment at a 5-hospital health system in southeastern Michigan. The study population included patients discharged from an inpatient general and specialty practice ward on oral antibiotics from November 2018 through April 2019. Patients were included with the following diagnoses: skin and soft-tissue infections (SSTIs), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), respiratory viral infections, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), intra-abdominal infections (IAIs), and urinary tract infections (UTIs). Other diagnoses were excluded. Data were extracted from medical records including antibiotic indication, selection, and duration, as well as patient characteristics. Results: In total, 1,574 patients were screened and 800 patients were eligible for inclusion. The most common antibiotic indications were respiratory tract infections, with 487 (60.9%) patients. These included 165 AECOPD cases (20.6%) and 200 CAP cases (25%) with no multidrug resistant organism (MDRO) risk factors; 57 patients (7.1%) with MDRO risk factors; HAP in 7 patients (0.9%); and influenza in 58 patients (7.2%). Also, 205 (25.6%) patients were diagnosed with UTIs: 71 with cystitis (8.9%), 86 (10.8%) with complicated UTI (cUTI), and 48 (6%) with pyelonephritis. Furthermore, 125 patients (15.6%) were diagnosed with SSTI: 59 (7.4%) purulent and 66 (8.3%) nonpurulent. 31 (3.9%) patients had an IAI. The most commonly used antibiotics were cephalosporins in 536 patients (67%), azithromycin in 252 patients (31.5%), and fluroquinolones and tetracyclines in 231 patients (28.9%). Fluroquinolones were the most frequent antibiotic prescribed at discharge in 210 patients (26.3%). Figure 1 displays the average DOT relative to specific indications. The median duration of total antibiotic therapy exceeded institutional guideline recommendation for multiple conditions, including AECOPD (7 days vs recommended 5 days), CAP with COPD (8.3 vs 7 days ), CAP without COPD (7.7 vs 5 days), and pyelonephritis (11 vs 7–10 days). Also, 269 (33.6%) patients received unnecessary therapy; 218 (27.3%) of these were due to excess duration. Conclusions: Among a cross-section of hospitalized patients, the average DOT, including after discharge, exceeded the optimal therapy for many patients. Further understanding of patterns and influences of antibiotic prescribing is necessary to design effective AMS interventions for improvement.Funding: This work was completed under CDC contract number 200-2018-02928.Disclosures: None

506 Poster - Effect of the COVID-19 pandemic on use of bone-modifying agents for metastatic breast cancer in a UK Oncology centre

Background: Bone-modifying agents (BMAs) prevent skeletal-related events (SREs) in breast cancer patients with bone metastases. Our centre uses mainly zoledronic acid (ZA). Denosumab is permitted, due to its high cost, only with a documented indication such as renal failure. ASCO/CCO guidelines have responded to Phase 3 trial evidence showing non-inferiority of 12-weekly ZA compared to 3 or 4-weekly, which may reduce adverse events (AEs) and cost. We report on patterns of prescription in our centre and how it has changed due to COVID-19. Materials and methods: Data was retrospectively collected on patients who received BMAs in two separate three-month periods (Oct-Dec 2019 and Apr-Jun 2020, total n = 389) including choice of BMA, frequency of administration, concurrent systemic therapy, and incidence of SREs and AEs. We searched the electronic prescribing record, outpatient letters, radiotherapy record and blood tests for each patient. Results: Of the patients receiving BMAs in period one, 88% were on ZA and 13% on denosumab. Of those on denosumab, the majority (79%) had a documented indication, of which the most common (68%) was poor renal function. Mean total duration of BMA therapy was 22 months, during which 26% received radiotherapy to the bone. We found 3 cases of osteonecrosis of the jaw (ONJ), no osteonecrosis of the auditory canal (ANAC), and no atypical femoral fractures (AFF) out of the patients still receiving BMAs in period one. 32% experienced hypocalcaemia, defined as any reading below the laboratory reference range since starting BMA therapy. In period two, 11% fewer patients received BMAs. There was a large variation in intervals prescribed within period one (Table 1) and a marked shift thereafter. The percentage of patients on 12-weekly treatment rose from 45% to 66%. The change resulted in a saving of approximately £1300 in medication cost and 60 hours of nursing time. If all patients were on 12-weekly dosing, this could save approximately a further £2400 and 120 nursing hours per year. Hypocalcaemia occurred in 8.5% of patients during period one and 7.0% during period two.Tabled 1Period one N = 205Period two N = 183ZA88%84%Denosumab13%16%4-weekly24%6%6-weekly13%10%8-weekly17%18%12-weekly45%66%Other frequency2%0%Concurrent chemotherapy30%34% Open table in a new tab Conclusions: Despite strong evidence supporting use of 12 weekly ZA, local practice was slow to change. During COVID-19 it became necessary to minimise exposure of patients to hospital. This resulted in a rapid shift in practice; leading to reduced treatment burden, less hypocalcaemia, liberation of nursing time and cost saving in the COVID-19 period and beyond. No conflict of interest.