scholarly journals 847. Trends in Stenotrophomonas maltophilia Antibiotic Resistance Rates

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S463-S464
Author(s):  
Aisling Caffrey ◽  
Emily T O’Neill ◽  
Haley J Appaneal ◽  
Vrishali Lopes ◽  
Kerry LaPlante
Keyword(s):  
Healthcare System ◽  
Stenotrophomonas Maltophilia ◽  
Panel Member ◽  
Positive Culture ◽  
Outpatient Setting ◽  
Medical Centers ◽  
Ocean Spray ◽  
Community Living Centers ◽  
Resistance Rates ◽  
Research Grant

Abstract Background Studies from the 1990’s and 2000’s identified increasing rates of Stenotrophomonas maltophilia, particularly among respiratory isolates and in intensive care populations. Additionally, resistance in S. maltophilia was found to be worsening. We aimed to quantify recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system. Methods We identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018, collected in either VA medical centers (VAMCs), community living centers (CLCs), or the outpatient (Outpt) setting. Multidrug resistance (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95% confidence intervals using Joinpoint Software. Results Over the 9-year study period, we identified 18,285 S. maltophilia cultures (57% VAMCs, 3% CLCs, 40% Outpt). S. maltophilia cultures made up 0.4% of all positive cultures in the VA. In VAMCs and CLCs, the number of S. maltophilia cultures decreased 5.1% and 8.5% per year, respectively. Alternatively, of all positive cultures in VAMCs, the proportion that were S. maltophilia increased significantly by 2.6% per year. SMX/TMP resistance decreased significantly by 8.5% (2010, 15%; 2018, 6%) per year in VAMCs, and decreased non-significantly by 8.7% (2010, 13%, 2018, 6%) per year in CLCs and 6.0% (2010, 12%; 2018, 7%) in the outpatient setting. No other significant changes in resistance were observed over the study period. MDR increased non-significantly by 1.2% per year. Conclusion While previous studies found increasing rates of S. maltophilia, the number of positive S. maltophilia cultures decreased in the national VA Healthcare System between 2010 and 2018. However, S. maltophilia is making up a greater proportion of positive culture over time. During the study period, resistance to SMX/TMP decreased and now more closely reflects previously reported resistance rates worldwide (0-10%). Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

scholarly journals 846. Trends in Acinetobacter baumanii Antibiotic Resistance Rates

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S463-S463
Author(s):  
Aisling Caffrey ◽  
Emily T O’Neill ◽  
Haley J Appaneal ◽  
Vrishali Lopes ◽  
Kerry LaPlante
Keyword(s):  
Healthcare System ◽  
Medical Center ◽  
Panel Member ◽  
Carbapenem Resistance ◽  
Acinetobacter Baumanii ◽  
Carbapenem Resistant ◽  
Ocean Spray ◽  
Control And Prevention ◽  
Resistance Rates ◽  
Research Grant

Abstract Background Carbapenem-resistant Acinetobacter baumannii is described as an urgent threat by the Centers for Disease Control and Prevention and several older studies have indicated increasing resistance in Acinetobacter. We sought to describe these trends in the national Veterans Affairs (VA) Healthcare System. Methods We assessed A. baumannii positive clinical cultures collected from VA patients (> 18 years) from 2010 to 2018. We categorized cultures based on location at the time of collection: VA medical center (VAMC), community living center (CLC), or outpatient (Outpt). Multidrug resistance (MDR) and extensive drug resistance (XDR) were defined as resistance to > 1 drug in > 3 or all of the following categories, respectively: extended-spectrum cephalosporins (es-CS), fluoroquinolones (FQ), aminoglycosides (AMG), carbapenems (CARB), piperacillin/tazobactam (PIP/TAZ), and ampicillin/sulbactam (AMP/SUL). Joinpoint Software was used for regression analyses of trends over time and to estimate annual average percent changes (AAPC) with 95% confidence intervals. Results We identified 19,376 A. baumannii positive cultures over the study period (53% VAMCs, 4% CLCs, 43% Outpts), which represented 0.5% of all positive cultures in the VA. In VAMCs, the number of A. baumannii cultures decreased significantly by 12.5% per year. Of all positive cultures in VAMCs, the proportion that were A. baumannii decreased significantly by 5.4% per year. Similar trends were observed in CLCs, while Outpt cultures remained stable. Over the 9-year study period, resistance decreased significantly, with MDR decreasing by 10.2% per year and XDR decreasing by 9.4%. Carbapenem resistance decreased significantly by 4.9% per year in VAMCs (2010, 39%; 2018 28%) and 11.3% in Outpts (2010, 12%; 2018, 6%). Similar annual significant decreases were observed with AMG (9.4%), es-CS (1.4%), and FQ (7.4%) in VAMCs; es-CS (2.7%) and FQ (5.6%) in CLCs; and AMG (9.5%) and FQ (8.2%) in Outpts. Conclusion In the national VA Healthcare System, the prevalence of A. baumannii is decreasing, as is the resistance previously observed with this organism. MDR A. baumannii still made up one-third of cultures in VAMCs and CLCs in 2018, and thus remains a treatment challenge. Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

scholarly journals 41. Impact of Discharge Antimicrobial Stewardship at an Academic Medical Center

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S142-S142
Author(s):  
Katie A Parsels ◽  
Wesley D Kufel ◽  
Jeni Burgess ◽  
Robert Seabury ◽  
Rahul Mahapatra ◽  
...  
Keyword(s):  
Antimicrobial Stewardship ◽  
Treatment Duration ◽  
Medical Center ◽  
Academic Medical Center ◽  
Panel Member ◽  
Outpatient Setting ◽  
Acceptance Rate ◽  
Inpatient Setting ◽  
Dose Selection ◽  
Research Grant

Abstract Background The Centers for Disease Control and Prevention estimates approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting and limited data describe AS interventions at hospital discharge. Acknowledging the potential for discharge AS, we used our existing resources to review discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy to potentially optimize antimicrobial therapy. Methods Discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious disease (ID) pharmacist, and recorded into the REDCap® data collection tool from September 1, 2020 to February 28, 2021 were evaluated retrospectively. Both adult and pediatric patients were included. The primary outcome was to identify the frequency a DRP was identified by an ID pharmacist while reviewing discharge antimicrobial prescriptions. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and the reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted. Results Of the 803 discharge antimicrobial prescriptions reviewed, at least one DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. The most common intervention categories included different antimicrobial duration, antimicrobial discontinuation, and different dose or frequency. At least one intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). When interventions to reduce the treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5 – 10) to 4 (0 – 5.5) days (P < 0.001). Conclusion ID pharmacist review of discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)

scholarly journals 550. Bamlanivimab and Casirivimab/Imdevimab Treatment Outcomes: Results from a Large Healthcare System’s Structured Implementation Experience

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S377-S378
Author(s):  
Christopher Polk ◽  
Anna Jacobs ◽  
Mindy Sampson ◽  
Michael Leonard ◽  
Leigh Ann Medaris ◽  
...  
Keyword(s):  
Healthcare System ◽  
Neutralizing Antibodies ◽  
Antibody Therapy ◽  
Panel Member ◽  
Neutralizing Antibody ◽  
Post Infusion ◽  
Ed Visits ◽  
Implementation Experience ◽  
Research Grant

Abstract Background Neutralizing antibody therapies targeting SARS-CoV-2 have been released for emergency use authorization by the FDA. Little is published on their real-world experience. In this retrospective study we share the results of our early experience on patient outcomes from use of these neutralizing antibodies within a large healthcare system. Methods We retrospectively analyzed results of a healthcare system wide program to pro-actively identify and treat COVID-19 patients with neutralizing antibody therapy. Results The 449 patients identified for SARS-CoV-2 neutralizing antibody therapy during the study period were retrospectively classified as falling in one of the three groups: untreated (199), bamlanivimab (87) and casirivimab/indevimab (125) treated patients (Table 1). Reasons identified patients were not treated most commonly were patient declined (n=74), unable to be contacted (n=36), out of treatment window (n=23), asymptomatic and feeling better (n=21) or did not have transportation (n=9). Bamlanivimab infusion did not reduce emergency room (ER) visits or hospitalization compared to untreated patient within 30-days of follow up (Table 2), and among all patients treated with antibody therapy only treatment with bamlanivimab and non-white race were predictors of need for hospitalization (Table 3). Casirivimab/indevimab did reduce subsequent ER visits or hospitalization within 30 days post-infusion when compared to the untreated group. However, patients treated with either antibody therapy had lower acuity of COVID-19 disease as reflected in need for intensive care unit (ICU) stay, mechanical ventilation or death (Table 2). Table 1. Characteristics of infused vs uninfused patients Table 2. Outcomes in treated vs untreated patients Table 3. Risk factors for ED visits or hospitalization in infused patients Conclusion Either neutralizing antibody therapy appears to markedly reduce acuity of COVID-19 disease even if patients do progress to requiring hospitalization. However, casirivimab/indevimab therapy also decreased ER visits and hospitalization suggesting better efficacy in our experience. Disclosures Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support) Mindy Sampson, MD, Regeneron (Grant/Research Support)

scholarly journals 1585. Stenotrophomonas maltophilia Infections and Approaches to Treatment

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S790-S790
Author(s):  
Aisling Caffrey ◽  
Haley J Appaneal ◽  
Vrishali Lopes ◽  
Kerry LaPlante
Keyword(s):  
Median Time ◽  
Stenotrophomonas Maltophilia ◽  
Hospital Admissions ◽  
Current Knowledge ◽  
Medical Center ◽  
Panel Member ◽  
Inpatient Mortality ◽  
Treatment Approaches ◽  
Antibiotic Drug ◽  
Research Grant

Abstract Background Current knowledge of the epidemiology of Stenotrophomonas maltophilia is limited to studies from several small international medical centers. Additionally, real-world approaches to treatment are not well described. Methods We included admissions to any Veterans Affairs (VA) medical center nationally, with positive S. maltophilia cultures collected from any culture site between January 2010 and April 2019. We reviewed epidemiologic factors of clinical characteristics and treatment. Treatment was assessed by mapping out all antibiotic exposures each day, and identifying differences (heterogeneity) in the antibiotics used and duration of their use. Results Over the study period, we identified 8,225 hospital admissions with positive S. maltophilia cultures. Patients were older (mean age 68.2 year) and male (97.6%), with 25.8% in the intensive care and 56.1% admitted from other healthcare settings. Respiratory cultures were most common (47.4%), followed by urine (21.4%), skin and soft tissue (17.4%), and blood (5.1%). Admissions were mostly 11 days long (median), with an inpatient mortality rate of 13.9%. The median time to culture collection from admission was day 3 of the hospitalization, and the median time to culture completion was 4 days. Changes in therapy occurred before culture completion for 67.3% of admissions. Most admissions utilized different treatment approaches (antibiotic drug and duration treatment heterogeneity 89.7%), with a median of 4 changes in therapy. Fluroquinolones were utilized in 40.6% of admissions (initiated median 4 days from admission) and sulfamethoxazole/trimethoprim in 26.3% (initiated median 7 days from admission). Inpatient mortality was significantly higher among those with changes in therapy versus those without changes (15.0% vs 5.7%, p< 0.0001), and among those without changes, mortality was significantly higher with monotherapy versus combination therapy (16.2% vs 2.6%, p< 0.0001). Conclusion Among more than 8,000 admissions with positive S. maltophilia cultures in the VA nationally, identification of the organism and targeted therapy did not occur until 4-7 days from admission. Differences in clinical outcomes were observed among the different treatment approaches. Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, PharmD, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

scholarly journals 57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S49-S50
Author(s):  
Bruce M Jones ◽  
Emily Plauche ◽  
Susan E Smith ◽  
Christopher M Bland
Keyword(s):  
Infectious Diseases ◽  
Health System ◽  
Community Health ◽  
Intervention Program ◽  
Primary Outcome ◽  
Panel Member ◽  
Penicillin Allergy ◽  
Secondary Outcome ◽  
Research Support ◽  
Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

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

scholarly journals 1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S739-S739
Author(s):  
Allison McGeer
Keyword(s):  
Pneumococcal Pneumonia ◽  
Herd Immunity ◽  
Panel Member ◽  
Population Based ◽  
Review Panel ◽  
Vaccine Type ◽  
Bacteremic Pneumococcal Pneumonia ◽  
Type Strains ◽  
Routine Infant ◽  
Research Grant

Abstract Background Herd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP). Methods The Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria. Results Since 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults.. Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia Conclusion Eight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP. Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

scholarly journals 66. Impact of a Pharmacist-Driven Azithromycin De-escalation Protocol for Community-Acquired Pneumonia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S52-S52
Author(s):  
Pegah Shakeraneh ◽  
Jeffrey Steele ◽  
Robert Seabury ◽  
Stephen J Thomas ◽  
Kristopher M Paolino ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Panel Member ◽  
Community Acquired Pneumonia ◽  
Hospital Length Of Stay ◽  
Post Intervention ◽  
Review Panel ◽  
Icu Patients ◽  
Significant Difference ◽  
Atypical Bacteria ◽  
Research Grant

Abstract Background Ceftriaxone and azithromycin are common empiric antibiotics for community-acquired pneumonia (CAP). Despite low suspicion for atypical infection, azithromycin is often continued for a full course. Negative laboratory data for atypical bacteria may assist with azithromycin de-escalation. Thus, a pharmacist-driven azithromycin de-escalation protocol was implemented for immunocompetent, non-intensive care unit (ICU) patients treated for CAP. The primary outcome was to compare azithromycin duration before and after protocol implementation. Secondary outcomes included hospital length of stay (LOS) and all-cause 30-day readmission. Methods This was a single-center, quasi-experimental study of hospitalized, non-ICU patients treated with azithromycin and a beta-lactam for CAP. The pre- and post-intervention cohorts were from 07/01/2018–04/30/2019 and 07/01/2019–04/30/2020, respectively. Patients were included if they were ≥18 years old, diagnosed with CAP, and had a negative Legionella pneumophila urinary antigen and negative nasopharyngeal swab PCR for Mycoplasma pneumoniae and Chlamydia pneumoniae. Patients were excluded if they were immunocompromised, admitted to an ICU, prescribed azithromycin for an alternative indication, or had evidence of atypical bacteria. Results After exclusion criteria were applied, 90 and 100 patients were included in the pre- and post-intervention cohorts, respectively. Demographic and clinical characteristics were mostly similar between cohorts. This initiative was associated with a statistically significant decrease in azithromycin duration (2 days (IQR 1–2.75) vs. 5 days (IQR 3–6), p < 0.001) and hospital LOS (3 days (IQR 2–5) vs. 5 days (IQR 3–8.25), p < 0.001). No statistically significant difference was observed for all-cause 30-day readmission (14 days (15.6%) vs 13 days (13.0%), p=0.614). Conclusion Implementation of a pharmacist-driven azithromycin de-escalation protocol for CAP was associated with reduced azithromycin duration and hospital LOS, but not all-cause 30-day readmission. Disclosures Jeffrey Steele, PharMD, Paratek Pharmaceuticals (Advisor or Review Panel member) Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)

scholarly journals 1484. Microbial Etiology of Community-acquired Pneumonia in Immunocompromised Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S743-S744
Author(s):  
Abhishek Deshpande ◽  
Pei-Chun Yu ◽  
Michael Rothberg
Keyword(s):  
Panel Member ◽  
Positive Culture ◽  
Empiric Therapy ◽  
Community Acquired Pneumonia ◽  
Immunocompromised Patients ◽  
Viral Pathogens ◽  
Chest X Ray ◽  
Microbial Etiology ◽  
Almost All ◽  
Immunocompetent Patients

Abstract Background Community-acquired pneumonia (CAP) is a leading cause of infection related mortality. Few studies have specifically evaluated the microbial etiology of CAP in immunocompromised patients. Using a large national inpatient database, we compared the microbial etiology of CAP in immunocompromised patients compared to immunocompetent patients. Methods We included adult patients admitted with pneumonia from 2010-2015 to 176 US hospitals participating in Premier. Patients were identified as having CAP if they had a chest X-ray and were on antimicrobials on the first day. Immunocompromised was defined by the receipt of immunosuppressive medications or ICD-9 codes for neutropenia/ hematological malignancy/ organ transplantation or comorbidities with AIDS. For microbial etiology, patients were included if they had a positive culture or test collected by hospital day 0 through 3. Patients with identical bacteria in blood and urine were excluded. Results A total of 168,159 patients had a diagnosis of CAP with a culture/test performed on first 3 days. A pathogen was detected in 18.8% of patients. Among pathogen positive patients, 4,851 patients were identified as immunocompromised and 26,752 as immunocompetent. Almost all patients (99%) had at least one culture, blood (96%) and respiratory (51%). Among patients who were immunocompromised, the most common bacterial pathogens (compared to immunocompetent patients) were, S. pneumoniae (17.7% vs 19.0%), MRSA (13.1% vs 14.4%), MSSA (12.0% vs 11.8%), P. aeruginosa (12.0% vs 9.9%), E. coli (7.4% vs 6.4%), K. pneumoniae (5.8% vs 4.9%), H. influenzae (5.5% vs 5.5%), M. pneumoniae (3.0% vs 3.0%) and L. pneumophila (0.93% vs 1.2%). Among viral pathogens, while the most common were influenza virus (12.9% vs 14.1%) followed by rhinovirus (1.5% vs 0.89%), immunocompromised patients has a higher prevalence of noninfluennza viruses (3.42% vs 2.43%). Conclusion In a large US inpatient sample, the causative organisms in immunocompromised patients did not differ much from those in immunocompetent patients. CAP pathogens in immunocompromised patients were more likely to involve gram-negative bacilli such as P.aeruginosa and E.coli, than gram-positive cocci. These findings may have implications when deciding on empiric therapy in these patients. Disclosures Abhishek Deshpande, MD, PhD, Ferring Pharmaceuticals (Advisor or Review Panel member)Merck (Consultant)

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