scholarly journals 105. Impact of a Multiplex Polymerase Chain Reaction Panel on Duration of Empiric Antibiotic Therapy in Suspected Bacterial Meningitis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S65-S66
Author(s):  
Justin J Choi ◽  
Lars Westblade ◽  
Lee S Gottesdiener ◽  
Kyle Liang ◽  
Han A Li ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Bacterial Meningitis ◽  
Antibiotic Therapy ◽  
Panel Member ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Empiric Antibiotic Therapy ◽  
Research Support ◽  
Review Panel ◽  
Empiric Antibiotic

Abstract Background Multiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing community-acquired meningitis and encephalitis (ME). However, the clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized. Methods We performed a retrospective pre-post study to evaluate the implementation of the FilmArray ME panel (BioFire Diagnostics, LLC) for diagnosis of bacterial meningitis at our institution. We included adults who presented with suspected bacterial meningitis, received empiric antibiotic therapy, and underwent cerebrospinal fluid microbiological testing in the emergency department. The primary outcome was duration of empiric antibiotic therapy. A bivariable analysis that compared baseline demographics, clinical characteristics, and study outcomes between the pre-ME panel and post-ME panel periods was performed using Mann-Whitney tests, chi-squared tests, or Fisher’s exact tests. Time-to-event analysis used the Kaplan-Meier method and log-rank statistics. Results In the pre-ME panel period, the positive detection rate of bacterial pathogens was 2.2% (3/137) by cerebrospinal fluid culture and 4.3% (3/69) in the post-ME panel period. Table 1 shows baseline characteristics of patients. Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (median 34.7 h, IQR 8.5–61.7, vs. 12.3 h, IQR 3.3–40.0, P=0.01), time to targeted therapy (59.3 h, IQR 36.5–74.6, vs 7.02 h, IQR 0.9–12.4, P< 0.001), and hospital length of stay (4 d, IQR 2–7, vs. 3 d, IQR 1–5, P=0.03), as shown in Table 2. There was also significant reduction in time to discontinuation or de-escalation of empiric antibiotic therapy (P=0.049) as shown in Figure 1. Table 1. Baseline characteristics for patients with suspected bacterial meningitis Table 2. Antimicrobial use and hospitalization outcomes Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (P=0.01), time to targeted therapy (P<0.001), and hospital length of stay (P=0.03). Figure 1. Probability of Empiric Antibiotic Therapy Between Pre- and Post-ME Panel Periods Kaplan-Meier analysis of the time from initiation of empiric antibiotic therapy to discontinuation or de-escalation of empiric antibiotic therapy between the pre- and post-ME panel periods. P value from log-rank test=0.049 (n=206). There was a significant difference in the time to discontinuation or de-escalation of empiric antibiotic therapy between the groups (sex- and immunosuppressant use-adjusted hazard ratio, 1.46 [95% confidence interval, 1.08–1.97]; P=0.01). Conclusion The implementation of the FilmArray ME panel for suspected bacterial meningitis appears to reduce the duration of empiric antibiotic therapy, time to targeted therapy, and hospital length of stay compared to traditional culture-based microbiological testing methods. Disclosures Justin J. Choi, MD, Allergan (Consultant, Grant/Research Support)Roche (Consultant, Grant/Research Support) Lars Westblade, PhD, Accelerate Diagnostics Inc (Grant/Research Support)BioFire Diagnostics (Grant/Research Support)Hardy Diagnostics (Grant/Research Support)Roche (Consultant, Advisor or Review Panel member)Shionogi Inc (Advisor or Review Panel member)Talis Biomedical (Advisor or Review Panel member) Marshall J. Glesby, MD, Enzychem (Consultant)Gilead (Grant/Research Support)ReAlta Life Sciences (Consultant)Regeneron (Consultant, Grant/Research Support)Sobi (Consultant)Springer (Other Financial or Material Support, Royalties)UpToDate (Other Financial or Material Support, Royalties)

scholarly journals Impact of a multiplex polymerase chain reaction panel on duration of empiric antibiotic therapy in suspected bacterial meningitis

2021 ◽  
Author(s):  
Justin J Choi ◽  
Lars F Westblade ◽  
Lee S Gottesdiener ◽  
Kyle Liang ◽  
Han A Li ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Antibiotic Therapy ◽  
Multiplex Pcr ◽  
Hospital Length ◽  
Clinical Impact ◽  
Hospital Length Of Stay ◽  
Empiric Antibiotic Therapy ◽  
Chain Reaction ◽  
Empiric Antibiotic ◽  
Polymerase Chain

Abstract Background Multiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing meningitis and encephalitis (ME). The clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized. Methods We performed a retrospective pre-post study at our institution that evaluated the clinical impact of a multiplex PCR ME panel among adults with suspected bacterial meningitis who received empiric antibiotic therapy and underwent lumbar puncture in the emergency department. The primary outcome was the duration of empiric antibiotic therapy. Results The positive pathogen detection rates were similar between pre- and post-multiplex PCR ME panel periods (17.5%, 24 of 137, vs. 20.3%, 14 of 69, respectively). The median duration of empiric antibiotic therapy was significantly reduced in the post-multiplex PCR ME panel period compared to the pre-multiplex PCR ME panel period (34.7 h vs. 12.3 h, P=0.01). At any point in time, 46% more patients in the post-multiplex PCR ME panel period had empiric antibiotic therapy discontinued or de-escalated compared to the pre-multiplex PCR ME panel period (sex- and immunosuppressant use-adjusted HR 1.46, P=0.01). The median hospital length of stay was shorter in the post-multiplex PCR ME panel period (3 d vs. 4 d, P=0.03). Conclusions The implementation of the multiplex PCR ME panel for bacterial meningitis reduced the duration of empiric antibiotic therapy and possibly hospital length of stay compared to traditional microbiological testing methods.

scholarly journals Antibiotics for Aspiration Pneumonia in Neurologically Impaired Children

2019 ◽  
Vol 15 (7) ◽  
pp. 395-402 ◽  
Author(s):  
Joanna Thomson ◽  
Matt Hall ◽  
Lilliam Ambroggio ◽  
Jay G Berry ◽  
Bryan Stone ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Length Of Stay ◽  
Aspiration Pneumonia ◽  
Health Information System ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Empiric Antibiotic Therapy ◽  
Gram Negative ◽  
Empiric Antibiotic ◽  
Icu Transfer

OBJECTIVE: To compare hospital outcomes associated with commonly used antibiotic therapies for aspiration pneumonia in children with neurologic impairment (NI). DESIGN/METHODS: A retrospective study of children with NI hospitalized with aspiration pneumonia at 39 children’s hospitals in the Pediatric Health Information System database. Exposure was empiric antibiotic therapy classified by antimicrobial activity. Outcomes included acute respiratory failure, intensive care unit (ICU) transfer, and hospital length of stay (LOS). Multivariable regression evaluated associations between exposure and outcomes and adjusted for confounders, including medical complexity and acute illness severity. RESULTS: In the adjusted analysis, children receiving Gram-negative coverage alone had two-fold greater odds of respiratory failure (odds ratio [OR] 2.15; 95% CI: 1.41-3.27), greater odds of ICU transfer (OR 1.80; 95% CI: 1.03-3.14), and longer LOS [adjusted rate ratio (RR) 1.28; 95% CI: 1.16-1.41] than those receiving anaerobic coverage alone. Children receiving anaerobic and Gram-negative coverage had higher odds of respiratory failure (OR 1.65; 95% CI: 1.19-2.28) than those receiving anaerobic coverage alone, but ICU transfer (OR 1.15; 95% CI: 0.73-1.80) and length of stay (RR 1.07; 95% CI: 0.98-1.16) did not statistically differ. For children receiving anaerobic, Gram-negative, and P. aeruginosa coverage, LOS was shorter (RR 0.83; 95% CI: 0.76-0.90) than those receiving anaerobic coverage alone; odds of respiratory failure and ICU transfer rates did not significantly differ. CONCLUSIONS: Anaerobic therapy appears to be important in the treatment of aspiration pneumonia in children with NI. While Gram-negative coverage alone was associated with worse outcomes, its addition to anaerobic therapy may not yield improved outcomes.

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
Charlotte-Paige M Rolle ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Dan Cruz ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Older Adults ◽  
Drug Interactions ◽  
Real World ◽  
Research Study ◽  
Panel Member ◽  
Median Number ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Hiv 1

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

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
Jadyn C Anderson ◽  
Amanda R Krueger ◽  
Elizabeth C Smith ◽  
Morgan L Bixby ◽  
Hunter V Brigman ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inhibitory Concentration ◽  
Panel Member ◽  
Colony Growth ◽  
The United States ◽  
Research Support ◽  
Review Panel ◽  
Agreement Rate ◽  
Future Studies ◽  
Agar Dilution

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

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 1465. Age-Dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children with Respiratory Syncytial Virus Infection (RSV) Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S734-S735
Author(s):  
Helena Brenes-Chacon ◽  
Cristina Garcia-Maurino ◽  
Melissa Moore-Clingenpeel ◽  
Sara Mertz ◽  
Fang Ye ◽  
...  
Keyword(s):  
Young Children ◽  
Disease Severity ◽  
Age Groups ◽  
Panel Member ◽  
Signs And Symptoms ◽  
Research Support ◽  
Review Panel ◽  
Viral Loads ◽  
Age Dependent ◽  
Rsv Infection

Abstract Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children < 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) < 3 months, (B) between 3 and 6 months, and (C) > 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children < 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-< 3, 3-6, and >6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (>3 months) than in inpatients (p< 0.01), while fever was more common in inpatients that outpatients (p< 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants >3 months, and higher RSV loads in children >6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

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)

Compliance With ATS-IDSA Guideline Recommendations for Empiric Antibiotic Therapy in Pneumonia

CHEST Journal ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 856A
Author(s):  
Kyle W. Bierman ◽  
Lee E. Morrow ◽  
Joshua D. Holweger ◽  
John T. Ratelle ◽  
Mark A. Malesker
Keyword(s):  
Antibiotic Therapy ◽  
Empiric Antibiotic Therapy ◽  
Empiric Antibiotic
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