The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain \u3e10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy

Antibiotic Review: Focus on Older Adults

Learning Objectives: Discuss spectrum of activity of antimicrobials commonly prescribed to geriatric patients. Review antimicrobial adverse reactions and drug interactions that occur in the geriatric population. Determine appropriate antimicrobial dosing recommendations for geriatric patients

Penicillin Allergy Assessment and Skin Testing in the Outpatient Setting

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may be appropriately prescribed when necessary for future infections. While allergists have primarily been responsible for PST in the outpatient setting, there is an increasing role for pharmacist involvement in the process. This review highlights the importance of penicillin allergy assessments, considerations for PST in the outpatient setting, education and advocacy for patients and clinicians, and the pharmacist’s role in outpatient PST

Impact of a Hospital’s Antibiotic Stewardship Team on Fluoroquinolone Use at a Long- Term Care Facility

The primary objective of this study was to assess whether a hospital-based antimicrobial stewardship team (H-AST) from an unaffiliated hospital could decrease inappropriate fluoroquinolone use at a local, long-term care facility (LTCF). The H-AST created a multi-faceted intervention campaign that included antibiogram development, provider and family education, and a telephone hotline. Pre- and post-intervention mean defined daily doses per 1000 resident days for antimicrobials were calculated to determine the impact of the campaign. The campaign resulted in a 38.70% decrease in ciprofloxacin utilization, a 16.20% decrease in total FQ consumption, and an 11.68% in total antibiotic consumption. In addition, during the study period the rate of Clostridium difficile infection decreased by 19.47%. Collaboration with a H-AST had a positive impact on antibiotic prescribing at this LTCF

Longitudinal Change in Common Impairments in Children with Cerebral Palsy from age 1.5 to 11 years

Purpose: This project aimed to determine if change occurs over time for impairments of balance, range of motion (ROM), endurance, and strength of children with cerebral palsy (CP), by Gross Motor Function Classification System (GMFCS) levels. Methods: Measurements were completed in 77 children at two sessions (T1, T2) on average 5.8 years apart. Mean ages were 2.9 years (SD .9) and 8.7 years (SD 1.1) at T1 and T2, respectively. Results: Significant differences were noted from T1 to T2 for some children (GMFCS levels I, II, and III/IV: balance increased, GMFCS levels I and II: strength increased, and GMFCS levels III/IV and V: ROM decreased). Endurance scores were not different. Endurance scores did not change. Conclusions: Longitudinal changes in most impairments occurred in children with CP. Monitoring and targeted interventions should support each child’s development

Antimicrobial Susceptibility Trends Observed in Urinary Pathogens Obtained From New York State

International guidelines recommend using local susceptibility data to direct empiric therapy for acute uncomplicated cystitis. We evaluated outpatient urinary isolate susceptibility trends in New York State. Nitrofurantoin had the lowest resistance prevalence whereas trimethoprim-sulfamethoxazole and fluoroquinolones had higher prevalences. This study highlights the need for local outpatient antimicrobial stewardship programs

Daptomycin-Nonsusceptible Vancomycin-Intermediate Staphylococcus aureus Vertebral Osteomyelitis Cases Complicated by Bacteremia Treated with High-Dose Daptomycin and Trimethoprim-Sulfamethoxazole

We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical isolates from the two patients were tested post hoc in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model to confirm the bactericidal activity and enhancement of daptomycin and trimethoprim-sulfamethoxazole. The combination of high-dose daptomycin and trimethoprim-sulfamethoxazole should be explored further for the treatment of DNS VISA strains.M.J.R. has received grant support, consulted for, or provided lectures for Astellas, Cubist, Forest, Clinical Therapeutics, Theravance, and Rib- X. L.M.A has served as an advisory board member (Forest) and provided lectures (Astellas) and owns stock (Merck). M.E.S., A.E.W., and M.H. have no potential conflicts of interest

Factors affecting the spatial and temporal distribution of E. coli in intertidal estuarine sediments

Funding: University of St Andrews, The James Hutton Institute. DMP received funding from the Marine Alliance for Science and Technology for Scotland (MASTS), funded by the Scottish Funding Council (grant reference HR09011).Microbiological water quality monitoring of bathing waters does not account for faecal indicator organisms in sediments. Intertidal deposits are a significant reservoir of FIOs and this indicates there is a substantial risk to bathers through direct contact with the sediment, or through the resuspension of bacteria to the water column. Recent modelling efforts include sediment as a secondary source of contamination, however, little is known about the driving factors behind spatial and temporal variation in FIO abundance. E. coli abundance, in conjunction with a wide range of measured variables, was used to construct models to explain E. coli abundance in intertidal sediments in two Scottish estuaries. E. coli concentrations up to 6 log10 CFU 100 g dry wt-1 were observed, with optimal models accounting for E. coli variation up to an adjusted R2 of 0.66. Introducing more complex models resulted in overfitting of models, detrimentally effected the transferability of models between datasets. Salinity was the most important single variable, with season, pH, colloidal carbohydrates, organic content, bulk density and maximum air temperature also featuring in optimal models. Transfer of models, using only lower cost variables, between systems explained an average deviance of 42 %. This study demonstrates the potential for cost-effective sediment characteristic monitoring to contribute to FIO fate and transport modelling and consequently the risk assessment of bathing water safety.PostprintPeer reviewe

Developmental Trajectories and Reference Percentiles for Range of Motion, Endurance, and Muscle Strength of Children With Cerebral Palsy.

BACKGROUND: Children with cerebral palsy (CP) frequently present with secondary impairments in spinal alignment and extremity range of motion, endurance for activity, and muscle strength. Creation of developmental trajectories for these impairments will help guide clinical decision-making. OBJECTIVE: For children in each level of the Gross Motor Function Classification System (GMFCS) this study aimed to: (1) create longitudinal developmental trajectories for range of motion (Spinal Alignment and Range of Motion Measures [SAROMM]), endurance (Early Activity Scale for Endurance [EASE]), and functional strength (Functional Strength Assessment [FSA]); and (2) develop age-specific reference percentiles and amount of change typical over 1 year for these outcomes. DESIGN: This study used a longitudinal cohort design. METHODS: Participants comprised 708 children with CP across GMFCS levels, aged 18 months up to the 12th birthday, and their families. In 2 to 5 assessments every 6 months over 2 years, trained therapists performed the SAROMM and FSA, and parents completed the EASE questionnaire. For children in each GMFCS level, longitudinal trajectories using linear and nonlinear mixed-effects models from all visits, and reference percentiles using quantile regression from the first, 12-month, and 24-month visits were created for each measure. RESULTS: Longitudinal trajectories and percentile graphs for SAROMM, FSA, and EASE were primarily linear, with different performance scores among GMFCS levels. There was much variability in both longitudinal trajectories and percentiles within GMFCS levels. LIMITATIONS: Limitations included a convenience sample and varying numbers of participants assessed at each visit. CONCLUSIONS: The longitudinal trajectories and percentile graphs have application for monitoring how children with CP are performing and changing over time compared with other children with CP. The resources presented allow therapists and families to collaboratively make decisions about intervention activities targeted to children\u27s unique needs

Longitudinal trajectories and reference centiles for the impact of health conditions on daily activities of children with cerebral palsy.

AIM: First, to describe the impact of health conditions on daily activities over time in children with cerebral palsy (CP) and to create age-specific reference centiles. Second, to determine the amount of change typical over a 1-year period, across Gross Motor Function Classification System (GMFCS) levels. METHOD: A prospective, cohort design, with five assessments over 2 years, involved 708 children with a confirmed diagnosis of CP participating in the On Track Study (396 males, 312 females; mean age 6y [SD 2y 7mo]; range 18mo-12y at first assessment; 32.1% in GMFCS level I, 22.7% in GMFCS level II, 11.2% in GMFCS level III, 18.2% in GMFCS level IV, 15.7% in GMFCS level V). The impact of health conditions on daily activities was assessed using the Child Health Conditions Questionnaire. Data were analyzed using mixed-effects models and quantile regression. RESULTS: Linear longitudinal trajectories describe the relatively stable impact of health conditions over time for each functional level for children aged 2 years to 12 years, with the lowest scores (least impact) in GMFCS level I and the highest scores (highest impact) in GMFCS level V. Centiles were created for children in each GMFCS level. A system to interpret the magnitude of change over time in centiles was developed. INTERPRETATION: Longitudinal trajectories of co-occurring health conditions assist with understanding children\u27s prognoses. Centiles assist in understanding a child\u27s experience relative to children in similar GMFCS levels. Guidelines are provided to determine if children are progressing \u27as expected\u27, \u27better than expected\u27 or \u27more poorly than expected\u27 in regard to the impact of health conditions on daily activities. WHAT THIS PAPER ADDS: For children with cerebral palsy, the mean impact of health conditions on daily activities is relatively stable. Significant intraindividual and interindividual variability for the impact of health conditions exists, which complicates prognosis. Centiles enable interpretation of the impact of health conditions relative to Gross Motor Function Classification System level