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Antimicrobial stewardship programs typically use days of therapy to assess antimicrobial use. However, this metric does not account for the antimicrobial spectrum of activity. We applied an antibiotic spectrum index to a population of very-low-birth-weight infants to assess its utility to evaluate the impact of antimicrobial stewardship interventions.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Antenna-pattern measurements obtained from a double-metal supra-terahertz-frequency (supra-THz) quantum cascade laser (QCL) are presented. The QCL is mounted within a mechanically micro-machined waveguide cavity containing dual diagonal feedhorns. Operating in continuous-wave mode at 3.5 THz, and at an ambient temperature of ~60 K, QCL emission has been directed via the feedhorns to a supra-THz detector mounted on a multi-axis linear scanner. Comparison of simulated and measured far-field antenna patterns shows an excellent degree of correlation between beamwidth (full-width-half-maximum) and sidelobe content and a very substantial improvement when compared with unmounted devices. Additionally, a single output has been used to successfully illuminate and demonstrate an optical breadboard arrangement associated with a future supra-THz Earth observation space-borne payload. Our novel device has therefore provided a valuable demonstration of the effectiveness of supra-THz diagonal feedhorns and QCL devices for future space-borne ultra-high-frequency Earth-observing heterodyne radiometers.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.
Standard metrics for antimicrobial use consider volume but not spectrum of antimicrobial prescribing. We developed an antibiotic spectrum index (ASI) to classify commonly used antibiotics based on activity against important pathogens. The application of this index to hospital antibiotic use reveals how this tool enhances current antimicrobial stewardship metrics.
We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.
Antimicrobial stewardship programs (ASPs) effectively optimize antibiotic use for inpatients; however, the extent of emergency department (ED) involvement in ASPs has not been described.
To determine current ED involvement in children’s hospital ASPs and to assess beliefs and preferred methods of implementation for ED-based ASPs.
A cross-sectional survey of 37 children’s hospitals participating in the Sharing Antimicrobial Resistance Practices collaboration was conducted. Surveys were distributed to ASP leaders and ED medical directors at each institution. Items assessed included beliefs regarding ED antibiotic prescribing, ED prescribing resources, ASP methods used in the ED such as clinical decision support and clinical care guidelines, ED participation in ASP activities, and preferred methods for ED-based ASP implementation.
A total of 36 ASP leaders (97.3%) and 32 ED directors (86.5%) responded; the overall response rate was 91.9%. Most ASP leaders (97.8%) and ED directors (93.7%) agreed that creation of ED-based ASPs was necessary. ED resources for antibiotic prescribing were obtained via the Internet or electronic health records (EHRs) for 29 hospitals (81.3%). The main ASP activities for the ED included production of antibiograms (77.8%) and creation of clinical care guidelines for pneumonia (83.3%). The ED was represented on 3 hospital ASP committees (8.3%). No hospital ASPs actively monitored outpatient ED prescribing. Most ASP leaders (77.8%) and ED directors (81.3%) preferred implementation of ED-based ASPs using clinical decision support integrated into the EHR.
Although ED involvement in ASPs is limited, both ASP and ED leaders believe that ED-based ASPs are necessary. Many children’s hospitals have the capability to implement ED-based ASPs via the preferred method: EHR clinical decision support.
To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.
Three-arm nonmasked randomized controlled trial.
Five academic medical centers in Southeastern Pennsylvania.
Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.
Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.
MAIN OUTCOME MEASURES
Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.
Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).
Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance
The costs of antimicrobial stewardship programs (ASPs) in children’s hospitals have not been described previously. We assessed ASP costs using an online survey administered to ASP leaders at U.S. children’s hospitals. ASP costs varied from $17,000 to $388,500 annually (median, $187,400). Overall costs were not correlated with hospital size.
Over the last twenty years political scientists and sociologists concerned primarily with western European developments since 1945 have attempted to define corporatism as an ideal model for use in analyzing this region's political economies. Several influential American historians in recent years have also employed the concept of corporatism in examining the development of the modern American political economy. Although these historians have not ignored the contemporary European-oriented social science literature, the relationship between the work of historians describing the evolution of America's political economy and the theoretical literature based primarily on more recent European experiences and European concerns remains problematic.
We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.
Infect. Control Hosp. Epidemiol. 2016;37(3):343–347
We analyzed the cost of antimicrobial prescribing across freestanding children’s hospitals. A few specific antimicrobials accounted for a large proportion of expenditures, and antimicrobial spending varied substantially across hospitals, even within specific clinical conditions. Antimicrobial stewardship programs should consider these data to incorporate high-value antimicrobial prescribing when clinically appropriate.
Infect Control Hosp Epidemiol 2015;36(10):1242–1244
To identify risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization.
Prospective cohort study conducted from January 1, 2010, through December 31, 2012.
Five adult and pediatric academic medical centers.
Subjects (ie, index cases) who presented with acute community-onset MRSA skin and soft-tissue infection.
Index cases and all household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as 2 consecutive sampling periods with negative surveillance cultures. Recurrent colonization was defined as any positive MRSA surveillance culture after clearance. Index cases with recurrent MRSA colonization were compared with those without recurrence on the basis of antibiotic exposure, household demographic characteristics, and presence of MRSA colonization in household members.
The study cohort comprised 195 index cases; recurrent MRSA colonization occurred in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36–84 days). Treatment with clindamycin was associated with lower risk of recurrence (odds ratio, 0.52; 95% CI, 0.29–0.93). Higher percentage of household members younger than 18 was associated with increased risk of recurrence (odds ratio, 1.01; 95% CI, 1.00–1.02). The association between MRSA colonization in household members and recurrent colonization in index cases did not reach statistical significance in primary analyses.
A large proportion of patients initially presenting with MRSA skin and soft-tissue infection will have recurrent colonization after clearance. The reduced rate of recurrent colonization associated with clindamycin may indicate a unique role for this antibiotic in the treatment of such infection.
Infect. Control Hosp. Epidemiol. 2015;36(7):786–793
Antimicrobial stewardship programs (ASPs) are a mechanism to ensure the appropriate use of antimicrobials. The extent to which ASPs are formally implemented in freestanding children's hospitals is unknown. The objective of this study was to determine the prevalence and characteristics of ASPs in freestanding children's hospitals.
We conducted an electronic survey of 42 freestanding children's hospitals that are members of the Children's Hospital Association to determine the presence and characteristics of their ASPs. For hospitals without an ASP, we determined whether stewardship strategies were in place and whether there were barriers to implementing a formal ASP.
We received responses from 38 (91%) of 42. Among responding institutions, 16 (38%) had a formal ASP, and 15 (36%) were in the process of implementing a program. Most ASPs (13 [81%] of 16) were started after 2007. The median number of full-time equivalents dedicated to ASPs was 0.63 (range, 0.1–1.8). The most common antimicrobials monitored by ASPs were linezolid, vancomycin, and carbapenems. Many hospitals without a formal ASP were performing stewardship activities, including elements of prospective audit and feedback (9 [41%] of 22), formulary restriction (9 [41%] of 22), and use of clinical guidelines (17 [77%] of 22). Antimicrobial outcomes were more likely to be monitored by hospitals with ASPs (100% vs 68%; P = .01), although only 1 program provided support for a data analyst.
Most freestanding children's hospitals have implemented or are developing an ASP. These programs differ in structure and function, and more data are needed to identify program characteristics that have the greatest impact.