Development and application of an antibiotic spectrum index for benchmarking antibiotic selection patterns across hospitals

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.Infect Control Hosp Epidemiol 2017;38:993–997</jats:p

Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/1/hae12119.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/2/hae12119-sup-0001-AppendixS1.pd

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD. Objectives: To identify disease-causingmutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD. Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis. Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P , 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEV1), compared with 75 age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.16Hz at 258C), but an abnormal, circular beat pattern. Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function

El desafío de la administración adecuada de antimicrobianos en pediatría.

Background: Antibiotics are among the drugs most commonly prescribed to children in hospitals and communities. Unfortunately, a great number of these prescriptions are unnecessary or inappropriate. Antibiotic abuse and misuse have several negative consequences, including drug-related adverse events, the emergence of multidrug resistant bacterial pathogens, the development of Clostridium difficile infection, the negative impact on microbiota, and undertreatment risks. In this paper, the principle of and strategies for paediatric antimicrobial stewardship (AS) programs, the effects of AS interventions and the common barriers to development and implementation of AS programs are discussed. Discussion: Over the last few years, there have been significant shortages in the development and availability of new antibiotics; therefore, the implementation of strategies to preserve the activity of existing antimicrobial agents has become an urgent public health priority. AS is one such approach. The need for formal AS programs in paediatrics was officially recognized only recently, considering the widespread use of antibiotics in children and the different antimicrobial resistance patterns that these subjects exhibit in comparison to adult and elderly patients. However, not all problems related to the implementation of AS programs among paediatric patients are solved. The most important remaining problems involve educating paediatricians, creating a multidisciplinary interprofessional AS team able to prepare guidelines, monitoring antibiotic prescriptions and defining corrective measures, and the availability of administrative consensuses with adequate financial support. Additionally, the problem of optimizing the duration of AS programs remains unsolved. Further studies are needed to solve the above mentioned problems. Conclusions: In paediatric patients, as in adults, the successful implementation of AS strategies has had a significant impact on reducing targeted- and nontargeted-antimicrobial use by improving the quality of care for hospitalized patients and preventing the emergence of resistance. Considering that rationalization of antibiotic misuse and abuse is the basis for reducing emergence of bacterial resistance and several clinical problems, all efforts must be made to develop multidisciplinary paediatric AS programs in hospital and community settings

Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study.

BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody® , is effective for treating aTTP episodes and is well tolerated. OBJECTIVES AND METHODS In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after cessation of daily TPE. RESULTS Thirty-one patients (placebo, n = 28; caplacizumab, n = 3) had an exacerbation during double-blind treatment. Twenty-eight patients switched to open-label caplacizumab (placebo, n = 26; caplacizumab, n = 2); the three others discontinued upon exacerbation. Median time to platelet count response (≥150 x 109 /L) was 3.49 days upon receiving caplacizumab. There were no deaths. During open-label treatment, further exacerbation or a major thromboembolic event (vena cava thrombosis) was experienced by one patient (3.6%) each. Consistent with the double-blind phase, the most frequent treatment-emergent adverse events were catheter site hemorrhage (28.6%), headache (21.4%), and epistaxis (17.9%). CONCLUSIONS These results suggest that caplacizumab was efficacious and well tolerated in patients with aTTP who experienced a disease exacerbation during double-blind treatment in HERCULES

Utilization of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list (listserv) by healthcare professionals

Optimizing pediatric antimicrobial stewardship is challenging. In this retrospective study, we evaluated 515 original e-mails to 482 members of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative electronic mailing list ([email protected]). The plurality of threads discussed clinical practice guidelines, and pharmacists were most likely to initiate and respond. Representation was geographically diverse within and outside the United States

Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis.

The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, TTP exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired TTP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at www.clinicaltrials.gov as #NCT01151423 and #NCT02553317