Rezafungin is a novel echinocandin currently in phase 2 studies, differentiated by a long half-life that allows once-weekly dosing and a safety profile that allows higher doses. Several potential areas of use for rezafungin were identified.
Patients with chronic liver disease (CLD) have frequent exposure to Clostridium difficile infection (CDI) risk factors but the incidence and aetiology of CDI on this population is poorly understood. The aim of this study was to assess the incidence, disease presentation and outcomes of CDI in patients with underlying CLD. The Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) 2009 dataset was used to identify patients with CLD who developed CDI along with matched non-CLD patients with CDI. Using the NIS dataset, the incidence rate of CDI was 189.4/10 000 discharges in CLD patients vs. 83.7/10 000 discharges in the non-CLD matched cohort (P < 0.001). Compared with non-CLD, comorbidity-matched controls with CDI, CLD patients with CDI had higher likelihood of in-hospital mortality (8.8% vs. 18.6%, P < 0.001), increased length of stay by 1.19 days (P < 0.001) and increased total costs by $8632 (P < 0.001). In separate analyses using a tertiary case database of hospitalised patients in Houston, Texas (2006-2016) with CLD and CDI (n = 41) compared with patients with CDI but not CLD (n = 111), CLD patients had significantly higher Charlson comorbidity index (P < 0.0001) but similar risk factors for CDI and CDI-related disease presentation compared with non-CLD patients. In conclusion, CDI-related risk factors were almost universally present in the CLD population. CDI resulted in worse outcomes in this population.
Background Pharmacists with residency training in infectious diseases (ID) optimize antimicrobial therapy outcomes in patients and support antimicrobial stewardship (AS) programs. Although most ID residencies are accredited and assessed by certain standards, the degree to which these programs are similar is not known. Methods A 19-item, cross-sectional, multicentered, electronic survey was distributed via e-mail to pharmacy residency program directors (RPDs) of all 101 second-year postgraduate (PGY-2) ID residency programs in the United States. Results Survey responses were collected from 71 RPDs (70.3%); 64.8% were associated with an academic medical center and 97.2% focused primarily in adult ID. Rotations in the microbiology laboratory, adult AS, and adult ID consult were required in 98.6% of residency programs. Only 28.2% of responding programs required pediatric AS and pediatric ID consult rotations. Programs at academic medical centers were more likely to offer immunocompromised host ID consult (P = .003), pediatric ID consult (P = .006), and hospital epidemiology (P = .047) rotations but less frequently offered outpatient AS (P = .003), viral hepatitis clinics (P = .001), and travel medicine clinics (P = .007) rotations compared to programs at nonacademic medical centers. Residents were frequently involved in AS committees (97.2%), pharmacokinetic dosing of antimicrobials (83.1%), precepting pharmacy trainees (80.3%), and performing research projects (91.5%). Conclusions The PGY-2 ID pharmacy residency programs demonstrated consistency in required adult ID consult, antimicrobial management activities, committee service, and teaching and research opportunities. Pediatric experiences were less common. The PGY-2 ID residency programs prepare pharmacists to become antimicrobial stewards for adult patients.
Objectives Reduced in vitro β-lactam activity against a dense bacterial population is well recognized. It is commonly attributed to the presence of β-lactamase(s) and it is unknown whether the inoculum effect could be diminished by a β-lactamase inhibitor. We evaluated different β-lactam/β-lactamase inhibitor combinations in suppressing a high inoculum of ESBL-producing bacteria. Methods Three clinical isolates expressing representative ESBLs (CTX-M-15 and SHV-12) were examined. The impact of escalating β-lactamase inhibitor (tazobactam or avibactam) concentrations on β-lactam (piperacillin or ceftazidime) MIC reduction was characterized by an inhibitory sigmoid Emax model. The effect of various dosing regimens of β-lactam/β-lactamase inhibitor combinations was predicted using %T>MICi and selected exposures were experimentally validated in a hollow-fibre infection model over 120 h. The threshold exposure to suppress bacterial regrowth was identified using recursive partitioning. Results A concentration-dependent reduction in β-lactam MIC was observed (r2 ≥0.93). Regrowth could be suppressed in all six experiments using %T>MICi ≥73.6%, but only one out of six experiments below the threshold (P = 0.015). The exposures to suppress regrowth might be attained using the clinical dose of avibactam, but a much higher dose than the standard dose would be needed for tazobactam. Conclusions A dense population of ESBL-producing bacteria could be suppressed by an optimized dosing regimen of selected β-lactam/β-lactamase inhibitor combinations. The reversibility of enzyme inhibition could play an important role in diminishing the inoculum effect. In vivo investigations to validate these findings are warranted.
With the large number of ID-related articles published each year, it can be challenging to stay current with the most relevant ID publications. This review of significant publications in 2016 may provide a starting point for that process.
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