Faculty Bibliography

OBJECTIVES/OBJECTIVE:To examine the in vitro selection of aztreonam/avibactam resistance among MBL-producing Klebsiella pneumoniae and to understand the mechanism of increased resistance. METHODS:The MICs of aztreonam were determined with and without avibactam (4 mg/L) using a broth microdilution method. Single-step and multi-step mutant selection was conducted on five MBL-producing K. pneumoniae strains, including two dual carbapenemase producers. Genomic sequencing and gene cloning were performed to investigate the mechanism of increased resistance. RESULTS:We examined the MICs for 68 MBL-producing K. pneumoniae isolates, including 13 dual carbapenemase producers. Compared with aztreonam alone, the addition of avibactam (4 mg/L) reduced the MICs for all isolates by >128-fold, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively. One NDM-1-, OXA-48-, CTX-M-15- and CMY-16-positive ST101 K. pneumoniae strain was selected to be resistant to aztreonam/avibactam, with a >16-fold increase in MIC (>128 mg/L). WGS revealed that the resistant mutants lost the blaNDM-1 gene, but acquired amino acid substitutions in CMY-16 (Tyr150Ser and Asn346His). Construction of blaCMY-16 mutants confirmed that the substitutions (Tyr150Ser and Asn346His) were primarily responsible for the decreased susceptibility to aztreonam/avibactam. In addition, transfer of blaCMY-16 mutant (Tyr150Ser and Asn346His) plasmid constructs into certain clinical carbapenemase-producing isolates demonstrated >64-fold increased MICs of aztreonam/avibactam and aztreonam/avibactam/ceftazidime. CONCLUSIONS:Aztreonam in combination with avibactam showed potent in vitro activity against MBL-producing K. pneumoniae. However, our study suggested the likelihood of aztreonam/avibactam resistance among MBL- and AmpC-co-producing strains and clinical practice should beware of the possibility of the emerging resistance.

BACKGROUND:Hepatosplenic T-cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step-up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated. AIMS/OBJECTIVE:To systematically characterise the association of HSTCL with biologic therapy for IBD. METHODS:We conducted a literature search and query of the Food and Drug Administration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti-TNF, anti-integrin, anti-interleukin 12/23). RESULTS:Sixty-two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28 years (range 12-81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab; all three also had anti-TNF and azathioprine/mercaptopurine exposure. Forty-three of 49 (87.8%) patients with known outcomes died with a median survival of 5 months. CONCLUSIONS:Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti-TNF exposure. These data suggest initiating a patient-centred discussion before starting anti-TNF therapy or other biologics.

Background/UNASSIGNED:Endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNA/FNB) has been traditionally used for making a tissue diagnosis. Several newer techniques are emerging as a viable alternative to EUS-FNA/FNB, including mucosal incision-assisted biopsy (MIAB), with a view to increasing the diagnostic yield for upper gastrointestinal (GI) subepithelial tumors (SETs). We conducted a systematic review and meta-analysis to describe the overall diagnostic yield of MIAB for upper GI SETs. Methods/UNASSIGNED:Multiple electronic databases (MEDLINE, EMBASE and Google Scholar) and conference abstracts were comprehensively searched. The primary outcome of our meta-analysis was the overall diagnostic yield of the MIAB. The secondary outcome was to study complications in terms of perforation and clinically significant bleeding. The meta-analysis was performed using a DerSimonian and Laird random-effect model. Results/UNASSIGNED:=57.43%) and no perforations were reported. Conclusions/UNASSIGNED:MIAB is a safe and effective technique for the diagnosis of upper GI SETs and can be considered as a viable alternative to EUS-FNA/FNB. MIAB can be performed during routine endoscopy and no advanced equipment is required.

BACKGROUND:The benefits of computed tomography pulmonary angiography (CTPA) for pulmonary embolism (PE) diagnosis must be weighed against its risks, radiation-induced malignancy, and contrast-induced nephropathy. Appropriate use of CTPA can be assessed by monitoring yield, the percentage of tests positive for PE. We identify factors that are associated low CTPA yield, which may predict overtesting. METHODS:This was a retrospective cohort study of six emergency departments between June 2014 and February 2017. The electronic health record was queried for CTPAs ordered for adult patients in the emergency department. We assessed the following patient factors: age, gender, body mass index, number of comorbidities, race, and ethnicity, provider factors: type (resident, fellow, attending, physician assistant) and environment factors: test time of day, season of visit, and crowdedness of the department. RESULTS:A total of 14,782 CTPAs were reviewed, of which 1366 were found to be positive for PE, resulting in an overall CTPA yield of 9.24%. Provider type was not associated with a difference in yield. Testing was less likely to be positive in younger patients, females, those with lower body mass indexes and those identifying as Asian or Hispanic. Testing was also less likely to be positive when ordered during the overnight shift and during the winter and spring seasons. CONCLUSION:Our study identified several patient and environmental factors associated with low CTPA yield suggesting potential targets for overtesting. Targeting education and clinical decision support to assist providers in these circumstances may meaningfully improve yields.

BACKGROUND:The development of guidelines for opioid prescribing, including those from the Society of Hospital Medicine and the Centers for Disease Control and Prevention, has been associated with changes in prescription patterns. However, many providers remain unaware of best practices surrounding appropriate opioid prescribing. METHODS:The research team implemented a multimodal quality improvement intervention, led by first-year medical students, designed to increase clinician adherence to current prescribing guidelines for patients discharged on opioids. This intervention included an awareness campaign, educational sessions for providers, and weekly performance feedback. RESULTS:A total of 4,993 discharges were identified in the baseline period and 4,811 discharges in the intervention period. During the baseline period, 12.3% of all patients discharged were discharged with opioid prescriptions vs. 11.4% during the intervention period (p = 0.165). Of these, approximately 60% were new opioid prescriptions during both periods (p = 0.991). The study's efforts were associated with a decrease in the percentage of patients discharged with opioid prescriptions longer than seven days (45.2% preintervention to 39.5% postintervention, p < 0.042); an increase in the percentage of patients with follow-up appointments within seven days of discharge (38.6% to 65.9%, p = 0.001); and an increase in documentation of prescription history obtained from the state Prescription Monitoring Program registry (32.5% to 39.7%, p = 0.042). CONCLUSION/CONCLUSIONS:This intervention provided a successful framework to engage learners in improving opioid prescribing practices. The results are promising, but the experiences highlight the significant effort and resources needed to change prescriber practices, potentially limiting sustainability.

Despite the rapid increase in the number of persons with dementia (PWD) receiving home health care (HHC), little is known of HHC services patterns to PWD of varied backgrounds, including language preference other than English. Analyzing data of 12,043 PWD from an urban home health agency, we found on average PWD received 2.48 skilled visits or 1.88-hour skilled care and 5.81 aide visits or 24.13-hour aide care weekly. Approximately 63% of the skilled visits were from nurses. More non-English preferred PWD received aide visits, compared to English preferred PWD (44% vs. 36%). The type and intensity of HHC services were associated with language preference; when stratified by insurance, non-English preference was still significantly associated with more HHC aide care. Our study indicated that HHC services (both type and amount) varied by language preference and insurance type as an indicator of access disparities was a significant contributor to the observed differences.