Hospital admissions and mortality due to complications of injection drug use in two hospitals in Regina, Canada: retrospective chart review.

BACKGROUND: Infectious complications of injection drug use (IDU) often require lengthy inpatient treatment. Our objective was to identify the number of admissions related to IDU in Regina, Canada, as well as describe patient demographics and comorbidities, yearly mortality, readmission rate, and cumulative cost of these hospitalizations between January 1 and December 31, 2018. Additionally, we sought to identify factors that increased risk of death or readmission. METHODS: This study is a retrospective chart review conducted at the two hospitals in Regina. Eligible study cases were identified by querying the discharge database for predetermined International Classification of Diseases code combinations. Electronic medical records were reviewed to assess whether each admission met inclusion criteria, and hospitalization and patient data were subsequently extracted for all included admissions. Mortality data were gleaned from hospital and Ministry of Health databases. Data were analyzed using Excel and IBM SPSS Statistics to identify common comorbidities, admission diagnoses, and costs, as well as to compare patients with a single admission during the study period to those with multiple admissions. Logistic regression analysis was used to identify the relationship between individual variables and in- and out-of-hospital annual mortality. RESULTS: One hundred and forty-nine admissions were included, with 102 unique patients identified. Common comorbidities included hepatitis C (47%), human immunodeficiency virus (HIV) (25%), and comorbid psychiatric disorders (19%). In 23% of all admissions, patients left hospital prior to treatment completion, and 27% of patients experienced multiple admissions. Female patients and those with chronic pain were more likely to be readmitted (p = 0.024 and p = 0.029, respectively). Patients admitted with infective endocarditis were more likely to die during hospitalization (p = 0.0001). The overall mortality was 15% in our cohort. The estimated cumulative cost of inpatient treatment of complications of IDU in Regina was $3.7 million CAD in 2018. CONCLUSION: Patients with history of IDU and hospital admission experience high mortality rates in Regina, a city with paucity of inpatient supports for persons who use injection drugs. Needle syringe programs, opioid agonist therapy, and safe consumption sites have been shown to improve outcomes as well as reduce healthcare costs for this patient population. We will use our findings to advocate for increased access to these harm reduction strategies in Regina, particularly for inpatients.

Synthesis of 4-methylumbelliferyl α-d-mannopyranosyl-(1→6)-ß-d-mannopyranoside and development of a coupled fluorescent assay for GH125 exo-α-1,6-mannosidases.

Certain bacterial pathogens possess a repertoire of carbohydrate processing enzymes that process host N-linked glycans and many of these enzymes are required for full virulence of harmful human pathogens such as Clostridium perfringens and Streptococcus pneumoniae. One bacterial carbohydrate processing enzyme that has been studied is the pneumococcal virulence factor SpGH125 from S. pneumoniae and its homologue, CpGH125, from C. perfringens. These exo-α-1,6-mannosidases from glycoside hydrolase family 125 show poor activity toward aryl α-mannopyranosides. To circumvent this problem, we describe a convenient synthesis of the fluorogenic disaccharide substrate 4-methylumbelliferone α-d-mannopyranosyl-(1→6)-ß-d-mannopyranoside. We show this substrate can be used in a coupled fluorescent assay by using ß-mannosidases from either Cellulomonas fimi or Helix pomatia as the coupling enzyme. We find that this disaccharide substrate is processed much more efficiently than aryl α-mannopyranosides by CpGH125, most likely because inclusion of the second mannose residue makes this substrate more like the natural host glycan substrates of this enzyme, which enables it to bind better. Using this sensitive coupled assay, the detailed characterization of these metal-independent exo-α-mannosidases GH125 enzymes should be possible, as should screening chemical libraries for inhibitors of these virulence factors.

Selective trihydroxyazepane NagZ inhibitors increase sensitivity of Pseudomonas aeruginosa to ß-lactams.

AmpC ß-lactamase confers resistance to ß-lactam antibiotics in many Gram negative bacteria. Inducible expression of AmpC requires an N-acetylglucosaminidase termed NagZ. Here we describe the synthesis and characterization of hydroxyazepane inhibitors of NagZ. We find that these inhibitors enhance the susceptibility of clinically relevant Pseudomonas aeruginosa to ß-lactams.