Opioid agonist treatment and risk of death or rehospitalization following injection drug use–associated bacterial and fungal infections: A cohort study in New South Wales, Australia

Thomas D. Brothers*, Dan Lewer, Nicola Jones, Samantha Colledge-Frisby, Michael Farrell, Matthew Hickman, Duncan Webster, Andrew Hayward, Louisa Degenhardt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background AU Injecting-related: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly bacterial and fungal infections are associated : with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Methods and findings Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants’ index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Conclusions Following hospitalizations with injection drug use–associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder.

Original languageEnglish
Article numbere1004049
JournalPLoS Medicine
Issue number7
Publication statusPublished - Jul 2022
Externally publishedYes

Bibliographical note

Funding Information:
TDB was supported by the Dalhousie University Internal Medicine Research Foundation Fellowship, Killam Postgraduate Scholarship, Ross Stewart Smith Memorial Fellowship in Medical Research and Clinician Investigator Programme Graduate Stipend (all from Dalhousie University Faculty of Medicine), a Canadian Institutes of Health Research Fellowship (CIHR-FRN# 171259), and through the Research in Addiction Medicine Scholars (RAMS) Program (National Institutes of Health/National Institute on Drug Abuse; R25DA033211) and the Fellow Immersion Training (FIT) Program in Addiction Medicine (National Institutes of Health/National Institute on Drug Abuse; R25DA013582). DL was funded by a National Institute of Health Research Doctoral Research Fellowship (DRF-2018–11-ST2-016). SC holds a Scientia PhD Scholarship from UNSW, Sydney and an Australian National Health and Medical Research Council (NHMRC) PhD Scholarship. LD is supported by an Australian National Health and Medical Research Council Senior Principal Research Fellowship (grant number 1135991). The OATS Study is supported by the National Institutes of Health (R01 DA044740 to LD). The National Drug and Alcohol Research Centre is supported by funding from the Australian Government Department of Health under the Drug and Alcohol Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data were provided, and linkage was conducted by the NSW Ministry of Health, Centre for Health Record Linkage, and Bureau of Crime Statistics and Research. We also acknowledge the support and expertise of the OATS Study Aboriginal Advisory Group in reviewing this manuscript. The authors acknowledge the Registries of Births, Deaths and Marriages, the Coroners and the National Coronial Information System for enabling Cause of Death Unit Record File (COD URF) data to be used for this publication. We thank the faculty and trainees in the Research in Addiction Medicine Scholars (RAMS) program and in the Fellows Immersion Training in Addiction Medicine (FIT) program for helpful feedback on the analysis plan.

Funding Information:
Funding:TDBwassupportedbytheDalhousie UniversityInternalMedicineResearchFoundation Fellowship,KillamPostgraduateScholarship,Ross StewartSmithMemorialFellowshipinMedical ResearchandClinicianInvestigatorProgramme GraduateStipend(allfromDalhousieUniversity FacultyofMedicine),aCanadianInstitutesof HealthResearchFellowship(CIHR-FRN#171259), andthroughtheResearchinAddictionMedicine Scholars(RAMS)Program(NationalInstitutesof Health/NationalInstituteonDrugAbuse; R25DA033211)andtheFellowImmersionTraining (FIT)PrograminAddictionMedicine(National InstitutesofHealth/NationalInstituteonDrug Abuse;R25DA013582).DLwasfundedbya NationalInstituteofHealthResearchDoctoral ResearchFellowship(DRF-2018–11-ST2-016).SC holdsaScientiaPhDScholarshipfromUNSW, SydneyandanAustralianNationalHealthand MedicalResearchCouncil(NHMRC)PhD Scholarship.LDissupportedbyanAustralian NationalHealthandMedicalResearchCouncil SeniorPrincipalResearchFellowship(grant number1135991).TheOATSStudyissupported bytheNationalInstitutesofHealth(R01DA044740 toLD).TheNationalDrugandAlcoholResearch CentreissupportedbyfundingfromtheAustralian GovernmentDepartmentofHealthundertheDrug andAlcoholProgram.Thefundershadnorolein studydesign,datacollectionandanalysis,decision topublish,orpreparationofthemanuscript.

Publisher Copyright:
© 2022 Brothers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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