A controlled-release oral opioid supports S. aureus survival in injection drug preparation equipment and may increase bacteremia and endocarditis risk

Abstract

Background Injection drug use-associated endocarditis (IDUaIE) incidence in Ontario has recently been associated with hydromorphone prescribing rates. Staphylococcus aureus causes the majority of cases of IDUaIE in Ontario and across North America. Hydromorphone controlled-release (Hydromorphone-CR) requires a complex technique for injection and therefore provides multiple opportunities for contamination. Hydromorphone-CR contains several excipients, which could enhance staphylococcal survival and increase risk of contaminating the injectate. Methods Used injection drug preparation equipment (cookers/filters) was collected from persons who inject drugs (PWID), rinsed with water, and plated on Mannitol salt agar. Bacterial isolates from bacteremic PWID were used to assess the survival of S . aureus and Streptococcus pyogenes on cookers/filters with Hydromorphone-CR, hydromorphone immediate-release (Hydromorphone-IR) or oxycodone controlled-release (Oxycodone-CR). The solutions spiked with S . aureus were heated and the remaining viable bacteria enumerated. Results S . aureus was detected in 12/87 (14%, 95%CI 8–23%) cookers/filters samples used for injection of Hydromorphone-CR. Hydromorphone-CR was the only opioid associated with greater survival of methicillin-sensitive S . aureus (MSSA) and methicillin-resistant S . aureus (MRSA) on cookers/filters when compared to sterile water vehicle control. There was a ~2 log reduction in the number of S . aureus that survived when cookers/filters were heated. Conclusion 14% of all cookers/filters used in the preparation of Hydromorphone-CR were contaminated with S . aureus . Hydromorphone-CR prolongs the survival of MRSA and MSSA in cookers/filters. Heating cookers/filters may be a harm-reduction strategy.

Risk Factors Of Infective Endocarditis In Persons Who Inject Drugs

“…Our population-wide study in Ontario with over 60,000 PWID showed a 3.3 fold higher risk of acquiring IE within 120 days when prescribed hydromorphone-CR compared with other opioids (p<0.0001) (24). Moreover, we have also shown that drug excipients within hydromorphone-CR preserve S. aureus survival in vitro (12). This was not the case for immediate release hydromorphone or controlled-release Oxycodone (12).…”

“…This was not the case for immediate release hydromorphone or controlled-release Oxycodone (12). Furthermore, we found that the injectate obtained from aspirating from equipment previously used to inject hydromorphone-CR was contaminated with S. aureus in 14% of cases and thus injection of this drug would commonly be associated with bacteremia (12). The protective effect of using a lighter to pulverize drugs in this study may reflect a greater likelihood of heating preparations prior to injection due to the accessibility to a heating source.…”

“…The protective effect of using a lighter to pulverize drugs in this study may reflect a greater likelihood of heating preparations prior to injection due to the accessibility to a heating source. This practice has been shown to reduce bacterial load within cookers which contain hydromorphone-CR (12).…”

“…This infectious complication of intravenous drug use (IVDU) is associated with significant morbidity and mortality requiring extensive and costly(1,2) multidisciplinary care (7). PWID are at risk of IE due to: comorbidities of HIV, hepatitis C and skin and soft tissue infections; non-sterile injection practices; and the reuse of injection drug preparation equipment (IDPE) (2,4,(8)(9)(10)(11)(12).…”

“…Furthermore, the components of hydromorphone-CR capsules that provide the controlled release, increase survival of HIV (19) and Staphylococcus aureus (12), which cause the vast majority of IE cases (7). Moreover, residual drug remains in cookers and filters after an initial injection, allowing PWID to resolubilize the remaining drug and conduct multiple injections (11,14,16,19,20) (Fig.…”