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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Opiates and injection equipment commonly used by PWID.

(A) Pill crusher with uncrushed hydromorphone controlled-release (Hydromorphone-CR) beads (removed from capsule). (B) Unused injection drug preparation equipment consisting of metal cooker and filter. This style of cooker with compressed cotton filter is distributed as part of a provincial harm-reduction initiative from the needle exchange along with clean needles, syringes and water. All cookers collected in the used equipment collection program have been in this style of cooker. (C) Hydromorphone-CR-containing sterile cooker and filter after a single wash in controlled laboratory environment. The large volume of remaining material available for repeat “washes” to get further opioid is visible. (D) Used cookers after three washes (donated by a person who injects drugs) with significant residual Hydromorphone-CR left in cooker. The cooker is often folded to retain residual opiate for later use and a “repeat wash”.

Fig 2. Persistence of S. aureus over time in immediate-release or controlled-release opioid solutions compared to sterile water control.

(A-B) Clinical strains of S. aureus, both MSSA and MRSA, persisted longer in Hydromorphone-CR solution compared to both hydromorphone immediate-release (Hydromorphone-IR) solution or sterile water control. (C-D) Both MSSA and MRSA persisted longer in sterile water control when compared to oxycodone controlled-release (Oxycodone-CR) solution.

Fig 3. Bacterial survival of clinical strains of MSSA, MRSA, and S. pyogenes on unused Cookers/Filters containing Hydromorphone-CR solution or sterile water control.

All Cookers/Filters underwent an initial wash with bacteria-spiked water for 5 minutes and were subsequently left dry at room temperature before a second five minute wash was performed at either 1 hour or 24 hours. Both (A) MSSA and (B) MRSA survived significantly better in Hydromorphone-CR than in the water vehicle control when the second wash happens after 24 hours. (C) S. pyogenes was not isolated from the drug equipment after 24 hours. Significance assessed by one way Anova with Tukey’s correction for multiple comparisons. ***P<0.001, NSD indicates no statistically significant difference. D = Drug, (Hydromorphone-CR), ND = No drug (sterile water vehicle control).

Fig 4. Cigarette lighter heating of S. aureus-"spiked" Hydromorphone-CR prepared in cookers/filters decreases the bacterial burden in the injected drug solution.

S. aureus-spiked samples in Hydromorphone-CR-containing Cookers/Filters were heated with a cigarette lighter (holding the flame under the cooker until bubbling) during either the initial wash or at the subsequent 1-hour or 24-hour second wash. Heating reduced S. aureus bacterial recovery by approximately 2 log10 when performed immediately after bacterial contamination, but delayed heating was less effective. Significance was assessed by one way Anova with Tukey’s correction for multiple comparisons. **P<0.01, ***P<0.001, NSD indicates no statistically significant difference.