Understanding the risk factors associated with IE in PWID is important in developing harm reduction strategies. We hypothesized that the use of hydromorphone-CR would be a risk for IE among PWID; however, we did not find a significant increase in hydromorphone-CR use in IE patients vs controls (91% vs 84%). In contrast, our previous work has demonstrated evidence of such a relationship. 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) . Moreover, we have also shown that drug excipients within hydromorphone-CR preserve S. aureus survival in vitro . This was not the case for immediate release hydromorphone or controlled-release Oxycodone . 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 . We suspect that the very high prevalence of hydromorphone-CR use in both cases and controls led to a lack of power to identify a difference in use between the two groups in this study.
There has been very little data assessing the detailed injection practices associated with developing IE. The literature primarily studies the clinical and epidemiological characteristics of PWID developing IE [3, 5, 7, 26, 27]. Some studies assessing injection practices of PWID are in relation to the development of skin and soft tissue infections  or infections in general [14, 20, 29]. To our knowledge, this is the largest study (n = 33) showcasing detailed survey data regarding injection practices of PWID with IE. Understanding PWID-IE risk factors are of importance to inform public health authorities in the development of harm reduction strategies reducing infections in this at-risk population. Our one-on-one surveys have allowed for the collection of comprehensive quantitative and qualitative data to thoroughly understand injection practices and behaviors of PWID in our region to elucidate the etiology of our high IE rates.
Previous studies suggested that IE in PWID was more frequently seen in males, younger patients, and those with concurrent HIV infections [3, 8, 9]. However, our cases and controls had similar ages, concurrent HIV, and HCV infections. Nearly a quarter of our cases and controls had HIV; the high incidence of HIV in this population is likely related to our co-existent local HIV epidemic . Hepatitis C rates were based on self-report, and a lack of awareness of status may have led to lower than expected rates in both cases and controls.
Unexpectedly, being a female PWID was a risk factor for IE in our population (OR 4.65; 95% 1.85–12.28). Wurcel et al. also showed a greater parity in PWID-IE distribution by sex (female = 53%) between the ages of 15–34 over a 13-year review of IE hospitalizations in the USA . We suspect that gender differences may exist with regards to injection technique. Women are more likely to have sex partners that initiate them into injection practices and are more likely to share IPDE than men [30, 31]. Women can be identified sub-populations for targeted harm reduction, and in particular, interventions should account for intimate partner dynamics concerning high-risk practices . Furthermore, female anatomy increases the difficulty of IVDU. We hypothesize that women have smaller veins, which may be difficult to visualize, often requiring increased manipulation during injections. This inability to find an adequate injection site with smaller veins can promote the usage of larger, more accessible central veins like the internal jugular, which further increases risks of infection. Additionally, local surveys in our region from the Middlesex-London Health Unit found that female PWID in London were more likely to borrow and share their IDPE . It was also anecdotally noted, through our other project in progress, that women were less likely to access supervised injection sites, leading to unsafe injection practices that place them at risk of IE.
Usage of provincial-distributed IDPE, i.e., the Stericup, for mixing drugs was found to be protective against IE. PWID who are more likely to use equipment from needle exchange programs are also more likely to be exposed to education on safe injection practices and consistently use sterile equipment. PWID with IE were also more likely to use objects for mixing and heating drugs that were not distributed through IDPE kits or commonly listed in our interview questions. This suggests that cases might be injecting in severe withdrawal states, where concern for safe practices do not take precedence over the need to use. Additionally, the increased use of a lighter may be suggestive that controls are using drugs that require heating such as heroin, crystal methamphetamine, and cocaine, and these may reflect a lower risk of using hydromorphone-CR. However, we did not see a significant protective effect of always heating hydromorphone-CR preparations (OR 1.57; 95% CI 0.57, 4.71). We feel this may be due to the variations in practice that PWID follow. It is likely that PWID heat their drugs depending on the circumstance (state of withdrawal, supervised site, environmental factors, etc.), and this information was not captured in our line of questioning. We asked participants to choose a definite answer of whether they heated all the time or never heated their hydromorphone-CR injectates, which does not reflect the reality of injection behaviors. In other local literature, heating drugs has been shown to reduce bacterial load within cookers which contain hydromorphone-CR . These findings have been translated into public health campaigns promoting “cooking one’s drugs” to reduce infectious complications of IVDU in London, Ontario . It may be that our cases and our controls were both engaging in this behavior, but our sample size was insufficient to detect any difference.
Another hypothesized risk factor for IE was the site used for injection. Entrenched drug users tend to have thickened scar tissue from chronic injections in the same location; in many cases, this will be near the veins of the arm . Furthermore, difficulty in accessing common sites may lead participants to inject in multiple sites for their hit, which can further increase the risk of infections given the multiple entry points for bacteria. Alternative sites of injection and IE likely reflects a greater difficulty in accessing safer sites, with alternate sites having a greater likelihood of contamination. Alternative injection sites may also be a surrogate marker for more venous damage from previous injections and thus entrenched drug use . In particular, one study of PWID in the UK found the high-risk practice of injecting into the jugular vein was associated with the female gender and multiple body-site injections . We found a significant difference between cases and controls with respect to the site of injection, which was driven by a higher frequency of cases using multiple sites. This was also seen in unadjusted logistic regression, where injection into multiple sites was associated with higher odds of IE (2.29; 95% CI 0.83, 6.07), albeit not statistically significant (p = 0.10). This effect was somewhat diminished when adjusting for sex and government-dispensed IDPE (OR 1.67; 95% CI 0.53, 4.97).
Our multivariable analyses did not include reuse of hydromorphone-CR for a second wash given the universality of this practise in our cohort and our sample size. A review of the literature had shown that conducting multiple washes of hydromorphone-CR injectates could also serve as a risk factor for IE. We did not find an increased likelihood of performing multiple washes with hydromorphone-CR (88% vs 74%). Our sample size was likely inadequate to identify these differences because the frequencies of both of these behaviours were much greater in both groups than expected. However, a companion study surveying PWID in London found that PWID with HIV were 22.12 (4.51 to 108.59) times more likely to share cookers, filters, or washes in their three-month recall period . The high-risk practice of injecting prescription opioids from equipment that is reused multiple times is prevalent in our region and appears to be related to a high incidence of infectious complications including Hepatitis C and a very high incidence of IE [4, 36]. The trend towards increased use of crystal methamphetamine in controls may be suggestive that participants using less hydromorphone but who substitute with other agents, may be at lower risk of IE.
Homelessness and unstable housing have been associated with injecting in public spaces and other high-risk injection practices [37, 38]. However, in exploratory analysis, cases (PWID IE+) were not more likely to lack stable housing compared to controls. This is supported by Roy et al. , who found that unstable housing was not associated with conducting multiple washes (utilizing residual drug for multiple injections), which is often the preparatory method used to inject prescription opioids, such as hydromorphone-CR. We hypothesize that PWID using hydromorphone-CR, which is a more costly illicit substance, can be associated with stable housing, which is reflective of financial stability. Hydromorphone is one of the most expensive prescription opioids to purchase illicitly, costing Canadian $5.57/mg (US$4.28/mg) or Canadian $100.26 for an 18-mg capsule .
Interestingly, we found that our cases were more likely to have completed secondary or post-secondary education (61.3% cases vs 33.7% controls). In contrast, previous studies have linked the incompletion of education to illicit substance use . Higher education likely is correlated with income and again may reflect greater accessibility to expensive prescription opiates such as hydromorphone-CR, which has properties that increase the risk of infections . Our evaluation of the relationships between housing status and education with IE were exploratory and will require further studies to confirm.