Rising rates of injection drug use associated infective endocarditis in Virginia with missed opportunities for addiction treatment referral: a retrospective cohort study

Injection drug use (IDU) is a serious public health threat due to the risk for transmission of Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and overdose related deaths [1, 2]. Bacterial infections caused by IDU are common, the most severe form being infective endocarditis (IE). Though the mortality of IDU has been a major research focus [3], the extent of associated morbidity from other complications, such as IE, has been less extensively characterized.

IDU has increased significantly since the year 2000 in conjunction with a national opioid epidemic, with total opioid overdose related deaths increasing by two-hundred percent in 14 years [3]. This drug epidemic is distinctive in that it primarily affects socioeconomically depressed, rural, and predominately non-Hispanic white populations [4‐6]. Sharing injection equipment in social networks of individuals with HIV or HCV infections can lead to viral outbreaks [5, 7]. In addition, using dirty equipment to inject drugs that contain particulate matter and diluents can provoke endothelial damage to heart valves and introduce pathogens into the bloodstream that cause IDU-IE and other localized infections [8].

The incidence of IE in people with IDU is 150–200 per 100,000 person years, approximately 100 times higher than the incidence of IE in the general population [9]. IDU-IE is more likely to affect the right side of the heart and is more frequently caused by Staphylococcal species or polymicrobial infections [9]. Treatment of IE requires long courses of intravenous antibiotics often administered through peripherally inserted central venous catheters. Despite appropriate treatment, recurrence of IE is more common in people who inject drugs (PWID) [10]. The mortality of IDU-IE has been reported to be 10% compared to 20–35% in IE due to other causes (non-IDU-IE) [9]. However, the mortality after valve replacement surgeries is higher in IDU-IE and more than half of those who undergo valve replacement surgeries will require repeated surgical intervention due to persistent injection of drugs [11, 12].

Virginia has one of the fastest growing rates of drug overdose related deaths in the United States [3] and is home to eight of the projected top 5% most vulnerable counties across the United States for viral outbreaks related to IDU [4]. In 2015, emergency department visits for heroin overdose during a nine month period had increased by 89% compared to the same nine month period in 2014, and fatal drug overdoses were the most common cause of unnatural death in 2013 [13]. This led to the declaration of a public health emergency by Virginia’s State Commissioner in October 2016 whereby a statewide standing order was issued that authorized pharmacists to dispense naloxone, an opioid antagonist that reverses the effects of opioids [13]. Several studies have described increasing rates of IDU-IE in the context of increasing IDU [14‐18], though no studies have evaluated IDU-IE in Virginia. Few studies have evaluated how IDU is being addressed in the context of a diagnosis of IDU-IE.

Needle and syringe sharing, reuse, and injecting drugs through uncleaned skin are highly implicated in the development of IE, and these practices are common among PWID [19, 20]. Evidence supports the efficacy of several underutilized harm reduction strategies for PWID, such as supervised injection facilities, needle-syringe exchange programs, medication-assisted treatment, and opioid antagonists for overdose treatment [19, 21‐26]. Unfortunately, there remains substantial stigma in relation to substance use disorders, which is a barrier to establishing public policies that benefit PWID, such as government funding for abstinence or maintenance-based treatment programs or regulations regarding insurance parity [27]. In order for beneficial policy and social change to take place, more needs to be known about patterns of IDU related morbidity. The purpose of this study was to describe the temporal, geographic and clinical trends and characteristics of IDU-IE in Virginia and to identify opportunities for better-quality care of PWID.

A dramatic increase in the number of admissions for IDU-IE was seen at UVA from 2000 to 2016. Individuals with IDU-IE were more likely to be non-Hispanic white race and were younger than those without IDU. Median hospital length of stay was 70% longer and the median hospital cost was nearly two times the cost for those without IDU. A larger percentage of patients IDU-IE were uninsured (55%) compared to patients with non-IDU-IE (7%). Evaluation of the clinical characteristics of IDU-IE found that many patients presented to the hospital acutely ill with high rates of septic shock (19.7%). This is more than double what was seen in a one-year French cohort study (9%) of IE cases [30]. There were additionally high requirements for chronic renal replacement therapy (15.8%). IDU-IE is associated with right heart involvement, our results showed that a significant number of patients 24 (36%) patients actually had left heart involvement. There were also noteworthy embolic complications with septic pulmonary emboli seen in 42 (55.3%) patients and cerebrovascular related events in 19 (25%) patients. IDU-IE did have less in-patient mortality (7.9% IDU-IE, 16.6% non-IDU-IE), however, censored 90-day mortality in those with IDU-IE approached the mortality of the non-IDU-IE group (21.8% IDU-IE vs 29.3% non-IDU-IE, p-value = 0.3). The number of patients with previous IE (31.6%) and readmissions (22.4%) highlights the need for further prevention strategies. The high acuity at the time of hospital admission may be affected by delayed patient presentation. This could be partially driven by anticipatory fear of legal repercussions, uninsured status, or concern for withdrawal symptoms.

Increasing rates of IDU-IE in Virginia are consistent with statewide data showing an over 350% increase in rates of acute HCV, which is highly correlated with IDU, during a similar time period [5]. The causes of increasing rates of IDU in Virginia and nationally over this period are at least in part due to increases in opioid prescribing. Prescriptions for opioids have increased nationally from 2007 to 2012 [31] and the southwest region of Virginia prescribes considerably more than the rest of the state [32]. Indeed, in our study the number of patients discharged with an opioid medication on their medication list increased by 22.4%.

IDU-IE and other acute bacterial infections associated with high morbidity, mortality, and costs, may be important metrics to define regions in need of funding for additional addiction treatment and harm reduction services. Policy-makers often allocate public funds for substance use disorder treatment or harm reduction strategies based on rates of HIV and viral hepatitis since there is infrastructure to measure these rates. In our study, known prevalence of HIV (6.6%) and acute and chronic HCV (42.5%) were relatively low. However, increasing rates of IDU-IE may herald potential viral outbreaks, and IDU-IE’s high morbidity and extensive healthcare costs are growing. Tracking of IDU-IE should be considered as an earlier warning sign of unsafe injection practices and the potential for blood-borne viral outbreaks. With this additional surveillance, regions with known increases in IDU-IE or other IDU-related bacterial infections could be targeted as priority areas for the development, authorization, and implementation of evidence-based substance use disorder treatment programs and harm reduction packages. This is especially important to consider in the context of Virginia’s Bill 2317, which allows for syringe service programs as of January 12, 2017 and was passed with a main goal of reducing the transmission of blood borne pathogens [33]. Unfortunately, infrastructure for tracking IDU-IE is not currently available. State level surveillance of IDU-IE could be possible with strategies such as mandatory reporting of inpatient admissions for this condition. National level surveillance could be streamlined with the addition of ICD codes to address IDU and both infectious and non-infectious complications of IDU.

In our study a minority of patients were offered resources for substance use disorder treatment by a social worker or seen by consulting physician teams regarding their IDU. Several factors contribute to these low levels of substance use disorder treatment discussion and initiation. The capacity of available maintenance therapy programs, abstinence therapy programs, and harm reduction strategies do not meet national or the state of Virginia’s demands. In 2014 the rate of opioid dependence in Virginia was 6.5–9.2 per 1000 person years, while the capacity for medication assisted treatment was 0.7–3 per 1000 person years [34]. Some rural areas in the United States have an average two year wait time for medication assisted treatment [35], in part due to insufficient physicians with the required expertise. Many addiction treatment programs are unable to bill insurance and do not receive needed state funding [36]. Deficiencies of available resources and the perception of recidivism by health care providers may make efforts to initiate treatment discussions feel futile. Lastly, stigmatization of IDU and substance use disorders may lead to the perception that the condition represents a moral failing rather than a medical illness [27].

Absence of addiction treatment is not unique to our study site. A similar study evaluating substance use disorder treatment among persons with IDU-IE showed high readmission rates for IDU-related infections, recurrent IDU-IE and high mortality. Only a quarter of patients were offered addiction consultations or psychiatry consultations for IDU [37]. Factors contributing to IDU, such as substance use disorder, must not be overlooked while the complications of IDU are treated in the hospital setting. In addition to enhancing availability of medication assisted treatment and treatment services, including treatment of withdrawal, a multidisciplinary approach with counseling by trained therapists is useful to address underlying factors such as childhood trauma [38]. An inpatient hospitalization is an opportunity to offer these services, link patients to care, and to offer harm reduction strategies. Specifically, education on safe injecting practices, the prescribing of naloxone to empower individuals to treat unintentional overdoses and the prescribing of HIV pre-exposure prophylaxis with adjunct HIV education and counseling [37, 39]. Relationships between healthcare staff and patients with IDU may be challenging due to many factors, not limited to real and perceived stigma [40]. Concerted efforts to better educate healthcare workers and the community regarding IDU-associated substance use disorders as curable diseases may reduce stigma and improve the care of PWID both inside and outside of the hospital setting [41].

The median 17 day hospital stay and six week intravenous antibiotic treatment course required for each case of IDU-IE is an additional opportunity for multidisciplinary addiction treatment. Almost half of all IDU-IE patients were discharged from the hospital with home health agencies and an additional quarter of patients were sent to some type of nursing facility. Residential addiction treatment services that offer antibiotic infusions for IE treatment have been shown to be cost effective in reducing hospital length of stay. There are concerns related to sending PWID home with peripherally inserted central catheters, largely related to risk for catheter infections from catheter misuse. In rural areas, this is often the only option due to lack of insurance and/or lack of facilities near patients’ residence. Therefore, in these settings, engaging home health agencies to assist in providing addiction treatment services in conjunction with antibiotic infusions could be helpful [21].

This study was limited by potential errors associated with coding, specifically the lack of an ICD code for IDU. The chart review process was done in part to account for these errors. The conservative criteria use to define both IDU and IE may have led to missed cases of IDU-IE. The study did not determine the total number of admissions for IE, therefore the true proportion of IE due to IDU could not be determined. Finally, our institution implemented a new electronic medical record in 2011, which resulted in some changes in documentation practices.

IDU-IE is a severe infection that leads to significant morbidity and healthcare related costs. IDU-IE rates are increasing and will likely continue to do so without targeted interventions to help PWID. The diagnosis and treatment of IDU-IE provides an opportunity for the delivery of addiction treatment, counseling, and harm reduction strategies.

Numbers of infective endocarditis cases related to injection drug use (IDU) have increased significantly in Virginia. While infective endocarditis is treated medically, opportunities for addiction treatment referral are missed.