In this article issues at the crossroads of opioid use disorder, antimicrobial stewardship, and infection control are discussed. Harm reduction is discussed at length.
Authored By: Jennifer X. Chen, PharmD Candidate 2020; Danielle L. Pavon, PharmD Candidate 2020; Alyssa M. Peckham, Pharm.D., BCPP
[Last updated: 7 September 2019]
Injection drug use (IDU) is a risk factor for the transmission of bloodborne pathogens that can lead to human immunodeficiency virus (HIV), hepatitis C virus (HCV), and bacterial or fungal infections [1]. The World Health Organization (WHO) estimates that over 13 million people engage in IDU worldwide and 1.7 million of these individuals has HIV [2]. According to the Centers for Disease Control and Prevention (CDC), 9% of almost 40,000 diagnoses of HIV in the US in 2016 were due to IDU [3]. Additionally, if unsafe injection techniques are eliminated, it is estimated that 43% of incident HCV infections can be prevented between 2018 and 2030 to help achieve the WHO’s goal to eliminate HCV as a public health threat by 2030 [4]. Persons who inject drugs (PWIDs) and their close contacts are the primary population of interest in harm reduction strategies.
Due to the clinical overlap between infectious disease (ID) and substance use disorders (SUD), a recent article in Clinical Infectious Diseases has called for a subspecialty within ID to address the ID-related complications of SUDs [5]. Therefore, as pharmacists (particularly ID specialists) start to engage in clinical conversations with this underserved population, tailored education toward harm reduction would be clinically impactful and improve patient outcomes [5].
1. What is harm reduction?
Harm reduction is an approach to promoting public health through various strategies in order to minimize the harms associated with IDU to both the individual and community [6]. In the context of SUDs, these strategies are targeted towards PWIDs that may or may not be ready to participate in treatment. Harm reduction includes, but is not limited to programs regarding syringe exchange/services programs (SSPs), supervised consumption sites, overdose and infection prevention, and naloxone provision [7].
The goal of SSPs is to provide sterile equipment to PWIDs and allow for safe disposal of used equipment [8]. Supervised consumption sites are also efficacious programs that exist to ensure safer drug use that go beyond the model of SSPs in that staff can teach and monitor safer injection techniques, test substances for the presence of fentanyl, administer naloxone in the event of an overdose, and more [9]. These programs may help engage PWIDs with other resources such as SUD clinics, sexually transmitted infection/HIV/HCV testing, vaccinations, case management, housing assistance, and more.
Furthermore, studies of SSPs have shown a clear benefit in reducing HCV and HIV transmission without increasing rates of drug use which has been, and continues to be, the primary reason to prevent these programs from existing in the United States [10]. There is substantial evidence that these programs are cost-effective and often cost-saving services by preventing and reducing risks associated with IDU [11].
2. What infectious diseases are persons who inject drugs at risk of?
The primary etiologies of infections from IDU are through the injection of particulate matter or pathogenic loads along with baseline abnormal immune function commonly seen in PWIDs [12]. Infectious complications that arise secondary to IDU include, but are not limited to, infective endocarditis (IE), skin and soft tissue infections (SSTIs), hepatitis B virus (HBV), HCV, and HIV. These complications are of particular interest amongst harm reductionists as preventative measures can be taken to avoid them.
Infective Endocarditis
It is reported that almost 30% of hospitalizations for IE are related to IDU [13]. Contrasting from other etiologies, the majority of IE associated with IDU is right-sided IE, primarily involving Staphylococcus aureus and streptococcal species. IE among PWIDs has also been reported to involve gram negative organisms, fungi, and diphtheroids [14]. PWIDs with HIV are considered to have compounded risk for developing IE, with more likely right-sided involvement. It is pertinent to take these factors into consideration when assessing suspected endocarditis as the practice of licking needles (to check the quality of drug or to “clean” the needle, see Section 4) has been associated with polymicrobial cases of IE, drastically modifying how the disease is treated [15].
Skin and Soft Tissue Infections
SSTIs are the most common ID-related reason for hospital admission among PWIDs and are often the most costly [16]. Among all community-acquired SSTIs, 17% is attributed to IDU [17]. Heroin and heroin-cocaine combination injections are independent risk factors for SSTIs, with methamphetamine injection having lower rates [18]. A cross-sectional study comparing black tar heroin users in Sacramento to powder heroin users in Boston found that black tar heroin users were more likely to have vein occlusion and abscess formation [19]. Secondary to loss of vein access, users reported purposeful soft tissue injection (as opposed to “missed hits” which is when one misses a vein during injection), which can independently contribute to abscess formation. This proposes that the type of drug administered intravenously can carry its own independent risk of infection and must be examined alongside safe injection practices.
Similar to IE, SSTIs in PWIDs can be complicated by the introduction of oral microbes. An observational study examined the risk factors among PWIDs in San Francisco associated with SSTIs from 2011-2014 [20]. The injection practices that are associated with SSTIs are the injection of nonpowder drugs (OR=3.57, p=0.01), needle licking before injection (OR=3.36, p=0.01), injecting with another user’s pre-used equipment (OR=7.97, p<0.001), receiving the injection from another person (OR=2.47, p=0.04), and frequent injections (p=0.02). Syringe/needle sharing remained statistically significant after multivariate analysis (adjusted OR=6.38). These risk factors are all targeted through SSPs and other harm reduction methods, emphasizing the importance of addressing these practices.
Hepatitis B Virus Infection
HBV, a highly infectious viral cause of hepatitis, can survive outside of the body for more than seven days [21]. The two most commonly reported sources of infection are IDU and having multiple sex partners [22]. The infection is largely preventable through vaccinations, with routine infant vaccinations successfully leading to the lowest incidences of infection in persons aged <19 years old. The CDC recommends pre-vaccination serologic testing in high-risk individuals including persons with HIV, men who have sex with men, and past or current IDU.
Although HBV vaccination at birth is preferred to confer long-term protection against HBV, there is speculation that the vaccination’s efficacy may wane over time [23]. Vaccination is indicated in PWIDs who test negative for antibodies to core (HBcAb), antibodies to surface antigens (HBsAb), and surface antigen (HBsAg) [24]. The extended follow-up necessary for completion of the vaccination schedule can be a barrier to care in this population (0, 1, and 6 months), though one study found that an accelerated vaccination schedule (0, 1, and 2 months) offered through SSPs, with the initial vaccination dose given at screening, could improve completion rates [24].
Hepatitis C Virus Infection
IDU is the primary risk factor for HCV infection [15], the most common chronic blood-borne infection in the United States [26]. Based on surveillance data, acute HCV incidence increased from 0.3 cases per 100,000 people in 2004 to 0.7 cases per 100,000 people nationwide in 2014 [27]. IDU was reported in greater than 60% of the cases in nearly each of the years assessed. In 2014 alone, 84% of the cases with risk factor data were attributed to IDU. Of particular concern was the 622% increase in persons aged 18 to 29 who were admitted for HCV related to opioid IDU.
Regarding these statistics, it is important to note the shift in demographics (from baby boomers to a younger generation) and risk factors (from blood transfusions to IDU) overtime. HCV infection incidence rates have surpassed that of HIV and HBV, and this may be due to the false security of HCV being a “curable” disease with direct-acting antiviral treatment [28]. A study published in Clinical Infectious Diseases addressed the increasing mortality related to HCV, noting that incidental death due to HCV infection alone had surpassed the combined number of deaths from 60 other nationally notifiable infectious diseases (including HIV, Staphylococcus aureus, and pneumococcal infections) [26]. The increasing mortality rate despite efficacious therapies is attributed to potential ineligibility due to co-infection with HIV, incomplete treatment, and economic burden. Most of these barriers to cure, if not all, are already particularly concerning in the context of PWIDs.
Human Immunodeficiency Virus Infection
Based on the CDC’s 2018 HIV Surveillance Supplemental Report, males with HIV infection attributed to IDU were the least likely to receive medical care after diagnosis [29]. Only 51% were reported to have received continuity of care. As of 2015, only 52% of PWIDs with HIV are virally suppressed, meaning the remainder of this population (48%) is capable of transmitting the infection to others. To combat this, safe injection kits often include condoms (to reduce unsafe sex practices) as well as sterile injection equipment (to reduce the practice of sharing and reusing needles).
In addition, SSPs are proven to reduce the risk of HIV infection. In a study examining individual-level protection against HIV through participation in SSPs in New York City, HIV incidence in those participating was 1.58 per 100 person-years and 1.38 per 100 person-years if also participating in the Vaccine Preparedness Initiative [30]. This is a significant reduction compared to 5.26 per 100 person-years in the Vaccine Preparedness Initiative and not participating in the SSP.
Although there is scarce data regarding pre-exposure prophylaxis (PrEP) amongst PWIDs, strong evidence suggests that PrEP should be implemented in select patients participating in IDU. The Bangkok Tenofovir Study showed a 49% reduction in HIV-acquisition in patients treated with tenofovir disoproxil fumarate (TDF) 300 mg compared to placebo during a follow-up of 4.6 years (n=2,413) [31]. The CDC recommends PrEP to be initiated in individuals at high risk of HIV infection, which includes PWIDs, with the highest risk associated with sharing needles or having an HIV-positive partner who injects drugs [32]. Before initiation of PrEP, patients should have documentation of HIV-negative status, no signs or symptoms of acute HIV infection, normal renal function, and documented HBV vaccination status. The current recommended regimen is the combination pill of TDF/emtricitabine (Truvada) taken once daily. More information regarding PrEP initiation and patient eligibility can be found in the CDC’s guidelines.
3. How do I ask persons who inject drugs about their injection practice?
One study completed in 2016 demonstrated the efficacy of harm reduction-informed services in an HIV clinic [33]. Of the patients enrolled in the clinic, 74% met the standards set by the U.S. Health Resources and Services Administration for retention of care, 95% were being prescribed antiretroviral therapy and 87% were virally suppressed, and the researchers believed that the high rates of clinical success were due to harm reduction strategies. In a separate study conducted in 2017, researchers sought to determine how harm reduction was utilized in that particular clinic, and their outcomes were developed into six main principles of harm reduction that can be applied to any healthcare setting [34]:
Ask: Will you talk me through how you inject?
The first principle, humanism, is defined by the requirement of providers to value, care for, respect, and dignify patients as individuals. Understanding why patients make certain decisions regarding their drug use is important to understand and can help determine a patient’s needs regarding harm reduction. By understanding how a patient injects drugs, a pharmacist can identify potential harmful practices and can target harm reduction strategies towards those needs. It is important to ask about drug preparation process, materials used, and injection practice including sites of injection. Some pointed follow-up questions may include: “where do you typically use?”, “do you use alone?”, “where do you get your syringes and supplies?”, “how often, if ever, do you re-use your own syringes/supplies?”, and “do you share supplies with others?”
Ask: What barriers prevent you from using safer injection procedures?
The second principle is pragmatism, which the researchers defined as the acknowledgement that no one will ever achieve perfect health behaviors and that health behaviors are influenced by social and community norms. After identifying harmful injection practices, it is important to understand the causes of these practices so that they may be addressed directly. Harmful injection practices may be due to a wide variety of reasons, such as lack of patient education or lack of accessibility to sterile needles/ syringes or other safer materials. Identifying these patient-specific barriers will help pharmacists to determine patient-specific harm reduction strategies.
Ask: What strategies would you be willing to use?
Individualism, the third principle, is centered around the idea that patients present with a spectrum of harm and receptivity to interventions, so harm reduction strategies must be flexible enough to reflect what the patient needs. The strengths and needs of each patient should be assessed and considered when recommending harm reduction strategies. Like the idea of individualism, autonomy is the fourth principle. Although pharmacists may provide multiple harm reduction strategies for PWIDs, patients will ultimately make their own decisions, and these strategies will only be effective if a patient actually uses them. These strategies are not universal, and pharmacists should have a conversation about what strategies the patient is able/willing to do.
Ask: What do you want/plan to do in case X occurs?
The fifth principle is incrementalism which focuses on the idea that any positive change is a step towards better health and that it may take time to occur, if it occurs at all. It is important to make plans in case harm does occur due to intravenous drug use. It is important to provide information about the various infections that may arise from unsafe intravenous drug use. Pharmacist and patients should discuss plans to address the harm that may occur.
Ask: Can you identify the consequences that may occur if safe injection practices are not used?
The sixth and final principle is accountability without termination, and it is focused on the idea that patients should accountable for the consequences of harmful health decision; however, they will not be punished for it. Pharmacists should explain the impact that may occur if harm reduction strategies are not followed, however, they should do so with a non-punitive approach. Patients should be aware of the risks of harmful injection practices, but pharmacists should emphasize that they will not be punished for these harmful decisions.
4. How do I teach persons who inject drugs about safer injection practices?
The information below, along with other educational publications for PWIDs, can be found at the Harm Reduction Coalition’s publications page [35]. Information on naloxone access, interventions for community pharmacists, and harm reduction can all be found on the College of Psychiatric & Neurologic Pharmacists (CPNP) website [36].
The following is a compiled, yet noncomprehensive list of practices from the sources above that can be implemented by PWIDs to reduce harm [37]:
1) One Shot = One New Needle and Syringe
a) Syringes can harbor infectious diseases after use, so they should not be shared. They also dull over time, and continued use can lead to unnecessary trauma to veins and surrounding tissue as well as lead to increased bleeding.
b) Sharpening needles should be advised against as this can cause a burr on the needle (causing damage to veins) and weaken the point (which could break off in the vein).
c) Cookers, cottons, and spoons should also not be shared amongst PWIDs as they carry a similar risk of spreading infection after use.
d) If equipment must be shared, each piece of equipment should be thoroughly cleaned. However, even after cleaning, PWIDs should be advised that the risk of infection is still not 100% eliminated.
2) Equipment
a) Cleaning Needles and Syringes. Rinse the needle and syringe with cold water and discard the water that is used. Fill the syringe completely with undiluted household bleach and keep the bleach inside for a full two minutes while shaking it. Discard the bleach and rinse the needle and syringe with cold water once more. It should be advised that bleach is not proven to kill HCV, but it may be effective against HBV and HIV.
b) Cookers. Cookers serve as a small dish/basin to dissolve or cook drugs for injection, though cookers are also vehicles for the transmission of diseases. Spoons are the most common cooker used because the handle allows for distance between fingers and flame. Therefore, if a bottle cap is used rather than a spoon, PWIDs should be advised to fashion a handle for the cooker (bobby pins, twist-ties, or paper clips) to avoid burning their fingers. Ideally, a sterile cooker with handle should be used.
c) Filters. These are used to filter out any unwanted particulate matter or objects and to utilize every drop of drug solution. It is recommended to use clean, 100% cotton from Q-tips or cotton balls. Filter paper or tampons are acceptable alternatives. Cigarette filters are not safe to use as they contain glass particles and, if already used, they may contain substances from smoke that are likely harmful when injected. PWIDs should be advised to clean their hands prior to preparing their filters.
i) Cotton Shots. This is a slang term for when cottons are saved, piled, and later re-dissolved to extract lingering drug content to inject in the case of inadequate drug supply. “Cotton shots” should be advised against as fungi and bacteria can gather inside the saved cottons, leading to what is referred to as cotton fever (fever, chills, sweating, etc.)
d) Water. Needed to dissolve the drug for injection, water is necessary and an important aspect in harm reduction. As a rule of thumb, sterile water is the absolute safest to use, followed by 10-minute boiled water, bottled water, and lastly tap water. If toilet water must be used, it is safer to use water from the tank over the bowl.
e) Tourniquets. Tourniquets are used to create easier access and visibility to veins. Elastic tourniquets or stockings are preferred over belts. A slip knot should be utilized to ensure easy removal. If the above options are not available, lubricated condoms or slick neckties are alternatives that also allow easy removal.
3) Preparation
a) Some drugs may not dissolve in water on their own (tar heroin, crack cocaine) and require an acidifier to aid in the process. Vitamin C powder, which can be obtained over-the-counter, is preferred over otherwise commonly used items such as lemon juice, which can transmit bacteria, and vinegar, which can irritate veins and should be avoided.
b) Crushed pills should be avoided for injection as they can be difficult to dissolve and can lead to abscesses.
4) Injection Technique
a) It is important to rotate sites, even if it is uncomfortable initially. Injecting into the same locations can interfere with circulation and veins can collapse or become leaky if they are not given time to heal.
i) For intravenous injection, forearms are preferred, followed by backs of hands, then legs, then feet. Ventral wrists, groin, and neck should be avoided as they are risky locations to inject drugs, and missing the vein in the groin or neck area could have fatal consequences.
ii) For intramuscular injection, the buttocks, thighs, and upper arms (deltoid) are the three preferred sites. This route may be used for the administration of steroids and hormones.
b) Clean the injection site using an alcohol pad/swab as any microbes living on the skin can be pushed into the bloodstream when the needle pierces the skin.
c) The needle should be inserted at a 15- to 35-degree angle with the bevel facing up, and injection should always be in the direction of the heart.
d) Register the injection by pulling back the plunger. If dark red, slow-moving blood comes up, this means a vein has been successfully punctured and the drugs can be injected. If the vein is missed, the injection will likely be painful and could lead to the formation of abscesses.
i) Test shots (injecting a small amount of the drug) are recommended to assess the potency of the drug. Taking turns with a partner is also recommended to prevent overdose because in the event of an overdose, the partner would be able to administer naloxone.
e) After the injection, the needle should be removed at the same angle that it was inserted. Do not use alcohol swabs to clean the wound afterwards as this may prevent the wound from healing/clotting.
5. What else do I need to know about harm reduction?
As the opioid crisis has evolved, harm reduction has become more integrated into communities outside of healthcare. IDU can affect much more than the individual’s health, and the concept of harm reduction addresses this issue through the support of social policies and laws. Many states have implemented “Good Samaritan” laws, which are policies designed to provide immunity to people who assist or administer naloxone in an overdose situation [38]. This helps encourage those using drugs to seek medical help without fear of criminal justice involvement. Many states have also enforced laws such as statewide protocols or standing orders for naloxone, which allows naloxone to be more readily available. The importance of the availability of naloxone and how to use it are central to the concept of harm reduction because it is one of the most direct ways to prevent fatal overdose [39].
Another proactive method for overdose prevention is the use of fentanyl test strips. According to the CDC, fentanyl has become a large contributor to opioid-related fatal overdoses, which increased by 47% from 2016 to 2017, as fentanyl is more potent that heroin [40]. Many overdoses due to fentanyl occur because the user is unaware of the presence of fentanyl in the drug supply. Fentanyl test strips can be used to test drugs for the presence of unsuspected fentanyl and, if detected, users can adjust their use [22].
Stigma toward drug use and SUDs is a large barrier to the accessibility of harm reduction because it often leads to social isolation and discrimination [38]. PWIDs often face stigma from many sources, such as employers, individuals, and even themselves. It is crucial, as health care professionals, to acknowledge the barriers that PWIDs face because of stigma and to understand the role that we can play in addressing and trying to eliminate it.
It is also important to understand that PWIDs who present for treatment may not have the same goals for themselves as we do for them. For those not identifying abstinence as their goal, we should recognize what PWIDs are willing and able to do in regard to reducing potential harm from drug use. Substance use is also not exclusively harmful in all individuals, as some may be using to self-treat other conditions or psychiatric illnesses. Finding the underlying cause for substance use is crucial for treating the individual’s use disorder. Foremost, drug users are more than their drug use and deserve the same respect and dignity as other patients seeking care for chronic illnesses [41].
SUDs, similar to diabetes or hypertension, are chronic conditions and should be treated as such. Frequent monitoring, patient-specific treatment regimens, and lifestyle modifications are all factors that are universally considered when treating a patient for any condition, and SUDs are not exceptions. Understanding that PWIDs may have additional barriers to health care such as homelessness, less education, and lack of peer support will help us to provide optimal care to this population.
Closing Comments
Persons with SUDs may not align with abstinence-based goals and may not be ready to enter treatment. In such cases, harm reduction approaches should be employed to maximize patient safety, improve patient outcomes, and minimize impact on the surrounding community. Harm reduction may include many strategies, though those targeted at reducing the transmission of infectious diseases is of utmost importance to the health of individual and the health of others. The primary intervention to reduce ID-related manifestations from IDU is to teach safe injection practices and educate PWIDs as to where they can obtain safe injection materials.
As pharmacists, we are the most accessible healthcare professional and are well-positioned to engage in harm reduction conversations with PWIDs. As a best practice, we should all have access to safe injection kits to give to PWIDs in need; however, in the absence of accessible safe injection kits, we should all be familiar with the nearest SSP or harm reduction facility to guide patients toward obtaining these materials and teach them how to safely use. Altogether, these interventions will positively impact the opioid crisis, reduce morbidity and mortality, and enhance the safety of our community.
ABOUT THE AUTHORS
Jennifer Chen Pharm.D. Candidate 2020
Jennifer Chen is a P4 pharmacy student at Northeastern University, School of Pharmacy in Boston, MA. Jennifer currently works part-time as a pharmacy intern at both CVS Specialty Pharmacy and New England Baptist Hospital. Clinically, she is interested in both infectious diseases (ID) and psychiatry/addiction after spending time at Beth Israel Deaconess Medical Center with inpatient ID pharmacy specialists, and Massachusetts General Hospital Bridge Clinic with an advanced practice psychiatry/addiction pharmacy specialist. Upon graduation, she plans to pursue a PGY1 residency to expand the depth and breadth of her clinical pharmacy knowledge.
Danielle Pavon Pharm.D. Candidate 2020
Danielle Pavon is a P4 pharmacy student at Northeastern University, School of Pharmacy in Boston, MA. Danielle currently works part-time as a pharmacy intern at Brigham and Women’s Hospital in Boston. Clinically, she is interested in psychiatry, oncology, and pediatrics. Upon graduation, she plans to pursue a PGY1 residency to expand upon her clinical pharmacy knowledge and narrow her specialty interests.
Alyssa M. Peckham, Pharm.D., BCPP
Dr. Alyssa Peckham is a Clinical Assistant Professor at Northeastern University, School of Pharmacy and a Substance Use Disorders (SUDs) Advanced Practice Pharmacist at Massachusetts General Hospital in the SUDs Initiative. She earned her Doctor of Pharmacy degree from the University of Rhode Island, completed two years of post-graduate residency training at the VA Connecticut Healthcare System where she specialized in psychiatry and addiction, and she holds board certification in psychiatric pharmacy. Her collaborative practice is in the Bridge Clinic at MGH which is an immediate access, low barrier, harm reduction, transitional, outpatient clinic that works to stabilize patients with SUDs and move them into long-term, community-based treatment. Dr. Peckham has given local, regional, and national talks regarding SUDs pharmacotherapy, harm reduction, and destigmatization. Her research focuses on misuse and overuse of prescription medication and illicit substances, with recent publications examining the epidemiology, economics, and policy implications of gabapentin misuse in concert with opioids.
REFERENCES
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32. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf. Published March 2018.
36. Substance Use Disorders. CPNP website. https://cpnp.org/resource/suds. Accessed August 20, 2019.
