To fully understand the modern opioid epidemic and the magnitude of the public health challenges that it encompasses, one has to first understand the scale of the crisis. Opioids have had a place in human usage for millennia and are one of the oldest known classes of drugs both medically and recreationally; there are references seen throughout ancient history alluding to their beneficial (and less desirable) properties. In the United States, there have been waves of addiction over time, notably as sequelae of medical prescribing. For example, in the 19th century, with widespread dissemination of morphine as a miracle drug, iatrogenic addiction drove a crisis peaking at roughly 4.6 opioid-addicted individuals per 1000.1 With advances in medical knowledge and more circumspect prescribing behavior, and efforts to limit sales, this epidemic abated. Further intermittent waves through the 20th century tended to arise from nonmedical use in urban areas, disproportionately impacting people of color.1
The late 1980s through the early 2000s marked the nascent stages of the current epidemic. In brief, a myriad of factors—including the promotion of pain as the “fifth vital sign” by several prominent medical societies and the rise of new formulations of medications that had purportedly low addictive potential—led to aggressive opioid prescribing practices.1 Both in acute and chronic settings, prescribing sky-rocketed. In the span of 15 years (1999-2011), consumption of oxycodone went up nearly 5-fold.2 As has become apparent, the consequences of the exuberant opioid prescribing for expanded indications have been dire. Three separate waves of the current epidemic have been described: the first involving prescription opioids in the 1990s, the second beginning around 2010 as individuals transitioned to heroin in the wake of stricter prescribing, and the third beginning in 2013 as synthetic opioids (especially fentanyl) became more prevalent on the black market.3 As it stands, per last available data in 2018, 2.9 million individuals in the United States reported misuse of a prescription pain medication within the past month; 2.0 million people had a concomitant DSM-IV diagnosis of opioid use disorder (OUD) or dependence in the past year; and 5.1 million people have tried heroin in their lifetimes.4
In 2014, as rates of opioid-related overdoses soared,5 the Centers for Disease Control and Prevention (CDC) named the epidemic one of the top 5 public health challenges facing the United States. Much of the focus nationally has centered on overdose prevention, with good reason. Per last available data, there were roughly 47,600 deaths directly attributable to opioid overdose in 2017, comprising 67.8% of all drug overdose deaths in the country.6 In context, opioid overdose alone therefore ranks among the top 10 causes of all-cause mortality in the United States.7 The incidence of death has unfortunately increased broadly across age groups, racial/ethnic groups, and in both rural and urban areas with an overall increase of 9.6% from 2016 to 2017, suggesting that the tide of overdose deaths has yet to turn.1,6
Overdose alone, however, does not adequately capture the scope of morbidity and mortality attributed to the current opioid epidemic. In recent years, there has been increasing alarm surrounding the infectious complications of OUD, especially as relates in persons who inject drugs (PWID). An estimated half-million to 1-million persons inject annually, and hospitalizations for injection drug use (IDU)-related infection have increased in the last several years.8 Concern falls largely along 2 avenues: disease that is introduced from the environment (ie, bacterial and fungal infections) and disease that is transmitted between individuals [ie, viral illnesses such as human immunodeficiency virus (HIV) and the hepatitides]. In both scenarios, contamination of the drug product, injection equipment, and unsterile technique play a significant role.
These infections have serious consequences, both for the individual and from a larger public health perspective. IDU is known to be a driver of HIV infection, currently representing 9% of new diagnoses per year; clusters and outbreaks of IDU-associated HIV have made national headlines in recent years.9–11 Hepatitis C (HCV) continues to present a serious challenge as well—nationally, an over 2-fold increase in acute HCV infection over the past decade is attributed to increases in IDU.12 Meanwhile, serious bacterial/fungal infections are on the uptrend. A recent study found that hospitalizations for infective endocarditis (IE), osteomyelitis (OM), septic arthritis, and/or spinal epidural abscess in individuals with known OUD doubled from 3421 annually to 6535 over the 2002-2012 period, whereas total hospitalizations remained constant; costs associated with these hospitalizations increased from $191 to $701 million.13 With respect to hospitalizations for OUD without infection, individuals were more likely to die while inpatient during these stays, and stays were 4-fold more costly.13 Even for comparatively less life-threatening infections, such as skin and soft tissue infection (SSTI), high burden of disease proves daunting; an estimated 44% of all PWID have had an SSTI during their lifetime, and other studies suggest even higher prevalence.14 The significant impact of both life-altering medical conditions and cost to the medical system necessitates that the infectious complications of OUD receive particular attention as a crisis within the overarching epidemic of opioid use in this country.
In this review, we will focus on infectious complications of OUD by examining mechanisms of transmission, further define the specific types of infection noted above, and detail the unique challenges posed by serious infection in the setting of OUD.
Mechanisms of transmission
Opioids can be taken in many ways, including ingestion, insufflation (“sniffing” or “snorting”), inhalation or smoking, injection into the soft tissues (“muscling” or “skin-popping”), and intravenous injection (mainlining). There can be non-negligible spread of infection due to sequela of the substance’s psychoactive effects and addictive potential, particularly in the case of sexually transmitted infections such as HIV and HCV. However, as noted above, primarily, infection is transmitted due to contamination during the multi-step process of injection, which will be the focus of our discussion.
There are multiple pieces of equipment (works) that are common or necessary for injection. These include needles, syringes, “cookers” or “spoons,” “cottons,” and water. Typically, the syringe is used to draw up water, which is placed into the cooker or spoon with the substance. Common cookers include bottle caps or an actual spoon. Heat is applied from below to aid in the dissolving process, and a piece of the syringe may also be used to stir the solution. Citrus peels or juice (lemon or orange) may be added to help acidify the solution, which further aids in dissolving the substance. A “cotton” (frequently cotton from a Q-tip or cotton ball, but also possibly cigarette filters) acts as a filter—it is placed in the cooker, absorbing the solution. The syringe tip is then advanced into the cotton and retracted to resorb the solution. The area of the body that will be injected is then cleaned with alcohol, the needle is inserted, and the substance is injected.15
As is evident, there are many aspects to the above process that are susceptible to contamination. Compounding risk attributed to IDU is the practice of needle and syringe sharing, or reuse; even if needles are not shared with other individuals, they are often reused multiple times. This not only contaminates the equipment but also dulls the needle, which may cause more trauma at the site of injection and predispose to infection. As a result, efforts at improving access to new needles have been on the rise. Still, the rest of the process raises high concern. Cookers, cottons, and water are all commonly shared between individuals and reused. Cookers can be cleaned with bleaching solutions, but how frequently this is performed is unclear. The water that is used to dissolve the solution typically is not sterile, and manipulation of the solution with other objects contaminates it regardless. Acidifying the solution with citrus, although more common with crack cocaine, is frequently done with brown heroin—this has been known to cause disseminated fungal infections.16–18 The efficacy of filtering large particulate matter through cottons is unclear, but drawing a substance up through unsterile material also poses an infection risk; use of cigarette filters or pocket lint likely exacerbates this risk. As there is likely residual drug in the cotton after use, PWID also commonly save the used cotton to further extract any retained substance at a future date. This further exposes the individual to contamination.15
Interestingly, the different forms of heroin specifically may be linked to increased risk for certain infections. Heroin comes primarily in 3 forms—white, black tar, and brown—which have differing degrees of solubility in water, necessitating the addition of acid (as above) or heat. White powder heroin is easily dissolvable, facilitating intravenous injection; black tar and brown are less so. As a result, HIV prevalence in PWID is higher in cities where white powder heroin is endemic compared with black tar.19 In contrast, there is an association with SSTIs with both black tar and brown heroin, likely due to more difficulty with intravenous administration.19,20
There are multiple hallmark bacterial/fungal infectious complications of IDU. These include bacteremia, IE, OM, spinal epidural abscess, septic arthritis, and SSTIs (Table 1).
Bacteremia is an unsurprising complication of IDU, and frequently presents concomitantly with other infections. Causative organisms range from expected skin or oral species including Staphylococcus aureus, Streptococcus spp., Candida spp. to more uncommon organisms such as Bacillus cereus.21–24 It is noteworthy that one common phenomenon, “cotton fever,” refers to a self-limited syndrome that produces a systemic inflammatory response syndrome-like response. Individuals who report utilization of cottons as a filter sometimes develop fever, myalgias, nausea, vomiting, etc., within half an hour of injecting; they are also frequently found to have brief lab abnormalities including leukocytosis. However, infectious workup can be negative and the syndrome resolves within 12 hours. It is still unclear why this occurs, but the leading theory (the endotoxin theory) posits that a transient bacteremia occurs with Enterobacter agglomerans, which colonizes cotton and releases endotoxins. Alternate theories include an immunologic response (in some individuals who have preformed antibodies against cotton) or a pharmacologic response (pyrogenic substances within cotton may cause the reaction).25
IE can present somewhat differently in PWID compared with the general population. Although it has been recently noted that there is an increasing proportion of PWID who develop left-sided IE (or involvement of multiple valves), classically, right-sided heart valves are more frequently involved.26,27 Ninety percent of right-sided IE occurs in PWID, whereas this group only comprises 20% of left-sided IE.27 There are several hypotheses for why this may occur—adulterants in substances (eg, talc) may cause endothelial damage to the tricuspid valve predisposing to infection, and repetitive IDU itself may cause subclinical damage. Right-sided IE leads to a higher rate of septic pulmonary emboli. The peripheral emboli and immunologic vascular phenomena typically associated with left-sided IE are seen less frequently. In addition, acute IE generally evolves too quickly for these phenomena to develop regardless; the most common symptoms are nonspecific constitutional ones.28 As a result, suspicion should remain high for IE even in the absence of “classic” findings; indeed, the modified Duke criteria list IDU itself as a minor criterion, given the high risk. It is noteworthy that although initial diagnostic imaging with a transthoracic echocardiogram may demonstrate large vegetations, the sensitivity for IE is only 55% despite advances in imaging technology; if clinical suspicion remains high, a negative transthoracic echocardiogram cannot rule out the diagnosis.29
Common pathogens isolated in PWID with IE include S. aureus, coagulase-negative staphylococci, and beta-hemolytic streptococci, that is, skin flora introduced through an unsterile injection technique. Similarly, polymicrobial infections can be seen, as can organisms from the environment (aerobic gram-negative rods including Pseudomonas aeruginosa, fungi including Candida spp.).28 Importantly, despite the less frequent degree of peripheral embolization, the high virulence of S. aureus should prompt careful monitoring for signs and symptoms of possible infection at other sites, such as the abdomen (eg, spleen), flank (eg, renal or psoas involvement), brain (abscess), and bone (especially spine). As with IE in other groups, IE ideally requires prolonged intravenous antibiotic therapy and consideration of surgical intervention. Certain uncomplicated methicillin-sensitive S. aureus infections may be feasible to manage with a 2-week course alone, but otherwise, a minimum of 4 weeks is recommended. Conversion to oral therapy has not yet been well studied.
One burgeoning area of concern surrounds PWID who require valve surgery for an index episode of IE. Given the relapsing and remitting nature of OUD, recurrent IDU can predispose to prosthetic valve endocarditis. As a result, there is a preference for medical management alone, but surgical intervention should be considered in patients with right heart failure due to severe tricuspid regurgitation, difficult-to-clear infection with fungi or resistant organisms, vegetation size over 20 mm, recurrent pulmonary septic emboli despite adequate medical therapy, or general lack of response to medical therapy. Valve repair is preferred over valve replacement for similar reasons.28
Vertebral OM generally occurs through hematogenous spread and is typically monomicrobial. Most commonly, S. aureus is the etiologic pathogen, although aerobic gram-negative bacilli are found in roughly one-third of cases. In PWID, occasionally, this includes P. aeruginosa and Serratia marcescens, and fungi can rarely occur as well.30 Definitive identification of the organism ideally occurs with deep culture, i.e. open bone biopsy or percutaneous needle/aspiration biopsy; cultures taken from more surface aspects, such as of any associated sinus tract, may be congruent in less than half of the cases.31 Blood cultures are the exception, as a positive with a likely pathogen as noted above can obviate the need for biopsy; however, these are frequently negative. Thus, to increase yield, antibiotics should be deferred until deep culture is obtained, if the patient is otherwise clinically stable. After identification of the organism, a minimum of 6 weeks of antibiotics is recommended. Given excellent bone penetration of certain highly bio-available oral agents, parenteral antibiotics are not necessarily required for the full course.32 Surgery should be considered in patients who have progression of disease despite medical therapy alone, those with new neurological deficits associated with onset of OM, possible or actual cord compression due to vertebral instability, or vertebral or epidural abscess requiring drainage. Given concern for hardware infection, antibiotics are frequently extended in these scenarios; however, there are limited data to guide optimal duration.
Spinal epidural abscess
Spinal epidural abscess overlaps significantly with vertebral OM, with similar mechanisms of pathogenesis. Microbiology is similar as well, with S. aureus comprising anywhere from 50% to 90% of cases.33 Other organisms include streptococci and again aerobic gram-negative bacilli; P. aeruginosa is more common in PWID.33 In contrast to OM, early surgical management or drainage of the space is critical in achieving source control. In one study, 41% of patients treated initially only with medical management had progressive neurological deficits or pain, ultimately requiring surgery.34 In accordance with this, there is less need to delay therapy while awaiting deep cultures, as antibiotics alone will likely not sterilize the entirety of an abscess. Duration of therapy is also shorter compared with OM, with a minimum of 4 to 6 weeks; if there is contiguous OM, however, duration should of course be extended as above. Oral antibiotics have not been well studied.
Septic arthritis similarly presents primarily due to hematogenous spread, as direct intra-articular inoculation during IDU is rare. Again, predominantly, S. aureus and streptococci are responsible; gram-negative bacilli, especially P. aeruginosa, are also more frequent in PWID, although to a lesser degree than in the above infections.35 Synovial aspiration and drainage is necessary for diagnostic purposes, and therapeutically for source control. Depending on the joint, this may be accomplished by needle aspiration, arthroscopy, or possibly surgically, should the previous measures fail. Antibiotic duration has not been well studied, but expert opinion suggests a minimum of 4 weeks; if the individual did not have concomitant bacteremia and a highly bio-available oral agent is available for the targeted organism, it is reasonable to pursue a short 1 to 2-week course of IV antibiotics before completing the course with oral agents.36
Skin and soft tissue infection
SSTI run the gamut from cellulitis and abscess, to deeper space infection. They tend to occur in the setting of nonsterile technique, inadvertent injection into the tissue space due to inexperience in finding a vein, or with “skin-popping” or “muscling.” Despite being relatively less severe than other infections mentioned above, they are incredibly common; one survey in San Francisco found that 68% of PWID had ever had an abscess and 32% of individuals had an SSTI noted on physical examination at the time of interview.37 Another study in Miami noted that of PWID who were hospitalized for an infectious complication, 64% were admitted for complicated SSTI.38 Abscess is predominantly due to S. aureus, which is the causative organism in up to 75% of cases.39 However, they can be polymicrobial. Oral anaerobes such as Fusobacterium, Prevotella, Peptostreptococcus, Actinomyces, and Veillonella are also frequently seen in PWID, as needles are sometimes licked.40 There have additionally been case reports of Clostridium spp. causing severe infection.20 Incision and drainage is typically sufficient for treatment, although if there is concern for more systemic infection or overlying cellulitis, a short course of antibiotics is reasonable.41 Cellulitis is typically caused by Streptococcus pyogenes or group A Streptococcus, and occasionally aerobic gram-negative bacilli. Imaging such as ultrasound can help differentiate between purulent or complicated cellulitis and abscess. Occasionally, these SSTI may become complicated by deep infections, such as pyomyositis, necrotizing fasciitis, etc. In one single center, necrotizing fasciitis involving PWID comprised half of all cases of necrotizing fasciitis over 15 years; there were no significant differences in microbiology compared with non–IDU-associated cases.42
Hepatitis A is an acute, vaccine-preventable infection that spreads through fecal-oral transmission. Although outbreaks have historically been attributable to contaminated food supply, recent US outbreaks associated with drug use and homelessness reflect a shift in the epidemiology of this infection.43 As such, all people who use drugs should be immunized for hepatitis A.
Hepatitis B is a chronic, vaccine-preventable infection that spreads through blood-borne and sexual transmission. Worldwide, there are 1.2 million PWID estimated to be chronically infected with hepatitis B.44 In the United States, as the overall incidence of hepatitis B virus (HBV) in the United States has declined due to the introduction of the HBV vaccine, the proportion of incidence attributable to drug use has increased,45 with outbreaks in drug-using populations being particularly marked in regions with limited access to OUD treatment and harm-reduction strategies such as needle and syringe programs.46 All people who use drugs should be tested for HBV status and vaccinated if nonimmune. Individuals chronically infected with HBV should be treated per the guidelines.
Hepatitis C is a chronic infection, which spreads through blood-borne and sexual transmission. As of 2013, hepatistis C virus (HCV) is responsible for more deaths in the United States than the other 60 nationally notifiable infectious complications, combined.47 Globally, 52.3% of PWID are HCV antibody positive,48 with IDU representing the predominant mode of HCV transmission in the United States.49 Recent HCV incidence in the United States has paralleled the rising opioid epidemic, with a 400% increase in acute HCV among 18 to 29 year-olds between 2004 and 2014, simultaneous with an 817% increase in admissions for injection of prescription opioids and a 600% increase in admissions for heroin injection.50 In addition, there has been an increase in HCV prevalence among pregnant women of child-bearing age, with a 93% increase in the rate of HCV infection among pregnant Wisconsin Medicaid recipients.51 Although there is no vaccine to prevent HCV infection, provision of opioid agonist therapy (OAT) decreases the incidence of HCV, in particular, when provided in combination with syringe service programs.52
The recent advent of oral direct-acting antivirals enables HCV cure with minimal side effects in over 90% of patients, with an 8 to 12-week course of treatment.53–56 Studies of HCV treatment in people with OUD have demonstrated high rates of cure in people stably on OAT,57 and those with recent IDU, with cure rates not impacted by ongoing drug use at the time of treatment.58 In addition, initiation of OAT concurrent to HCV treatment has been associated with improved rates of HCV cure and reduced risk behaviors in people with OUD and ongoing IDU.59 Although the rate of HCV reinfection is around 5.9/100 person-years among people with recent drug use,60 scale-up of OAT, harm-reduction services, and expansion of access to HCV treatment for people with OUD should further reduce prevalence and reinfection in this population.61 All patients should receive HCV testing at least once, with annual retesting in individuals with ongoing risk factors.62 All individuals chronically infected with HCV should be offered HCV treatment and retreatment, without restrictions based on drug use.
HIV infection linked to IDU typically occurs in 1 of 10 new infections. PWID are at risk of HIV transmission both through the process of sharing HIV-infected needles and other drug paraphernalia but also through high-risk sexual practices.63 Recently, there have been several notable outbreaks of HIV that have raised concerns that the ongoing opioid crisis is mitigating the efforts to eliminate new HIV infections in this country, the goal of the Ending the HIV Epidemic initiative.64 A large outbreak in rural Scott County, Indiana, epitomized the potentially dire consequences of HIV being transmitted in an IDU population where over 200 individuals were infected with HIV within a group of individuals who shared needles when injecting a prescription opioid, oxymorphone.65,66 The impact on the local health care system was immense as HIV providers were not readily available to address this health crisis, individuals trained to address addiction were unavailable, and there was no needle-exchange program that could have interrupted the transmission network. The outbreak was finally controlled after a multi-faceted effort from government agencies at all levels (local, state, and federal) and academic medical institutions that resulted in on-site programs to provide comprehensive services that included contact tracing, HIV and hepatitis C virus testing, HIV treatment, syringe exchange, and even insurance enrollment.67 Delivering HIV and HCV care requires an expanded set of resources often lacking in rural areas and it is likely that such clusters of HIV infections will be repeated in other rural regions largely unprepared to handle this type of health crisis.68
This type of outbreak is occurring elsewhere and not limited to those areas of rural America hit hardest by the opioid epidemic. In Massachusetts, a similar cluster of new HIV infections was identified, with over a hundred new infections linked epidemiologically.69,70 The reported increased frequency of fentanyl injection may have increased transmission in this outbreak and the frequency of homelessness and incarceration among injection drug users resulted in challenges in identifying individuals at risk and those who needed treatment. In 2018, the number of HIV diagnoses among heterosexuals in King County, Washington, who inject drugs increased 286%, again demonstrating the need for broad surveillance of this at-risk population.71
HIV-infected patients with OUD have improvements in their HIV viral load and retention in care when they are treated with medications for addiction treatment (MAT).72 Prevention of new HIV infections is the goal, but once an individual is HIV infected, engagement with these individuals and treatment of both their HIV and OUD is necessary, ideally in the same medical home, and efforts to ensure that both of these treatments are widely available to PWID are required.73–75
Unique challenges and harm reduction
PWID often suffer unique challenges in obtaining, and maintaining, access to care. Comorbid mental health disorders, limited resources and social support, housing instability, legal concerns, and other issues all play into a person’s difficulty in seeking or staying engaged in the health care environment. Unfortunately, these factors often present major barriers to completing therapy for the above serious infections. Whether parenterally or orally, individuals ideally should commit to weeks of therapy and attend close follow-up appointments, both in the short and in the long term. Stigma and mistrust of health care institutions also play a role in engagement in care. Finally, treatment of underlying OUD is of paramount importance, but recognition of this need has only recently risen to the forefront of practitioners’ awareness. PWID often suffer worsened morbidity and mortality compared with individuals without IDU, despite being younger and with fewer comorbidities.26
For example, the standard of care for individuals with severe infection, without IDU, typically includes outpatient parenteral antimicrobial therapy (OPAT) when available. This allows people to return to their home setting and functioning while still obtaining treatment, typically through durable venous access (eg, a peripherally inserted central venous catheter, or PICC). Studies have shown that the rate of cure is superior for OPAT compared with completing therapy as an inpatient; patient satisfaction is greater due to comfort and privacy; there is a reduction in nosocomial infection; and it is less cost-intensive.76,77 However, PWID are usually not offered OPAT, given concern for misuse of a PICC for substance use, and concern for nonadherence to follow-up appointments.78 As a result, for PWID, up to 75% of cases nationally result in an entire treatment course in the hospital or at another supervised facility—if the course is completed at all.8 During prolonged inpatient hospitalization, a noninsignificant proportion of PWID will leave against medical advice; in one multi-center study, this represented roughly a quarter of all cases.79
It is important to recognize that weeks of inpatient stay may be an insurmountable challenge for many PWID. These are individuals who already suffer from mistrust of the health care system, who feel deeply stigmatized, who may have trauma histories lending to maladaptive coping behaviors, and whose underlying OUD may not be adequately managed. A large international review noted that negative attitudes of health care providers toward PWID were common, resulting in less engagement and diminished empathy, contributing to worsened subsequent health outcomes.80 Several studies have described suboptimal linkage to addiction care and MAT, both during hospitalization and in discharge planning.79,81 Nationally, a survey of infectious disease providers found that only 35% of respondents felt that there was comprehensive OUD management at their health care facility.8 It is perhaps understandable that PWID feel that their needs are not adequately met in the constraints of the current health care system.
Within this context, recent studies have begun re-examining whether OPAT is a feasible mechanism for PWID with serious infection in the United States. Internationally, many centers report experience with this, and only 11% of 64 surveyed centers (in Australia, New Zealand, Asia, North America, the United Kingdom, and Europe) reported IDU history being an exclusion from OPAT.82 In the United States, a recent review78 found that OPAT in PWID may be comparable in completion rates, mortality, and catheter-related complications; most of the reviewed studies involved discharge with PICC to home, with antibiotics administered either during scheduled visits to an infusion center, or at home with a visiting nurse for assistance. In terms of possible PICC misuse, the review identified one study that noted a 2% rate; other studies did not find evidence of this. Given the paucity of data and lack of randomized controlled trials, further study is needed to best clarify the risks/benefits of OPAT in PWID; however, it appears that this may be a viable strategy.78 In addition, new long-acting antibiotics may help further address this issue. For instance, dalbavancin, a once-weekly antimicrobial with gram-positive activity including against methicillin-resistant S. aureus, is currently cleared for use only in SSTIs. However, review of the literature reveals encouraging data for off-label use for OM, endovascular infection, and uncomplicated bacteremia.83
Treating the underlying OUD, however, may be one of the most critical aspects to preventing recurrent infection. As noted previously, tackling this requires a deep understanding of the many complex challenges facing someone struggling with OUD. When patients are in medical care for an infection, providers should recognize an opportunity to engage someone in addiction management. If available, consultation with Social Work and Addiction is recommended. Discussion surrounding medication, such as buprenorphine, methadone, and intramuscular naltrexone, should be initiated as well. At minimum, discharge planning should include OUD as an issue; harm-reduction strategies and naloxone distribution for overdose prevention should also be given to the patient. Currently, providers are not consistently meeting these proposed standards. For instance, 2 recent studies at separate institutions found that discharge planning included OUD as an issue in only roughly half of hospitalizations; 0 prescriptions were written for naloxone on discharge in either study. Linkage to medication was also suboptimal. One study found only 11% of patients had a plan for outpatient MAT; the other study found that only 25% of patients received any medication while inpatient, and only 2% had a clear outpatient treatment plan.79,81 Further efforts to educate providers about the importance of robust addiction care should be stressed.
As health care systems continue building comprehensive treatment frameworks for PWID, harm-reduction practices are critical. Specifically, with respect to infectious complications of OUD, safe injection practice resources should be provided to all PWID. This includes counseling about access to needle and syringe programs, if available. When access to new needles and syringes is not available, as noted previously, patients should be counseled on cleaning equipment with bleach and water between uses, and never sharing equipment. With respect to preventing HIV acquisition, patients should be considered for preexposure prophylaxis, an intervention shown to be remarkably effective in preventing sexual transmission of HIV.84 Starting PWID on preexposure prophylaxis medications (tenofovir/emtricitabine) is recommended per the CDC and newly so per the US Preventive Services Task Force, but the uptake of this strategy by both providers and PWID is inadequate to date.85,86
In summary, the infectious complications of OUD present a serious challenge to individuals, the health care system, and the country at large. The scope of these issues continues to mount, posing a significant crisis in terms of morbidity, mortality, and cost. The infectious sequelae of IDU comprise a wide set of clinical syndromes that require a multidisciplinary approach to care. These infections may, however, represent opportunities to link PWID to treatment for their OUD. As health care providers, it is critical that we utilize these opportunities to build rapport with our patients, offer empathetic and nonjudgmental care, plan for optimization of addiction services including medication, and provide harm-reduction strategies.
Conflict of interest disclosure
The authors declare that they have nothing to disclose.
1. Kolodny A, Courtwright DT, Hwang CS, et al. The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annu Rev Public Health. 2015;36:559–574.
2. Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control. Trends in the distribution of selected opioids by state, US, 1999–2011. Available at: https://c.ymcdn.com/sites/safestates.site-ym.com/resource/resmgr/imported/Jones.pdf
. Accessed November 17, 2019.
3. Centers for Disease Control and Prevention (CDC) Injury Center. Understanding the epidemic. Drug overdose. 2018. Available at: www.cdc.gov/drugoverdose/epidemic/index.html
. Accessed November 14, 2019.
4. CBHSQ. 2018 NSDUH detailed tables. 2019. Available at: www.samhsa.gov/data/report/2018-nsduh-detailed-tables
. Accessed November 13, 2019.
5. Warner M, Chen L-H. Trends in drug-poisoning deaths involving opioid analgesics and heroin: United States, 1999-2012. 2014. Available at: www.cdc.gov/nchs/data/databriefs/db166.htm
. Accessed November 13, 2019.
6. Scholl L, Seth P, Kariisa M, et al. Drug and opioid-involved overdose deaths—United States, 2013–2017. MMWR Morb Mortal Wkly Rep. 2019;67:1419–1427.
7. Heron M. National Vital Statistics Reports, Volume 68, Number 6, June 24, 2019, Deaths: Leading Causes for 2017. 2019. Available at: www.cdc.gov/nchs/products/index.htm
. Accessed November 13, 2019.
8. Rapoport AB, Beekmann SE, Polgreen PM, et al. Injection drug use and infectious disease practice: a National Provider Survey. Open Forum Infect Dis. 2017;4(suppl 1):S340–S340.
9. Centers for Disease Control and Prevention (CDC). HIV among people who inject drugs. HIV by Group. HIV/AIDS. 2018. Available at: www.cdc.gov/hiv/group/hiv-idu.html
. Accessed November 14, 2019.
10. Ramachandran S, Thai H, Forbi JC, et al. A large HCV transmission network enabled a fast-growing HIV outbreak in rural Indiana, 2015. EBioMedicine. 2018;37:374–381.
11. Conrad C, Bradley HM, Broz D, et al. Community outbreak of hiv infection linked to injection drug use of oxymorphone—Indiana, 2015. Morb Mortal Wkly Rep. 2015;64:443–444.
12. Zibbell JE, Asher AK, Patel RC, et al. Increases in acute hepatitis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014. Am J Public Health. 2018;108:175–181.
13. Ronan MV, Herzig SJ. Hospitalizations related to opioid abuse/dependence and associated serious infections increased sharply, 2002-12. Health Aff. 2016;35:832–837.
14. Moradi-Joo M, Ghiasvand H, Noroozi M, et al. Prevalence of skin and soft tissue infections and its related high-risk behaviors among people who inject drugs: a systematic review and meta-analysis. J Subst Use. 2019;24:350–360.
15. Getting Off Right: A Safety Manual for Injection Drug Users. 2012. Available at: https://harmreduction.org/drugs-and-drug-users/drug-tools/getting-off-right/
. Accessed November 20, 2019.
16. Newton-John HF, Wise K, Looke DF. Role of the lemon in disseminated candidiasis of heroin abusers. Med J Aust. 1984;140:780–781.
17. Shankland GS, Richardson MD. Epidemiology of an outbreak of candida endophthalmitis in heroin addicts: identification of possible source of infection by biotyping. Med Mycol. 1988;26:199–202.
18. Trpin S, Gracner T, Pahor D, et al. Phacoemulsification in isolated endogenous Candida albicans
anterior uveitis with lens abscess in an intravenous methadone user. J Cataract Refract Surg. 2006;32:1581–1583.
19. Ciccarone D, Bourgois P. Explaining the geographical variation of HIV among injection drug users in the United States. Subst Use Misuse. 2003;38:2049–2063.
20. Ebright JR, Pieper B. Skin and soft tissue infections in injection drug users. Infect Dis Clin North Am. 2002;16:697–712.
21. Barter DM, Johnston HL, Williams SR, et al. Candida bloodstream infections among persons who inject drugs–Denver Metropolitan Area, Colorado, 2017-2018. MMWR Morb Mortal Wkly Rep. 2019;68:285–288.
22. Ball SC, Sepkowitz K. Infection due to Bacillus cereus
in an injection drug user with AIDS: bacteremia without morbidity. Clin Infect Dis. 1994;19:216–217.
23. Schaefer G, Campbell W, Jenks J, et al. Persistent Bacillus cereus
bacteremia in 3 persons who inject drugs, San Diego, California, USA. Emerg Infect Dis. 2016;22:1621–1623.
24. Benusic MA, Hoang LMN, Press NM, et al. A cluster of Bacillus cereus
bacteremia cases among injection drug users. Can J Infect Dis Med Microbiol. 2015;26:103–104.
25. Zerr AM, Ku K, Kara A. Cotton fever: a condition self-diagnosed by IV drug users. J Am Board Fam Med. 2016;29:276–279.
26. Leahey PA, Lasalvia MT, Rosenthal ES, et al. High morbidity and mortality among patients with sentinel admission for injection drug use-related infective endocarditis. Open Forum Infect Dis. 2019;6:ofz089.
27. Moreillon P, Que Y-A. Infective endocarditis. Lancet (London, England). 2004;363:139–149.
28. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435–1486.
29. Reynolds HR, Jagen MA, Tunick PA, et al. Sensitivity of transthoracic versus transesophageal echocardiography for the detection of native valve vegetations in the modern era. J Am Soc Echocardiogr. 2003;16:67–70.
30. Holzman RS, Bishko F. Osteomyelitis in heroin addicts. Ann Intern Med. 1971;75:693–696.
31. Mackowiak PA, Smith JW, Jones SR. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA J Am Med Assoc. 1978;239:2772–2775.
32. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61:e26–e46.
33. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th ed. Elsevier. 2019:1265.
34. Patel AR, Alton TB, Bransford RJ, et al. Spinal epidural abscesses: risk factors, medical versus surgical management, a retrospective review of 128 cases. Spine J. 2014;14:326–330.
35. Allison DC, Holtom PD, Patzakis MJ, et al. Microbiology of bone and joint infections in injecting drug abusers. Clin Orthop Relat Res. 2010;468:2107–2112.
36. Septic arthritis in adults—UpToDate. 2019. Available at: www.uptodate.com/contents/septic-arthritis-in-adults
. Accessed December 3, 2019.
37. Binswanger IA, Kral AH, Bluthenthal RN, et al. High prevalence of abscesses and cellulitis among community-recruited injection drug users in San Francisco. Clin Infect Dis. 2000;30:579–581.
38. Tookes H, Diaz C, Li H, et al. A cost analysis of hospitalizations for infections related to injection drug use at a county safety-net hospital in Miami, Florida. PLoS One. 2015;10:0129360.
39. Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666–674.
40. Summanen PH, Talan DA, Strong C, et al. Bacteriology of skin and soft-tissue infections: comparison of infections in Intravenous Drug users and individuals with no history of Intravenous Drug use. Clin Infect Dis. 1995;20:S279–S282.
41. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:e10–e52.
42. Chen JL, Fullerton KE, Flynn NM. Necrotizing fasciitis associated with injection drug use. Clin Infect Dis. 2001;33:6–15.
43. Foster M, Ramachandran S, Myatt K, et al. Hepatitis A virus outbreaks associated with drug use and homelessness—California, Kentucky, Michigan, and Utah, 2017. MMWR Morb Mortal Wkly Rep. 2018;67:1208–1210.
44. Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378:571–583.
45. Iqbal K, Klevens RM, Kainer MA, et al. Epidemiology of acute hepatitis B in the United States from population-based surveillance, 2006-2011. Clin Infect Dis. 2015;61:584–592.
46. Harris AM, Iqbal K, Schillie S, et al. Increases in acute hepatitis B virus infections—Kentucky, Tennessee, and West Virginia, 2006-2013. MMWR Morb Mortal Wkly Rep. 2016;65:47–50.
47. Ly KN, Hughes EM, Jiles RB, et al. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016;62:1287–1288.
48. Degenhardt L, Peacock A, Colledge S, et al. Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review. Lancet Glob Health. 2017;5:e1192–e1207.
49. Hepatitis C questions and answers for health professionals. 2018. Available at: www.cdc.gov/hepatitis/hcv/hcvfaq.htm
. Accessed November 24, 2019.
50. Zibbell P, Kashif I, Patel R, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years—Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012. CDC MMWR Morb Mortal Wkly Rep. 2015;64:453–458.
51. Watts T, Stockman L, Martin J, et al. Increased risk for mother-to-infant transmission of hepatitis C virus among medicaid recipients—Wisconsin, 2011-2015. MMWR Morb Mortal Wkly Rep. 2017;66:1136–1139.
52. Platt L, Minozzi S, Reed J, et al. Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis. Addiction. 2017:545–563.
53. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med. 2015;163:1–13.
54. Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17:1062–1068.
55. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889–1898.
56. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373:2599–2607.
57. Dore GJ, Altice F, Litwin AH, et al. Elbasvir-Grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: a randomized trial. Ann Intern Med. 2016;165:625–634.
58. Grebely J, Dalgard O, Conway B, et al. Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3:153–161.
59. Rosenthal ES, Mathur P, Gross C, et al. Concurrent initiation of hepatitis C and opioid use disorder treatment in people who inject drugs. Clin Infect Dis. 2020. [Epub ahead of print].
60. Hajarizadeh B, Cunningham EB, Valerio H, et al. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: a meta-analysis. J Hepatol. 2019. [Epub ahead of print].
61. Martin NK, Hickman M, Hutchinson SJ, et al. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013;57(suppl 2):S39–S45.
62. AASLD/IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2019. Available at: www.hcvguidelines.org
. Accessed November 24, 2019.
63. Burnett JC, Broz D, Spiller MW, et al. HIV infection and HIV-associated behaviors among persons who inject drugs—20 Cities, United States, 2015. MMWR Morb Mortal Wkly Rep. 2018;67:23–28.
64. Fauci AS, Redfield RR, Sigounas G, et al. Ending the HIV epidemic: a plan for the United States. JAMA. 2019;321:844–845.
65. Peters PJ, Pontones P, Hoover KW, et al. HIV infection linked to injection use of oxymorphone in Indiana, 2014-2015. N Engl J Med. 2016;375:229–239.
66. Gonsalves GS, Crawford FW. Dynamics of the HIV outbreak and response in Scott County, IN, USA, 2011-15: a modelling study. Lancet HIV. 2018;5:e569–e577.
67. Janowicz DM. HIV transmission and injection drug use: lessons from the Indiana outbreak. Top Antivir Med. 2016;24:90–92.
68. Schranz AJ, Barrett J, Hurt CB, et al. Challenges facing a rural opioid epidemic: treatment and prevention of HIV and hepatitis C. Curr HIV/AIDS Rep. 2018;15:245–254.
69. Cranston K, Alpren C, John B, et al. Notes from the field: HIV diagnoses among persons who inject drugs—Northeastern Massachusetts, 2015-2018. MMWR Morb Mortal Wkly Rep. 2019;68:253–254.
70. Alpren C, Dawson EL, John B, et al. Opioid use fueling HIV transmission in an urban setting: an outbreak of HIV infection among people who inject drugs-Massachusetts, 2015-2018. Am J Public Health. 2020;110:37–44.
71. Golden MR, Lechtenberg R, Glick SN, et al. Outbreak of human immunodeficiency virus infection among heterosexual persons who are living homeless and inject drugs—Seattle, Washington, 2018. MMWR Morb Mortal Wkly Rep. 2019;68:344–349.
72. Adams JW, Marshall BDL, Mohd Salleh NA, et al. Receipt of opioid agonist treatment halves the risk of HIV-1 RNA viral load rebound through improved ART adherence for HIV-infected women who use illicit drugs. Drug Alcohol Depend. 2019:107670.
73. Carroll JJ, Colasanti J, Lira MC, et al. HIV physicians and chronic opioid therapy: it’s time to raise the bar. AIDS Behav. 2019;23:1057–1061.
74. Fanucchi L, Springer SA, Korthuis PT. Medications for treatment of opioid use disorder among persons living with HIV. Curr HIV/AIDS Rep. 2019;16:1–6.
75. Oldfield BJ, Munoz N, McGovern MP, et al. Integration of care for HIV and opioid use disorder. AIDS. 2019;33:873–884.
76. Seaton RA, Barr DA. Outpatient parenteral antibiotic therapy: principles and practice. Eur J Intern Med. 2013;24:617–623.
77. Mitchell ED, Murray CC, Meads D, et al. Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review. BMJ Open. 2017;7:013560.
78. Suzuki J, Johnson J, Montgomery M, et al. Outpatient parenteral antimicrobial therapy among people who inject drugs: a review of the literature. Open Forum Infect Dis. 2018;5:ofy194.
79. Serota DP, Niehaus ED, Schechter MC, et al. Disparity in quality of infectious disease vs addiction care among patients with injection drug use–associated Staphylococcus aureus
bacteremia. Open Forum Infect Dis. 2019;6:ofz289.
80. Van Boekel LC, Brouwers EPM, Van Weeghel J, et al. Stigma among health professionals towards patients with substance use disorders and its consequences for healthcare delivery: systematic review. Drug Alcohol Depend. 2013;131:23–35.
81. Rosenthal ES, Karchmer AW, Theisen-Toupal J, et al. suboptimal addiction interventions for patients hospitalized with injection drug use-associated infective endocarditis. Am J Med. 2016;129:481–485.
82. Ho J, Archuleta S, Tice A, et al. International approaches to treating intravenous drug users in outpatient parenteral antibiotic services. Infect Dis Clin Pract. 2012;20:192–195.
83. Bork JT, Heil EL, Berry S, et al. Dalbavancin use in vulnerable patients receiving outpatient parenteral antibiotic therapy for invasive gram-positive infections. Infect Dis Ther. 2019;8:171–184.
84. Riddell Jt, Amico KR, Mayer KH. HIV preexposure prophylaxis: a review. JAMA. 2018;319:1261–1268.
85. Smith DK, Martin M, Lansky A, et al. Update to interim guidance for preexposure prophylaxis (PrEP) for the prevention of HIV infection: PrEP for injecting drug users. MMWR Morb Mortal Wkly Rep. 2013;62:463–465.
86. Bazzi AR, Biancarelli DL, Childs E, et al. Limited knowledge and mixed interest in pre-exposure prophylaxis for HIV prevention among people who inject drugs. AIDS Patient Care STDS. 2018;32:529–537.