Psychiatric Annals

CME Article 

Infectious Disease Complications in People Who Inject Drugs

Phillip P. Santoiemma, MD, MSE, MTR; Stephen H. Dinwiddie, MD; Michael P. Angarone, DO

Abstract

Injection drug use (IDU) is a complicated social and medical issue. Infectious diseases often affect morbidity and mortality in people who inject drugs and can complicate the management of comorbid medical and psychiatric conditions. The major complications of IDU include viral and bacterial infections, namely HIV, hepatitis B virus, hepatitis C virus, and bacteremia/endocarditis. These infections, as well as the other medical and psychiatric conditions associated with IDU, complicate treatment, management, and societal prevention of substance use. There are various resources and recommendations that clinicians should track when treating patients who inject drugs; these patients require a multidisciplinary team to manage their challenging medical care. [Psychiatr Ann. 2017;47(1):33–37.]

Abstract

Injection drug use (IDU) is a complicated social and medical issue. Infectious diseases often affect morbidity and mortality in people who inject drugs and can complicate the management of comorbid medical and psychiatric conditions. The major complications of IDU include viral and bacterial infections, namely HIV, hepatitis B virus, hepatitis C virus, and bacteremia/endocarditis. These infections, as well as the other medical and psychiatric conditions associated with IDU, complicate treatment, management, and societal prevention of substance use. There are various resources and recommendations that clinicians should track when treating patients who inject drugs; these patients require a multidisciplinary team to manage their challenging medical care. [Psychiatr Ann. 2017;47(1):33–37.]

Infectious diseases often complicate the medical and psychiatric treatment of patient's who inject drugs. This article presents the background of injection drug use (IDU) in the United States, focusing on the viral- and bacterial-infectious complications. Furthermore, the article discusses the medical and psychiatric comorbidities that occur with IDU, pharmacological complications, as well as efforts to reduce the prevalence of IDU.

The Epidemiology of Injection Drug Use

IDU has been prevalent in the US since the early 1900s. Intravenous injection is the most common means of administration but users may also inject drugs using subcutaneous (ie, skin popping) or intramuscular techniques. These practices can foster various infectious and other medical complications, especially HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and bacteremia/endocarditis (Table 1). The sharing of needles and syringes is the major risk factor for the acquisition of blood-borne pathogens such as HIV, HBV, and HCV, whereas the use of contaminated drugs and nonsterile drug paraphernalia and injection techniques increases the possibility for systemic infections, such as bacteremia, endocarditis, and cellulitis.1–3


            Medical and Psychiatric Complications of Injection Drug Use

Table 1.

Medical and Psychiatric Complications of Injection Drug Use

Infections Associated with Injection Drug Use

HIV. The Centers for Disease Control and Prevention (CDC) estimates that there are approximately 1.2 million people living with HIV, with approximately 50,000 new infections occurring annually in the US—a number that is, fortunately, trending downwards.4 Nonetheless, it is estimated that of the new annual infections, approximately 11% are due, in part, to IDU (7% directly attributable to IDU and 4% related to high-risk sexual behaviors combined with IDU).4,5 Extrapolating yearly data on IDU, approximately 10% to 40% of people who inject drugs (PWIDs) are infected with HIV; therefore, an estimated 260,000 people with HIV potentially acquired the virus through IDU.6 The IDU transmission rate of HIV has been estimated to be 1 in 150 exposures.7 As many as one-third of the PWIDs share needles and syringes, which dramatically increases the risk of HIV infection.8

People who have HIV and inject drugs often lack access to appropriate health care in general as well as HIV treatment. The CDC estimates that ≥60% of people with HIV who also inject drugs are either homeless or have been incarcerated; ≥40% also lack health insurance, making it difficult to find appropriate care, start HIV therapy, or start substance-dependence treatment.8 Treatment access is particularly important given that a major advance in HIV care has been the advent of combination antiretroviral therapy, which has substantially extended life expectancy and is currently recommended no matter the CD4 T-cell count or HIV viral load (Table 2).


            Current Recommendations for Antiviral Treatments for HBV, HCV, and HIVa

Table 2.

Current Recommendations for Antiviral Treatments for HBV, HCV, and HIV

HBV. According to the CDC, approximately 20,000 new HBV cases occur each year in the US, with 17% of those cases resulting from IDU; approximately 4% to 6% of PWIDs are infected with HBV.9,10 Prevention of virus acquisition can be accomplished through vaccination, with ≥90% efficacy. Currently, the CDC and Advisory Committee on Immunization Practices recommend HBV vaccination for all adults who use injection drugs and are seronegative for HBV infection. A person who presents after an exposure can be given the HBV vaccine series or the HBV vaccine series with HBV immunoglobulin if the contact source is HBV positive.11 Like the patients with HIV as described above, people with HBV often lack access to medical care, making them less likely to receive appropriate screening and treatment (Table 2).

HCV. There are approximately 30,000 new cases of HCV annually, with that number rising recently.9 The age distribution of HCV is bimodal, with most patients with HCV having been born between 1945 and 1965 in which the likely transmission was through blood transfusions and IDU earlier in life, whereas young adolescents/adults acquire the virus mainly from IDU (although high-risk sexual practices are also known to be a factor).12 IDU accounts for a large proportion of new infections, with estimates ≥54% in the US, and at 90% globally.13 Due to the indolent state and often asymptomatic nature of the virus, 40% to 80% of all PWIDs currently have HCV,14,15 which is higher than the prevalence of HIV because HCV is more transmissible.

Because there is no vaccine for HCV, prevention efforts currently focus on needle-exchange programs and education about proper injection techniques as well as the identification of those people infected with HCV. The CDC recommends screening for HCV infection by using a serum HCV antibody test. People who continue to use intravenous drugs should be screened periodically, although no recommended time interval for screening exists.16

It is important to realize that, although acute infection may be asymptomatic or manifest with only mild symptoms, if left untreated, those people will ultimately develop cirrhosis and/or hepatocellular carcinoma. Moreover, concurrent heavy alcohol use is associated with worse outcome.17 Thus, prompt identification of people with HCV is vital and should lead to assessment of the degree of liver damage, determination of treatment needs, and education to help regulate behaviors related to substance abuse. In this light, over the past 3 years there has been a revolution in the available HCV treatments. These new agents are direct antivirals targeted against HCV and have >90% cure rates.18 Recommendations for HCV treatment are constantly changing19 (Table 2). Further details related to HCV treatment with concurrent psychiatric diseases is reviewed elsewhere;20 exact treatment plans should be discussed with a hepatologist.

Bacteremia/endocarditis. IDU can lead to the transmission of other nonviral, blood-borne illnesses. Most nonviral infections among PWIDs stem from improper cleaning of skin and needles prior to injection, which can result in skin flora (eg, bacteria or fungi) being injected. Thus, active drug users may have various physical examination results indicative of IDU. Common injection sites include the veins of the forearm, wrist, antecubital fossa, ankle, and dorsum of one's hand; therefore, patients who inject frequently may exhibit track marks, scarring, and toxin build-up along the length of the veins. “Skin popping,” injecting drugs subcutaneously or intradermally rather than intravenously, can often produce nodules or open wounds seen on physical examination. Local cellulitis or skin abscesses can occur from these two methods of drug injection as well; although these are generally self-treated, they may be evident in one-third of PWIDs and sometimes can progress to more severe infections such as necrotizing fasciitis.21

Of greater concern is development of bacteremia from commensal skin flora such as Staphylococcus aureus (including methicillin-resistant strains or MRSA) or Streptococcus species, which can lead to widespread dissemination and result in complications including brain abscess, osteomyelitis, renal abscess, or even endophthalmitis. Of these complications, endocarditis, an infection of the cardiac valves or other endovascular structures, may be particularly common. Actual incidence rates of bacterial endocarditis in PWIDs are unclear, but estimates vary from 0.15% to 2% per year.22 Approximately 76% of bacterial endocarditis in PWIDs occurs on the right side (usually the tricuspid valve), which causes more morbidity, albeit less mortality with left-sided endocarditis.22 The mortality rate for right-sided endocarditis is approximately 6%, with vegetation size (larger worse than smaller) and etiology (fungal worse than bacterial) being the major determinants of death.23

A major issue with managing patients with infective endocarditis is ensuring adequate treatment. The mainstay of therapy is a prolonged course of intravenous antibacterial drugs, but many of the patients are unwilling to remain hospitalized for the full duration of treatment.

Medical Complications of Intravenous Drug Use

Altered behaviors, such as slurred speech, staggering gait, frequent itching, poor hygiene, and an odd affect, are often clinical clues for drug intoxication/withdrawal. Signs and symptoms of HBV or HCV are often absent given their frequent indolent or subclinical nature, but fevers, rashes, ascites, weight loss, and jaundice can present. HIV has a wide constellation of symptoms and can vary based on timing of infection and the degree of immunodeficiency.

Bacteremia or endocarditis should be suspected in a patient with signs and symptoms of an infection (tachycardia, hypotension, fever, and a new heart murmur). A murmur is a frequent discovery in patients with endocarditis; a murmur involving the tricuspid valve (usually an early systolic murmur with a decrescendo configuration) should raise the suspicion for right-sided endocarditis. Dermatologic findings from showering of septic emboli include splinter hemorrhages (tiny blood clots running vertically under nail beds), Osler nodes (painful raised, red lesions on the hands and feet), and Janeway lesions (nodular lesions on the palms and soles). If there is suspicion for bacteremia or endocarditis, a patient should be referred for hospital admission and three sets of blood cultures should be obtained prior to antibacterial administration.

Although not directly related to IDU, illicit drug users are also at high risk for tuberculosis (TB), with an estimated latent prevalence rate between 10% and 59%.24 Immunological resistance to TB or other infections may be lower among PWIDs not only because of coinfection with HIV, but because of factors such as crowded living conditions, poor hygiene, and malnutrition.21 We recommend screening for TB with a standard tuberculin skin test. Cutoffs for positive testing in PWIDs is >10 mm and in HIV positive patients >5 mm.25 A positive test should trigger further testing for TB and a referral to an infectious disease specialist.

The pharmacological effects of the agent injected can also have significant consequences. Agents used to “cut” the pure drug (or injection of talc-containing drugs meant to be taken orally) may cause pulmonary granulomas, fibrosis, or hypertension, and in some instances, unusual infections such as clostridium stemming from injection of “black tar” heroin.21,26 Thus, IDU can lead to a dizzying array of physical complaints and results, potentially affecting the skin, central nervous system, cardiovascular system, and lungs, as well as leading to abscess formation wherever septic emboli may lodge.

The CDC recommends screening PWIDs for hepatitis A virus (HAV), HBV, and HCV, as well as annual testing for HIV.27 HAV, which is not a blood-borne pathogen, can be spread through percutaneous and fecal-oral routes, and outbreaks have been reported among PWIDs. Screening for HCV infection is indicated in patients born between 1945 and 1965 or those with high-risk behaviors, including IDU.28 In addition, sexually active patients should be screened for syphilis and other sexually transmitted infections on a periodic basis per CDC recommendations.27 History and/or physical examination results should guide further laboratory or radiological evaluation.

Pharmacological Issues in Treating Injection Drug Use

It is estimated that approximately 40% of PWIDs have significant comorbid psychiatric and medical conditions as described above.29 The medications used to treat some of the infectious diseases associated with IDU often have unique metabolism or pharmacology properties that interact with the drugs used to treat psychiatric disorders.

Antiretroviral agents used to treat HIV have significant drug-drug interactions with various psychotropic medications.30 HIV antiretroviral medications can alter the cytochrome P450 metabolic system, altering the amount of drug the person is exposed to. The protease inhibitors, such as ritonavir, inhibit P450 metabolism and can lead to an increase in the amount of drug in the system. The nonnucleoside reverse transcriptase inhibitors, such as efavirenz, induce P450 metabolism resulting in decreased drug levels and decreased efficacy of certain agents. The newer HCV therapies also have many effects on the cytochrome P450 system and can also alter metabolism of other agents, either increasing toxicity or decreasing the effectiveness. It is important for providers to be aware of the various drug-drug interactions related to antiviral, antibacterial, and other medications to avoid toxicity and improve efficacy of the agents being prescribed.

Effectiveness of Risk-Reduction Efforts

Numerous strategies have been implemented to reduce the transmission of infections among PWIDs. Many strategies are often hindered by factors including political policies, social alienation, and inaccessibility of resources to those at risk.31 The 2004 World Health Organization study summarizes the effectiveness of many strategies in combating infection transfer from PWIDs.32,33 That research has shown that needle-exchange programs reduce the spread of HIV among PWIDs without increasing the frequency of IDU, and that community-based outreach programs offer increased opportunities for contact and education.

Conclusions

Despite many efforts to curb IDU in the US, it remains a significant problem. Any patient with a history of IDU, regardless of injection frequency or time passed since the last use, should raise suspicion for the infectious diseases discussed above. Screening for common viruses, managing interactions between psychotropic and antiviral drugs, and assisting with the social welfare of these patients are often difficult tasks. Therefore, it is recommended that a multidisciplinary effort with a psychiatrist, an infectious disease specialist, and a primary care doctor work to manage the comorbid conditions in IDU.

References

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Medical and Psychiatric Complications of Injection Drug Use

Infectious <list-item>

HIV

</list-item><list-item>

Hepatitis B virus

</list-item><list-item>

Hepatitis C virus

</list-item><list-item>

Endocarditis/bacteremia (typically rightsided)

</list-item><list-item>

Staphylococcus aureus

</list-item><list-item>

Rare cases of Pseudomonas aeruginosa

</list-item><list-item>

Candida albicans

</list-item><list-item>

Mycobacterium tuberculosis

</list-item>
Neurologic <list-item>

Seizures

</list-item><list-item>

Stroke

</list-item>
Caridopulmonary <list-item>

Pneumonia and pneumonitis

</list-item><list-item>

Pulmonary embolisms

</list-item><list-item>

Apnea

</list-item><list-item>

Pulmonary hypertension

</list-item><list-item>

Myocardial infarction

</list-item><list-item>

Hypertension

</list-item><list-item>

Endocarditis

</list-item>
Pregnancy <list-item>

Miscarriage

</list-item><list-item>

Preterm labor

</list-item><list-item>

Abruptio placenta

</list-item><list-item>

Low birth weight

</list-item><list-item>

Neonatal withdrawal

</list-item>
Renal <list-item>

Nephrotic syndrome

</list-item><list-item>

Glomerulonephritis

</list-item><list-item>

Interstitial nephritis

</list-item><list-item>

Amyloidosis

</list-item><list-item>

Rhabdomyolysis

</list-item>
Psychiatric <list-item>

Major depression

</list-item><list-item>

Alcohol dependence

</list-item><list-item>

Antisocial personality disorder

</list-item><list-item>

Borderline personality disorder

</list-item>
Liver <list-item>

Acute hepatitis (drug-induced or infectious)

</list-item><list-item>

Cirrhosis

</list-item>

Current Recommendations for Antiviral Treatments for HBV, HCV, and HIVa

Chronic hepatitis B virusb,34 <list-item>

Adefovir

</list-item><list-item>

Lamivudine

</list-item><list-item>

Pegylated-interferon

</list-item><list-item>

Telbivudine

</list-item><list-item>

Tenofovir

</list-item>
Chronic hepatitis C virusc,35 <list-item>

Elbasvir/grazoprevir

</list-item><list-item>

Ledipasvir/sofosbuvir

</list-item><list-item>

Paritaprevir/ritonavir/ombitavsvir

</list-item><list-item>

Sofosbuvir/velpatasvir

</list-item><list-item>

Simeprivir plus sofosbuvir

</list-item>
HIVd,36 <list-item>

Dolutegravir/abacavir/lamivudinee

</list-item><list-item>

Dolutegravir plus TDF/emtricitabine

</list-item><list-item>

Elvitegravir/cobicistat/tenofoviralafenamide/emtricitabinef

</list-item><list-item>

Elvitegravir/cobicistat/TDF/emtricitabine

</list-item><list-item>

Raltegravir plus TDF/emtricitabine

</list-item><list-item>

Darunavir/ritonavir plus TDF/emtricitabine

</list-item>
Authors

Phillip P. Santoiemma, MD, MSE, MTR, is a Medicine Resident, Department of Internal Medicine, Northwestern University Feinberg School of Medicine. Stephen H. Dinwiddie, MD, is a Professor, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine. Michael P. Angarone, DO, is an Assistant Professor of Medicine and Medical Education, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine.

Address correspondence to Michael P. Angarone, DO, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611; email: m-angarone@northwestern.edu.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00485713-20161206-03

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