Chapter 296: Injection Drug Users

Illicit drug use is a major health issue globally. It is estimated that in 2011 between 167 and 315 million people worldwide used illicit substances.¹ In 2012, an estimated 23.9 million Americans ≥12 years of age used an illicit drug within the previous month, and of these, 669,000 used heroin, nearly triple the prevalence in 2008.² Between 2006 and 2011, heroin-related ED visits increased from 189,780 to 258,482, with the majority of visits made by men (69%) and patients age 35 to 44 years.² More recently, ED visits due to severe overdoses have been precipitated by drug distributor substitution of the synthetic opiate fentanyl for heroin as a "super high."³

The practice of injection drug use and the lifestyle and culture of the injection drug user place the individual at risk for a wide variety of complications, including human immunodeficiency virus (HIV) infection, hepatitis, tetanus, sexually transmitted diseases, trauma, and intimate partner violence.⁴ The high incidence of migration, incarceration, homelessness, nutritional deficiencies, coincident smoking and alcohol use, and mental illness further compromises this population's health.⁵

Injection drug use is associated with immune dysregulation. Exaggerated and atypical lymphocytosis, diminished lymphocyte responsiveness to mitogenic stimulation and depressed chemotaxis, hypergammaglobulinemia, increased opsonin production, decreased T-cell and natural killer cell activity, high levels of circulating immune complexes, and reticuloendothelial abnormalities have been found in injection drug users. False-positive results on nontreponemal syphilis serologic tests, positive results on Coombs tests, low measured antibody response to vaccination, and thrombotic thrombocytopenic purpura are some described abnormalities. HIV-infected patients who inject drugs are found to be less likely to suppress HIV-1 RNA than those who do not inject drugs. Given the immune dysfunction, febrile injection drug users should be suspected of having infections, even when the fever is low grade and WBC counts and erythrocyte sedimentation rates are normal.

To adequately evaluate the histories of injection drug users, be aware of the drugs used locally and regionally, drug street names (e.g., "smack," "H," "Mexican mud," "junk," "bud light," "theraflu"), and drug adulterants. Ask about drug type(s) and amount, preparation of materials for injection (e.g., crushing capsules in the mouth, licking needles, blowing on injection sites or blowing out clots in needles, or using saliva, lemon juice, or tap or toilet water for drug reconstitution), reuse of needles, needle sharing, use of antibiotics, and coincident medical and mental illness. Consider socioeconomic issues, such as the ability to purchase medications and access to outpatient follow-up, in patient disposition.

Complications of injection drug use may be obvious, such as a painful, erythematous, fluctuant skin abscess. However, subtle constitutional symptoms such as weakness, anorexia, body pains, myalgias and arthralgias, weight loss, and fever are common and may be the only signs of serious underlying disease (Table 296-1).

FEVER

Fever is associated with infection in more than two thirds of patients. Noninfectious causes of fever include acute toxic reactions to substances of abuse, reactions to injected adulterants, and withdrawal syndromes. Cocaine and amphetamines can cause acute fever, occasionally in excess of 40°C (104°F). Adulterants used to dilute active substances may also cause dramatic febrile reactions accompanied by alteration in mental status and leukocytosis. "Cotton fever" is a flulike syndrome developing within hours of injection, after the use of cotton balls as filters for drug suspensions. Physical findings may include tachypnea, tachycardia, abdominal pain, and inflammatory retinal nodules. Chest radiographs typically show normal findings but may demonstrate inflammatory pulmonary granulomata. This syndrome spontaneously resolves within 24 hours.⁶ Drug withdrawal from benzodiazepines, barbiturates, or heroin also may cause acute illness with chest and abdominal pain, diaphoresis, tachycardia, and fever.

Because no reliable markers are available to exclude serious illness in the febrile injection drug user, common practice has been to obtain specimens for blood culture and admit such patients for observation while culture results are awaited (also see "Infective Endocarditis" section below). In clinically well patients for whom follow-up can be ensured, outpatient evaluation is reasonable as long as appropriate culture specimens are obtained.

DYSPNEA

A wide range of both infectious and noninfectious entities may produce dyspnea and cough in injection drug users. Pneumonia is typically community acquired (see "Pulmonary Infections" section below). However, dyspnea may have other infectious causes, including infections related to aspiration during drug intoxication, tuberculosis, opportunistic infections, and septic pulmonary emboli complicating right-sided endocarditis. The febrile injection drug user with dyspnea, cough, or abnormal findings on chest radiograph should be placed in respiratory isolation until tuberculosis has been excluded and/or an alternative diagnosis is found.⁷

Noninfectious causes of dyspnea include pneumothorax, hemothorax, toxic reaction to injected substances, and hypersensitivity reaction. Pneumothorax and hemothorax are seen most commonly in association with the practice of "pocket shooting," in which drug users, or their drug-injecting partners, inject into veins in the supraclavicular fossa to access the subclavian, jugular, or brachiocephalic vein. "Talc lung" is a syndrome of progressive respiratory distress and diffuse interstitial infiltrates caused by the injection of adulterant talc. Hypersensitivity reactions, associated with both heroin and cocaine injection, cause cough and wheezing and typically respond to inhaled β-agonist therapy. Noncardiogenic pulmonary edema is associated with both heroin and cocaine use. Signs and symptoms include dyspnea, hypoxia, and diffuse alveolar infiltrates on chest x-ray. Treatment is supportive. Finally, septic, air, or needle fragment emboli can produce dyspnea.

ALTERED MENTAL STATUS AND NEUROLOGIC ABNORMALITIES

Drug intoxication or withdrawal, stroke syndromes, hypoxia, delayed leukoencephalopathy, infectious diseases, mycotic aneurysms, and secondary trauma from either loss of consciousness and fall or drug-related violence may all produce altered mental status or other neurologic impairment in the injection drug user. CNS infections may result from contiguous spread of overlying soft tissue infection, embolic complications of distant infections (e.g., endocarditis), or extension of local infections (e.g., vertebral osteomyelitis). Infections that affect the nervous system and commonly occur in this population include epidural abscess, bacterial and fungal meningitis, and brain abscess. Meningococcus, pneumococcus, and Staphylococcus aureus bacteremia from primary endocarditis are the common causes of bacterial meningitis. Both tetanus and botulism are reported, with cranial nerve involvement, altered mental status, and progressive symmetric paralysis.⁸

Infections caused by opportunistic organisms, such as Toxoplasma, are common in patients with coincident HIV infection who have low CD4 counts (especially <100). Stroke syndromes may occur secondary to low-flow states during heroin intoxication; hypertensive hemorrhage from amphetamines, phencyclidine, or cocaine; and embolized vegetations associated with infectious endocarditis. Delayed leukoencephalopathies, both hypoxic and nonhypoxic, have been reported in injection drug users, but are rare.

BACK PAIN

Back pain may result from an epidural abscess, vertebral osteomyelitis, or complications from trauma. In patients with coincident HIV infection, opportunistic infections may present with a more indolent course, and the only symptom may be local pain. Nontraumatic focal back pain usually requires imaging studies such as CT and MRI to evaluate for possible infection.

HUMAN IMMUNODEFICIENCY VIRUS INFECTION

The use of IV drugs continues to play a major role in the acquisition and transmission of HIV; however, data from the United States and Central and South America have demonstrated a gradual decline in the prevalence of HIV infection due to injection drug use. From 2003 to 2009, the prevalence decreased from 19% to 16%.⁹ See chapter 154, "Human Immunodeficiency Virus Infection" for further management.

INFECTIVE ENDOCARDITIS

The incidence of endocarditis in injection drug users is rising,¹⁰ and this patient group appears to be driving the increased incidence of infective endocarditis in North America.¹¹ Prior incidence estimates of endocarditis in injection drug users presenting with fever to the ED (13% in general^12,13 and 40% in an inner-city population¹⁴) were based on data two to three decades old. Two studies published since 2011 based on 485 patients reveal that 7.8% of febrile injection drug users hospitalized with "fever without a source" have evidence of endocarditis on echocardiography.^15,16 Unlike endocarditis in the general population, endocarditis in injection drug users involves the right side of the heart (57% to 86% of cases).^15,17 The most common causative organism for infective endocarditis in injection drug users is S. aureus (70%), and one third of those cases involve methicillin-resistant S. aureus.^17,18 Licking needles prior to injection has been implicated in infections with Eikenella corrodens, Haemophilus parainfluenzae, Bacteroides species, and Neisseria species. Up to 20% of cases of injection drug use–related endocarditis are polymicrobial infections.⁸

Clinical features of endocarditis in injection drug users are dominated by right-side heart involvement with respiratory complaints, including dyspnea, cough, and hemoptysis. Multiple opacities on chest radiograph, consistent with septic pulmonary emboli, are common (Figures 296-1 and 296-2). Other findings include pyuria (22%) and hematuria (35%) and are due to glomerulonephritis from immune complex deposition, embolic renal infarction, and perinephric abscess.^16,19 A clinical prediction rule to identify endocarditis in febrile injection drug users has been derived¹⁵ and internally validated¹⁶ and assesses sequentially for the presence of a pulse rate >100, absence of skin infection, and presence of murmur. The rule was 100% sensitive (95% confidence interval, 84% to 100%) in the derivation and validation cohorts, but specificity was only 13%,¹⁶ and the scoring system used is complex, requiring comparison to a nomogram. The prediction rule has not been externally validated and cannot be recommended at this time. For further direction regarding diagnosis of endocarditis, treatment with antibiotics, and management of complications see chapter 155, "Endocarditis."

PULMONARY INFECTIONS

Community-acquired pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae remains the most common pulmonary infection in injection drug users, with a 10-fold increased risk for community-acquired pneumonia in the injection drug user population.⁸ Patients are also at high risk for pneumonia due to S. aureus, including methicillin-resistant S. aureus; Klebsiella pneumoniae infection; aspiration pneumonia; tuberculosis; and, in HIV-positive patients, opportunistic infections caused by Pneumocystis jiroveci, cytomegalovirus, and atypical mycobacteria.⁸ Results of the purified protein derivative (tuberculin) skin test may be negative in these patients. Patients may present with atypical clinical and radiographic findings of tuberculosis²⁰ (see chapter 67, "Tuberculosis").

Because of the risk of atypical infection, coincident bacteremia, and potential for endocarditis in patients with multiple infiltrates on chest radiograph, admission to the hospital is recommended, and respiratory isolation should be maintained until tuberculosis is excluded.^8,14 In patients without risk for Pseudomonas infection, IV quinolone and IV ceftriaxone or cefotaxime provide reasonable empiric coverage until culture results are available. In those at risk for Pseudomonas infection (structural lung disease, malnutrition, current or recent corticosteroid use or antibiotic use), a preferred regimen is an IV antipseudomonal β-lactamase agent (cefepime, imipenem, meropenem, or piperacillin/tazobactam) and an IV antipseudomonal fluoroquinolone or an antipseudomonal β-lactamase agent, IV aminoglycoside, and fluoroquinolone.²¹ For further discussion, see chapter 65, "Pneumonia and Pulmonary Infiltrates."

SKIN AND SOFT TISSUE INFECTIONS

Skin and soft tissue infections are some of the most common infections among injection drug users and include cellulitis, subcutaneous abscesses, septic phlebitis, necrotizing fasciitis, Fournier's gangrene, gas gangrene, and pyomyositis. Most are caused by the user's own commensal flora, with S. aureus and streptococcal species remaining the most common pathogens. Because these infections are often self-treated and reporting is not required, the prevalence is difficult to determine but is estimated to be as high as 32%.²²

Tap water, toilet water, lemon juice, or saliva may be used to dissolve narcotics or cocaine, and each has been implicated as a source of causative organisms, such as Pseudomonas and Candida, in both skin and blood-borne infections.⁸ In 2013, an outbreak (43 individuals, 13 deaths in Scotland) of cutaneous anthrax in heroin users was reported from the United Kingdom.²³ The recent use of desomorphine (street name Krokodil), an extremely addictive morphine derivative that typically contains large amounts of toxic synthesis components, including iodine and phosphorus, demonstrates the serious damage to skin, blood vessels, bone, and muscles that illegal drug injection can produce. Many long-term desomorphine users have required limb amputation, which has given this drug the nickname "the flesh-eating drug."²⁴

CLINICAL FEATURES AND DIAGNOSIS

Presenting signs and symptoms of cutaneous infections, including pyomyositis, are fever, pain, localized erythema, and edema. Carefully inspect the painful area for fluctuance, crepitus, and lymphangitis. Diagnosis is primarily clinical, except when evaluating an abscess where pulsations are present. Cellulitis and abscesses are typically caused by S. aureus (primarily community-acquired methicillin-resistant S. aureus) and Streptococcus species.²⁵ Cultures of specimens from cutaneous abscesses may also demonstrate polymicrobial growth, with aerobic gram-negative rods, anaerobic cocci, and bacilli.⁸ Increased rates of Clostridium botulinum infection have also been found in injection drug users who engage in skin popping, particularly those using Mexican black tar heroin. Mortality rates due to tetanus are highest in older, unvaccinated patients. Other concerns include retained portions of broken needles, which act as a nidus for infection and, in addition, pose an increased risk to the examining healthcare provider. Needles may be identified by radiograph prior to exploration. Individuals may have already attempted to treat abscesses before coming to seek medical care by incision and drainage, illegally purchased antibiotics, or some form of homeopathic care. This is particularly prevalent in Latino populations and those who do not have a usual place of health care.²⁶

Infections overlying venipuncture sites may produce thrombophlebitis and infected pseudoaneurysms. Femoral vein injection ("groin hit") has been associated with the development of local gangrene as well as rapidly progressive and fatal Fournier's gangrene. Injection into the jugular vein ("pocket shot") may lead to cutaneous abscess formation involving the carotid triangle and produce airway obstruction, vocal cord paralysis, and laryngeal edema.⁸

IMAGING

For nonpulsatile areas of induration, bedside US can define an underlying abscess. Pulsatile masses, however, must be imaged with Doppler US prior to incision and drainage, because attempts to aspirate or incise and drain an infected pseudoaneurysm can result in severe hemorrhage (see section titled "Vascular Infections" below). CT angiography may identify vasospasm, thrombosis, emboli, or mycotic aneurysms. Plain radiographs can demonstrate air in the soft tissues as well as radiopaque foreign bodies. CT delineates the involvement of other structures and the extent of deep abscesses, especially in complex areas such as the neck.

TREATMENT

Uncomplicated abscesses, large furuncles, and carbuncles should be incised, drained, and packed. Injection drug users with superficial cellulitis without evidence of systemic involvement can be managed as outpatients with oral antibiotics to cover streptococci and methicillin-resistant S. aureus. See chapter 152, "Soft Tissue Infections," for discussion of antibiotic choices, abscess drainage, care for the septic patient, and disposition decision making.

VASCULAR INFECTIONS

Distal vascular injury and endovascular infections associated with injection drug use include inadvertent arterial injection with resultant vasospasm or thrombosis, septic thrombophlebitis, venous and arterial pseudoaneurysms, and infected hematomas. Arterial injection rarely results in major vessel occlusion; instead, pain, edema, and patchy mottling of the affected limb occur due to ischemia. Tissue necrosis and gangrene are the consequence of persistent focal ischemia, the cause of which is thought to be a combination of vasospasm, embolization of particulate matter, and endothelial injury leading to thrombosis and vasculitis.²⁷

When limb ischemia is suspected, a vascular surgeon should determine whether surgical intervention or intra-arterial thrombolysis is indicated. However, the majority of cases involve distal vessels, and treatment is limited to anticoagulation and supportive care. Limb edema can progress to compartment syndrome, which may require fasciotomy, or may be complicated by rhabdomyolysis.

Infected pseudoaneurysm is a commonly reported vascular complication in injection drug users due to accidental or intentional intra-arterial drug injection and is most often reported in the femoral artery, followed by the radial and brachial arteries.²⁷ Figure 296-3 shows a radial artery pseudoaneurysm. Venous pseudoaneurysms are relatively rare and are usually secondary to septic phlebitis, with the femoral vein most often involved. Signs are typically fever and a painful mass. This is a severe complication that can result in life-threatening hemorrhage and sepsis, chronic claudication, chronic skin and soft tissue infections and posttraumatic ulcers, and limb loss. A 23% amputation rate is reported with involvement of the femoral bifurcation. Although the lesion is similar in gross appearance to an abscess, the presence of pulsations and a bruit suggest this diagnosis. Because of the disastrous hemorrhagic consequences of attempted incision and drainage, all painful masses, particularly in the groin, should be expeditiously imaged with US or contrast CT.

In all cases of suspected endovascular infection, antibiotic therapy should be initiated and may be guided by the therapeutic recommendations for endocarditis given above (see "Infective Endocarditis"). Surgical treatment options for infected femoral artery pseudoaneurysm are limited due to infection of the surgical field, lack of available autologous graft materials because of deep and superficial venous thromboses from long-term injection, and a high likelihood of continued injection drug use, which increases the risk of postoperative infection and other complications. One therapeutic option is the ligation and resection of the infected pseudoaneurysm without revascularization. Initial outcomes may be favorable; however, long-term morbidity includes claudication, which can become severe, leading to eventual limb amputation.^28,29 A second option is ligation of the common femoral artery without revascularization, accompanied by excision and drainage of the internal femoral artery pseudoaneurysm and routine selective revascularization via either arterial reconstruction with an autologous greater saphenous vein graft or synthetic graft in situ or extra-anatomically.

BONE AND JOINT INFECTIONS

EPIDEMIOLOGY AND PATHOLOGY

Musculoskeletal infections usually occur either through contiguous spread from an overlying skin or soft tissue infection or, more commonly, through hematogenous spread from a distant site. Infecting microorganisms in injection drug users may be unusual, with Candida and gram-negative organisms seen, especially Pseudomonas aeruginosa. Likely organisms include S. aureus (including methicillin-resistant S. aureus), Staphylococcus epidermidis, P. aeruginosa, and Streptococcus species.³⁰ Because of the high incidence of sexually transmitted diseases in this population, also consider gonococcal arthritis and tenosynovitis. E. corrodens osteomyelitis is reported in those who lick their needles prior to injection.

CLINICAL FEATURES AND DIAGNOSIS OF OSTEOMYELITIS

Osteomyelitis can develop in the axial skeleton, with another common location being the tibia, often in association with hardware from treatment of a prior fracture.³⁰ Contiguous septic arthritis can coexist with osteomyelitis.³⁰ Candidal infections are postulated to be hematogenous in origin and have been related to the use of contaminated reconstituted lemon juice to mix drugs before injection.⁸ Some patients report an initial flulike syndrome lasting 3 to 4 days, followed by the appearance of metastatic lesions involving the skin, eye (chorioretinitis and endophthalmitis; see "Ophthalmologic Infections" section below), and the bones and joints several days to weeks later. Rarely, Aspergillus species may cause osteomyelitis of the sternum in injection drug users.

Vertebral osteomyelitis usually presents with localized pain and tenderness to palpation over the involved bone, and a soft tissue mass may be palpable. Osteomyelitis may coexist with spinal epidural abscess.³¹ Symptoms may be present for days in the case of bacterial infections to weeks in the case of fungal or mycobacterial infections. The presence of both fever and leukocytosis and an elevated erythrocyte sedimentation rate and C-reactive protein level are helpful, if present, but their absence does not exclude these infections. Drainage from contiguous abscesses should be cultured. Biopsy or needle aspiration of joint spaces and bony infections may be necessary, especially in the case of infection with unusual or fastidious organisms, such as Mycobacterium, Candida, or Eikenella.

Imaging for Osteomyelitis Imaging for patients with suspected osteomyelitis varies by institution, but MRI is generally the imaging modality of choice. CT may reveal disk space narrowing and bony lysis suggesting osteomyelitis, but it is neither as sensitive nor as specific as MRI.³¹ Patients with osteomyelitis warrant admission, and unless the patient appears septic or has focal neurologic complaints or coincident endocarditis is a concern, antibiotic therapy should be withheld until culture results are obtained.

Treatment of Osteomyelitis Early consultation with the orthopedist or neurosurgeon should guide the timing of antimicrobial coverage, because blood culture results may not be sufficient, and a CT-guided needle biopsy for epidural abscess or a bone sample for culture for osteomyelitis may be required.²⁵ Antimicrobial choice should be based on culture results (for a biopsy specimen), and therapy is typically required for 4 to 6 weeks. Injection drug use patients in unsTable condition who are suspected of having osteomyelitis should receive vancomycin to cover S. aureus and ceftazidime to cover Pseudomonas (see chapter 281, "Hip and Knee Pain," for further discussion).

SEPTIC ARTHRITIS

Septic arthritis in injection drug users usually involves the knee or hip but may coexist with osteomyelitis in approximately 16% of cases.³⁰ Sternoclavicular septic arthritis strongly suggests injection drug use.³² For further discussion of diagnosis and treatment of septic arthritis, see chapter 284, "Joints and Bursae."

OPHTHALMOLOGIC INFECTIONS

Ophthalmologic infections in injection drug users are usually the result of hematogenous seeding from a primary source of infection, such as endocarditis, or of opportunistic infections associated with HIV disease. Bacterial endophthalmitis often presents acutely, with pain, redness, lid swelling, and decrease in visual acuity. Inflammation is usually present in both the anterior and posterior chambers. White-centered, flame-shaped embolic hemorrhages (Roth spots), cotton-wool exudates, and macular holes may be present. S. aureus is the most commonly isolated organism, followed by Streptococcus species. Treatment involves subconjunctival and systemic antibiotic therapy, most commonly vancomycin and ceftazidime.³³ Surgical intervention may be needed. Visual prognosis is poor.³³

Fungal organisms, usually Candida, are an important cause of endophthalmitis among injection drug users. Such fungal infections were considered rare until Mexican black tar heroin arrived in the 1980s, and lemon juice was used to dissolve this relatively water-insoluble compound.³⁴ Symptoms include blurred vision, pain, poorly reactive pupil, and decreased visual acuity and can progress over days to weeks. White cotton-like lesions are seen on the choroid retina, with vitreous haziness. Uveitis, papillitis, and vitreitis also have been reported. Presumptive diagnosis is defined as the presence of typical ocular lesions in an injection drug user. Microbiologic diagnosis is made from the results of blood and vitreous culture. Treatment includes amphotericin B and voriconazole.³³ Aspergillosis is the second most common fungal cause of endophthalmitis in injection drug users, producing ocular symptoms and signs without cutaneous or musculoskeletal involvement. The visual prognosis for fungal endophthalmitis depends on prompt diagnosis and treatment but frequently is poor.³³ Immediate consultation with an ophthalmologist is necessary to ensure appropriate management and a positive outcome. In injection drug users co-infected with HIV, cytomegalovirus infection, toxoplasmosis retinitis, and choroidal Cryptococcus and Mycobacterium avium-intracellulare complex infections must also be considered.