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.
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 general12,13 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."
Chest radiograph showing septic emboli. Multiple opacities are seen in this chest radiograph of an injection drug–using female patient who was found to have bacterial endocarditis.
CT image showing multiple peripheral cavitary lesions (arrows) consistent with septic pulmonary emboli.
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
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.
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.
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.
Volume-rendering CT of the wrist showing a radial artery pseudoaneurysm in the inferior portion of the image. The pseudoaneurysm has displaced the radial artery away from the bony radius.
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 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 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.