Acute infections in people who inject drugs
BMJ 2022; 379 doi: https://doi.org/10.1136/bmj-2022-072635 (Published 07 October 2022) Cite this as: BMJ 2022;379:e072635
- Neil Stevenson, specialty registrar in infectious diseases1,
- Stuart Suttie, consultant vascular surgeon2,
- Eduardo Fernandes, assistant professor3,
- Nikolas Rae
, consultant physician in infectious diseases and acute medicine1
- 1Infection Unit, Ninewells Hospital, Dundee DD1 9SY, UK
- 2Department of Vascular Surgery, Ninewells Hospital, Dundee
- 3Department of Surgery, University of Illinois Health Science System, Chicago, Illinois, USA
- Correspondence to: N Rae nikolas.rae@nhs.scot
What you need to know
Have a low threshold for imaging with computed tomography (CT) angiography, thoracic CT, and echocardiography in people who inject drugs presenting with acute infections
Arrange urgent surgical referral for patients with pseudoaneurysm, abscess, necrotising soft tissue infection, or septic arthritis
Early switch to oral antimicrobial therapy, once clinically stable, may improve compliance and can be as effective as intravenous therapy
A39 year old man presents to the emergency department with a seven day history of fever and rigors associated with pain and swelling in the right leg. He had recently injected heroin into the right groin before the onset of pain. On admission he was febrile, tachycardic, and tachypnoeic with audible crackles in both lung fields, and had cellulitis of the right leg.
About 275 million people inject drugs according to the UN 2021 World Drug Report, an increase of 22% from 2010.1 Acute bacterial infections are common in people who inject drugs. The diagnosis is often delayed as they may hesitate to seek prompt care due to stigma and fear. Mortality can be high due to complications and delayed treatment.
This article aims to highlight key points for the generalist in the initial assessment and management of common infections in people who inject drugs.
Why is it important?
People who inject drugs are less likely to receive primary care than the general population.2 This may worsen severity of disease. A Canadian retrospective study (663 patients) showed higher rates of emergency department attendance and hospital admission than in the general population.3
Estimates from the United States suggest 20 000 hospital admissions for infective endocarditis and 98000 hospitalizations and emergency department visits for skin and soft-tissue infections related to injecting drug use in 2017.4 A retrospective cohort study from a teaching hospital in London revealed infections contributed to at least 90% of admissions in people who inject drugs (191 admissions) between 2005 and 2009, with challenges including unplanned discharges and injecting during admission.5 In a multicentre UK survey (855 patients), 44% of respondents with abscess related to injecting drug use waited at least five days from symptom onset before seeking care.6 A seven year retrospective review of 558 admissions (330 patients) for limb related complications of drug use in Scotland in 2022 found 15.2% mortality across median follow-up of 38 months, with mean patient age of 37 years.7
What are common infections related to injecting drug use?
In addition to common community-acquired infections, people who inject drugs may present with undifferentiated sepsis or with one or more localising features suggesting common infections described below.
Skin and soft tissue infection
Skin and soft tissue infections are the most common infections affecting people who inject drugs. Cellulitis and abscess are most frequently encountered.58 A systematic review found that abscess formation is more commonly seen in women, and with greater frequency of injecting, and in those who inject in tissues rather than veins (“popping”).9 Cellulitis is diagnosed clinically with erythema, tenderness, and warmth at injection sites. Abscesses may accompany cellulitis or occur alone. The classic fluctuant mass may not be apparent.10
Necrotising soft tissue infection
Necrotising soft tissue infection is a severe form of skin and soft tissue infection, with estimated mortality of 23.1% in a recent systematic review.11 The initial presentation can be similar to uncomplicated skin and soft tissue infection. In a systematic review of 1463 patients, more than 75% of patients with necrotising soft tissue infection from any cause were initially misdiagnosed.12 Patients may be admitted to a range of hospital specialties, which can delay recognition and appropriate surgical management.13 Pain, erythema, and oedema are the most common symptoms. Pain disproportionate to other features, indistinct margins of infection, rapid progression, and tenderness of seemingly unaffected skin are other key clues.12 Hypotension, skin necrosis, and bullae occur later in the course of disease.
Infected pseudoaneurysm
Non-sterile arterial injection may result in damage to the vessel wall, leading to the formation of an infected pseudoaneurysm. In a single centre review (72 patients), the femoral artery was most commonly affected, followed by the brachial, radial, and axillary arteries.14 Little high quality data exist on presenting features of infected pseudoaneurysms. Pain and swelling at the site are common features, followed by a pulsatile mass. In late presentations, bleeding or limb ischaemia can occur.1415
Septic thrombophlebitis
A retrospective observational study (70 patients) in Scotland suggested leg pain and fever are the most common features, with or without swelling. Some patients present with predominantly respiratory symptoms, suggesting concurrent septic pulmonary embolism.16 Injecting drug use was noted in up to 48% of patients with deep vein thrombosis (DVT) aged less than 40 years in a retrospective study (232 episodes of lower limb DVT).17 Suspect septic thrombophlebitis if there are features of DVT such as limb pain or swelling combined with evidence of local or systemic infection.
Septic pulmonary embolism
Septic pulmonary embolism occurs when thrombi containing microorganisms embolise into the pulmonary vessels, leading to infarction and abscess formation, occasionally complicated by empyema.18 A systematic review (168 patients) found that fever, chest pain, and dyspnoea were common symptoms, and in most cases a primary infective focus was identifiable, often septic thrombophlebitis or right sided infective endocarditis.19
Infective endocarditis
An international cohort study of 7616 patients in 2021 reported that about 8.4% of people who inject drugs contracted infective endocarditis.20 People who inject drugs accounted for 29% of the 123 776 patients with infective endocarditis in the United States in 2015.21 Compared with the general population, people who inject drugs tend to be younger and infection is more commonly right sided. Presentation is often non-specific, involving fever, weight loss, and malaise.22
Staphylococcus aureus is the leading cause and usually presents acutely. Typical pathogens such as viridans group streptococci and enterococci are also well recognised. Other pathogens such as Pseudomonas aeruginosa and fungi, while rare, are also more common in this group.22
Bone and joint infection
Septic arthritis and osteomyelitis generally occur by haematogenous spread in people who inject drugs, with the axial skeleton commonly affected.10 Patients with septic arthritis are usually unwell with acute joint pain and swelling. Localised bone pain may be the only feature of osteomyelitis. Back pain with or without fever or acute neurological symptoms (especially bilateral limb weakness) suggests the possibility of vertebral osteomyelitis or epidural abscess.23
What to cover on initial evaluation?
Ask for a history of drug use in patients with unexplained sepsis or signs of one of the infections above. Avoid the use of stigmatising terms such as “addiction” or “substance abuse.”24
On examination, look for physical signs of drug use such as injection sites or bruising.3 A small survey of people who inject drugs suggested large groin veins may be preferentially used to conceal evidence of injecting that may lead to stigma.25
A history of injecting followed by localised pain and swelling raises suspicion of abscess, pseudoaneurysm, or septic thrombophlebitis. Injecting into tissues rather than veins (“popping”), particularly with contaminated heroin, increases risk of severe clostridial infections, including botulism and tetanus.26
What investigations to consider?
Laboratory investigations
Request a full blood count, renal function and liver function tests, C reactive protein, and coagulation profile in patients with signs suggestive of an infection. In addition, we recommend discussing and offering opportunistic screening for HIV infection, hepatitis B, and hepatitis C. In a retrospective US study, 90% of people who were seeking health care for reasons related to injected drug use were not tested for bloodborne viruses.27
Microbiological sampling is critical to guide ongoing management. Obtain at least two sets of blood cultures before starting antimicrobial therapy if there is suspicion of sepsis. Bacteraemia may be present in 90% or more of patients with septic thrombophlebitis, infective endocarditis, or septic pulmonary embolism.1928 In patients with suspected necrotising soft tissue infection, abscess, or pseudoaneurysm, obtain samples of pus or tissue at time of surgical debridement for microscopy and culture.29 In suspected bone and joint infection, blood culture is advised even if fever is absent.30 Joint aspiration can be performed for Gram stain and culture in patients with possible septic arthritis. In patients with osteomyelitis, multiple bone biopsy samples are sent for culture and histopathology. Superficial samples correlate poorly with bone and are discouraged.31
Imaging
Early imaging in people who inject drugs with sepsis can minimise delay in appropriate treatment. Chest x ray may show pulmonary airspace opacification, rounded lesions (with or without cavitation), and/or pleural effusions (fig 1a). Thoracic computed tomography (CT) is the optimal method for distinguishing septic pulmonary embolism from primary pulmonary infection (fig 1b).19 CT angiography identifies pseudoaneurysms (fig 2) in addition to deeper extension of soft tissue infection.1532 It can also suggest septic thrombophlebitis with features such as gas within thrombus or venous wall enhancement.33
Chest radiograph (a) and CT pulmonary angiogram (b) of a person with history of injecting drug use admitted with sepsis and respiratory failure. They show (a) bilateral consolidation with (b) evidence of bilateral cavitating lung lesions (arrows) consistent with septic pulmonary emboli, originating from septic thrombophlebitis of right superficial femoral vein identified on CT angiography.
Arterial phased contrast CTs showing right profunda femoris infected pseudoaneurysm in axial view (a) and sagittal view (b): orange arrows show the superficial femoral artery, and white arrows show a false aneurysm deep to the superficial femoral artery
Echocardiography is undertaken if there is an audible murmur, stigmata of infective endocarditis, evidence of septic pulmonary emboli, or bacteraemia. Transoesophageal echocardiography is recommended if transthoracic echocardiography is not diagnostic but suspicion remains high.34
Consider imaging for osteoarticular infection only if localising symptoms suggest osteomyelitis. Plain radiography may show signs of osteomyelitis after 7-10 days, but non-contrast magnetic resonance imaging (MRI) is often needed, especially in more acute presentations.31 MRI is recommended if vertebral osteomyelitis is suspected.23
In the absence of clear guidelines, our practice is to undertake CT angiography in people who inject drugs presenting with sepsis with a history of groin injecting or when there is suspicion of deep infection or vessel injury such as localised pain or swelling. This can allow prompt diagnosis or exclusion of common potentially life-threatening infections such as necrotising soft tissue infection, pseudoaneurysm, septic thrombophlebitis and deep abscesses. Thoracic CT can be undertaken simultaneously if there is suspicion of septic pulmonary embolism.
When to refer?
Urgently refer patients with necrotising soft tissue infection, deep abscess or pseudoaneurysm detected on imaging to the appropriate surgical subspeciality (plastic/general surgery, vascular surgery) for emergent operative management. Any untoward feature on imaging, such as the presence of gas or oedema below the fascial layer must be promptly surgically explored. Orthopaedic surgery referral is needed for washout of septic arthritis.30 In cases of vertebral osteomyelitis, surgery is reserved for those with associated epidural abscess or neurological compression.23
How are infections managed in people who inject drugs?
Initial treatment includes providing pain relief and antimicrobial treatment. Systemically well patients with uncomplicated soft tissue infection may be managed with oral antibiotics. Superficial abscesses may only require incision and drainage.
Initial antimicrobial therapy should include an agent active against Staphylococcus aureus and streptococci, the most common pathogens for all infections in people who inject drugs. Local prevalence of methicillin-resistant S aureus (MRSA) will influence choice of therapy. Anaerobic cover may be added if there are risk factors such as licking needles.8 In cases of severely ill patients or suspected necrotising soft tissue infection, therapy should be broadened to cover anaerobes and Gram negative bacilli. Table 1 lists suggested empirical antimicrobial regimens, amalgamated from guidelines.232930313435
Central venous access may be required in patients with sepsis. Prolonged parenteral antimicrobial therapy was previously routine for more complex infections. Pragmatic use of oral therapy could improve treatment compliance. Recent randomised controlled trials suggest that, in patients who are stable, early switch after 7-10 days to oral therapy (usually to complete up to 4-6 weeks therapy in total) is equivalent to intravenous therapy for endocarditis,36 septic arthritis, and osteomyelitis,37 although these studies were not exclusively performed in people who inject drugs. A retrospective cohort study (293 patients) showed that oral antibiotics for people who inject drugs discharging against medical advice resulted in similar re-admission rates at 90 days as inpatient treatment.38
Anticoagulation with subcutaneous low molecular weight heparin or direct oral anticoagulants (such as rivaroxaban) for septic thrombophlebitis is contentious but is unlikely to cause harm with short term therapy.39
What are preventive measures?
Harm reduction strategies are vital. A cross-sectional survey of 1876 people who inject drugs suggests that opiate substitution therapy and use of safe injecting equipment reduce the risk of developing skin and soft tissue infections.40 A systematic review including 138 716 people who inject drugs suggested that opiate substitution therapy reduced all-cause mortality.41 Reduction in infectious complications of injecting drug use has been observed with implementation of several harm reduction policies in Canada, including supervised injection facilities, needle exchange programmes, and opiate substitution therapy, although marginalised groups of people who inject drugs may require more targeted services to improve access.42
Discuss treatment of substance use, for example with titrated doses of methadone or buprenorphine for opiate withdrawal initially.43 A retrospective cohort study of 220 people who inject drugs admitted with invasive infections described increased completion of parenteral antimicrobial therapy and reduced readmission rates with provision of opiate replacement.44
Sources and selection criteria
We searched the PubMed database for English language articles using the terms “sepsis,” “endocarditis,” “soft tissue infection,” “pseudoaneurysm, “septic thrombophlebitis,” “septic arthritis,” and “osteomyelitis” combined with “IVDU.” Because of the limited number of randomised controlled trials, relevant observational or retrospective studies were reviewed and selected by two authors with additional publications supplied from personal archives of references. We have also consulted relevant guidelines from European Society of Cardiology and Infectious Diseases Society of America.
Additional educational resources
World Health Organization. Improving prevention and treatment for drug use disorders. https://www.who.int/activities/improving-prevention-and-treatment-for-drug-use-disorders
Centers for Disease Control (CDC). Persons who inject drugs (PWID). https://www.cdc.gov/pwid/index.html
Public Health England. People who inject drugs: infection risks, guidance and data. 2013. https://www.gov.uk/guidance/people-who-inject-drugs-infection-risks-guidance-and-data
Information resources for patients
National Institute of Drug Abuse. Drug facts. https://www.drugabuse.gov/drug-topics/publications/drug-facts
Harm Reduction Works. Safer injecting. https://www.harmreductionworks.org.uk/safer_injecting.html
Education in practice
How often do you see people who inject drugs presenting with acute infections? How many of them required investigation and inpatient management?
How would you develop a local policy for management of people who inject drugss presenting with sepsis?
How patients were involved in the creation of this article
We sought to involve patients by using clinical images from consenting patients who were also able to read the full manuscript. One patient provided a written account of his experience. We are grateful to these patients for their contribution.
Patient’s perspective
I had called an ambulance [for back pain with leg pain and swelling] and was told it wasn’t an emergency. I went to hospital and told them what happened. They told me that I had pulled my tendon and had damaged a nerve in my back. A week later it wasn’t getting any better. I went to see my doctor, and he took a blood sample and sent me home. He phoned me that evening and apologised and told me that I had a really bad infection. He advised me to go to the hospital straight away. I then got taken into the hospital. I was in agony. They gave me fluids and pain medicine. It was about a day before they knew exactly what was going on. I got a lot of scans and was rushed straight into surgery. I had an infection in my heart and bones and blood. I’ve had 2 weeks of IV antibiotics, and I’m trying to get walking again thanks to the help I’ve received.