Differential Diagnosis

While the differential diagnosis is extremely broad and includes infectious and non-infectious causes of fever, persons who inject drugs (PWID) are at increased risk for the following infections:

• Skin, soft tissue, and bone infections: abscesses, cellulitis, osteomyelitis, septic arthritis, epidural abscess, and necrotizing soft tissue infections.
  • Organisms include S. aureus (specifically MRSA), Strep species (e.g. group A Streptococcus), Pseudomonas, other GNRs, oral anaerobes, and TB.
• Endovascular infections: endocarditis (right and left sided), mycotic aneurysm, septic thrombophlebitis, bacteremia.
  • Organisms include S. aureus, Strep species, Pseudomonas and other GNR, Candida.
• Toxin-mediated disease: botulism (associated with black tar heroin), tetanus (inquire about last tetanus vaccine), Strep and Staph mediated toxic shock syndrome.
• Pulmonary infection: CAP (10-fold increased risk compared to general population), lung abscesses, aspiration PNA, HIV-opportunistic infections, TB.
• STDs: chlamydia, gonorrhea, syphilis.
• Other: acute HIV, acute hepatitis B and C, “cotton fever” (benign, self-limited sepsis mimicker from re-using cotton filters when injecting).

Evaluation

• Risk factors: prior history of SSTI, history of skin-popping/muscle popping, injecting speed-balls (cocaine and heroin), HIV positive, sharing or re-using needles or other drug paraphernalia, non-sterile water source for cooking heroin, lack of cleaning skin prior to injection, licking needles, history of endocarditis, valvular disease, or prosthetic valve, and homelessness. Ask patients about their injection drug use techniques to assess for risk factors.
• Physical exam:
  • Careful skin exam for abscess, cellulitis, peripheral stigmata of endocarditis (Osler’s nodes, Janeway lesions, and splinter hemorrhages) and new skin rashes. Consider necrotizing soft tissue infections or evidence of toxic shock syndrome with cutaneous lesions. Make sure to have the patient undress fully.
  • Palpate bones, especially spine for osteomyelitis and epidural abscess.
  • Examine for possible septic arthritis; increased susceptibility to infections of sternoclavicular joint, sacroiliac joint. Ask the patient to move all extremities and joints because septic joints are extremely painful. Patients with septic joints usually have severely restricted range of motion due to pain.
  • Evaluate for CVA or LUQ tenderness for renal or splenic abscesses, respectively.
  • Conduct a neuro exam to evaluate for focal deficits or AMS (CNS septic emboli, botulism, tetanus, severe sepsis).
  • Evaluate heart for new murmurs and lungs for evidence of infection or consolidation.
  • Pelvic exam in women to rule out pelvic inflammatory disease (PID) if indicated.
• Laboratory and radiological evaluation:
  • Order CBC with diff, CMP, urinalysis, CXR.
  • Order blood cultures x 2, urine culture.
  • HIV Ag/Ab testing (and viral load if suspect acute HIV), hepatitis B Core IgM Ab/Surface Ab/Surface Ag, hepatitis C Ab, RPR/GC/Chlamydia (for GC/CT, ask about sexual activity and consider ordering rectal + pharyngeal + urine depending on history)
  • Order TTE if positive blood culture or high clinical suspicion for endocarditis.
  • Consider MRI spine with contrast if concern for osteomyelitis or epidural abscess.
  • ECG to assess for PR interval prolongation that may indicate an aortic valve or mitral valve ring abscess if high concern for endocarditis.

Management

Fever in the setting of injection drug use usually warrants admission. If your clinical suspicion for a severe bacterial infection is low, it is acceptable to observe the patient in the hospital without antibiotics but in most cases empiric antibiotic therapy is given following appropriate cultures.

• Empiric treatment depends on the suspected source: almost always include vancomycin but consider broader coverage for gram negatives and anaerobes based on the clinical presentation. For example, if there is no obvious source and/or endocarditis is suspected, then vancomycin plus ceftriaxone is reasonable empiric coverage.
• Treat drug withdrawal and connect patients with appropriate resources and services:
  • Needle-exchange programs and teaching of safe injection practices.
  • Referral for Medication-Assisted Treatment (MAT). Ideally start while inpatient if patient is interested and it is possible at your institution.
  • HIV counseling.
  • Pre-exposure prophylaxis for HIV (PrEP).
  • Discharge with naloxone (Narcan).
  • CDC on Persons Who Inject Drugs (PWID): https://www.cdc.gov/pwid/index.html

Key Points

• A thorough and complete history and physical examination along with targeted testing are essential

Hind CR. Pulmonary complications of intravenous drug misuse. 2. Infective and HIV related complications. Thorax. 1990;45(12):957‐961. doi:10.1136/thx.45.12.957

Baddour LM, Wilson WR, Bayer AS, et.al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005:111:e394-e433.

Torka, Pallawi, and Sonja Gill. "Cotton Fever: An Evanescent Process Mimicking Sepsis in an Intravenous Drug Abuser." The Journal of emergency medicine 44.6 (2013): e385-e387.

Fowler VG Jr., Miro JM, Hoen B, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005;293:3012-3021.

Gordon RJ, Lowy FD. Bacterial infections in drug users. N Engl J Med 2005 353(18):1945-1954

Key words: PWID, endocarditis, skin and soft tissue infection, staph aureus, abscess