What is post-injection cellulitis?

Post-Injection Cellulitis: Definition, Diagnosis, and Management

Post-injection cellulitis is a bacterial infection of the deep dermis and subcutaneous tissue that occurs at an injection site, characterized by expanding erythema, warmth, tenderness, and swelling. It must be distinguished from normal post-vaccination reactions and robust takes (RTs), which can mimic bacterial cellulitis but have different management approaches.

Types of Post-Injection Reactions

1. True Bacterial Cellulitis

• Definition: Secondary bacterial infection at injection site
• Causative organisms: Most commonly Streptococcus species and Staphylococcus aureus 1
• Timing: Typically occurs within 5 days of injection or >30 days post-injection 1
• Clinical course: Progressive worsening without treatment 1
• Incidence: Uncommon (0.55 per 10,000 vaccinees) 1

2. Robust Take (RT) / Non-infectious Inflammatory Reaction

• Definition: A vaccinial cellulitis or inflammatory reaction >3 inches (7.5 cm) in diameter 1
• Timing: Peaks 8-10 days post-vaccination 1
• Clinical course: Self-limited, improves within 24-72 hours of peak symptoms 1
• Incidence: Can occur in up to 16% of vaccinees 1

Distinguishing Features

Bacterial Cellulitis:

• Progressive worsening without treatment
• May have fluctuant enlarged lymph nodes
• Responds to appropriate antibiotic therapy
• Risk factors include children, frequent manipulation of injection site, and occlusive dressings 1
• Secondary streptococcal bacterial infections have been reported, but anaerobic organisms and mixed infections may also occur 1

Robust Take/Non-infectious Reaction:

• Predictable timing (peaks 8-10 days post-vaccination)
• Self-limited course (improves within 72 hours of peak symptoms)
• Does not progress clinically
• Fever may be present but is not helpful in distinguishing from bacterial cellulitis 1
• Antibiotics do not shorten duration or lessen severity of symptoms 1

Diagnostic Approach

1. Timing assessment: When did symptoms begin relative to injection?

   • Early (<5 days) or late (>30 days): More likely bacterial cellulitis
   • 8-10 days post-injection: Consider robust take/inflammatory reaction

2. Clinical progression:

   • Worsening despite observation: Bacterial cellulitis
   • Improvement within 24-72 hours of peak: Likely robust take

3. Microbiological confirmation:

   • Bacterial cultures can be obtained by swabs or aspiration
   • Gram stains are useful only when unusual pathogens are present 1
   • Blood cultures are positive in only 5% of cellulitis cases 1

Management Algorithm

For Suspected Bacterial Cellulitis:

1. Initiate antibiotic therapy targeting streptococci and staphylococci:

   • Oral options: Dicloxacillin, cephalexin, clindamycin, or erythromycin 1
   • Parenteral options (for severe cases): Nafcillin, cefazolin, clindamycin, or vancomycin 1
   • Consider MRSA coverage if risk factors present (athletes, children, prisoners, prior MRSA exposure, IV drug users) 2

2. Duration: 5 days is sufficient for uncomplicated cases, with extension if symptoms are not improved 2

3. Adjust therapy based on culture results if available

For Suspected Robust Take/Non-infectious Reaction:

1. Vigilant observation
2. Patient education about expected course
3. Supportive care:
   • Rest of affected limb
   • Oral non-aspirin analgesics
   • Oral antipruritic agents if needed 1
4. Avoid topical medications including steroids or antibacterial agents 1

Common Pitfalls and Caveats

1. Misdiagnosis: Robust takes are frequently misdiagnosed as bacterial cellulitis, leading to unnecessary antibiotic use 1

2. Unnecessary antibiotics: In a CDC study, 6 of 9 vaccinees with robust takes were treated for suspected bacterial cellulitis, but all improved within 24-72 hours regardless of antibiotic treatment 1

3. Failure to recognize mimics: Venous insufficiency, eczema, deep vein thrombosis, and gout are frequently mistaken for cellulitis 3

4. Risk of recurrence: Each episode of cellulitis causes lymphatic inflammation and possibly permanent damage, which may predispose to recurrent episodes 1

5. Vaccine-specific reactions: Some vaccines (like Zostavax®, pneumococcal, and pertussis-containing vaccines) can cause cellulitic-appearing reactions that do not respond to antibiotics 4

Prevention of Recurrence

For patients with recurrent post-injection cellulitis:

• Address underlying risk factors (obesity, venous insufficiency, lymphedema)
• Consider prophylactic antibiotics for frequent recurrences:
  • Monthly intramuscular benzathine penicillin injections (1.2 MU in adults)
  • Oral therapy with twice-daily doses of either 250 mg erythromycin or 1 g penicillin V 1
• Penicillin V is the preferred antibiotic for prevention 5

By understanding the differences between true bacterial cellulitis and non-infectious inflammatory reactions at injection sites, clinicians can provide appropriate management and avoid unnecessary antibiotic use.