What is the recommended empiric antibiotic therapy for hospitalized patients with autoinflammatory pustulosis, considering potential allergies and underlying medical conditions?

Empiric Antibiotic Therapy for Hospitalized Patients with Autoinflammatory Pustulosis

Critical Recognition: Autoinflammatory Pustulosis is NOT an Infection

Autoinflammatory pustulosis (including conditions like SAPHO syndrome and acute generalized exanthematous pustulosis/AGEP) does NOT require empiric antibiotic therapy—in fact, antibiotics are contraindicated as they are the most common trigger for AGEP. 1, 2, 3

Understanding the Disease Process

Autoinflammatory pustulosis represents a sterile inflammatory condition, not a bacterial infection:

• AGEP is a severe cutaneous adverse reaction caused by drugs in >90% of cases, with antibiotics being the most common culprits (particularly beta-lactams like piperacillin-tazobactam, cephalosporins, and aminopenicillins). 2, 3

• The pustules are sterile, characterized histopathologically by intraepidermal neutrophilic pustules with eosinophilic infiltration—not bacterial infection. 2, 3

• SAPHO syndrome is an autoinflammatory disease involving synovitis, acne, pustulosis, hyperostosis, and osteitis, driven by IL-23/Th17 axis activation and neutrophil activation—not infection. 4

Immediate Management Algorithm

Step 1: Identify and Stop the Offending Agent

• Immediately discontinue ALL antibiotics if AGEP is suspected (rapid onset of sterile pustules, fever, leukocytosis within hours to days of antibiotic exposure). 1, 2, 3

• Look for danger signs of severe cutaneous adverse reactions: tiny vesicles or crusts, grey-violaceous lesions, painful/burning skin with fever and malaise, exanthema with pustules, facial edema, acute fever ≥38.5°C. 1

Step 2: Provide Supportive Care (NOT Antibiotics)

• Potent topical corticosteroids are the mainstay of treatment for AGEP. 3

• Supportive care with prevention of further antibiotic exposure is critical. 3

• Symptoms typically resolve within 3 days of stopping the causative medication, with desquamation following. 2, 3

Step 3: Advanced Therapy for Refractory Cases

For chronic autoinflammatory pustulosis (like SAPHO syndrome) that requires systemic therapy:

• Apremilast (pan-cytokine approach) has shown success in refractory SAPHO syndrome. 4

• Biologics targeting IL-23/Th17 axis (ustekinumab, secukinumab) or TNF inhibitors may be considered, though these require specialist consultation. 4

Critical Pitfalls to Avoid

The most dangerous error is initiating or continuing antibiotics in a patient with autoinflammatory pustulosis:

• Do NOT empirically treat with antibiotics based on the presence of pustules—these are sterile inflammatory lesions, not infectious. 2, 3

• Do NOT mistake AGEP for bacterial skin infection—the rapid onset (hours to days), sterile pustules, and temporal relationship to antibiotic exposure distinguish AGEP from infectious processes. 1, 2, 3

• Continuing antibiotics will worsen AGEP and delay resolution. 2, 3

When Infection IS Present (Rare Scenario)

If a hospitalized patient with known autoinflammatory pustulosis develops a separate, documented bacterial infection (positive cultures, clear infectious source):

• Avoid beta-lactam antibiotics entirely given their high association with AGEP. 2, 3

• Consider alternative agents based on the specific infection site and local resistance patterns, selecting from non-beta-lactam classes (fluoroquinolones, vancomycin, linezolid) as appropriate for the documented pathogen. 1, 5

• Document the severe cutaneous adverse reaction history prominently to prevent future beta-lactam exposure. 1