An adult patient with recent hemorrhagic stroke who is now septic and receiving intravenous piperacillin‑tazobactam 4.5 g three times daily and linezolid 600 mg twice daily has developed multiple vesicular lesions in skin folds and other covered areas; what is the most likely cause and the appropriate initial management?

Severe Cutaneous Adverse Reaction to Piperacillin-Tazobactam

Immediately discontinue piperacillin-tazobactam—this patient has developed a severe cutaneous adverse reaction (SCAR), most likely drug reaction with eosinophilia and systemic symptoms (DRESS) or acute generalized exanthematous pustulosis (AGEP), which are known complications of piperacillin-tazobactam therapy. 1

Immediate Management Algorithm

Step 1: Stop the Offending Agent

• Discontinue piperacillin-tazobactam immediately. The FDA label explicitly warns that piperacillin-tazobactam may cause severe cutaneous adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, and AGEP, and mandates discontinuation if lesions progress. 1
• Do not wait for dermatology consultation to stop the drug—every hour of continued exposure worsens the reaction and increases mortality risk.

Step 2: Replace Antibiotic Coverage

• Switch to meropenem 1 g IV every 8 hours (given as extended infusion over 3-4 hours) plus vancomycin 15 mg/kg IV every 12 hours to maintain broad-spectrum coverage for sepsis while avoiding beta-lactam/beta-lactamase inhibitor combinations. 2, 3
• Meropenem provides equivalent antipseudomonal and gram-negative coverage without the tazobactam component that is likely driving the hypersensitivity reaction. 2
• Continue linezolid 600 mg IV twice daily for MRSA coverage—linezolid is not implicated in this reaction. 2

Step 3: Assess Severity and Type of Cutaneous Reaction

• Examine for the following high-risk features:

  • Mucosal involvement (oral, ocular, genital)—suggests Stevens-Johnson syndrome/toxic epidermal necrolysis
  • Facial edema, fever >38.5°C, eosinophilia >1,000/μL—suggests DRESS syndrome
  • Sterile pustules on erythematous base—suggests AGEP
  • Body surface area involvement >30%—indicates severe disease 1

• Order immediate laboratory tests: complete blood count with differential (looking for eosinophilia), comprehensive metabolic panel (hepatic and renal function), and consider skin biopsy if diagnosis is uncertain. 1

Step 4: Initiate Supportive Care

• For DRESS syndrome (most likely given body fold distribution and sepsis context):

  • Start systemic corticosteroids: methylprednisolone 1-2 mg/kg/day IV if severe systemic involvement or organ dysfunction is present
  • Monitor liver enzymes, renal function, and complete blood count daily—DRESS can cause hepatitis, nephritis, and hematologic abnormalities
  • Provide aggressive wound care and infection prevention for denuded skin areas 1

• For AGEP (if sterile pustules are present):

  • Supportive care is usually sufficient—AGEP typically resolves within 2 weeks of drug discontinuation
  • Topical corticosteroids may provide symptomatic relief
  • Systemic corticosteroids are generally not required unless severe 1

Critical Considerations in This Septic Post-Stroke Patient

Hemorrhagic Stroke Complication

• This patient's recent hemorrhagic stroke creates additional risk—avoid medications that may increase bleeding risk or interact with anticoagulation if it needs to be restarted. 2
• Monitor neurological status closely, as systemic inflammatory response from DRESS can potentially worsen cerebral edema. 2

Sepsis Management During Antibiotic Transition

• Do not allow any gap in antibiotic coverage—administer the first dose of meropenem immediately after stopping piperacillin-tazobactam, as each hour of inadequate antibiotic therapy in sepsis increases mortality by 7.6%. 4
• Continue aggressive sepsis management per Surviving Sepsis Campaign guidelines: fluid resuscitation targeting mean arterial pressure ≥65 mmHg, vasopressor support if needed, and source control. 2

Renal Function Monitoring

• The FDA label warns that piperacillin-tazobactam is an independent risk factor for acute kidney injury in critically ill patients, and combined use with vancomycin further increases this risk. 1
• Monitor serum creatinine daily and adjust meropenem dosing based on creatinine clearance—for CrCl 26-50 mL/min, reduce to 1 g every 12 hours; for CrCl 10-25 mL/min, reduce to 500 mg every 12 hours. 3

Common Pitfalls to Avoid

• Do not continue piperacillin-tazobactam "just one more day" while awaiting dermatology consultation—SCARs can progress rapidly to life-threatening conditions, and the FDA label mandates immediate discontinuation. 1

• Do not substitute another beta-lactam/beta-lactamase inhibitor combination (such as ampicillin-sulbactam or amoxicillin-clavulanate)—cross-reactivity is likely, and the tazobactam component is the probable culprit. 1

• Do not underdose the replacement antibiotic—meropenem must be given at full sepsis dosing (1 g every 8 hours) with extended infusion to maintain adequate time above MIC for critically ill patients. 3

• Do not assume the rash is simply "antibiotic rash" or contact dermatitis—vesicular lesions in body folds during piperacillin-tazobactam therapy are a red flag for SCAR, which carries significant morbidity and mortality if not recognized early. 1