What antibiotic should be added to ceftazidime (Ceftazidime) for a patient with Sickle Cell Disease who underwent a bone marrow transplant, developed a fever 1 day post-procedure, and failed to improve after 72 hours of treatment?

Add Vancomycin to Ceftazidime

For a bone marrow transplant patient with persistent fever after 72 hours of ceftazidime monotherapy, vancomycin (Option D) should be added to cover gram-positive organisms, particularly methicillin-resistant staphylococci and viridans streptococci that commonly cause breakthrough bacteremia in this high-risk population. 1

Rationale for Vancomycin Addition

• Gram-positive organisms account for 63% of bacterial pathogens in febrile neutropenia and are the most likely cause of treatment failure after 72 hours of ceftazidime monotherapy 2
• Breakthrough bacteremias with gram-positive organisms, especially viridans streptococci, can be fatal when vancomycin therapy is delayed in post-BMT patients 1, 2
• The EORTC Trial V demonstrated significant benefit when vancomycin was added to ceftazidime-based regimens, with response rates improving from 45% to 71% (p=0.004) and reduced mortality from infection 2

Why Not the Other Options

• Tazobactam (Option A): Adding a beta-lactamase inhibitor provides no additional benefit since ceftazidime already has anti-pseudomonal activity, and the clinical scenario suggests gram-positive rather than resistant gram-negative infection 1
• Ceftriaxone (Option B): Switching to ceftriaxone offers no advantage as both are third-generation cephalosporins with similar gram-negative coverage, but ceftriaxone lacks the superior anti-pseudomonal activity of ceftazidime that is critical in post-transplant settings 1, 2
• Sulfamethoxazole (Option C): Trimethoprim-sulfamethoxazole has no role in empiric treatment of febrile neutropenia 1

Clinical Algorithm for This Scenario

• At 72 hours post-ceftazidime initiation, reassess the patient clinically for new signs of infection, particularly looking for central line infection, skin/soft tissue infection, or signs of sepsis 1
• Add vancomycin to maintain gram-positive coverage while continuing ceftazidime for ongoing gram-negative and anti-pseudomonal protection 1, 2
• If blood cultures remain negative at 48 hours after vancomycin addition, consider discontinuing vancomycin to reduce toxicity and cost 3
• If fever persists after 4-7 days of appropriate antibacterial therapy (ceftazidime plus vancomycin), empirical antifungal therapy should be initiated and chest CT obtained to evaluate for invasive aspergillosis 1, 3

Important Caveats

• The median time to defervescence in high-risk BMT patients is 5-7 days, so some persistent fever is expected even with appropriate therapy 1
• Prospective randomized trials demonstrate that adding vancomycin after 96 hours of persistent fever on ceftazidime produces equivalent outcomes to starting vancomycin upfront, with similar response rates and survival 4
• Monitor for vancomycin toxicity, particularly nephrotoxicity and cutaneous reactions, which occur more frequently when vancomycin is combined with ceftazidime 2, 4
• Non-bacterial infections (CMV, HSV, fungi) become increasingly likely after 4-7 days of persistent fever despite appropriate antibacterials 1