The Immunocompromised Host

• When ANC <0.5 and T ≥38.3 (or ≥38.0 ×1 h): cultures, then antipseudomonal β-lactam inside 1 h.
• Reserve vancomycin for line infection, skin/soft tissue involvement, hypotension, MRSA colonization, or severe mucositis; if cultures remain negative and there is no ongoing indication for Gram-positive coverage, discontinue after 48–72 h.
• Persistent fever after 4–7 days despite broad-spectrum antibiotics with expected prolonged neutropenia: consider empiric antifungal therapy (echinocandin/voriconazole).
• Examine daily with focus on lines, mouth, perianal area, lungs; avoid rectal exams.
• Use the MASCC risk index to identify low-risk patients suitable for oral/step-down therapy.

Managing Neutropenic Fever

• Temperature ≥38.3 °C (or sustained ≥38.0 °C for at least 1 hr) AND ANC ≤500/mm³ (or ≥500/mm³ but expected to fall to ≤500/mm³)
• Chest radiograph, blood cultures ×2, urinalysis and urine culture; further testing as indicated (nasopharyngeal swab for influenza and other respiratory viruses; Clostridioides difficile toxin)
• Begin empiric gram-negative antibiotics*; when indicated** add vancomycin 1 g q12hr × 72 hours
• Suspected intra-abdominal source or C. difficile infection → consider adding metronidazole 500 mg PO/IV q8hr
• Clinical instability → consider double gram-negative coverage with an aminoglycoside × 72 hours (stop if cultures negative after 72 hours)
• New fever following ≥48 hours afebrile, OR still febrile ≥72 hours with negative cultures?
• Clinically unstable: switch gram-negative coverage; consider adding vancomycin**
• Clinically stable: cultures positive → treat per culture and sensitivities; cultures negative → stay on the same regimen
• Still febrile ≥5 days with negative cultures: consider infectious disease consult; consider an antifungal (voriconazole vs liposomal amphotericin B)
• Keep current regimen; reassess daily (lines, mouth, perianal, chest)
• (*) Gram-negative options: meropenem 500 mg IV q6hr OR cefepime 2 g IV q8hr OR piperacillin-tazobactam 3.375 g IV q6hr. Penicillin allergy: aztreonam 2 g IV q8hr OR ciprofloxacin 400 mg IV q12hr
• (**) Vancomycin indications: severe mucositis · clinical evidence of catheter-related infection · known colonization with resistant streptococci or staphylococci · sudden temperature spike >40 °C · hypotension. Stop vancomycin after 72 hours when cultures are negative for coagulase-negative staphylococci, MRSA, or cephalosporin-resistant streptococci