Wednesday, April 16, 2025

🩸🦠🤒 Febrile Neutropenia—Empiric Anti‐Pseudomonal Coverage


Scenario:
A 57‑year‑old woman with acute myeloid leukaemia is 7 days post‑induction chemotherapy. Her absolute neutrophil count is 80 cells/µL. She presents with a single episode of fever (38.6 °C) and mild malaise. There are no focal signs of infection on exam, and chest X‑ray is clear.


Question:
Which empiric IV antibiotic is most appropriate to cover her risk of Gram‑negative bacteraemia, including Pseudomonas?

A) Cefepime
B) Piperacillin–Tazobactam
C) Meropenem
D) Ceftazidime
E) Aztreonam



 Preferred Answer: A) Cefepime


📘 Mini‑Lesson & Explanation

  1. Why Cefepime?

    • Broad Gram‑negative coverage including Pseudomonas aeruginosa

    • Reliable Gram‑positive activity against Streptococcus spp. and MSSA (No MRSA coverage —add vancomycin if needed)

    • Lower propensity to select for carbapenem‑resistant organisms compared with meropenem

  2. Why Not Piperacillin–Tazobactam?

    • Also covers Pseudomonas, but its anaerobic spectrum is unnecessary in neutropenic fever without a clear source

    • Higher risk of Clostridioides difficile infection

    • May alter the gut microbiome more profoundly

  3. Why Not Meropenem?

    • Excellent anti‑Pseudomonal and ESBL coverage, but

    • Reserve carbapenems for suspected resistant organisms or documented ESBL bacteremia to preserve efficacy and limit resistance

  4. Why Not Ceftazidime?

    • Covers Pseudomonas well, but

    • Poor Streptococcal activity—leaving a gap against Gram‑positives common even in febrile neutropenia

    • Often requires combination with another agent for Gram‑positive coverage

  5. Why Not Aztreonam?

    • Covers Pseudomonas and most Gram‑negatives, but

    • No Gram‑positive activity—would need a second agent (e.g. vancomycin) empirically

    • Typically reserved for patients with severe β‑lactam allergy


💡 Teaching Pearls

  • Febrile Neutropenia Protocols: First‑line monotherapy is an anti‑Pseudomonal β‑lactam with reliable Gram‑negative and some Gram‑positive coverage (cefepime, ceftazidime, piperacillin‑tazobactam, or a carbapenem).

  • Agent Selection: Choose the narrowest-spectrum agent that still covers P. aeruginosa; cefepime is often favoured unless local resistance patterns dictate otherwise.

  • Escalation & De‑escalation:

    • Escalate if fever persists after 48 hours or cultures grow resistant organisms.

    • De‑escalate based on culture results and clinical response to minimise collateral damage.

  • MRSA Coverage: Add vancomycin or linezolid only if there are signs of catheter‑related infection, skin/soft tissue infection, or known colonisation.


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