1. Broad-Spectrum ICU Empiric Therapy

A. Severe Sepsis / Septic Shock (unknown source)

Option 1 (most common):
✔ Piperacillin–Tazobactam (Zosyn)
4.5 g IV q6h
Covers gram +/–, anaerobes, Pseudomonas

•  

✔ Vancomycin
(15–20 mg/kg; trough goal 15–20)
Covers MRSA

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Option 2 (if renal failure or concern for ESBL):
✔ Meropenem 1–2 g IV q8h (extended infusion)
+
✔ Vancomycin

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Option 3 (if hemodynamic instability with high MDR risk):
✔ Meropenem
+
✔ Vancomycin
+
✔ Amikacin or Tobramycin (single loading dose)

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2. Pneumonia (ICU CAP, HAP, VAP)

A. Community-Acquired Pneumonia (ICU)

✔ Ceftriaxone 2 g IV daily
+
✔ Azithromycin 500 mg IV daily
or
✔ Levofloxacin 750 mg IV daily

If MRSA concern:

• Vancomycin or Linezolid

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B. Hospital-Acquired (HAP) / Ventilator-Associated Pneumonia (VAP)

✔ Zosyn 4.5 g q6h or Cefepime 2 g q8h
Covers Pseudomonas

•  

✔ Vancomycin (MRSA)

•  

If high MDR risk:
✔ Amikacin 15–20 mg/kg once
or
✔ Levofloxacin

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3. Meningitis / Encephalitis (ICU)

✔ Ceftriaxone 2 g q12h
✔ Vancomycin
+
✔ Acyclovir 10 mg/kg q8h
+
Age > 50 or immunocompromised:
✔ Ampicillin (Listeria coverage)

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4. Abdominal Infection / Intra-abdominal Sepsis

✔ Zosyn
or
✔ Meropenem (if severe or ESBL risk)
+
✔ Vancomycin (if source unclear or healthcare-associated)

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5. Urosepsis / Pyelonephritis

✔ Cefepime
or
✔ Zosyn
If ESBL risk:
✔ Ertapenem or Meropenem

Add Vanco if concern for catheter-associated or MRSA.

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6. Skin & Soft-Tissue Infection / Cellulitis (ICU)

✔ Vancomycin
+
If necrotizing / toxic-appearing:
✔ Piperacillin–Tazobactam
+
✔ Clindamycin (to block toxin production)

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7. Endocarditis (ICU)

• Vancomycin

• Cefepime (or gentamicin depending on organism)
  Specialized regimens based on organism & French endocarditis guidelines.

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8. C. difficile colitis (Severe/Fulminant)

✔ Oral Vancomycin 125–500 mg q6h
+
✔ IV Metronidazole for fulminant disease
Avoid IV-only therapy (ineffective in gut lumen).

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9. Antifungals (ICU)

Used when high suspicion for invasive fungal infection:

✔ Micafungin 100 mg IV daily
✔ Fluconazole 400–800 mg IV daily (if Candida albicans)

If immunocompromised / mold coverage:
✔ Voriconazole or Posaconazole

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10. Antivirals (ICU)

Respiratory viral infections:

✔ Oseltamivir 75 mg BID
✔ Acyclovir for HSV/VZV encephalitis
✔ Ganciclovir for CMV reactivation

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Renal Adjustment (CRRT, AKI)

• Vancomycin: trough goal 15–20; careful in renal failure

• Zosyn: extend to q8h in CRRT

• Meropenem: extended infusion (3-hour infusion) improves outcomes

• Aminoglycosides: single high dose only (concentration-dependent)

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ICU Antibiotic Principles

• Time matters: Start antibiotics within 1 hour in shock

• De-escalate after cultures return

• Use extended infusions for β-lactams in septic shock

• Source control is often more important than antibiotics alone

• Check MICs for Pseudomonas and MRSA

• Beware nephrotoxicity: Vanco + Zosyn together increases AKI risk