ICU infections, stewardship and the immunocompromised

Antibiotic PK/PD, TDM, procalcitonin and stewardship

Reviewed Nov 2026·10 references
New· views rounded down, updated weekly

Dose antibiotics for critical illness (loading, extended infusion, AUC-guided vancomycin), use procalcitonin to stop, and keep courses short.

Definition
Beta-lactams are time-dependent (target fT > MIC), aminoglycosides concentration-dependent (Cmax/MIC 8-10), and vancomycin AUC-dependent (AUC/MIC 400-600). Critical illness alters volume of distribution and clearance (augmented renal clearance, AKI, CRRT, hypoalbuminaemia).

At the bedside

  1. 1

    Load fully

    Give full loading doses regardless of renal function (Vd is increased in sepsis); adjust only maintenance doses.

  2. 2

    Prolonged beta-lactam infusion

    After a 30-min loading dose, give piperacillin-tazobactam, meropenem, cefepime as extended (3-4 h) or continuous infusion; meta-analysis showed lower 90-day mortality.

  3. 3

    Aminoglycosides once daily

    Amikacin 15-25 mg/kg or gentamicin 5-7 mg/kg once daily (if used); trough monitoring.

  4. 4

    Vancomycin AUC dosing

    Load 20-35 mg/kg; AUC 400-600 mg·h/L by two levels or Bayesian software; trough 15-20 as surrogate where AUC not feasible.

  5. 5

    Procalcitonin to stop

    Stop antibiotics when PCT < 0.5 ng/mL or falls ≥ 80% from peak, if clinically improving (not to start antibiotics in shock).

  6. 6

    Short courses

    CAP 5-7 days; HAP/VAP 7; intra-abdominal infection with source control 4 days (STOP-IT); uncomplicated Gram-negative bacteraemia 7 days (BALANCE).

  7. 7

    Stewardship time-out at 48-72 h

    Review cultures, de-escalate, IV-to-oral switch, document indication and stop date; unit antibiogram every 6-12 months.

Serious MRSA infection

Vancomycin

IV
Dose
Load 25 mg/kg, maintenance AUC-guided
Worked example
70 kg: 1,750 mg load in 500 mL NS over 2 h; then 15 mg/kg q12h (1 g) adjusted to AUC
Open Creatinine clearance (Cockcroft-Gault)

Extended infusion example

Meropenem

IV
Dose
1 g q8h over 3 h after 30-min first dose
Preparation
1 g in 100 mL NS
Worked example
100 mL over 3 h = 33 mL/h

PK/PD targets

ClassPD driverPractical dosing
Beta-lactamsfT > MIC (40-100%)Extended/continuous infusion; frequent dosing
AminoglycosidesCmax/MIC 8-10Once-daily high dose
VancomycinAUC/MIC 400-600Load + AUC-guided maintenance
PolymyxinsAUC/MICLoad; polymyxin B no renal adjustment
FluoroquinolonesAUC/MICFull doses

Evidence-based durations

InfectionDuration
CAP (stable)5-7 days
HAP/VAP7 days
Intra-abdominal with source control4 days (STOP-IT)
Gram-negative bacteraemia, uncomplicated7 days (BALANCE)
Candidaemia14 days after first negative culture
Red flag · call your senior now
Young trauma/sepsis patient with high urine output and low creatinine (CrCl > 130 mL/min): augmented renal clearance - standard doses may be subtherapeutic.
Pitfall
Halving the first dose of a beta-lactam because of AKI.
Pitfall
Continuing 'just to complete 14 days' when the evidence supports shorter courses.
Pearl
Write the stop date when you start an antibiotic.

Calculators for this topic

Creatinine clearance (Cockcroft-Gault)

(140 − age) × weight ÷ (72 × creatinine), × 0.85 if female. Not valid in unstable AKI.

References

  1. 1

    Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs intermittent infusions of beta-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis. JAMA 2024;332:638-48.

  2. 2

    Dulhunty JM, Brett SJ, De Waele JJ, et al. Continuous vs intermittent beta-lactam antibiotic infusions in critically ill patients with sepsis (BLING III). JAMA 2024;332:629-37.

  3. 3

    Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline. Am J Health Syst Pharm 2020;77:835-64.

  4. 4

    de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients (SAPS). Lancet Infect Dis 2016;16:819-27.

  5. 5

    Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection (STOP-IT). N Engl J Med 2015;372:1996-2005.

  6. 6

    BALANCE Investigators. Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections. N Engl J Med 2025;392:1065-78.

  7. 7

    Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the IDSA and ATS. Clin Infect Dis 2016;63:e61-111.

  8. 8

    Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the IDSA. Clin Infect Dis 2016;62:e1-50.

  9. 9

    National Centre for Disease Control (DGHS, MoHFW) and Indian Council of Medical Research. National Treatment Guidelines for Antimicrobial Use in Infectious Disease Syndromes, Version 2.0. New Delhi: MoHFW; November 2025.

  10. 10

    Tsuji BT, Pogue JM, Zavascki AP, et al. International consensus guidelines for the optimal use of the polymyxins. Pharmacotherapy 2019;39:10-39.

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