1

What Are Infusion Strategies?

Beta-lactams kill bacteria based on time above MIC — the longer the free drug concentration stays above the MIC, the better the bacterial kill. Changing how you infuse the same total dose can dramatically alter fT>MIC.

Infusion Strategy
Dosing
Cmax,SS
-- mg/L
Cmin,SS
-- mg/L
fT>MIC
-- %
AUC₂₄
-- mg·hr/L
Try it: Switch between strategies while keeping the same dose — watch the curve reshape from sharp peaks to a flat line. Notice how fT>MIC improves even though you give the same total daily dose.
fT>MIC: --
Key concept: All three strategies deliver the same total daily dose — only the infusion duration changes. Longer infusions sacrifice peak height for sustained time above MIC.
2

Side-by-Side Comparison

Overlay multiple strategies on one chart to directly compare concentration profiles and target attainment.

Strategies to Compare
Dosing
Strategy Cmax Cmin fT>MIC AUC₂₄
Notice: The blue intermittent curve has the highest peaks but drops below MIC the earliest. Extended (green) and continuous (orange) keep concentrations above MIC for longer — at the cost of lower peaks.
3

Clinical Application

When to use each strategy and what to consider in practice.

Intermittent Infusion

0.5h infusion

When to use

  • Standard dosing for non-critically ill patients
  • Outpatient parenteral antibiotic therapy (OPAT)
  • Low MIC organisms (susceptible pathogens)
  • When nursing workflow requires quick administration

Advantages

  • Simplest to administer — standard clinical practice
  • High peak concentrations (concentration-dependent effect for some drugs)
  • Compatible with most Y-site medications
  • No stability concerns (short infusion time)

Limitations

  • Lowest fT>MIC of all strategies at equivalent doses
  • May be insufficient for organisms with higher MICs
  • Deep trough periods with no bactericidal activity

Extended Infusion

3–4h infusion

When to use

  • ICU patients with serious infections
  • Organisms with higher MICs (near breakpoint)
  • Augmented renal clearance (CrCL > 130 mL/min)
  • When fT>MIC target is not met with intermittent dosing

Advantages

  • Significantly improved fT>MIC vs intermittent
  • Same total daily dose — no extra drug cost
  • Well-supported by clinical evidence (mortality benefit in meta-analyses)
  • Practical compromise between intermittent and continuous

Limitations

  • Requires dedicated IV line during infusion
  • Must verify drug stability at room temperature for infusion duration
  • May conflict with other time-critical infusions

Continuous Infusion

24h infusion

When to use

  • Critically ill patients with high MIC organisms
  • When extended infusion still does not achieve target
  • Maximizing fT>MIC (approaches 100%)
  • Select centers with established CI protocols

Advantages

  • Maximum fT>MIC — steady-state concentration always above MIC (if Css > MIC)
  • Most efficient use of total daily dose
  • Predictable steady-state (Css = Dose/τ ÷ CL)
  • Easiest to target a specific concentration

Limitations

  • Requires dedicated IV lumen for 24 hours
  • Drug stability at room temperature must be confirmed (24h+)
  • Not all beta-lactams are stable for 24h (check stability data)
  • Usually requires a loading dose to reach Css quickly
  • Less clinical outcome data than extended infusion

Summary Reference

Strategy Typical Setting fT>MIC Optimization Key Consideration
Intermittent General ward, OPAT Lowest Simple, standard practice
Extended ICU, high MIC Improved Best evidence for mortality benefit
Continuous ICU, very high MIC Maximum Requires stability data + dedicated line

Key References

  1. Roberts JA, et al. Continuous versus intermittent β-lactam infusion in severe sepsis: a meta-analysis of individual patient data. Clin Infect Dis. 2016;63(4):418-425.
  2. Dulhunty JM, et al. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis. 2013;56(2):236-244.
  3. Rhodes NJ, et al. Prolonged infusion piperacillin-tazobactam decreases mortality and improves outcomes in severely ill patients. Crit Care Med. 2018;46(2):236-243.
  4. Abdul-Aziz MH, et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? J Antimicrob Chemother. 2012;67(10):2607-2615.