Is there published data supporting extended or prolonged infusion of ceftazidime in critically ill adults with severe Gram‑negative infections such as ventilator‑associated pneumonia, bloodstream infection, or intra‑abdominal sepsis?

Extended Infusion of Ceftazidime: Evidence-Based Recommendations

Yes, there is robust published data supporting extended or continuous infusion of ceftazidime in critically ill adults with severe Gram-negative infections, and this approach should be strongly considered for patients with septic shock, high severity scores (APACHE II ≥20), or infections caused by organisms with elevated MICs.

Guideline Recommendations for Extended/Continuous Infusion

The French Society of Pharmacology and Therapeutics (SFPT) and French Society of Anaesthesia and Intensive Care Medicine (SFAR) 2019 guidelines explicitly recommend administering beta-lactam antibiotics (including ceftazidime) by prolonged or continuous infusions in critical care patients with septic shock and/or high severity scores to improve clinical cure rates. 1

Specific Clinical Scenarios Where Extended Infusion Is Recommended:

• Septic shock and high severity illness: Meta-analyses demonstrate improved clinical cure rates in patients with APACHE II scores ≥20 or SAPS II scores ≥52 treated with continuous beta-lactam infusion (RR 1.162 [1.042–1.296]). 1

• Lower respiratory tract infections/VAP: Continuous infusion significantly improves clinical cure rates in ICU patients with respiratory infections (RR 1.177 [1.065–1.300]) and nosocomial pneumonia due to Gram-negative bacteria (OR 2.45 [1.12–5.37]). 1

• Non-fermenting Gram-negative bacilli (including Pseudomonas aeruginosa): Extended infusion is particularly beneficial when treating infections caused by organisms with higher MICs (>2 mg/L for ceftazidime against P. aeruginosa). 1

• Intra-abdominal infections in critically ill patients: Prolonged or continuous infusions should be considered for treatment of critically ill patients with healthcare-associated intra-abdominal infections. 1

Published Clinical Data on Ceftazidime Extended Infusion

Pharmacokinetic/Pharmacodynamic Studies:

A 1996 randomized crossover trial in 12 critically ill patients demonstrated that continuous infusion of ceftazidime (2g loading dose followed by 3g over 24h) achieved 100% time above MIC compared to 92% for intermittent dosing (2g every 8h), using only half the total daily dose. 2

A 2015 randomized controlled trial in 34 patients with ventilator-associated pneumonia showed that continuous infusion (loading dose 20mg/kg followed by 60mg/kg/day) achieved 100% time above the 20mg/L threshold in 14/17 patients versus only 1/17 patients with intermittent dosing. 3

Epithelial Lining Fluid Penetration:

In the 2015 VAP study, median ceftazidime concentrations in epithelial lining fluid were twice as high with continuous infusion (12 mg/L) compared to intermittent dosing (6 mg/L), with the 8 mg/L therapeutic threshold achieved twice as often in the continuous infusion group. 3

A 2004 study of 15 critically ill patients with severe nosocomial pneumonia demonstrated that continuous infusion of 4g ceftazidime over 24h (after 2g loading dose) achieved mean steady-state plasma concentrations of 39.6±15.2 µg/mL and ELF concentrations of 8.2±4.8 µg/mL. 4

Practical Dosing Strategies

Standard Approach for Severe Infections:

• Loading dose: 2g IV over 30 minutes 2, 3, 4
• Maintenance: 3-6g continuous infusion over 24 hours 2, 3, 4
• Alternative: Extended infusion over 3-4 hours every 8 hours 1

For Augmented Renal Clearance or Severe Infections:

Recent 2024 simulation data suggest that for severe infections in patients with normal or augmented renal clearance, infusion duration should be extended to 3-4 hours to achieve 100% fT≥MIC targets, and continuous infusion at higher dosages may be required to achieve 100% fT≥4×MIC. 5

For Carbapenem-Resistant Organisms (Ceftazidime-Avibactam):

A 2023 case series demonstrated that continuous infusion of ceftazidime-avibactam enabled optimal joint PK/PD targets in 8/10 critically ill renal patients with carbapenem-resistant Gram-negative infections, helping to minimize microbiological failure. 6

Critical Considerations and Caveats

For Pseudomonas aeruginosa with MIC >2 mg/L, higher doses (6g/24h continuous infusion) or combination therapy should be considered, as standard 4g/24h continuous infusion may be insufficient. 4

The WSES 2016 and 2017 guidelines note that increased doses of ceftazidime are required to reach adequate concentrations in patients with severe intra-abdominal infections due to concentration gradients between plasma and peritoneal space. 1

Always administer a full loading dose regardless of renal function in critically ill patients, as fluid resuscitation-induced volume expansion necessitates this approach to rapidly achieve therapeutic concentrations. 1

Meta-analyses focusing specifically on anti-pseudomonal beta-lactams (including ceftazidime) reported reduced mortality in septic patients treated with extended/continuous administration (RR 0.70 [0.56–0.87]), with the effect most pronounced in critically ill patients with APACHE II scores >20. 1