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Dosing for prolonged infusions of beta-lactams[1-8]

Dosing for prolonged infusions of beta-lactams[1-8]
  Creatinine clearance Dose Dosing interval Infusion time
Piperacillin-tazobactam* >20 mL/minute 3.375 or 4.5 g Every 8 hours 4 hours
≤20 mL/minute or intermittent HD or PD 3.375 or 4.5 g Every 12 hours 4 hours
CRRT 3.375 or 4.5 g Every 8 hours 4 hours
CefepimeΔ ≥50 mL/minute 2 g Every 8 hours 3 to 4 hours
30 to 49 mL/minute 2 g Every 12 hours 3 to 4 hours
15 to 29 mL/minute 1 g Every 12 hours 3 to 4 hours
<15 mL/minute or intermittent HD 1 g Every 24 hours 3 to 4 hours
CRRT 2 g Every 12 hours 3 to 4 hours
Imipenem◊ >70 mL/minute 500 mg or 1 g Every 6 hours 3 hours
41 to 70 mL/minute 500 mg or 750 mg Every 8 hours 3 hours
21 to 40 mL/minute 250 or 500 mg Every 6 hours 3 hours
6 to 20 mL/minute or intermittent HD or PD 250 or 500 mg Every 12 hours 3 hours
CRRT 500 mg Every 6 hours 3 hours
Meropenem§ ≥50 mL/minute 1 or 2 g Every 8 hours 3 hours
25 to 49 mL/minute 1 or 2 g Every 12 hours 3 hours
10 to 24 mL/minute 500 mg or 1 g Every 12 hours 3 hours
<10 mL/minute or intermittent HD 500 mg or 1 g Every 24 hours, given after HD 3 hours
CRRT 1 or 2 g Every 12 hours 3 hours
Ceftazidime-avibactam¥ >50 mL/minute 2.5 g Every 8 hours 2 to 3 hours
31 to 50 mL/minute 1.25 g Every 8 hours 2 to 3 hours
16 to 30 mL/minute 0.94 g Every 12 hours 2 to 3 hours
6 to 15 mL/minute 0.94 g Every 24 hours 2 to 3 hours
<5 mL/minute or intermittent HD 0.94 g Every 48 hours, given after HD 2 to 3 hours
CRRT 1.25 g Every 8 hours 2 to 3 hours
Ceftolozane-tazobactam >50 mL/minute 1500 or 3000 mg Every 8 hours 3 hours
30 to 50 mL/minute 750 or 1500 mg Every 8 hours 3 hours
15 to 29 mL/minute 375 or 750 mg Every 8 hours 3 hours
<15 mL/minute or intermittent HD 150 or 375 mg Every 8 hours (start after loading dose) 3 hours
CRRT 750 or 1500 mg Every 8 hours 3 hours
Cefiderocol ≥60 mL/minute 2 g Every 6 hours 3 hours
30 to 59 mL/minute 1.5 g Every 8 hours 3 hours
15 to 29 mL/minute 1 g Every 8 hours 3 hours
<15 mL/minute or intermittent HD 750 mg Every 12 hours 3 hours
CRRT 1.5 g Every 12 hours 3 hours
  Estimated glomerular filtration rate Dose Dosing interval Infusion time
Meropenem-vaborbactam ≥50 mL/minute 4 g Every 8 hours 3 hours
30 to 49 mL/minute 2 g Every 8 hours 3 hours
15 to 29 mL/minute 2 g Every 12 hours 3 hours
<15 mL/minute or intermittent HD 1 g Every 12 hours 3 hours
CRRT 2 g Every 8 hours 3 hours
The dosing recommendations reflect the opinion of UpToDate authors for adult patients with adequate intravenous access. The dosing strategies outlined may not be appropriate for all practice settings; they are based on pharmacodynamic models that use MIC distribution assumptions that may not match local patterns. Indications for use of extended infusions of beta-lactams are discussed in the dedicated topic on this issue. Separate calculators for estimation of creatinine clearance or glomerular filtration rate in conventional or International System of Units are available within UpToDate.
HD: hemodialysis; PD: peritoneal dialysis; CRRT: continuous renal replacement therapy; CVVHDF: continuous venovenous hemodiafiltration; MIC: minimum inhibitory concentration.
* The higher dose of piperacillin-tazobactam (4.5 g) is used in certain situations, such as expected augmented drug clearance (as with critical illness or cystic fibrosis) or in cases of infections with pathogens that have high, but still susceptible, MICs to piperacillin-tazobactam when alternative agents are not appropriate. This higher dose can also be used for empiric treatment in communities or institutions where the P. aeruginosa MICs to piperacillin-tazobactam range higher than 32. Some studies have also used a dose of 4.5 g every 6 hours infused over 3 hours.
¶ The recommendations for CRRT dosing are based off of CVVHDF with a flow rate of 1 liter per hour and minimal residual renal function.
Δ Some studies have also used a 3-hour infusion time for cefepime.
◊ Imipenem is dosed by both weight and renal function. Dosing above is based on patient weight >70 kg.
§ The higher dose of meropenem is used in patients with infections of the central nervous system or other life-threatening infections such as necrotizing fasciitis.
¥ Prolonged infusion ceftolozane-tazobactam may be used for multidrug-resistant organisms, including P. aeruginosa; clinical studies evaluating its benefit are ongoing.
Data from:
  1. Lodise TP, Lomaestro BM, Drusano GL, Society of Infectious Diseases Pharmacists. Application of antimicrobial pharmacodynamic concepts into clinical practice: focus on beta-lactam antibiotics: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2006; 26:1320.
  2. Bauer KA, West JE, O'Brien JM, Goff DA. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother 2013; 57:2907.
  3. Hershberger E, Moukasassi MS, Steenbergen J, et al. CXA-101/Tazobactam (CXA/TAZ) probability of target attainment using population pharmacokinetic analysis. Presented at the 21st European Congress of Clinical Microbiology and Infectious Diseases, Milan Italy May 2011.
  4. Avycaz [Prescribing Information]. Cincinnati, OH: Forrest Pharmaceuticals, Inc.; 2015.
  5. Hughes DW, Frei CR, Maxwell PR, et al. Continuous versus intermittent infusion of oxacillin for treatment of infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother 2009; 53:2014.
  6. Cheatham SC, Shea KM, Healy DP, et al. Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients. Int J Antimicrob Agents 2011; 37:46.
  7. Patel N, Scheetz MH, Drusano GL, Lodise TP. Identification of optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother 2010; 54:460.
  8. Koomanachai P, Bulik CC, Kuti JL, Nicolau DP. Pharmacodynamic modeling of intravenous antibiotics against gram-negative bacteria collected in the United States. Clin Ther 2010; 32:766.
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