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
Cefepime^Δ	≥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
Ampicillin-sulbactam^¥	≥30 mL/minute	9 g	Every 8 hours	4 hours
	15 to 29 mL/min	6 g	Every 8 hours	4 hours
	<15 mL/min or intermittent HD	6 g	Every 12 hours	4 hours
	CRRT^¶	9 g	Every 8 hours	4 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	3 g	Every 8 hours	3 hours
	30 to 50 mL/minute	750 mg or 1.5 g	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 450 mg	Every 8 hours (start after loading dose)	3 hours
	CRRT^¶	750 mg or 1.5 g	Every 8 hours	3 hours
Cefiderocol	≥120 mL/min	2 g	Every 6 hours	3 hours
	60 to 119 mL/minute	2 g	Every 8 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
Aztreonam^† (in combination with ceftazidime-avibactam)	≥30 mL/min	2 g	Every 6 to 8 hours	3 hours
	10 to 29 mL/min	1 g	Every 6 to 8 hours	3 hours
	<10 mL/min or intermittent HD	2 g	Every 24 hours	3 hours
	CRRT^¶	2 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.

CRRT: continuous renal replacement therapy; CVVHDF: continuous venovenous hemodiafiltration; HD: hemodialysis; MIC: minimum inhibitory concentration; PD: peritoneal dialysis.

* 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.

¥ High dosing of the sulbactam component with extended infusion times is recommended for carbapenem-resistant Acinetobacter infections^[9]. Note that for patients with normal kidney function, an alternative dosing strategy is 27 g IV as a continuous infusion over 24 hours for patients with normal renal function.

‡ Some experts prefer a 3-hour extended infusion time (instead of standard 2 hours) for ceftazidime-avibactam for infections caused by carbapenem-resistant Enterobacterales, difficult-to-treat P. aeruginosa, and S. maltophilia.

† Extended infusion aztreonam is preferred when used in combination with ceftazidime-avibactam for treatment of multidrug-resistant pathogens (eg, carbapenem-resistant Enterobacterales or Stenotrophomonas). In these cases, it is preferred that both agents are administered at the same time over 3 hours. Note the guideline panel suggests dosing aztreonam every 6 hours of aztreonam, but clinical data are lacking. Dosing every 8 hours is also reasonable and is logistically simpler, especially if clinical stability has been achieved^[9-12].

Data from:

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.
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.
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.
Avycaz [Prescribing Information]. Cincinnati, OH: Forrest Pharmaceuticals, Inc.; 2015.
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.
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.
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.
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.
IDSA 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Infectious Diseases Society of America. Available at: https://www.idsociety.org/practice-guideline/amr-guidance/. (Accessed on July 13, 2023).
Lodise TP, Smith NM, O'Donnell N, et al. Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model. J Antimicrob Chemother 2020; 75:2622.
Falcone M, Daikos GL, Tiseo G, et al. Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales. Clin Infect Dis 2021; 72:1871.
Falcone M, Menichetti F, Cattaneo D, et al. Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients. J Antimicrob Chemother 2021; 76:1025.

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

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