UptoDate: Dosing for Prolonged Infusions of Beta Lactams
|
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
|
500 mg or 1 g
|
Every 6 hours
|
3 hours
|
41 to 70
|
500 mg or 750 mg
|
Every 8 hours
|
3 hours
|
|
21 to 40
|
250 or 500 mg
|
Every 6 hours
|
3 hours
|
|
6 to 20 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
|
© 2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
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 six hours infused over three 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.
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.
Guide to Antimicrobial Therapy in the ICU 2017
The use of
extended or continuous infusions of s-lactam antibiotics has been shown to
improve the time the free drug remains above MIC which predicts the killing
characteristic of the antibiotic. This is pertinent when dealing with
multi-drug resistant organisms. A loading dose must be given prior to regular
dosing of the antimicrobial followed by either:
• Extended
infusion: Infusion lasting 3-4 hours, usually 50% of dosing interval.
•
Continuous infusion: Infusion over 24 hours at a fixed rate.
The
diluted antibiotic should be stable throughout the infusion duration at room
temperature of less than 24°C and has no incompatibilities with other
medication administered concurrently. The stability may differ with different
manufacturers.
Antibiotic
|
Loading dose over 30 mins
|
Duration of infusion
|
Notes
|
Ampicillin
/ Sulbactam
*
For High dose sulbactam
|
|
Over
4 hrs
|
3g
of Ampicillin/Sulbactam dilute in 70 mL NS / D5
|
Cefepime
|
2
g
|
Over
4 hrs
Or
Continuous
infusion over interval prescribed
|
1-2
g in 50mL NS
|
Ceftazidime
|
2
g
|
Over
4 hrs
Or
Continuous
infusion over interval prescribed
|
1-2
g in 50mL NS
|
Imipenem
|
1
g
|
Over
4 hrs
|
500mg
or 1g : Dilute in 100-200 mL NS (5 mg/mL)
|
Meropenem
|
1-2
g
|
Over
4 hrs
|
500mg
or 1g : Dilute in 50 mL NS
2g
: Dilute in 100 mL NS
|
Piperacillin
/ Tazobactam
|
4.5
g
|
Over
4 hrs
Or
Continuous
infusion over interval prescribed
|
2.25g
or 4.5g : Dilute in 50 mL NS
|
Data from Product Leaflet:
Piptazo
|
AUROTAZ: Recon each vial with 10mL SWFI / NS,
inject over at least 3-5 mins; or further dilute with at least 50 mL SWFI / NS
/ D5. Store in a refrigerator can use within 24 hrs.
|
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Cefepime
|
CEFMEX: IV infusion of a volume between
50-100 mL should be administered over ~30 mins. Compatible at 1-40 mg/ml with
SWFI, D5, NS ; stable for 48 hrs at 2-8°C
|
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Imipenem
|
TIENAM: Recon each vial with 100 mL of NS
/ D5 / D10 / NSD5 / HSD5 / QSD5 / Maniitol 5% / Mannitol 10% (LACTATE
INCOMPATIBLE). Stable at 25°C for 4 hrs or at 4°C for 24 hrs.
|
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Meropenem
|
NURONEM: Recon each 500mg with 10mL SWFI,
then may be further diluted with 50-200 mL diluents, producing concentration
of 1-20 mg/mL.
.
|
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