General dosing, susceptible infection:
Weight-directed dosing (Bradley 2019): IV, IM:
Body Weight |
Postnatal Age |
Dose |
---|---|---|
AIf pathogen minimum inhibitory concentration is ≥8 mg/L, doses may need to be infused over 3 hours or frequency increased to every 6 hours. | ||
≤2 kg |
≤28 days |
30 mg/kg/dose every 12 hours |
29 to 60 days |
50 mg/kg/dose every 8 hoursA | |
>2 kg |
≤28 days |
50 mg/kg/dose every 12 hours |
29 to 60 days |
50 mg/kg/dose every 8 hoursA |
GA-directed dosing (Red Book [AAP 2018]; Shoji 2016):
GA <36 weeks: IV: 30 mg/kg/dose every 12 hours.
GA ≥36 weeks: IV: 50 mg/kg/dose every 12 hours.
General dosing, susceptible infection:
Traditional intermittent-infusion method: Infants, Children, and Adolescents:
Non-Pseudomonas spp. infections: IM, IV: 50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose (Red Book [AAP 2018]). Note: Every-12-hour dosing may be suboptimal for infections caused by bacteria with minimum inhibitory concentrations (MICs) ≥1 mg/L based on pharmacokinetic modeling (Courter 2009; Shoji 2016).
Pseudomonas spp. infections (suspected or proven): IM, IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Red Book [AAP 2018]).
Extended-infusion method: Limited data available: Infants, Children, and Adolescents: IV: 50 mg/kg/dose infused over 3 to 4 hours every 8 hours; maximum dose: 2,000 mg/dose; dosing based on a pharmacokinetic modeling study, a case series, and a retrospective comparative study (Beauchamp 2019; Nichols 2015; Shoji 2016). Note: Extended-infusion dosing may be preferred for susceptible dose-dependent pathogens (MIC of 4 or 8 mg/L) (Red Book [AAP 2018]; Shoji 2016).
Cystic fibrosis, acute pulmonary exacerbation: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose; patients with more resistant pseudomonal isolates (MIC ≥16 mg/L) may require 50 mg/kg/dose every 6 hours (Zobell 2013). Note: Some experts prefer extended or continuous infusion methods to optimize antipseudomonal beta-lactam exposure in patients with cystic fibrosis (Han 2006; Molloy 2015; Prescott 2011; Thompson 2016).
Endocarditis, prosthetic valve, treatment within 1 year of replacement: Children and Adolescents: IV: 50 mg/kg/dose every 8 to 12 hours in combination with vancomycin and rifampin for 6 weeks plus gentamicin for the first 2 weeks; maximum dose: 2,000 mg/dose (AHA [Baltimore 2015]).
Febrile neutropenia, empiric therapy: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Red Book [AAP 2018]); duration of therapy dependent upon febrile neutropenia risk-status; in high-risk patients, may discontinue empiric antibiotics if all of the following criteria met: Negative blood cultures at 48 hours; afebrile for at least 24 hours, and evidence of marrow recovery. In low-risk patients, may discontinue empiric antibiotics after 72 hours duration in patients with a negative blood culture and who have been afebrile for 24 hours regardless of marrow recovery status; follow-up closely (Lehrnbecher 2017).
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours in combination with metronidazole; maximum dose: 2,000 mg/dose. Note: IDSA guidelines recommend duration of 4 to 7 days (provided source controlled) (IDSA [Solomkin 2010]).
Meningitis including health care-associated ventriculitis/meningitis: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose. Duration should be individualized based on patient characteristics and response; treatment duration for gram-negative bacilli is a minimum of 10 to 14 days, although some experts recommend ≥21 days and at least 14 days after first negative cerebrospinal fluid culture (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]): Infants, Children, and Adolescents: Intraperitoneal:
Intermittent: 15 mg/kg/dose every 24 hours into the long dwell.
Continuous: Loading dose: 500 mg per liter of dialysate; maintenance dose: 125 mg per liter.
Pneumonia, moderate to severe: Infants ≥2 months, Children, and Adolescents:
Due to P. aeruginosa: IV: 50 mg/kg/dose every 8 hours for 10 days; maximum dose: 2,000 mg/dose.
Not due to P. aeruginosa: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose.
Skin and skin structure infections, uncomplicated: Infants ≥2 months, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose.
Urinary tract infection, complicated and uncomplicated: Infants ≥2 months, Children, and Adolescents:
Mild to moderate infection: IM, IV: 50 mg/kg/dose every 12 hours for 7 to 10 days; maximum dose: 1,000 mg/dose. Note: IM may only be considered for mild to moderate infections due to E. coli.
Severe infection: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult studies, manufacturer labeling, and expert opinion.
Altered kidney function:
Infants, Children, and Adolescents: IV, IM:
CrCl |
Recommended Dosing Schedule | ||
---|---|---|---|
Note: Dosing regimens reflect the similarity in cefepime pharmacokinetics between adult and pediatric patients and are generally proportional to the changes made in adult patients. Based on minimum inhibitory concentrations (MIC) of bacteria, higher doses may be indicated (Shoji 2016). a Choose usual recommended dose based on indication and disease severity (see "Dosing: Pediatric"), then choose the adjusted dose from that column corresponding to the patient's CrCl. | |||
>60 mL/minute/1.73 m2 (Usual recommended dose)a |
50 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose |
50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose |
50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose |
30 to 60 mL/minute/1.73 m2 |
50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose |
50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose |
50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose |
11 to 29 mL/minute/1.73 m2 |
25 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose |
25 to 50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose |
50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose |
<11 mL/minute/1.73 m2 |
25 mg/kg/dose every 24 hours; maximum dose: 250 mg/dose |
25 to 50 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose |
25 to 50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose |
Hemodialysis, intermittent: Dialyzable (based on adult studies: 70% to 85% reduction in serum concentration from a 3.5- to 4-hour hemodialysis treatment with high flux filters [Descombes 2016; Schmaldienst 2000]).
Note: Appropriate dosing requires consideration of drug penetration to site of infection, MIC of bacteria, severity of illness, residual kidney function, interval between dialysis sessions, receipt of any initial loading doses, etc. Monitor closely for response and adverse reactions due to drug accumulation (eg, neurotoxicity) (Guzman-Limon 2017).
Infants, Children, and Adolescents: IV or via dialysis circuit return line:
Intermittent (posthemodialysis) dosing: 50 mg/kg/dose following dialysis; maximum dose: 2,000 mg/dose. Note: Regimen based on 3 to 4 hour dialysis sessions at least 3 times per week. For pediatric patients receiving <3 hours of hemodialysis, consider further dose reduction (Schmaldienst 2000; expert opinion).
Daily dosing (when scheduled dose falls on a dialysis day, administer after dialysis): Initial (day 1): 50 mg/kg (maximum dose: 1,000 mg/dose) followed by 12.5 to 25 mg/kg/dose once daily. Note: Maintenance and maximum doses are determined based on the usual recommended dose for patient-specific clinical scenario; recommended doses are as follows: If usual recommended dose is 50 mg/kg/dose every 8 hours, use 25 mg/kg/dose (maximum dose: 1,000 mg/dose) once daily; if usual recommended dose is 50 mg/kg/dose every 12 hours, use 12.5 mg/kg/dose (maximum dose: 500 mg/dose) once daily (Guzman-Limon 2017; Lodise 2006; manufacturer's labeling; expert opinion).
Peritoneal dialysis (manual or automated):
Note: Appropriate dosing requires consideration of drug penetration to site of infection, MIC of bacteria, severity of illness, residual kidney function, receipt of any initial loading doses, etc. Monitor closely for response and adverse reactions due to drug accumulation (eg, neurotoxicity) (Guzman-Limon 2017).
Infants, Children, and Adolescents: IV, IM: 25 to 50 mg/kg/dose every 48 hours. Usual maximum dose: 1,000 mg/dose; in severe infections or for bacteria with elevated MICs, 2,000 mg/dose maximum may be considered. Alternatively, 25 to 50 mg/kg/dose every 24 hours may be considered for severe infections (eg, septic shock) (Barbhaiya 1992; Lodise 2006; manufacturer's labeling; expert opinion).
CRRT:
Infants, Children, Adolescents:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of ~2,000 mL/hour/1.73 m2 unless otherwise noted. Appropriate dosing requires consideration of drug penetration to site of infection, MIC of bacteria, severity of illness, receipt of any initial loading doses, etc. Monitor closely for response and adverse reactions due to drug accumulation (eg, neurotoxicity) (Guzman-Limon 2017). Due to minimal data in pediatric patients receiving CRRT, consider monitoring serum concentrations (eg, trough concentration) if available.
CVVH/CVVHD/CVVHDF: IV: 50 mg/kg/dose (maximum dose: 2,000 mg/dose) every 8 to 12 hours. Note: Adult data suggest that in severe infections or sepsis, the risks/benefits favor dosing on the higher side of the recommended frequency. For higher effluent rates (>2,000 mL/hour/1.73 m2), bacteria with higher MICs, or deep-seated infections in severely ill pediatric patients, consider extended infusions or more frequent administration (Lodise 2006; Shaw 2016; Stitt 2019; expert opinion).
No dosage adjustments necessary.
(For additional information see "Cefepime: Drug information")
Usual dosage range:
Traditional intermittent infusion method (over 30 minutes): IV: 1 to 2 g every 8 to 12 hours. For coverage of serious Pseudomonas aeruginosa infections: 2 g every 8 hours (Crandon 2010; Koomanachai 2010; Su 2017). For infections caused by an organism with a minimum inhibitory concentration (MIC) <4 mg/L, 1 g every 6 hours achieves pharmacodynamic parameters comparable to 2 g every 8 hours; reserve for use in less serious infections (Lodise 2006; Roos 2006; Tam 2003).
Extended infusion method (off-label method): IV: 2 g every 8 hours infused over 3 or 4 hours (Arnold 2013; Bauer 2013; Koomanachai 2010; Nicasio 2009; Wrenn 2018); may give first dose over 30 minutes (Wrenn 2018).
Continuous infusion method (off-label method): IV: 4 to 6 g infused over 24 hours (Abdul-Aziz 2016; Georges 2005; Rhodes 2017a); may give first dose of 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations (eg, sepsis) is desired (Abdul-Aziz 2016; SCCM [Rhodes 2017b]).
Note: Extended and continuous infusion methods are based largely on pharmacokinetic and pharmacodynamic modeling data; clinical efficacy data are limited (Abdul-Aziz 2016; Bauer 2013; Burgess 2015; Georges 2005; MacVane 2014b; Moehring 2021a; Rhodes 2017a).
Bloodstream infection (gram-negative bacteremia) (off-label use):
Community-acquired infection, without sepsis or septic shock (immunocompetent host and no infections with P. aeruginosa in prior 3 to 6 months): IV: 2 g every 12 hours (Moehring 2019b).
Health care–associated infection (including catheter-related infection, infection in immunocompromised hosts, patients with sepsis or septic shock, or for coverage of P. aeruginosa): IV: 2 g every 8 hours (IDSA [Mermel 2009]; Moehring 2019b; Su 2017). Note: For empiric therapy of gram-negative bloodstream infection in patients with sepsis or septic shock and for empiric therapy of P. aeruginosa bloodstream infection in patients with neutropenia or severe burns, some experts recommend giving cefepime with a second gram-negative active agent (Kanj 2019a; Moehring 2019b; SCCM [Rhodes 2017b]). Some experts also prefer extended or continuous infusion for critical illness or when treating a susceptible organism with an elevated MIC (Moehring 2021a; SCCM [Rhodes 2017b]).
Duration of therapy: Usual duration is 7 to 14 days; individualize duration depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019b; Yahav 2018). If neutropenic, extend treatment until afebrile for ≥48 hours and recovery of neutrophils (ANC ≥500 cells/mm3 and increasing) (IDSA [Freifeld 2011]). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Kanj 2019b).
Cystic fibrosis, acute pulmonary exacerbation (off-label use): For empiric or targeted therapy of P. aeruginosa or other gram-negative bacilli:
IV: 2 g every 8 hours, usually given as part of an appropriate combination regimen (Flume 2009; Zobell 2013). Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Han 2006; Simon 2022; Thompson 2016).
Duration of therapy: Duration is usually 10 to 14 days depending on clinical response (Flume 2009; Goss 2021).
Diabetic foot infection, moderate to severe (off-label use): IV: 2 g every 8 to 12 hours in combination with other appropriate agents (Gentry 1991; IDSA [Lipsky 2012]; So 2016; Weintrob 2020).
Duration of therapy: Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2020).
Intra-abdominal infection, health care–associated or high-risk community-acquired infection:
Note: For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2021; SIS/IDSA [Solomkin 2010]):
Cholecystitis, acute: IV: 2 g every 8 to 12 hours; if P. aeruginosa is suspected, use 2 g every 8 hours. Continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2021).
Other intra-abdominal infections (eg, cholangitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 2 g every 8 to 12 hours in combination with metronidazole, and, when appropriate, other agents; if P. aeruginosa is suspected, use 2 g every 8 hours. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021). Note: For patients who are critically ill or are at high risk for infection with drug-resistant pathogens, some experts favor the extended or continuous infusion method (Barshak 2021; WSES [Sartelli 2017]).
Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (off-label use): As a component of empiric therapy in patients at risk for P. aeruginosa or another resistant gram-negative bacteria (eg, neurosurgical or immunocompromised patients):
IV: 2 g every 8 hours as part of an appropriate combination regimen; duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Bodilsen 2018; Sexton 2021; Sexton 2019b; Southwick 2020).
Meningitis, bacterial (off-label use): Note: As a component of empiric therapy for health care–associated infections or infections in immunocompromised patients, or as pathogen-specific therapy (eg, gram-negative bacteria, including P. aeruginosa):
IV: 2 g every 8 hours; for empiric therapy, use in combination with other appropriate agents (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Treatment duration for gram-negative bacilli is a minimum of 10 to 14 days, although some experts recommend ≥21 days (Hasbun 2019; IDSA [Tunkel 2017]).
Neutropenic enterocolitis (typhlitis) (off-label use): IV: 2 g every 8 hours in combination with metronidazole (IDSA [Freifeld 2011]; Wong Kee Song 2020). In patients who have clinical resolution following neutropenia and who did not have signs of severe disease at the time of diagnosis, the duration of antibiotics is 14 days following recovery from neutropenia; many patients can be switched to an appropriate oral antibiotic regimen once neutropenia has resolved (Wong Kee Song 2020).
Neutropenic fever, high-risk cancer patients (empiric therapy): Note: High-risk patients are those expected to have an ANC ≤100 cells/mm3 for >7 days or an ANC ≤100 cells/mm3 for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (IDSA [Freifeld 2011]; some experts use an ANC cutoff of <500 cells/mm3 to define high-risk patients (Wingard 2020).
IV: 2 g every 8 hours until afebrile for ≥48 hours and resolution of neutropenia (ANC ≥500 cells/mm3 and increasing) or standard duration for the specific infection identified, if longer than the duration of neutropenia. Additional agent(s) may be needed depending on clinical status (IDSA [Freifeld 2011]). Some experts prefer extended or continuous infusions for critical illness (Moehring 2021a; SCCM [Rhodes 2017b]; Wingard 2020).
Osteomyelitis and/or discitis (off-label use): IV: 2 g every 8 to 12 hours for ≥6 weeks (IDSA [Berbari 2015]; Osmon 2019). For empiric therapy, use in combination with other appropriate agents (IDSA [Berbari 2015]).
Peritonitis, treatment (peritoneal dialysis patients) (off-label use): As a component of empiric therapy or as pathogen-directed therapy for gram-negative bacteria (eg, P. aeruginosa):
Note: Intraperitoneal is preferred to IV administration unless the patient shows signs of systemic infection, then IV is preferred (ISPD [Li 2016]).
Automated peritoneal dialysis (APD): Intraperitoneal: 1 g every 24 hours given in the longest dwell is preferred (ISPD [Li 2016]).
CAPD:
Intermittent: Intraperitoneal: 1 g added to one exchange of dialysis solution every 24 hours (to be given in the longest daily dwell) (ISPD [Li 2016]).
Continuous (with every exchange): Intraperitoneal: Loading dose: 250 to 500 mg/L of dialysate with first exchange of dialysate. Maintenance dose: 100 to 125 mg/L of dialysate with each subsequent exchange of dialysate (ISPD [Li 2016]).
Note: Consider 25% dose increase in patients on APD or CAPD with significant residual kidney function (urine output >100 mL/day) (Mancini 2018; Szeto 2018).
Pneumonia:
Community-acquired pneumonia:For empiric therapy of inpatients at risk of infection with a resistant gram-negative pathogen(s), including P. aeruginosa:
IV: 2 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; a longer course may be required for patients with an immunocompromising condition, severe or complicated infection, or for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (IDSA/ATS [Metlay 2019]; Ramirez 2020).
Hospital-acquired pneumonia or ventilator-associated pneumonia:For empiric therapy (often as part of an appropriate combination regimen) or pathogen-specific therapy of resistant gram-negative pathogen(s), including P. aeruginosa:
IV: 2 g every 8 hours. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]). Note: Some experts prefer extended or continuous infusions for critical illness or when treating a susceptible organism with an elevated MIC (Klompas 2022; Moehring 2021a; SCCM [Rhodes 2017b]).
Prosthetic joint infection, pathogen-specific therapy for gram-negative bacilli (off-label use): IV: 2 g every 8 to 12 hours; duration varies but is generally 4 to 6 weeks for patients who undergo resection arthroplasty (Berbari 2019; IDSA [Osmon 2013]).
Sepsis and septic shock (broad-spectrum empiric coverage, including P. aeruginosa) (off-label use): IV: 2 g every 8 hours (Alves 2014); use in combination with other appropriate agents. Initiate therapy as soon as possible and preferably within 1 hour of recognition of sepsis or septic shock. Usual duration of treatment is dependent on underlying source, but is typically 7 to 10 days or longer, depending on clinical response (SCCM [Rhodes 2017b]). Consider discontinuation if a noninfectious etiology is identified (SCCM [Rhodes 2017b]; Schmidt 2020). Some experts prefer extended or continuous infusions (Moehring 2021a; SCCM [Rhodes 2017b]).
Septic arthritis, without prosthetic material (off-label use): As a component of empiric therapy or pathogen-specific therapy for gram-negative pathogens (including P. aeruginosa): IV: 2 g every 8 to 12 hours; for empiric therapy, use in combination with other appropriate agents. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy (Goldenberg 2019).
Skin and soft tissue infections, moderate to severe: As empiric or pathogen-directed therapy in patients with or at risk for gram-negative bacteria (eg, P. aeruginosa):
IV: 2 g every 8 to 12 hours. Usual duration is 10 to 14 days based on response to therapy (Hoepelman 1993; Kanj 2021).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): IV: 1 to 2 g every 12 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; IDSA/ESCMID [Gupta 2011]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV:
CrCl (mL/minute)b |
Dose | |||
---|---|---|---|---|
a Kuti 2010; Lodise 2006; Tam 2003; manufacturer's labeling. | ||||
b CrCl can be calculated using the Cockcroft-Gault equation (Jonckheere 2016). | ||||
c Choose usual recommended dose based on indication and disease severity (see adult dosing), then choose the adjusted dose from that column corresponding to the patient’s CrCl. | ||||
d Dose is decreased from 1 g every 6 hours to 1 g every 8 hours at CrCl <50 (Lodise 2006). | ||||
e 1 g every 12 hours increases the likelihood of pharmacodynamic target attainment and is preferred for serious infections or organisms with less susceptible MICs (Kuti 2010; Tam 2003). Administer a 2 g loading dose when rapid attainment of therapeutic concentrations is desired (expert opinion). | ||||
>60 (usual recommended dose)c |
1 g every 12 hours |
2 g every 12 hours |
1 g every 6 hours |
2 g every 8 hours |
30 to 60 |
1 g every 24 hours |
1 g every 12 hours |
1 g every 8 hoursd |
2 g every 12 hours |
11 to 29 |
500 mg every 24 hours |
1 g every 24 hours |
1 g every 12 hours |
1 g every 12 hourse or 2 g every 24 hours |
<11 |
250 mg every 24 hours |
500 mg every 24 hours |
1 g every 24 hours |
1 g every 24 hours |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without significant organ dysfunction. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematological malignancies. A measured urinary clearance is necessary to identify these patients.
Note: Limited data available; dosing based on Monte Carlo simulation and expert opinion.
IV: Initial: 2 g every 6 hours infused over 3 hours when used empirically or in patients with known minimum inhibitory concentrations (MICs) >4 mg/L (Zasowski 2015). Closely monitor patient for response and adverse reactions (eg, neurotoxicity) due to drug accumulation. Consider obtaining drug concentrations when available.
Hemodialysis, intermittent (thrice weekly): Note: Achievement of cefepime pharmacodynamic targets is dependent on organism MIC, the absence or presence of residual kidney function, and interval between dialysis sessions (ie, 2- or 3-day interdialytic interval) (Descombes 2016; Perez 2012; Schmaldienst 2000). Factors such as severity of illness, location of infection, and patient weight should be considered when selecting between the higher and lower dosing regimens as well.
IV: Dialyzable (70% to 85% reduction in serum concentration from a 3.5- to 4-hour hemodialysis treatment with high flux filters [Descombes 2016; Schmaldienst 2000]).
Daily dosing (administer after hemodialysis on dialysis days): IV: Initial: 1 g (single dose) on day 1. Maintenance: 500 mg to 1 g every 24 hours (Heintz 2009; manufacturer’s labeling). Note: If the usual recommended dose for normal renal function is 2 g every 8 hours or 1 g every 6 hours, utilize 1 g every 24 hours; use 500 mg every 24 hours for all other doses (Lodise 2006; manufacturer’s labeling).
Thrice-Weekly (postdialysis) Dosinga | ||
---|---|---|
Residual kidney function and organism susceptibility |
Cefepime dose for a 2-day interdialytic interval (ie, next dialysis expected in 48 hours) |
Cefepime dose for a 3-day interdialytic interval (ie, next dialysis expected in 72 hours) |
a Expert opinion derived from Descombes 2016; Perez 2012; Schmaldienst 2000. | ||
Patient is anuric AND the organism MIC <4 mg/L |
1.5 g after hemodialysis |
2 g after hemodialysis |
Any of the following: Empiric therapy OR Patient has residual kidney function OR Organism MIC ≥4 mg/L |
2 g after hemodialysis |
2 g after hemodialysis |
Peritoneal dialysis:
IV: 1 g every 24 hours (Lodise 2006; expert opinion).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or approximately 1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: IV: 2 g every 8 to 12 hours (Beumier 2014; Carlier 2015; Chaijamorn 2018; Philpott 2019; Shaw 2016).
Note: For severe infections or sepsis, the risks/benefits favor dosing on the higher side of the recommended frequency (Shaw 2016). For CRRT with other effluent rates: If effluent rate is <20 mL/kg/hour, 2 g every 12 hours is preferred (Allaouchiche 1997; Malone 2001). If effluent rate is ≥35 mL/kg/hour, 2 g every 8 hours is preferred (Chaijamorn 2018, Droege 2013).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Note: Regimens developed through Monte Carlo simulation only and based on daily treatments with 4 to 5 L/hour of dialysate/ultrafiltrate flow rate for each 8- to 10-hour session (Jang 2018).
Option 1: IV: 2 g loading dose, followed by 1 g every 6 hours regardless of when prolonged intermittent renal replacement therapy (PIRRT) treatments occur relative to cefepime infusions (Jang 2018).
Option 2 (if every 6 hours not desired [eg, patient self-administering]): IV: 2 g at beginning of PIRRT session, then 3 g after PIRRT session ends. Repeat regimen with every PIRRT session (Jang 2018).
Non-PIRRT days: IV: Select dose based on assessment of nondialysis kidney function (eg, CrCl <11, then 1 g every 24 hours).
No dosage adjustment necessary.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as hydrochloride:
Generic: 2 g/100 mL (100 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Generic: 1 g/50 mL (50 mL)
Solution Reconstituted, Injection, as hydrochloride:
Generic: 1 g (1 ea [DSC])
Solution Reconstituted, Injection, as hydrochloride [preservative free]:
Maxipime: 1 g (1 ea [DSC]); 2 g (1 ea [DSC])
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:
Maxipime: 1 g (1 ea [DSC]); 2 g (1 ea [DSC])
Generic: 100 g (1 ea); 1-5 GM-%(50ML) (1 ea); 2-5 GM-%(50ML) (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as hydrochloride:
Generic: 1 g (1 ea); 2 g (1 ea)
Parenteral:
Intermittent IV infusion: Administer as an intermittent IV infusion over 30 minutes; in adult clinical trials, cefepime has been administered by direct IV injection over 3 to 5 minutes at final concentrations of 40 mg/mL (Garrelts 1999) and 100 mg/mL (Jaruratanasirikul 2002; Lipman 1999) for severe infections.
Extended IV infusion: Administer over 3 to 4 hours (Beauchamp 2018; Nichols 2015; Shoji 2016).
IM: Administer by deep IM injection into large muscle mass.
IM: Inject deep IM into large muscle mass.
IV: Administer as an intermittent infusion over 30 minutes.
Off-label:
Direct IV: Inject direct IV over 5 minutes (Garrelts 1999)
Extended infusion: In certain patients where extended infusions may be appropriate, doses are usually infused over 3 to 4 hours (Bauer 2013; Nicasio 2010).
Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. After reconstitution, stable in NS and D5W for 24 hours at 20°C to 25°C (68°F to 77°F) and 7 days at 2°C to 8°C (36°F to 46°F). Refer to the manufacturer's product labeling for other acceptable reconstitution solutions.
Dual chamber containers: Store unactivated containers at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 85°F). Do not freeze. Following reconstitution, use within 12 hours if stored at room temperature or within 5 days if stored under refrigeration.
Premixed solution: Store frozen at -20°C (-4°F). Thawed solution is stable for 24 hours at room temperature or 7 days under refrigeration; do not refreeze.
Treatment of pneumonia, uncomplicated skin and soft tissue infections, and complicated and uncomplicated urinary tract infections (including pyelonephritis) caused by susceptible organisms; empiric therapy for febrile neutropenic patients (FDA approved in ages ≥2 months and adults); treatment of complicated intra-abdominal infections in combination with metronidazole (FDA approved in adults); has also been used for meningitis, endocarditis, and the treatment of peritonitis in patients with peritoneal catheters.
Cefepime may be confused with cefixime, cefTAZidime
Clostridioides difficile infection (CDI) has been reported with use (Ref).
Onset: Variable; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref); a retrospective, case-controlled study suggests cefepime resulted in CDI after a median time of 8 days, as compared with cefazolin with a median time of 6 days (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor) (Ref)
• Type of antibiotic (third-/fourth-generation cephalosporins among the highest risk) (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older patients (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors, H2 blockers) (Ref)
• Chemotherapy (Ref)
Immediate (including anaphylaxis, angioedema, and urticaria) (Ref) and delayed hypersensitivity reactions have been reported. Delayed hypersensitivity reactions range from maculopapular skin rash to rare severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref).
Mechanism: Non-dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) are IgE-mediated (Ref). Delayed hypersensitivity reactions, including maculopapular rash and SCARs, are mediated by T-cells (Ref).
Onset:
• Immediate: Rapid; IgE-mediated reactions (anaphylaxis, angioedema, urticaria) generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref).
• Delayed: Variable; typically, maculopapular reactions occur 7 to 10 days after initiation. Other delayed hypersensitivity reactions, including SCARs, generally manifest after 7 to 14 days of therapy (although the onset of these reactions may be delayed up to 3 months) (Ref).
Risk factors:
• Cross-reactivity between penicillins and cephalosporins, and among cephalosporins, is mainly related to side chain similarity (Ref).
• Potential cross-reactions may occur between cefepime, ceftriaxone, cefuroxime, ceftazidime, and cefotaxime (Ref).
Severe neurotoxicity has been reported with cefepime use, including encephalopathy, aphasia, myoclonus, opsoclonus, seizure, and nonconvulsive status epilepticus (Ref).
Mechanism: Not fully understood; may be associated with concentration-dependent inhibition of GABAA-mediated neurotransmission, resulting in a decreased seizure threshold (Ref); other mechanisms have been suggested, including tumor necrosis factor-alpha or enhanced glutaminergic activity (Ref).
Onset: Rapid; reported to occur in a median time of 2 to 4 days from initiation (Ref).
Risk factors:
• Kidney impairment (Ref)
• Excessive dosing (Ref)
• Elevated serum concentrations (Ref)
• Preexisting brain injury (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Hematologic & oncologic: Positive direct Coombs test (without hemolysis: 16%)
1% to 10%:
Cardiovascular: Localized phlebitis (1%)
Dermatologic: Pruritus (≤1%), skin rash (1% to 4%)
Endocrine & metabolic: Hypophosphatemia (3%)
Gastrointestinal: Diarrhea (≤3%), nausea (≤2%), vomiting (≤1%)
Hematologic & oncologic: Abnormal partial thromboplastin time (2%), change in prothrombin time (1%), eosinophilia (2%)
Hepatic: Increased serum alanine aminotransferase (3%), increased serum aspartate aminotransferase (2%)
Hypersensitivity: Hypersensitivity reaction (in patients with a history of penicillin allergy: ≤10%)
Nervous system: Headache (≤1%)
Miscellaneous: Fever (≤1%)
<1%:
Dermatologic: Erythema of skin, urticaria
Endocrine & metabolic: Hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia
Gastrointestinal: Clostridioides difficile colitis, oral candidiasis
Genitourinary: Vaginitis
Hematologic & oncologic: Anemia
Hepatic: Increased alkaline phosphatase, increased serum bilirubin
Local: Local inflammation, local pain
Renal: Increased blood urea nitrogen, increased serum creatinine
Postmarketing:
Dermatologic: Acute generalized erythematous pustulosis (Botelho 2010), Stevens-Johnson syndrome (Marco-del Rio 2017)
Gastrointestinal: Clostridioides difficile-associated diarrhea (rare: <1%) (Thabit 2019)
Hematologic & oncologic: Agranulocytosis (rare: <1%) (Medrano-Casique 2015), leukopenia (rare: <1%) (Jauregui 1993), neutropenia (rare: <1%) (Malincarne 2010), thrombocytopenia (rare: <1%) (Lim 2011)
Hypersensitivity: Anaphylaxis (rare: <1%) (Moreno 2007), angioedema (rare: <1%) (Orhan 2004)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Qadri 2017)
Nervous system: Aphasia (rare: <1%) (Isitan 2017), coma (rare: <1%) (Sonck 2008), confusion (rare: <1%) (Triplett 2019), encephalopathy (rare: <1%) (Triplett 2019), hallucination (rare: <1%) (Lamoth 2010), myoclonus (rare: <1%) (Lizarraga 2019), neurotoxicity (incidence variable in literature from less frequent: ≥1 to <4% to common: ≥10%) (Boschung-Pasquier 2020; Durand-Maugard 2012; Payne 2017), seizure (rare: <1%) (Triplett 2019), status epilepticus (nonconvulsive) (rare: <1%) (Garin 2019), stupor (rare: <1%) (Kim 2013)
Renal: Acute interstitial nephritis (rare: <1%) (Qadri 2017)
Hypersensitivity to cefepime, other cephalosporins, penicillins, other beta-lactam antibiotics, or any component of the formulation
Concerns related to adverse effects:
• Elevated INR: May be associated with increased INR, especially in nutritionally deficient patients, prolonged treatment, hepatic or renal disease.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Seizure disorders: Use with caution in patients with a history of seizure disorder.
Special populations:
• Elderly: Serious adverse reactions have occurred in elderly patients with renal insufficiency given unadjusted doses of cefepime, including life-threatening or fatal occurrences of encephalopathy, myoclonus, and seizures.
The manufacturer does not recommend the use of cefepime in pediatric patients for the treatment of serious infections due to Haemophilus influenzae type b, for suspected meningitis, or for meningeal seeding from a distant infection site. However, cefepime has been shown to achieve adequate concentrations in the cerebrospinal fluid and has been evaluated in the treatment of CNS infections (including those caused by H. influenzae type b) (Ellis 2007; Sáez-Llorens 1995; Sáez-Llorens 2001; Sullins 2013). It is currently recommended for empiric treatment of health care-associated ventriculitis or meningitis, in combination with vancomycin, or for the directed treatment of susceptible bacterial meningitis (including that caused by Pseudomonas aeruginosa) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
None known.
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Cefepime crosses the placenta (Ozyuncu 2010).
An increased risk of major birth defects or other adverse fetal or maternal outcomes has generally not been observed following use of cephalosporin antibiotics during pregnancy.
When an antibiotic is needed for the treatment of maternal infection, cefepime can be considered. However, other, more well-studied cephalosporins are preferred for use in pregnancy (Betschart 2020; ERS/TSANZ [Middleton 2020]; Panchaud 2016).
With prolonged therapy, monitor renal and hepatic function periodically; number and type of stools/day for diarrhea; serum phosphorus (Knoderer 2018); CBC with differential. Observe for signs and symptoms of anaphylaxis during first dose.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysis and murein hydrolases) while cell wall assembly is arrested.
Absorption: IM: Rapid and complete.
Distribution:
Vd:
Neonates (Capparelli 2005):
PMA <30 weeks: 0.51 L/kg.
PMA >30 weeks: 0.39 L/kg.
Infants and children 2 months to 11 years of age: 0.3 L/kg.
Adults: 18 L, 0.26 L/kg; penetrates into inflammatory fluid at concentrations ~80% of serum concentrations and into bronchial mucosa at concentrations ~60% of plasma concentrations; crosses the blood-brain barrier.
Bone:
CSF:serum ratio: 4% to 34% (AUC); 5% to 58% (Cmin) (Rhoney 2003).
Lung:
Epithelial lining fluid:serum ratio: ~100% (Boselli 2003; Breilh 2001).
Protein binding, plasma: ~20%.
Metabolism: Minimally hepatic.
Half-life elimination:
Neonates: 4 to 5 hours (Lima-Rogel 2008).
Children 2 months to 6 years of age: 1.77 to 1.96 hours.
Adults: 2 hours.
Hemodialysis: 13.5 hours.
Continuous peritoneal dialysis: 19 hours.
Time to peak: IM: 1 to 2 hours; IV: 0.5 hours.
Excretion: Urine (85% as unchanged drug).
Renal function impairment: Total body clearance is decreased proportionally with creatinine clearance.
Anti-infective considerations:
Parameters associated with efficacy: Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).
Organism specific:
Staphylococcus spp.: Goal: 40% fT > MIC (bactericidal in vitro) (Craig 1995).
Streptococcus spp.: Goal: 40% fT > MIC (bacteriostatic in vitro), 60% to 70% fT > MIC (bactericidal in vitro) (Craig 1995).
Gram negative bacteria (including P. aeruginosa): Goal: 40% fT > MIC (bacteriostatic in vitro); 60% to 70% fT > MIC (bactericidal in vitro); 53% to 60% fT > MIC (microbiological response) (Craig 1995; Craig 1998; Crandon 2010; MacVane 2014a; Roos 2006).
Population specific:
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Roberts 2014); some experts favor ≥100% fT >4 times the MIC (Guilhaumou 2019).
Postantibiotic effect: Generally little to no postantibiotic effect for Streptococcus spp. and gram negative bacilli (including P. aeruginosa); prolonged postantibiotic effect for Staphylococcus spp. (Craig 1991; Craig 1995; Craig 1998; Ozbek 2009).
Parameters associated with toxicity: Neurotoxicity (eg, confusion, altered consciousness, seizures) is associated with elevated Cmin (trough) concentrations; risk increases with increasing Cmin (Boschung-Pasquier 2020; Huwyler 2017). In one study assessing cefepime therapeutic drug monitoring in 319 adult patients, Cmin <7.7 mg/L resulted in no neurotoxicity, Cmin ≥12 mg/L was associated with a 25% probability of neurotoxicity, Cmin ≥16 mg/L was associated with a 50% probability of neurotoxicity, and Cmin ≥38.1 mg/L was always associated with neurotoxicity (Boschung-Pasquier 2020). In a smaller study, Cmin >35 mg/L was associated with neurotoxicity, but patients without neurotoxicity exhibited Cmin up to 89 mg/L (Huwyler 2017).
Expected drug concentrations in patients with normal renal function:
Infants and children 2 months to 16 years of age; hospitalized: Cmax (peak): IV:
50 mg/kg/dose every 8 hours, steady state: 184.2 ± 38 mg/L (Reed 1997).
Adults: Cmax (peak): IV:
30-minute infusion, healthy volunteers:
1 g, single dose: 81.7 ± 5.1 mg/L.
1 g every 8 hours, steady state (day 6): 70.5 ± 8.5 mg/L (Barbhaiya 1992).
2 g, single dose: 163.9 ± 25.3 mg/L.
2 g every 8 hours, steady state (day 6): 129 ± 27.1 mg/L (Barbhaiya 1992).
4-hour infusion, hospitalized patients requiring antibiotics:
1 g every 8 hours, steady state: 32.5 ± 13.5 mg/L (Cheatham 2011).
Solution (Cefepime HCl Intravenous)
1 gm/50 mL (per mL): $0.64
2 g/100 mL (per mL): $0.51
Solution (reconstituted) (Cefepime HCl Injection)
1 g (per each): $3.77 - $20.33
2 g (per each): $6.84 - $40.36
Solution (reconstituted) (Cefepime HCl Intravenous)
100 g (per each): $540.00
Solution (reconstituted) (Cefepime-Dextrose Intravenous)
1GM 5%(50ML) (per each): $20.43
2GM 5%(50ML) (per each): $29.15
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