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Cefepime

Medically reviewed by Drugs.com. Last updated on May 26, 2020.

Pronunciation

(SEF e pim)

Index Terms

  • Cefepime HCl
  • Cefepime HCl/D5W
  • Cefepime Hydrochloride

Dosage Forms

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)

Brand Names: U.S.

  • Maxipime [DSC]

Pharmacologic Category

  • Antibiotic, Cephalosporin (Fourth Generation)

Pharmacology

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).

Metabolism

Minimally hepatic

Excretion

Urine (85% as unchanged drug)

Time to Peak

IM: 1 to 2 hours; IV: 0.5 hours

Half-Life Elimination

Neonates: 4 to 5 hours (Lima-Rogel 2008)

Children 2 months to 6 years: 1.77 to 1.96 hours

Adults: 2 hours

Hemodialysis: 13.5 hours

Continuous peritoneal dialysis: 19 hours

Protein Binding

Plasma: ~20%

Special Populations: Renal Function Impairment

Total body clearance is decreased proportionally with creatinine clearance.

Special Populations Note

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).

Use: Labeled Indications

Intra-abdominal infection: Treatment, in combination with metronidazole, of complicated intra-abdominal infections caused by Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis.

Neutropenic fever: Empiric treatment of febrile neutropenic patients.

Pneumonia (moderate to severe): Treatment of moderate to severe pneumonia caused by Streptococcus pneumoniae, including cases associated with concurrent bacteremia, P. aeruginosa, K. pneumoniae, or Enterobacter species.

Skin and soft tissue infection: Treatment of moderate to severe skin and soft tissue infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes.

Urinary tract infection, including pyelonephritis: Treatment of urinary tract infections, including pyelonephritis, caused by E. coli, K. pneumoniae, or Proteus mirabilis, including cases associated with concurrent bacteremia with these microorganisms.

Off Label Uses

Bloodstream infection (gram-negative bacteremia)

Data from a prospective, randomized, open-comparison study support the use of cefepime in the treatment of gram-negative bacteremia [Schrank 1995].

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, cefepime is effective and recommended for the treatment of intravascular catheter-related infection caused by Pseudomonas aeruginosa.

Cystic fibrosis, exacerbation

Based on the Cystic Fibrosis Foundation's cystic fibrosis pulmonary guidelines, cefepime, as part of an appropriate combination regimen (which should include an additional antipseudomonal agent), is effective and recommended for the treatment of P. aeruginosa infection during an acute exacerbation of cystic fibrosis pulmonary disease.

Diabetic foot infection, moderate to severe

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, cefepime, in combination with other appropriate agents, is an effective and recommended treatment option for diabetic foot infections.

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess

Clinical experience suggests the utility of cefepime in the management of brain abscess, intracranial epidural abscess, and spinal epidural abscess [Bond 2016], [Sexton 2019a], [Sexton 2019b], [Southwick 2020].

Meningitis, bacterial

Based on the IDSA guidelines for the management of bacterial meningitis and health careassociated ventriculitis and meningitis, cefepime is effective and recommended for the treatment of bacterial meningitis caused by P. aeruginosa; as an alternative agent for the treatment of meningitis caused by extended-spectrum beta-lactamase-producing gram-negative bacilli, H. influenzae, or S. pneumoniae (with a penicillin MIC ≥0.12 mcg/mL and cefotaxime or ceftriaxone MIC <1 mcg/mL); and as empiric therapy (in combination with vancomycin) for health careassociated ventriculitis or meningitis.

Neutropenic enterocolitis (typhlitis)

Based on the IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer, cefepime, in combination with metronidazole, is effective and recommended for the management of neutropenic enterocolitis (typhlitis).

Osteomyelitis and/or discitis

Data from a limited number of patients suggest that cefepime may be beneficial for the treatment of osteomyelitis [Jauregui 1993].

Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, cefepime is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to P. aeruginosa or Enterobacteriaceae.

Prosthetic joint infection

Based on the IDSA guidelines for the diagnosis and management of prosthetic joint infection, cefepime is an effective and recommended agent for the treatment of prosthetic joint infection due to P. aeruginosa or Enterobacter spp.

Sepsis and septic shock

Based on the Society of Critical Care Medicine international guidelines for management of sepsis and septic shock, cefepime, in combination with other appropriate agents, is effective and recommended for broad-spectrum antibacterial coverage (including P. aeruginosa) in the management of sepsis and septic shock.

Septic arthritis

Clinical experience suggests the utility of cefepime for the treatment of septic arthritis [Goldenberg 2019].

Contraindications

Hypersensitivity to cefepime, other cephalosporins, penicillins, other beta-lactam antibiotics, or any component of the formulation

Dosing: Adult

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 2019a; 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 the extended-infusion method in critical illness or if treating a susceptible organism with an elevated MIC (Moehring 2019a; 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 2019; Thompson 2016).

Duration of therapy: Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).

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 2020; 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 2019).

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 oral step-down therapy) is 4 to 7 days following adequate source control (Barshak 2020; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration of therapy may be necessary (Barshak 2020; Pemberton 2019). 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 2020; 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 2019a; Sexton 2019b; Southwick 2020).

Meningitis, bacterial (off-label use): Note: As a component of empiric therapy for health careassociated 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 2019). 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 2019).

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 2019).

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 the extended infusion method, particularly in those who are critically ill (Moehring 2019a; SCCM [Rhodes 2017b]; Wingard 2019).

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 P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (IDSA/ATS [Metlay 2019]).

Hospital-acquired pneumonia or ventilator-associated pneumonia: For empiric therapy or pathogen-specific therapy of resistant gram-negative pathogen(s), including P. aeruginosa:

IV: 2 g every 8 hours, as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but longer courses may be warranted for severe or complicated infection or for P. aeruginosa infection (Kanj 2019b; Klompas 2020). Note: Some experts prefer the extended-infusion method, particularly in those who are critically ill or to optimize exposure if treating a susceptible organism with an elevated MIC (Klompas 2020; Moehring 2019a; 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 the extended-infusion method (Moehring 2019a; 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 2019c).

Urinary tract infection, complicated (including pyelonephritis): IV: 1 to 2 g every 12 hours; some experts prefer 2 g every 8 hours if P. aeruginosa is suspected. Switch to an appropriate oral regimen once patient has improvement in symptoms, if culture and susceptibility results allow. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019; IDSA [Gupta 2011]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Dosing: Obesity

The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Principles of body weight dosing:

Note: There are limited data on the effect of obesity on dosing requirements for cefepime. Currently, data are available from noncritically and critically ill, hospitalized patients. Lower trough concentrations and increased Vd estimates are reported in patients who are obese compared with patients who are not obese (Hites 2013; Hites 2014).

BMI ≥30 kg/m2: Note: Use of traditional (intermittent) dosing in patients who are obese is generally appropriate.

Traditional intermittent infusion method: IV: 2 g every 8 hours infused over 30 minutes (Meng 2017; Santibañez 2019; expert opinion).

Extended-infusion method: Note: Preferred for patients with BMI >40 kg/m2, for life-threatening infections caused by resistant pathogens (eg, minimum inhibitory concentrations ~8 mg/L), with infection-site penetration limitations, or for critically ill patients with augmented renal function (Meng 2017; Rich 2012; expert opinion).

IV: 2 g every 8 hours infused over 3 to 4 hours. Note: May give a loading dose of 2 g over 30 minutes when rapid attainment of therapeutic drug concentrations is necessary (eg, sepsis) (SCCM [Rhodes 2017b]; Wrenn 2018).

Reconstitution

IV: Reconstitute 500 mg vial with 5 mL and 1 or 2 g vial with 10 mL of a compatible diluent (resulting concentration of 100 mg/mL for 500 mg and 1 g vial and 160 mg/mL for 2 g vial) and further dilute in a compatible IV infusion fluid.

IM: Reconstitute 500 mg or 1 g vial with 1.3 mL or 2.4 mL, respectively, of SWFI, NS, D5W, lidocaine 0.5% or 1%, or bacteriostatic water for injection; resulting concentration is 280 mg/mL.

Administration

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).

Storage

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.

Drug Interactions

Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Cephalosporins. 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. 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. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction, false-positive urinary proteins and steroids

Adverse Reactions

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)

Warnings/Precautions

Concerns related to adverse effects:

• Elevated INR: May be associated with increased INR, especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.

• Hypersensitivity: May occur; use caution in patients with a history of penicillin sensitivity; cross-hypersensitivity may occur. If a hypersensitivity reaction occurs, discontinue therapy and institute supportive measures.

• Neurotoxicity: Severe neurological reactions (some fatal) have been reported, including encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus. Risk may be increased in the presence of renal impairment; ensure dose adjusted for renal function and discontinue therapy if patient develops neurotoxicity; effects are often reversible upon discontinuation of cefepime.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (CrCl ≤60 mL/minute); dosage adjustments recommended. May increase risk of encephalopathy, myoclonus, and seizures.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

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.

Monitoring Parameters

Monitor renal function. Observe for signs and symptoms of anaphylaxis during first dose.

Pregnancy Considerations

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).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Severe fatigue

• Bruising

• Bleeding

• Severe loss of strength and energy

• Chills

• Sore throat

• Unable to pass urine

• Change in amount of urine passed

• Dark urine

• Yellow skin

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Confusion

• Seizures

• Trouble speaking

• Sensing things that seem real but are not

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.