Cefepime is a fourth-generation cephalosporin that inhibits the formation of bacterial cell walls through its anti-pseudomonal effect. It is indicated in the treatment of the following infections:

• Using metronidazole in addition, complex intra-abdominal infections caused by:

  • Escherichia coli
  • Viridans group streptococci
  • Pseudomonas aeruginosa
  • Klebsiella pneumoniae
  • Enterobacter species
  • Bacteroides fragilis

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• Empiric treatment of febrile Neutropenic patients:

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• Treatment of moderate to severe Pneumonia caused by:

  • Streptococcus pneumoniae
  • P. aeruginosa
  • K. pneumoniae
  • Enterobacter species

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• Treatment of moderate to severe Skin and soft tissue infections caused by:

  • Methicillin-susceptible isolates of Staphylococcus aureus
  • Streptococcus pyogenes

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• Treatment of Urinary tract infections including pyelonephritis caused by:

  • E. coli
  • K. pneumoniae
  • Proteus mirabilis

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• Off-Label Use of Cefepime in Adults include:

  • Bloodstream infection caused by gram-negative bacteremia.
  • Exacerbation of Cystic fibrosis
  • Moderate to severe Diabetic foot infection
  • Intracranial abscesses (brain abscess and epidural abscess)
  • Bacterial Meningitis
  • Neutropenic enterocolitis (typhlitis)
  • Osteomyelitis
  • Prosthetic joint infection
  • Sepsis and septic shock
  • Septic arthritis

Cefepime Dose in Adults

The Usual dosage range of Cefepime:

• Traditional infusion method:

  • 1 to 2 g intravenous twice or thrice daily over half an hour.

• For the coverage of serious Pseudomonas aeruginosa infections:

  • • 2 gms intravenous thrice daily.

• Off-label use as the extended-infusion method:

  • 2 g intravenous thrice daily infused over 3 or 4 hours. The first dose may be administered over 30 minutes.

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Off-label use of Cefepime in the treatment of Bloodstream infection caused by gram-negative bacteremia:

• Community-acquired infection, without sepsis or septic shock in the immunocompetent host and no infections with P. aeruginosa in the past 3 - 6 months:

  • 2 gms intravenous twice daily (ref: principles of antibiotics use)

• Healthcare-associated infection including catheter-related infections, infections in immunocompromised hosts, patients with sepsis or septic shock, or for the coverage of P. aeruginosa:

  • 2 gms intravenous thrice daily.

Note: Combination of a second agent that covers gram-negative infections may be used in patients with sepsis or septic shock and for empiric therapy of P. aeruginosa bloodstream infections in patients with neutropenia or severe burns.

• Duration of therapy:

  • The typical time frame is 7–14 days, however this should be customised based on the severity and scope of the condition as well as the clinical outcome of the treatment.
  • Patients with uncomplicated infection who respond to the therapy may be advised a 7-days treatment.
  • In neutropenic patients, treatment may be extended until the patient is afebrile for 48 hours or more and the ANC is 500 cells/mm³ or more.
  • In neutropenic patients with P. aeruginosa bacteremia, a minimum of 14 days treatment and until recovery of neutrophils is recommended.

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Off-label use of Cefepime in the treatment of Cystic fibrosis in acute severe  pulmonary exacerbation or failure of oral therapy:

• 2 gms intravenous thrice daily.
• A combination of an additional anti-pseudomonal agent may be added.

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Off-label use of Cefepime in treatment of moderate to severe Diabetic foot infection:

• 2 gms intravenously administered twice or three times a day, along with other necessary antibiotics
• For P. aeruginosa infection, use 2 gms intravenous thrice daily.

• Duration of therapy:
  • In the absence of osteomyelitis, cefepime may be administered for a total of 2 - 4 weeks.

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Use in treatment of intraabdominal healthcare-associated or high-risk community-acquired infection:

• 2 gms intravenous twice or thrice daily in combination with metronidazole or other appropriate agents.
• For infections caused by P. aeruginosa, use a higher dose i.e. 2 gms intravenous thrice daily.
• With adequate source control, a 4 - 7 days therapy may be adequate.

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Off-label use of Cefepime in the treatment of Intracranial abscesses like a brain or an epidural abscess:

• 2 gms intravenous thrice daily in combination with other appropriate agents.

Off-label use in the treatment of bacterial Meningitis:

Note: It should be used as empiric therapy for healthcare-associated infections or infections in the immunocompromised patients, or as pathogen-specific therapy in gram-negative bacteria, including P. aeruginosa:

• 2 gms intravenous thrice daily in combination with other appropriate agents.

Off-label use of Cefepime in the treatment of Neutropenic enterocolitis (typhlitis):

• 2 gms intravenous thrice daily in combination with metronidazole for 14 days following recovery from neutropenia in patients without signs of severe disease at the time of diagnosis.
• IV therapy may be switched to oral after the resolution of neutropenia.

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Use of Cefepime empiric therapy in the treatment of  for Neutropenic fever and high-risk cancer patients with ANC expected to be less than 100 cells/mm³ for more than 7 days in clinically unstable patients or those with significant comorbidity:

• 2 gms intravenous thrice daily until afebrile for 48 hours or more and ANC is 500 cells/mm³ or more and increasing.

Off-label use in the treatment of Osteomyelitis and/or discitis:

• 2 gms intravenous twice or thrice daily for 6 weeks or more.

Use in the treatment of Pneumonia:

• Community-acquired pneumonia as empiric therapy for patients at risk for P. aeruginosa infection:
  • Depending on the response to therapy, 2 gms intravenously three times per day in combination with other suitable drugs for a minimum of five days.

• Hospital-acquired pneumonia or ventilator-associated pneumonia:
  • 2 gms intravenously given three times a day, usually for 7 days but possibly longer depending on the patient's response.

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Off-label use of Cefepime in the treatment of Prosthetic joint infection as pathogen-specific therapy for gram-negative bacilli:

• 2 gms intravenous twice or thrice daily.

Off-label use in the treatment of Sepsis and septic shock.

• Depending on the person's clinical reaction, 2 gms intravenously three times per day in combination with other suitable medications for the typical duration of 7 to 10 days.
• Therapy should be initiated within one hour of recognition of clinical signs of sepsis or shock.

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Off-label use in the treatment of Septic arthritis without prosthetic material:

• In the absence of osteomyelitis, use 2 gms intravenously twice or three times a day in combination with other suitable medications for a total of 3–4 weeks.

Use in the treatment of moderate to severe Skin and soft tissue infections:

• 2 gms intravenous twice daily for 5 - 14 days, based on the individual's response.

Use in the treatment of acute complicated Urinary tract infection including pyelonephritis:

• 1-2 grams intravenously administered twice day for 10–14 days.
• Use a greater dose, i.e. 2 gm intravenously given three times per day, for infections brought on by P. aeruginosa.

Cefepime Dose in Children

General dosing of cefepime in susceptible infections:

• Infants, Children, and Adolescents:
  • Mild to moderate infections:
    • 50 mg/kg/dose intravenous or Intramuscular twice daily to a maximum dose of 2,000 mg/dose.
  • Severe infections:
    • 50 mg/kg/dose intravenous twice or thrice daily to a maximum dose of 2,000 mg/dose

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Use in the treatment of acute pulmonary exacerbation of Cystic fibrosis:

• Infants, Children, and Adolescents:
  • 50 mg/kg/dose intravenous thrice daily to a maximum dose of 2,000 mg/dose.
  • Patients with resistant pseudomonal isolates (MIC of 16 mg/L or more) may require 50 mg/kg/dose intravenous four times a day.

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Use in the treatment of prosthetic valve Endocarditis (within 1 year of valve replacement):

• Children and Adolescents:
  • 50 mg/kg/dose intravenous twice or thrice daily to a maximum dose of 2,000 mg/dose in combination with vancomycin and rifampin for 6 weeks plus gentamicin for the first 2 weeks.

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Use in the treatment of empiric therapy of Febrile neutropenia:

• Infants, Children, and Adolescents:

  • 50 mg/kg/dose intravenous thrice daily to a maximum dose of 2,000 mg/dose.

• Duration of therapy depends upon febrile neutropenia risk-status:

  • High-risk patients may discontinue empiric antibiotics if all of the following criteria are meeting:
    • Afebrile for at least 24 hours and negative blood cultures at 48 hours with signs of marrow recovery
  • Regardless of the state of the patient's marrow recovery, empiric antibiotics for low-risk patients may be stopped after 72 hours in those with a negative blood culture and who have been afebrile for 24 hours.

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Use in the treatment of complicated Intra-abdominal infection:

• Infants, Children, and Adolescents:
  • 50 mg/kg/dose intravenous twice daily in combination with metronidazole to a maximum dose of 2,000 mg/dose.

Note: IDSA guidelines recommend a duration of 4 - 7 days provided source controlled.

Use in the treatment of Bacterial Meningitis:

• Infants, Children, and Adolescents:
  • 50 mg/kg/dose intravenous thrice daily to a maximum dose of 2,000 mg/dose.

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Use in the Treatment of Peritonitis in patients on peritoneal dialysis:

• Infants, Children, and Adolescents:

  • Intraperitoneal:

    • Intermittent administration:
    • 15 mg/kg/dose once a day into the long dwell

  • Continuous:

    • Loading dose:
      • 500 mg per liter of dialysate
      • maintenance dose of 125 mg per liter

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Use in the treatment of moderate to severe Pneumonia:

• Infants older than 2 months, Children, and Adolescents:
  • Due to P. aeruginosa:
    • For ten days, provide 50 mg/kg/dosage intravenously three times day, up to a dose cap of 2,000 mg.
  • Not due to P. aeruginosa:
    • 50 mg/kg/dose intravenous twice daily for 10 days to a maximum dose of 2,000 mg/dose.

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Use in the treatment of Uncomplicated Skin and soft tissue infections:

• Infants older than 2 months, Children, and Adolescents:
  • 50 mg/kg/dose intravenous twice daily for 10 days to a maximum dose of 2,000 mg/dose.

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Use in the treatment of complicated and uncomplicated  Urinary tract infection:

• Infants older than 2 months, Children, and Adolescents:
  • Mild to moderate infection:
    • For 7 to 10 days, provide 50 mg/kg/dose intravenously or intramuscularly twice day, with a maximum dose of 1,000 mg/dose.

Note: Intramuscular administration may only be considered for mild to moderate infections due to E. coli.

• Severe infection:
  • For ten days, provide 50 mg/kg/dose intravenously twice day, with a dose cap of 2,000 mg/dose.

Pregnancy Risk Factor B

• Cefepime crosses over the placenta. 
• Cefepime has not been linked to any fetal adverse reactions. 
• It is therefore safe to be used by pregnant women with susceptible infections.

Cefepime use duringBreastfeeding:

• Cefepime can be absorbed into breastmilk in small quantities. 
• Cefepime is safe to use in breastfeeding women. 
• It is possible for infants to develop gastrointestinal problems and should be closely monitored.

Cefepime Dose in Renal Disease:

Cefepime dosage adjustment in Renal disease:

Cefepime Hydrochloride

• Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days):
  • 1 g intravenous as a single dose on day 1, followed by a
  • Maintenance dose of:
    • 0.5 to 1 gm once a day or
    • 1 to 2 gms every 2nd or 3rd day or
    • 2 g thrice weekly after dialysis.

Peritoneal dialysis (PD):

Every second day, provide the usual suggested dose.

• Continuous renal replacement therapy (CRRT)

  • CVVH: A 2 gm loading dosage, followed by 1 to 2 g twice each day.
  • CVVHD/CVVHDF: A Loading dose of 2 gms followed by either 1 g thrice daily or 2 g twice daily.

A higher dosage of 4 gms/day may be used in infections caused by Pseudomonas or in life-threatening infections. Dosage of 2 gms thrice daily may be used for gram-negative rods with MIC ≥4 mg/L.

Cefepime Dose in Liver Disease:

Dose adjustment in patients with liver disease is not recommended.

Common Side Effects Of Cefepime Include:

• Hematologic & oncologic:

  • Positive direct Coombs test

Less Common Side Effects Of Cefepime Include:

• Cardiovascular:

  • Localized phlebitis

• Central nervous system:

  • Headache

• Dermatologic:

  • Skin rash
  • Pruritus

• Endocrine & metabolic:

  • Hypophosphatemia

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Vomiting

• Hematologic & oncologic:

  • Eosinophilia

• Hepatic:

  • Increased serum ALT
  • Abnormal partial thromboplastin time
  • Increased serum AST
  • Abnormal prothrombin time

• Hypersensitivity:

  • Hypersensitivity

• Miscellaneous:

  • Fever

Contraindication to Cefepime include:

• Allergy reactions to penicillins, cefepime, other cephalosporins and other beta-lactam antibiotics or any component of this formulation

Warnings and Precautions

• Elevated INR
  • Cefepime therapy may be used to treat coagulopathy, which is a condition characterized by an increase INR.
  • This is particularly true for people with poor nutritional status, renal impairment, or hepatitis.
• Hypersensitivity
  • Cefepime therapy can cause severe allergic reactions, particularly in penicillin- and cephalosporin-allergic patients. 
  • If allergic reactions are detected, therapy should be stopped immediately.
• Neurotoxicity:
  • Cefepime-treated patients, particularly those who are on high doses or have impaired renal function, can develop severe neurological reactions such as encephalopathy and myoclonus, seizures and nonconvulsive state epilepticus.
  • Patients with impaired renal function should have their dose adjusted. 
  • The neurological effects may be reversed if therapy is stopped.
• Superinfection
  • Cefepime-treated patients for more than two months may contract superinfections, including fungal or bacterial superinfections. 
  • C. difficile-associated diarrhea, (CDAD), and pseudomembranous collitis can occur.
• Renal impairment
  • Patients with impaired renal function should be cautious when taking the drug. Adjusting the dose may be necessary.
• Seizure disorders:
  • Patients taking large doses or those with compromised renal function are at risk for seizures.
  • Patients with seizure disorders or a history of seizures should not take this medication.

Cefepime: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

Monitor renal functions and observe for clinical features of anaphylaxis during administration of the first dose.

How to administer Cefepime?

• As Intramuscular injection:

  • Inject deep into a large muscle mass.

• Intravenous injection or infusion:

  • Administer as an intermittent infusion over half an hour.

• Direct Intravenous injection (off-label):

  • Inject intravenously directly over 5 minutes.

• Extended infusion:

  • Infuse over 3 - 4 hours where appropriate.

Mechanism of action of Cefepime:

Cefepime

• This is a fourth-generation cephalosporin. It inhibits the formation proteins and peptidoglycans.
• It binds to penicillin-binding proteins, eventually leading to cell lysis through the use of autolytic enzymes.

It's fast and complete.absorbed after intramuscular administration. It crosses the blood-brain border, enters the inflammatory fluid at 80% of its serum concentration, and into the bronchial mucilage at 60% of its plasma concentration. 20% of the drug isPlasma proteins bound. It is minimallyMetabolizedThe liver is responsible for a large part of the dietary intake.half-life eliminationBetween 4 and 5 hoursneonates1.7 to 1.9 Hours inChildren2 hours in, 2 months to 6 year oldAdults13.5 hours for patientsHemodialysis, and 19 hours in patientscontinuous peritoneal dialysis.

Peak timePlasma concentrations after intramuscular injection are 1 - 2 hours, and intravenous injections are 0.5 hours.

The drug contains 85%.excretedThe urine remains unchanged.

Cefepime brands (International):

• APO-Cefepime
• Abypim
• Acedrin
• Alcemax
• Amfapime
• Axepim
• Axera
• Biocepime
• Cebopim
• Cefamax
• Cefemax
• Cefemet
• Cefepima
• Ceficad
• Cefipex
• Cefpas
• Cepimax
• Cepiram
• Curafep
• Deltacef
• Epime
• Exepime
• Falocef
• Forgen
• Forzyn Beta
• Funjapin
• Imation
• Interprim
• Macef
• Macepim
• Maxapin
• Maxcef
• Maxef
• Maxicef
• Maxilan
• Maxipime
• Megapime
• Pimcef
• Pime
• Pozine G
• Pozineg
• Procepim
• Protec
• Qpime
• Quadrocef
• Rapime
• Rovatim
• Salapime
• Sanpime
• Sefpime
• Sepime
• Silex
• Supecef
• Superpime
• Tetracef
• Tsepim
• Uniceme
• Unipim
• Vidapime
• Vifepime
• Wincef
• Zepim
• Zepime
• Zepym

Cefepime brands in Pakistan: