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Fourth generation Cephalosporins

Gram-positive: "They are extended-spectrum agents with similar activity against gram-positive organisms as first-generation cephalosporins."
Gram-negative: "Fourth-generation cephalosporins are zwitterions that can penetrate the outer membrane of gram-negative bacteria. They also have a greater resistance to beta-lactamases than the third-generation cephalosporins. Many can cross the blood–brain barrier and are effective in meningitis. They are also used against Pseudomonas aeruginosa."

Antimicrobials - Infectious Disease

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Sulfonamide antibiotics Tetracyclines Tuberculosis (anti) agents

Navigation (cephalosporins)

  1. First generation cephalosporins
  2. Second generation cephalosporins
  3. Third generation cephalosporins
  4. Fourth generation cephalosporins  led
  5. Fifth generation cephalosporins

Cefepime (Maxipime ®)

Cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Cefepime has a low affinity for chromosomally-encoded beta-lactamases. Cefepime is highly resistant to hydrolysis by most beta-lactamases and exhibits rapid penetration into gram-negative bacterial cells. Within bacterial cells, the molecular targets of cefepime are the penicillin binding proteins (PBP).

Cefepime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic Gram-Negative Microorganisms
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa

Aerobic Gram-Positive Microorganisms
Staphylococcus aureus (methicillin-susceptible isolates only)
Streptococcus pneumoniae
Streptococcus pyogenes (Lancefield’s Group A streptococci)
Viridans group streptococci

The following in vitro data are available, but their clinical significance is unknown. Cefepime has been shown to have in vitro activity against most isolates of the following microorganisms; however, the safety and effectiveness of cefepime in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms
Staphylococcus epidermidis (methicillin-susceptible isolates only)
Staphylococcus saprophyticus
Streptococcus agalactiae (Lancefield’s Group B streptococci)

NOTE: Most isolates of enterococci, eg, Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to cefepime.

Aerobic Gram-Negative Microorganisms
Acinetobacter calcoaceticus subsp. lwoffii
Citrobacter diversus
Citrobacter freundii
Enterobacter agglomerans
Haemophilus influenzae (including beta-lactamase producing isolates)
Hafnia alvei
Klebsiella oxytoca
Moraxella catarrhalis (including beta-lactamase producing isolates)
Morganella morganii
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Serratia marcescens

NOTE: Cefepime is inactive against many isolates of Stenotrophomonas (formerly Xanthomonas maltophilia and Pseudomonas maltophilia).

Anaerobic Microorganisms
NOTE: Cefepime is inactive against most isolates of Clostridium difficile.

Cefepime for injection, USP is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms.

Pneumonia (moderate to severe) caused by Streptococcus pneumoniae, including cases associated with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter species.

Empiric Therapy for Febrile Neutropenic Patients. Cefepime as monotherapy is indicated for empiric treatment of febrile neutropenic patients. In patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate. Insufficient data exist to support the efficacy of cefepime monotherapy in such patients. (See PACKAGE INSERT FOR CLINICAL STUDIES.)

Uncomplicated and Complicated Urinary Tract Infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae, when the infection is severe, or caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms.

Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes.

Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis. (See PACKAGE INSERT FOR CLINICAL STUDIES.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefepime for injection, USP and other antibacterial drugs, cefepime for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The recommended adult and pediatric dosages and routes of administration are outlined in the following table. Cefepime for injection should be administered intravenously over approximately 30 minutes.

Recommended Dosage Schedule for Cefepime for Injection, USP in Patients with CrCL >60 mL/min:

Site and Type of Infection Dose Frequency Duration (days)
Moderate to Severe Pneumonia due to S. pneumoniae*, P. aeruginosa, K. pneumoniae, or Enterobacter species 1-2 g IV every 12 hours 10
Empiric therapy for febrile neutropenic patients. 2 g IV every 8 hours 7†
Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli, K. pneumoniae, or P. mirabilis* 0.5-1 g
every 12 hours 7-10
Severe Uncomplicated or Complicated Urinary Tract Infections, including pyelonephritis, due to E. coli or K. pneumoniae* 2 g IV every 12 hours 10
Moderate to Severe Uncomplicated Skin and Skin Structure Infections due to S. aureus or S. pyogenes 2 g IV every 12 hours 10
Complicated Intra-abdominal Infections (used in combination with metronidazole) caused by E. coli, viridans group streptococci, P. aeruginosa, K. pneumoniae, Enterobacter species, or B. fragilis. 2 g IV every 12 hours 7-10
Pediatric Patients (2 months up to 16 years)
The maximum dose for pediatric patients should not exceed the recommended adult dose.
The usual recommended dosage in pediatric patients up to 40 kg in weight for uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia is 50 mg/kg/dose, administered every 12 hours (50 mg/kg/dose, every 8 hours for febrile neutropenic patients), for durations as given above.

* including cases associated with concurrent bacteremia
† or until resolution of neutropenia. In patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be re-evaluated frequently.
‡ intramuscular route of administration is indicated only for mild to moderate, uncomplicated or complicated UTIs due to E. coli when the intramuscular route is considered to be a more appropriate route of drug administration.

Renal Dosing:
In patients with creatinine clearance less than or equal to 60 mL/min, the dose of cefepime for injection should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose of cefepime for injection should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses of cefepime for injection in patients with renal impairment are presented below.

When only serum creatinine is available, the following formula (Cockcroft and Gault equation)3 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

Males: Creatinine Clearance (mL/min) = Weight (kg) × (140-age)  /  [72 × serum creatinine (mg/dL)]
Females: 0.85 × above value

Recommended Dosing Schedule for Cefepime for Injection in Adult Patients (Normal Renal Function, Renal Impairment, and Hemodialysis):

Clearance (mL/min)
Recommended Maintenance Schedule
>60 Normal recommended dosing schedule 500 mg every 12 hours 1 g every 12 hours 2 g every 12 hours 2 g every 8 hours
30-60 500 mg every 24 hours 1 g every 24 hours 2 g every 24 hours 2 g every 12 hours
11-29 500 mg every 24 hours 500 mg every 24 hours 1 g every 24 hours 2 g every 24 hours
<11 250 mg every 24 hours 250 mg every 24 hours 500 mg every 24 hours 1 g every 24 hours
CAPD 500 mg every 48 hours 1 g every 48 hours 2 g every 48 hours 2g every 48 hours
Hemodialysis* 1 g on day 1, then 500 mg every 24 hours thereafter 1 g every 24 hours

*On hemodialysis days, cefepime should be administered following hemodialysis.
Whenever possible, cefepime should be administered at the same time each day.

In patients undergoing continuous ambulatory peritoneal dialysis, cefepime for injection may be administered at normally recommended doses at a dosage interval of every 48 hours.

In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. The dosage of cefepime for injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia, which is 1 g every 24 hours. Cefepime for injection should be administered at the same time each day and following the completion of hemodialysis on hemodialysis days.

Data in pediatric patients with impaired renal function are not available; however, since cefepime pharmacokinetics are similar in adults and pediatric patients, changes in the dosing regimen proportional to those in adults are recommended for pediatric patients.

Package insert data:


National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Fourth Generation Cephalosporins