Cefepim

An antibacterial agent from the group of cephalosporins of the fourth generation. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. It has a wide spectrum of action against gram-positive and gram-negative bacteria , strains resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation. It is highly resistant to the hydrolysis of most beta-lactamases and quickly penetrates into gram-negative bacterial cells . Inside the bacterial cell, the penicillin-binding proteins are the molecular target. Active in vivo and in vitro against gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pneumoniae , Streptococcus pyogenes (group A), Streptococcus viridans ; Gram-negative aerobes: Enterobacter spp. , Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , Pseudomonas aeruginosa . in vitro active (but clinical significance unknown) against gram-positive aerobes: Staphylococcus epidermidis (methicillin-sensitive strains only), Staphylococcus saprophyticus , Streptococcus agalactiae (group B); Gram-negative aerobes: Acinetobacter calcoaceticus subsp. Iwoff , Citrobacter diversus , Citrobacter freundii , Enterobacter agglomerans , Haemophilus influenzae (including strains producing beta-lactamase), Hafnia alvei , Klebsiella oxytoca , Moraxella catarrhalis, including strains producing beta- lactamirusi , Moroteganis beta , Protera morgangeri morgangeri , Morotageris morgangeris , Providencia stuartii , Serratia marcescens . Most Enterococci strains, including Enterococcus faecalis , methicillin-resistant staphylococci , Stenotrophomonas (formerly known as Xanthomonas maltophilia and Pseudomonas maltophilia ), Clostridium difficile are not sensitive to cefepime.

Bioavailability of 100%. TCmax after intravenous and intramuscular administration at a dose of 0.5 g - by the end of the infusion and 1-2 hours, respectively. Cmax with intramuscular administration in doses of 0.5, 1 and 2 g - 14, 30 and 57 μg / ml, respectively; with intravenous administration in doses of 0.25, 0.5, 1 and 2 g - 18, 39, 82 and 164 μg / ml, respectively; the time to reach the average therapeutic plasma concentration is 12 hours; the average therapeutic concentration with intramuscular injection is 0.2 μg / ml, with intravenous administration - 0.7 μg / ml. High concentrations are determined in urine , bile , peritoneal fluid , blister exudate , bronchial mucosa , sputum , prostate gland , appendix and gall bladder . Distribution volume - 0.25 l / kg, in children from 2 months to 16 years - 0.33 l / kg. Communication with plasma proteins - 20%. It is metabolized in the liver and kidneys by 15%. T _1/2 - 2 hours, total clearance - 120 ml / min, renal clearance - 110 ml / min. It is excreted by the kidneys (by glomerular filtration unchanged - 85%), with breast milk . T _1/2 with hemodialysis - 13 hours, with continuous peritoneal dialysis - 19 hours.

Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia ), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .. Febrile neutropenia (empirical therapy). Complicated and uncomplicated urinary tract infections (including pyelonephritis ) caused by Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis. Uncomplicated infections of the skin and soft tissues caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes . Complicated intra-abdominal infections (in combination with metronidazole ) caused by Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis.

Hypersensitivity (including to other cephalosporins, penicillins, other beta-lactam antibiotics), children's age (up to 2 months).

Caution

Pregnancy , lactation , diseases of the gastrointestinal tract (including a history ), especially colitis , severe chronic renal failure .

Intravenously infusion (for at least 30 minutes) or intramuscularly (only for complicated or uncomplicated urinary tract infections of mild and moderate severity caused by E. coli ). Pneumonia (moderate and severe) caused by Streptococcus pneumoniae (including cases of association with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .: intravenously 1-2 g every 12 hours for 10 days. Febrile neutropenia (empirical therapy): 2 g intravenously every 8 hours for 7 days or until neutropenia resolves. Complicated or uncomplicated urinary tract infections of mild and moderate severity caused by E. coli , Klebsiella pneumoniae , Proteus mirabilis: intravenously or intramuscularly (only for infections caused by E. coli ), 0.5-1 g every 12 hours for 7-10 days. Severe, complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by E. coli or Klebsiella pneumoniae : 2 g intravenously every 12 hours for 10 days. Moderate and severe infections of the skin and soft tissues caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes : 2 g intravenously every 12 hours for 10 days. Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis: 2 g intravenously every 12 hours for 7-10 days. In children from 2 months to 16 years and weighing up to 40 kg, the recommended dosage regimen for all indications (excluding febrile neutropenia) is 50 mg / kg every 12 hours intravenously; with febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment as in adults. In chronic renal failure, the dose is prescribed depending on the severity of the infection and creatinine clearance (CC): more than 60 ml / min - 0.5-1-2 g every 12 hours or 2 g every 8 hours, CC 30-60 ml / min - 0.5-1-2 g every 24 hours or 2 g every 12 hours, with QC 11-29 ml / min - 0.5-1-2 g every 24 hours, less than 11 ml / min - 0.25-0 5-1 g every 24 hours; continuous outpatient peritoneal dialysis - 0.5-1-2 g every 48 hours. Patients undergoing hemodialysis on the 1st day are given 1 g, then 0.5 g every 24 hours for all infections and 1 g every 24 hours for the treatment of febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is advisable to administer cefepime every day at the same time. Data on the use of the drug in children with concomitant chronic renal failure are not available, however, given the similar pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between doses) in children with chronic renal failure is similar to the dosage regimen in adults. For intravenous administration, dissolve in sterile water for injection, 5% dextrose solution or 0.9% NaCl solution ; for intramuscular administration - in sterile water for injection with paraben or benzyl alcohol , in 0.5 and 1% lidocaine solution.

• Allergic reactions: skin rash (including erythematous rashes), itching, fever , anaphylactoid reactions , Coombs positive reaction , eosinophilia , erythema multiforme exudative (including Stevens-Johnson syndrome ), rarely - toxic epidermal necrolysis (Lyell's syndrome) .
• Local reactions: with intravenous administration - phlebitis , with intramuscular administration - hyperemia and pain at the injection site.
• From the nervous system: headache , dizziness , insomnia , paresthesia , anxiety, confusion, convulsions .
• From the genitourinary system: vaginitis .
• From the urinary system: impaired renal function.
• From the digestive system: diarrhea , nausea , vomiting , constipation , abdominal pain, dyspepsia , pseudomembranous enterocolitis .
• From the hemopoietic organs: anemia , thrombocytopenia , leukopenia , neutropenia , pancytopenia , hemolytic anemia , bleeding.
• From the respiratory system: cough .
• From the cardiovascular system: tachycardia , shortness of breath , peripheral edema .
• Laboratory indicators: a decrease in hematocrit , an increase in prothrombin time , an increase in urea concentration, hypercreatininemia , hypercalcemia , an increase in the activity of hepatic transaminases and alkaline phosphatase , and hyperbilirubinemia .
• Other: sore throat , thoracalgia , increased sweating, back pain, asthenia , the development of superinfection, oropharyngeal candidiasis .

Overdose

Symptoms (often occur in patients with chronic renal failure): convulsions, encephalopathy , neuromuscular agitation.

Treatment: hemodialysis.

If pseudomembranous colitis with prolonged diarrhea occurs, stop taking it and prescribe vancomycin (by mouth) or metronidazole . Cross-hypersensitivity is possible in patients with allergic reactions to penicillins. With combined severe renal and hepatic insufficiency , the plasma concentration of the drug should be regularly determined (dose adjustment is carried out depending on the CC). With prolonged treatment, regular monitoring of peripheral blood , indicators of the functional state of the liver and kidneys is necessary. In mixed aerobic-anaerobic infections, identification of pathogens requires a combination with drugs active against anaerobes. Patients who have meningeal dissemination from a remote site of infection have suspected meningitis or the diagnosis of meningitis is confirmed, an alternative antibiotic with clinical efficacy confirmed for this situation should be prescribed. Possible detection of a positive Coombs test, false positive test for glucose in the urine . Store the prepared solution for no more than 24 hours at room temperature or for 7 days in the refrigerator . Color change does not affect the activity of the drug.

Pharmaceutically incompatible with other antimicrobial drugs and heparin . Incompatible with metronidazole solution (before the introduction of metronidazole solution for the prevention of infections during surgical procedures, the infusion system should be flushed with cefepime solution). Increases nephro- and ototoxicity of aminoglycosides .