Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2015 Publisher: MIP Pharma GmbH, Kirkeler Str. 41, 66440, Blieskastel, Germany
Pharmacotherapeutic group: First-generation cephalosporin
ATC code: J01DB04
Cefazolin is a bactericidal cephalosporin antibiotic of the first generation for parenteral administration.
Cephalosporins inhibit cell wall synthesis (in the growth stage) through blocking the penicillin-binding proteins (PBPs) like transpeptidases. The outcome is a bactericidal action.
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefazolin for individual target species (i.e. %T>MIC).
Resistance to cefazolin can rest upon one of the following mechanisms:
There is a partial or total cross-resistance of cefazolin with other cephalosporins and penicillins.
The minimum inhibitory concentrations (MIC) breakpoints according to EUCAST (European Committee on Antimicrobial Susceptibility Testing; 2013-02-11) are:
| Species | sensitive | resistant |
|---|---|---|
| Staphylococcus spp. | NoteA | NoteA |
| Streptococcus groups A, B, C and G | NoteB | NoteB |
| Viridans group streptococci | <0.5 mg/l | >0.5 mg/l |
| PK/PD (Non-species related) breakpoints | ≤1 mg/l | >2 mg/l |
A Susceptibility of staphylococci to cephalosporins is inferred from the cefoxitin susceptibility except for ceftazidime, cefixime and ceftibuten, which do not have breakpoints and should not be used for staphylococcal infections. Some methicillin-resistant S. aureus are susceptible to ceftaroline.
B The beta-lactam susceptibility of streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.
he following table shows clinically relevant pathogens classified as sensitive or resistant on the basis of in vitro and in vivo data. Cefazolin is effective against some species in vitro, but not clinically, thus these species are classified here as resistant.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information is desirable, particularly when treating severe infections. If necessary, expert advice should be sought when the local prevalence of resistance is such that the efficacy of cefazolin is questionable. Especially in case of severe infections or failure of therapy, a microbiological diagnosis including identification of the microorganism and its susceptibility to cefazolin should be conducted.
Aerobe Gram-positive:
Staphylococcus aureus (methicillin-sensitive)
Aerobe Gram-positive:
Group A, B, C and G beta-haemolytic streptococci
Staphylococcus epidermidis (methicillin-sensitive)
Streptococcus pneumoniae
Aerobe Gram-negative:
Haemophilus influenzae
Aerobe Gram-positive:
Staphylococcus aureus, methicillin-resistant
Aerobe Gram-negative:
Citrobacter spp.
Enterobacter spp.
Klebsiella pneumoniae
Morganella morganii
Proteus mirabilis
Proteus stuartii
Proteus vulgaris
Pseudomonas aeruginosa
Serratia spp.
Cefazolin is administered parenterally. After administration of 500 mg intramuscular injection, maximum serum levels obtained after approximately an hour were 20-40 micrograms/ml. After administration of 1 g maximum serum levels of 37-63 micrograms/ml were obtained. In one continuous intravenous infusion of cefazolin study in healthy adults at doses of 3.5 mg/kg for one hour (approx 250 mg) followed by 1.5 mg/kg for the next two hours (approx 100 mg) a stable serum concentration of approx. 28 micrograms/ml was demonstrated in the third hour. The following table shows the meanserum concentration of cefazolin after intravenous injection of a single dose of 1 g.
Serum concentration (μg/ml) after intravenous administration of 1 g:
| 5 min | 15 min | 30 min | 1 hr | 2 hr | 4 hr |
| 188.4 | 135.8 | 106.8 | 73.7 | 45.6 | 16.5 |
Cefazolin for 70%-86% bound to plasma proteins. The volume of distribution is approximately 11 l/1.73 m². When cefazolin is administered to patients without obstruction of the bile ducts the antibiotic levels 90-120 minutes after administration were generally higher than antibiotic levels in the serum.
Conversely, where obstruction exists the concentrations of antibiotic in the bile were much lower than serum levels. After administration of therapeutic doses in patients with inflamed meninges, varying concentrations of cefazolin from 0 to 0.4 micrograms/ml were measured in cerebrospinal fluid. Cefazolin can easily pass through inflamed synovial membranes and the antibiotic concentration achieved in joints is similar to serum levels.
Cefazolin is not metabolised.
The serum half-life is about 1 hour 35 minutes. Cefazolin is excreted in a microbiologically active form in the urine. Approximately 56-89% of an intramuscular dose of 500 mg is excreted in the first six hours, 80% to almost 100% is excreted within 24 hours. After intramuscular administration of 500 mg and 1 g urine levels can reach 500-4000 μg/ml. Cefazolin is mainly removed from the serum by glomerular filtration, the renal clearance is 65 ml/min/1.73 m².
The acute toxicity of cefazolin is low. By intravenous application the LD50 in rats is 2400-3700 mg/kg body weight. Studies of chronic toxicity in different animal species (rat, dog) revealed no evidence of toxic effects. However, in dogs, muscle injury by repeated intramuscular administration was observed. Studies on the renal toxicity in rabbits showed a low nephrotoxic potential of cefazolin. Mutagenicity or animal experimental studies on the tumorigenic potential of cefazolin are not available. Animal studies showed no evidence of teratogenic effects of cefazolin.
Fertility studies and studies on peri- and postnatal toxicity showed no evidence of harmful effects of cefazolin.
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