Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: Medochemie Ltd, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus.
Pharmacotherapeutic group: Second-generation cephalosporins, Other Beta-Lactam Antibacterials
ATC code: J01DC04
Cefaclor is a semi-synthetic bactericidal and broad-spectrum beta-lactam antibiotic that belongs to the second generation cephalosporins.
All cephalosporins (ß-lactam antibiotics) inhibit cell wall production and are selective inhibitors of peptidoglycan synthesis. The first step of the work mechanism is the binding of the drug to cell receptors (penicillin-binding proteins). After this binding, the transpeptidation reaction is hindered, and therefore the synthesis of peptidoglycan is blocked. This process leads to the lysis of the bacterium.
The β-lactam antibiotics contain a so-called beta-lactam ring, which is essential for the anti-microbial activity. By splitting of this ring, the antibiotic becomes ineffective. However, different bacteria have enzymes (beta lactamases) which affect this ring by opening it, therefore they are resistant to this kind of antibiotics.
As with all cephalosporins and other beta-lactam antibiotics, different resistance mechanisms have been acquired by each group of bacteria and include: changes in targets (penicillin-binding proteins, PBPs), enzymatic degradation by beta-lactamases and altered access the point of action There is cross-resistance between cephalosporins and penicillins. Gramnegative micro-organisms, which are inducible chromosome-linked beta – containing lactamases, such as Enterobacter spp, Serratia spp, Citrobacter spp, and Providentia spp should be considered as resistant to cephalexin in spite of their in vitro susceptibility.
The minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cefaclor are:
Streptococcus Pneumoniae S ≤0.032 mg/L, R >0.5 mg/L
Haemophilus Influenzae: S ≤0.5 mg/L, R >0.5 mg/L
Moraxella catarrhalis: S ≤0.125 mg/L, R >0.125 mg/L
Staphylococcus spp.: Susceptibility is inferred from cefoxitin susceptibility
Streptococcus groups A, B, C and G: Susceptibility is inferred is from penicillin susceptibility
The prevalence of resistance may vary geographically; the differences in the time for the selected micro-organisms and local information on resistance is desirable, particularly when treating severe infections. If necessary, expert advice should be sought in particular, when the local prevalence of resistance is such that use of the agent in at least some types of infections is questionable.
Sensitive species:
Staphylococcus aureus (including beta-lactamase producing strains),
Staphylococcus epidermidis (including beta-lactamase producing strains)
Staphylococcus saprophyticus Streptococcus pyogenes
Strains in which resistance can be a problem:
Streptococcus pneumoniae
Resistant species:
Staphylococci, methicillin-resistant
Enterococci
Acinetobacter calcoaceticus Citrobacter spp.
Enterobacter spp.
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Moraxella catarrhalis
Morganella morganii
Proteus mirabilis
Povidencia rettgeri Pseudomonas spp.
Serratia spp.
Gram-negative anaerobic spp.
Gram-positive anaerobic spp.
In Streptococcus pneumoniae, reduced sensitivity to beta-lactams may occur by accumulation of mutations in the penicillin-binding proteins. In typical cases, more than one penicillin-binding is changed, and the strains are cross-resistant to most of the beta-lactam antibiotics. This is the only mechanism of resistance that is present at Streptococcus pneumonia and other alpha haemolytic streptococci.
For Moraxella catharralis and Haemophilus influenzae, resistance to beta-lactam antibiotics is normally due to a beta-lactamase protein that is encoded on a plasmid. Cefaclor is not efficiently degraded by most of these beta-lactamases, and ampicillinresistant Haemophilus and Moraxella are normally sensitive. The ROB-1 betalactamase is uncommon in Haemophilus influenzae and cefaclor may be inactivated as many other beta-lactam antibiotics. In rare cases, due to resistance in Haemophilus influenzae penicillin-binding proteins can be altered.
For staphylococci, the “methicillin-resistant” or “oxacillin resistant” strains (also known as with Staphylococcus aureus MRSA), resistance is due to the presence of the mecA gene, a penicillin-binding protein with low the affinity for beta-lactams. Strains that have acquired resistance are resistant to all beta-lactams.
For Escherichia coli and other enterobacteriaceae, resistance to beta-lactam antibiotics can occur in the presence of one or more beta-lactamases, or because of altered permeability. Although cefaclor is stable for the most common beta-lactams, it is necessary to use tests in order to determine the sensitivity.
Cefaclor is rapidly absorbed either on an empty stomach or with meals.
Following doses of 250 mg, 500 mg or 1000 mg, mean peak of about 7, 13 and 23 micrograms per ml occur in the blood after 30 to 60 minutes. The presence of food in the digestive tract and slows down the absorption and lowers the serum peaks, but does not affect the total amount of absorbed cefaclor.
A concentration of 0.4 ug/ml was measured in the sputum following a 500 mg dose administration. Effusion concentrations of 2-5 ug/ml was measured in the middle ear after a dose of 20 mg/kg. Average saliva concentrations of 1.4 to 1.7 ug/ml were measured 2 hours after administration of a dose of 15 mg/kg. Concentrations of 3.8 mg/g, 4.4 g/g and 7.7 mg/g were obtained in bronchial mucosa after a dose of 250 mg, 500 mg and 1000 mg, respectively.
Cefaclor is not significantly metabolized.
The half-life of cefaclor is about 1 hour. Approximately 60 to 65% of the drug is excreted unchanged – and, consequently, in active form in the urine, within 8 hours after administration. During this period, the maximum concentration in the urine is approximately 500, 1200 and 2000 ug per ml after doses of 250 mg, 500 mg and 1000 mg.
Non-clinical data reveal no special hazard for humans. These data are from conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity.
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