Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2019 Publisher: Novartis New Zealand Limited, PO Box 99102, Newmarket, AUCKLAND 1149 Telephone: 0800 354 335
Pharmacotherapeutic group: J01CA04 – Penicillins with extended spectrum, amoxicillin.
Inhibition of bacterial cell wall synthesis.
Amoxicillin is a semi-synthetic aminopenicillin of the beta-lactam group of antibiotics.
Beta-lactam antibiotic.
Amoxicillin is an aminobenzyl penicillin that has a bactericidal action due to its inhibition of the synthesis of the bacterial cell wall. It exerts a bactericidal effect against many Gram-positive and Gram-negative microorganisms. Amoxicillin is not effective against betalactamase producing organisms.
Amoxicillin has a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative microorganisms, acting through the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin is active in vitro against beta-lactamase negative strains of Proteus mirabilis, and Haemophilus influenza. In vitro studies have also demonstrated activity against most strains of alpha- and beta-haemolytic streptococci. Streptococcus pneumoniae, and betalactamase negative strains of staphylococci, Neisseria gonorrhoeae, Neisseria meningitidis and Enterococcus faecalis. However, some of the organisms are sensitive to amoxicillin only at concentrations achieved in the urine. Strains of gonococci, which are relatively resistant to benzyl penicillin, may also be resistant to amoxicillin.
Amoxicillin is susceptible to degradation by beta-lactamases and therefore it is ineffective against bacteria which produce these enzymes particularly resistant staphylococci, which now have a high prevalence. All strains of Pseudomonas, Klebsiella and Enterobacter, indole positive Proteus, Serratia marcescens, Citrobacter, penicillinase producing N. gonorrhoeae and penicillinase producing H. influenzae are also resistant. Escherichia coli isolates are becoming increasingly resistant to amoxicillin in vitro due to the presence of penicillinase-producing strains.
The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
The MIC breakpoints for susceptible organisms vary according to species. Enterobacteriaceae are considered susceptible when inhibited at NMT 8 mcg/ml amoxicillin and resistant at NLT 32 mcg/ml.
From NCCLS recommendations and using NCCLS-specified methods, M. catarrhalis (betalactamase negative) and H. influenzae (beta-lactamase negative) are considered susceptible at NMT 1 mcg/ml and resistant at NLT 4 mcg/ml; Str. pneumoniae are considered susceptible to amoxicillin at MIC NMT 2 mcg/ml and resistant at NLT 8 mcg/ml.
Strains of the following named organisms are generally sensitive to the bactericidal action of amoxicillin in vitro.
Susceptible Gram-positive aerobes include Enterococcus faecalis (Note 2), Streptococcus pneumoniae (Notes 1, 3), Streptococcus pyogenes (Notes 1, 3), Streptococcus viridans (Note 2), Streptococcus agalactiae, Streptococcus bovis, Staphylococcus aureus (penicillin sensitive), Corynebacterium species (Note 2), Bacillus anthracis, Listeria monocytogenes.
Susceptible Gram-negative aerobes include Haemophilus influenzae (Note 3), Haemophilus parainfluenzae (Note 3), Escherichia coli (Note 3), Proteus mirabilis, Salmonella species (Note 2), Shigella species (Note 2), Bordetella pertussis, Brucella species (Note 1), Neisseria gonorrhoeae (Note 2), Neisseria meningitidis (Note 1), Pasteurella septica, Helicobacter pylori, Leptospira spp, Vibrio Cholerae.
Susceptible anaerobes include Bacteroides melaninogenicus (Note 2), Clostridium species, Fusobacterium spp. (Note 2), Peptostreptococci.
Other susceptible organisms include Borrelia burgdorferi.
Note 1: No beta-lactamase producers have as yet been reported for these bacterial species.
Note 2: Inconstantly susceptible; susceptibility is therefore unpredictable in the absence of susceptibility testing.
Note 3: Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications.
Bacteria may be resistant to amoxicillin due to production of beta-lactamases, which hydrolyse aminopenicillins, due to alteration in penicillin-binding proteins, due to impermeability to the drug, or due to drug efflux pumps. One or more of these mechanisms may co-exist in the same organism, leading to a variable and unpredictable cross-resistance to other beta-lactams and to antibacterial drugs of other classes.
Resistant Gram-positive aerobes include Staphylococcus (beta-lactamase producing strains).
Resistant Gram-negative aerobes include Acinetobacter spp., Citrobacter spp., Enterobacter spp., Klebsiella spp., Moraxella catarrhalis (non-susceptible isolates), Proteus spp. (indole positive), Proteus vulgaris, Providencia spp., Pseudomonas spp., Serratia spp.
Resistant anaerobes include: Bacteroides fragilis.
Other resistant organisms include: Chlamydia, Mycoplasma, Rickettsia.
No data available.
Amoxicillin is stable in the presence of gastric acid and rapidly absorbed from the gut to an extent of 72 to 93%. Absorption is independent of food intake. Peak blood levels are achieved 1 to 2 hours after administration. After 250 and 500 mg doses of amoxicillin, average peak serum concentrations of 5.2 mcg/ml and 8.3 mcg/ml respectively have been reported.
Amoxicillin is not highly protein bound. Approximately 18% of total plasma drug content is bound to protein. Amoxicillin diffuses readily into most body tissues and fluids, including sputum and saliva but not the brain and spinal fluid. Inflammation generally increases the permeability of the meninges to penicillins and this may apply to amoxicillin. Amoxicillin diffuses across the placenta and a small percentage is excreted into the breast milk.
Amoxicillin is excreted mainly via the urine where it exists in a high concentration. Amoxicillin is also partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10 to 25% of the initial dose. Small amounts of the drug are also excreted in faeces and bile. Concentrations in the bile may vary and are dependent upon normal biliary function.
Approximately 60 to 70% of amoxicillin is excreted unchanged in urine during the first 6 hours after administration of a standard dose. The elimination half-life is approximately 1 hour. Concurrent administration of probenecid delays amoxicillin excretion. In patients with endstage renal failure, the half-life ranges between 5 to 20 hours. The substance is haemodialysable.
No data available.
No data available.
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