The activity of these semisynthetic penicillins extends beyond the Gram-positive and Gram-negative cocci which are susceptible to benzylpenicillin, and includes many Gram-negative bacilli. They do not resist P-lactamases and their usefulness has reduced markedly in recent years because of the increased prevalence of organisms that produce these enzymes.
As a general rule these agents are rather less active than benzylpenicillin against Gram-positive cocci, but more active than the P-lactamase-resistant penicillins (above). They have useful activity against Enterococcus faecalis and many strains of Haemophilus influenzae. Enterobacteriaceae are variably sensitive and laboratory testing for sensitivity is important. The differences between the members of this group are pharmacological rather than bacteriological.
Amoxicillin (t:/2 1 h; previously known as amoxycillin) is a structural analogue of ampicillin (below) and is better absorbed from the gut (especially after food), and for the same dose achieves approximately double the plasma concentration. Diarrhoea is less frequent with amoxicillin than with ampicillin. The oral dose is 250 mg 8-hourly; a parenteral form is available but offers no advantage over ampicillin. For oral use, however, amoxicillin is preferred because of its greater bioavailability and fewer adverse effects.
Co-amoxiclav (Augmentin). Clavulanic acid is a P-lactam molecule which has little intrinsic antibacterial activity but binds irreversibly to p-lactamases. Thereby it competitively protects the penicillin, so potentiating it against bacteria which owe their resistance to production of P-lactamases, i.e. clavulanic acid acts as a 'suicide' inhibitor. It is formulated in tablets as its potassium salt (equivalent to 125 mg of clavulanic acid) in combination with amoxicillin (250 or 500 mg), as co-amoxiclav, and is a satisfactory oral treatment for infections due to P-lactamase-producing organisms, notably in the respiratory or urogenital tracts. It should be used when p-lactamase-producing amoxicillin resistant organisms are either suspected or proven by culture. These include many strains of Staphylococcus aureus, many strains of Escherichia coli and an increasing number of strains of Haemophilus influenzae. It also has useful activity against p-lactamase-producing Bacteroides spp. The t'/2 is 1 h and the dose one tablet 8-hourly.
Ampicillin 1 h) is acid-stable and is moderately well absorbed when swallowed. The oral dose is 250 mg-1 g 6-8-hourly; or i.m. or i.v. 500 mg 4-6-hourly. Approximately one-third of a dose appears unchanged in the urine. The drug is concentrated in the bile.
Adverse effects. Ampicillin may cause diarrhoea but the incidence (12%) is less with amoxicillin. Ampicillin and amoxicillin are the commonest antibiotics to be associated with Clostridium difficile diarrhoea, although this is related to the frequency of their use rather than to their innate risk of causing the disease (this is probably highest for the injectable cephalosporins). Ampicillin and its analogues have a peculiar capacity to cause a macular rash resembling measles or rubella, usually unaccompanied by other signs of allergy. These rashes are very common in patients with disease of the lymphoid system, notably infectious mononucleosis and lymphoid leukaemia. A macular rash should not be taken to imply allergy to other penicillins which tend to cause a true urticarial reaction. Patients with renal failure and those taking allopurinol for hyperuricaemia also seem more prone to ampicillin rashes. Cholestatic jaundice has been associated with use of co-amoxiclav even up to 6 weeks after cessation of the drug; the clavulanic acid may be responsible.
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