Scottish Medical Journal

The resistance of bacteria to β-lactam antibiotics, penicillins or cephalosporins, is usually associated with the production of β-lactamase enzymes which are capable of inactivating these compounds. A number of recent surveys have reported a significant increase in the frequency of isolation of β-lactamase-producing strains of bacteria from infections in general practice in the United Kingdom. A wide variety of bacterial β-lactamases with different properties have been described and it is now recognised that most bacteria produce a chromosomally-mediated β-lactamase which is characteristic of each species. In addition, Gram-negative bacteria may acquire β-lactamases which are mediated by plasmids which are readily transferable by cell to cell contact. Schemes for the classification of bacterial β-lactamases are outlined.

The destruction of amoxycillin by β-lactamase action represents an important mechanism of bacterial resistance to the drug. Data is presented to illustrate that clavulanic acid used in the form of its potassium salt inhibits the amoxycillin destroying action of many different types of β-lactamase for example: the staphylococcal enzyme, the clinically important plasmid mediated enzymes of the TEM, SHV, OXA and PSE types and the chromosomally controlled enzymes produced by Proteus mirabilis and Klebsiella pneumoniae. The mechanisms by which clavulanic acid inhibits β-lactamases and potentiates the antibacterial action of amoxycillin are discussed.

Augmentin was used to treat 40 patients in general practice with exacerbations of bronchiectasis or chronic obstructive airways disease who had not responded clinically to treatment with antimicrobial agents. After ten days treatment 15 patients (38%) were clinically free from infection, 21 (52%) had improved but their sputum still contained pus. Four patients (10%) did not respond to treatment. Pathogens were isolated from 63 per cent of the patients; Haemophilus influenzae was the most common. The clinical response was significantly better in patients from whom recognised pathogens were not isolated.

Clavulanic acid is a β-lactam antibiotic which, although it has little intrinsic activity, is a potent inhibitor of bacterial β-lactamases. When combined with amoxycillin its range of activity includes penicillinase-producing strains of Staphylococcus aureus and many of the β-lactamase-producing strains of Gram-negative bacilli. Bacteria sensitive to augmentin include amoxycillin-resistant strains of Haemophilus influenzae and Escherichia coli, in addition strains of Klebsiella aerogenes, Proteus mirabilis, Proteus vulgaris and Bacteroides fragilis are usually sensitive. The β-lactamases produced by Enterobacter spp, Proteus morgani, Serratia marcescens and Pseudomonas aeruginosa are less susceptible to clavulanic acid and these bacteria are usually resistant to augmentin (1).

Twenty-three patients were treated with Augmentin for severe respiratory tract infections caused by β-lactamase producing organisms. The success rate, clinically and bacteriologically, was 19 out of 23. One non β-lactamase producing H. influenzae, and three mixed organisms including Staph aureus accounted for the four failures.

The elimination of the organisms, sensitive to Augmentin were quick and clinical improvement was seen in 72 hours. The only side effects noted were nausea in three patients, which abated on taking the tablets with meals.

Augmentin is a useful drug in the treatment of respiratory tract infection particularly in acute exacerbation of chronic bronchitis.

Augmentin (amoxycillin and clavulanic acid) is a new oral antibiotic combination which is particularly indicated in the treatment of urinary tract infections. Potentiation of amoxycillin by the clavulanic acid reduces the level of resistance in most Gram-negative urinary pathogens and these organisms are then sensitive to urinary levels of amoxycillin achieved on standard dosage. Clinical trials in urinary tract infections have shown a success rate of about 70 per cent for amoxycillin-resistant organisms. Augmentin in a dose of 375 mg tds is well tolerated and minimal gastrointestinal side effects occur.

Augmentin is a novel antibiotic combination and will be particularly valuable in the oral treatment of urinary tract infections caused by multiply resistant bacteria.

Thirty-two patients with skin infections were treated with Augmentin, a combination of amoxycillin with the β-lactamase inhibitor clavulanic acid. These infections were primary skin sepsis (7), infected eczema (11), infected trauma (10) and leg ulcers (4). The majority of cases were caused by amoxycillin-resistant Staphylococcus aureus either alone or in combination with Streptococcus pyogenes.

Thirty patients (94%) responded to treatment with only one withdrawal (for side effects). Side effects were limited to nausea (9%) diarrhoea (9%) and rash (3%). No patient with diarrhoea showed evidence of Clostridium difficile toxin production in the stools.

Augmentin appears to be a safe, useful, effective antibiotic for the treatment of skin infections in general practice and in hospital. It may prove of particular value when mixed infections of penicillin-resistant staphylococci and Streptococcus pyogenes are present.

Fifty-three years after their discovery the penicillins still present a challenge to laboratory workers and clinicians. They are members of the broader beta-lactam group and are susceptible to inactivation by beta-lactamases from Gram-positive and Gram-negative bacteria. Countering these enzymes is achieved by producing more stable penicillin molecules or by using enzyme-blocking agents like clavulanic acid to protect the antibiotics.

The field is confusing and to assist in defining the present-day role of the group, the concept of a microbiological profile is considered. The modes and sites of action of the penicillins and the beta-lactamases are presented and both are classified. The place of penicillins in the treatment of life-threatening and lesser infections, and in prophylaxis, is discussed.