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    In the 1970s, combining the broad-spectrum antibiotic amoxicillin with the beta-lactamase inhibitor clavulanic acid proved a highly effective answer to the dual problems of emerging penicillin resistance and increased mixed infection,“The amoxicillin and clavulanate combination kept the activity of amoxicillin against streptococci, including pneumococci, but restored the activity of amoxicillin against beta-lactamase producing organisms, such as staphylococci, Expansion of the penicillin group of antibiotics began in the 1950s when microbiologist George Rolinson joined Beecham Research Laboratories to establish a microbiological research division. On the advice of Sir Ernst Chain, who shared the Nobel Prize for Physiology or Medicine for his work on penicillin, Rolinson and his team set about the chemical modification of the acyl side chain of penicillin to make semi-synthetic penicillins with new properties. They used the penicillin nucleus, 6-aminopenicillanic acid (6-APA), with the three carbon, one nitrogen ß-lactam ring at its centre, to develop meticillin (launched in 1960), ampicillin (launched in 1961) and cloxacillin (launched in 1962). Ampicillin had a broader spectrum of activity than penicillin G or V and increased activity against Gram-negative organisms but, early on, there were resistant isolates that were attributed to the breakdown of the ß-lactam ring by bacterial ß-lactamase enzymes and to intrinsic mechanisms. Continued research at Beecham yielded a further broad spectrum penicillin with a similar range of activity to ampicillin but with much better oral absorption, resulting in blood levels twice those achieved with similar doses of ampicillin. Rolinson subsequently described in vivid terms the inhibitory effects of amoxicillin and other ß-lactam antibiotics on division of bacterial cells, and the subsequent cell lysis, which he recorded as time lapse sequences on cine film: “The cell wall could be seen to rupture abruptly, usually at a division site, allowing the cytoplasmic membrane to bulge out, forming a spheroplast. Rupture of the spheroplast then followed, due to osmotic pressure, resulting in loss of the cytoplasmic contents and lysis of the cell… With certain ß-lactams, for example amoxycillin, the onset of lysis was seen very early, cell growth barely reaching two cell units in length before rupture of the wall occurred.”Despite its impressive bioavailability and bactericidal activity, amoxicillin’s ß-lactam ring proved just as easy a target for bacterial ß-lactamases as its predecessors.“By 1965, the frequency of clinical isolates producing ß-lactamases had risen dramatically, and it was shown that the ability to make the enzymes was transferred between bacteria via plasmids. This meant that resistance could be spread very rapidly and even passed between different species of bacteria,” explains Professor Geddes. amoxicillin 500mg capsules for tooth infection PACKAGE LEAFLET: INFORMATION FOR THE USER Co-Amoxiclav 500 mg/125 mg film-coated tablets amoxicillin/clavulanic acid Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you. • This medicine has been prescribed for you (or for your child) only. It may harm them, even if their signs of illness are the same as yours. It contains two different medicines called amoxicillin and clavulanic acid. • If you have any further questions, ask your doctor or your pharmacist. WHAT CO-AMOXICLAV TABLETS ARE AND WHAT THEY ARE USED FOR Co-Amoxiclav tablets are an antibiotic and works by killing bacteria that cause infections. • If you get any side effects, talk to your doctor or pharmacist. What Co-Amoxiclav tablets are and what they are used for 2. Amoxicillin belongs to a group of medicines called “penicillins” that can sometimes be stopped from working (made inactive). This includes any possible side effects not listed in this leaflet. What you need to know before you take Co-Amoxiclav tablets 3. The other active component (clavulanic acid) stops this from happening. Co-Amoxiclav tablets are used in adults and children to treat the following infections: • middle ear and sinus infections • respiratory tract infections • urinary tract infections • skin and soft tissue infections including dental infections • bone and joint infections. WHAT YOU NEED TO KNOW BEFORE YOU TAKE CO-AMOXICLAV TABLETS Do not take Co-Amoxiclav: • if you are allergic to amoxicillin, clavulanic acid, penicillin or any of the other ingredients of your medicine (listed in section 6) • if you have ever had a severe allergic reaction to any other antibiotic. This can include a skin rash or swelling of the face or neck • if you have ever had liver problems or jaundice (yellowing of the skin) when taking an antibiotic. Do not take your medicine if any of the above apply to you.

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    Co-amoxiclav is used to treat a variety of bacterial infections, including middle ear and sinus infections, skin and dental infections, cystitis, bronchitis and pneumonia, and bone and joint infections. Co-amoxiclav contains a mixture of two active components. This is a member of the penicillin group of antibiotics, which kills the bacteria responsible for the infection by preventing them from forming cell walls. The problem is that some bacteria are able to develop defence mechanisms that inactivate amoxicillin. Clavulanic acid, which is the second constituent of co-amoxiclav, stops this from happening and makes sure that the amoxicillin component remains effective. The two ingredients, therefore, work in harmony to ensure that all the bacteria at the site of infection are killed thereby allowing symptoms to clear up. Co-amoxiclav is prescribed as tablets of different dose strengths depending on the infection being treated. It is also available in liquid form for children (The Online Clinic does not prescribe for children however). Each film-coated tablet contains amoxicillin trihydrate equivalent to 500 mg amoxicillin with potassium clavulanate equivalent to 125 mg clavulanic acid. Co-amoxiclav is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1): • Acute bacterial sinusitis (adequately diagnosed) • Acute otitis media • Acute exacerbations of chronic bronchitis (adequately diagnosed) • Community acquired pneumonia • Cystitis • Pyelonephritis • Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis. • Bone and joint infections, in particular osteomyelitis. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Doses are expressed throughout in terms of amoxicillin/clavulanic acid content except when doses are stated in terms of an individual component. The dose of Co-amoxiclav that is selected to treat an individual infection should take into account: • The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4) • The severity and the site of the infection • The age, weight and renal function of the patient as shown below. The use of alternative presentations of amoxicillin/clavulanic acid (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1).

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