Amoxycillin resistance

Broad spectrum therapy is started on an empirical basis. Intra-abdominal infections can be treated by ampicillin (or amoxycillin) or clindamycin combined with aminoglycosides, penicillin-beta-lacta-mase inhibitors such as amoxycillin-clavulanic acid or a second or third generation cephalosporin combined with metronidazole are good alternatives. In patients with impaired immunity and/or prior use of antibiotics, i.e. when it is reasonable to expect resistant pathogens, a broad spectrum penicillin plus beta-lactamase inhibitor or a carbapenem can be used empirically in monotherapy. In septic patients, the rapidly bactericidal action of aminoglycosides is useful. Aminoglycosides should preferentially not be given for more than 3-5 days. 

Amoxycillin is also used in combination with clavulanate potassium. The formulation of amoxycillin with clavulanic acid protects amoxycillin from degradation by beta lactamase enzymes and effectively extends the antibiotic spectrum of amoxycillin to include P lactamase producing bacteria normally resistant to amoxycillin and other betalactam antibiotics. 

Finally, it is universally accepted at present that Helicobacter pylori infection has a definitive ethiological role in peptic ulcer disease, and that erradication therapy is warranted in these clinical scenarios. The majority of therapeutic trials have included the application of triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxycillin or metronidazol and is to date the treatment of choice. However, recent studies have reported antibiotic resistance which can be one reason for failure of treatment of Helicobacter pylori infection [101-103], and new treatment strategies are therefore Wellcome. Flavonoids, in addition to their gastroprotective activity previously commented, have been also shown to inhibit Helicobacter pylori growth in vitro. In this way, Beil et al. [50]... 

In E.coli, resistance to all /1-lactams except cephamycins (40) and carba-penems (37) may be caused by extended-spectrum /1-lactamases [183]. These enzymes are, however, sensitive to clavulanic acid and strains producing these /1-lactamases are often, but not always, sensitive to /l-lactam-/ -lactam-ase inhibitor combinations [183], In contrast, inhibitor-resistant TEM /1-lactamases that are resistant to amoxycillin (41)-clavulanic acid combinations have also been described in E. coli [184]. 

The discovery of clavulanic acid in 1976 heralded a new era in antibacterial chemotherapy. The enormous success of Augmentin (amoxycillin in combination with clavulanic acid) for the treatment of infections caused by /5-lactamase producing bacteria has established that /5-lactamase inhibitors have an important role to play in solving the problem of bacterial resistance. The widespread interest and enthusiasm created by the discovery of clavulanic acid has culminated in the development of two additional /5-lactamase inhibitors, namely, sulbactam and tazobactam. 

Ducons JA, Santolaria S, Guirao R, Ferrero M, Montoro M, GomoUon F. Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer. Aliment Pharmacol Ther 1999 13(6) 775-80. 

Sharara AI, Chedid M, Araj GF, Barada KA, Mourad FH. Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin and tetracycline in Lebanon. Int J Antimicrob Agents 2002 19(2) 155-8. 

Continuing use of the third-generation cephalosporins and the introduction of p-lactamase inhibitor combinations (clavulanate with amoxycillin or ticarcillin, sulbactam with ampicillin, and tazobactam with piperacillin see section 4.2) resulted in the appearance of plasmids encoding class C P-lactamases. After several unconfirmed reports, the first proof that a class C P-lactamase had been captured on a plasmid came in 1990 when transmissible resistance to a-methoxy and oxyimino-P-lactams was shown to be mediated by an enzyme whose gene was 90% identical to the ampC gene of E. cloacae. They have subsequently been found worldwide. Strains with plasmid-mediated AmpC enzymes are typically resistant to aminopenicillins (ampicillin or amoxycillin), carboxypenicillins (carbenicillin or ticarcillin) and ureidopenicillins (piperacillin). The enzymes also provide resistance to the oxyimino cephalosporins (ceftazidime, cefo-... 

Plasmid-mediated resistance to penicillins and cephalosporins ((3-lactam antibiotics) is due to the formation of (3-lactamase enzymes by Staphylococcus aureus or enteric Gram-negative rods. Some (3-lactamases can be firmly bound by compounds such as clavulanic acid (combined with amoxycillin or ticar-cillin) and sulbactam (combined with ampicillin) and can thus be prevented from attacking hydrolysable penicillins. Gram-positive bacteria, apart from staphylococci, generally lack the ability to acquire R plasmids. 

Streptomyces clavuligerus. This was essentially devoid of antibacterial activity but was a very effective inhibitor of beta-lactamases produced by a wide variety of bacteria. Some idea of the excitement these results caused can be seen from Beecham s data for the minimum inhibitory dose of ampicillin needed for a typical resistant staphylococcus without clavulanic acid (500 fig ml-1) and with clavulanic acid (less than 0.4 fig ml-1)- Five years later, they were able to demonstrate that the combination of the broad-spectrum penicillin - amoxycillin - with clavulanic acid was very effective in clinical use. This combination was marketed as Augmentin and soon became one of the best-selling drugs in the world market. 

Amoxycillin 13.9a) and ampicillin 13.9b) resemble penicillin V in being well absorbed orally (amoxycillin, best of all), principally because they are resistant to gastric acidity, and (like penicillin V) they are inactivated by )8-lactamase. 

Bell G, Powell K, Weil J et al (1991) Experience with omeprazole in combination with either amoxycillin or colloidal bismuth subcitrate in patients with metronidazole-resistant Helicobacter pylori. Eur J Gastroenterol Hepatol 3 923-926... 

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