Penicillins with Beta-Lactamase Inhibitor

Augmentin and Timentin are frequently used for diabetic foot infections and urinary tract infections. 

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Oral beta-lactam antibiotics such as amoxycillin, cotrimoxazole or doxycycline for 7-10 days are suitable for the treatment of bacterial sinusitis. Furuncles of the nose should be treated with an anti-staphyloccal drug for 5 days. Standard treatment for streptococcal pharyngitis consists of 10 days of penicillin. Malignant otitis externa responds to high dose quinolone therapy (e.g. ciprofloxacin 750 mg 2 t.d.) administered orally. For parapharyngeal abscess, high dose penicillin plus beta-lactamase inhibitors such as amoxycillin-clavulanic acid can be used. Duration of treatment is guided by clinical and parameters of inflammation, and abscesses often need several weeks to resolve by conservative treatment. 

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. 

Co-amoxiclav consists of the combination of amoxicillin (penicillin antibacterial agent) and clavulanic acid (beta-lactamase inhibitor) which is associated with a risk of crystalluria in patients with renal impairment who are receiving high doses, particularly during parenteral therapy. 

Obstetric infections can be treated with penicillin-beta-lactamase inhibitors such as amoxicillin-clavulanic acid, with extended spectrum penicillins (with or without beta-lacamase inhibitors if justified by local resistance surveillance data), with a first or second generation cephalosporin combined with metronidazole. In severe cases of streptococcal infection high doses of penicillin in combination with clindamycin is the treatment of choice. In amnionitis, maternal morbidity resolves with delivery. In endometritis, antibiotics should be stopped after the... 

Ampicillin, amoxicillin, ticarcillin, and piperacillin are also available in combination with one of several 3-lactamase inhibitors davulanic acid, sulbactam, or tazobactam. The addition of a 3-lactamase inhibitor extends the activity of these penicillins to include 3-lactamase-producing strains of S aureus as well as some 3-lactamase-producing gram-negative bacteria (see Beta-Lactamase Inhibitors). 

Some common combinations of penicillins and specific beta-lactamase inhibitors are listed in Table 33-2. Administration of these drug combinations may produce side effects that are caused primarily by the penicillin component that is, penicillin-related side effects such as headache, gastrointestinal problems, and allergic reactions. Nonetheless, combining a beta-lactamase inhibitor with a penicillin can be an effective way of treating bacterial infections that might otherwise be resistant to traditional antibacterial therapy. 

Degradation prodncts spontaneously formed in aqueous solutions, for example cnltnre media, rather than the parent molecnles themselves, may be responsible for the observed effects (4). Antiproliferative activities were generally more prononnced with cephalosporins than with penicillins, while monobactams appear to be practically free from snch effects. Carbapenems have not been thoronghly stndied in this respect, and some data on clavnlanic acid and two other beta-lactamase inhibitors do not clearly reflect the same kind of toxicity as observed with penicillins and cephalosporins (20). 

Beta-Lactamase Inhibitors Clavulanic acid, suibactam, and tazobactam are used in fixed combinations with certain hydrolyzable penicillins. They are most active against plasmid-encoded beta-lactamases such as those produced by gonococci, streptococci, E coli, and H influenzae. They are not good inhibitors of inducible chromosomal beta-lactamases formed by en-terobacter and pseudomonas. 

Supra-additive interactions and potentiation appear to be much less common than antagonism and the simple additive interactions described above. Supra-additive (synergistic) interaction is said to occur if the result of interaction is greater than the sum of the drugs used alone the best example is the therapeutic synergism of certain antibiotic combinations such as sulfonamides and dihydrofolic acid reductase inhibitors such as trimethoprim. Potentiation is said to occur when a drug s effect is increased by another agent that has no such effect. The best example of this type of interaction is the therapeutic interaction of beta-lactamase inhibitors such as clavulanic acid with lactamase-susceptible penicillins. 

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. 

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