Antibiotics clavulanic acid

Oxidation of an allylic alcohol. This reagent has been used successfully to oxidize the benzyl ester of the /S-lactam antibiotic clavulanic acid (1) to the labile allylic aldehyde 2. Attempted oxidation with the Pfitzner-Moffatt reagent resulted in formation of a 1,3-diene by a 1,4-elimination. ... 

Biosynthesis of the 8-lactam antibiotic clavulanic acid begins with a TPP-dependent reaction between D-glyceraldehyde 3-phosphate and arginine. 

P-Lactams. AH 3-lactams are chemically characterized by having a 3-lactam ring. Substmcture groups are the penicillins, cephalosporias, carbapenems, monobactams, nocardicias, and clavulanic acid. Commercially this family is the most important group of antibiotics used to control bacterial infections. The 3-lactams act by inhibition of bacterial cell wall biosynthesis. 

Antibiotics, P-Lactams, Clavulanic Acid, Thienamycin, and Others," in ECT 3rd ed.. Supplement, pp. 83—131, by Allan Brown, Beecham Research Laboratories. 

When combined with a (i-lactam antibiotic, both clavulanic acid and sulbactam provide very effective treatments for general bacterial infections, and overcome the resistance that would otherwise been encountered due to the expression of (i-lactamases. Clavulanic acid is sold in combination with the antibiotic amoxicillin and sulbactam is sold in combination with ampicillin. 

Lactams are a broad class of antibiotics that include penicillin derivatives, cephalosporins, monobactams, carbapenems, and clavams (/8-lactamase inhibitors). The metabolic engineering of penicillin and cephalosporins production has been summarized by several good reviews [71,72], so the focus here is clavulanic acid, which has attracted interest in recent years. 

In a recent study, the bacterial populations contaminating the upper gut in SIBO patients and their antibiotic susceptibility were determined. Amoxicillin-clavulanic acid and cefoxitin were effective against >90% of anaerobic strains, while aminopenicillins, cephalosporins and cotrimoxazole were effective against the microaerophilic population. Erythromycin, clindamycin and rifampicin were ineffective. Data on metronidazole and fluoroquinolones are not available [32]. 

Another recent controlled trial showed a good therapeutic effect of both amoxicillin-clavulanic acid and norfloxacin in SIBO patients [45]. However, a rapid relapse of diarrhea just few days after the withdrawal of antibiotics was evident. In this paper, the efficacy of probiotics in SIBO patients was also evaluated, but no significant effect was described. While on the one hand these results confirm the frequent need of several courses of antibiotic therapy in SIBO patients, on the other they support the idea that rifaximin may represent a good choice on the basis of its excellent tolerability. 

The answer is d. (Hardman, pp 1097—1098.) The antibiotic clavu-lanic acid is a potent inhibitor of p-lactamases. The mode of inhibition is irreversible. Although clavulanic acid does not effectively inhibit the transpeptidase, it maybe used in conjunction with a p-lactamase-sensitive penicillin to potentiate its activity... 

The role of antimicrobials for noninfected dog bite wounds remains controversial because only 20% of wounds become infected. Antibiotic recommendations for empiric treatment include a 3- to 5-day course of therapy. Amoxicillin-clavulanic acid is commonly recommended for oral outpatient therapy. Alternative agents include doxycycline, or the combination of penicillin VK and dicloxaciHin. 

Patients with noninfected bite injuries should be given prophylactic antibiotic therapy for 3 to 5 days. Amoxicillin-clavulanic acid (500 mg every 8 hours) is commonly recommended. Alternatives for penicillin-allergic patients include fluoroquinolones or trimethoprim-sulfamethoxazole in combination with clindamycin or metronidazole. First-generation cephalosporins, macrolides, clindamycin alone, or aminoglycosides are not recommended, as the sensitivity to E. corrodens is variable. 

The real breakthrough in identifying a -lactamase inhibitor came in 1976 with the isolation of a bicyclic -lactam, called clavulanic acid la (Fig. 3), produced by a strain of Streptomyces clavuligerus [21,22], In itself, this bicyclic -lactam is a weak antibiotic, but a powerful inhibitor of most class A en-... 

Combinations of /3-lactamase inhibitors with /3-lactam antibiotics are very useful in the treatment of infections, since they are relatively immune to the emergence of new resistance. However, a /3-lactamase resistant to inactivation by clavulanic acid has been identified [52],... 

Transition metal ions cause a dramatic increase in the rate of hydrolysis of /Madam antibiotics [75][133][134], For example, copper(II) and zinc(II) ions increase the rate of alkaline hydrolysis ca. 108-fold and 104-fold, respectively [76], It has been suggested that the metal ion coordinates with both the carboxylate group and the /3-lactam N-atom of penicillins (A, Fig. 5.20). This complex stabilizes the tetrahedral intermediate and, thus, facilitates cleavage of the C-N bond catalyzed by the HO ion [74] [75], Such a model appears applicable also to clavulanic acid, imipenem, and monobactams, but it re-... 

Of particular note is the combination of amoxicillin and clavulanic acid. The latter is a potent inhibitor of enzymes that degrade amoxicillin and many other p-lactam antibiotics. This combination, marketed as Augmentin, increases the efficacy of amoxicillin against organisms that would be otherwise resistant to it. It is among the most widely used antibiotics in the United States. 

Timentin Antibiotic Inj 3.1 gm (ticarcillin 3 gm, clavulanic acid 0.1 gm) 3.1 gmlVq4-6h hypokalemia. 

Clavulanic acid is isolated from Streptomyces clavuligerus [60-66], and sulbactam, a sulfone of penicillanic acid, is synthesized from 6-APA [67-69], Both compounds have extremely weak antibacterial properties and act by forming irreversible complexes with beta-lactamase, which inactivates the enzyme, and as a result the beta-lactam antibiotic has time to destroy the microorganism. Currently, a number of combined drugs containing various combinations of beta-lactamase antibiotics and inhibitors are used. 

Beta-lactamase inhibitors include clavulanic acid, sulbactam and tazobactam. They are structurally related to the beta-lactam antibiotics however the antibacterial activity of these compounds is very weak or negligible. They are strong inhibitors of bacterial beta-lactamases and can protect beta-lactam antibiotics from hydrolysis by these enzymes. 

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... 

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. 

Successful antibiotic treatment should be continued until return of the temperature and peripheral leukocyte count to normal. However, persisting or returning fever and leukocytosis should lead to discontinuation of the antibiotics and prompt re-evaluation with imaging and surgical re-exploration rather than an escalation of the antibiotic treatment. Open complicated fractures should be treated for 5 days. Animal and human bites are treated with amoxycillin-clavulanic acid for 5 days. 

Efforts to overcome the actions of the p-lactamases have led to the development of such p-lactamase inhibitors as clavulanic acid, sulbactam, and tazobactam. They are called suicide inhibitors because they permanently bind when they inactivate p-lactamases. Among the p-lactamase inhibitors, only clavulanic acid is available for oral use. Chemical inhibition of p-lactamases, however, is not a permanent solution to antibiotic resistance, since some p-lactamases are resistant to clavulanic acid, tazobactam, or sulbactam. Enzymes resistant to clavulanic acid include the cephalosporinases produced by Citrobacter spp., Enterobacter spp., and Pseudomonas aeruginosa. 

All mycobacteria produce (3-lactamase. In vitro, several (3-lactamase-resistant antibiotics or a combination of a (3-lactam with (3-lactamase inhibitors, such as clavulanic acid, are active against M tuberculosis and nontubercu-lous mycobacteria. However, the activity of (3-lactam agents against intracellular mycobacteria is generally poor. The (3-lactam agents may be useful in the treatment of MDR tuberculosis in combination with other antitubercular drugs but never as monotherapy. 

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