P-lactamases stable penicillins

The aminopenicillins are, however, not stable to bacterial P-lactamases. Several steps have been taken to extend their activity to P-lactamase-producing organisms and these include co-formulation with P-lactamase stable penicillins and the use of P-lactamase inhibitors. 

Combination treatments often involve the use of broad-spectrum penicillin and P-lactamase-stable penicillin. Clinically useful combinations include ampidox (ampi-dllin and doxadllin) and magnapen (ampidUin and fludoxadllin). These combinations are usually indicated for infections caused by susceptible organisms where a mixed infection is present and includes penidllin-resistant staphylococd. 

After the influx of several a-amino penicillins such as ampicillin (Table 1) and related analogues, and the p-lactamase stable isoxazolyl penicillins in the 1950s and early 1960s, attention turned to identifying derivatives having a broader spectrum of activity. Carbenicillin and later, ticarcillin, reached the marketplace by the early 1970s. Effort then focused on the acyl and ureido ampicillin derivatives and culminated in the commercialization first of azlocillin and mezlocillin, then of piperacillin. Many thousands of derivatives were synthesized and some of the more active examples that have made tittle or no commercial impact are shown in Tables 2 and 3. 

Similar to Penicillin G (destroyed by p lactamase) but acid-stable and more active against gram-negative bacteria. Carbenicillin has -COONa instead of NH2 group. 

Correct answer a D. Amoxicillin plus clavulanic acid is an extended spectrum formulation that is penicillinase resistant because of the presence of a p-lactamase inhibitor, and is stable in acid. Methicillin, an antistaphylococcal penicillin, is penicillinase resistant but is not stable in acid. Carbeniciliin and piperacillin, antipseudomonai penicillins, are neither penicillinase resistant nor stable in acid. Penicillin V is a narrow spectrum antibiotic that is not penicillinase resistant but is stable in acid. 

Boronic acid derivatives have been shown to inhibit -lactamases [168]. The boronic acid function, which is isoelectronic with a protonated carboxyl group, is presumed to block enzymatic activity by forming a stable tetrahedral borate complex with the active serine residue. Boronic acids 319, structurally related to penicillin G and methicillin, were synthesised in three steps from dibutyl iodomethaneboronate [169] (Scheme 97). They are inhibitors of P-lactamase I from B. cereus. There are presently no reports of boronic acid derivatives acting as inhibitors of bacterial D,D-peptidases. 

The nucleus of cephalosporin C was named 7-aminocephalosporanic acid (7-AC A). Cephalosporin C strongly absorbed ultraviolet fight, was stable to acid and to penicillin P-lactamase, was non-toxic and had in vivo activity in mice. Its mode of action was the same as that of the penicillins that is, inhibition of bacterial cell wall formation. Although neither penicillin N nor cephalosporin C was ever commercialized, they led to important knowledge on the biosynthesis of these compounds and the development of many powerful semi-synthetic cephalosporins of great use in medicine. 

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