Antipseudomonal activity

Analogous to azloci11i n-mezloci11i n, acylation of the amino group of 2-phenyl glycine containing cephalosporins is consistent with antipseudomonal activity. There are many... 

Cefsulodin (60) has a sulfonic acid nx)iety on the C-7 acyl side chain. This moiety conveys antipseudomonal activity to certain penicillins, and it is interesting to note that this artifice works with cefsulodin as well. It is also interesting that, in contrast to the other so-called third-generation cephalosporins, the spectrum of cefsulodin is rather narrow and its clinical success will place a premium upon accurate diagnosis. Its synthesis begins by acylation of... 

Bisphenols are composed of two phenolic groups connected by various linkages. Hydroxy halogenated derivatives, such as hexachlorophane (Fig. 10.7D) and triclosan, are the most active microbiologically, but are bacteriostatic at use-concentrations and have little antipseudomonal activity. The use of hexachlorophane is also limited by its serious toxicity. Both hexachlorophane and trichlosan have limited application in medicated soaps and washing creams. 

In complicated exacerbations with risk of Pseudomonas aeruginosa, recommended therapy includes a fluoroquinolone with enhanced pneumococcal and P. aeruginosa activity (levofloxacin). If IV therapy is required, a /f lactamase resistant penicillin with antipseudomonal activity or a third- or fourth-generation cephalosporin with antipseudomonal activity should be used. 

The unique advantages of piperacillin are broad spectrum of antibacterial activity and excellent antipseudomonal activity. 

The sulphate salt of the title quaternary compound, cephalosporin, 221, showing high antipseudomonal activity, has been synthesized224,225 in six steps for metabolism and pharmacokinetic studies (equation 92). 

While not strictly a penicillin, it has a similar spe action including some antipseudomonal activity. 

The oxyacetic acid residue of the monoxacetams is bioisosteric with the sulfate moiety of the monosulfactams. In addition, the presence of the carboxylate moiety provided opportunity for the preparation of esters that could act as orally absorbed prodrugs. Based on structure-activity relationships, SQ 82,291 (45) [90898-90-1]y C12H15N506S, the nonacidic methoxime side chain of which was necessary to maintain oral absorption of the prodrugs, was prepared. SQ 82,291 has a high, specific affinity for the PBP-3 transpeptidase of gram-negative bacteria. However, it lacks the isobutyric acid moiety of aztreonam (17) on the oxime residue and whereas the activity of SQ 82,291 vs the Enterobacteriaceae was maintained, antipseudomonal activity was significandy diminished (37). 

It was discovered that the A -formimidoyl derivative both stabilised the molecular and enhanced the antipseudomonal activity [7]. The basic starting material for both imipenem and meropenem is 4-acetoxy-2-azetidinone (4-AA) (8), a well known heterocycle synthon which can readily be converted to 9 [8]. 

Oliphant CM, Postelnick M, Noskin GA, Peterson LR. The impact of use reduction on the antipseudomonal activity of fluoroquinolones (abslr). 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco,... 

Carbenidllin is used by itself or in combination with gentamicin for the treatment of infections by sensitive strains of Pseudomonas aeruginosa. The replacement of the phenyl moiety with 3-thienyl groups to produce ticarcillin leads to an increase in antipseudomonal activity. However, the carboxy penidllins show diminished activity against streptococci and enterococd due to reduced binding to the PBPs. 

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