Pseudomonas aeruginosa cephalosporin activity

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. 

Ceftazidime is the latest third generation cephalosporin to reach the market. It has one of the broadest spectrums of the cephalosporins, similar in many regards to that of cefotaxime. It is particularly active against Pseudomonas aeruginosa, being perhaps 4-5 times more potent vitro than moxedactam and cefotaucime. 

Some natural antibiotics contain a siderophore structure, for instance, 5i-albomycin 35, which is produced by Streptomyces subtropicus. The linear tripeptide portion chelates Fe(III) and, thereby, is able to utilize the iron-transport system of a range of microorganisms. Subsequent to uptake, peptidases localized in the cytoplasmic membrane hydrolytically release the toxic thioribosyl moiety. In principle, this property can be used for selective drug delivery. Preliminary studies indicated that substantial modification of the siderophore framework can be tolerated by microbial iron-transport systems. Surprisingly, simple modifications can be made to cephalosporin molecules, which endow them with the ability to interact with microorganism iron-transport mechanisms. Thus, simple incorporation of a catechol moiety, as in 36, endows this molecule with enhanced activity against Pseudomonas aeruginosa when compared... 

Enzyme inhibitors such as cloxacillin and methicillin have been shown to potentiate the action of certain penicillins and cephalosporins against Ps. aeruginosa Figure 7.7). Thus, the presence of cloxacillin, which is a strong inhibitor of the inducible enzyme, potentiates the effect of cephaloridine which alone is susceptible to hydrolysis by the pseudomonas lactamase. Cloxacillin shows no antibacterial activity against... 

In conclusion, the majority, if not all, of the strains of Ps. aeruginosa produce an inducible -lactamase which plays an important role in the resistance of the organisms to certain penicillins and cephalosporins. In addition to this enzyme, strains of Ps. aeruginosa can also produce a further /3-lactamase which may be constitutive or R factor mediated. Unlike the inducible enzyme, these additional enzymes have the ability to hydrolyse carbenicillin. Table 7.9 shows the substrate profile of all three enzymes. The new /3-lactam antibiotics with anti pseudomonas activity... 

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