Pseudomonas activity

New B lactam compounds with anti-pseudomonas activity Carbenicillin esters Ticarcillin Lilacillin BL-P1654... 

BL-P1654. A penicillin with broad spectrum anti-microbial activity [86] (See Table 7.1), it is more active than carbenicillin against strains of Ps. aeruginosa, the majority of strains being inhibited by 8 /rg/ml [75]. The sulphoamino penicillins. A number of these compounds have been investigated for their anti-pseudomonas activity and for their j3 -lactamase resistance [87]. BL-P1462 (Table 7.1) [88] is one such compound. 

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... 

Sanchez, J. R, Domagala, J. M., Heifetz, C. L., Priebe, S. R., Sesnie, J. A., Trehan, A. K. Quinolone antibacterial agents. Synthesis and structure—activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-l-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity. J. Med. Chem. 1992, 35, 1764-1773. 

Acylated arylglycyl side chains on penicillins and cephalosporins have proven to be an excellent source of antibiotics with zxAi-Pseudomonas activity. Figure 2 displays examples of acylated arylglycyl side chains that have been used for this purpose. 

Although a number of new penicillins have been evaluated clinically since 1972, all have about the same pharmacokinetic behavior. Most of these new penicillins are derivatives of ampicillin with broader microbiological spectra, especially with respect to anti-Pseudomonas activity (Section 1,(1 ). 

Specific bacteriostatic activity against Escherichia coli (681, 896, 899), Staphylococcus aureus (681, 896), Cocci (900), Shigella dysenteriae (681), Salmonella ryphi (681), Proteus vulgaris (681), Pseudomonas aeruginosa (681), Streptococcus (889, 901, 902) and Pneumococcus (901-904). 

Pseudomonads also have the abiUty for xenobiotic metaboHsm and are capable of carrying out diverse sets of chemical reactions. Pseudomonas species is used ia the commercial productioa of acrylamide (qv) (18). Several operoas iavolved ia the metaboHsm of xeaobiotic compouads have beea studied. Use of Pseudomonads for the clean up of the environment and for the production of novel chemical iatermediates is likely to be an area of active research ia the 1990s. 

The sulfated compounds MM 13902 (3, n = (5) and MM 17880 (4) are also broad-spectmm agents, but not as potent as thienamycia and all lack any significant activity against Pseudomonas (73). Many carbapenems are excellent inhibitors of isolated P-lactamases, particularly the olivanic acid sulfoxide MM 4550 (3, n = 1) (3). The possible mechanism of action of the carbapenems as inhibitors of P-lactamases has been discussed in some detail (74). Other carbapenems such as PS-5 (5) (75), the carpetimycins (76), asparenomycins (77), and pluracidomycins (8) are all highly active as antibiotics or P-lactamase inhibitors. The parent nucleus itself (1, X = CH2) is intrinsically active, but chemically unstable (9). 

Continued efforts to improve the activity of the monobactams against nonfermenting gram-negative rods such as Pseudomonas aeruginosa led to the discovery of SQ 83,360 [104393-00-2] (58), C22H24N q0 2 2 3-hydroxy-4-pyridone containing monocarbam. The enhanced activity of SQ 83,360 is... 

Sudol uses fractions of coal tar rich in xylenols and ethylphenols. It is much more active and less corrosive than lysol, and remains more active in the presence of organic matter. The phenol coefficients of sudol against Mycobacterium tuberculosis, Staphylococcus aureus, and Pseudomonas aeruginosa are 6.3, 6, and 4, respectively. It also is slowly sporicidal (97). 

Whereas these preparations do not possess the high bacteriostatic activity of quaternary ammonium germicides, they have the alternate advantage of being rapidly functional in acid solution. In comparative experiments of several different disinfectants, the acid—anionic killed bacteria at lower concentration than five other disinfectants. Only sodium hypochlorite and an iodine product were effective at higher dilution than the acid—anionic. By the AO AC use dilution test, the acid—anionic killed Pseudomonas aeruginosa at 225 ppm. Salmonella choleraesuis at 175 ppm, and Staphylococcus aureus at 325 ppm (172). 

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocycUc lactones and liuear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,(D-diacids with a,(D-dialcohols catalyzed by Candida glindracea or Pseudomonas sp. Upases leads to macrocycUc lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predorninates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum Upase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-meth5ladipate and 1,6-hexanediol (92). 

These compounds showed a remarkable activity toward Gram-positive (e.g.. Bacillus cereus, Staphylococcus aureus, Sarcina luted) and Gram-negative bacteria (e.g.. Pseudomonas sp.) the activity was somewhat lower in the styryl derivatives (82MI2). 

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