Peptides, Pseudomonas aeruginosa, polysaccharides …

Direct hydroxylation in the biosynthesis of hydroxy fatty acid in lipid a of Pseudomonas ovalis.

to the core of Pseudomonas aeruginosa lipopolysaccharide ..

. Nordstrom K, Sykes RB. Induction kinetics of beta-lactamase biosynthesis in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1974;6:734-40. []

Molecular characterization of the Pseudomonas aeruginosa ..

. Meyer RD, Liu S. In vitro synergy with ciprofloxacin and selected beta-lactam agents and aminoglycosides against multi-drug resistant Pseudomonas aeruginosa. Diag Microbiol Infect Dis 1988;11:151-7. []

. Johnson DE, Thompson B, Calia FM. Comparative activities of piperacillin, ceftazidime, and amikacin, alone and in all possible combinations, against experimental Pseudomonas aeruginosa infections in neutropenic rats. Antimicrob Agents Chemother 1985;27:735-9. []


Genetics of O-Antigen Biosynthesis in Pseudomonas aeruginosa

Production of stably derepressed mutants is a concern during therapy with beta-lactam agents that are weak inducers of beta-lactamase production, such as extended-spectrum and third generation cephalosporins. These mutants produce increased quantities of beta-lactamases (hyperproduction) despite removal of the inducible antibiotic. This is most likely to occur with the chromosomally- mediated Bush Group I enzymes for which the preferred substrate is cephalosporins. Rapid emergence of resistance can occur in this circumstance, particularly in infections caused by Pseudomonas aeruginosa or Enterobacter cloacae (, ), due to selection of the mutants after the more susceptible organisms are killed during treatment. In this instance, the mutants can proliferate and can become the predominant infecting organism. The only effective beta-lactam would be a carbapenem, as Class I beta-lactamases can hydrolyze all other types of beta-lactams agents.

Genetics of O-Antigen Biosynthesis inPseudomonas ..

These findings were also supported by studies of Klebsiella pneumoniae pneumonia in rats (), in Klebsiella pneumoniae lung and thigh infections in neutropenic mice (),Pseudomonas aeruginosa infection in neutropenic rats (), Staphylococcus aureus in rats recovering from hemorrhagic shock (), and in Enterococcal endocarditis (). Additional data () demonstrated that for gram-negative infections, a Time > MIC of 100% of the dosing interval was most closely associated with outcome, whereas for gram-positive organisms, a Time > MIC of approximately 50% was all that was needed to be effective. For gram-negative infections, continuous infusion of the penicillin may be most appropriate to maintain serum concentrations above the MIC for the entire dosing interval.

core of Pseudomonas aeruginosa lipopolysaccharide ..

Data from animal models supports Time > MIC as the primary determinant of efficacy for beta-lactam agents (, ). In a neutropenic mouse model infected with Pseudomonas aeruginosa, the impact of different dosing intervals of ticarcillin was studied. Equivalent daily doses were administered every hour or every 3 hours. The mice that received drug every hour (a lower dose administered more frequently) had a greater antibacterial effect ().

Pseudomonas aeruginosa - essential for growth and survival ..

Other organisms for which synergy seems to be important with regard to the penicillins includes Pseudomonas aeruginosa. Again, a combination of an antipseudomonal penicillin plus an aminoglycoside may result in increased bactericidal activity. This has been demonstrated in vitro and animal studies (, , ), but there is limited data in humans to support these findings. In vitro synergy between the extended spectrum penicillins (azlocillin, mezlocillin) and ciprofloxacin has also been demonstrated (, , ). Immunocompromised patients are a population who may benefit the most from antipseudomonal synergy. There is data to suggest that synergistic combination therapy results in increased survival versus non-synergistic combinations of drugs (, , ).