A new 1,8-naphthyridine quinolone antimicrobial, PD131628, was found to be as, or more active than ciprofloxacin or ofloxacin against Escherichia coli and considerably more active than the two 4-quinolone agents against staphylococci in terms of both MIC and OBC (the optimum bactericidal concentration, at which the rate of kill is greatest). In common with ciprofloxacin and ofloxacin, the rate of kill of PD131628 against Enterococcus faecalis was considerably slower than against the other three species tested. Bacterial protein synthesis, RNA synthesis and cell division were not required for the bactericidal activity of PD131628 against E. coli or the staphylococci, although the lethality of PD131628 in the absence of these activities was reduced.
SmithJ. T.,
LewinC. S. Chemistry and mechanisms of action of the quinolone antibacterials. In
AndrioleV. T.
(ed) The quinolones London: Academic Press; 198823–82
LewinC. S.,
MorrisseyI.,
SmithJ. T. The mode of action of quinolones–the paradox in activity of low and high concentrations and activity in the anaerobic environment. Eur J Clin Microbiol Infect Dis1991; 10:240–248
SanchezJ. P.,
DomagalaJ. M.,
HagenS. E. Quinolone antibacterial agents. Synthesis and structure-activity relationships of 8-substituted quinolone-3-carboxylic acids and 1, 8 naphthyridine-3-carboxylic acids. J Med Chem1988; 31:983–991
CohenM. A.,
HubandM. D.,
MaillouxG. B. In vitro antibacterial activities of PD 131628, a new 1-8-naphthyr-idine anti-infective agent. Antimicrob Agents Chemother1991; 35:141–146
FuchsP. C.,
BarryA. L.,
PfallerM. A.,
AllenS. D.,
GerlachE. H. Multicentre evaluation of the in-vitro activities of three new quinolones, sparfloxacin, CI-960 and PD 131, 628, compared with the activity of ciprofloxacin against 5252 clinical bacterial isolates. Antimicrob Agents Chemother1991; 35:764–766
PiddockL. J. V.,
WaltersR. N.,
DiverJ. M. Correlation of quinolone MIC and inhibition of DNA, RNA, and protein synthesis and induction of the SOS response in Escherichia coli. Antimicrob Agents Chemother1990; 34:2331–2336
SmithS. M.,
EngR. H. K.,
BaisP.,
Fan-HavardP. Tecson-Tumang,. F., Epidemiology of ciprofloxacin resistance among patients with methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother1990; 26:567–572