In vitro activity of CP-99,219, a novel 7-(3-azabicyclo[3.1.0]hexyl) naphthyridone antimicrobial.
The in vitro activity of CP-99,219 was compared with that of ciprofloxacin and sparfloxacin against 814 clinical bacterial isolates using a microdilution method with brain-heart infusion broth. CP-99,219 was the most potent agent tested against methicillin-resistant, ciprofloxacin-susceptible staphylocci (minimum inhibitory concentration [MIC]90 < or = 0.25 microgram/ml). CP-99,219 was 32-fold and fourfold more potent than ciprofloxacin and sparfloxacin, respectively, against Streptococcus pneumoniae, including strains resistant to penicillin G and erythromycin (MIC90 < or = 0.25 microgram/ml). CP-99,219 was also the most potent agent tested against S. pyogenes and Enterococcus faecalis (MIC90 < or = 0.5 microgram/ml). The activity of CP-99,219 against Enterobacteriaceae was comparable to that of sparfloxacin, with 90% of Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Citrobacter freundii, C. diversus, Helicobacter pylori, and K. oxytoca being inhibited by < or = 0.5 microgram/ml. Serratia marcescens, Morganella morganii, and Pseudomonas aeruginosa were less susceptible, with MIC90 values to CP-99,219 of 4, 2, and 2 micrograms/ml, respectively. The MIC90 for Bacteroides fragilis was 0.39 microgram/ml for CP-99,219 compared with 12.5 micrograms/ml for ciprofloxacin. CP-99,219 was highly bactericidal at 1 x to 4 x MIC against both Gram-positive and Gram-negative organisms; its activity was similar in nutrient, trypticase soy, and cation-supplemented Mueller-Hinton broths. The spectrum and potency observed with CP-99,219 warrant further testing with this novel quinolone.
Gootz
T D
TD
Central Research Division, Pfizer Incorporated, Groton, Connecticut.
Brighty
K E
KE
Anderson
M R
MR
Schmieder
B J
BJ
Haskell
S L
SL
Sutcliffe
J A
JA
Castaldi
M J
MJ
McGuirk
P R
PR
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II; D004269:DNA, Bacterial / Q000187:drug effects; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; D002939:Ciprofloxacin; C080163:trovafloxacin; D004250:DNA Topoisomerases, Type II; C061363:sparfloxacin