F1-2037. Effect of pH on the In Vitro Activity of Finafloxacin against Gram-negative and Gram-positive Bacteria
Session: Poster Session: New Topoisomerase Inhibitors
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: Finafloxacin (FIN) is a novel 8-cyano-fluoroquinolone, that exhibits an in vitro spectrum of activity similar to that of ciprofloxacin (CIP). The present study was performed to study the effect of pH on the in vitro activity of FIN in comparison to CIP against selected strains of various aerobic Gram- and Gram+ bacterial species known to cause genito-urinary tract infections. Methods: The susceptibilities of 100 clinical isolates to FIN and CIP were tested at pH 5, 6, 7.3, and 8. There were 22 Escherichia coli (ECO), 13 Klebsiella pneumoniae (KPN), 11 Morganella morganii (MOM), 10 Proteus mirabilis (PRM), 10 Pseudomonas aeruginosa (PSA), 12 Staphylococcus aureus (SAU), 11 Staphylococcus saprophyticus (SSA), and 11 Streptococcus agalactiae (SAG). Of these, 66 were sensitive and 34 exhibited reduced susceptibilities to CIP. MICs were determined using the CLSI broth microdilution method. Results: Results are presented in Tables 1 and 2. Conclusions: Overall, FIN demonstrated superior activity to CIP under acidic conditions against isolates of all species including resistant strains. Furthermore, FIN showed comparable activity to CIP against Gram+ cocci at pH 7.3. Hence, FIN appears to be a promising new antimicrobial agent for the treatment of infections at acidic sites.
Table 1: MIC-50/90s (mg/L) of FIN and CIP for Gram- bacteria
FIN - pH 5/6/7.3/8CIP - pH 5/6/7.3/8
SpeciesMIC-50MIC-90MIC-50MIC-90
ECO
(n=22)
0.063/0.031/
0.25/0.5
16/16/
≥32/≥32
0.5/0.25/
0.031/≤0.008
≥16/≥16/
≥16/≥16
KPN
(n=13)
0.5/0.5/
2/2
8/8/
≥32/≥32
≥16/8/
2/0.5
≥16/≥16/
≥16/8
MOM
(n=11)
0.25/0.25/
1/2
4/4/
16/16
1/0.063/
≤0.008/≤0.008
≥16/≥16/
4/2
PRM
(n=10)
0.125/0.25/
1/1
4/4/
16/16
1/0.125/
0.016/0.016
≥16/8/
2/1
PSA
(n=10)
2/2/
8/16
≥32/≥32/
≥32/≥32
2/1/
0.5/0.5
≥16/≥16/
≥16/≥16

Table 2: MIC-50/90s (mg/L) of FIN and CIP for Gram+ bacteria
FIN - pH 5/6/7.3/8CIP - pH 5/6/7.3/8
SpeciesMIC-50MIC-90MIC-50MIC-90
SAU
(n=12)
0.125/0.063/
0.25/0.5
8/4/
8/>32
2/1/
0.5/0.5
>16/>16/
>16/>16
SSA
(n=11)
0.063/0.125/
0.5/1
0.125/0.125/
0.5/1
0.5/0.5/
0.25/0.5
1/0.5/
0.5/0.5
SAG
(n=11)
0.25/0.25/
1/2
0.5/0.5/
2/4
2/1/
1/1
4/2/
2/2
Barbara Körber-Irrgang, PhD, Antiinfectives Intelligence GmbH, Harald Labischinski, PhD, Combinature Biopharm AG, Berlin, Germany, Michael Kresken, PhD, Antiinfectives Intelligence GmbH, Rheinbach, Germany, Will Stubbings, PhD, MerLion Pharmaceuticals Pte Ltd and  M. Kresken,
Merlion Role(s): Research Contractor, Received: Research Grant.
Wyeth Role(s): Research Contractor, Received: Research Grant.
Novartis Role(s): Research Contractor, Speaker's Bureau, Received: Research Grant, Speaker Honorarium.
Johnson & Johnson Role(s): Research Contractor, Received: Research Grant.


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