Novel S-649266 Cephalosporin Potent Against Gram-Negative Bacteria



PHILADELPHIA, PA—S-649266, a novel catechol-substituted siderophore cephalosporin for injection, showed potent in vitro activity against a broad spectrum of Gram-negative bacteria, a study reported at IDWeek 2014.

S-649266, discovered by Shionogi & Co., Ltd., demonstrated potent antimicrobial activity against a variety of Gram-negative bacteria including strains not susceptible to ceftazidime, meropenem, levofloxacin or ciprofloxacin, reported Roger Echols, MD, Shionogi, Florham Park, NJ.

Tested isolates were collected from multiple sites in North America, Europe, Asia and other regions from 2000–2011. S-649266 activity was evaluated using MIC, measured by broth microdilution method according to Clinical and Laboratory Standard Institute, except that CAMHB was supplemented with 20µM of apo-transferrin (apo-T). For Acinetobacter baumannii, Iso-Sensitest Broth (ISB) supplemented with 20µM of apo-T was used to suppress the trailing effect.

MIC90 against Pseudomonas aeruginosa, Stenotrophomonas maltophilia and most of Enterobacteriaceae was ≤1µg/mL, and MIC90 against A. baumannii was 2µg/mL. In addition, S-649266 demonstrated in vitro antimicrobial activity against drug resistant clinical isolates, including carbapenemase producers (KPCs, NFM-1, VIMs) MIC90 4µg/mL, multi-drug resistant P. aeruginosa (MDRP) MIC90 2µg/mL, and A. baumannii (MDRA) MIC90 4µg/mL. Antimicrobial activity of S-649266 against anaerobes and aerobic Gram-positive bacteria was variable.

“S-649266 is a promising siderophore cephalosporin for treatment of Gram-negative bacterial infections including multidrug-resistant strains,” concluded Dr. Echols.

                            

Species

N

MIC90 (µg/mL)

S-649266

Ceftazidime

Meropenem

Levofloxacin

Cefepime

Pseudomonas aeruginosa

104

1

>32

>16

>8

32

Klebsiella pneumoniae

105

0.12

>32

0.12

>8

>32

Escherichia coli

106

1

2

≤0.06

>8

8

Stenotrophomonas maltophilia

108

0.5

>32

>16

8

>32

Serratia marcescens

103

≤0.06

1

2

2

1

Enterobacter aerogenes

100

0.5

>32

≤0.06

0.5

4

Enterobacter cloacae

103

1

>32

0.12

4

8

Citrobacter freundii

100

0.12

>32

≤0.06

8

8

Acinetobacter baumannii

102

2

>32

>16

>8

>32

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