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In vitro and in vivo activity of SB006, a novel branched antimicrobial peptide selectively active against Gram-negative bacteria.

Abstract number: P560

Fabiole Nicoletto S., Baster I., Pirri G., Giuliani A.

Objectives: The aim of this study was to investigate the in vitro and in vivo activity of SB006 against selected MDR Gram-negative clinical isolates.

Methods: MICs and MBCs were determined in MHB by the broth microdilution methodology, according to CLSI procedure. MIC was defined as the lowest drug concentration causing complete suppression of visible bacterial or fungal growth. MBC was defined as the antibiotic concentration that induced at least a 3 log reduction of the initial bacterial inoculum.

The in vivo activity of SB006 has been evaluated using a neutropenic mouse model of infection. Mice were infected intraperitonally using a 0.2-ml volume of a high dose inoculum (3xLD50) of Pseudomonas aeruginosa (clinical isolate). Several single dosages of SB006 were administered at 1 hour post-challenge. The total dose required for survival of 50% of mice at 72 h (ED50) was determined.

Results: The in vitro activity of SB006 and reference compounds against an expanded panel of clinical bacteria recently collected has been determined; all tested strains show resistance to several currently used antibacterial agents. SB006 was active against Gram-negative bacteria; the MICs of SB006 against Acinetobacter spp. (2 strains), Enterobacter spp. (4 strains), Escherichia coli (12 strains), Klebsiella pneumoniae (6 strains), Pseudomonas aeruginosa (16 strains), Salmonella enteritidis (1 strain), and Stenotrophomonas maltophilia (1 strain) were between 4 and 32 mg/L, while colistin showed MICs ranging between 0.25 and 8 mg/L. The MIC and MBC values of SB006 ranged between 8 and 32 mg/L, while those of colistin ranged between 0.25 and 4 mg/L. The MBC/MIC ratio was always 1 for SB006 and colistin. Moreover, in vivo studies showed that SB006 was active in an experimental mouse model of infection against a clinical isolate of P. aeruginosa.

Conclusion: SB006 showed good activity against different Gram-negative bacteria isolates with a potency and spectrum of antimicrobial activity comparable to those of colistin and showed to be bactericidal. As colistin, SB006 seems to selectively perturb the bacterial membrane: this mechanism of action is expected to circumvent the problem of resistance. These features make the antimicrobial branched peptide SB006 a promising template for the development of new antibacterial drugs.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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