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Antimicrob Agents Chemother. Activity of fosfomycin, tigecycline, colistin and gentamicin against extended spectrum beta-lactamase (ESBL)-producing E. coli in a foreign-body infection model
[Source: Antimicrob Agents Chemother., full page: (LINK). Abstract, edited.]
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Activity of fosfomycin, tigecycline, colistin and gentamicin against extended spectrum beta-lactamase (ESBL)-producing E. coli in a foreign-body infection model
St?phane Corvec 1,2, Ulrika Furustrand Tafin 1, Bertrand Betrisey 1, Olivier Borens 3 and Andrej Trampuz 1,4,#
Author Affiliations: <SUP>1</SUP>Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland <SUP>2</SUP>Service de Bact?riologie-Hygi?ne, CHU de Nantes, Institut de Biologie, Nantes Cedex, France <SUP>3</SUP>Department of Orthopedic Surgery and Traumatology, Lausanne University Hospital, Lausanne, Switzerland <SUP>4</SUP>Center for Musculoskeletal Surgery, Charit?, University Medicine, Free and Humboldt-University of Berlin, Berlin, Germany
ABSTRACT
Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolones-resistant gram-negative bacilli. We compared the activity of fosfomycin, tigecycline, colistin and gentamicin (alone or in combination) against a CTX-M15-producing E. coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC, minimal bactericidal concentration in logarithmic phase (MBC<SUB>log</SUB>) and stationary phase (MBC<SUB>stat</SUB>) were 0.12, 0.12 and 8 μg/ml for fosfomycin; 0.25, 32, 32 μg/ml for tigecycline; 0.25, 0.5, 2 μg/ml for colistin and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at MIC and no regrowth occurred. Synergistic activity was observed between fosfomycin and colistin in vitro with undetectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log<SUB>10</SUB> CFU/ml, whereas in combination with colistin, tigecycline or gentamicin the reduction was >6 log<SUB>10</SUB> CFU/ml. Fosfomycin was the only single agent, which was able to eradicate E. coli biofilms (cure rate 17% of cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (p<0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than fosfomycin alone (p <0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant gram-negative bacilli.
FOOTNOTES
#Correspondence: Andrej Trampuz, Center for Musculoskeletal Surgery, Charit?, University Medicine, Free and Humboldt-University of Berlin, Charit?platz 1, D-10117 Berlin, Germany, Phone: +41 79 128 1440, Fax: +49 30 4505 15900, E-mail: andrej.trampuz@gmail.com.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-St?phane Corvec 1,2, Ulrika Furustrand Tafin 1, Bertrand Betrisey 1, Olivier Borens 3 and Andrej Trampuz 1,4,#
Author Affiliations: <SUP>1</SUP>Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland <SUP>2</SUP>Service de Bact?riologie-Hygi?ne, CHU de Nantes, Institut de Biologie, Nantes Cedex, France <SUP>3</SUP>Department of Orthopedic Surgery and Traumatology, Lausanne University Hospital, Lausanne, Switzerland <SUP>4</SUP>Center for Musculoskeletal Surgery, Charit?, University Medicine, Free and Humboldt-University of Berlin, Berlin, Germany
ABSTRACT
Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolones-resistant gram-negative bacilli. We compared the activity of fosfomycin, tigecycline, colistin and gentamicin (alone or in combination) against a CTX-M15-producing E. coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC, minimal bactericidal concentration in logarithmic phase (MBC<SUB>log</SUB>) and stationary phase (MBC<SUB>stat</SUB>) were 0.12, 0.12 and 8 μg/ml for fosfomycin; 0.25, 32, 32 μg/ml for tigecycline; 0.25, 0.5, 2 μg/ml for colistin and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at MIC and no regrowth occurred. Synergistic activity was observed between fosfomycin and colistin in vitro with undetectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log<SUB>10</SUB> CFU/ml, whereas in combination with colistin, tigecycline or gentamicin the reduction was >6 log<SUB>10</SUB> CFU/ml. Fosfomycin was the only single agent, which was able to eradicate E. coli biofilms (cure rate 17% of cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (p<0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than fosfomycin alone (p <0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant gram-negative bacilli.
FOOTNOTES
#Correspondence: Andrej Trampuz, Center for Musculoskeletal Surgery, Charit?, University Medicine, Free and Humboldt-University of Berlin, Charit?platz 1, D-10117 Berlin, Germany, Phone: +41 79 128 1440, Fax: +49 30 4505 15900, E-mail: andrej.trampuz@gmail.com.
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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