Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli.
J Antimicrob Chemother
; 71(7): 1899-904, 2016 07.
Article
in En
| MEDLINE
| ID: mdl-27029848
ABSTRACT
OBJECTIVES:
Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli.METHODS:
Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal fluid (PF) and spleen were collected; 24 h survival and sterility rates were assessed.RESULTS:
Temocillin MICs were 8, 16, 32, and 256 mg/L for the susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains, respectively. In mice treated with temocillin, significant bacterial reduction was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and KPC-3-producing strains (Pâ<â0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (Pâ<â0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (Pâ<â0.001), while survival rates were 97%, 97%, 57%, 0% (Pâ<â0.001) for mice infected with the susceptible strain and KPC-2-, KPC-3- and OXA-48-producing strains, respectively.CONCLUSIONS:
In a lethal-infection model with bacteraemia from intra-abdominal origin, temocillin retained significant activity in PF, blood and spleen and prevented death in mice by effectively working against KPC-producing E. coli with temocillin MICs ≤16 mg/L.
Full text:
1
Collection:
01-internacional
Health context:
2_ODS3
/
3_ND
Database:
MEDLINE
Main subject:
Penicillins
/
Bacterial Proteins
/
Beta-Lactamases
/
Bacteremia
/
Escherichia coli
/
Escherichia coli Infections
/
Intraabdominal Infections
/
Anti-Bacterial Agents
Limits:
Animals
Language:
En
Journal:
J Antimicrob Chemother
Year:
2016
Document type:
Article