K Alexandre1, F Chau2, F Guérin3, L Massias4, A Lefort5, V Cattoir3, B Fantin6. 1. INSERM, IAME, UMR 1137, F-75018 Paris, France. 2. INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France. 3. Université de Caen Basse-Normandie, EA 4655 (Équipe "Antibio-résistance"), F-14032 Caen, France CHU de Caen, Service de Microbiologie, F-14033 Caen, France. 4. INSERM, IAME, UMR 1137, F-75018 Paris, France AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Laboratoire de Pharmacologie, F-75018 Paris, France. 5. INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Service de Médecine Interne, F-92210 Clichy, France. 6. INSERM, IAME, UMR 1137, F-75018 Paris, France Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Groupe Hospitalier Paris Nord Val de Seine, Service de Médecine Interne, F-92210 Clichy, France bruno.fantin@bjn.aphp.fr.
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 (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) 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.
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 (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) 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.
Authors: Elise T Zeiser; Scott A Becka; Melissa D Barnes; Magdalena A Taracila; John J LiPuma; Krisztina M Papp-Wallace Journal: Antimicrob Agents Chemother Date: 2019-03-27 Impact factor: 5.191
Authors: F Scasso; G Ferrari; G C DE Vincentiis; A Arosio; S Bottero; M Carretti; A Ciardo; S Cocuzza; A Colombo; B Conti; A Cordone; M DE Ciccio; E Delehaye; L Della Vecchia; I DE Macina; C Dentone; P DI Mauro; R Dorati; R Fazio; A Ferrari; G Ferrea; S Giannantonio; I Genta; M Giuliani; D Lucidi; L Maiolino; G Marini; P Marsella; D Meucci; T Modena; B Montemurri; A Odone; S Palma; M L Panatta; M Piemonte; P Pisani; S Pisani; L Prioglio; A Scorpecci; L Scotto DI Santillo; A Serra; C Signorelli; E Sitzia; M L Tropiano; M Trozzi; F M Tucci; L Vezzosi; B Viaggi Journal: Acta Otorhinolaryngol Ital Date: 2018-04 Impact factor: 2.124
Authors: Tommaso Lupia; Ilaria De Benedetto; Giacomo Stroffolini; Stefano Di Bella; Simone Mornese Pinna; Verena Zerbato; Barbara Rizzello; Roberta Bosio; Nour Shbaklo; Silvia Corcione; Francesco Giuseppe De Rosa Journal: Antibiotics (Basel) Date: 2022-04-07