Efficacy of doripenem in the treatment of Pseudomonas aeruginosa experimental pneumonia versus imipenem and meropenem.
OBJECTIVE
The aim of this study was to compare doripenem with imipenem and meropenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia and then to compare different doripenem doses and methods of intravenous administration.


METHODS
Using a rabbit experimental model of pneumonia, efficacy was assessed following 2 days of treatment by colony counts of different tissues (lung, spleen and blood culture).


RESULTS
Mean pulmonary bacterial loads were 3.17 ± 0.53, 3.42 ± 0.61 and 2.75 ± 0.59 log(10) cfu/g for imipenem, doripenem (0.5 g three times daily) and meropenem, respectively, compared with 7.57 ± 0.99 cfu/g for control animals. At a higher dose (1 g three times daily), doripenem showed significantly better efficacy (2.70 ± 0.65 log(10) cfu/g) than the standard regimen of doripenem. Sterilization of spleen cultures was achieved with standard regimens of imipenem (1 g three times daily) and a higher dose of doripenem.


CONCLUSIONS
In this model of P. aeruginosa pneumonia, doripenem had an efficacy equivalent to that of meropenem and imipenem at a high dose of 1 g three times a day and lower efficacy at a standard dose (0.5 g three times daily) than the other two agents in terms of bacteria cultivated from spleens. Doripenem is a new drug that offers new therapeutic options, especially for difficult-to-treat infections such as pneumonia due to non-fermenting Gram-negative bacteria.
Bretonnière
Cédric
C
Université de Nantes, Faculté de Médecine, UPRES EA 3826, 1 rue Gaston Veil, 44000 Nantes, France. cedric.bretonniere@chu-nantes.fr
Jacqueline
Cédric
C
Caillon
Jocelyne
J
Guitton
Christophe
C
Le Mabecque
Virginie
V
Miégeville
Anne Françoise
AF
Villers
Daniel
D
Potel
Gilles
G
Boutoille
David
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D058491:Bacterial Load; D001769:Blood / Q000382:microbiology; D015780:Carbapenems / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D000077726:Doripenem; D005260:Female; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008168:Lung / Q000382:microbiology; D000077731:Meropenem; D010949:Plasma / Q000737:chemistry; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011817:Rabbits; D013154:Spleen / Q000382:microbiology; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D015378:Imipenem; D000077726:Doripenem; D000077731:Meropenem