O Pajot1, C Burdet2, C Couffignal2, L Massias3, L Armand-Lefevre4, A Foucrier5, D Da Silva5, S Lasocki6, C Laouénan2, H Mentec7, F Mentré2, M Wolff8. 1. Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France olivier.pajot@ch-argenteuil.fr. 2. AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France. 3. AP-HP, Bichat Hospital, Pharmacy Department, Paris F-75018, France. 4. IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Bichat Hospital, Bacteriology Department, F-75018 Paris, France. 5. AP-HP, Bichat Hospital, Intensive Care Unit, F-75018 Paris, France. 6. AP-HP, Bichat Hospital, Surgical Intensive Care Unit, F-75018 Paris, France. 7. Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France. 8. AP-HP, Bichat Hospital, Intensive Care Unit, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
Abstract
OBJECTIVES: Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. PATIENTS AND METHODS: Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. RESULTS: Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). CONCLUSIONS: In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.
OBJECTIVES: Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. PATIENTS AND METHODS: Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. RESULTS: Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). CONCLUSIONS: In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.
Authors: J G Coen van Hasselt; Matthew L Rizk; Mallika Lala; Cynthia Chavez-Eng; Sandra A G Visser; Thomas Kerbusch; Meindert Danhof; Gauri Rao; Piet H van der Graaf Journal: Br J Clin Pharmacol Date: 2016-04-01 Impact factor: 4.335
Authors: Jean-François Timsit; Matteo Bassetti; Olaf Cremer; George Daikos; Jan de Waele; Andre Kallil; Eric Kipnis; Marin Kollef; Kevin Laupland; Jose-Artur Paiva; Jesús Rodríguez-Baño; Étienne Ruppé; Jorge Salluh; Fabio Silvio Taccone; Emmanuel Weiss; François Barbier Journal: Intensive Care Med Date: 2019-01-18 Impact factor: 17.440
Authors: Nicolas Allou; Astrid Bouteau; Jérôme Allyn; Aurélie Snauwaert; Dorothée Valance; Julien Jabot; Bruno Bouchet; Richard Galliot; Laure Corradi; Philippe Montravers; Pascal Augustin Journal: Ann Intensive Care Date: 2016-11-02 Impact factor: 6.925