title: Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.
abstract: OBJECTIVE
  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.
  
  
  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: Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France olivier.pajot@ch-argenteuil.fr.
authors: O
authors: O
authors: Pajot
authors: AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
authors: C
authors: C
authors: Burdet
authors: AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
authors: C
authors: C
authors: Couffignal
authors: AP-HP, Bichat Hospital, Pharmacy Department, Paris F-75018, France.
authors: L
authors: L
authors: Massias
authors: IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France AP-HP, Bichat Hospital, Bacteriology Department, F-75018 Paris, France.
authors: L
authors: L
authors: Armand-Lefevre
authors: AP-HP, Bichat Hospital, Intensive Care Unit, F-75018 Paris, France.
authors: A
authors: A
authors: Foucrier
authors: AP-HP, Bichat Hospital, Intensive Care Unit, F-75018 Paris, France.
authors: D
authors: D
authors: Da Silva
authors: AP-HP, Bichat Hospital, Surgical Intensive Care Unit, F-75018 Paris, France.
authors: S
authors: S
authors: Lasocki
authors: AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
authors: C
authors: C
authors: Laouénan
authors: Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France.
authors: H
authors: H
authors: Mentec
authors: AP-HP, Bichat Hospital, Biostatistics Department, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
authors: F
authors: F
authors: Mentré
authors: AP-HP, Bichat Hospital, Intensive Care Unit, F-75018 Paris, France IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
authors: M
authors: M
authors: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D000583:Amikacin
keywords: ICUs; PD; PK; VAP; antibiotics