title: Comparison of Short Versus Prolonged Infusion of Standard Dose of Meropenem Against Carbapenemase-Producing Klebsiella pneumoniae Isolates in Different Patient Groups: A Pharmacokinetic-Pharmacodynamic Approach.
abstract: Dose optimization is required to increase carbapenem's efficacy against carbapenemase-producing isolates. Four clinical Klebsiella pneumoniae isolates were used: one susceptible to meropenem with minimum inhibitory concentration (MIC) 0.031 mg/L and 3 verona integron-borne metallo bete-lactamase-1-producing isolates with MICs 8, 16, and 128 mg/L. The human pharmacokinetics of short (0.5-h) and prolonged (3-h) infusion regimens of 1 g meropenem every 8 h were simulated in an in vitro pharmacokinetic-pharmacodynamic model. Time-kill curves were constructed for each isolate and dosing regimen, and the %T > MIC associated with maximal bactericidal activity was estimated. The percentage of pharmacodynamic target attainment for isolates with different MICs was calculated for 350 ICU, surgical, and internal medicine patients. The isolates with MIC ≤8 mg/L were killed with both dosing regimens. The %T > MIC corresponding to maximal bactericidal activity was ∼40%. The percentages of target attainment were >90%, 61%-83%, 23%-33%, and <3% with the short infusion regimen and >90%, 98%-99%, 55%-79%, and <5% with the prolonged infusion regimen for isolates with MIC ≤2, 4, 8, and ≥16 mg/L, respectively. The lowest target attainment rates were observed for the ICU patients and the highest for internal medicine patients. The prolonged infusion regimen was more effective than the short infusion regimen against isolates with MIC 4-8 mg/L.
authors.affiliation: Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462, Athens, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Vourli
authors.affiliation: Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462, Athens, Greece.
authors.forename: Marilena
authors.initials: M
authors.lastname: Tsala
authors.affiliation: Laboratory of Bacteriology, Hellenic Pasteur Institute, 11521, Athens, Greece.
authors.forename: Stathis
authors.initials: S
authors.lastname: Kotsakis
authors.affiliation: First Department of Propaedeutic Medicine, University of Athens, 11527, Athens, Greece.
authors.forename: George L
authors.initials: GL
authors.lastname: Daikos
authors.affiliation: Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Tzouvelekis
authors.affiliation: Laboratory of Bacteriology, Hellenic Pasteur Institute, 11521, Athens, Greece.
authors.forename: Vivi
authors.initials: V
authors.lastname: Miriagou
authors.affiliation: Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462, Athens, Greece.
authors.forename: Loukia
authors.initials: L
authors.lastname: Zerva
authors.affiliation: Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462, Athens, Greece; Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, 3015CE Rotterdam, The Netherlands. Electronic address: jmeletiadis@med.uoa.gr.
authors.forename: Joseph
authors.initials: J
authors.lastname: Meletiadis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004867:Equipment Design; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D008954:Models, Biological; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: Klebsiella pneumoniae; VIM; meropenem; metallo-beta-lactamases; prolonged infusion