title: A pharmacodynamic strategy to optimize empirical antibiotic therapy for gram-negative bacteria in a Brazilian Intensive Care Unit.
abstract: Pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Gram-negative bacteria isolated in a Brazilian ICU. Due to high resistance rates, standard regimens of cefepime, ciprofloxacin, meropenem, and piperacillin/tazobactam were not able to attain significant bactericidal CFR. Prolonged infusion of meropenem achieved 88% CFR, making it a possible empirical regimen in this ICU until susceptibilities become available. Still, even through administration of high dose prolonged infusions, 12.0% of simulated subjects did not achieve bactericidal exposure, suggesting that combination therapy would frequently be required in this setting. In conclusion, we recommend that in the presence of identified resistance problems among Gram-negative bacteria in a unit or hospital, MIC testing of formulary agents should be conducted along with pharmacodynamic simulation to assist in choosing an optimal antibiotic and dosage regimen for empirical use of severe infections until cultures and susceptibilities become available.
authors.affiliation: Microbiology Section, Fleury Institute, Avenida General Waldomiro de Lima 508, 04344-070 Jabaquara, São Paulo, SP, Brazil. carlos.kiffer@fleury.com.br
authors.forename: Carlos R V
authors.initials: CR
authors.lastname: Kiffer
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.forename: Caio M F
authors.initials: CM
authors.lastname: Mendes
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Oplustil
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Amarante
authors.forename: Maria L
authors.initials: ML
authors.lastname: Biancalana
authors.forename: Nelson
authors.initials: N
authors.lastname: Xavier
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001938:Brazil; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method
chemical_list: D000900:Anti-Bacterial Agents