title: Bactericidal and synergistic activity of double-carbapenem regimen for infections caused by carbapenemase-producing Klebsiella pneumoniae.
abstract: Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy. Electronic address: alessandra.oliva@uniroma1.it.
authors.forename: A
authors.initials: A
authors.lastname: Oliva
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Gizzi
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Mascellino
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cipolla
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Abramo
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: D'Agostino
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Trinchieri
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tierno
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Iannetta
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: C M
authors.initials: CM
authors.lastname: Mastroianni
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Vullo
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D000077727:Ertapenem; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013845:Thienamycins / Q000008:administration & dosage* / Q000494:pharmacology; D047090:beta-Lactams / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D047090:beta-Lactams; D000077731:Meropenem; D000077727:Ertapenem
keywords: Bactericidal activity; carbapenem-resistant Klebsiella pneumoniae; double-carbapenem regimen; sepsis; synergy; time-kill studies