Objectives: Ceftazidime-avibactam (CAZ-AVI)-based treatments have been associated with emergence of resistance in KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates following antimicrobial exposure. Herein, we evaluated the CAZ-AVI-resistance development in KPC-Kp isolated from patients treated with CAZ-AVI-based therapy. Methods: We enrolled adult patients treated with CAZ-AVI-based regimens between January 2020 and January 2021. Carbapenemase-producing isolates collected from clinical samples and rectal swabs were evaluated for CAZ-AVI-resistance development following antimicrobial exposure. KPC-Kp developing CAZ-AVI-resistance and parental susceptible strains were genomically characterized. Whole genome sequencing was performed by using Illumina iSeq100 platform and genomes were analyzed for antimicrobial resistance genes, plasmid and porins sequences. Results: We enrolled 90 patients treated with CAZ-AVI-based therapy and 62.2% (56/90) of them were colonized by KPC-producers prior CAZ-AVI-based treatment and 6.6% acquired colonization during therapy. 6 (6,6%) patients developed infections due to resistant KPC-Kp following CAZ-AVI exposure and 3 (3.3%) of them developed CAZ-AVI-resistance in rectum. Development of resistance among KPC in rectum occurred after 32 (IQR 9-35) days of therapy and after 30 (IQR 22-40) days in clinical specimens. Genetic analysis demonstrated that development of CAZ-AVI-resistance was associated with mutated blaKPC-3 (blaKPC-31, blaKPC-53, blaKPC-89, blaKPC-130) and phylogenetic analysis demonstrated a close genomic relationship between KCP-Kp collected from rectum and clinical samples of the same patient. Conclusions: Antimicrobial exposure induce higher incidence of CAZ-AVI -resistance development in blood and respiratory tract than in rectum (6.7% vs 3.3%) of CAZ-AVI-treated patients and genome analysis showed that resistance was associated to mutated blaKPC-3 variants.
Colonization by ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae following therapy in critically ill patients / Gaibani, Paolo; Bovo, Federica; Bussini, Linda; Bartoletti, Michele; Lazzarotto, Tiziana; Viale, Pierluigi; Pea, Federico; Ambretti, Simone. - In: CLINICAL MICROBIOLOGY AND INFECTION. - ISSN 1198-743X. - ELETTRONICO. - 29:5(2023), pp. 654.e1-654.e4. [10.1016/j.cmi.2023.01.012]
Colonization by ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae following therapy in critically ill patients
Gaibani, Paolo
;Bovo, Federica;Bussini, Linda;Bartoletti, Michele;Lazzarotto, Tiziana;Viale, Pierluigi;Pea, Federico;Ambretti, Simone
2023
Abstract
Objectives: Ceftazidime-avibactam (CAZ-AVI)-based treatments have been associated with emergence of resistance in KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates following antimicrobial exposure. Herein, we evaluated the CAZ-AVI-resistance development in KPC-Kp isolated from patients treated with CAZ-AVI-based therapy. Methods: We enrolled adult patients treated with CAZ-AVI-based regimens between January 2020 and January 2021. Carbapenemase-producing isolates collected from clinical samples and rectal swabs were evaluated for CAZ-AVI-resistance development following antimicrobial exposure. KPC-Kp developing CAZ-AVI-resistance and parental susceptible strains were genomically characterized. Whole genome sequencing was performed by using Illumina iSeq100 platform and genomes were analyzed for antimicrobial resistance genes, plasmid and porins sequences. Results: We enrolled 90 patients treated with CAZ-AVI-based therapy and 62.2% (56/90) of them were colonized by KPC-producers prior CAZ-AVI-based treatment and 6.6% acquired colonization during therapy. 6 (6,6%) patients developed infections due to resistant KPC-Kp following CAZ-AVI exposure and 3 (3.3%) of them developed CAZ-AVI-resistance in rectum. Development of resistance among KPC in rectum occurred after 32 (IQR 9-35) days of therapy and after 30 (IQR 22-40) days in clinical specimens. Genetic analysis demonstrated that development of CAZ-AVI-resistance was associated with mutated blaKPC-3 (blaKPC-31, blaKPC-53, blaKPC-89, blaKPC-130) and phylogenetic analysis demonstrated a close genomic relationship between KCP-Kp collected from rectum and clinical samples of the same patient. Conclusions: Antimicrobial exposure induce higher incidence of CAZ-AVI -resistance development in blood and respiratory tract than in rectum (6.7% vs 3.3%) of CAZ-AVI-treated patients and genome analysis showed that resistance was associated to mutated blaKPC-3 variants.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
