Multiple Novel Ceftazidime-Avibactam-Resistant Variants of bla KPC-2 -Positive Klebsiella pneumoniae in Two Patients

• DOI: 10.1128/spectrum.01714-21
• Publication Date: 2022-05-19T13:00:24Z
• Authors: Qingyu Shi; Renru Han; Yan Guo; Yang Yang; Shi Wu; Li Ding; Rong Zhang; Dandan Yin; Fupin Hu
• Keywords: Ceftazidime/avibactam

As the first-line antimicrobial agent for infection caused by carbapenem-resistant Enterobacterales, ceftazidime-avibactam develops drug resistance during its ever-growing clinical use. In this study, we report multiple novel variants in blaKPC-2-positive Klebsiella pneumoniae from two separate patients their exposure to ceftazidime-avibactam. For one patient, blaKPC-2 gene carried K. mutated into blaKPC-35, blaKPC-78, and blaKPC-33 over same period, while that other patient blaKPC-79 further evolved blaKPC-76 enhance level, among which were reported first time. contrast with blaKPC-2, emergent mutations within Ω-loop conferred high-level a sharp reduction of carbapenemase activity. These blaKPC-positive isolated sputum (both patients) cerebrospinal fluid (patient 2) belonged ST11 ST859, respectively. All strains located blaKPC alleles on IncFII/IncR plasmids, except an IncFII plasmid. Such appeared after 9 18 days usage, but lack feasible detection method often led assumption sensitivity resulting incorrect usage. Subsequent substitution carbapenems also failed, because blaKPC-2-containing dominated again. Ultimately, treatment failed even therapeutic regimen combined carbapenems, inadequate concentration avibactam sites decreased increased expression point mutation ompK35 ompK36. KPC conferring are constantly emerging worldwide, quick efficient laboratory surveillance urgently needed control. IMPORTANCE Carbapenem-resistant was classified as most urgent threat World Health Organization, is critical public health concern due high mortality rate. Recently, rapid has occurred anti-infective therapy, posed unexpected challenge both diagnostic practice.