Whole-Genome Sequencing and Molecular Analysis of Ceftazidime–Avibactam-Resistant KPC-Producing <i>Klebsiella pneumoniae</i> from Intestinal Colonization in Elderly Patients
Giulia Errico,
Maria Del Grosso,
Michela Pagnotta,
Manuela Marra,
Maria Carollo,
Marina Cerquetti,
Elena Fogato,
Elisabetta Cesana,
Flaminia Gentiloni Silverj,
Dorjan Zabzuni,
Angelo Rossini,
Annalisa Pantosti,
Marco Tinelli,
Monica Monaco,
Maria Giufrè
Affiliations
Giulia Errico
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Maria Del Grosso
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Michela Pagnotta
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Manuela Marra
Core Facilities Technical-Scientific Service (FAST), Istituto Superiore di Sanità, 00161 Rome, Italy
Maria Carollo
Core Facilities Technical-Scientific Service (FAST), Istituto Superiore di Sanità, 00161 Rome, Italy
Marina Cerquetti
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Elena Fogato
Laboratory of Clinical Microbiology, ASP ‘Golgi-Redaelli’, 20146 Milan, Italy
Elisabetta Cesana
IRCCS Istituto Auxologico Italiano, San Luca Hospital, 20149 Milan, Italy
Flaminia Gentiloni Silverj
Medical Direction, Fondazione IRCCS, Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
Dorjan Zabzuni
IRCCS Istituto Auxologico Italiano, San Luca Hospital, 20149 Milan, Italy
Angelo Rossini
IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
Annalisa Pantosti
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Marco Tinelli
IRCCS Istituto Auxologico Italiano, San Luca Hospital, 20149 Milan, Italy
Monica Monaco
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Maria Giufrè
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Ceftazidime–avibactam (CAZ-AVI) is an active antibiotic combination of a β-lactam–β-lactamase inhibitor against carbapenemase-producing Enterobacterales. Reports of resistance to CAZ-AVI other than metallo-β-lactamases have increased in recent years. The aim of this study was to analyze KPC-Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI from the intestinal carriage of hospitalized elderly patients in Italy, in February 2018–January 2020. Characterization of CAZ-AVI-resistant KP isolates, including MLST, resistome, virulome and plasmid content, was performed by WGS analysis. Out of six CAZ-AVI-resistant KP isolates, three belonged to ST101 and three to ST512; two isolates produced KPC-3 (both ST512), four had mutated KPC-3 (KPC-31, in ST101 and ST512, and KPC-46, both ST101). All CAZ-AVI-resistant KP isolates were multidrug-resistant and carried several resistance genes. The yersiniabactin ybt9 gene cluster was present in all ST101 isolates, while, in ST512 isolates, no virulence genes were detected. Several plasmids were detected: IncF was present in all isolates, as well as IncR and Col440 in ST101 and IncX3 in ST512 isolates. In conclusion, it is important to monitor the circulation of K. pneumoniae resistant to CAZ-AVI to prevent the spread of clones causing difficult-to-treat infections. The presence of mutated KPC-3 in high-risk K. pneumoniae clones resistant to CAZ-AVI in hospitalized patients deserves attention.