Evolution of Klebsiella pneumoniae Sequence Type 512 during Ceftazidime/Avibactam, Meropenem/Vaborbactam, and Cefiderocol Treatment, Italy

In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitaliza-tion, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bac-terial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infect-ing the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 re-sistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA sid-erophore receptor gene, resulting in high levels of ce-fiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other in-fective agents. K. pneumoniae can stably colonize a pa-tient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicat-ing a substantial public health threat.