Tigecycline resistance caused by rpsJ evolution in a 59-year-old male patient infected with KPC-producing Klebsiella pneumoniae during tigecycline treatment

Abstract

Carbapenem resistant Klebsiella pneumoniae (CRKP) nosocomial infection increased rapidly in recent years. By far, the anti-infection drugs for CRKP infection are limited. Tigecycline is one of the last resort treatments for CRKP infections. In this study, curative effect of tigecycline therapy was monitored in a 59-year-old male patient infected with KPC-producing K. pneumoniae. Consecutive clonal consistent K. pneumoniae isolates were cultured during tigecycline treatment. Whole genome sequencing of the isolates was performed, and bioinformatics analysis was further performed. Five isolates, four of which were susceptible and one resistant were collected. All of the isolates belong to Sequence Type 11 (ST11), and harbouring 11 gene sequences relevant to antibiotic resistance including blaKPC-2. One amino acid substitution V57L in rpsJ was identified in the tigecycline resistant isolates. Subsequent transformation experiment confirmed the contribution of the rpsJ variant (V57L) to reduced tigecycline susceptibility. To our knowledge, this study is the first report to provide direct in vivo evidence that evolution in the rpsJ gene can lead to tigecycline resistance in patients infected with KPC-producing K. pneumoniae during tigecycline treatment. This finding serves as a therapeutic warning as the rpsJ gene is on the chromosome of CRKP strains. Under selective pressure from tigecycline, the rpsJ mutation may occur and lead to tigecycline resistant.