Emerging pan-aminoglycoside resistance among carbapenemase-producing Enterobacterales, Spain

Using hybrid whole-genome sequencing, we investigated the prevalence, genomics, and molecular epidemiology of 16S rRNA methyltransferases (RMTs) in a set of 471 carbapenemase-producing Enterobacterales (CPE) recovered from 41 Spanish hospitals during a large-scale multicenter study. Twenty-four isolates recovered from 9 hospitals spanning 5 regions showed resistance to all aminoglycosides, including plazomicin, and were positive for an RMT. The RMT-positive isolates were global clones of K. pneumoniae (ST147, ST101, ST395) and E. cloacae (ST93) species producing OXA-48, NDM-1 or VIM-1 carbapenemases. The most common RMT was rmtF, followed by armA and rmtC. High-risk ST147 and ST101 rmtF-positive isolates were identified in up to 5 hospitals. All RMTs were located in multidrug-resistant plasmids and linked to mobile platforms able to promote their mobilization. RMTs are emerging among CPE from Spain and should be closely monitored to preserve the clinical utility of aminoglycosides and plazomicin in the future.