Spread of hypervirulent multidrug-resistant ST147 Klebsiella pneumoniae in patients with severe COVID-19: An observational study from Italy, 2020-21

Objectives: To report an outbreak of hypervirulent Klebsiella pneumoniae (hvKp) in COVID-19 patients. Methods: Prospective, observational study including consecutive COVID-19 patients with hvKp infections admitted to the University Hospital of Pisa (Italy). Clinical data and outcome of patients were collected. All patients were followed-up to 30 days from the diagnosis of infection. Mortality within 30 days of the diagnosis of hvKp infection was reported. The hypermucoviscous phenotype was determined by the 'string test'. Molecular typing was performed on three strains collected during different periods of the outbreak. The strains underwent whole genome sequencing using the Illumina MiSeq instrument. The complete circular assemblies were also obtained for the chromosome and a large plasmid using the Unicycler tool. Results: From November 2020 to March 2021, hvKp has been isolated from 36 COVID-19 patients: 29/36 (80.6%) had infections (15 bloodstream infections, 8 ventilator-associated pneumonias and 6 complicated urinary tract infections), while 7/36 (19.4%) had colonization (3 urine, 2 rectal and 2 skin). The isolates belonged to ST147 and their plasmid carried three replicons of the IncFIB (Mar), IncR and IncHI1B types and several resistance genes, including the rmpADC genes encoding enhancers of capsular synthesis. The hvKp isolates displayed an ESBL phenotype, with resistance to piperacillin/tazobactam and ceftolozane/tazobactam and susceptibility only to meropenem and ceftazidime/avibactam. The majority of patients were treated with meropenem alone or in combination with fosfomycin. Thirty-day mortality was 48.3% (14/29). Conclusions: ST147 ESBL-producing hvKp is associated with high mortality in COVID-19 patients. Strict microbiological surveillance and infection control measures are needed in this population.