A worrying increase has been detected in the incidence of the hypervirulent variant of Klebsiella pneumoniae (HvKp), which is responsible for severe invasive community-acquired infections. HvKp is normally susceptible to the majority of antimicrobials, but recent research has identified hypervirulent and highly resistant strains.1
Current reports indicate an increase in the geographical distribution of these strains. Furthermore, the European Centre for Disease Prevention and Control (ECDC) has published an alert related to HvKp, ST23 carrying OXA-48 carbapenemase genes, verifying its continued spread.2
We present the case of a 41-year-old male, originally from Estonia and resident in Tenerife for five years. His medical history included obstructive jaundice two years previously caused by a pancreatic pseudocyst, which was treated surgically with a metal biliary stent. The patient was admitted with a two-week history of obstructive jaundice and persistent pruritus. On admission, the patient had no fever, so no invasive procedures were performed and no samples were taken for microbiology. Empirical treatment was prescribed with piperacillin/tazobactam 4000/500mg/8h. Due to progressive clinical deterioration, two weeks after admission, percutaneous biliary drainage was performed. Drainage fluid samples were collected and blood cultures taken. In both, Klebsiella pneumoniae was isolated with high mucus production in the plates with a positive string test (6mm). In addition, Candida albicans, Candida glabrata and Streptococcus parasanguinis were isolated from the drainage culture.
Antibiograms were performed using VITEK® 2 (bioMérieux, France) and EUCAST breakpoints were applied. The K. pneumoniae isolate was resistant to amoxicillin/clavulanic acid, piperacillin/tazobactam and ertapenem (MIC of ≥32/2, ≥128/4 and 2mg/l, respectively), and sensitive to imipenem, meropenem and ceftazidime/avibactam (MIC 1, 0.25 and 0.125/4mg/l, respectively). Using the double-disk diffusion method on Mueller Hinton agar, an extended-spectrum beta-lactamase was ruled out. Due to resistance to ertapenem, an immunochromatographic test was performed (O.K.N.V.I. RESIST-5, Coris BioConcept, Belgium), which was positive for OXA-48-like.
Based on the findings of these cultures, the treatment was changed to meropenem 1000mg/8h and anidulafungin 100mg/24h.
Two weeks later, surgery was scheduled to remove the biliary stent. Bile was collected for culture where K. pneumoniae was isolated with MIC to meropenem >32mg/l, in addition to an OXA-48-like carbapenemase-producing Morganella morganii and C. albicans. Due to this culture, the treatment was escalated from meropenem to ceftazidime/avibactam at doses of 2000/500mg/8h.
Finally, after being in hospital for 56 days, the patient made a good recovery and was discharged.
After performing whole-genome sequencing using the Illumina MiSeq™ high-throughput sequencing platform (Illumina, Inc., USA), the assembly generated a sequence type not previously known (PubMLST3), presenting a difference allele (gapA) with ST380, usually described as hypervirulent.4 This is an isolate of clonal group 380, serotype K2, hypermucoviscous in phenotypic tests (string-test).
Using VFDB, Kleborate and BLAST tools, the genome was screened for virulence genes. The genes yersiniabactin (ybt), colibactin (clb), salmochelin (iro), regulator of mucoid phenotype A (rmpA) and aerobactin (iuc) were detected as virulence factors. The detection of the OXA-48-like carbapenemase in the resistome using rgi-CARD,5 without associated extended-spectrum beta-lactamase, was important. Using the PlasmidFinder database,6 the plasmids IncL, IncFIB(K) and IncFIA(HI1) were found. Plasmids IncL and IncFIB(K), along with other types of replicon, have been identified as carriers of carbapenem-resistance genes7 and the IncL/M is specifically involved in the worldwide spread of blaOXA-488. Finally, the sequences were deposited in BIGSdb-Pasteur, which assigned a new sequence type: ST6423, and are available in NCBI GenBank® (GCA_037150565.1, BioProject ID: PRJNA1078582).
The presence of HvKp with its distinctive hypermucoviscosity, especially in the context of biomedical device-related infections, poses a challenge due to its ability to form biofilm. This phenomenon, associated with OXA-48-like carbapenemase, complicated the management and treatment of the patient.
The detection of HvKp cases justifies exhaustive genomic surveillance, as its characterisation is crucial to understanding both its genetic drift and the resistance mechanisms it may acquire. Ultimately, the comprehensive study of HvKp provides an opportunity to address the clinical and epidemiological challenges associated with these microorganisms.
FundingThis study received no specific funding from public, private or non-profit organisations.
We would like to thank the teams at Institut Pasteur for the preservation and maintenance of the BIGSdb-Pasteur databases at https://bigsdb.pasteur.fr/.
