Severe co-infection caused by difficult-to-diagnose hypermucoviscous Klebsiella pneumoniae K1-ST82 in a patient with COVID-19: a case report

Background: Co-infection with Klebsiella pneumoniae presents a significant concern in hospitalized patients with coronavirus disease (COVID-19), increasing the risk of severe disease progression. Hypervirulent (hv) and hypermucoviscous (hm) K. pneumoniae (Kp) has gained prominence in Asia due to its capacity to cause invasive community-acquired infections. However, recognition of hvKp/hmKp co-infections in the context of COVID-19 remains limited. We report a severe case of rapidly progressing co-infection with hmKp exhibiting "difficult-to-diagnose" phenotypes in a hospitalized patient with COVID-19.

Case presentation: A 61-year-old woman with COVID-19 initially exhibited mild symptoms resembling the common cold. However, her condition rapidly deteriorated over 7 days, leading to hospital admission with the development of dyspnea. The patient required supplemental oxygen, antibiotic treatment, and mechanical ventilation. Gram-negative bacteria with atypical phenotypes were isolated from alveolar lavage fluid and blood cultures. Both strains formed small, glossy, non-lactose-fermenting colonies on clinically relevant media and were susceptible to ampicillin. Conventional biochemical tests failed to identify the Enterobacteriales strains owing to the urease-negative phenotype. Consequently, the identification of K. pneumoniae was difficult until matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis was performed. A positive string test indicated mucoviscosity, but with variability in the material used for stretching colonies. Whole-genome sequencing performed on the MiSeq and GridION platforms revealed the blood-derived strain JARB-RN-0063 as belonging to serotype K1 and sequence type (ST) 82. The hvKp-associated genes rmpA and iroCD were located on a 5.0-Mb chromosome, and iucABCD-iutA was identified on a 217.9-kb IncFIB(K)/IncR-type plasmid. Therefore, JARB-RN-0063 was genetically classified as hvKp with a Kleborate virulence score of 3. The intrinsic penicillinase gene bla_SHV was defective owing to an IS1F element insertion, resulting in the strain being atypically susceptible to ampicillin.

Conclusions: This is the first case of severe COVID-19-associated co-infection with a difficult-to-diagnose K. penummoniae strain. Notably, co-infection by the hmKp K1-ST82 clone exhibited atypical phenotypes, including stunted growth, non-lactose fermentation, urease-negative reaction, ampicillin susceptibility, and abnormal mucoviscosity, posing diagnostic challenges for clinical laboratories and impedes the identification of hvKp/hmKp. Delayed identification may worsen patient outcomes, highlighting the need for increased clinical awareness of such difficult-to-diagnose clones to prevent deterioration.