Background: There is a growing interest in Klebsiella variicola as a causative pathogen in humans, though its clinical features and the impact of co-infection or secondary infection with COVID-19 remain unknown. Case presentation: A 71-year-old man presented with fever, altered mental status and generalized weakness and was admitted to ICU due to severe COVID-19 pneumonia. He was newly diagnosed with type II diabetes mellitus upon admission. On hospital day 3, his respiratory status deteriorated, requiring invasive mechanical ventilation. On hospital day 10, superimposed bacterial pneumonia was suspected and subsequently, broad-spectrum antibiotics were administered for the associated bloodstream infection. On hospital day 13, despite administration of active antibiotics and appropriate source control, he decompensated and died. The causative organism isolated from blood cultures was initially reported as K. pneumoniae, but it was identified as K. variicola by a genetic analysis. A representative isolate (FUJ01370) had a novel multilocus sequence typing allelic profile (gapA-infB-mdh-pgi-phoE-rpoB-tonB: 16-24-21-27-52-17-152), to which sequence type 5794 was assigned (GenBank assembly accession: GCA_019042755.1). Conclusions: We report a fatal case of respiratory and bloodstream infection due to K. variicola complicating severe COVID-19. Co-infection or secondary infection of K. variicola in COVID-19 is likely under-recognized and can be fulminant as in this case.
Keywords: COVID-19; Klebsiella variicola; Klebsiella pneumoniae complex; Whole genome sequencing; Case report
Co-infections or secondary infections with bacteria is uncommon among novel coronavirus disease 2019 (COVID-19) patients, seen in 1% of all patients according to a UK national surveillance study [[
Here, we present a case of fatal secondary infection caused by K. variicola that complicated the clinical course of severe COVID-19.
In May 2021, a 71-year-old man presented with fever, altered mental status and generalized weakness. He had had fever over 38.0 °C for 4 days prior to admission and had a positive SARS-CoV-2 PCR test at a primary care clinic. He had no known past medical history but was newly diagnosed with type II diabetes mellitus (hemoglobin A1c of 10.3%) upon admission. His vital signs included body temperature of 40.0 °C, blood pressure of 155/86 mmHg, pulse rate of 100 beats/min, respiratory rate of 35 breaths/min, and oxygen saturation of 85% with ambient air. Computed tomography scan of the chest showed bilateral ground-glass opacities and consolidations, consistent with COVID-19 pneumonia. Initial laboratory data showed white blood cells count of 4000/μL, C-reactive protein of 14.14 mg/dL (reference, 0.00–0.14).
He was admitted to intensive care unit and received dexamethasone (6.6 mg/day), remdesivir, and intravenous unfractionated heparin. He subsequently required high flow nasal cannula. No empiric antibiotics were given as no bacterial infection was suspected on admission. Initial bacterial cultures of blood, sputum and urine were all negative.
On hospital day 3, his respiratory status deteriorated and he was intubated (Figs. 1, 2). On hospital day 6, blood and sputum cultures were repeated due to fever but the blood cultures revealed no growth. His fever persisted and sputum cultures were repeated on hospital day 8. Gram stain of the sputum samples collected on hospital days 6 and 8 revealed Gram-positive cocci (GPC) in clusters. GPC was becoming more predominant and seen within phagocytes in the sample on hospital day 8. The sputum cultures on hospital days 6 and 8 subsequently grew methicillin-susceptible Staphylococcus aureus (MSSA) and Klebsiella pneumoniae complex. Superimposed MSSA pneumonia was suspected and cefazolin was started on hospital day 10.
Graph: Fig. 1 Clinical parameters of the COVID-19 case with K. variicola. SOFA sequential organ failure assessment, Max BT maximum body temperature in a day, P/F ratio (partial pressure of arterial oxygen, PaO2/fraction of inspired oxygen, FiO2, %) ratio, CT computed tomography, CEZ Cefazolin, PIPC/TAZ Piperacillin/Tazobactam, VCM Vancomycin, MEPM Meropenem
Graph: Fig. 2 The serial chest radiographs of the patient
On hospital day 11, cefazolin was switched to piperacillin–tazobactam. On hospital day 12, the blood culture taken on hospital day 11 grew Gram-negative rods. All the intravenous catheters were replaced. On hospital day 13, he rapidly developed hypotension, worsening oxygenation and lactic acidosis (Fig. 1). The serial chest radiographs remained unchanged between hospital days 10 and 13 (Fig. 2). Despite prompt interventions including escalation of antibiotics to vancomycin and meropenem, he died on the same day.
Subsequently, blood and sputum cultures collected on hospital days 11, 12 and 13 all grew K. pneumoniae complex identified using MicroScan (Beckman Coulter, CA, USA). All isolates were susceptible to cefazolin, piperacillin–tazobactam, meropenem, sulfamethoxazole-trimethoprim, levofloxacin and fosfomycin except the isolates from sputum cultures collected on hospital days 8 and 13 were intermediate to fosfomycin.
The isolates from the sputum cultures collected on hospital days 6, 12 and 13, the blood cultures collected on hospital days 12 and 13, and the culture of the central venous catheter removed on hospital day 12 were subjected to molecular characterization. All isolates were identified as K. variicola by a multiplex PCR protocol, which distinguishes the phylogroups of the K. pneumoniae complex based on polymorphisms of the SHV-type β-lactamase gene [[
We report a case of fatal respiratory and bloodstream infection of K. variicola complicating severe COVID-19. The causative organism was initially reported as K. pneumoniae, but genetic analysis revealed that it was indeed K. variicola. K. variicola have been reported among patients with immunocompromising conditions such as malignancy and diabetes [[
Klebsiella variicola is a member of the K. pneumoniae complex, originally reported as a bacterium in plants, but there have been an increasing number of reports on human infections in recent years. Conventional biochemical methods and automated instruments are unable to distinguish K. variicola from K. pneumoniae, and genetic analysis is required [[
The pathogenic potential of K. variicola remains uncertain. In a single-center study in Sweden, K. variicola was a significant risk factor for 30-day mortality [[
Although K. variicola infection was fatal in our patient, the strains detected were neither highly viscous nor associated with cardinal virulence genes. It is reported that some strains have no known microbiological and genetic characteristics of virulence but are hypervirulent clinically [[
In conclusion, we report a fatal case of K. variicola infection complicating severe COVID-19. Co-infection or secondary infection of K. variicola with COVID-19 is likely under-recognized and can be fulminant as in this case. Further research is required to better describe the epidemiological, clinical, biological and genetic characteristics of K. variicola.
None.
RT and HS conceived the concept of this manuscript and all others participated in the conception of the work. RT wrote the first draft as well as the final draft of the manuscript. SH, HS, KO, and YD substantively contributed to the editing, critically reviewed and revised the manuscript. SH, YD, and MS performed microbiological testing/analysis and provided interpretation of case findings. MS supervised the overall project and revised the final version of the manuscript. All authors read and approved the final manuscript.
No funding has been obtained for this manuscript.
Not applicable.
As this is a case report, ethics approval is not required from the institutional ethics committee according to national guidelines.
Written informed consent for personal clinical details of the patient to be published has been obtained by a patient and his wife.
Authors declared no competing interests.
- COVID-19
- Coronavirus disease 2019
- K. variicola
- Klebsiella variicola
• ICU
- Intensive Care Unit
• HAI
- Hospital-acquired infection
• MSSA
- Methicillin-susceptible Staphylococcus aureus
• PCR
- Polymerase chain reaction
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By Rimi Tanii; Sohei Harada; Hiroki Saito; Koh Okamoto; Yohei Doi and Masahiro Suzuki
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