In May 2021, a 71-year-old man presented with a fever, altered mental status, and general weakness. Four days before admission, he had a fever of over 38.0 °C and a positive SARS-CoV-2 PCR test in a family doctor’s office. He had no known medical history, but was newly diagnosed with type II diabetes mellitus (hemoglobin A1c of 10.3%) on admission. His vital signs included a body temperature of 40.0 °C, blood pressure of 155/86 mmHg, pulse rate of 100 bpm, respiratory rate of 35 breaths/min, and oxygen saturation of 85% with ambient air. Chest computed tomography scan showed bilateral ground-glass opacities and densities consistent with COVID-19 pneumonia. Initial laboratory data showed a white blood cell count of 4000/μl, C-reactive protein of 14.14 mg/dl (reference, 0.00-0.14).
He was admitted to the intensive care unit and received dexamethasone (6.6 mg/day), remdesivir and intravenous unfractionated heparin. He then required a high-flow nasal cannula. No empiric antibiotics were given because there was no suspicion of bacterial infection on admission. Initial bacterial cultures from blood, sputum, and urine were all negative.
On the third day of hospitalization his respiratory condition deteriorated and he was intubated (Fig. 1, 2). On hospital day 6, blood and sputum cultures were repeated for fever, but the blood cultures showed no growth. His fever persisted and sputum cultures were repeated on the 8th day of hospitalization. Gram staining of sputum samples collected on hospital days 6 and 8 showed clusters of Gram-positive cocci (GPC). GPC was more prevalent and observed within phagocytes in the hospital day 8 sample. Sputum cultures on hospital days 6 and 8 subsequently became methicillin sensitive Staphylococcus aureus (MSSA) and Klebsiella pneumoniae Complex. Superimposed MSSA pneumonia was suspected and cefazolin was started on hospital day 10.
Clinical parameters of the COVID-19 case with K. variicola. SOFA sequential assessment of organ failure, Max Bt maximum body temperature in one day, P/F ratio (Partial pressure of arterial oxygen, PaO2/fraction of inspired oxygen, FiO2%) Relationship, CT Computed Tomography, CEZ cefazoline, PIPC/TAZ piperacillin/tazobactam, VCM vancomycin, MEPM meropenem
The serial chest radiographs of the patient
On the 11th day of hospitalization, cefazolin was switched to piperacillin-tazobactam. On the 12th day of hospitalization, gram-negative rods grew in the blood culture taken on the 11th day of hospitalization. All intravenous catheters were replaced. On the 13th day of hospitalization he rapidly developed hypotension, decreased oxygenation and lactic acidosis (Fig. 1). Serial chest radiographs remained unchanged between hospital days 10 and 13 (Fig. 2). Despite immediate interventions, including an escalation of antibiotics to vancomycin and meropenem, he died that same day.
Subsequently, all blood and sputum cultures collected on hospital days 11, 12 and 13 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.
Isolates from sputum cultures collected on hospital days 6, 12, and 13, blood cultures collected on hospital days 12 and 13, and culture from 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 that distinguishes the phylogroups of K. pneumoniae Complex based on polymorphisms of the SHV type β-lactamase gene [7]. Another multiplex PCR examining the virulence gene profile showed that all strains were carriers kfu, entBAnd mrkB. These results suggested that the isolates obtained on different dates at different body sites were clonal K. variicola isolated. A representative isolate (FUJ01370), which was a hospital day 12 blood culture isolate, was further analyzed with whole genome sequencing using NextSeq 2000 (Illumina) as previously described [6], and genetic traits were characterized using the Pathogenwatch website (https://pathogen.watch/). Capsule genotype and O locus type were determined to be KL11 and O3, respectively. The isolate carried a gene for LEN-type β-lactamase (blahLEN-16), which is a distinctive genetic trait of K. variicola [8]And oqxA, oqxB, fosA as antimicrobial resistance genes. Replicons for plasmid IncFIB (pNDM-Mar), plasmid FIA (pBK30683) and plasmid IncHI1B (pNDM-MAR) have also been identified. The isolate had a novel multilocus sequence typing allelic profile (GapA-on Facebook-mdh–PGI–phoE–rpoB–tonB: 16-24-21-27-52-17-152) assigned sequence type 5794 (GenBank Assembly Access: GCA_019042755.1).
