Evidence of pediatric sepsis caused by a drug resistant Lactococcus garvieae contaminated platelet concentrate

Abstract

Owing to an increasing number of infections in adults, Lactococcus (L.) garvieae has gained recognition as an emerging human pathogen, causing bacteraemia and septicaemia. In September 2020, four paediatric onco-hematologic patients received a platelet concentrate from the same adult donor at Bambino Gesù Children’s Hospital IRCCS, Rome. Three of four patients experienced L. garvieae sepsis one day after transfusion. The L. garvieae pediatric isolates and the donor’s platelet concentrates were retrospectively collected for whole-genome sequencing and shot-gun metagenomics, respectively (Illumina HiSeq). By de novo assembly of the L. garvieae genomes, we found that all three pediatric isolates shared a 99.9% identity and were characterized by 440 common SNPs. Plasmid pUC11C (conferring virulence properties) and the temperate prophage Plg-Tb25 were detected in all three strains. Core SNP genome-based maximum likelihood and Bayesian trees confirmed their phylogenetic common origin and revealed their relationship with L. garvieae strains affecting cows and humans (bootstrap values >100 and posterior probabilities = 1.00). Bacterial reads obtained by the donor’s platelet concentrate have been profiled with MetaPhlAn2 (v.2.7.5); among these, 29.9% belonged to Firmicutes, and 5.16% to Streptococcaceae (>97% identity with L. garvieae ), confirming the presence of L. garvieae in the platelet concentrate transfusion. These data showed three episodes of sepsis for the first time due to a transfusion-associated transmission of L. garvieae in three pediatric hospitalized hematology patients. This highlights the importance to implement the screening of platelet components with new human-defined pathogens for ensuring the safety of blood supply, and more broadly, for the surveillance of emerging pathogens.

Comparative Genomic Analyses of Lactococcus garvieae Isolated from Bovine Mastitis in China

“…The core genome SNP analysis underlies potential host adaptation of L. garvieae . Meanwhile, adhesins, hemolysin, fibronectin-binding proteins, penicillin acylase and WxL domain-containing proteins are considered to actively promote bacterial colonization ( 67 ); most had high similarity across hosts in those coding sequences. Regardless, the underlying mechanisms remain unclear.…”

Comparative genomic analyses of Lactococcus garvieae isolated from bovine mastitis in China

“…The core genome SNP analysis underlies the potential host adaptation of L. garvieae . Meanwhile, adhesins, haemolysin, fibronectin-binding proteins, penicillin acylase and WxL domain-containing proteins are considered to actively promote bacterial colonization ( 66 ); most had high similarity across host in those coding sequences. Regardless, underlying mechanisms remain unclear.…”

Prevalence, Virulence, and Antibiotics Gene Profiles in Lactococcus garvieae Isolated from Cows with Clinical Mastitis in China

“…L. garvieae was known as an emergent disease affecting many fish species and it is considered a potential zoonotic microorganism [ 7 ]. This is because it is known to cause several opportunistic human infections, such as endocarditis [ 8 ], diverticulitis [ 9 ], peritonitis [ 9 ], infective spondylodiscitis [ 10 ], liver abscess [ 11 ], urinary infection [ 12 ], subdural hematoma [ 13 ], sepsis [ 14 , 15 , 16 ], bacteremia [ 9 ], and late onset periprosthetic infection of the hip [ 17 ]. More recently, L. garvieae has been reported in sepsis cases in human patients receiving platelet concentrates from the same donor, one day after transfusion [ 16 ].…”

“…This is because it is known to cause several opportunistic human infections, such as endocarditis [ 8 ], diverticulitis [ 9 ], peritonitis [ 9 ], infective spondylodiscitis [ 10 ], liver abscess [ 11 ], urinary infection [ 12 ], subdural hematoma [ 13 ], sepsis [ 14 , 15 , 16 ], bacteremia [ 9 ], and late onset periprosthetic infection of the hip [ 17 ]. More recently, L. garvieae has been reported in sepsis cases in human patients receiving platelet concentrates from the same donor, one day after transfusion [ 16 ]. This highlights the importance of surveillance of this emerging pathogen for humans, especially those who have predisposing health conditions [ 10 ].…”