Case Highlights Need for Adequate Neutrophil Count and Function in the Clearance of E coli Bacteremia

Microbiologic data obtained from Escherichia coli isolates from an immunocompromised pediatric patient showed the emergence of antibiotic resistance genes and plasmids over time, highlighting the need for adequate neutrophil number and function to recover from severe invasive bacterial infection, according to study results published in Open Forum Infectious Diseases.¹

Researchers obtained 33 isolates over the course of 7 months from an adolescent patient referred for treatment of relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia at St. Jude Children’s Research Hospital in Memphis, Tennessee. He had multiple episodes of bacteremia resulting from infection with resistant strains of E coli (twice) and Streptococcus viridans (once); he therefore also experienced significant and prolonged exposure to antibiotics over the course of the 7 months of cancer therapy until his death.

Of the 33 isolates, 23 were obtained from blood cultures, 9 were obtained from perianal surveillance cultures (PASCs), and 1 was obtained from a wound culture. The 33 isolates belonged to 1 of 4 identifiable sequence types (STs): ST-167 (22 isolates), ST-940 (3 isolates), ST-405 (3 isolates), and ST-648 (4 isolates). One isolate did not have an identifiable ST.

The first sequence type resistant to all carbapenems was ST-940, which carried the bla_NDM-5 gene as well as the IncFII plasmid. The bla_NDM-5 gene, present in 72.7% of isolates, and phenotypic carbapenem resistance were not present in the first E coli isolate in this series (of ST-167), although the IncFII plasmid had been identified. “Subsequently, following prolonged carbapenem exposure for treatment of a perianal abscess, an ST-167 isolate identified in a PASC was found to be carbapenem-resistant and carried the bla_NDM-5 gene,” noted the researchers.

This was the first isolate that carried the IncX3 plasmid, they added. They stated, “All subsequent ST-167 isolates harbored the IncX3 plasmid and the bla_NDM-5 gene. Subsequent ST-940 isolates were also found to have the IncX3 plasmid, as well as the bla_NDM-5 gene; the IncFII plasmid was no longer present in these ST-940 isolates but was variably present in the ST-167 isolates.”

The IncX3 plasmid appeared to be more stable over time compared with the IncFII plasmid, and may confer “a fitness advantage in the presence of selective antibiotic pressure,” as noted in a previous study.²

Although the patient received appropriate dosing of antibiotics that appeared, based on phenotypic testing, to be adequate (no phenotypic colistin or tigecycline resistance was detected in vitro), the researchers presumed “the treatment failure resulted from prolonged profound immune suppression, which highlights the importance of host immune competence in the treatment of severe infection.”

References

1. Flerlage T, Brazelton de Cardenas JN, Garner CD, et al. Multiple NDM-5-expressing Escherichia coli isolates from an immunocompromised pediatric host. Open Forum Infect Dis. 2020;7(2):ofaa018.

2. Liakopoulos A, van der Goot J, Bossers A, et al. Genomic and functional characterization of IncX3 plasmids encoding bla_SHV-12 in Escherichia coli from human and animal origin. Sci Rep. 2018;8(1):7674.