Bacteremia and Liver Failure Due to Non-K1 Escherichia coli With iss Gene in Two Full-Term Infants

Introduction

MICROBIOLOGICAL AND MOLECULAR DIAGNOSTIC INFORMATION:

Bacterial strains were isolated from clinical samples in the bacteriological laboratory and sent to the Kagoshima University Graduate School of Medical and Dental Sciences for further analysis. O serogroups were determined by slide agglutination using pathogenic E. coli antisera (Denka Seiken, Japan) and by polymerase chain reaction (PCR) for O1, O18, O25, O6, O75, O2, O4, O15, O7, O8, O16, and O21. H serogroups were identified by PCR-based flagellar genotyping. Phylogenetic groups were assigned by multiplex PCR, and phylogenetic group B2 isolates were further subtyped using a B2-specific scheme. Sequence types were determined by multilocus sequence typing. The presence of blaCTX-M was detected by PCR, and CTX-M subtypes were identified by sequencing. Capsular genes (neuC [K1], kpsMT K5) and virulence genes associated with uropathogenic, diarrheagenic, and enteroaggregative E. coli, as well as iss and ibeA, were detected by PCR using published protocols.

Case Reports

CASE 1:

A male infant was born at 37 weeks and 6 days of gestation by spontaneous vaginal delivery, with a birth weight of 2214 g. The pregnancy and perinatal course were unremarkable. The infant developed fever and poor feeding on day of life (DOL) 15. He was admitted in a state of shock with respiratory distress, poor peripheral perfusion, and coagulopathy. Laboratory findings (Table 1) were consistent with acute liver failure (hepatic-based coagulopathy defined as a prothrombin time exceeding 15 s or an international normalized ratio above 1.5, biochemical evidence of acute liver injury, and no known evidence of chronic liver disease) [6]. Based on the presence of systemic inflammatory response and multiorgan dysfunction, the infant was diagnosed with septic shock. Intensive care management was initiated, including broad-spectrum antimicrobial therapy, mechanical ventilation, vasoactive support, plasma exchange, and continuous renal replacement therapy. Blood cultures obtained on admission yielded E. coli. Urine culture findings were negative, and cerebrospinal fluid examination was deferred due to severe coagulopathy. Despite gradual stabilization of systemic inflammation, hepatic function did not recover, and the patient was transferred for liver transplantation on DOL 26. Metabolic disease screening revealed no specific inborn errors of metabolism. The clinical course is shown in Figure 1.

Microbiological analysis identified an untypeable O serogroup, H2 flagellar antigen, sequence type 348, and phylogenetic group B1. The isolate lacked the K1 and K5 capsule genes but harbored the iss gene. No major uropathogenic E. coli- or diarrheagenic E. coli-associated virulence genes, including blaCTX-M, were detected.

CASE 2:

A male infant was born at 38 weeks and 6 days of gestation by spontaneous vaginal delivery, with a birth weight of 2782 g. No abnormalities were detected on newborn metabolic screening. The infant developed fever and feeding difficulty on DOL 7. He rapidly progressed to shock with respiratory and circulatory failure. Laboratory findings (Table 1) were consistent with acute liver failure and disseminated intravascular coagulation [6]. Sepsis was suspected; intensive treatment was initiated, including broad-spectrum antibiotics, mechanical ventilation, vasoactive agents, plasma exchange, and continuous renal replacement therapy. Blood cultures obtained on admission showed E. coli, whereas cerebrospinal fluid and urine cultures yielded negative findings. Although systemic inflammation improved, hepatic failure persisted, and the patient was transferred for liver transplantation on DOL 16. The clinical course is shown in Figure 2.

Microbiological analysis revealed the O25: H4 serotype, sequence type 131, and phylogenetic group B2. The isolate carried the iss gene, the kpsMT K5 gene, and the aer gene associated with iron acquisition; the K1 capsule gene and blaCTX-M were absent.

Discussion

This case series demonstrates that non-K1 E. coli strains harboring the iss gene can cause severe invasive infections in full-term infants with liver failure. The principal lesson from these cases is the importance of host-pathogen interactions, whereby impaired innate immunity due to liver failure may reveal the pathogenic potential of otherwise uncommon E. coli genotypes.

The liver plays a central role in host defense via complement synthesis, bacterial clearance by the reticuloendothelial system, and immune surveillance [4,5]. Acute liver failure results in quantitative and qualitative complement deficiencies, which may predispose patients to bloodstream infections. In this context, the iss gene likely confers a survival advantage by enhancing resistance to complement-mediated killing through group 4 capsule formation [3].

Although complement levels were not directly measured in our patients, both exhibited severe liver dysfunction requiring transplantation, which strongly suggested humoral innate immunity impairment. The identification of iss-positive isolates in both cases supports a mechanistic link between host immune compromise and pathogen-specific serum resistance. From a clinical perspective, these findings underscore the need for heightened vigilance concerning invasive bacterial infections in infants with liver failure, even when classical virulence markers such as the K1 capsule are absent. Further studies are required to determine whether iss-positive extraintestinal pathogenic E. coli strains are associated with distinct clinical outcomes or therapeutic vulnerabilities in pediatric populations.

Conclusions

Liver failure in infants may predispose to bacteremia caused by non-K1 E. coli. The iss gene appears to play a key role in bacterial survival in the bloodstream by enhancing resistance to complement-mediated host defenses. Recognition of this host-pathogen interaction may improve diagnostic and clinical management strategies in infants with severe liver disease.

Data Availability

The data that support the findings of this study are available on request from the corresponding author. These data are not publicly available due to privacy or ethical restrictions.