Shigella flexneri 1c bacteremia in a child: a case report

Shigella infections primarily affect the gastrointestinal system. In contrast, extraintestinal infections, such as those affecting the bloodstream, are rare and mainly occur in children and immunocompromised adults [10, 11]. Specifically, bacteremia is seen in only 0.4% to 7.3% of cases in heterogeneous populations, including children to adults and in patients with cystic fibrosis, and this is mainly linked to infections caused by S. flexneri and S. dysenteriae [11‐14]. Shigella-induced bacteremia should be regarded with seriousness because it can significantly increase mortality rates [12, 15, 16]. In this case, the infection was caused by S. flexneri, consistent with previous case reports [17‐19]. However, some studies indicate that other Shigella species can also cause bacteremia [11, 20‐22].

Multiplex PCR results indicated that S. flexneri serotype 1c, which was detected in the patient, has increased in developing countries over the past decade [23]. The result was inconsistent with previous results done in the adult population, which documented serotypes 1b, 2, 2a, 3, and 4a as the responsible serotypes [24‐26]. Notably, these earlier serotypes were isolated from adult populations.

The reasons behind the development of bacteremia after a gastrointestinal infection are not fully understood. However, several factors may contribute, including the virulence of the pathogen, the initial bacterial burden, damaged mucosal barriers, and weakened host immunity [7].

Shigella pathogenesis involves several virulence factors encoded on chromosomal pathogenicity islands and a virulence plasmid. The ipa and ipg genes are crucial in invading epithelial cells and initiating Shigella infection [27]. The invasion plasmid antigen H (ipaH), a key target for the molecular identification of Shigella species, is essential in invading and modulating host inflammatory responses during bacterial infections [28]. We also identified the ipaB, ipaC, and ipaD genes, which encode proteins playing a crucial role in colonic epithelial cell invasion and intracellular survival, as well as translocating various effector proteins [9]. The invasion plasmid gene D (ipgD), which enhances immune evasion and facilitates cell-to-cell spread by disrupting communication between host cells, was identified in our isolate [27, 29]. The virA is another virulence factor in our isolate and is involved in Shigella’s uptake, invasion, and cell-to-cell transmission within the human host [30]. Our patient continued to have watery diarrhea during the hospitalization, which is hypothesized to be associated with the presence of the sen gene [27]. The World Health Organization (WHO) claims that all cases of bloody diarrhea should be treated with antibiotics. Effective antibiotic therapy lowers the risk of serious complications and death, shortens symptom duration, and decreases the shedding of organisms in stools [16, 31]. In our case, S. flexneri was resistant to ampicillin, cefotaxime, ceftriaxone, cefixime, and cotrimoxazole. There are different mechanisms by which Shigella spp. can develop resistance to the therapeutic antibiotics, including production of enzymes (such as β-lactamases), cellular impermeability, alternate metabolic pathways, extrusion of drugs by efflux pumps overexpression, and drug treatment mutation [32, 33]. As a result, the initial empirical treatment with ceftriaxone was unsuccessful. However, a subsequent change in the treatment regimen to gentamicin and ciprofloxacin, to which the isolate was susceptible, resulted in a successful clinical outcome and complete resolution of the infection. Jain et al., from Delhi, reported a case of S. flexneri septicemia in an infant that was also resistant to ceftriaxone, resulting in the patient’s death [19]. In contrast, some studies indicated that ceftriaxone remains an appropriate option for treating S. flexneri bloodstream infection [7, 17, 18].

Along with antibiotic resistance, other risk factors, rather than antibiotic resistance, should also be considered in the development of Shigella bacteremia and its associated mortality. Few studies have addressed these risks. However, host factors such as age, malnutrition, non-breastfeeding, and immunocompromised status have been linked to death from Shigella bacteremia [34, 35].

In conclusion, although S. flexneri bacteremia is rare, it occurs mainly in children under five years of age. Therefore, blood and stool cultures should be taken for better management and prognosis in bloody gastroenteritis with fever in children. An early and accurate diagnosis is crucial because appropriate antibiotics and supportive care can be lifesaving for such patients. This study was the first report of Shigella flexneri serotype 1c isolated from blood in Iran, which possessed all investigated virulence factors. However, it remains uncertain whether this serotype possesses increased virulence. This rare case highlights the need for clinicians and microbiologists to characterize the role of these genes and other related virulence factors of Shigella spp. for successfully spreading this pathogen into blood circulation.