Lacticaseibacillus paracasei bacteremia and mediastinitis secondary to esophageal invasion by left hilar pleomorphic carcinoma: case report.

Introduction

Lactobacilli are widely found in nature, are commensal microbes in humans, and are commonly used as probiotics [1]. The genus Lacticaseibacillus is generally recognized as safe and extensively used as probiotics. It rarely causes systemic infections such as bacteremia, accounting for approximately 0.1% of all bacteremia cases [2]. The L. paracasei strain Shirota, in particular, has been shown in animal models to have negligible pathogenicity compared with clinical isolates [3]. Reports of bacteremia due to this strain are extremely rare, with only one previous case documented in the literature [4]. We report the second case of bacteremia caused by L. paracasei strain Shirota in a patient with advanced lung cancer that had invaded the esophagus. This case report was written in accordance with the CARE guidelines.

Case presentation
The patient was a 71-year-old man with a medical history of type 2 diabetes and hypertension, both under treatment. He had a 54 pack-year smoking history (30 cigarettes/day for 36 years). Forty-two days before admission, he presented to a local physician with recurrent postprandial vomiting. Chest CT revealed a posterior mediastinal mass, raising suspicion of a mediastinal tumor (Fig. 1). Upper gastrointestinal endoscopy demonstrated external compression of the esophageal wall. Twenty-four days before admission, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of an enlarged mediastinal lymph node established the diagnosis of lung cancer (giant cell carcinoma, BRAF V600E-positive, high PD-L1 tumor proportion score).

He was subsequently referred to our department three days before admission. No anticancer therapy had been initiated at the previous hospital. Given the advanced disease, we planned outpatient staging with PET-CT, followed by admission to initiate treatment. PET-CT performed one day before admission revealed a large hypermetabolic mass in the left pulmonary hilum with extensive mediastinal invasion and necrosis. Widespread metastases were identified in the lymph nodes, pleura, peritoneum, muscles, and bones, consistent with clinical Stage IVB disease (T4N3M1c2) (Fig. 2).

On admission day, he was brought to the emergency department due to worsening general malaise and dyspnea. On arrival, his vital signs were as follows: temperature 39.0 °C, heart rate 110 beats/min, and respiratory rate 28 breaths/min, with an SpO₂ of 94% on 5 L/min of oxygen via a face mask. Physical examination revealed crackles in his chest. Serum C-reactive protein was 33.88 mg/dL. Given the high fever and elevated inflammatory markers, severe infection was suspected. Chest CT showed that the posterior mediastinal mass, containing foam-like material resembling food debris, had extended to the right mediastinum, suggesting an esophagomediastinal fistula. The lesion also extended into the right lung (Fig. 3).

He was admitted with a diagnosis of sepsis secondary to mediastinitis and pneumonia, and meropenem was initiated. He was managed with bowel rest and started on central venous nutrition. Due to his unstable general condition, mediastinal drainage was not performed. Although his inflammatory markers and oxygenation initially improved, chest CT on Day 8 showed progression of right lung infiltrates (Fig. 4). Sputum Gram stain showed gram-positive cocci, therefore linezolid was added for suspected MRSA. Blood cultures obtained on admission grew L. paracasei in all four bottles. Although antimicrobial susceptibility testing was attempted, accurate interpretation was not possible due to the lack of established interpretive criteria (breakpoints) for this organism. Therefore, antibiotic selection was guided by previously published data regarding the intrinsic susceptibility profile of L. paracasei. Meropenem was changed to ampicillin/sulbactam on Day 8, but the regimen was switched to clindamycin on Day 9. His respiratory status and inflammatory markers improved over time. However, recurrent aspiration due to esophageal obstruction increased sputum volume and led to repeated airway obstruction starting on Day 14. He died on Day 21 of hospitalization from respiratory failure.

To determine the source of bacteremia, the patient’s blood isolate was sent to the Yakult Central Institute. Species-specific and strain-specific PCR [4] and ELISA [5] confirmed that the isolate was genetically and immunologically identical to the L. paracasei (the previous taxonomic nomenclature was Lactobacillus casei) strain Shirota contained in commercially available probiotic-fermented milk (Fig. 5). On detailed questioning, he reported that he had voluntarily been regularly consuming this probiotic-fermented milk containing the Shirota strain to “boost immunity,” as solid food intake had been limited by esophageal stenosis.

Pathological autopsy revealed pleomorphic carcinoma of the left pulmonary hilum (predominantly giant cell component), staged as pT4N3M1c2 (Figs. 6 and 7). Tumor invasion of the mediastinum and esophagus was evident, along with metastases to the right pleura, right diaphragm, thyroid, stomach, small and large intestines, mesentery, lesser omentum, and lymph nodes (supraclavicular, mediastinal, and hilar). Additional findings included mediastinitis, pulmonary abscess, bilateral aspiration and bacterial pneumonia, candidiasis, and pulmonary edema. The cause of death was determined to be respiratory failure due to the primary malignancy.

Although giant cell carcinoma component predominated, spindle cell carcinoma elements were also present, supporting the diagnosis of pleomorphic carcinoma. The tumor originated in the left pulmonary hilum, extensively invaded the mediastinum, and ruptured the mid-esophagus wall. A lung abscess was present in the right lower lobe adjacent to the esophageal perforation site. Aspiration pneumonia and bronchopneumonia were observed throughout both lungs.
L. paracasei was not identified on histopathology. However, gram-positive and gram-negative cocci, as well as Candida, were observed in the lungs, consistent with polymicrobial aspiration pneumonia. Postmortem blood cultures identified Enterococcus faecium, suggesting that the infection control remained incomplete.

Discussion
This case represents an extremely rare instance in which L. paracasei strain Shirota, a probiotic with established safety, became the caused bacteremia in the setting of multiple predisposing factors. The primary pathophysiological mechanism was likely bacterial translocation facilitated by tumor-related perforation of the esophageal wall. Autopsy findings confirmed that the mediastinal tumor (a pleomorphic carcinoma) had invaded and perforated the esophageal wall. Furthermore, because of severe esophageal stenosis, the patient had voluntarily been regularly consuming liquid probiotics to “boost immunity.” This frequent exposure of the perforation site to a high load of viable organisms likely facilitated direct translocation of the organism into the bloodstream.
Invasive infections by Lactobacillus species are uncommon because of their low virulence. In a rabbit model of infective endocarditis, Asahara et al. demonstrated that the pathogenicity of L. paracasei strain Shirota was minimal, with rapid clearance from the bloodstream and from cardiac vegetations after inoculation [3]. These findings suggest that, in immunocompetent hosts, this strain is effectively eliminated by innate immune defenses, including macrophage-mediated bactericidal activity [3]. However, our case highlights that structural disruption of the gastrointestinal tract is a key risk factor. Additional contributing factors included the patient’s immunocompromised state due to advanced malignancy and malnutrition.
The Shirota strain has been reported to have low susceptibility to many empiric antimicrobials, with low susceptibility to most aminoglycosides, cephalosporins, quinolones, carbapenems, β-lactams, fosfomycin, sulfamethoxazole, and trimethoprim [6]. In contrast, it remains susceptible to tetracycline and macrolides [6]. Accurate identification of the causative organism is therefore essential to guide appropriate antimicrobial therapy. In this case, recognition of the patient’s probiotic intake and the known susceptibility profile of the Shirota strain supported switching therapy to clindamycin, which was associated with clearance of bacteremia. Unfortunately, the advanced progression of the underlying malignancy precluded recovery; however, improvement in inflammatory parameters and autopsy findings support that antimicrobial therapy controlled the Shirota strain bacteremia.
Although probiotics are generally considered safe, serious complications such as bacteremia and infective endocarditis have been documented [7]. This is the second reported case of bacteremia caused by an L. paracasei strain genetically identical to the Shirota strain. The first involved an 8-month-old girl who developed bacteremia after ingesting probiotics containing the Shirota strain following jejunojejunostomy for intestinal ganglion cell hypoplasia [5]. These cases highlight that, although exceedingly rare, even probiotics with proven benefits [7, 8] can cause bacteremia in severely immunocompromised patients or in those with structural disruption of gastrointestinal barriers due to malignancy, surgery, or other conditions.

Conclusion
We report a case of mediastinitis due to esophageal invasion by pleomorphic carcinoma, complicated by bacteremia caused by L. paracasei, genetically identical to the strain contained in commercially available probiotic-fermented milk. This case indicates that probiotics can cause bacteremia in immunocompromised patients with structural disruption of the gastrointestinal barrier.

Supplementary Information
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