Noniatrogenic Meningitis Caused by Streptococcus salivarius Associated with Early Esophageal Cancer and Early Gastric Cancer

Abstract

Streptococcus salivarius is part of the normal oral cavity and gastrointestinal tract microflora and an unusual cause of acute bacterial meningitis. We herein report an 81-year-old man with S. salivarius meningitis, which led to a diagnosis of early esophageal cancer and early gastric cancer. S. salivarius infection may occur through the gastrointestinal mucosa when it is disrupted in association with early gastrointestinal cancer. To our knowledge, this is the first report describing S. salivarius meningitis associated with multiple early gastrointestinal cancers in the absence of other sources of infection.

Introduction

Streptococcus salivarius is part of the normal microflora of the oral cavity and gastrointestinal tract. Although this bacterium is usually nonpathogenic, in rare cases, it causes bacteremia, endocarditis, and meningitis (1). S. salivarius meningitis is mainly caused by medical procedures, such as epidural anesthesia, spinal myelography (1,2) and endoscopic treatment of gastrointestinal disease (3,4). In addition, some cases of S. salivarius meningitis associated with gastrointestinal carcinoma have been reported (5-7).

We herein report a case of S. salivarius meningitis that led to the diagnosis of early esophageal cancer and early gastric cancer.

Case Report

An 81-year-old Japanese man was admitted to our hospital with an acute onset of consciousness disturbance. He had had a headache from the day before admission and developed consciousness disturbances one hour before coming to our hospital. His medical history included chronic atrial fibrillation, hypertension and chronic kidney disease. He had no diseases, nor was he receiving any treatment that suppressed the immune system. He had no history of head injury, surgery or dental procedures.

He was febrile with a body temperature of 39.2°C. His other vital signs were normal. A physical examination revealed no crackles, heart murmur or abdominal tenderness. His oral cavity was clean. No papilledema or cerebrospinal fluid (CSF) leakage was identified. He was disoriented and unresponsive to verbal commands, with a Glasgow Coma Scale (GCS) score of 11 (E2, V4, M5). He showed marked nuchal rigidity, and Brudzinski's sign was positive. The cranial nerves were intact. There was no motor weakness or cerebellar ataxia. His tendon reflexes were slightly increased in the lower extremities, without any pathological reflexes.

Laboratory tests revealed the following: white blood cell count, 9,160 /μL; C-reactive protein, 4.57 mg/dL; and procalcitonin, 0.14 ng/mL. A urinalysis with microscopy showed normal results. Urinary culture revealed no infectious pathogens. The CSF was cloudy, and the initial pressure was 27 cmH₂O. A CSF analysis revealed pleocytosis (2,671 /μL, 98% polymorphonuclear leukocytes), elevated protein (446 mg/dL) and hypoglycemia (37 mg/dL, while the circulating blood glucose was 136 mg/dL). Findings of brain magnetic resonance imaging (MRI) performed the day after receiving primary treatment were consistent with acute ventriculitis without evidence of brain abscess (Fig. 1). There were no abnormal signals in the sulcus or cisterna. No definite vegetation or valvular disease was detected on transthoracic echocardiography.

Figure 1.

Brain magnetic resonance images of the patient. Axial diffusion-weighted imaging showed pus layering within the lateral ventricles (arrowheads, A). There was no parenchymal brain abscess (B).

Bacterial meningitis was suspected, and vancomycin (1.5 g followed by 0.5 g every 12 hours), meropenem (1 g every 12 hours), and dexamethasone (0.15 mg/kg every 6 hours for 4 days) were administered empirically. Because he was not immunosuppressed, we decided that initial treatment for tuberculous or fungal meningitis was unnecessary. His consciousness improved, and his fever subsided the day after the initiation of treatment. Two sets of blood cultures were positive for S. salivarius, but the CSF culture remained sterile after seven days of incubation, including enriched culture media. CSF India ink staining and Ziehl-Neelsen staining were negative.

We diagnosed the patient with S. salivarius bacteremia and meningitis. On day 3, antimicrobial therapy was switched to ceftriaxone (CTRX) (2 g every 12 hours), guided by the results of the susceptibility testing. His headache and nuchal rigidity resolved on hospital day 7.

CTRX was discontinued on day 14 because of drug eruption and normal results of the second CSF analysis on day 15. Additional workup, including whole-body computed tomography and colonoscopy, did not reveal an abscess or tumor, while esophagogastroduodenoscopy revealed a protruding and slightly elevated lesion (Paris classification 0-Is+IIa) located 36 cm from the incisors (Fig. 2A) and a slightly elevated lesion (Paris classification 0-IIa) in the greater curvature of the lower gastric body (Fig. 2B). The biopsy specimens of these lesions demonstrated moderately differentiated squamous cell carcinoma of the esophagus (Fig. 2C) and well-differentiated tubular adenocarcinoma of the stomach (Fig. 2D). Serological testing for Helicobacter pylori was negative.

Figure 2.

Esophagogastroduodenoscopic images and biopsy specimens (Hematoxylin and Eosin staining, ×100). Esophagogastroduodenoscopy revealed a protruding and slightly elevated lesion (Paris classification 0-Is+IIa) 36 cm from the incisors (A) and a slightly elevated lesion (Paris classification 0-IIa) in the greater curvature of the lower gastric body (B). Histological examinations showed moderately differentiated squamous cell carcinoma of the esophagus (C) and well-differentiated tubular adenocarcinoma of the stomach (D).

The patient was discharged without clinical sequelae on day 29. Subsequently, he underwent endoscopic submucosal dissection for each malignant lesion by the gastroenterology department of our hospital.

Discussion

S. salivarius is an unusual cause of acute bacterial meningitis. S. salivarius meningitis occurs in patients of all ages, from children to elderly individuals, and a review of the relevant literature revealed no marked sex difference in prevalence (1). The most common cause of S. salivarius meningitis is iatrogenic procedures, such as spinal anesthesia and myelography (1). In such cases of iatrogenic meningitis caused by S. salivarius, the S. salivarius isolated from the CSF of the patients and the bacterium isolated from the oral flora of anesthesiologists or radiology physicians who performed spinal anesthesia or myelography were genetically indistinguishable (2,8). Although most cases of S. sarivalius meningitis improve without sequelae, some fatal cases have been reported (9,10). Therefore, the use of a facemask and proper aseptic technique are important for preventing iatrogenic central nervous system infections. In the present case, there was no evidence of S. salivarius infection through medical procedures, as the patient had no history of spinal surgery or spinal anesthesia. In addition, some cases of S. salivarius meningitis associated with gastrointestinal carcinoma have been reported (5-7). Ijyuuin et al. reported that early gastric adenocarcinoma was found in an S. salivarius meningitis patient (7). Our case resembled the one from that report, except that two early gastrointestinal tract malignancies were found at the same time in our patient.

Recently, alterations in the gut microbiome have been reported to be a marker for gastric cancer (11). In addition to the fecal microbiome, it has been reported that the salivary microbiota may be key to the early detection of gastrointestinal cancer (12,13). S. salivarius has been suggested to be significantly increased in the saliva of patients with esophageal squamous cell carcinoma in comparison to healthy controls (12). In a murine model, coinfection with S. salivarius and H. pylori induced significantly more severe gastric pathology than H. pylori infection alone (14). The mechanism underlying the action of S. salivarius in the H. pylori-infected gastric mucosa remains to be elucidated. Some strains of S. salivarius are suggested to induce proinflammatory cytokine production (15), whereas other strains function as probiotics and show anti-inflammatory properties (16). These cytokine production responses may be involved in the pathological changes in the H. pylori-infected gastric mucosa. Although our patient was negative for H. pylori, S. salivarius itself may have affected the esophagus and gastric mucosa.

Bacteremia in cancer patients is commonly associated with hematological malignancies or complications after chemotherapy or surgical treatment for solid cancers; however, some cases are suggested to be associated with solid cancers themselves. In particular, Streptococcus bovis bacteremia is significantly associated with colorectal neoplasms (17). The biochemical heterogeneity and phenotypic characteristics of S. bovis are close to those of S. salivarius (18,19). Most reports on the relationship between bacteremia and cancer involve patients with advanced-stage cancer. However, a Japanese case of early gastric cancer diagnosed based on the detection of bacteremia due to Raoultella planticola - a normal inhabitant of feces and sputum - has been reported (20). Although our case was suspected of being associated with bacteremia and biliary tract infection, a possible association with early cancer was also considered. The further accumulation of cases is necessary to clarify the relationship between early cancer and bacteremia.

In our case, it is reasonable to assume that S. salivarius meningitis was associated with multiple early gastrointestinal cancers in the absence of other sources of infection. S. salivarius infection may have occurred due to the disruption of the gastrointestinal mucosa in association with early esophageal cancer and early gastric cancer.

Conclusions

The present and previous cases suggest that S. salivarius can affect the gastrointestinal mucosa. Gastrointestinal cancer damages mucosal tissue, resulting in bacteremia due to the normal microflora of the gastrointestinal tract. We propose screening for gastrointestinal tract malignancies in patients with bacteremia or meningitis caused by S. salivarius.

Informed and voluntary consent for publication was obtained from the patient described in the article.

The authors state that they have no Conflict of Interest (COI).