We report on a case of C. fetus bacteremia and meningitis successfully treated with meropenem in a patient with ALL.
Notably, the patient consumed undercooked beef and subsequently developed meningitis, as previously reported [6]. Although she denied any abdominal pain or diarrhea, considering that approximately half of the patients with C. fetus meningitis were without any gastrointestinal symptom, we assumed that the origin of infection could be the gastrointestinal tract [3, 7]. C. fetus is a part of the normal flora in the gastrointestinal tracts of sheep and cattle [8]. A previous study reported 38% of the 19 cases had frequent contact with domestic animals [3] and 62–73% cases of C. fetus bacteremia or meningitis had a significant underlying disease, such as diabetes, alcoholism, or cardiovascular diseases [3, 9]. Since this patient underwent maintenance therapy for ALL, the white blood cell count on admission was low, especially a neutrophil count of approximately 1000/μL was noted for at least 1 month, and the patient was considered immunocompromised. On the contrary, immunocompetent individuals also experience C. fetus bacteremia [10, 11], and we should always pay attention when spiral gram-negative rods are obtained on blood culture.
In previous studies, a neutropenic diet has referred to a low bacterial diet, and neutropenic patients have been instructed to avoid mainly fresh fruits or vegetables [12, 13]. A recent study showed that a neutropenic diet was not associated with a reduced risk of infection in neutropenic patients [14]; therefore, we did not instruct the patient to adhere to a neutropenic diet. However, safe food handling [15] may have been insufficient, and the entry of C. fetus was due to lack of instruction to the patient. In Japan, eating raw or undercooked meat is customary and the guidance on safe food handling is seemingly not thorough. Since food habits in Japan are often different from those in Western countries, it was considered necessary to create Japanese versions of safe food handling protocols. Furthermore, owing to limited evidence regarding consumption of undercooked meat or fish among neutropenic patients, further studies are needed to establish safe management of immunocompromised patients.
Since the patient did not have fever or neck stiffness or jolt accentuation, lumbar puncture was not performed on the day of admission. We considered that central nervous system infiltration of ALL or chemical meningitis was the primary differential diagnosis. However, she developed fever and was noted to present these signs on the second day; thus, we performed lumbar puncture and confirmed the diagnosis of meningitis. According to previous studies, clinical manifestations of C. fetus meningitis vary and only 64 and 59% had headache and neck stiffness, respectively, although fever was noted in approximately 90% of patients [3, 8]. Therefore, even if the patient has no neck stiffness or neurological abnormalities, clinicians should consider the possibility of C. fetus meningitis in immunocompromised or immunocompetent patients with high-risk dietary habits.
The recommended antimicrobials and duration of treatment for C. fetus infections are yet to be established. Previous studies reported the susceptibilities of C. fetus (MIC90) were as followed: meropenem 0.12 μg/mL, imipenem ≤0.06 μg/mL, cefotaxime 16–64 μg/mL, ampicillin 2–32 μg/mL, gentamycin 1–2 μg/mL, tetracycline 0.5–128 μg/mL, and ciprofloxacin 0.5–1 μg/mL [16,17,18]. The lowest MICs were obtained with imipenem and meropenem. Cefotaxime is not an appropriate antimicrobial for C. fetus infection, since lower bactericidal activities in vitro were reported than those of ampicillin, gentamicin, and imipenem [14]. In accordance with this and E-test results, we switched from ceftriaxone to meropenem and continued the treatment for 3 weeks. Meropenem 2 g IV every 8 h would be the first choice for C. fetus meningitis, considering imipenem poses a risk of causing seizure [19]. Although intrathecal therapy for meningitis is sometimes considered [20], there are no reports for C. fetus meningitis. Since it would be a possible treatment option, more cases need to be accumulated.
In conclusion, we encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness, or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered. No standard treatment for C. fetus infection has been established, and its susceptibility to antibacterial agents is insufficient. Further studies combining clinical symptoms and susceptibility data are warranted.