Clostridium Tertium Meningitis as the Presenting Sign of a Meningocele in a Twelve-Year-Old Child

Anaerobic bacterial meningitis is a rare entity, usually seen as a complication of anaerobic brain abscesses.1 Clostridial meningitis comprises a small percentage of anaerobic meningitis cases. It can develop as a result of hematogenous dissemination from a focus in the gastrointestinal tract or from direct introduction of the bacterium into the central nervous system. Meningitis caused by Clostridium tertium has not been described before, although a case of a C. tertium intracranial abscess after a penetrating head injury from a lawn dart has been reported in a young girl.2 We present a case of meningitis caused by C. tertium in a 12-year-old immunocompetent patient that led to the diagnosis of occult congenital vaginal and rectal fistulae to an anterior meningocele. Case report. A 12-year-old girl was admitted to our hospital with complaints of headache and backache for ∼1 month. The symptoms had been managed as sinusitis by her primary physician, and she had received two courses of antibiotic therapy with amoxicillin/clavulanate and clarithomycin. She also complained of intermittent low grade fever and a recent episode of vomiting. About 6 weeks before admission the patient had been sexually assaulted by a relative. Pelvic examination and cultures performed at that time had been negative, although she had complained of yellowish vaginal discharge since. Otherwise her past medical history was unremarkable. There had been no recent travel and no unusual animal exposures, and her immunizations were up to date. On admission her temperature was 38.7°C, the heart rate was 120/min, respiratory rate was 20/min and blood pressure 113/61 mm Hg. She was normally developed, alert and oriented but very agitated. Genital and rectal examination were refused by the patient. She refused to sit, flex her neck or fully extend her legs because of back stiffness and pain; her gait was stiff and shuffling. The remainder of the neurologic examination showed normal fundi and cranial nerves, deep tendon reflexes +1 and equal bilaterally and normal muscle strength. The sensory and cerebellar examinations were normal. The remainder of the physical examination was normal. A cerebrospinal fluid (CSF) examination revealed a white blood cell count of 7000/mm3 with 81% neutrophils, 6% lymphocytes and 13% monocytes; red blood cell count was 300/mm3, protein was 190 mg/dl and glucose was 2 mg/dl. Gram stain of the CSF demonstrated Gram-negative rods. Blood and CSF cultures were obtained and therapy was begun with vancomycin, cefotaxime and gentamicin. Fever resolved rapidly and the leg and back pain and stiffness gradually resolved during the next few days. On the second hospital day the CSF (cultured aerobically only) grew Gram-variable rods from the culture broth. An anaerobic organism was suspected and metronidazole was added. The next day Gram-variable rods grew from the aerobic plate as well; subculture under anaerobic conditions (on ACDC blood agar) also yielded growth. The organism was susceptible in vitro to vancomycin and resistant to colistin and kanamycin and was spore-producing under anaerobic conditions. Cefotaxime and gentamicin were discontinued. On the fifth hospital day the organism was identified as C. tertium based on its saccharolytic characteristics; it did not grow in subculture for further susceptibility testing. C. tertium is a difficult organism to identify because it is aerotolerant and can present with variable Gram stain results, thus causing incorrect early identification as a Bacillus species or as a Gram-negative enteric organism.2, 3 Lack of catalase production, the gas chromatography profile and other biochemical tests (saccharolytic but not proteolytic), as well as spore production under anaerobic conditions, help to differentiate C. tertium from these other organisms. Other distinct characteristics are the large size (1.5 × 10 μm), and its unusual "squarish" morphology on Gram-stained smear. Clostridium histolyticum and Clostridium carnis are the other two aerotolerant species of clostridia. Workup for a source of the meningitis included computed tomographic scans of the sinuses and the brain that were normal, with small amounts of intraventricular air seen initially, which disappeared on follow-up study 3 days later. An HIV test was negative. The patient was taken to the operating room for a pelvic examination under anesthesia to culture the genital tract and to evaluate for a possible rectovaginal fistula that might have resulted from the sexual assault. Two fistulous tracts were found connecting the vagina and the rectum with an approximately 3- by 4-cm cavity positioned anteriorly to the sacrum. With injection of contrast material into the cavity, purulent drainage exited from the vagina; the contrast extended to the meningeal area through the communication with the cyst. Cultures from the cyst contents grew Enterococcus species and rare Clostridium innocuum. Magnetic resonance imaging of the spine showed a dysplastic sacrum with the cystic lesion positioned between the sacrum and the rectum and contiguous with the thecal sac (Fig. 1). Dysplastic neural tissue was seen in the sac, and the spinal cord was tethered, terminating at the L2 to L3 level. The cyst was thought to represent an anterior meningocele.Fig. 1: Magnetic resonance image of the spine (sagittal section), showing the presence of a meningocele positioned anterior to the sacrum and posterior to the rectum (arrow). Probes in the fistulous tracts connecting the sac with the vagina and the rectum can be seen. Dysplastic neural tissue is evident in the thecal sac.The patient subsequently underwent a diverting colostomy. At the completion of a 3-week course of vancomycin and metronidazole, she underwent a combined surgical and neurosurgical procedure, anteriorly to close the fistulae and posteriorly to resect the cyst and untether the spinal cord. Discussion.C. tertium is an aerotolerant anaerobic Grampositive bacillus that has been traditionally thought of as nonpathogenic to humans,2-6 although during World War I it was a cause of gas gangrene.2 It is isolated mostly from the gastrointestinal tract, but it has also been reported in oral flora.4, 7, 8 Three recent case series and a few case reports have identified C. tertium as a cause of septicemia in patients with neutropenia, particularly those with hematologic malignancies.3-7, 9 In a review of 402 hospital admissions of patients with acute leukemia, 6 of 116 septicemia episodes were caused by anaerobes.9 Of those, 3 were caused by Bacteroides species, 2 by Fusobacterium species and 1 by C. tertium. All patients were receiving broad spectrum antibiotics at the time of the bacteremia episode. Five patients with C. tertium septicemia had clinically apparent sources of infection, associated with the gastrointestinal tract. A cluster of 7 febrile and severely neutropenic patients who developed C. tertium bacteremia in a 13-month period was described from Finland.6 Two patients had perirectal and 1 had pericecal cellulitis. In a review of 10 patients with C. tertium bacteremia and neutropenia,5 the abdomen was the source of the infection in 7 of the cases, in most cases being perirectal cellulitis. In another case series covering a 7-year period, 18 patients with hematologic malignancy and C. tertium bacteremia were described.4 Fifteen of these had abdominal pain, diarrhea or colonic bleeding, and 3 had perianal cellulitis. A case of neutropenic enterocolitis with bacteremia was described in a 15-year-old boy with acute lymphocytic leukemia.7 The majority of the isolates tested in these case series had MICs to penicillin ≥1 μg/ml, and most had MICs to clindamycin ≥2 μg/ml.4-6 In one patient C. tertium grew from blood cultures despite 2 days of intravenous metronidazole therapy,6 although all strains were reported to be susceptible in vitro to metronidazole, vancomycin, rifampin, chloramphenicol and imipenem.4-6 The unusual pattern of resistance of this clostridial species to many standard antimicrobial agents emphasizes the need for accurate speciation, particularly in patients with neutropenia, and in those with a possible source of infection in the gastrointestinal tract. This becomes more important because the organism may be difficult to identify by being Gram-variable and aerotolerant. Focal infections outside the gastrointestinal tract associated with C. tertium bacteremia have been reported in a few cases. Bacteremia associated with pneumonia was reported in two 7-year-old immunologically normal patients during an influenza epidemic10 and in an immunocompetent patient with aspiration pneumonia.8 To our knowledge this is the first report of C. tertium meningitis. The only other central nervous system infection caused by C. tertium described before is that of a brain abscess after penetrating head injury in a previously healthy child.2 The presence of this unusual organism in the CSF led to the diagnosis of a congenital communication between the central nervous system and the gastrointestinal and genital tracts. Athena P. Kourtis, M.D., Ph.D. Risa Weiner, M.S. Karen Belson, M.D. Frank O. Richards Jr., M.D. Department of Pediatrics; Emory University School of Medicine; Atlanta, GA