CAPNOCYTOPHAGA MENINGITIS IN A CANCER PATIENT

Capnocytophaga spp. have been implicated in a spectrum of diseases from periodontitis to severe local infections leading to sepsis in the normal, immunocompetent host. Recently the organism has been recovered in cases of bacteremia in the immunocompromised, granulocytopenic host, most often leading to sepsis.1, 2 There have been three published reports to date of Capnocytophaga meningitis in immunocompetent hosts3-5 and several reports of Capnocytophaga canimorsus meningitis in splenectomized patients who had contact with dogs.6 We report here the first case of Capnocytophaga meningitis in an immunocompromised host, an oncology patient with granulocytopenia resulting from both his disease and therapy. Case history. A previously healthy 15-year-old Caucasian male was admitted with a new diagnosis of acute myeloblastic leukemia and exhibited fever, upper respiratory tract symptoms and pallor. The initial evaluation showed that the hemoglobin was 11.5 g/dl; white blood cell count was 15 800/mm3 with 23% neutrophils, 56%blasts, and 16% lymphocytes; and platelet count was 18 000/mm3. Five days after hospitalization he was given oxacillin, gentamicin and ceftazidime for empiric treatment of fever and neutropenia. Blood and cerebrospinal fluid cultures were obtained and were sterile. The patient defervesced soon after initiation of antimicrobials with resolution of presenting symptoms. He was then given aggressive chemotherapy with cytarabine (intrathecal and intravenous), idarubicin, dexamethasone, etoposide and 6-thioguanine, receiving two courses during the following 2 weeks. On the 18th day of hospitalization, 4 days into his second round of chemotherapy, the patient developed acute onset of fever, throbbing diffuse headache and neck and back pain. His examination at that time was significant for meningismus with positive Brudzinski and Kernig signs and a decreased range of lateral neck motion. A lumbar puncture revealed xanthochromia with 4 white blood cells/mm3, 51 000 red blood cells/mm3, protein 889 mg/dl and glucose 52 mg/dl, and a Gram stain showed rare Gram-negative rods. The peripheral white blood cell count was 200/mm3 with 100% lymphocytes; hemoglobin was 8.8 g/dl and the platelet count was 13 000/mm3, which had been unchanged during the previous week. Because the patient developed these changes while receiving broad spectrum antibiotics, coverage was changed empirically to imipenem/cilastatin and amikacin while we awaited identification and susceptibility testing of the organism. In addition oxacillin was replaced with vancomycin to cover Gram-positive organisms in the presence of a central venous catheter in a febrile, neutropenic patient, and amphotericin B was begun for similar reasons. The cerebrospinal fluid culture grew Capnocytophaga gingivalis whereas a blood culture obtained at the same time had no growth. The organism was susceptible to imipenem and extended spectrum penicillins but intermediately susceptible to amikacin, gentamicin and tobramycin and resistant to ceftazidime. Disc diffusion and broth dilution testing were performed following National Committee for Clinical Laboratory Standards recommendations.7 In light of the susceptibility pattern the patient was treated with imipenem alone. During the next 2 days the patient showed marked symptomatic improvement with defervescence and resolution of meningismus. He was maintained on imipenem for 3 weeks and developed no complications from meningitis. Discussion. The Capnocytophaga genus was first identified in 1979 as a microaerophilic Gram-negative bacillus. It was formerly classified as Bacteroides ochraceus, also known as dysgonic fermenter-1 (DF-1) before identification as a separate genus.8 To date there are four identifiable species, Capnocytophaga ochraceus, Capnocytophaga sputigena, C. gingivalis, and C. canimorsus, each of which is characterized by a group-specific and type-specific antigen. The in vitro properties of the organism are distinct in that Capnocytophaga spp. are unable to grow on MacConkey agar but grow well on blood agar, appearing nonhemolytic with a pale beige to yellow-orange pigment after 2 to 4 days of incubation in anaerobic or 5 to 8% CO2 conditions at 37°C. The organism is fusiform and the colonies exhibit a gliding motility across blood agar. Its biochemical profile shows that Capnocytophaga spp. are indole-negative and weakly ferment glucose, lactose, mannose and sucrose; with the exception of C. canimorsus they are also oxidase- and catalase-negative. Most species are susceptible to penicillin, amoxicillin, erythromycin, clindamycin, tetracycline, chloramphenicol and metronidazole, as well as the cephalosporins, and they are uniformly resistant to semisynthetic penicillins, vancomycin and the aminoglycosides.9 The clinical setting of Capnocytophaga infections has been well described in the normal immunocompetent host and includes local infections, i.e. juvenile periodontitis, rapid progressive periodontitis eroding into the bone,10 sepsis and occasionally meningitis. In the immunocompromised host such as our oncology patient with granulocytopenia, Capnocytophaga infections most often present as sepsis, usually after breakdown of the oral mucosa secondary to chemotherapy.11 Our patient had minimal evidence of mucosal injury and had no documented bacteremia preceding or during the active meningitis. One might suspect that in this patient meningitis occurred secondary to an undetected transient bacteremia. This case demonstrates the need to consider normal oral flora as possible pathogens in the febrile immunocompromised patient. In addition the possibility of resistant organisms must be considered in the patient who has received broad spectrum antibiotics before onset of infection. In our case therapy had been started with antibiotics according to the protocol for febrile, neutropenic patients that is standard at our institution. The resistance pattern of the recovered C. gingivalis raises the issues of acquisition of new organisms during periods of neutropenia and development of new resistance patterns during prolonged broad antibiotic coverage. Therefore standard empiric therapy should be closely monitored and adjusted with new physical examination and laboratory findings suggesting the presence of such organisms. Jean O. Kim, M.D.; Jill Ginsberg, M.D.; Karin L. McGowan, Ph.D. Divisions of Allergy, Immunology and Infectious Diseases (JOK, KLM) and Hematology and Oncology (JG) Children's Hospital of Philadelphia Departments of Pediatrics and Microbiology (KLM) University of Pennsylvania School of Medicine Philadelphia, PA