Methylobacterium Mesophilica as a Cause of Persistent Bacteremia in a Child With Lymphoma

Methylobacterium mesophilica, a Gram-negative, pink-pigmented rod bacterium, was first isolated from leaf surfaces.1 It is an opportunistic pathogen that causes disease primarily in immunocompromised patients. Its low virulence probably accounts for the low attendant mortality, but this organism can cause morbidity in the immunosuppressed. Among the infectious manifestations reported in such patients, those associated with indwelling intravascular devices are common.2, 3 These infections have been indolent and non-life-threatening, leading Kaye et al.2 to recommend monotherapy with an aminoglycoside, without removal of the intravascular device. We present a pediatric patient with protracted central venous catheter-associated infection caused by M. mesophilica. Our patient's bacteremia and prolonged febrile episodes did not resolve until the catheter was removed. Case report. A 5-year-old Caucasian boy undergoing intensive, highly immunosuppressive systemic chemotherapy for T cell lymphoma diagnosed 7 months previously was evaluated at Texas Children's Hospital for a 4-month history of intermittent fever. His oral temperature ranged from 101 to 104°F and was experienced during, but not limited to, periods of neutropenia (absolute neutrophil count, <1000/mm3). He received a course of maintenance chemotherapy on October 9, 1996, and was hospitalized 6 days later with fever (101°F), nausea, vomiting and abdominal pain. Physical examination revealed a febrile child who was well-nourished and nontoxic, without localizing findings. The Hickman catheter site (placed at the time of diagnosis) appeared normal. Blood cultures were obtained from a peripheral vein and through the Hickman catheter, and the patient was treated with intravenous gentamicin and ticarcillin/clavulanate for 10 days. Blood cultures were sterile. The fever resolved briefly but reappeared after therapy was discontinued, prompting studies that included abdominal computed tomography, echocardiography and serologic testing. Bone marrow aspiration, biopsy and cultures also were obtained. Approximately 6 weeks after presentation, fever persisted without an apparent explanation, and the patient was again admitted to the hospital. Aerobic, anaerobic, fungal and acid-fast bacterial cultures of the blood and various serologic studies were obtained. No antimicrobial therapy was instituted because the patient appeared to be healthy except for fever. After 8 days of incubation, four of six acid-fast bacterial cultures of blood and the previous bone marrow aspirate acid-fast bacterial culture yielded a Gram-negative bacterium. Ticarcillin/clavulanate and gentamicin therapy was initiated. The microorganism could not be identified either by the hospital or the Houston City Health Department laboratories so it was sent to the Centers for Disease Control and Prevention. While awaiting identification of the microorganism, the patient remained febrile except during a 5-day interval of intravenous gentamicin therapy. In January, 1997, the Gram-negative organism isolated from bone marrow culture from late October, 1996, was identified as M. mesophilica. Blood cultures obtained from the Hickman catheter on December 23, 24 and 25, 1996, and a bone marrow aspirate culture from January 15, 1997, subsequently grew the same microorganism. The Hickman catheter was removed on January 23, 1997. Since then the patient has been afebrile and blood cultures have been sterile. Discussion.M. mesophilica has distinctive microbiological characteristics.4 The nomenclature of the organism is confusing given that it has been designated by several names, including Pseudomonas mesophilica, Vibrio extorquens, Mycoplana rubra and Protaminobacter ruber. The species M. mesophilica and Methylobacterium extorquens are considered synonymous,5 although DNA analyses indicate that they actually are different species.6 M. mesophilica has been isolated from a variety of clinical and environmental sources and recovered from cultures of blood,2, 3, 7 peritoneal fluid,8 skin lesions9 and corneal tissue.10 It has been reported to cause colonization,7 contamination11 and clinical infectious disease. In our patient clinical infection was proved by the isolation of M. mesophilica from several blood cultures during a 2-month interval when the patient was symptomatic, and from the bone marrow culture. Although this microorganism is most commonly isolated from immunosuppressed patients, it has not been reported in patients infected with the human immunodeficiency virus. M. mesophilica should be suspected as a cause of infection when Gram-negative rods that are pink-pigmented are isolated from the culture of an immunocompromised patient, especially if its isolation from routine blood culture media has been difficult. In our patient the organism was first isolated from blood cultures using the BACTEC® system (13A Tb bottle), after prolonged incubation as also reported by Gilchrist et al.7 Later in the clinical course routine anaerobic and aerobic cultures also grew the organism, perhaps reflecting a higher inoculum. There is controversy regarding the need for removal of an intravascular device in patients with Methylobacterium infection.2, 3 Poirer et al.3 were able to eradicate the infection leaving the catheter in place. Although the central venous catheter was removed in all but one patient reported by Kaye et al.,2 these authors recommend antimicrobial therapy without removal of the catheter. Gentamicin, amikacin, trimethoprim-sulfamethoxazole and ciprofloxacin inhibit the growth of Methylobacterium, but this organism is resistant to most beta-lactams except for ceftriaxone and ceftizoxime.12 Our patient received several antimicrobial agents to which the organism was susceptible in vitro (e.g. gentamicin)12 but fever and bacteremia persisted until the central catheter was removed. We believe that serious consideration should be given to removal of the catheter if Methylobacterium is isolated. It also is important for physicians involved in the care of immunocompromised patients to be aware of unusual organisms such as M. mesophilica, and alert the microbiology laboratory to hold cultures for prolonged periods of incubation. Special blood culture media and prolonged incubation may be necessary for its isolation. Prompt identification facilitates the initiation of appropriate therapy, thus decreasing the morbidity associated with this infection and limiting the interruption of essential cancer therapy. Marisol Fernandez, M.D. ZoAnn Dreyer, M.D. Marilyn Hockenberry-Eaton, Ph.D. Carol J. Baker, M.D. Department of Pediatrics; Sections of Infectious Diseases (MF, CJB) and Hematology/Oncology (ZD, MHE); Baylor College of Medicine; Houston, TX