Osteomyelitis due to Chryseobacterium (Flavobacterium) meningosepticum

an update. Drugs 49(Supp1.2): 159-163. Martell M, deBen S, Weingerger M, Beltrami G: 1996. Growth and development on preterm infants receiving fluoroquinolones. J Pediat Med 24:287-291. Maxwell A: 1992. The molecular basis of quinolone action. J Antimicrob Chemother 30:409-414. McGarvey WC, Singh D, Trevino SG: 1996. Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review. Foot Ankle Intemat 17:496-498. Moore MR: 1993. Biochemistry of porphyria. Int J Biochem 10:1353-1368. Moreau NJ, Robaux H, Baron L, Tabary X: 1990. Inhibitory effects of quinolones on pro and eukaryotic DNA topoisomerases 1 and II. Antimicrob Agents Chemother 341955-1960. Norrby SR, Lietman PS: 1993. Safety and tolerability of fluoroquinolones. Drugs 45(Suppl. 3):S59-S64. Osheroff N, Corbett AH, Elsea SH, Westergaard M: 1994. Defining func-

tional drug-interaction domains on topoisomerase II by exploiting mechanistic differences between drug classes. Cancer Chemother Pharmacol34(Suppl.):S19-S25. Paton JH, Reeves DS: 1991. Clinical features and management of adverse effects of quinolone antibacterials. Drug Safety 6:8-27. Percival A: 1991. Impact of chemical structure on quinolone potency, spectrum, and side effects. J Antimicrob Chemother 28(SupplC):Sl-S8. Pipek R, Vulfsons S, Wolfovitz E, Har-Shai Y, Taran A, Peled IJ: 1996. Case report: ofloxacin-induced hypersensitivity vasculitis. Am J Medical Sci 311:82-83. Robinson MJ, Martin BA, Gootz TD, McGuirk PR, Osterhoff N: 1992. Effects of novel fluoroquinolones on the catalytic activities of eukaryotic topoisomerase II: influence of the C-8 fluorine group. Antimicrob Agents Chemother 36:75 l-756. Schaad UB: 1993. Use of quinolones in paediatrics. Drugs 45(Suppl3):S37-S41. Shen LL, Pemet AG: 1985. Mechanism of

inhibition of DNA gyrase by analogues of nalidixic acid: the target of the drugs is DNA. Proc Nat1 Acad Sci USA 82:307-3 11. Stahlmann R: 1990. Safety profile of the quinolones: J Antimicrob Chemother 26(SupplD):S31-S44. Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA: 1992. Fluoroquinolones: relationships between structural variation, mammalian cell cytotoxicity, and antimicrobial activity. J Medicinal Chem 35:4745-4760. Tillotson GS: 1996. Quinolones: structureactivity relationships and future predictions. J Medical Microbial 44:320-324. Vosberg HD: 1985. Topoisomerases: enzymes that control DNA conformations. Curr Top Microbial Immunol 114:19-102. Wang JC: 1985. DNA topoisomerases. Annu Rev Biochem 54:655-697. Wolfson JS, Hooper DC: 1989. Fluoroquinolone antimicrobial agents. Clin Microbial Rev 2:378-424.

Case Report

Osteomyelitis Due to Chryseobacterium (Flavobacterium) Lawrence A. Cone’s* Timothy J. Cronin’ Mario Curti* David Friscia’ ‘Departments of Medicine, Pathology, and Surgery Eisenhower Medical Center Ranch0 Mirage, CA 92270 2Department of Medicine Harbor-UCLA Medical Center Torrance, CA 90502

Introduction Chryseobacterium (formerly Flavobacterium) meningosepticum is a saprophytic, rarely encapsulated, non-fermentative, non-motile thin, Gram-negative bacillus that is widely distributed in soil, water, and food. Chryseobacteria are also common colonizers in the hospital environment and have beenisolated from ice machines, vials of intravenous drugs, nebulizers, topical disinfectants, and hand cultures of hospital personnel. C. meningosepticum also can colonize the upper respiratory tract.

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C. meningosepticumis an uncommon human pathogen and causesdisease predominantly in premature newborns and infants due to the immaturity of their natural barriers againstinfection. Meningitis, ordinarily accompaniedby bacteremia,is the most common clinical presentationwith 79 casesglobally having beenrecorded by May, 1998. Most seriousinfections in adults occur in patients with significant underlying diseasesuchasmalignant neoplasms,tuberculosis, leukemia, aplastic anemia, bone marrow and solid organ transplants,and treatment in intensive care settings.Bolivar and Abromovits reported a cutaneousinfection due to C. meningosepticumin a healthy 57-year-old female, while Abter et al. describeda 74-year-old-male with cellulitis and bacteremia.We describe the first recorded caseof C. meningosepticumosteomyelitis with localized, recurrent skin infections.

Case Report A 43-year-old, healthy, white female

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meningosepticum

developed a painful nodule on her left heeljust below the Achilles tendon about two years earlier. She received treatment from a local podiatrist who incised the erythematous and swollen site and treated the infection with oral cephelexin. Subsequently,the patient experienced similar episodesof pain, erythema, and ulceration recurring at the identical site two to three times annually: theserecurrenceswere always treated with cephelexin and gradually healed.Cultures were never obtained. A magnetic resonanceimaging study was performed in July 1998 that revealed osteomyelitis of the calcaneus. The patient was hospitalized at the Eisenhower Medical Center for bone biopsy and cultures. On admission,the physical examination was unremarkable other than for a 3 cm x 3.5 cm clean ulcer of the left heel. A CBC, blood chemistries,urinalysis, and chest x-rays were normal. A bone biopsy revealed nonnecrotizing granulomatousinflam-

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mation and focal collections of mononuclear cells. Histological stains and cultures for acid-fast bacilli and fungi were negative/sterile. Bacterial cultures however, grew a very rare colony of coagulase-negative staphylococci and C. meningosepticum. The latter colonies were 1.0 to 1.5 mm on blood agar, nonhemolytic, and yellow in color. They were both catalase and oxidase positive. There was no growth on SalmonellaShigella agar. Urea was not hydrolyzed, nitrates were not reduced, and citrate was not utilized as a source of carbon. Tryptophan deamination, esculin hydrolysis, gelatinase, paranitrophenyl-8-o-galactopyranoside (PNPG), and assimilation for p-glucose, L-arabinose, D-mannose, D-mannitol, N-acetyl-D-glucosamine, and maltose were positive. Sensitivity studies by disc diffusion (Kirby-Bauer) revealed that the organism was sensitive to vancomycin, clindamycin, trimethoprim/sulfamethoxazole, and ofloxacin, intermediately sensitive to gentamicin, and resistant to ceftazidime and ticarcillin/clavulanate. MICs were as follows: vancomycin = 8 pg/ml, trimethoprim/sulfamethoxazole = 0.5 pg/ml, ofloxacin = 0.5 pg/ml, gentamicin = 12 pg/ml, ceftazidime = 256 pg/ml, and ticarcillin/clavulanate = 256 pglml. The patient was started on trimethoprim/sulfamethoxazole, 1501800 mg every 12 hours orally and discharged from the hospital. Ten days later, she developed fever, malaise, myalgia, and an urticarial eruption. The drug was discontinued and the patient then received 500 mg of levofloxacin daily for an additional 18 days. Eight months later, there has been no recurrence of her heel pain and erythema, and a recent MR of the calcaneous revealed near total resolution of the osteomyelitis.

Discussion In 1944, Shulman and Johnson reported a case of meningitis in a premature infant due to an unidentified Gramnegative bacillus. Fifteen years later, King, while studying unclassified bacteria associated with meningitis in infants, named the organism Flavobacterium, (recently Hellenized to Chryseobacterium) “the yellow bacillus” and meningosepticum associated with “meningitis and sepsis.” Since then,

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the organism has been identified in a number of different infections. These include 79 infants with meningitis, 25 adults with pneumonia, 19 with postoperative bacteremia or infected arterial catheters, 11 with meningitis, and two each with bacteremia, endocarditis, cellulitis, abdominal and eye infections, and one each with epididymitis, sinusitis, and bronchitis. C. meningosepticum is a water bacillus that is capable of multiplying at room temperatures in aqueous environments devoid of organic carbon and nitrogen. It is a Gram-negative, nonsporulating, slender, slightly curved, rarely encapsulated rod. Colonies do not exhibit hemolysis on blood agar where pigment production is either beige or light yellow. C. meningosepticum is non-motile, catalase-, oxidase-, and phosphatase-positive. The appearance of tiny, oxidase-positive, light yellow colonies on blood agar after 24 hours of incubation is very suggestive of the organism. Although the organisms are fermentative, acid production is slight. The carbohydrates most frequently attacked are glucose, fructose, maltose, and trehalose. Six serologic groups (A-F) of C. meningosepticum are recognized and most of the typed strains causing disease belong to serovar C. Although serotyping is of value in epidemiologic studies, it is otherwise not widely used nor available. The pathogenicity C. meningosepticum appears to be variable. For example, this microorganism is not pathogenic for mice or rabbits but has been reported to cause meningitis in a cat. The ability of C. meningosepticum to cause disease in humans is somewhat the same. In infants with neonatal meningitis, the microorganism causes a serious infection in which the mortality exceeds 50%, yet in nursery outbreaks, many infants had positive nasal and throat cultures but remained healthy. Although C. meningosepticum is not often associated with disease in adults, clinical presentations vary from systemic infection with an isolate that is resistant to most antimicrobial agents to instances when the infection resolved spontaneously without antimicrobial therapy. Serious illness with this organism in adults often is related to underlying diseases such as malignant neoplasms,

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tuberculosis, leukemia, aplastic anemia, bone marrow and solid organ transplants, as well as prolonged stay in intensive care settings. On rare occasions, C. meningosepticum causes disease in healthy persons. Cellulitis was described in 1989 in a healthy woman and, in 1993, in an elderly male with mild heart failure. We record an otherwise healthy female who presented with recurrent cellulitis of the foot and was shown to have underlying osteomyelitis of the calcaneus. C. meningosepticum has never previously been reported as a cause of osteomyelitis. Although most instances of osteomyelitis in non-diabetic adults are either caused by Staphylococcus aureus, streptococci, or Gram-negative enteric bacilli including Salmonella, since the 1970’s non-enteric, nonfermentive Gram-negative rods have been increasingly recognized etiologies. Pseudomonas aeruginosa, Alcaligenes xylosoxidans, and Acinetobacter spp. are examples of such infections. It is of interest to note that a granulomatous reaction in bone was noted in our patient with osteomyelitis due to C. meningosepticum. Granulomatous skin reactions have previously been noted by Findlay et al. in a patient with skin lesions due to Flavobacterium capsulatum. The histology of this case is reinforced as being consistent with C. meningosepticum because of the failure to histologically demonstrate or culture either acid-fast bacilli or fungi. Finally, therapy of C. meningosepticum infections is somewhat unique since the antimicrobial sensitivity pattern more closely resembles that of Gram-positive rather than Gramnegative bacteria. It is the only Gramnegative rod for which vancomycin therapy has been successfully employed. Previous authors have shown that the combination of vancomycin and rifampin based upon clinical outcomes appears to be the most appropriate therapy for patients with meningitis or bacteremia, although this therapeutic approach has recently been questioned. For less acute and life-threatening illnesses such as cutaneous or skeletal infections, trimethoprim/sulfamethoxazole, minocycline, the newer quinolones, clindamycin and linezolid, an oxazolidinone currently under clinical study for Gram-positive infections, appear

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appropriate. C. meningosepticum is resistant to the penicillins, the penicillin/ beta-lactamase inhibitors, cephalosporins, and carbapenems and are only intermediately sensitive to the aminoglycosides. Thus, an antimicrobial sensitivity pattern described above with a Gram-negative isolate is highly suggestive of a Chryseobacterium infection. In summary, C. meningosepticum is an unusual, but very real pathogen. The lessons learned in dealing with this patbogens are important because increasing encounters with such non-enteric, nonfermentive Gram-negative rods in skin, soft tissue, and skeletal infections is to be anticipated in the future.

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