Bacteremia Caused by Mycobacterium Neoaurum MALCOLM B

Bacteremia Caused by Mycobacterium neoaurum MALCOLM B. DAVISON,' JOSEPH G. McCORMACK,1* ZETA M. BLACKLOCK,2 DAVID J. DAWSON,2 MARTYN H. TILSE,3 AND FRANCIS B. CRIMMINS' Department of Medicine, University of Queensland, Mater Misericordiae Hospital, South Brisbane, Queensland 4101,' and Tuberculosis Laboratory, Laboratory of Microbiology and Pathology,2 and Department ofMicrobiology,3 Downloaded from Mater Misericordiae Adult Hospital, Brisbane, Queensland, Australia Received 18 September 1987/Accepted 14 December 1987

An immunocompromised patient with an indwelling Hickman catheter developed Mycobacterium neoaurum bacteremia. This rapidly growing mycobacterium was previously isolated from soil, dust, and water but has not been described as a human pathogen. The infection responded to therapy with cefoxitin and gentamicin. It was not necessary to remove the Hickman catheter. http://jcm.asm.org/

The first convincing evidence that mycobacteria other ethambutol per ml but not on MacConkey agar. Tests for than tubercle bacilli (MOTT) are potential pathogens was niacin production and p-aminosalicylate degradation were provided by Timpe and Runyon in 1954 (13). Since then, negative, while tests for nitrate reduction, Tween 80 hydrol- there has been increasing interest in their importance as the ysis (10 days), arylsulfatase (14 days), and iron uptake were causative agents of a variety of conditions, particularly in positive. Catalase activity was low. Glucose, fructose, ino- immunocompromised patients. The list of potential patho- sitol, and mannitol were utilized as carbon sources; sodium gens continues to grow. We describe here the first reported citrate was not utilized. Tests for the enzymes acetamidase,

human infection caused by Mycobacterium neoaurum. urease, nicotinamidase, pyrazinamidase, allantoinase, and on September 15, 2016 by University of Queensland Library The patient, a housewife born in 1933, had a history of valeramidase were positive, but tests for benzamidase, iso- cystadenocarcinoma of the ovary with involvement of ab- nicotinamidase, salicylamidase, and succinamidase were dominal nodes and peritoneal metastases. Bilateral salpingo- negative. Acid was produced from arabinose, glucose, glyc- oophorectomy and omentectomy had been performed in erol, inositol, mannitol, mannose, trehalose, and xylose but 1983. This was followed by radiotherapy and chemotherapy. not adonitol, erythritol, lactose, maltose, melibiose, raf- a Continuing total parenteral nutrition via Hickman catheter finose, rhamnose, and sorbitol. These properties are in has been required because of unremitting bowel obstruction keeping with the description of M. neoaurum by Tsukamura secondary to radiation enteritis and fibrosis. The course of et al. which differentiate the patient strain the patient has been punctuated by several episodes of (15). Properties fungemia and bacteremia caused by Saccharomyces cerevi- and M. neoaurum from M. aurum and M. parafortuitum are siae, Staphylococcus epidermidis (twice), and Enterobacter shown in Table 1. was the method cloacae, requiring temporary removal of the Hickman cath- Thin-layer chromatography performed by of Brennan et al. (3). The solvent mixture used was chloro- eter. In 1986, the patient developed fever and was readmit- ted to the hospital. In the following 72 h, nine blood form-methanol-water (65:25:4). M. aurum and M. parafor- specimens were collected (three from the Hickman catheter, tuitum gave essentially the same patterns, characterized by six from peripheral veins) and cultured aerobically and two brown bands with Rfvalues of 0.01 and 0.17. The patient anaerobically by using the BACTEC system (Becton Dick- strain and M. neoaurum also gave identical patterns, with inson and Co., Paramus, N.J.). There was radiometric one large broad band (perhaps two adjoining bands) in the evidence of growth after 2 to 5 days at 37°C (mode, 2 days) lower portion of the chromatogram (Rf, 0.10 to 0.21) and in the aerobic bottles only. After 2 days, subcultures on lighter bands of blue-purple in the upper half of the chroma- horse blood agar grew small, smooth, yellow colonies which togram. stained as gram-variable, acid-fast bacilli. Eight of the nine Subcultures were sent to M. Tsukamura, National Chubu cultures were positive. Hospital, Obu, Japan. In 120 tests, the strain was found to Because the isolate appeared to be a rapidly growing have a matching coefficient of 91% to the hypothetical scotochromogenic mycobacterium, an appropriate set of median organism for M. neoaurum, thus supporting identity tests was performed (5, 9, 15, 16). Tests indicated that the as this species. isolate belonged to the Mycobacterium aurum-M. neoau- Susceptibility to antimycobacterial compounds was tested rum-M. parafortuitum complex, so comparative tests were by using the resistance ratio method (4). The strain was repeated with the following strains: M. aurum 15006 susceptible to streptomycin and capreomycin, intermedi- (=ATCC 23366=NCTC 10437 [type strain]), M. neoaurum ately susceptible to ethionamide, and resistant to isoniazid, 10002 (=ATCC 25795=NCTC 10818 [type strain]), and M. ethambutol, rifampin, cycloserine, and thiacetazone. Disk parafortuitum 16002 (=ATCC 19686=NCTC 10411 [type diffusion susceptibility tests were also done (17), and zone strain]). sizes were measured after 48 h. Zones of inhibition of The patient strain was pigmented but not photochromo- .30-mm diameter were seen with amikacin (30 ,ug), kanamy- genic. It grew at 25 and 35°C (<5 days) but not at 45°C. cin (30 kg), gentamicin (10 ,ug), tetracycline (30 ,ug), mino- Growth was seen on media containing 5% NaCl-8 Lg of cycline (30 Fg), doxycline (30 F.g), sulfamethoxazole-tri- methoprim (25 ,ug), cefoxitin (30 ,ug), vancomycin (30 ,ug), imipenem (10 Fg), and enoxacin (10 ,ug). Cefotaxime (30 ,ug) * Corresponding author. and amoxycillin (25 xLg) gave zones of inhibition of 6 and 18 762 VOL. 26, 1988 NOTES 763

TABLE 1. Differentiating properties of four strains tested

Nitrate Enzymes Inositol as sole Resistance to Acid from: Organism Morphology reduction sourcea ethambutol (2 h) Acetamidase Allantoinase (8 p.g/ml) Adonitol Erythritol Glycerol Maltose Patient strain Short to normal, + + + + + - - + (5108/86) cigar shaped M. neoaurum (ATCC Short to normal, + + + + + - - + 25795, NCTC cigar shaped 10818, 10002) Downloaded from M. aurum (ATCC Fat coccobacilli - - - - - + + + 23366, NCTC 10437, 15006) M. parafortuitum Fat coccobacilli + + - - - + + - + (ATCC 19686, NCTC 10411, 16002) mm, respectively. The reference strain of M. neoaurum lonae (1), M. fortuitum (20), M. avium-M. intracellulare http://jcm.asm.org/ showed results similar to those of the patient strain. (10), and M. gastri (8) have been documented as the causes In deciding on an appropriate therapeutic approach, sev- of peritoneal sepsis in patients undergoing chronic ambula- eral factors were considered important. In keeping with tory dialysis. Rapidly growing mycobacteria have caused general principles of antimycobacterial therapy, we believed infections attributable to catheters of various types (2, 11, that at least two drugs should be given. Since absorption 12), as well as to prosthetic heart valves and augmentation from the oral route was unreliable in this patient and mammoplasties (19). long-term therapy was likely to be required, a system of Response to antimicrobial therapy in patients with non- infusion which could be largely managed by the patient at pulmonary infection caused by rapidly growing mycobac- home was needed. Tetracycline was considered unsuitable teria has usually been good. In a report of 123 cases (18), on September 15, 2016 by University of Queensland Library because of its instability with other drugs in infusion solu- 83% of patients were considered to be successfully treated. tions. Gentamicin and cefoxitin were found to be stable Surgical removal of involved tissue is undoubtedly the most when mixed together in a single 100-ml bag of normal saline, effective therapy, but in the present case venous access and and a twice-daily regimen provided satisfactory levels of catheter relocation had become a problem, so chemotherapy gentamicin in serum and allowed infusion of total parenteral was attempted. Amikacin, other aminoglycosides, cefoxitin, nutrition between doses. The patient was taught to prepare doxycycline, and sulfonamides are reportedly effective an infusion of gentamicin and cefoxitin which would run for agents; treatment time varies, depending on the type of 1 h before and after the overnight total parenteral nutrition infection (18). The choice of a treatment protocol for the infusion. She was mobile for the remaining hours of the day. present patient was based on results of disk susceptibility This regimen resulted in defervesence in less than a week tests. Although the treatment time of 7 weeks was empiric, it and was continued for a total of 7 weeks. Satisfactory peak reflected previous experience with chemotherapy of infec- and trough levels of gentamicin in serum were maintained. tions caused by rapidly growing mycobacteria. The patient remains well without symptoms and with nega- This case highlights the ever-widening spectrum of patho- tive blood cultures 18 months after the cessation of therapy. genicity of MOT] in humans. This group of organisms We have been unable to locate any previous report of should be not only considered but actively sought when human infection caused by M. neoaurum. The species was dealing with an infection in patients with indwelling foreign described originally by Tsukamura in 1972 (14) after being bodies. Our experience suggests that the outcome in a case isolated from soil in Japan. The taxonomy ofthis species and of infection with M. neoaurum will be satisfactory, providing other related rapidly growing scotochromogenic mycobac- that appropriate chemotherapy is administered. teria isolated from soil, dust, and water has been well documented in recent numerical studies (15). We acknowledge the assistance of M. Tsukamura, who provided An unidentified rapidly growing scotochromogenic myco- the reference strains and confirmed identity of the isolate. We also bacterium was reported from a bacteremic patient with a thank N. Dwyer for secretarial assistance. subclavian catheter (7). The isolate differed from M. neoaurum in that it was negative for iron uptake, nitrate reduction, LITERATURE CITED tolerance to 5% and 1. Bolan, G., A. L. Reingold, L. A. Carson, V. A. Silcox, C. L. NaCl, utilization of mannitol and Woodley, P. S. Hayes, A. W. Hightower, L. McFarland, J. W. inositol. Brown III, N. J. Petersen, M. S. Favero, R. C. Good, and C. V. The patient in the present study could be considered Broome. 1985. Infections with Mycobacterium chelonei in pa- susceptible to opportunistic infections because of her history tients receiving dialysis and using processed haemodialyzers. J. of advanced malignancy, chemotherapy, and radiotherapy, Infect. Dis. 152:1013-1019. but the most significant predisposing factor was probably the 2. Brannan, D. P., R. E. Dubois, M. J. Ramirez, M. J. R. Ravry, indwelling central venous Hickman catheter. In a recent and E. O. Harrison. 1984. Cefoxitin therapy for Mycobacterium review of the complications of 77 Hickman catheters, Har- fortuitum bacteremia with associated granulomatous hepatitis. vey and colleagues (6) found that 25 (33%) became infected South. Med. J. 77:381-384. and that removal was necessary in eight 3. Brennan, P. J., M. Heifets, and B. P. Ullom. 1982. Thin-layer cases. The orga- chromatography of lipid antigens as a means of identifying nisms most commonly identified from blood cultures were S. nontuberculous mycobacteria. J. Clin. Microbiol. 15:447-455. epidermidis, diphtheroids, and gram-negative bacilli. 4. Canetti, G., W. Fox, A. Khomenko, H. T. Mahler, N. K. Menon, MOTT have been described as the cause of opportunistic D. A. Mitchison, N. Rist, and N. A. Smelev. 1969. Advances in infections relatable to foreign bodies. Mycobacterium che- techniques of testing mycobacterial drug sensitivity, and the use 764 NOTES J. CLIN. MICROBIOL.

of sensitivity tests in tuberculosis control programmes. Bull. acid-fast bacilli to human disease: preliminary report. J. Lab. W.H.O. 41:21-43. Clin. Med. 44:202-209. 5. Dawson, D. J. 1971. A simple identification scheme for myco- 14. Tsukamura, M. 1972. A new species of rapidly growing, scoto- bacteria. Aust. J. Med. Technol. 2:7-15. chromogenic mycobacteria. Mycobacterium neoaurum. Med. 6. Harvey, M. P., R. J. Trent, D. E. Joshua, G. Ramsey-Stewart, Biol. (Tokyo) 85:229-233. D. W. Storey, and H. Kronenberg. 1986. Complications associ- 15. Tsukamura, M., H. J. Van Der Meulen, and W. O. K. Grabow. ated with indwelling venous Hickman catheters in patients with 1983. Numerical taxonomy of rapidly growing, scotochromo- haematological disorders. Aust. N.Z. J. Med. 16:211-215. genic mycobacteria of the Mycobacterium parafortuitum com- 7. Jadeja, L., R. Bolivar, R. J. Wallace, Jr., V. A. Silcox, and G. P. plex: Mycobacterium austroafricanum sp. nov. and Mycobac- Bodey. 1983. Bacteremia caused by a previously unidentified terium diernhoferi sp. nov., nom. rev. Int. J. Syst. Bacteriol. Downloaded from species of rapidly growing mycobacterium successfully treated 33:460-469. with vancomycin. Ann. Intern. Med. 99:475-477. 16. Vestal, A. L. 1975. Procedures for the isolation and identifica- 8. Linton, I. M., S. I. Leahy, and G. W. Thomas. 1986. Mycobac- tion of mycobacteria. U.S. Department of Health, Education, terium gastri peritonitis in a patient undergoing chronic ambu- and Welfare publication no. (CDC) 75-8230. Center for Disease latory peritoneal dialysis. Aust. N.Z. J. Med. 16:224-225. Control, Atlanta. 9. Mishra, S. K., R. E. Gordon, and D. A. Barnett. 1980. Identifi- 17. Wallace, R. J., Jr., J. R. Dalovisio, and G. A. Pankey. 1979. Disk cation of nocardiae and streptomycetes of medical importance. diffusion testing of susceptibility of Mycobacterium fortuitum J. Clin. Microbiol. 11:728-736. and Mycobacterium chelonei to antibacterial agents. Antimi- 10. Pulliam, J. P., D. D. Vernon, S. R. Alexander, A. I. Hartstein, crob. Agents Chemother. 16:611-614. and T. A. Golper. 1983. Nontuberculous mycobacterial perito- 18. Wallace, R. J., Jr., J. M. Swenson, V. A. Silcox, and M. G. http://jcm.asm.org/ nitis associated with continuous ambulatory peritoneal dialysis. Bullen. 1985. Treatment of nonpulmonary infections due to Am. J. Kidney Dis. 2:610-614. Mycobacterium fortuitum and Mycobacterium chelonei on the 11. Speert, D. P., D. Munson, C. Mitchell, D. E. Johnson, T. R. basis of in vitro susceptibilities. J. Infect. Dis. 152:500-514. Thompson, P. Ferrieri, and L. W. Wannamaker. 1980. Myco- 19. Wallace, R. J., Jr., J. M. Swenson, V. A. Silcox, R. C. Good, bacterium chelonei septicemia in a premature infant. J. Pediatr. J. A. Tschen, and M. Seabury Stone. 1983. Spectrum of disease 96:681-683. due to rapidly growing mycobacteria. Rev. Infect. Dis. 5:657- 12. Svirbely, J. R., W. J. Buesching, L. W. Ayers, P. B. Baker, and 679. A. J. Britton. 1983. Mycobacterium fortuitum infection of a 20. Woods, G. L., G. S. Hall, and M. J. Schreiber. 1986. Mycobac- Hickman catheter site. Am. J. Clin. Pathol. 80:733-735. teriumfortuitum peritonitis associated with continuous ambula- 13. Timpe, A., and E. H. Runyon. 1954. Relationship of "atypical" tory peritoneal dialysis. J. Clin. Microbiol. 23:786-788. on September 15, 2016 by University of Queensland Library