Tubercle 62 (1981 ), 281-284 © Longman Group Ltd.
INFECTION WITH MYCOBACTERIUM IN A H A E N I O D I A L Y S I S P A T I E N T
B. S. Azadian, A. Beck, J. R. Curtis ~, L. E. Cherrington, P. E. Gower*, M. Phillips ~, J. B. Eastwood ~, J. Nichollst Department of Microbiology, ~Department of Medicine and tDepartment of Surgery, Charing Cross Hospital, Fulham Palace Road, London W6 8FR
Summary M. chelonei ssp. chelonei was isolated over a period of 5 months from abscesses on various sites of hands and feet of a patient on maintenance dialysis. The organism was resistant in vitro to a great number of antimicrobials and treatment in turn with gentamicin, vancomycin, erythromycin, doxycycline and co-trimoxazole had to be supplemented by surgical drainage of abscesses. Examination of the dialysis circuit revealed repeatedly the presence of M. chelonei and M. fortuitum in the water softener resin and other sites. The significance of this finding is discussed. R6sum6 Au cours d'une p~riode de 5 mois, on a isol6 M. chelonei esp. chelonei ~ partir d'abc~s de Iocalisations diverses aux pieds et aux mains chez un malade maintenu en vie par h6modialyse. Le bacille 6tait r6sistant in vitro ~ un grand nombre d'antimicrobiens et le traitement r6alis6 successivement par la gentamycine, la vancomycine, 1"6rythromycine, la doxycycline et le co-trimoxazone a d0 6tre compl6td par le drainage chirurgical de I'abc6s. L'6tude du circuit de dialyse a r6v616 ~ plusieurs reprises la pr6sence de M. chelonei et de M. fortuitum dans la r6sine d'adoucissement de I'eau et dans d'autres parties. Les auteurs discutent la signification de ces r6sultats.
Resumen Durante un periodo de 5 meses, se aisl6 M, chelonei a partir de abscesos Iocalizados en varios sitios de las manos y pies de un pacien'te en hemodidlisis. El micro-organismo era resistente in vitro a un gran nLimero de agentes antimicrobianos y el tratamiento, que gir6 en torno a la gentamicina, la vancomicina, la eritromicina, la desoxiciclina y la co-trimoxazole, tuvo que ser completado con drenaje quir~rgico de los abscesos. El examen del circuito de la di,~lisis revel6, en forma repetida, la presencia de M. chelonei y M. fortuitum en la resina utilizada para ablandar el agua yen otros sitios. Se discute el significado de estos hallazgos. Patients with severe chronic renal failure show an increased susceptibility to infection and are liable to opportunist infections. This report records an infection caused by M. chelonei in a maintenance haemodialysis patient and describes attempts at tracing the source of this infection.
Case report The patient, a man aged 59, had been on maintenance haemodialysis for renal failure due to polycystic kidneys since January 1977. In mid December 1978 he had a cadaveric kidney
Azadian and others
transplant but irreversible graft rejection occurred within 6 weeks and he was returned to maintenance haemodialysis. Eight months later he complained of redness and swelling in one of his metacarpophalangeal joints and on his left foot. Initial treatment with penicillin V and flucloxacillin had no effect and gentamicin was added to the regime. Despite this treatment, new lesions continued to appear on both hands and feet (Figures 1 and 2) and progressed to form abscesses which had to be drained surgically. Cultures of pus obtained on drainage and aspiration grew, after 48 to 72 hours, an acid alcohol fast bacillus which was later identified as M. chelonei ssp. cheloneL A Mantoux test with tuberculin 1/1000 was negative after 48 hours. A chelonin skin test was negative after 48 and 72 hours, but 3 weeks later a papule was noticed at the injection site with erythema of 9 mm and induration of 4 mm diameter. A biopsy of it showed an area of chronic inflammation with lymphocytic infiltration in the subcutis, with a few granulomas composed of epithelioid type histiocytes and occasional giant cells. Following sensitivity testing of the organism erythromycin and vancomycin were added to the gentamicin medication, but failed to arrest the development of new lesions. After 7 weeks of this regime the patient developed signs of auditory nerve damage and vancomycin and gentamicin had to be stopped. Treatment continued with erythromycin and doxycycline to which co-trimoxazole was later added. However, new abscesses continued to appear until the end of March 1980 since when the patient has remained free of new lesions and his general condition has improved. Treatment continues with this medication. Bacteriology The organism was present in moderate numbers in the direct ZiehI-Neelsen film of pus. It grew on blood agar incubated aerobically for 48 to 72 hours as whitish, shiny colonies with an entire edge measuring 0.5 mm in diameter. Identification tests  gave the following results : Good growth at 30 °C and 37 °C ; Moderate growth at room temperature ; No growth at 42 °C. Niacin, Tween hydrolysis, nitrate reduction, growth in 5% NaCI: negative. Catalase ( > 4 5 ram), arylsulphatase(3 days), citrate utilisation, growth on McConkey (without colour change): positive. Dr. J. Stanford confirmed our identification of the organism both by biochemical and double immunodiffusion tests. On preliminary disc diffusion testing the organism was found to be sensitive to erythromycin, gentamicin, kanamycin and partially sensitive to amikacin and vancomycin. It was resistant to sulphonamides and co-trimoxazole, the penicillins and cephalosporins, rifampicin, chloram-
Disseminated infection with M. chelonei 283 phenicol and doxycycline; the Dulwich Regional Tuberculosis Laboratory reported that it was also resistant to streptomycin, INH, PAS and ethambutol. Antimicrobials showing some evidence in the disc test of activity against the organism, were further examined quantitatively by plate dilution method . We also included in these tests some antimicrobials reported by previous investigators [2, 3, 4] as being of clinical value. The minimum inhibitory concentration of these drugs were erythromycin, gentamicin and vancomycin : 20 mg/L each; kanamycin: 40 mg/L; amikacin: 160 mg/L; sulphadimidine: >800 mg/L; tetracycline: >320 m g / L Checkerboard titrations of amikacin and erythromycin showed no synergy. There was, however, some evidence of synergy between gentamicin and erythromycin. Epidemiological Investigations To exclude the shunt site as a possible portal of entry, swabs of this site were taken on 12 occasions, but failed to yield any acid fast bacilli. Fourteen blood cultures taken over a period of 5 months were sterile. As the patient was a keen gardener, soil from his garden, his gardening shoes and gloves were examined following the methods of Kubica et al  but were all negative. Various components and sites of the dialysis circuit, at both the hospital and patient's home, were then examined by the methods of McSwiggan and Collins  and Bullin et al  for the presence of fast growing mycobacteria. The water softener resins of 7 other home dialysis patients and fresh resin supplied by the manufacturer were also examined. In 11 out of 27 specimens examined, fast growing mycobacteria were isolated (Table 1). Eight of these were identified as M. chelonei and 3 others were M. fortuitum. Culture of the fresh resin obtained from the manufacturer did not grow any mycobacteria. No attempt was made to investigate the possible presence of slow growing mycobacteria. The M. chelonei strains isolated from parts of the dialysis circuit showed similar biochemical reactions to the strains isolated from the patient's abscesses, except that some of them grew on LSwensteinJensen media containing 5% NaCI. Attempts were made to eliminate M. chelonei from the water softener resin by soaking the resin in 3.6% solution of formaldehyde for 24 hours. The resin was then washed with sterile water until a negative reaction with Shift's reagent indicated its freedom from formaldehyde. There was still growth of M. chelonei from the treated resin. Table I.
Isolates from dialysis circuit.
Water softener resin column 1 RDU* Water softener resin column 2 RDU Water softener resin column 2~ RDU Water softener resin column 2 ~ RDU Sediment strainer RDU Housing of above RDU Dylade filter RDU Housing of above RDU Water softener resin patient H D*~ Water softener resin Mrs. C. HD Water softener resin Mrs. B. HD
M. fortuitum M. chelonei M. chelonei M. chelonei M. chelonei M. chelonei M. chelonei M. fortuitum M. fortuitum M, chelonei M. chelonei
*RDU = Renal Dialysis Unit * * H D = Home Dialysis tRepeat examination 1tArter disinfection
284 Azadian and others Discussion The severe and protracted course of this patient's infection, together with his delayed reaction to chelonin suggests some impairment of his immunity. This was likely to be due to his renal failure, which is a condition known to be associated with depressed immunity. In view of the long incubation time of M. chelonei infections, which may extend from 1 to 13 months , it is conceivable that the immunosuppressive treatment he had at the time of his kidney transplant may have been a contributory factor. Water softener resins are notorious reservoirs of contaminants , and their disinfection is very difficult. Our finding of survival of M. chelonei in resin exposed to an aqueous solution 3.6 % formaldehyde for 24 hours is in keeping with similar observations by Carson et al . Because of the ubiquitous occurrence of M. chelonei we are unable to draw firm conclusions as to the source and portal of entry of the organism. Nevertheless, in view of the fact that M. chelonei was isolated on a number of occasions from water softener resins and some of the succeeding sites of the dialysis circuit, it is conceivable that the water softener columns were the occasional reservoirs from which the infection originated. Consideration may, therefore, have to be given to alternative forms of water treatment, such as reverse osmosis. A ckno wledgements We wish to thank Dr John Stanford for his help with the identification of cultures and supplying the chelonin antigen, Dr Donald Mitchell for the chelonin test biopsy a n d M r David Ransi for collecting the environmental specimens. References
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