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Recurrent skin infection with Rhodococcus in an immunosuppressed patient
Journal of Infection (I983) 6, 39-41
Recurrent skin infection with Rhodococcus in an immunosuppressed patient Roderick B. Ellis-Pegler, D i n a h H. Parr* and Valerie A. O r c h a r d t
Infectious Disease Unit and *Microbiology Department, Auckland Hospital, Auckland, New Zealand t Soil Bureau, Department of Scientific and Industrial Research, Lower Hurt, New Zealand Summary A renal transplant patient taking prednisone and azathioprine has had repeated episodes of skin infection with the soil saphrophyte Rhodococcus. Human disease with this organism has not been proved before. Although the lesions have always responded to antibiotics, frequent recurrence makes the long-term outlook uncertain. Introduction T h e pathogenic role in humans of the recently defined genus Rhodococcus is uncertain. None of the case reports in the English literature clearly shows these organisms, previously termed 'Mycobacterium rhodochrous' or 'rhodochrous' complex or taxon, to be unequivocally responsible for the clinical illnesses described?, 2, 3 T h e immunosuppressed patient described here had several clinically similar skin infections with Rhodococcus. We believe that this is the first certain example of h u m a n disease caused by this genus.
Case history B.H., a white New Zealand storeman and gardener was aged 35 years in I972, when following a period of renal dialysis he received a cadaveric renal transplant for chronic renal failure due to gouty nephropathy. He took prednisone and azathioprine daily from the time of operation. Since transplantation he has been successfully treated for pulmonary nocardiosis, recurrent pseudomonas cellulitis and staphylococcal skin lesions. In March I975 he burnt his left arm. T h e burn became infected and did not heal. He was then taking prednisone I5 mg and azathioprine 75 mg per day. Initial antibacterial management was directed unsuccessfully at common pyogenic Gram-positive cocci and Gram-negative bacilli isolated from the lesion. Over several weeks it extended, becoming granulomatous, ulcerated and developed deep pockets of pus. Initial skin biopsy grew no pathogens, but when repeated (May I975) revealed acute and chronic inflammatory cells and Gram-positive beaded organisms identified as 'rhodochrous' complex. Ampicillin 25o mg q.i.d, was prescribed on the basis of in vitro sensitivity tests; he took this for IO weeks and the lesion healed. Correspondence and requests for reprints to R. B. Ellis-Pegler. ox63-4453/83/oroo39+o 3 $o2.oo/o
© I983 The British Society for The Study of Infection
4o
R. B. E L L I S - P E G L E R ,
D. H. P A R R A N D V. A. O R C H A R D
Two months later (August 1975) without recognised local trauma, an area near the previously infected site became similarly involved. T h e same organism was seen in the lesion and isolated in pure culture. Management was made difficult by other concurrent infective complications and he did not receive uninterrupted therapy. However, the lesion did eventually resolve on amoxycillin 25o mg t.d.s, which he took for io months. In July 1977 he developed a similar lesion on the right forearm again without recognised trauma when prednisone dosage was 7"5 mg and azathioprine 75 mg per day. T h e same organism was isolated and he took amoxycillin 5oo mg t.d.s. for seven months in another attempt at eradication. Two weeks after completing this course the infection recurred close by on the same arm and was managed similarly. A further prolonged course of amoxycillin was taken for another recurrence beginning late in 1978 and at present he continues this drug again after isolation of this organism in July I98O from a new lesion on his right thigh. Immunosuppressive therapy has been slowly reduced over these years and he now takes prednisone 7"5 mg and azathioprine 25 mg per day. Renal function has remained stable with serum creatinine concentrations persisting between o"I3 and o.I6 mmol/l.
Microbiology G r o u n d biopsy material or pus from the six separate lesions showed short beaded Gram-positive, acid-fast filaments. Repeated sampling of the lesions was sometimes needed. Culture on Sabouraud's dextrose agar at 27 °C and blood agar at 37 °C yielded growths of o'5 m m diameter dull pink colonies at three days. After one week they became rough, deep pink and reached 2 m m in diameter, subsequently changing to bright orange-red. T h e initial isolate was provisionally identified as a member of the ' rhodochrous' complex on the following criteria: the presence of acid-fast filaments, the lack of true branching on slide culture, urease production and failure to hydrolyse tyrosine, casein and xanthine. This identification was confirmed by the Centers for Disease Control, Atlanta, Georgia, U.S.A. Later isolates were similar. All isolates were reclassified as members of the newly described Rhodococcus genus on the basis of acid methanolysis of whole cells using thin-layer chromatography. 4 This showed the presence of mycolic acids characteristic of the genera Nocardia, Rhodococcus and Corynebacterium. Strains were also partially acid fast and produced no aerial hyphae. Biochemical, physiological and growth characters used to differentiate rhodococcis showed one isolate to be Rhodococcus corallinus, but the other five isolates tested had aberrant characteristics making species identification uncertain. T h e tests used to differentiate rhodococci included decomposition of adenine and tyrosine, growth on (one per cent wt/vol.) glycerol, inositol, maltose, rhamnose, sorbitol and trehalose as sole carbon sources, growth at zo °C and in the presence of crystal violet (o.oooi per cent wt/vol.) and sodium azide (o-o2 per cent wt/vol.). T h e enzymic activities of alpha and beta esterases were not tested and determination of the predominant menaquinone was not carried out. Disc sensitivity testing on Oxoid D.S.T. agar showed all isolates sensitive to ampicillin, amoxycillin, carbenicillin, tetracycline, erythromycin, kanamycin
Rhodococcus skin infection
4I
and gentamicin. All were resistant to t r i m e t h o p r i m , b u t sulphonamide and penicillin sensitivities were variable. M i n i m u m inhibitory concentrations of ampiciUin and amoxycillin to all isolates were 3"I mg/1 m e a s u r e d by the b r o t h dilution technique in penassay broth. Soil samples, lime, various fertilisers, cement and weed-killers with which the patient worked were studied. Strains of Nocardia, Rhodococcus (Io~/g dry weight) and other actinomycete genera (e.g. Streptomyces, Io~/g dry weight) were isolated from soil and also from the lime. Rhodococcus strains were isolated from elsewhere on the patient's b o d y surface after the development of the thigh lesion b u t never at other times and never f r o m his faeces. We did not speciate these or the environmental Rhodococcus strains. Discussion
Rhodococci are c o m m o n l y f o u n d in soil in the n u m b e r s we d e m o n s t r a t e d s t h o u g h the n u m b e r s in lime were unusual. Either seems the likely source in our patient, and his u n i q u e susceptibility is presumably due to his i m m u n o suppression. G u i n e a pigs treated with steroids and infected w i t h ' rhodochrous' taxon experimentally have been shown to have an increased incidence and severity of clinical illness) T h e close anatomical and temporal relationships of some of these recurrences clearly suggest that the same strain was responsible and had not been eradicated despite prolonged therapy. By contrast, the development of lesions at remote sites and times on other occasions argues for repeated infections with different strains. Given that definite disease due to this organism has not been described before, repeated infection is surprising, b u t seems the only reasonable explanation for the latter recurrences. In s u m m a r y , Rhodococcus strains have been repeatedly isolated in pure culture f r o m clinically similar recurrent lesions in an i m m u n o s u p p r e s s e d man. T h i s organism has been seen in pus and biopsy tissue along with inflammatory cells. T h e lesions have r e s p o n d e d clinically to several courses of antibiotic selected on the basis of in vitro sensitivity. T h i s case demonstrates a secure relationship between the genus Rhodococcus and clinical disease. References
I. Alture-Weber E, O'Hare D, Louria DB. Infections caused by 'Mycobacterium rhodochrous' and Scotochromogens. Am Rev Respir Dis I968; 97: 694-7oi. 2. Porres JM. Isolationof'Mycobacteriumrhodochrous'fromacutaneous lesion. ArchDermatol I973; IO8: 4II-412. 3- Harburchak DR, Jeffery B, Higbee JW, Everett ED. Infections caused by 'rhodochrous'. Amff Med I978; 65: 298-302. 4- Minnikin DE, Alshamaony L, Goodfellow M. Differentiation of Mycobacteriurn, Nocardia and related taxa by thin layer chromatographic analysis of whole cell methanolysates. J Gen Microbial I975 ; 88 : 200-204. 5. Goodfellow M, Schaal KP. Identification methods for Nocardia, Actinomadura and Rhodococcus. In: Lovelock DW, Skinner FA, eds. Society of Applied Bacteriology Technical Series. No. I4. London: Academic Press (in press).
Recurrent skin infection with Rhodococcus in an immunosuppressed patient Roderick B. Ellis-Pegler, D i n a h H. Parr* and Valerie A. O r c h a r d t
Infectious Disease Unit and *Microbiology Department, Auckland Hospital, Auckland, New Zealand t Soil Bureau, Department of Scientific and Industrial Research, Lower Hurt, New Zealand Summary A renal transplant patient taking prednisone and azathioprine has had repeated episodes of skin infection with the soil saphrophyte Rhodococcus. Human disease with this organism has not been proved before. Although the lesions have always responded to antibiotics, frequent recurrence makes the long-term outlook uncertain. Introduction T h e pathogenic role in humans of the recently defined genus Rhodococcus is uncertain. None of the case reports in the English literature clearly shows these organisms, previously termed 'Mycobacterium rhodochrous' or 'rhodochrous' complex or taxon, to be unequivocally responsible for the clinical illnesses described?, 2, 3 T h e immunosuppressed patient described here had several clinically similar skin infections with Rhodococcus. We believe that this is the first certain example of h u m a n disease caused by this genus.
Case history B.H., a white New Zealand storeman and gardener was aged 35 years in I972, when following a period of renal dialysis he received a cadaveric renal transplant for chronic renal failure due to gouty nephropathy. He took prednisone and azathioprine daily from the time of operation. Since transplantation he has been successfully treated for pulmonary nocardiosis, recurrent pseudomonas cellulitis and staphylococcal skin lesions. In March I975 he burnt his left arm. T h e burn became infected and did not heal. He was then taking prednisone I5 mg and azathioprine 75 mg per day. Initial antibacterial management was directed unsuccessfully at common pyogenic Gram-positive cocci and Gram-negative bacilli isolated from the lesion. Over several weeks it extended, becoming granulomatous, ulcerated and developed deep pockets of pus. Initial skin biopsy grew no pathogens, but when repeated (May I975) revealed acute and chronic inflammatory cells and Gram-positive beaded organisms identified as 'rhodochrous' complex. Ampicillin 25o mg q.i.d, was prescribed on the basis of in vitro sensitivity tests; he took this for IO weeks and the lesion healed. Correspondence and requests for reprints to R. B. Ellis-Pegler. ox63-4453/83/oroo39+o 3 $o2.oo/o
© I983 The British Society for The Study of Infection
4o
R. B. E L L I S - P E G L E R ,
D. H. P A R R A N D V. A. O R C H A R D
Two months later (August 1975) without recognised local trauma, an area near the previously infected site became similarly involved. T h e same organism was seen in the lesion and isolated in pure culture. Management was made difficult by other concurrent infective complications and he did not receive uninterrupted therapy. However, the lesion did eventually resolve on amoxycillin 25o mg t.d.s, which he took for io months. In July 1977 he developed a similar lesion on the right forearm again without recognised trauma when prednisone dosage was 7"5 mg and azathioprine 75 mg per day. T h e same organism was isolated and he took amoxycillin 5oo mg t.d.s. for seven months in another attempt at eradication. Two weeks after completing this course the infection recurred close by on the same arm and was managed similarly. A further prolonged course of amoxycillin was taken for another recurrence beginning late in 1978 and at present he continues this drug again after isolation of this organism in July I98O from a new lesion on his right thigh. Immunosuppressive therapy has been slowly reduced over these years and he now takes prednisone 7"5 mg and azathioprine 25 mg per day. Renal function has remained stable with serum creatinine concentrations persisting between o"I3 and o.I6 mmol/l.
Microbiology G r o u n d biopsy material or pus from the six separate lesions showed short beaded Gram-positive, acid-fast filaments. Repeated sampling of the lesions was sometimes needed. Culture on Sabouraud's dextrose agar at 27 °C and blood agar at 37 °C yielded growths of o'5 m m diameter dull pink colonies at three days. After one week they became rough, deep pink and reached 2 m m in diameter, subsequently changing to bright orange-red. T h e initial isolate was provisionally identified as a member of the ' rhodochrous' complex on the following criteria: the presence of acid-fast filaments, the lack of true branching on slide culture, urease production and failure to hydrolyse tyrosine, casein and xanthine. This identification was confirmed by the Centers for Disease Control, Atlanta, Georgia, U.S.A. Later isolates were similar. All isolates were reclassified as members of the newly described Rhodococcus genus on the basis of acid methanolysis of whole cells using thin-layer chromatography. 4 This showed the presence of mycolic acids characteristic of the genera Nocardia, Rhodococcus and Corynebacterium. Strains were also partially acid fast and produced no aerial hyphae. Biochemical, physiological and growth characters used to differentiate rhodococcis showed one isolate to be Rhodococcus corallinus, but the other five isolates tested had aberrant characteristics making species identification uncertain. T h e tests used to differentiate rhodococci included decomposition of adenine and tyrosine, growth on (one per cent wt/vol.) glycerol, inositol, maltose, rhamnose, sorbitol and trehalose as sole carbon sources, growth at zo °C and in the presence of crystal violet (o.oooi per cent wt/vol.) and sodium azide (o-o2 per cent wt/vol.). T h e enzymic activities of alpha and beta esterases were not tested and determination of the predominant menaquinone was not carried out. Disc sensitivity testing on Oxoid D.S.T. agar showed all isolates sensitive to ampicillin, amoxycillin, carbenicillin, tetracycline, erythromycin, kanamycin
Rhodococcus skin infection
4I
and gentamicin. All were resistant to t r i m e t h o p r i m , b u t sulphonamide and penicillin sensitivities were variable. M i n i m u m inhibitory concentrations of ampiciUin and amoxycillin to all isolates were 3"I mg/1 m e a s u r e d by the b r o t h dilution technique in penassay broth. Soil samples, lime, various fertilisers, cement and weed-killers with which the patient worked were studied. Strains of Nocardia, Rhodococcus (Io~/g dry weight) and other actinomycete genera (e.g. Streptomyces, Io~/g dry weight) were isolated from soil and also from the lime. Rhodococcus strains were isolated from elsewhere on the patient's b o d y surface after the development of the thigh lesion b u t never at other times and never f r o m his faeces. We did not speciate these or the environmental Rhodococcus strains. Discussion
Rhodococci are c o m m o n l y f o u n d in soil in the n u m b e r s we d e m o n s t r a t e d s t h o u g h the n u m b e r s in lime were unusual. Either seems the likely source in our patient, and his u n i q u e susceptibility is presumably due to his i m m u n o suppression. G u i n e a pigs treated with steroids and infected w i t h ' rhodochrous' taxon experimentally have been shown to have an increased incidence and severity of clinical illness) T h e close anatomical and temporal relationships of some of these recurrences clearly suggest that the same strain was responsible and had not been eradicated despite prolonged therapy. By contrast, the development of lesions at remote sites and times on other occasions argues for repeated infections with different strains. Given that definite disease due to this organism has not been described before, repeated infection is surprising, b u t seems the only reasonable explanation for the latter recurrences. In s u m m a r y , Rhodococcus strains have been repeatedly isolated in pure culture f r o m clinically similar recurrent lesions in an i m m u n o s u p p r e s s e d man. T h i s organism has been seen in pus and biopsy tissue along with inflammatory cells. T h e lesions have r e s p o n d e d clinically to several courses of antibiotic selected on the basis of in vitro sensitivity. T h i s case demonstrates a secure relationship between the genus Rhodococcus and clinical disease. References
I. Alture-Weber E, O'Hare D, Louria DB. Infections caused by 'Mycobacterium rhodochrous' and Scotochromogens. Am Rev Respir Dis I968; 97: 694-7oi. 2. Porres JM. Isolationof'Mycobacteriumrhodochrous'fromacutaneous lesion. ArchDermatol I973; IO8: 4II-412. 3- Harburchak DR, Jeffery B, Higbee JW, Everett ED. Infections caused by 'rhodochrous'. Amff Med I978; 65: 298-302. 4- Minnikin DE, Alshamaony L, Goodfellow M. Differentiation of Mycobacteriurn, Nocardia and related taxa by thin layer chromatographic analysis of whole cell methanolysates. J Gen Microbial I975 ; 88 : 200-204. 5. Goodfellow M, Schaal KP. Identification methods for Nocardia, Actinomadura and Rhodococcus. In: Lovelock DW, Skinner FA, eds. Society of Applied Bacteriology Technical Series. No. I4. London: Academic Press (in press).