Journal of Infection (1991) 23, 73-76
CASE REPORTS
Corynebacterium rninutissimum i n f e c t i o n C. L. Golledge* and G. P h i l l i p s t
* Central Microbiological Laboratories, Western General Hospital, Edinburgh and t Medical Microbiology Department, University of Dundee Medical School, Ninewells Hospital, Dundee, Scotland, U.K. Accepted for publication 3 January I99I Summary Two cases o f infection due to Corynebacterium minutissimum are described. On the basis of biochemical tests the organisms were thought at first to be Corynebacterium jeikeium. Methods of distinguishing between these species and the role of C. minutissimum in the pathogenesis of erythrasma and other skin infections are discussed.
Introduction
Corynebacterium minutissimum was first described in I96I as the cause of erythrasma, 1 a common superficial infection of the skin characterised by scaly, reddish-brown macular patches in intertriginous areas. ~ T h e diagnosis may be confirmed by the demonstration of coral-red fluorescence of the lesions under Wood's light. T h r e e cases of serious infection due to C. minutissimum have been described in the literature: a fatal case of septicaemia in a neutropaenic patient with chronic myeloid leukaemiafl a case of infective endocarditis in a patient with mitral valve prolapse who suffered embolic retinopathy 4 and severe, recurrent abscesses following biopsy of a breast lump in a 42-year-old female. 5 Two further cases are reported here. Case reports Case I
An 8I-year-old male received melphalan and prednisolone for treatment of multiple myeloma and local irradiation for humeral pain. During the course of chemotherapy he developed disseminated herpes zoster and became bacteraemic following secondary staphylococcal infection of the skin lesions. He responded well to treatment with intravenous acyclovir and flucloxacillin. One week after discontinuing antibiotics, he became febrile and two sets of blood cultures from separate venepuncture sites yielded Gram-positive bacilli in both aerobic and anaerobic bottles (Bactec N R 66o, Becton Dickinson, Maryland, U.S.A.). T h e organism was identified provisionally on biochemical testing as an antibiotic-sensitive strain of C. jeikeium and intravenous benzylpenicillin was commenced. Recovery was slow and complicated by a further episode of skin oi63-4453/9I/O4OO73+04 $03.00/0
© I991 The British Society for the Study of Infection
74
C.L. GOLLEDGE
A N D G. P H I L L I P S
sepsis requiring treatment with intravenous flucloxacillin. T h e patient died 3 m o n t h s later with an undiagnosed infection. Case 2
A previously well 43-year-old male damaged his neck while lifting a weight. Conservative management failed and cervical discectomy and fusion were performed. Recovery was uneventful until the eighth week post-operatively, when an abscess developed at the lower end of the wound. Pus (6 ml) was drained by needle aspiration and on microscopic examination large numbers of neutrophils and Gram-positive bacilli were seen. A pure heavy growth of an antibiotic-sensitive strain of a diphtheroid bacillus, provisionally identified as C. jeikeium, was obtained on culture. T h e infection resolved with drainage and treatment with amoxycillin and clavulanic acid. Bacteriology
T h e biochemical reactions of the organisms are shown in Table I and are compared to the expected reactions for C. jeikeium and C. minutissimum. Both clinical isolates were susceptible to penicillin, tetracycline, erythromycin, cephalexin, rifampicin, ciprofloxacin and vancomycin when tested by Stokes' disc diffusion m e t h o d on Isosensitest agar (Oxoid, Basingstoke, U.K.) supplemented with 5 % horse blood. Discussion
Serious infection with C. minutissimum is rare, but it is possible that this organism may be wrongly identified as C. jeikeium or other Corynebacterium spp. as happened in the two cases reported here. Preliminary identification of diphtheroid-like bacteria in the routine diagnostic laboratory is often based on tests such as catalase and urease production, motility, nitrate reduction and rapid carbohydrate fermentation reactions (glucose, maltose, sucrose, xylose and mannitol. 6 using this scheme it is impossible to distinguish reliably between C. minutissimum and C. jeikeium as both give very similar results (Table I). But unlike C. jeikeium, C. minutissimum is not lipid dependent and grows well on triple sugar iron agar (producing an acid or alkaline slant) and in u n s u p p l e m e n t e d peptone water. 7 Fluorescence was not noted amongst 14 strains of C. jeikeium grown on media used by Somerville 8 to demonstrate this feature in corynebacteria isolated from patients with erythrasma (C. L. G., personal observation). Although C. jeikeium sensitivity is variable, strains are frequently multiresistant and only predictably sensitive to vancomycin or teicoplanin. 9' 10 T h e r e do not appear to be any reports of antibiotic-resistant C. minutissimum strains but antibiograms cannot be relied u p o n to distinguish between the species. Corynebacterium minutissimum is now accepted as a valid species 11 and has been considered to be the cause of erythrasma. 12 However, Somerville, 8 while investigating the pathogenesis of erythrasma, found that skin changes preceded the demonstration of skin colonisation with fluorescent diphtheroids, sug-
Corynebacterium minutissimum infection
75
Table I Identification of clinical isolates Case I Catalase Motility Haemolysis Nitrate reduction Urease Acidification of Glucose Maltose Sucrose Mannitol Xylose Lipid dependency F l u o r e s c e n c e at 365 n m G r o w t h on triple sugar iron agar G r o w t h in u n s u p p l e m e n t e d peptone water
+ . . . . + + + . . + + +
Case 2
Corynebacterium minutissimum
C. jeikeium
+
+
+ . . . .
. . . .
. . . . + V -
. . + +
+ + V . . + +
+
+
-
+ + . .
+ -
+ , P o s i t i v e in > 90 % . - , N e g a t i v e in > 90 % . V, V a r i a b l e r e a c t i o n .
gesting that these bacteria are not the primary infecting organism. Fluorescent diphtheroids have also been demonstrated on normal skin in large numbers 1~ and in addition skin colonised by these bacteria does not always fluoresce. Other studies have also cast doubt on the role of C. minutissimum in erythrasma. McBride et al., 14 found that less than half of the isolates of fluorescent diphtheroids from 25 cases of erythrasma gave biochemical reactions consistent with C. minutissimum. T h e demonstration of fluorescence however may vary between laboratories depending on the culture media used. Corynebacterium minutissimum may be more pathogenic than previously realised. Laboratory workers should be aware of its similarity to C. jeikeium and be prepared to perform additional tests to distinguish between the two. Lack of growth on triple sugar iron agar and in unsupplemented peptone water suggests that the organism is C. jeikeium. Further tests such as demonstration of fluorescence and lipid dependancy are best performed in reference laboratories. All patients with invasive infections caused by C. minutissimum have had skin lesions, although none have been suggestive of erythrasma. T h e infective agent causing erythrasma is in doubt and until this is resolved the diagnosis should continue to be made on clinical grounds without the need to confirm by culturing C. minutissimum. References I. S a r k a n y I, T a p l i n D , B l a n k H . E r y t h r a s m a - - c o m m o n ffAMA I 9 6 I ; 1 7 7 : 1 3 o - 1 3 1 .
bacterial i n f e c t i o n o f t h e skin.
76
C. L. GOLLEDGE AND G. P H I L L I P S
2. Sindhuphak W, MacDonald E, Smith EB. Erythrasma. Overlooked or misdiagnosed ? Int J Dermatol I985; 24: 95-96. 3. Guarderas J, Karnard A, Alverez S, Berk SL. Corynebacterium minutissimum bacteremia in a patient with chronic myeloid leukaemia in blast crisis. Diagn Microbiol Infect Dis I986; 5: 327-33o. 4. Herschorn BJ, Brucker AJ. Embolic retinopathy due to Corynebacterium minutissimum endocarditis. Br ff Opthalmol r985; 69: 29--3I. 5. Berger SA, Gorea A, Stadler J, Dan M, Zilberamn M. Recurrent breast abscesses caused by Corynebacterium minutissimum. J Clin Microbiol I984; 20: I219-I22O. 6. Thompson JS, Gates-Davis DR, Yong DCT. Rapid microbiological identification of Corynebacterium diphtheriae and other medically important corynebacteria, ff Clin Microbiol r983; I8: 926-929. 7. Erspaard H, Justesen T. Multiresistant lipophilic corynebacteria from clinical specimens. Acta Path Microbiol Immunol Scand Sect B I984:92 39-43. 8. Somerville DA. Erythrasma in normal young adults. J Med Microbiol I97o; 3: 57-64. 9. Riley PS, Hollis DG, Utter GB, Weaver RE, Baker CN. Characterization and identification of 95 diphtheroid (group JK) cultures isolated from clinical specimens. J Clin Microbiol I979; 9: 418-424. IO. Coyle MB, Lipsky BA. Coryneform bacteria in infectious diseases; clinical and laboratory aspects. Clin Microbiol Rev I99O; 3: 227-246. I I. Collins MD, Jones D. Corynebacterium minutissimum sp. nov., nom. rev. Int ff System Bacteriol r983 ; 33 : 87o-87 I. r2. Sarkany I, Taplin D, Blank H. Organism causing erythrasma. Lancet I962; ii: 3o4-3o5. r3. Marples RR. Diphtheroids of normal human skin. Br J Dermatol I969; 8x (Suppl I); 47-54. x4. McBride ME, Montes LF, Knox JM. The characterization of fluorescent skin diphtheroids. Can ff Microbiol I97O; x6:941-946.
CASE REPORTS
Corynebacterium rninutissimum i n f e c t i o n C. L. Golledge* and G. P h i l l i p s t
* Central Microbiological Laboratories, Western General Hospital, Edinburgh and t Medical Microbiology Department, University of Dundee Medical School, Ninewells Hospital, Dundee, Scotland, U.K. Accepted for publication 3 January I99I Summary Two cases o f infection due to Corynebacterium minutissimum are described. On the basis of biochemical tests the organisms were thought at first to be Corynebacterium jeikeium. Methods of distinguishing between these species and the role of C. minutissimum in the pathogenesis of erythrasma and other skin infections are discussed.
Introduction
Corynebacterium minutissimum was first described in I96I as the cause of erythrasma, 1 a common superficial infection of the skin characterised by scaly, reddish-brown macular patches in intertriginous areas. ~ T h e diagnosis may be confirmed by the demonstration of coral-red fluorescence of the lesions under Wood's light. T h r e e cases of serious infection due to C. minutissimum have been described in the literature: a fatal case of septicaemia in a neutropaenic patient with chronic myeloid leukaemiafl a case of infective endocarditis in a patient with mitral valve prolapse who suffered embolic retinopathy 4 and severe, recurrent abscesses following biopsy of a breast lump in a 42-year-old female. 5 Two further cases are reported here. Case reports Case I
An 8I-year-old male received melphalan and prednisolone for treatment of multiple myeloma and local irradiation for humeral pain. During the course of chemotherapy he developed disseminated herpes zoster and became bacteraemic following secondary staphylococcal infection of the skin lesions. He responded well to treatment with intravenous acyclovir and flucloxacillin. One week after discontinuing antibiotics, he became febrile and two sets of blood cultures from separate venepuncture sites yielded Gram-positive bacilli in both aerobic and anaerobic bottles (Bactec N R 66o, Becton Dickinson, Maryland, U.S.A.). T h e organism was identified provisionally on biochemical testing as an antibiotic-sensitive strain of C. jeikeium and intravenous benzylpenicillin was commenced. Recovery was slow and complicated by a further episode of skin oi63-4453/9I/O4OO73+04 $03.00/0
© I991 The British Society for the Study of Infection
74
C.L. GOLLEDGE
A N D G. P H I L L I P S
sepsis requiring treatment with intravenous flucloxacillin. T h e patient died 3 m o n t h s later with an undiagnosed infection. Case 2
A previously well 43-year-old male damaged his neck while lifting a weight. Conservative management failed and cervical discectomy and fusion were performed. Recovery was uneventful until the eighth week post-operatively, when an abscess developed at the lower end of the wound. Pus (6 ml) was drained by needle aspiration and on microscopic examination large numbers of neutrophils and Gram-positive bacilli were seen. A pure heavy growth of an antibiotic-sensitive strain of a diphtheroid bacillus, provisionally identified as C. jeikeium, was obtained on culture. T h e infection resolved with drainage and treatment with amoxycillin and clavulanic acid. Bacteriology
T h e biochemical reactions of the organisms are shown in Table I and are compared to the expected reactions for C. jeikeium and C. minutissimum. Both clinical isolates were susceptible to penicillin, tetracycline, erythromycin, cephalexin, rifampicin, ciprofloxacin and vancomycin when tested by Stokes' disc diffusion m e t h o d on Isosensitest agar (Oxoid, Basingstoke, U.K.) supplemented with 5 % horse blood. Discussion
Serious infection with C. minutissimum is rare, but it is possible that this organism may be wrongly identified as C. jeikeium or other Corynebacterium spp. as happened in the two cases reported here. Preliminary identification of diphtheroid-like bacteria in the routine diagnostic laboratory is often based on tests such as catalase and urease production, motility, nitrate reduction and rapid carbohydrate fermentation reactions (glucose, maltose, sucrose, xylose and mannitol. 6 using this scheme it is impossible to distinguish reliably between C. minutissimum and C. jeikeium as both give very similar results (Table I). But unlike C. jeikeium, C. minutissimum is not lipid dependent and grows well on triple sugar iron agar (producing an acid or alkaline slant) and in u n s u p p l e m e n t e d peptone water. 7 Fluorescence was not noted amongst 14 strains of C. jeikeium grown on media used by Somerville 8 to demonstrate this feature in corynebacteria isolated from patients with erythrasma (C. L. G., personal observation). Although C. jeikeium sensitivity is variable, strains are frequently multiresistant and only predictably sensitive to vancomycin or teicoplanin. 9' 10 T h e r e do not appear to be any reports of antibiotic-resistant C. minutissimum strains but antibiograms cannot be relied u p o n to distinguish between the species. Corynebacterium minutissimum is now accepted as a valid species 11 and has been considered to be the cause of erythrasma. 12 However, Somerville, 8 while investigating the pathogenesis of erythrasma, found that skin changes preceded the demonstration of skin colonisation with fluorescent diphtheroids, sug-
Corynebacterium minutissimum infection
75
Table I Identification of clinical isolates Case I Catalase Motility Haemolysis Nitrate reduction Urease Acidification of Glucose Maltose Sucrose Mannitol Xylose Lipid dependency F l u o r e s c e n c e at 365 n m G r o w t h on triple sugar iron agar G r o w t h in u n s u p p l e m e n t e d peptone water
+ . . . . + + + . . + + +
Case 2
Corynebacterium minutissimum
C. jeikeium
+
+
+ . . . .
. . . .
. . . . + V -
. . + +
+ + V . . + +
+
+
-
+ + . .
+ -
+ , P o s i t i v e in > 90 % . - , N e g a t i v e in > 90 % . V, V a r i a b l e r e a c t i o n .
gesting that these bacteria are not the primary infecting organism. Fluorescent diphtheroids have also been demonstrated on normal skin in large numbers 1~ and in addition skin colonised by these bacteria does not always fluoresce. Other studies have also cast doubt on the role of C. minutissimum in erythrasma. McBride et al., 14 found that less than half of the isolates of fluorescent diphtheroids from 25 cases of erythrasma gave biochemical reactions consistent with C. minutissimum. T h e demonstration of fluorescence however may vary between laboratories depending on the culture media used. Corynebacterium minutissimum may be more pathogenic than previously realised. Laboratory workers should be aware of its similarity to C. jeikeium and be prepared to perform additional tests to distinguish between the two. Lack of growth on triple sugar iron agar and in unsupplemented peptone water suggests that the organism is C. jeikeium. Further tests such as demonstration of fluorescence and lipid dependancy are best performed in reference laboratories. All patients with invasive infections caused by C. minutissimum have had skin lesions, although none have been suggestive of erythrasma. T h e infective agent causing erythrasma is in doubt and until this is resolved the diagnosis should continue to be made on clinical grounds without the need to confirm by culturing C. minutissimum. References I. S a r k a n y I, T a p l i n D , B l a n k H . E r y t h r a s m a - - c o m m o n ffAMA I 9 6 I ; 1 7 7 : 1 3 o - 1 3 1 .
bacterial i n f e c t i o n o f t h e skin.
76
C. L. GOLLEDGE AND G. P H I L L I P S
2. Sindhuphak W, MacDonald E, Smith EB. Erythrasma. Overlooked or misdiagnosed ? Int J Dermatol I985; 24: 95-96. 3. Guarderas J, Karnard A, Alverez S, Berk SL. Corynebacterium minutissimum bacteremia in a patient with chronic myeloid leukaemia in blast crisis. Diagn Microbiol Infect Dis I986; 5: 327-33o. 4. Herschorn BJ, Brucker AJ. Embolic retinopathy due to Corynebacterium minutissimum endocarditis. Br ff Opthalmol r985; 69: 29--3I. 5. Berger SA, Gorea A, Stadler J, Dan M, Zilberamn M. Recurrent breast abscesses caused by Corynebacterium minutissimum. J Clin Microbiol I984; 20: I219-I22O. 6. Thompson JS, Gates-Davis DR, Yong DCT. Rapid microbiological identification of Corynebacterium diphtheriae and other medically important corynebacteria, ff Clin Microbiol r983; I8: 926-929. 7. Erspaard H, Justesen T. Multiresistant lipophilic corynebacteria from clinical specimens. Acta Path Microbiol Immunol Scand Sect B I984:92 39-43. 8. Somerville DA. Erythrasma in normal young adults. J Med Microbiol I97o; 3: 57-64. 9. Riley PS, Hollis DG, Utter GB, Weaver RE, Baker CN. Characterization and identification of 95 diphtheroid (group JK) cultures isolated from clinical specimens. J Clin Microbiol I979; 9: 418-424. IO. Coyle MB, Lipsky BA. Coryneform bacteria in infectious diseases; clinical and laboratory aspects. Clin Microbiol Rev I99O; 3: 227-246. I I. Collins MD, Jones D. Corynebacterium minutissimum sp. nov., nom. rev. Int ff System Bacteriol r983 ; 33 : 87o-87 I. r2. Sarkany I, Taplin D, Blank H. Organism causing erythrasma. Lancet I962; ii: 3o4-3o5. r3. Marples RR. Diphtheroids of normal human skin. Br J Dermatol I969; 8x (Suppl I); 47-54. x4. McBride ME, Montes LF, Knox JM. The characterization of fluorescent skin diphtheroids. Can ff Microbiol I97O; x6:941-946.
