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Candida and hands
Journal
of Hospital
Infection
(1986) 8, l-4
LEADING
Candida
ARTICLE
and hands
Systemic candidosis is a disease of increasing incidence with a high mortality and no typical clinical picture (Gold, 1984). The mainstay of treatment is amphotericin B which has been associated with nephrotoxicity (de Repentigny & Reiss, 1984). Difficulties in diagnosis and treatment have led to the use of numerous different oral antifungal agents as chemoprophylaxis, but since no regime has proved completely successful (Donnelly et al., 1984), treatment with parenteral amphotericin B is often given to immunocompromised patients whose pyrexia fails to resolve after antibacterial therapy (Holleran, Wilbur & De Gregorio, 1985). Infection has usually been attributed to autoinfection by yeasts colonizing the patient’s bowel or iv catheters (Krause, Matheis & Wulf, 1969; Stone, 1974). However, the recent report (Burnie et al., 1985~) of an outbreak of systemic candidosis in the intensive care unit at the London Hospital marks a new approach to the control of this infection. Thirteen patients on the unit developed systemic candidosis (due to an epidemic strain) as defined by either cultural and histological evidence from a deep organ biopsy or by positive blood cultures obtained from different iv sites at least 24 h apart. The outbreak isolates typed as serotype A (Hasenclever & Mitchell, 1961), 1968) and biotype o/i/5/5/, (Odds & morphotype Al (Brown-Thomson, Abbott, 1980). The same type also caused 44% of the superficial candidal infections in the unit compared with 17% of the candidal infections in other parts of the same hospital. No environmental source was identified during this outbreak but the strain was isolated from the mouths of four of 65 nurses and the hands/of one of these individuals. Two of 17 nurses acquired the strain on their hands immediately after nursing patients with systemic candidosis. A further nurse developed vaginal candidosis due to an outbreak isolate. There appeared to be a cycle of infection between patients and staff in the unit, with hands acting as the major route of transmission. Since Candidu ulbicuns is rarely demonstrable in the atmosphere (Midgley & Clayton, 1972) even near infants with oral thrush (Kozinn et al., 1959) the suspected cycle of infection demonstrated in the unit was not surprising. Two previous outbreaks of cutaneous candidal infection have been documented and in both of these the source was shown to be contaminated fomites (Cremer & De Groot, 1967; Malamatinis, Mattmiller & Westfall, 1968). An outbreak of Cund. purupsilosis septicaemia due to contaminated iv feeds (Solomon et al., 1984) has also been reported. 01954701/86/040001+04
0
SO3.00/0
1
1986 The Hospital
Infection
Society
2
J. P. Burnie
The possibility that hand transmission was important in the pathogenesis of systemic candidosis led us to examine the survival of the outbreak strain on the hands of volunteers. It was compared with another clinical isolate of Cand. albicans serotype B, and with two laboratory strains, Cand. albicans NCTC 3153, serotype A and Cand. albicans NCTC 3156 serotype B. The survival on hands and blocks of formica was assessed as described by Casewell & Desai, (1983) for klebsiellas. The results of survival on blocks of formica was used as a measure of environmental survival and showed no significant differences between the four strains. With an inoculum of lo4 cells, a reduction of about one logarithm was seen after 15 min, and about two logarithms after 90 min (Burnie et al., 1985a). However, the outbreak strain survived better on hands than the three control strains over a 60-min period. This difference was further accentuated if the hands were washed with chlorhexidine detergent mixture (‘Hibiscrub’, ICI) one h after inoculation. The serotype B NCTC strain disappeared completely and there was an appreciable drop in the counts of both the serotype B clinical isolate and serotype A NCTC strain. Thirty minutes after handwashing, the serotype B clinical isolate had disappeared and the serotype A NCTC strain was present in only small numbers, but the outbreak strain was still present at > 100 organisms per ml. In further experiments when hands were washed 1 min after inoculation of the fingers with lo4 cells, rather than after 60 mins, chlorhexidine completely removed the NCTC serotype B strain but caused only a two-logarithm reduction in the levels of the other strains (Burnie et al., 19853). A similar picture was seen with unmedicated soap except that all strains showed a 2 log drop. In contrast, an alcoholic chlorhexidine handrub (‘Hibisol’, ICI), povidone-iodine detergent mixture (Napp Laboratories Ltd) and 70% isopropyl alcohol completely eliminated all strains within 3 mins. The failure of chlorhexidine to eliminate the outbreak strain could have been due to either intrinsic resistance to chlorhexidine or an increased ability of the strain to adhere to epithelial surfaces. The outbreak and non-outbreak isolates were found to be equally susceptible (Burnie, 1985a) using a microtitre technique (Pitt, Gaston & Hoffman, 1983). Killing curves showed that the outbreak strain was only slightly more resistant than the control organisms. The adherence of the four organisms to Hep 2 cells, buccal epithelial cells and acrylic CT. Douglas, personal communication) differed significantly, the epidemic strain being the most adherent and with a relative order of adherence of: outbreak strain> serotype B clinical isolate > NCTC 3 153 serotype A > NCTC 3 156 serotype B. The resistance of the outbreak strain to handwashing with chlorhexidine was therefore due more to its increased ability to adhere to epithelial cells than an intrinsic resistance. Yeast binding has been shown to be time-dependent (King, Lee & Morris, 1980) which would explain the difference between the results obtained after handwashing at different times.
Candida
and hands
3
‘Hibiscrub’ was the agent used for handwashing in the unit at the time of the outbreak. Handwashing with agents with better in vitro activity were introduced, but it is difficult to assess their impact on the control of the outbreak, since routine prophylaxis with ketoconazole had been introduced some 4 months earlier (Burnie et al., 19853). However, ketoconazole prophylaxis had failed to prevent infection in six patients and the overall mortality from systemic candidosis remained high, despite the use of an antigen detection system to aid early diagnosis (Burnie, 198%). It is possible that the high incidence of systemic candidosis recorded in other units is also due in part to cross-infection. The occurrence of manual transmission and its prevention with fungicidal handwashing agents, rather than oral chemoprophylaxis, merits further study. J. P. Burnie
The London Hospital Medical College, Department of Medical Microbiology, Turner Street, London El 2AD References
Brown-Thomsen, J. (1968). Variability in Candidu albicans (Robin) Berkhout. I. Studies on morphology and biochemical activity. Hereditas 60, 355-398. Burnie, J. P. (19850). MD Thesis, the University of Cambridge. Burnie, J. P. (19856). A reverse passive latex agglutination test for the diagnosis of systemic candidosis. Journal of Immunological Methods 82, 267-280. Burnie, J. P., Lee, W., Williams, J. D., Matthews, R. C. & Odds, F. C. (19853). Con&o1 of an outbreak of systemic Cundidu ulbicuns. British Medical Journal 291, 1092-1093. Burnie, J. P., Odds, F. C., Lee, W., Webster, C. & Williams, J. D. (1985~). Outbreak of systemic Cundidu ulbicuns in intensive care unit caused by cross-infection. British Medical Journal, 290, 74&748. Casewell, M. W. & Desai, N. (1983). S urvival of multiply-resistant Klebsiellu uerogenes and other Gram-negative bacilli on finger-tips. Journal of Hospital Infection 4, 350-360. Cremer, G. & DeGroot, W. P. (1967). An epidemic of thrush in a premature nursery. Dermutologiu 135, 107-l 14. Donnelly, J. P., Starke, I. D., Galton, D. A. G., Catovski, D., Goldman, J. M. & Darrell, J. H. (1984). Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia. Journal of Hospital Infection 5, 83-91. Gold, J. W. M. (1984). Opportunistic fungal infections in patients with neoplastic disease. American Journal of Medicine 76, 458-463. Hasenclever, H. F. & Mitchell, W. 0. (1961). Antigenic studies of Candida I. Observation of two antigenic groups in Cundidu ulbicuns. Journal of Bacteriology 82, 57Ck.573. Holleran, W. M., Wilbur, J. R. & De Gregorio, M. W. (1985). Empiric amphotericin B therapy in patients with acute leukaemia. Reviews of Infectious Diseases 7, 619-624. King, R. D., Lee, J. C. & Morris, A. L. (1980). Adherence of Cundidu ulbicuns and other Cundidu species to mucosal epithelial cells. Infection and Immunity 27, 667-674. Kozinn, P. J., Wiener, H., Taschdjian, C. L., & Burchall, J. J. (1959). Is isolation of infants with thrush necessary? Journal of the American Medical Association 170, 1172-l 174. Krause, W., Matheis, H. & Wulf, K. (1969). Fungaemia and funguria after oral administration of Cundidu ulbicuns. Luncet, 598-599. Malamatinis, J. E., Mattmiller, E. D. & Westfall, J. N. (1968). Cutaneous moniliasis affecting varsity athletes. Journal of the American College Health Association 16, 294-295. Midgley, G. & Clayton, Y. M. (1972). Distribution of dermatophytes and candida spores in the environment. British Journal of Dermatology 86, 69-77.
J. P. Burnie
4 Odds,
F. C. & Abbott,
A. B. (1980) A simple system for the presumptive of strains within the species.
Candida albicans and differentiation
identification
Sabouraudia
of 18,
301-317. Pitt, T. L., Gaston, M. A. & Hoffman, P. N. (1983). In vitro susceptibility of hospital isolates Journal of Hospital Infection 4, 173-l 76, of various bacterial genera to chlorhexidine. de Repentigny, L. & Reiss, E. (1984). C urrent trends in immunodiagnosis of candidosis and aspergillosis. Reviews of Infectious Diseases 6, 301-312. Solomon, S. L., Khabbaz, R. F., Parker, R. H., Anderson, R. L., Geraghty, M. A., Furman, R. M. & Marton, W. J. (1984). An outbreak of Candida parapsilosis blood stream infections in patients receiving parenteral nutrition. Journal of Infectious Diseases 149, 98-103. Stone, H. H. (1974). Studies in the pathogenesis, diagnosis and treatment of candida sepsis in children. Journal of Pediatric Surgery 9, 127-133.
of Hospital
Infection
(1986) 8, l-4
LEADING
Candida
ARTICLE
and hands
Systemic candidosis is a disease of increasing incidence with a high mortality and no typical clinical picture (Gold, 1984). The mainstay of treatment is amphotericin B which has been associated with nephrotoxicity (de Repentigny & Reiss, 1984). Difficulties in diagnosis and treatment have led to the use of numerous different oral antifungal agents as chemoprophylaxis, but since no regime has proved completely successful (Donnelly et al., 1984), treatment with parenteral amphotericin B is often given to immunocompromised patients whose pyrexia fails to resolve after antibacterial therapy (Holleran, Wilbur & De Gregorio, 1985). Infection has usually been attributed to autoinfection by yeasts colonizing the patient’s bowel or iv catheters (Krause, Matheis & Wulf, 1969; Stone, 1974). However, the recent report (Burnie et al., 1985~) of an outbreak of systemic candidosis in the intensive care unit at the London Hospital marks a new approach to the control of this infection. Thirteen patients on the unit developed systemic candidosis (due to an epidemic strain) as defined by either cultural and histological evidence from a deep organ biopsy or by positive blood cultures obtained from different iv sites at least 24 h apart. The outbreak isolates typed as serotype A (Hasenclever & Mitchell, 1961), 1968) and biotype o/i/5/5/, (Odds & morphotype Al (Brown-Thomson, Abbott, 1980). The same type also caused 44% of the superficial candidal infections in the unit compared with 17% of the candidal infections in other parts of the same hospital. No environmental source was identified during this outbreak but the strain was isolated from the mouths of four of 65 nurses and the hands/of one of these individuals. Two of 17 nurses acquired the strain on their hands immediately after nursing patients with systemic candidosis. A further nurse developed vaginal candidosis due to an outbreak isolate. There appeared to be a cycle of infection between patients and staff in the unit, with hands acting as the major route of transmission. Since Candidu ulbicuns is rarely demonstrable in the atmosphere (Midgley & Clayton, 1972) even near infants with oral thrush (Kozinn et al., 1959) the suspected cycle of infection demonstrated in the unit was not surprising. Two previous outbreaks of cutaneous candidal infection have been documented and in both of these the source was shown to be contaminated fomites (Cremer & De Groot, 1967; Malamatinis, Mattmiller & Westfall, 1968). An outbreak of Cund. purupsilosis septicaemia due to contaminated iv feeds (Solomon et al., 1984) has also been reported. 01954701/86/040001+04
0
SO3.00/0
1
1986 The Hospital
Infection
Society
2
J. P. Burnie
The possibility that hand transmission was important in the pathogenesis of systemic candidosis led us to examine the survival of the outbreak strain on the hands of volunteers. It was compared with another clinical isolate of Cand. albicans serotype B, and with two laboratory strains, Cand. albicans NCTC 3153, serotype A and Cand. albicans NCTC 3156 serotype B. The survival on hands and blocks of formica was assessed as described by Casewell & Desai, (1983) for klebsiellas. The results of survival on blocks of formica was used as a measure of environmental survival and showed no significant differences between the four strains. With an inoculum of lo4 cells, a reduction of about one logarithm was seen after 15 min, and about two logarithms after 90 min (Burnie et al., 1985a). However, the outbreak strain survived better on hands than the three control strains over a 60-min period. This difference was further accentuated if the hands were washed with chlorhexidine detergent mixture (‘Hibiscrub’, ICI) one h after inoculation. The serotype B NCTC strain disappeared completely and there was an appreciable drop in the counts of both the serotype B clinical isolate and serotype A NCTC strain. Thirty minutes after handwashing, the serotype B clinical isolate had disappeared and the serotype A NCTC strain was present in only small numbers, but the outbreak strain was still present at > 100 organisms per ml. In further experiments when hands were washed 1 min after inoculation of the fingers with lo4 cells, rather than after 60 mins, chlorhexidine completely removed the NCTC serotype B strain but caused only a two-logarithm reduction in the levels of the other strains (Burnie et al., 19853). A similar picture was seen with unmedicated soap except that all strains showed a 2 log drop. In contrast, an alcoholic chlorhexidine handrub (‘Hibisol’, ICI), povidone-iodine detergent mixture (Napp Laboratories Ltd) and 70% isopropyl alcohol completely eliminated all strains within 3 mins. The failure of chlorhexidine to eliminate the outbreak strain could have been due to either intrinsic resistance to chlorhexidine or an increased ability of the strain to adhere to epithelial surfaces. The outbreak and non-outbreak isolates were found to be equally susceptible (Burnie, 1985a) using a microtitre technique (Pitt, Gaston & Hoffman, 1983). Killing curves showed that the outbreak strain was only slightly more resistant than the control organisms. The adherence of the four organisms to Hep 2 cells, buccal epithelial cells and acrylic CT. Douglas, personal communication) differed significantly, the epidemic strain being the most adherent and with a relative order of adherence of: outbreak strain> serotype B clinical isolate > NCTC 3 153 serotype A > NCTC 3 156 serotype B. The resistance of the outbreak strain to handwashing with chlorhexidine was therefore due more to its increased ability to adhere to epithelial cells than an intrinsic resistance. Yeast binding has been shown to be time-dependent (King, Lee & Morris, 1980) which would explain the difference between the results obtained after handwashing at different times.
Candida
and hands
3
‘Hibiscrub’ was the agent used for handwashing in the unit at the time of the outbreak. Handwashing with agents with better in vitro activity were introduced, but it is difficult to assess their impact on the control of the outbreak, since routine prophylaxis with ketoconazole had been introduced some 4 months earlier (Burnie et al., 19853). However, ketoconazole prophylaxis had failed to prevent infection in six patients and the overall mortality from systemic candidosis remained high, despite the use of an antigen detection system to aid early diagnosis (Burnie, 198%). It is possible that the high incidence of systemic candidosis recorded in other units is also due in part to cross-infection. The occurrence of manual transmission and its prevention with fungicidal handwashing agents, rather than oral chemoprophylaxis, merits further study. J. P. Burnie
The London Hospital Medical College, Department of Medical Microbiology, Turner Street, London El 2AD References
Brown-Thomsen, J. (1968). Variability in Candidu albicans (Robin) Berkhout. I. Studies on morphology and biochemical activity. Hereditas 60, 355-398. Burnie, J. P. (19850). MD Thesis, the University of Cambridge. Burnie, J. P. (19856). A reverse passive latex agglutination test for the diagnosis of systemic candidosis. Journal of Immunological Methods 82, 267-280. Burnie, J. P., Lee, W., Williams, J. D., Matthews, R. C. & Odds, F. C. (19853). Con&o1 of an outbreak of systemic Cundidu ulbicuns. British Medical Journal 291, 1092-1093. Burnie, J. P., Odds, F. C., Lee, W., Webster, C. & Williams, J. D. (1985~). Outbreak of systemic Cundidu ulbicuns in intensive care unit caused by cross-infection. British Medical Journal, 290, 74&748. Casewell, M. W. & Desai, N. (1983). S urvival of multiply-resistant Klebsiellu uerogenes and other Gram-negative bacilli on finger-tips. Journal of Hospital Infection 4, 350-360. Cremer, G. & DeGroot, W. P. (1967). An epidemic of thrush in a premature nursery. Dermutologiu 135, 107-l 14. Donnelly, J. P., Starke, I. D., Galton, D. A. G., Catovski, D., Goldman, J. M. & Darrell, J. H. (1984). Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia. Journal of Hospital Infection 5, 83-91. Gold, J. W. M. (1984). Opportunistic fungal infections in patients with neoplastic disease. American Journal of Medicine 76, 458-463. Hasenclever, H. F. & Mitchell, W. 0. (1961). Antigenic studies of Candida I. Observation of two antigenic groups in Cundidu ulbicuns. Journal of Bacteriology 82, 57Ck.573. Holleran, W. M., Wilbur, J. R. & De Gregorio, M. W. (1985). Empiric amphotericin B therapy in patients with acute leukaemia. Reviews of Infectious Diseases 7, 619-624. King, R. D., Lee, J. C. & Morris, A. L. (1980). Adherence of Cundidu ulbicuns and other Cundidu species to mucosal epithelial cells. Infection and Immunity 27, 667-674. Kozinn, P. J., Wiener, H., Taschdjian, C. L., & Burchall, J. J. (1959). Is isolation of infants with thrush necessary? Journal of the American Medical Association 170, 1172-l 174. Krause, W., Matheis, H. & Wulf, K. (1969). Fungaemia and funguria after oral administration of Cundidu ulbicuns. Luncet, 598-599. Malamatinis, J. E., Mattmiller, E. D. & Westfall, J. N. (1968). Cutaneous moniliasis affecting varsity athletes. Journal of the American College Health Association 16, 294-295. Midgley, G. & Clayton, Y. M. (1972). Distribution of dermatophytes and candida spores in the environment. British Journal of Dermatology 86, 69-77.
J. P. Burnie
4 Odds,
F. C. & Abbott,
A. B. (1980) A simple system for the presumptive of strains within the species.
Candida albicans and differentiation
identification
Sabouraudia
of 18,
301-317. Pitt, T. L., Gaston, M. A. & Hoffman, P. N. (1983). In vitro susceptibility of hospital isolates Journal of Hospital Infection 4, 173-l 76, of various bacterial genera to chlorhexidine. de Repentigny, L. & Reiss, E. (1984). C urrent trends in immunodiagnosis of candidosis and aspergillosis. Reviews of Infectious Diseases 6, 301-312. Solomon, S. L., Khabbaz, R. F., Parker, R. H., Anderson, R. L., Geraghty, M. A., Furman, R. M. & Marton, W. J. (1984). An outbreak of Candida parapsilosis blood stream infections in patients receiving parenteral nutrition. Journal of Infectious Diseases 149, 98-103. Stone, H. H. (1974). Studies in the pathogenesis, diagnosis and treatment of candida sepsis in children. Journal of Pediatric Surgery 9, 127-133.