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Epidemiology of fungal infection in burns: Therapeutic implications
burns 38 (2012) 942–948
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/burns
Letter to the Editor Epidemiology of fungal infection in burns: Therapeutic implications Keywords: Epidemiology Candida Echinocandins Burns
Dear Editors We are very interested in the study of Sarabahi and colleagues [1] on epidemiology of invasive fungal burn wound infections. Fungal infections now represent a serious problem in burn units, because they are associated with a high morbidity and mortality. This article emphasizes an important problem in burns: the changing epidemiology in fungal wound infections, and the necessity for clinicians to adapt empirical antifungal therapy. In the author’s unit, nonalbicans Candida species become the predominant fungal agents causing wound infections in burned patients (66–93% of all fungal infections) [1]. In the intensive care unit, nonalbicans Candida sp. and especially Candida glabrata and Candida krusei, have become more frequent in invasive candidiasis (nearly one case on five) [2]. These species exhibit resistance to traditional azole antifungals like Fluconazole. Therefore, recent guidelines have recommended an echinocandin as primary therapy for nonneutropenic or neutropenic patients [3]. However, in our center, wound biome epidemiology is different [4]. We retrospectively examined all positive fungal isolates on 134 burned patients for 8 months (July 2008–March 2009). Incidence of these positive isolates was high (17.2%), but we found no candidaemia. 84.4% of these isolates were positive for Candida albicans and only 12.8% were positive for nonalbicans candida sp. Our situation is not so isolated, and these findings are quite consistent with other studies. For example, we see the French study of Vinsonneau and colleagues who retrospectively analyzed 20 instances of candidemia in burns [5]. They isolated 65% of C. albicans, 25% of Candida parapsilosis and 10% of Candida tropicalis. Thus, changing pattern of fungal infection has not occurred in our unit for the moment. In most cases, we identify C. albicans in our fungal colonizations or infections. That is why we rarely use Echinocandins; Fluconazole remains our first line empirical therapy in fungal wound
infections, when fungus is not identified yet. In case of suspected invasive fungal infections in hemodynamicaly unstable patients, we currently use Amphotericin B with lipid formulation (5 mg/kg daily) as empirical antifungal therapy. This molecule is one of the recommended treatments for C. krusei, C. glabrata and covers dreaded Aspergillus sp. and mucor [3]. Echinocandins also have activity against Aspergillus sp. But, nowadays Echinocandins is indicated in patients with probable or proven invasive aspergillosis refractory to or intolerant of other approved therapies. Data on the use of Echinocandins in burned patients are scarce; we need some clinical studies to confirm the place of Echinocandins in antifungal strategy in burns, and to define pharmacological characteristics of such treatment in burned patients. Moreover, in vivo and in vitro resistances to Caspofungin in non-burned patients receiving Echinocandins have been reported for Candida and Aspergillus species [6]. Clinicians have to be aware of development of antimicrobial resistances in case of massive use of new anti-infectious molecules. Experience shows that this phenomenon can occur. So, utilization of Echinocandins shall be used with caution according fungal epidemiology in each unit, the suspected agents, and the lack of knowledge of these molecules in burns.
Conflict of interest statement None of the authors has a financial assistance in any of the products, devices or drugs that was mentioned in the article.
references
[1] Sarabahi S, Tiwari VK, Arora S, Capoor MR, Pandey. A Changing pattern of fungal infection in burn patients. Burns 2011. doi: 10.1016/j.burns.2011.09.013. [2] Leroy O, Mira JP, Montravers P, Gangneux JP, Lortholary O. AmarCand Study Group. Comparison of albicans vs. nonalbicans candidemia in French intensive care units. Crit Care 2010;14:R98. [3] Pappas PG, Kauffman CA, Andes D, Benjamin Jr DK, Calandra TF, Edwards Jr JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48:503–35. [4] Monpeurt C, Pasquier P, Cottez-Gacia S, Mac Nab C, Soler C, Bargues L. Incidence et microbiologie des infections et
burns 38 (2012) 942–948
colonisations fongiques chez le bruˆle´ grave. Bruˆlures 2009;10:31. [5] Vinsonneau C, Benyamina M, Baixench MT, Stephanazzi J, Augris C, Grabar S, et al. Effects of candidaemia on outcome of burns. Burns 2009;35:561–4. [6] Mayr A, Aigner M, Lass-Flo¨rl C. Caspofungin: when and how? The microbiologist’s view. Mycoses 2012;55:27–35.
Jean-Vivien Schaal* Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France Thomas Leclerc Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France Pierre Pasquier Department of Emergency and Intensive Care Medicine, Military hospital Be´gin, 69 avenue de Paris, 94067, Saint-Mande´, France Laurent Bargues Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France *Corresponding author. Tel.: +33 662072859 E-mail address: [email protected] (J.-V. Schaal) Accepted 7 February 2012 0305-4179/$36.00 # 2012 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2012.02.028
943
patients from our centre from 2001 to 2003 [2]. In our pilot study C. albicans was isolated in 10% and N. candida in 75%. However in our subsequent studies there was alarming change in species pattern from 16.7% C. albicans and 66.7% N. candida in the first study to 0% C. albicans and 90% N. candida in our second study of which 33% grew Candida tropicalis and 40% Candida krusei. This therefore shows that not only is there a shift from C. albicans to N. candida, but there is also a change in the isolated species of N. candida from the burn wounds. The increasing incidence of C. tropicalis and C. krusei is alarming. They are associated with deep fungal invasion with high mortality and indicate nosocomial infection unlike C. albicans which is a normal commensal. This is also supported by studies of other authors [3,4]. In our initial studies we were using azoles as empirical therapy but considering the change in the spectrum of species from C. albicans to N. candida emerging resistance to azoles was also noticed. This prompted us to use echinocandins (Caspofungin) or amphoteracin b as empirical antifungal agent for critically ill patients. The use of conventional amphoteracin B in critically ill burn patients was associated with severe toxicity, therefore echinocandins (caspofungin) and even the lipid emulsion of amphoteracin B were found to be safe alternatives. Once the species is identified and the sensitivity pattern is known, either the empirical therapy is continued or deescalated as per requirements. In our unit we have not noticed any resistance to echinocandins with this rational use.
Conflict of interest statement The authors have no conflict of interest to declare.
Letter to the Editor Response to Letter to the Editor: ‘Epidemiology of Fungal Infection in Burns’ Keywords: Nonalbicans Candida Burn wound Echinocandins
Dear Editors This is with reference to the letter to editor entitled ‘Epidemiology of fungal infection in burns’ by Jean Vivien Schaal et al. who have stated that in their unit the incidence of fungal isolates in burn patients is 17.2% without any candidemia. This is comparable to our study where the incidence of fungal infection in burn patients is 12%. However candidemia was seen in 4% of total patients who were critically ill [1]. The authors also stated that incidence of Candida albicans was much higher (84.4%) than that of Nonalbicans candida (12.8%). Similarly higher incidence of C. albicans (54%) was found in a detailed summary of candida infection of burn
references
[1] Schaal J-V, Leclerc T, Pasquier P, Bargues L. Epidemiology of fungal infection in burns. Burns (Letter to Editor), doi:10.1016/j.burns.2012.02.026, in press. [2] Gupta N, Hague A, Latif AA, Narayan RP, Mukhopadhyay G, Prasad R. Epidemiology and molecular typing of Candida isolates from burn patients. Mycopathologia 2005;158: 397–405. [3] Alangaden GJ. Nosocomial fungal infection: epidemiology, infection control and prevention. Infect Dis Clin North Am 2011;25:201–25. [4] Hope W, Morton A, Eisen DP. Increase in prevalence of nosocomial non Candida albicans candidemia and the association of c krusei with fluconazole use. J Hosp Infect 2002;50(1):56–65.
Sujata Sarabahi* V.K. Tiwari Savita Arora Department of Burns and Plastic Surgery, VMMC and Safdarjung Hospital, New Delhi, India Malini R. Capoor Department of Microbiology, VMMC and Safdarjung Hospital, New Delhi, India
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/burns
Letter to the Editor Epidemiology of fungal infection in burns: Therapeutic implications Keywords: Epidemiology Candida Echinocandins Burns
Dear Editors We are very interested in the study of Sarabahi and colleagues [1] on epidemiology of invasive fungal burn wound infections. Fungal infections now represent a serious problem in burn units, because they are associated with a high morbidity and mortality. This article emphasizes an important problem in burns: the changing epidemiology in fungal wound infections, and the necessity for clinicians to adapt empirical antifungal therapy. In the author’s unit, nonalbicans Candida species become the predominant fungal agents causing wound infections in burned patients (66–93% of all fungal infections) [1]. In the intensive care unit, nonalbicans Candida sp. and especially Candida glabrata and Candida krusei, have become more frequent in invasive candidiasis (nearly one case on five) [2]. These species exhibit resistance to traditional azole antifungals like Fluconazole. Therefore, recent guidelines have recommended an echinocandin as primary therapy for nonneutropenic or neutropenic patients [3]. However, in our center, wound biome epidemiology is different [4]. We retrospectively examined all positive fungal isolates on 134 burned patients for 8 months (July 2008–March 2009). Incidence of these positive isolates was high (17.2%), but we found no candidaemia. 84.4% of these isolates were positive for Candida albicans and only 12.8% were positive for nonalbicans candida sp. Our situation is not so isolated, and these findings are quite consistent with other studies. For example, we see the French study of Vinsonneau and colleagues who retrospectively analyzed 20 instances of candidemia in burns [5]. They isolated 65% of C. albicans, 25% of Candida parapsilosis and 10% of Candida tropicalis. Thus, changing pattern of fungal infection has not occurred in our unit for the moment. In most cases, we identify C. albicans in our fungal colonizations or infections. That is why we rarely use Echinocandins; Fluconazole remains our first line empirical therapy in fungal wound
infections, when fungus is not identified yet. In case of suspected invasive fungal infections in hemodynamicaly unstable patients, we currently use Amphotericin B with lipid formulation (5 mg/kg daily) as empirical antifungal therapy. This molecule is one of the recommended treatments for C. krusei, C. glabrata and covers dreaded Aspergillus sp. and mucor [3]. Echinocandins also have activity against Aspergillus sp. But, nowadays Echinocandins is indicated in patients with probable or proven invasive aspergillosis refractory to or intolerant of other approved therapies. Data on the use of Echinocandins in burned patients are scarce; we need some clinical studies to confirm the place of Echinocandins in antifungal strategy in burns, and to define pharmacological characteristics of such treatment in burned patients. Moreover, in vivo and in vitro resistances to Caspofungin in non-burned patients receiving Echinocandins have been reported for Candida and Aspergillus species [6]. Clinicians have to be aware of development of antimicrobial resistances in case of massive use of new anti-infectious molecules. Experience shows that this phenomenon can occur. So, utilization of Echinocandins shall be used with caution according fungal epidemiology in each unit, the suspected agents, and the lack of knowledge of these molecules in burns.
Conflict of interest statement None of the authors has a financial assistance in any of the products, devices or drugs that was mentioned in the article.
references
[1] Sarabahi S, Tiwari VK, Arora S, Capoor MR, Pandey. A Changing pattern of fungal infection in burn patients. Burns 2011. doi: 10.1016/j.burns.2011.09.013. [2] Leroy O, Mira JP, Montravers P, Gangneux JP, Lortholary O. AmarCand Study Group. Comparison of albicans vs. nonalbicans candidemia in French intensive care units. Crit Care 2010;14:R98. [3] Pappas PG, Kauffman CA, Andes D, Benjamin Jr DK, Calandra TF, Edwards Jr JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48:503–35. [4] Monpeurt C, Pasquier P, Cottez-Gacia S, Mac Nab C, Soler C, Bargues L. Incidence et microbiologie des infections et
burns 38 (2012) 942–948
colonisations fongiques chez le bruˆle´ grave. Bruˆlures 2009;10:31. [5] Vinsonneau C, Benyamina M, Baixench MT, Stephanazzi J, Augris C, Grabar S, et al. Effects of candidaemia on outcome of burns. Burns 2009;35:561–4. [6] Mayr A, Aigner M, Lass-Flo¨rl C. Caspofungin: when and how? The microbiologist’s view. Mycoses 2012;55:27–35.
Jean-Vivien Schaal* Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France Thomas Leclerc Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France Pierre Pasquier Department of Emergency and Intensive Care Medicine, Military hospital Be´gin, 69 avenue de Paris, 94067, Saint-Mande´, France Laurent Bargues Burn Center, Military hospital Percy, 101 Avenue Henry Barbusse, 92140 Clamart, France *Corresponding author. Tel.: +33 662072859 E-mail address: [email protected] (J.-V. Schaal) Accepted 7 February 2012 0305-4179/$36.00 # 2012 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2012.02.028
943
patients from our centre from 2001 to 2003 [2]. In our pilot study C. albicans was isolated in 10% and N. candida in 75%. However in our subsequent studies there was alarming change in species pattern from 16.7% C. albicans and 66.7% N. candida in the first study to 0% C. albicans and 90% N. candida in our second study of which 33% grew Candida tropicalis and 40% Candida krusei. This therefore shows that not only is there a shift from C. albicans to N. candida, but there is also a change in the isolated species of N. candida from the burn wounds. The increasing incidence of C. tropicalis and C. krusei is alarming. They are associated with deep fungal invasion with high mortality and indicate nosocomial infection unlike C. albicans which is a normal commensal. This is also supported by studies of other authors [3,4]. In our initial studies we were using azoles as empirical therapy but considering the change in the spectrum of species from C. albicans to N. candida emerging resistance to azoles was also noticed. This prompted us to use echinocandins (Caspofungin) or amphoteracin b as empirical antifungal agent for critically ill patients. The use of conventional amphoteracin B in critically ill burn patients was associated with severe toxicity, therefore echinocandins (caspofungin) and even the lipid emulsion of amphoteracin B were found to be safe alternatives. Once the species is identified and the sensitivity pattern is known, either the empirical therapy is continued or deescalated as per requirements. In our unit we have not noticed any resistance to echinocandins with this rational use.
Conflict of interest statement The authors have no conflict of interest to declare.
Letter to the Editor Response to Letter to the Editor: ‘Epidemiology of Fungal Infection in Burns’ Keywords: Nonalbicans Candida Burn wound Echinocandins
Dear Editors This is with reference to the letter to editor entitled ‘Epidemiology of fungal infection in burns’ by Jean Vivien Schaal et al. who have stated that in their unit the incidence of fungal isolates in burn patients is 17.2% without any candidemia. This is comparable to our study where the incidence of fungal infection in burn patients is 12%. However candidemia was seen in 4% of total patients who were critically ill [1]. The authors also stated that incidence of Candida albicans was much higher (84.4%) than that of Nonalbicans candida (12.8%). Similarly higher incidence of C. albicans (54%) was found in a detailed summary of candida infection of burn
references
[1] Schaal J-V, Leclerc T, Pasquier P, Bargues L. Epidemiology of fungal infection in burns. Burns (Letter to Editor), doi:10.1016/j.burns.2012.02.026, in press. [2] Gupta N, Hague A, Latif AA, Narayan RP, Mukhopadhyay G, Prasad R. Epidemiology and molecular typing of Candida isolates from burn patients. Mycopathologia 2005;158: 397–405. [3] Alangaden GJ. Nosocomial fungal infection: epidemiology, infection control and prevention. Infect Dis Clin North Am 2011;25:201–25. [4] Hope W, Morton A, Eisen DP. Increase in prevalence of nosocomial non Candida albicans candidemia and the association of c krusei with fluconazole use. J Hosp Infect 2002;50(1):56–65.
Sujata Sarabahi* V.K. Tiwari Savita Arora Department of Burns and Plastic Surgery, VMMC and Safdarjung Hospital, New Delhi, India Malini R. Capoor Department of Microbiology, VMMC and Safdarjung Hospital, New Delhi, India