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Trends in antifungal use and species distribution among Candida isolates in a large paediatric hospital
Letters to the Editor / International Journal of Antimicrobial Agents 24 (2004) 622–630
T.G. Winstanleya,∗ E.J. Ridgwaya,b,c B.T. Parysb N. Woodfordc E. Wardc D.M. Livermorec a Department
of Microbiology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK b Rotherham District General Hospital Moorgate Road, Rotherham S60 2UD, UK c Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory London NW9 5HT, UK ∗ Corresponding author E-mail address: [email protected] (T.G. Winstanley)
doi:10.1016/j.ijantimicag.2004.09.007
Trends in antifungal use and species distribution among Candida isolates in a large paediatric hospital Sir, Nosocomial infections due to Candida spp. are increasingly being reported in paediatric patients. Surveillance data indicate that Candida spp. are one of the leading cause of bloodstream infections, accounting for 9% of such infections in a recent European multicentre study in children [1]. In the present study, we evaluated retrospectively, antifungal use and species distribution in consecutive Candida strains isolated from various body sites of children hospitalised at the G. Gaslini Institute in Genoa from 1995 to 2001. The use of antifungal agents was calculated as defined daily doses/1000 patient/days (DDDs). Table 1 shows the number of different Candida spp. isolated during the observation period. The distribution of these isolates by unit or service were as follows: intensive care, 25%; surgery, 23%; infectious diseases, 22%; paediatrics, 13%; respiratory, 17%. Candida albicans was the most frequent species isolated, representing two-third of the isolates. Forty-one of the 195 strains of C. albicans were isolated from HIV-1-infected children. Of note, C. glabrata was the second most frequently isolated species (23 strains), followed by C. parapsilosis (12) and C. tropicalis (12). The proportion of yeasts other than C. albicans isolated, increased significantly during the observation period (χ2 for linear trend 18.3; P < 0.001). Of the 48 episodes of candidaemia recorded, 28 (58%) occurred in intensive care units and 12 (25%) in surgical patients. C. albicans was identified in 32 (66%) of these episodes, C. parapsilosis in 8 (16.6%) and C. glabrata in
627
Table 1 Species distribution of Candida strains isolated from children during a 5 years observation period (January 1996–December 2001) Species
No. (%) of isolates All sitesa
Blood
C. albicans C. glabrata C. parapsilosis C. tropicalis Othersb
195 23 12 12 13
32 3 8 1 4
Total
255 (100)
(76) (9) (4.7) (4.7) (5.0)
(66) (6.2) (16.6) (2.0) (8.3)
48 (18.8)
a
Including isolates from urine (30%), mucocutaneous specimens (26%), sputum (18%), BAL and gastric aspirates (7%). b Including five isolates of Candida spp., two isolates of C. lusitaniae, and one each of C. paratropicalis, C. pelliculosa, C. incospicua, C. humicola, C. rugosa and C. krusei.
3 (6.2%). All episodes of candidaemia due to non-C. albicans species occurred in intensive care units (11) or surgical patients (5). The frequency of candidaemia due to nonalbicans Candida rose during the study period, but this trend was not statistically significant (χ2 for linear trend 2.84; P = 0.09). The use of antifungal agent used did not vary significantly during the study period (Fig. 1). Mean (S.D.) DDDs were: fluconazole, 1.616 (±0.2286); flucytosine,0.209 (±0.063); itraconazole, 0.882 (±0.128); amphotericin, 1.645 (±0.397). Our data show that the epidemiology of Candida infection in our children’s hospital is changing. Though the predominant isolate during the study period remained C. albicans, we observed a significant rise in the proportion of infection or colonisation with non-albicans strains. The increasing importance of C. glabrata infection with increasing patient age is well known, though not universally documented [2,3]. In contrast, C. glabrata is rarely reported as responsible for bloodstream infection in neonates and children [2–5]. Our data are in agreement with those of a study conducted in six neonatal intensive care units in USA [6]. In this survey, 22 of 35 (63%) episodes of bloodstream
Fig. 1. Antifungal use (DDDs/1000 patients/days) and Candida spp. distribution at the G. Gaslini Institute of Genoa, from 1996 to 2000.
628
Letters to the Editor / International Journal of Antimicrobial Agents 24 (2004) 622–630
infection were due to C. albicans, 10 (29%) to C. parapsilosis and 2 (6%) to C. glabrata. However, in our series C. glabrata was the second most frequent species responsible for infection or colonisation, with an overall rate of 9% which is much higher than those already reported. For instance, only 1.5% of patients in the neonatal intensive care units in the American survey were found to be colonised with C. glabrata [6]. Our data are consistent with previous reports showing C. parapsilosis to be one of the predominant species responsible for candidaemia in paediatric patients [4,6,7]. Changes in the pattern of Candida spp. infection might be partly attributed to the widespread use of prophylactic or empirical antifungal therapy with fluconazole. Several investigators have noted increases in the frequency of C. glabrata isolation in conjunction with the selective pressure exerted by azole use [8,9]. It has been argued that one of the reason for the lower incidence of C. glabrata infections in paediatric populations is the tendency for neonatologists and paediatricians to use amphotericin B preferentially to fluconazole in the treatment of fungal infection. Of note, in our paediatric hospital, the use of fluconazole approached the use of amphotericin B and itraconazole was the third most commonly prescribed agent (Fig. 1). In conclusion, our report supports previous observations on the increasing clinical relevance of non-albicans Candida species in nosocomial paediatric infections and highlights the need for establishing surveillance programmes focused on fungal infections.
References [1] Raymond J, Aujard Y. Nosocomial infections in pediatric patients: a European, multicenter prospective study. European Study Group. Infect Control Hosp Epidemiol 2000;21:260–3. [2] Pfaller MA, Diekeman DJ, Jones RN, Messer SA, Hollis RJ, The SENTRY participants group. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY antimicrobial surveillance program, 1997 to 2000. Antimicrob Agents Chemother 2002;40:852–6. [3] Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J Hosp Infect 2002;50:243–60. [4] Paganini H, Rodriguez Brieshcke T, Santos P, Seu’ S, Rosanova MT. Risk factors for nosocomial candidaemia: a case-control study in children. J Hosp Infect 2002;50:304–8. [5] Huang YC, Lin TY, Lien RI, et al. Candidaemia in special care nurseries: comparison of albicans and parapsilosis infection. J Infect 2000;40:171–5. [6] Rangel-Frausto MS, Wiblin T, Blumberg HM, et al. National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis 1999;29:253–8. [7] Levy I, Rubin LG, Vasishta S, Tucci V, Sood SK. Emergence of Candida parapsilosis as the predominant species causing candidemia in children. Clin Infect Dis 1998;26:1086–8. [8] Nguyen MH, Peacock JE, Morris AJ, et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617–23.
[9] Wingard JR. Importance of Candida spp. other than C. albicans as pathogens in oncology patients. Clin Infect Dis 1995;20:115–25.
Graziana Manno∗ Angelo Scaramuccia Infectious Diseases Research and Diagnosis Laboratory Department of Paediatrics, University of Genoa and Clinical Pathology, G. Gaslini Children’s Hospital Largo G. Gaslini 5, 16147 Genoa, Italy Rossella Rossi Angela Coppini Pharmacy Department, Gaslini Children’s Hospital Genoa, Italy Mario Cruciani Centre of Preventive Medicine, USL 20 Verona, Italy ∗ Corresponding
author. Tel.: +39 0105636780 fax: +39 0103773210 E-mail address: [email protected] (G. Manno) doi:10.1016/j.ijantimicag.2004.08.007
Treatment with linezolid and rifampicin for 18 months for recurrent infection of a megaprosthesis in a patient with Ewing’s sarcoma Sir, The main complications in long-term survivors of Ewing’s sarcoma are metastases, local recurrence, secondary malignancies, pathological fractures, radiation- and chemotherapy-associated morbidities, the majority of which occur about 5 years after diagnosis [1]. In addition, the rate of infection in particular in association with a tumour prosthesis is high [2]. Management of prosthetic jointinfections remains a therapeutic challenge and encounters numerous host and organism factors. Among them, the emergence of resistant Gram-positive bacteria is of particular concern and requires novel therapeutic approaches. Linezolid, the first approved oxazolidinone, appears to be a promising new agent for the treatment of serious Grampositive infections [3]. Linezolid is orally, as well as intravenously, active and has a favourable pharmacokinetic and toxicity profile, which can be of particular value for the treatment of infections that require a prolonged antibiotic course [4]. Here, we report a patient with a 12-year history of Ewing’s sarcoma and methicillin-resistant Staphylococcus epidermidis infection of a prosthetic tumour prosthesis, successfully treated with linezolid and rifampicin for 18 months. A 36-year-old woman with a history of Ewing’s sarcoma had a medullar femur and tibia replacement implantation in May 1992. In July 1994, the prosthesis became infected with S. epidermidis and the patient underwent de-
T.G. Winstanleya,∗ E.J. Ridgwaya,b,c B.T. Parysb N. Woodfordc E. Wardc D.M. Livermorec a Department
of Microbiology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK b Rotherham District General Hospital Moorgate Road, Rotherham S60 2UD, UK c Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory London NW9 5HT, UK ∗ Corresponding author E-mail address: [email protected] (T.G. Winstanley)
doi:10.1016/j.ijantimicag.2004.09.007
Trends in antifungal use and species distribution among Candida isolates in a large paediatric hospital Sir, Nosocomial infections due to Candida spp. are increasingly being reported in paediatric patients. Surveillance data indicate that Candida spp. are one of the leading cause of bloodstream infections, accounting for 9% of such infections in a recent European multicentre study in children [1]. In the present study, we evaluated retrospectively, antifungal use and species distribution in consecutive Candida strains isolated from various body sites of children hospitalised at the G. Gaslini Institute in Genoa from 1995 to 2001. The use of antifungal agents was calculated as defined daily doses/1000 patient/days (DDDs). Table 1 shows the number of different Candida spp. isolated during the observation period. The distribution of these isolates by unit or service were as follows: intensive care, 25%; surgery, 23%; infectious diseases, 22%; paediatrics, 13%; respiratory, 17%. Candida albicans was the most frequent species isolated, representing two-third of the isolates. Forty-one of the 195 strains of C. albicans were isolated from HIV-1-infected children. Of note, C. glabrata was the second most frequently isolated species (23 strains), followed by C. parapsilosis (12) and C. tropicalis (12). The proportion of yeasts other than C. albicans isolated, increased significantly during the observation period (χ2 for linear trend 18.3; P < 0.001). Of the 48 episodes of candidaemia recorded, 28 (58%) occurred in intensive care units and 12 (25%) in surgical patients. C. albicans was identified in 32 (66%) of these episodes, C. parapsilosis in 8 (16.6%) and C. glabrata in
627
Table 1 Species distribution of Candida strains isolated from children during a 5 years observation period (January 1996–December 2001) Species
No. (%) of isolates All sitesa
Blood
C. albicans C. glabrata C. parapsilosis C. tropicalis Othersb
195 23 12 12 13
32 3 8 1 4
Total
255 (100)
(76) (9) (4.7) (4.7) (5.0)
(66) (6.2) (16.6) (2.0) (8.3)
48 (18.8)
a
Including isolates from urine (30%), mucocutaneous specimens (26%), sputum (18%), BAL and gastric aspirates (7%). b Including five isolates of Candida spp., two isolates of C. lusitaniae, and one each of C. paratropicalis, C. pelliculosa, C. incospicua, C. humicola, C. rugosa and C. krusei.
3 (6.2%). All episodes of candidaemia due to non-C. albicans species occurred in intensive care units (11) or surgical patients (5). The frequency of candidaemia due to nonalbicans Candida rose during the study period, but this trend was not statistically significant (χ2 for linear trend 2.84; P = 0.09). The use of antifungal agent used did not vary significantly during the study period (Fig. 1). Mean (S.D.) DDDs were: fluconazole, 1.616 (±0.2286); flucytosine,0.209 (±0.063); itraconazole, 0.882 (±0.128); amphotericin, 1.645 (±0.397). Our data show that the epidemiology of Candida infection in our children’s hospital is changing. Though the predominant isolate during the study period remained C. albicans, we observed a significant rise in the proportion of infection or colonisation with non-albicans strains. The increasing importance of C. glabrata infection with increasing patient age is well known, though not universally documented [2,3]. In contrast, C. glabrata is rarely reported as responsible for bloodstream infection in neonates and children [2–5]. Our data are in agreement with those of a study conducted in six neonatal intensive care units in USA [6]. In this survey, 22 of 35 (63%) episodes of bloodstream
Fig. 1. Antifungal use (DDDs/1000 patients/days) and Candida spp. distribution at the G. Gaslini Institute of Genoa, from 1996 to 2000.
628
Letters to the Editor / International Journal of Antimicrobial Agents 24 (2004) 622–630
infection were due to C. albicans, 10 (29%) to C. parapsilosis and 2 (6%) to C. glabrata. However, in our series C. glabrata was the second most frequent species responsible for infection or colonisation, with an overall rate of 9% which is much higher than those already reported. For instance, only 1.5% of patients in the neonatal intensive care units in the American survey were found to be colonised with C. glabrata [6]. Our data are consistent with previous reports showing C. parapsilosis to be one of the predominant species responsible for candidaemia in paediatric patients [4,6,7]. Changes in the pattern of Candida spp. infection might be partly attributed to the widespread use of prophylactic or empirical antifungal therapy with fluconazole. Several investigators have noted increases in the frequency of C. glabrata isolation in conjunction with the selective pressure exerted by azole use [8,9]. It has been argued that one of the reason for the lower incidence of C. glabrata infections in paediatric populations is the tendency for neonatologists and paediatricians to use amphotericin B preferentially to fluconazole in the treatment of fungal infection. Of note, in our paediatric hospital, the use of fluconazole approached the use of amphotericin B and itraconazole was the third most commonly prescribed agent (Fig. 1). In conclusion, our report supports previous observations on the increasing clinical relevance of non-albicans Candida species in nosocomial paediatric infections and highlights the need for establishing surveillance programmes focused on fungal infections.
References [1] Raymond J, Aujard Y. Nosocomial infections in pediatric patients: a European, multicenter prospective study. European Study Group. Infect Control Hosp Epidemiol 2000;21:260–3. [2] Pfaller MA, Diekeman DJ, Jones RN, Messer SA, Hollis RJ, The SENTRY participants group. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY antimicrobial surveillance program, 1997 to 2000. Antimicrob Agents Chemother 2002;40:852–6. [3] Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J Hosp Infect 2002;50:243–60. [4] Paganini H, Rodriguez Brieshcke T, Santos P, Seu’ S, Rosanova MT. Risk factors for nosocomial candidaemia: a case-control study in children. J Hosp Infect 2002;50:304–8. [5] Huang YC, Lin TY, Lien RI, et al. Candidaemia in special care nurseries: comparison of albicans and parapsilosis infection. J Infect 2000;40:171–5. [6] Rangel-Frausto MS, Wiblin T, Blumberg HM, et al. National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units. Clin Infect Dis 1999;29:253–8. [7] Levy I, Rubin LG, Vasishta S, Tucci V, Sood SK. Emergence of Candida parapsilosis as the predominant species causing candidemia in children. Clin Infect Dis 1998;26:1086–8. [8] Nguyen MH, Peacock JE, Morris AJ, et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617–23.
[9] Wingard JR. Importance of Candida spp. other than C. albicans as pathogens in oncology patients. Clin Infect Dis 1995;20:115–25.
Graziana Manno∗ Angelo Scaramuccia Infectious Diseases Research and Diagnosis Laboratory Department of Paediatrics, University of Genoa and Clinical Pathology, G. Gaslini Children’s Hospital Largo G. Gaslini 5, 16147 Genoa, Italy Rossella Rossi Angela Coppini Pharmacy Department, Gaslini Children’s Hospital Genoa, Italy Mario Cruciani Centre of Preventive Medicine, USL 20 Verona, Italy ∗ Corresponding
author. Tel.: +39 0105636780 fax: +39 0103773210 E-mail address: [email protected] (G. Manno) doi:10.1016/j.ijantimicag.2004.08.007
Treatment with linezolid and rifampicin for 18 months for recurrent infection of a megaprosthesis in a patient with Ewing’s sarcoma Sir, The main complications in long-term survivors of Ewing’s sarcoma are metastases, local recurrence, secondary malignancies, pathological fractures, radiation- and chemotherapy-associated morbidities, the majority of which occur about 5 years after diagnosis [1]. In addition, the rate of infection in particular in association with a tumour prosthesis is high [2]. Management of prosthetic jointinfections remains a therapeutic challenge and encounters numerous host and organism factors. Among them, the emergence of resistant Gram-positive bacteria is of particular concern and requires novel therapeutic approaches. Linezolid, the first approved oxazolidinone, appears to be a promising new agent for the treatment of serious Grampositive infections [3]. Linezolid is orally, as well as intravenously, active and has a favourable pharmacokinetic and toxicity profile, which can be of particular value for the treatment of infections that require a prolonged antibiotic course [4]. Here, we report a patient with a 12-year history of Ewing’s sarcoma and methicillin-resistant Staphylococcus epidermidis infection of a prosthetic tumour prosthesis, successfully treated with linezolid and rifampicin for 18 months. A 36-year-old woman with a history of Ewing’s sarcoma had a medullar femur and tibia replacement implantation in May 1992. In July 1994, the prosthesis became infected with S. epidermidis and the patient underwent de-