Reliability of 1-3-β-D-glucan monitoring during treatment of peritoneal candidiasis in a child in. continuous peritoneal dialysis: a case report

Transcription

1 CVI Accepts, published online ahead of print on 22 February 2012 Clin. Vaccine Immunol. doi: /cvi Copyright 2012, American Society for Microbiology. All Rights Reserved. 1 2 Reliability of 1-3-β-D-glucan monitoring during treatment of peritoneal candidiasis in a child in continuous peritoneal dialysis: a case report 3 4 Francesca Ginocchio 1, Enrico Verrina 2, Elisa Furfaro 3, Rossella Cannavò 2, Roberto Bandettini 4, Elio Castagnola Infectious Diseases Unit, G. Gaslini Children s Hospital, Genoa, Italy 2Nephrology and Dialysis Unit, G. Gaslini Children s Hospital, Genoa, Italy 3Infectious Diseases Department, University of Genoa, Genoa, Italy 4Central Laboratory of Analysis - Gaslini Children's Hospital, Genoa, Italy Running title: 1-3-β-D-glucan in peritoneal candidiasis Keywords: 1-3-β-D-glucan, invasive candidiasis, children, continuous peritoneal dialysis Correspondence: Elio Castagnola, MD Infectious Diseases Unit, Department of Pediatrics G. Gaslini Children s Hospital Largo G. Gaslini, Genova Italy Phone: Fax: eliocastagnola@ospedale-gaslini.ge.it 28

2 Abstract Fungal peritonitis is an unusual but severe complication of continuous peritoneal dialysis. The role of 1-3-β-Dglucan is unknown in early diagnosis and in treatment monitoring of peritoneal candidiasis. This case report shows the utility of 1-3-β-D-glucan monitoring in management of Candida peritonitis in a child undergoing continuous peritoneal dialysis Case report A four year-old male receiving peritoneal dialysis for chronic renal failure at the Nephrology and Dialysis Unit of G. Gaslini Children s Hospital, Genoa Italy was admitted because of the sudden onset of fever, abdominal pain and weakness. A short-term polyurethane venous catheter was inserted for management. Blood cultures were performed through this catheter and cultures of the peritoneal fluid through the silicon catheter used for peritoneal dialysis. Empirical antibacterial therapy was started according to internal protocol, and intravenous fluconazole 10 mg/kg once a day associated with intraperitoneal administration of 200 mg daily was added when laboratory reported yeasts (subsequently identified as C.parapsilosis) growing from peritoneal fluid and blood cultures. After 2 days of this therapy, clinical condition and inflammatory parameters did not improve and cultures from peritoneum still remained positive. Therefore fluconazole was substituted with caspofungin (50 mg/m 2 once a day) in order to administer a fungicidal drug that did not need dose reduction in patients with renal function impairment and without renal toxicity, and the peritoneal catheter was removed. Meanwhile, a polyurethane central venous catheter was inserted for administration of systemic antifungal therapy and to perform hemodialysis (on alternate day basis). With this management clinical conditions improved and there was negativization of blood and peritoneal cultures. Antifungal treatment with caspofungin was administered for a total of four weeks without side effects. Seriate determinations of 1-3-β-D-glucan (BDG) in peritoneal fluid and in serum were performed using the Fungitell assay (Associates of Cape Cod, Inc., Falmouth, MA), with a positive cut-off of 60 pg/ml, according to the manufacturer s recommendations. Peritoneal samples were taken through the silicon catheter for peritoneal dialysis and then by paracentesis after catheter removal. Serum samples were taken from the polyurethane catheters. When the patient underwent hemodialysis samples were taken the day the patient did not receive the procedure in order to reduce the risk of false-positive BDG test due to hemodialysis membranes. Sampling performed after the end of the episode was again performed through the silicon catheter re-inserted for

3 peritoneal dialysis. As shown in Figure 1, BDG resulted positive at very high levels (> 523 pg/ml, that is the upper limit of detection of the text) in the peritoneal fluid in the first days, with lower, but still positive levels in serum. After catheter removal the values of BDG rapidly dropped and become negatives. BDG in the peritoneal fluid and blood resulted negative also 3 weeks later when a new catheter for peritoneal dialysis was inserted Comments Peritoneal dialysis is a good alternative to hemodialysis but infections are a severe complication of this procedure. Fungal peritonitis is reported in 2-15% of patients, with Candida albicans, C.tropicalis and C.parapsilosis representing the most frequently isolated fungi [2]. Recent Guidelines for the treatment of this infection recommend prompt catheter removal and administration of fungicidal agents [7], while there is no mention of the possible role of BDG for monitoring effectiveness of treatment. Our case-report shows that BDG monitoring both in serum and peritoneal fluid may be useful to assess response to therapy, with concomitant evaluation of clinical conditions and microbiology. The major problem existing in this case-report is the possibility of false positive BDG test [10]. While hemodialysis with cellulose membranes is reported as a risk factor for false-positive results [4, 5], the role of membranes for peritoneal dialysis is unknown. As regards the components of the intravenous or peritoneal dialysis catheters as a possible cause of false positive test, a MEDLINE search using as keywords 1-3-β-D-glucan, silicon catheter or polyurethane catheter did not show any report. Even if the marked difference in BDG levels founded in peritoneal fluid before and after catheter removal could also be due to a BDG release by yeasts present in the infected catheter lumen, the clinical and microbiological course of our patient paralleled the modifications of BDG levels both in serum and peritoneal fluid, with reductions and negativization of the values clearly related with the management (catheter removal and antifungal therapy), and therefore excluding the possible risk of false positive tests by external factors (catheters materials). A further indirect support to this assumption is the fact that after the end of therapy samples for cultures and BDG taken through silicon peritoneal dialysis catheter resulted negative, in absence of local and general signs of infection. Finally, and as supplemental information, this case report also confirms that catheter removal is essential for treatment [7] and that caspofungin may represent an effective therapy for invasive disease due to C.parapsilosis, in spite of in vitro data suggesting a possible lower efficacy [3]. Studies and meta-analysis show that BDG is an useful test for diagnosis of invasive fungal infections in adults with hematologic malignancies or admitted in intensive care units, when combined with clinical, radiological, and

4 microbiological findings [1, 8, 6]. On the contrary, few data are available in pediatrics and these are derived from healthy subjects or small case series of immunocompromised children with otherwise documented invasive mycoses [9, 11]. The present case-report shows the reliability of BDG in the management of Candida peritonitis in patients undergoing peritoneal dialysis, with a good correspondence between 1-3-β-D-glucan levels in peritoneal fluid and serum, and microbiological and clinical outcome of the patient References 1. Del Bono, V., Delfino, E., Furfaro, E., Mikulska, M., Nicco, E., Bruzzi, P., Mularoni, A., Bassetti, M., Viscoli, C Clinical performance of (1,3)-{beta}-d-glucan assay in early diagnosis of nosocomial Candida blood stream infections. Clin. Vaccine Immunol. 18: Gandhi, B.V., Bahadur, M.M., Dodeja, H., Aggrwal, V., Thamba, A., Mali, M Systemic fungal infections in renal diseases. J. Postgrad. Med. 51:S Kale-Pradhan, P.B., Morgan, G., Wilhelm, S.M., Johnson, L.B Comparative efficacy of echinocandins and nonechinocandins for the treatment of Candida parapsilosis Infections: a meta-analysis. Pharmacotherapy. 30: Kanda, H., Kubo, K., Hamasaki, K., Kanda, Y., Nakao, A., Kitamura, T., Fujita, T., Yamamoto, K., Mimura, T Influence of various hemodialysis membranes on the plasma (1/3)-beta-D-glucan level. Kidney Int. 60: Kato, A., Takita, T., Furuhashi, M., Takahashi, T., Maruyama, Y., Hishida, A Elevation of blood (1/3)-beta-D-glucan concentrations in hemodialysis patients. Nephron. 89: Lamoth, F., Cruciani, M., Mengoli, C., Castagnola, E., Lortholary, O., Richardson, M., Marchetti, O.; on behalf of the Third European Conference on Infections in Leukemia (ECIL-3) β- Glucan Antigenemia Assay for the Diagnosis of Invasive Fungal Infections in Patients With Hematological Malignancies: A Systematic Review and Meta-Analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3). Clin. Infect. Dis. 54: Li, P.K., Szeto, C.C., Piraino, B., Bernardini, J., Figueiredo, A.E., Gupta, A., Johnson, D.W., Kuijper, E.J., Lye, W.C., Salzer, W., Schaefer, F., Struijk, D.G.; International Society for Peritoneal Dialysis Peritoneal dialysis-related infections recommendations: 2010 update. Perit. Dial. Int. 30: Mohr, J.F., Sims, C., Paetznick, V., Rodriguez, J., Finkelman, M.A., Rex, J.H., Ostrosky-Zeichner, L Prospective survey of (1-3)-β-D-Glucan and its relationship to invasive candidiasis in the surgical

5 intensive care unit setting. J. Clin. Microbiol. 49: Mularoni, A., Furfaro, E., Faraci, M., Franceschi, A., Mezzano, P., Bandettini, R., Viscoli, C., Castagnola, E High levels of beta-d-glucan in immunocompromised chidren with proven invasive fungal disease. Clin. Vaccine Immunol. 17: Racil, Z., Kocmanova, I., Lengerova, M., Weinbergerova, B., Buresova, L., Toskova, M., Winterova, J., Timilsina, S., Rodriguez, I., Mayer, J Difficulties in using 1,3-b-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies high frequency of false-positive results and their analysis. J Med Microbiol. 59: Smith, W.J., Benjamin, D.K. Jr, Alexander, B.D., Johnson, M.D., Finkelman, M.A., Steinbach, W.J Quantification of 1,3-beta-D-glucan levels in children: preliminary data for diagnostic use of the betaglucan assay in a pediatric setting. Clin. Vaccine Immunol. 14:

6 Figure 1. Treatment course, glucan levels and cultures in blood and perioneal fluid in a child with Candida peritonitis 133

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