Fc o m p l i c a t i o n o f c o n t i n u o u s

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1 Fusarium Peritonitis in A Patient on Peritoneal Dialysis Asmita Sagar Sakle* Abstract Fungal pathogens account for a small but well recognised proportion of peritonitis infections in continuous ambulatory peritoneal dialysis (CAPD) patients. This report presents a case of peritonitis by Fusarium in a patient on CAPD. A literature review of previously reported cases of Fusarium peritonitis was conducted to determine features common to infections caused by Fusarium. Emphasis was also placed on unique characteristics of the organism that may affect patient management. The relative drug resistance of this organism and the apparent propensity to invade the CAPD cannula wall make this fungus potentially sinister pathogen in CAPD patients. The most prudent management of these infections is early cannula removal and administration of antifungal agents, which was done in present case. Although fungi are rarely a cause of peritonitis, Candida albicans being the most common, the possibility should be considered of isolating other genera, such as Fusarium. Introduction ungal peritonitis is an infrequent Fc o m p l i c a t i o n o f c o n t i n u o u s ambulatory peritoneal dialysis (CAPD), typically occurring after a course of a n t i b i o t i c t h e r a p y f o r b a c t e r i a l 1,2,3 peritonitis. Most recommendations for therapy of fungal peritonitis have emphasised the necessity of removing the indwelling catheter to achieve a complete 2, cure of the infection. Despite such measures, mortality from fungal 2 peritonitis remains high and reported rates of successful return to peritoneal 5,6 dialysis (PD) have been low. Fusarium species belong to the class Deuteromycetes (Fungi Imperfecti). These *Incharge Microbiologist, Department of Pathology, Bombay Hospital and Medical Research Centre, Mumbai organisms are found in soil and air and are 7 predominantly plant pathogens. Fusarium infections are often associated 8 with a relatively high mortality. The potential pathogenicity of this group of fungi in CAPD patients is particularly worthy of note because of the relative drug resistance of these organisms and their apparent ability to invade and obstruct the 9 cannulae used in CAPD. This is a case report of an old female patient on CAPD who developed Fusarium peritonitis shortly after recovering from bacterial peritonitis. A review of previously reported cases of Fusarium peritonitis was conducted focusing on the unique aspects of infection due to Fusarium that affect patient management. Case Report A 69 year old housewife with end stage renal 336

2 disease was being maintained on CAPD since 6 months. She presented with four days history of diffuse abdominal pain, puffiness of face, reduced appetite, malaise and cloudy dialysate. She was afebrile. She has had a previous episode of bacterial peritonitis due to Staphylococcus aureus, one month back, during which she was given Vancomycin. Hence, this time she was empirically given Vancomycin and Meropenem. PD fluid cell count was 1800 WBCs/cu.mm with neutrophil predominance (70%). Gram staining of the fluid revealed no organisms. Bacterial culture was negative. Fungal culture on Sabouraud's Dextrose agar yielded cottony white colonies (Fig. 1). From reverse, the Fig. 1 : Cottony white colonies on sabouraud's Dextrose Agar colonies were brown. Microscopy of the colonies showed hyaline septate hyphae, macroconidia and microconidia and chlamydospores. Macroconidia were fusiform, slightly curved (sickle shaped) with not more than 3 septa and had developed at the extremities of slender hyphae (Fig. 2). The fungus Fig. 2 : Macroconidia (Sickle shaped) and Microconidia (spherical) of Fusarium was identified as Fusarium solani. The PD catheter was removed and patient was shifted on haemodialysis after the isolation of Fusarium. She was given antifungal therapy for about weeks on OPD basis (exact antifungal agent could not be known). Patient was maintained on haemodialysis thereafter. Discussion Fusarium associated human disease has been known since at least 1913, when infection of the Russian grain supply by a toxin-producing Fusarium led to a widespread illness characterised by gastrointestinal symptoms, weakness, 10 and aplastic anaemia. In otherwise healthy individuals, Fusarium species are recognised as causing superficial 7,11 infections of the cornea, skin, and nails. Patients with burn wounds are especially susceptible to colonisation and infection of the skin by Fusarium and such infection m a y b e f o l l o w e d b y s y s t e m i c 12 dissemination. Although fungal peritonitis is uncommon in patients undergoing CAPD, it accounts for serious morbidity and 13 mortality. Fungi enter the peritoneal cavity through touch contamination of dialysis tubing or by direct extension of the 1 infection from the catheter exit site. Antimicrobial therapy causes alteration of faecal flora and transmigration of organisms into the peritoneal cavity. The fungus colonises the peritoneal catheter and is embedded in the amorphous matrix on the surface of the catheter leading to 15 fungal peritonitis. Factors that increase the risk of fungal peritonitis include prior antibiotic therapy for bacterial peritonitis, intestinal perforation, and immunosuppressive 7,15,16,17 therapy. The broad spectrum 337

3 antibiotic that our patient received for Staphylococcal peritonitis put her at increased risk for subsequent fungal peritonitis. Dialysis patients can be considered a special population at increased risk for developing any type of infection because of the numerous immunological defects caused by chronic 18 renal failure. In addition, in patients on PD, the indwelling foreign body provides a unique portal of access for pathogenic 1 organisms. The first cases of Fusarium peritonitis 9 were described by McNeely et al. in 1981 in 2 CAPD patients. Also as in our patient, the effectiveness of PD was compromised by the infection. Neither patient responded to antifungal therapy alone, but both improved after catheter removal. Subsequent reports by Kerr et al., Young et al., Heldman, Rippon et al. Chiaradia et al., and Roiz et al., have detailed the characteristics of Fusarium peritonitis in PD patients. The usual signs and symptoms of peritonitis - cloudy dialysate, diffuse abdominal pain, and fever - were present in most, but not all patients described. This patient presented with cloudy dialysate and diffuse abdominal pain but no fever. Most reports, including the present, had a preceding bacterial peritonitis (Table 1), which is felt to be a characteristic of fungal peritonitis in 1,2,3,,15,16,17 general by most authors. Failure to improve with standard antibiotic therapy (prior to the culture of a fungus) 20,22 was also noted. Kerr reported that Fusarium attached to the catheter wall, impeding the drainage of dialysate. 20 Heldman reported positive cultures for Fusarium from her patient's catheter tip and subcutaneous cuff. Therapy included antifungal drugs and the removal of the PD catheter in the majority of cases. All patients survived their episodes of Fusarium peritonitis, although 2 patients died later of unrelated causes. Table 1: Characteristics of patients on CAPD with Fusarium peritonitis Number of cases reviewed: 13 and Present case Characteristic * IV Amphotericin B - 6patients PO Ketoconazole - 1 patient PO Miconazole - 1 patient PO Flucytosine - 1 patient Not known - 2 patients Status YES NO UNKNOWN Previous episodes of 6 bacterial peritonitis Previous antibiotic therapy 6 Catheter removal Antifungal therapy* Survival Return to CAPD 7 3 There was no uniform approach to the treatment of Fusarium peritonitis in the reported cases (Table 1). Most of this variation is probably due to the rarity of infection with this organism. However, by reviewing treatment of fusariosis at other anatomic sites, several factors that affect therapy can be identified. The first of these is the site and/or extent of infection. Superficial or well-localised infections, especially in fully immunocompetent individuals, are generally amenable to 11 antifungal chemotherapy. Disseminated or deep seated infections may be more difficult to treat, however, because of the difficulty of achieving therapeutic drug levels at these sites. In addition, Fusarium species may not be uniformly susceptible 338

4 11,23 to Amphotericin B. Thus reliance on Amphotericin B alone may not result in successful treatment. Despite these difficulties, treatment with high dose Amphotericin B ( mg/kg/day) with or without a second agent like Flucytosine, or Miconazole appears to be the recommended treatment for serious 7,2 infections with Fusarium. Fusarium's propensity to invade or attach to foreign bodies like intravascular or PD catheters is the final factor that may adversely affect treatment of deep seated infections like 7 peritonitis. With respect to Fusarium peritonitis specifically, catheter removal would appear to be indicated, since most of the previously reported patients required catheter removal to successfully overcome the infection (Table 1). This included several patients who were initially treated with their PD catheters in place, but eventually came to catheter removal because of persistent symptoms, and one who developed intra-abdominal adhesions and bowel obstruction when the catheter was left in place. In addition, it is felt that infections caused by Fusarium are more difficult to treat than infections caused by other fungi such as Candida or 11 Aspergillus, therefore making the more aggressive approach of catheter removal necessary. There are indications from the International Society of Peritoneal Dialysis, which recommend the removal of the peritoneal catheter along with 15,16 administration of antifungal agents. Conclusion In conclusion, Fusarium peritonitis in peritoneal dialysis is a rare but serious complication, which stops the technique from functioning, requiring transfer to haemodialysis. Previous episodes of bacterial peritonitis and antibiotic therapy are the most common risk factors. Treatment requires removal of the peritoneal catheter and administration of antifungal agents. Early diagnosis and treatment reduce morbidity and mortality. References 1. Vas SI. Infections of continuous ambulatory peritoneal dialysis catheters. Infect Dis Clin North Am 1989;3: Hartman BJ. Fungal peritonitis. Infect Med 1985; 2: Oh SH, Conley SB, Rose GM, et al. Fungal peritonitis in children undergoing peritoneal dialysis. Pediatr Infect Dis J 1985; : Kerr CM, Perfect JR, Craven PC, et al. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis. Ann Intern Med 1983; 99: Eisenberg ES, Leviton I, Soeiro R. Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature. Rev I nfect Dis 1986; 8: Forwell MA, Smith WGJ, Tsakiris D, et al. Morbidity of fungal peritonitis. Contrib Nephrol 1987; 57: Flynn JT, Meislich D, Kaiser BA, et al. Fusarium peritonitis in a child on peritoneal dialysis: case report and review of the literature. Perit Dial Int 1996;16: Rippon JW, Larson RA, Rosenthal DM, et al. Disseminated cutaneous and peritoneal hyalohyphomycosis caused by Fusarium species: three cases and a review of the literature. Mycopathologica 1988; 101: McNeely DJ, Vas SI, Dombros N, et al. Fusarium peritonitis: an uncommon complication of continuous ambulatory peritoneal dialysis. Perit Dial Bull 1981; 1: Mayer CF. Endemic panmyelotoxicosis in the Russian grain belt. Part one: The clinical aspects of alimentary toxic aleukia (ATA): a comprehensive review. Military Surg 1953;113:

5 11. Richardson SE, Bannatyne RM, Summerbell RC, et al. Disseminated fusarial infection in the immunocompromised host. Rev Infect Dis 1988; 10: Wheeler MS, McGinnis MR, Schell WA, Walker DH. Fusarium infection in burned patients. Am J Clin Pathol 1981; 75: Kean WF, Vas SL, Peritonitis international. In: Gokal R, Nolph KD, editors. Text book of peritoneal dialysis Dordrecht. Netherland: Kluwer; 199. p Johnson RJ, Ramsey PG, Gallagher N, Ahmad S. Fungal peritonitis in patients on CAPD, Incidence, clinical features and prognosis. Am J Nephrol 1985;5: I n d h u m a t h i E, C h a n d r a s e k a r a n V, Jagadeswaran D, et al. The risk factors and outcome of fungal peritonitis in continuous ambulatory peritoneal dialysis patients. Indian J Med Microbiol 2009;27: Martos PG, De Sola F.G., Marin P, Garcia- Agudo, L., Garcia-Agudo R,Tejuca F., Calle L. Nefrologia 2009; 29 (6), Prasad KN, Prasad N, Gupta A, et al. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis: a single centre Indian experience. J Infect 200;8: Walshe JJ, Morse GD. Infectious complications of peritoneal dialysis. In: Nissenson AR, Fine RN, Gentile DE, eds. Clinical dialysis. 2nded. Norwalk: Appleton and Lange,1990;chap 1: Young JB, Ahmed-Jushuf LH, Brownjohn AM, et al. Opportunistic peritonitis in continuous ambulatory peritoneal dialysis. Clin Nephrol 198; 22: Heldman DA. Peritonitis in a patient on continuous ambulatory peritoneal dialysis. North Carolina Med J 1985; 6: Chiaradia V, Schinella D, Pascoli L, et al. Fusarium peritonitis in peritoneal dialysis: report of two cases. Microbiologia 1990; 13: Roiz MP, del Palacio A, Cuandacute;tara MS, et al. Peritonitis en un paciente sometido a di and acute; lisis peritoneal continua ambulatoria. Enferm Infecc Microbiol Clin 1993; 11: Ruben A, Anaissie E, Nelson PE, et al. Antifungal susceptibility of clinical isolates of Fusarium species determined by using a broth micro dilution method. Antimicrob Agents Chemother 1989; 33: Anaissie EJ, Bodey G P, Rinaldi M G.Emerging fungal pathogens. Eur J Clin Microbiol Infect Dis 1989; 8: Eye markers of cardiovascular disease Xanthelasmata are predictive, but arcus corneae is not Most clinicians are aware that arcus corneae and xanthelasmata are related to hyperlipidaemia, but results have been conflicting on whether they provide extra information compared with traditional risk factors when predicting the risk of cardiovascular disease. Arcus corneae and xanthelasmata are recognised signs of hyperlipidaemia when seen in younger patients. Xanthelasmata palpebrarum is the most common cutaneous xanthoma. It consists of soft, yellow, plaques that appear on the medial aspects of the eyelids bilaterally. It most often occurs in middle aged and older adults. Raised low density lipoprotein-cholesterol is the most common dyslipidaemia associated with xanthelasmata. These results indicate that xanthelasmata are an important predictor of cardiovascular disease events and death beyond its known association with hyperlipidaemia. As with any study, the current study has some limitations. What do these results mean in practice? Overall, the evidence highlights the importance of a comprehensive physical examination and suggests that xanthelasmata could be used by general clinicians to help identify people at higher risk of cardiovascular disease. BMJ, 2011; Vol. 33, 70 30