Urinary tract infection (UTI) is the third leading cause of nosocomial infection in paediatrics.1 Although most infections are of bacterial origin, fungal aetiology is increasing due to Candida species with less sensitivity to azoles.2 The treatment of these infections is complex due to a lack of therapeutic options.
We present the case of a 16-year-old patient with a left pelvic metastatic osteosarcoma undergoing chemotherapy who required permanent bladder catheterisation because of tumour compression. He had a history of urinary infections in the previous two months caused by Candida parapsilosis and Meyerozyma guilliermondii (Candida guilliermondii), which had been resolved by replacing the catheter and treatment with fluconazole. After receiving a cycle of chemotherapy and being in a state of neutropenia, the patient developed sepsis of abdominal origin, requiring broad-spectrum antibiotic therapy with meropenem, amikacin and vancomycin. In this context, M. guilliermondii was isolated in his urine, persisting in successive urine cultures despite the catheter being replaced once again and treatment with intravenous fluconazole for two weeks. Blood cultures were negative and renal ultrasound showed no significant findings apart from bilateral pyelocalyceal dilation secondary to obstruction caused by the tumour mass. The antifungal susceptibility tests showed resistance to fluconazole (MIC 16 μg/mL), with sensitivity to the other antifungals tested. With these findings, it was decided to start combined treatment with intravenous micafungin, which was continued for 14 days, and daily bladder irrigation with liposomal amphotericin B (30 mg/100 ml); 100 ml was introduced through the catheter, clamped for 10 min only. The treatment was well tolerated, with no adverse effects detected, and it was continued for five days, achieving microbiological eradication.
Treating asymptomatic candiduria is not indicated in paediatrics unless the patient develops symptoms or belongs to a group at risk of spread (neutropenia, need for urological manipulation, newborn or a kidney transplant). The treatment of choice is oral fluconazole,3,4 with amphotericin B deoxycholate, flucytosine, or bladder irrigation with amphotericin B deoxycholate recommended for resistant species.3 In our case, amphotericin B deoxycholate is not available for use in Spain, and flucytosine was ruled out because it is associated with myelotoxicity in up to 22% of patients.5 Liposomal amphotericin B, triazole derivatives and echinocandins have limited excretion in the urine. We opted for intermittent bladder irrigation with liposomal amphotericin B, in combination with micafungin as systemic treatment in view of the patient's neutropenia. The concentration of echinocandins in urine is very low (0.7% of the plasma concentration in the case of mucafungin). Still, there are reported cases of successful use in the treatment of candiduria due to Candida species resistant to fluconazole,6,7 although there have also been therapeutic failures.8 We cannot, therefore, rule out that micafungin may have contributed to our patient being cured.
Most of the literature consulted for bladder irrigation with amphotericin B refers to using the deoxycholate form. We only found one case of intravesical administration of the liposomal form. This was a 65-year-old female patient who developed septic shock of abdominal origin, with isolation of C. parapsilosis in blood culture, urine culture and surgical wound. As part of the treatment of candiduria, bladder irrigation with liposomal amphotericin B was used continuously for three days at a concentration of 50 mg/l with a good outcome.9 Our case is the first to be described in a paediatric patient.
Intravesical administration of amphotericin B deoxycholate is more effective using continuous rather than intermittent irrigation. The most commonly used concentration is 50 mg/l, although a higher concentration is used in intermittent administrations.10 In our case, intermittent instillations of liposomal amphotericin B were administered as the urinary catheter had only one lumen, and catheter replacement was difficult. The concentration we used was effective in intermittent irrigation with amphotericin B deoxycholate10 and was used for five consecutive days with good results.
We would conclude that intravesical instillation of liposomal amphotericin B may be a safe alternative in treating azole-resistant Candida species cystitis. However, more extensive studies are needed to support this assertion.
FundingNone.
Conflicts of interestThe authors declare that they have no conflicts of interest.
