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Intermittent bladder irrigation with liposomal amphotericin B for the treatment of fluconazole-resistant Meyerozyma guilliermondii cystitis in an immunosuppressed adolescent
Instilaciones vesicales intermitentes con anfotericina B liposomal para el tratamiento de una cistitis por Meyerozyma guilliermondii resistente a fluconazol en un adolescente inmunodeprimido
Ana Capilla-Mirandaa,
Corresponding author
anacapillam@gmail.com

Corresponding author.
, Diego Plaza-Lópezb, Paloma Garcia-Clementec, Fernando Baquero-Artigaod,e
a Servicio de Inmunología, Reumatología e Infectología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain
b Servicio de Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid, Spain
c Servicio de Microbiología, Hospital Universitario La Paz, Madrid, Spain
d Servicio de Pediatría, Enfermedades Infecciosas y Patología Tropical, Hospital Universitario La Paz, Madrid, Spain
e CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Urinary tract infection &#40;UTI&#41; is the third leading cause of nosocomial infection in paediatrics&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although most infections are of bacterial origin&#44; fungal aetiology is increasing due to <span class="elsevierStyleItalic">Candida</span> species with less sensitivity to azoles&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The treatment of these infections is complex due to a lack of therapeutic options&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">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&#46; He had a history of urinary infections in the previous two months caused by <span class="elsevierStyleItalic">Candida parapsilosis</span> and <span class="elsevierStyleItalic">Meyerozyma guilliermondii</span> &#40;<span class="elsevierStyleItalic">Candida guilliermondii</span>&#41;&#44; which had been resolved by replacing the catheter and treatment with fluconazole&#46; After receiving a cycle of chemotherapy and being in a state of neutropenia&#44; the patient developed sepsis of abdominal origin&#44; requiring broad-spectrum antibiotic therapy with meropenem&#44; amikacin and vancomycin&#46; In this context&#44; <span class="elsevierStyleItalic">M&#46; guilliermondii</span> was isolated in his urine&#44; persisting in successive urine cultures despite the catheter being replaced once again and treatment with intravenous fluconazole for two weeks&#46; Blood cultures were negative and renal ultrasound showed no significant findings apart from bilateral pyelocalyceal dilation secondary to obstruction caused by the tumour mass&#46; The antifungal susceptibility tests showed resistance to fluconazole &#40;MIC 16&#8239;&#956;g&#47;mL&#41;&#44; with sensitivity to the other antifungals tested&#46; With these findings&#44; it was decided to start combined treatment with intravenous micafungin&#44; which was continued for 14 days&#44; and daily bladder irrigation with liposomal amphotericin B &#40;30&#8239;mg&#47;100&#8239;ml&#41;&#59; 100&#8239;ml was introduced through the catheter&#44; clamped for 10&#8239;min only&#46; The treatment was well tolerated&#44; with no adverse effects detected&#44; and it was continued for five days&#44; achieving microbiological eradication&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Treating asymptomatic candiduria is not indicated in paediatrics unless the patient develops symptoms or belongs to a group at risk of spread &#40;neutropenia&#44; need for urological manipulation&#44; newborn or a kidney transplant&#41;&#46; The treatment of choice is oral fluconazole&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> with amphotericin B deoxycholate&#44; flucytosine&#44; or bladder irrigation with amphotericin B deoxycholate recommended for resistant species&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In our case&#44; amphotericin B deoxycholate is not available for use in Spain&#44; and flucytosine was ruled out because it is associated with myelotoxicity in up to 22&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Liposomal amphotericin B&#44; triazole derivatives and echinocandins have limited excretion in the urine&#46; We opted for intermittent bladder irrigation with liposomal amphotericin B&#44; in combination with micafungin as systemic treatment in view of the patient&#39;s neutropenia&#46; The concentration of echinocandins in urine is very low &#40;0&#46;7&#37; of the plasma concentration in the case of mucafungin&#41;&#46; Still&#44; there are reported cases of successful use in the treatment of candiduria due to <span class="elsevierStyleItalic">Candida</span> species resistant to fluconazole&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> although there have also been therapeutic failures&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> We cannot&#44; therefore&#44; rule out that micafungin may have contributed to our patient being cured&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Most of the literature consulted for bladder irrigation with amphotericin B refers to using the deoxycholate form&#46; We only found one case of intravesical administration of the liposomal form&#46; This was a 65-year-old female patient who developed septic shock of abdominal origin&#44; with isolation of <span class="elsevierStyleItalic">C&#46; parapsilosis</span> in blood culture&#44; urine culture and surgical wound&#46; As part of the treatment of candiduria&#44; bladder irrigation with liposomal amphotericin B was used continuously for three days at a concentration of 50&#8239;mg&#47;l with a good outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Our case is the first to be described in a paediatric patient&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Intravesical administration of amphotericin B deoxycholate is more effective using continuous rather than intermittent irrigation&#46; The most commonly used concentration is 50&#8239;mg&#47;l&#44; although a higher concentration is used in intermittent administrations&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In our case&#44; intermittent instillations of liposomal amphotericin B were administered as the urinary catheter had only one lumen&#44; and catheter replacement was difficult&#46; The concentration we used was effective in intermittent irrigation with amphotericin B deoxycholate<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and was used for five consecutive days with good results&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We would conclude that intravesical instillation of liposomal amphotericin B may be a safe alternative in treating azole-resistant <span class="elsevierStyleItalic">Candida</span> species cystitis&#46; However&#44; more extensive studies are needed to support this assertion&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0035" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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