+ Models
MYCMED-533; No. of Pages 4 Journal de Mycologie Médicale (2015) xxx, xxx—xxx
Available online at
ScienceDirect www.sciencedirect.com
CASE REPORT/CAS CLINIQUE
Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria ´ sistante Traitement d’une candidurie symptomatique re ´ lostomie au fluconazole par irrigation de caspofungine via une pye et flucytosine per-os H. Garcia a, J. Guitard b, J. Peltier a, M. Tligui c, S. Benbouzid c, S. Ait Elhaj a, E. Rondeau a, C. Hennequin b,* a
´ phrologie et transplantation re ´ nale, ho ˆ pitaux universitaires de l’Est-Parisien, Service de ne ˆ pital St-Antoine, 184, rue du Faubourg St-Antoine, 75012 Paris, France ho b ˆ pitaux universitaires de l’Est-Parisien, ho ˆ pital St-Antoine, Service de parasitologie-mycologie, ho 184, rue du Faubourg St-Antoine, 75012 Paris, France c ˆ pitaux universitaires de l’Est-Parisien, ho ˆ pital St-Antoine, 184, Service d’urologie, ho rue du Faubourg St-Antoine, 75012 Paris, France Received 17 November 2014; received in revised form 23 December 2014; accepted 30 December 2014
KEYWORDS Candida; Candiduria; Azole resistance; Caspofungin; Local irrigation
Summary Candiduria may be a marker of serious fungal infections such as pyelonephritis. With the exception of fluconazole and flucytosine, antifungals drugs are not excreted into the urine as active drugs, making the management of infection due to fluconazole-resistant Candida difficult. We report a case of recurrent Candida parapsilosis candiduria in a kidney transplant recipient suffering from chronic ureteral obstruction requiring permanent ureteral catheterization (double-J stent). Attempts to remove the stent led to pyelonephritis episodes during which only Candida was isolated from the urine. Following several courses of azole-based therapy, the causative agent became resistant to fluconazole. Clinical and mycological cure were obtained combining irrigations of caspofungin through a percutaneous calicostomy catheter and oral
* Corresponding author. Service de parasitologie-mycologie, hôpitaux universitaires de l’Est-Parisien, hôpital St-Antoine, 184, rue du Faubourg St-Antoine, 75012 Paris, France. E-mail address: [email protected] (C. Hennequin). http://dx.doi.org/10.1016/j.mycmed.2014.12.003 1156-5233/# 2015 Published by Elsevier Masson SAS.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
2
H. Garcia et al. flucytosine. This strategy may represent an interesting therapeutic alternative in case of fluconazole-resistant symptomatic candiduria. # 2015 Published by Elsevier Masson SAS.
MOTS CLÉS Candida ; Candidurie ; Resistance aux azolés ; Caspofungine ; Irrigation locale
Re ´sume ´ Bien que souvent asymptomatique, la candidurie peut témoigner d’infections sévères comme les pyélonéprites candidosiques. Hormis le fluconazole et la flucytosine, les antifongiques systémiques ne sont pas éliminés sous forme active dans les urines. En cas d’infection à germe fluconazole-résistant, le traitement de ces infections devient alors difficile. Nous rapportons le cas d’une candidurie récurrente à Candida parapsilosis chez un patient transplanté rénal présentant une obstruction urétérale nécessitant un cathétérisme permanent des voies urinaires par sonde double-J. L’ablation répétée du matériel étranger conduisait à des épisodes de pyélonéphrite pour lesquels, seule la levure était isolée des urines. Après plusieurs cures de traitement par dérivés azolés, la souche devenait résistante à ces molécules mais restait sensible aux échinocandines. Un traitement combinant irrigation de caspofungine à travers une pyélostomie et flucytosine per-os permettait une guérison clinique et une éradication mycologique de la levure malgré le maintien de la sonde double-J. Cette stratégie représente une alternative thérapeutique intéressante en cas de candidurie par une souche résistante au fluconazole. # 2015 Publié par Elsevier Masson SAS.
Introduction Candiduria is one of the most common nosocomial infections [13]. Patients with foreign material in urinary tract, notably kidney transplant recipients, are at a particularly high risk [12]. Although most of these infections are asymptomatic, some patients will develop typical clinical features of cystitis. More rarely, candiduria may result in obstruction that may possibly be complicated by urinary sepsis with a possible renal parenchymal involvement and even candidemia [8,5]. In these cases, therapeutic approach, apart from external material withdrawal, is challenging because only fluconazole and flucytosine have activity in the urine [9]. Thus, this condition may represent almost a therapeutic impasse when the causative agent is or becomes resistant to these drugs. We report on the use of local-irrigation of caspofungin in the case of a double-J stent-associated candiduria due to a fluconazole-resistant Candida parapsilosis strain. A 39-year-old male presented in January 2013 to our institution with a 2-day history of dysuria and oliguria. In 2006, he underwent a renal transplantation that further complicated with chronic distal ureter stenosis leading to recurrent obstructive acute kidney injuries or urosepsis requiring multiple double-J catheterizations. A first episode of candiduria due to C. parapsilosis was observed in May 2011 (Table 1). During the following months, he relapsed several times, and following several courses of fluconazole and voriconazole, the strain became resistant to azole derivatives. On admission, his temperature was 36.8 8C, his blood pressure was at 125/80 mmHg. Physical examination only revealed graft tenderness in the right iliac fossa. Laboratory evaluation showed elevated creatinine serum level at 4.54 mg/dL. There was also a mild neutrophilia (8.2 109/L), and an elevated C-reactive protein plasma concentration at 208 mg/L (reference < 4.0 mg/L). Ultrasonography demonstrated hydronephrosis of the kidney graft (renal pelvis 24 mm and ureter 12 mm) despite the correct in situ position of a double-J stent.
The patient was treated empirically with piperacillin/ tazobactam, vancomycin and oral fluconazole at 200 mg per day. C. parapsilosis grew in pure culture from a sample of the renal calix urine. Blood cultures remained negative. Antibiotics were withheld, and fluconazole was changed on day 3 to intravenous caspofungin (70-mg loading dose followed by 50 mg daily). However, urine culture remained positive. Since ultrasonography still showed signs of obstruction, a percutaneous calicostomy was performed on day 12. Double-J stent was changed again on day 17. Because candiduria persisted, an antifungal combination therapy with oral 5-flucytosine (500 mg bid) and continuous irrigation of caspofungin through percutaneous calicostomy catheter (50 mg in 100 mL 0.9% sodium chloride infused during 24 hours) was begun on day 20. Because an ureteroplasty was planned in order to permanently remove any foreign material in the urinary tract and prevent any recurrence of candiduria or urosepsis, the therapy was continued until day 67 when the patient was discharged. On day 23, urine culture turned negative and remained negative. On day 46, an intravenous pyelogram confirmed the persistence of the stenosis of distal ureter. Weekly blood cell count surveillance did not show any sign of toxicity of 5-flucytosine. Creatinine at discharge was stable at 2.2 mg/dL. Ureteroplasty was performed 2 months later. During a 2-year followup, all urine cultures performed routinely remained negative for Candida. Therapeutic management for candiduria depends on the occurrence of clinical manifestations and the presence of underlying predisposing factors for bloodstream dissemination [1]. Immunosuppression, indwelling catheters and ureteral stenosis classified our patient at high risk of dissemination [10]. When antifungal therapy is mandatory, therapeutic options are limited because of the poor urinary diffusion of the active form of most of the antifungal drugs, including the new triazole derivatives and the echinocandins [9,1]. About 20% of amphotericin B administered intravenously is excreted in the urine [4], but renal toxicity limits the use of this drug, particularly in patients with underlying
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
Caspofungin irrigation through percutaneous calicostomy catheter
3
Table 1 Chronology of symptoms, urine culture, antifungal therapy and MICs of the sequential isolates. ˆ mes, des donne ´ es mycologiques (culture urinaire et sensibilite ´ aux antifongiques) et des traitements Chronologie des sympto ´ s. antifongiques administre 2011
2012
May Sep Symptoms + C. parapsilosis urine culture Double-J stent removal/reimplantation x Percutaneous calicostomy Antifungal therapy Fluconazole po
+ + x
Nov
Dec
+
+ + x
2013
Jan Oct Jan +
200 mg/d 25 days
+ + x x
Mar Jul
+
200 mg/d 3 days
Voriconazole po
200 md bid 21 days
Caspofungin iv
50 mg/d 17 days
Caspofungin pci
50 mg/d 47 days 500 mg bid 47 days
Flucytosine po MICs (mg/L) a Amb Flu Vor Cas 5-FC
Feb
ND ND ND ND ND
1 (S) 0.18 (S) 0.006 (S) 0.38 (NA) 0.006 (NA)
0.5 (S) 24 (R) 0.38 (R) 0.5 (NA) 0.032 (NA)
0.750 (S) > 256 (R) 1 (R) 0.750 (NA) 0.016 (NA)
ND ND ND ND ND
0.250 (S) > 256 (R) 4 (R) 0.380 (NA) 0.125 (NA)
0.750 (S) > 256 (R) 2 (R) 0.5 (NA) 0.016 (NA)
In vitro susceptibility tests were performed using the E-test (BioMérieux) method as recommended by the manufacturer. po: oral; iv: intravenous; pci: percutaneous calicostomy irrigation; ND: not determined; NA: non available. a MICs are interpreted according to the breakpoints proposed by the EUCAST (v7.0 2014/08).
renal injury and/or kidney transplant patients, as it was the case of our patient. On the other side, flucytosine monotherapy is not recommended, as the emergence of resistance is common with this molecule [14]. Thus, fluconazole is most often the drug of choice but may be inadequate in case of candiduria due to an organism with fluconazole resistance, either naturally, such as Candida glabrata or Candida krusei, or acquired as seen in our case. There are some reports of irrigations with amphotericin through percutaneous calicostomy device to treat Candida infections of the upper urinary tract [3], but results are inconstant [2,6]. Echinocandins have a wide-spectrum activity against Candida species. In addition, contrary to azole derivatives and conventional amphotericin B, this activity remains intact when yeasts grow in condition of biofilms, as it is the case on the surface of catheter material [11]. This may be important when the withdrawing of the material is impossible, as it was the case for our patient. In addition, caspofungin has been shown to be fungicidal against Candida species [7], and the MIC of caspofungin against the C. parapsilosis isolate of our patient was at 0.5 mg/L, consistent with susceptibility to this drug. In order to achieve efficient concentrations in the urine, we decided to instil caspofungin directly into the urinary tract through the percutaneous calicostomy catheter. In order to guarantee a constant antifungal action, caspofungin was infused in continuous. This treatment, combined with oral flucytosine, was well tolerated, notably no medullar toxicity was noticed, and allowed a rapid
(72 hours) sterilization of the urine culture. No relapse was noted 120 days after the treatment was stopped. This combination therapy may be a valuable alternative in case of symptomatic candiduria with fluconazole-resistant pathogen. Optimization of dosages may be required in the future.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References [1] Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev 2010;23:253—73. [2] Babu R, Hutton KA. Renal fungal balls and pelvi-ureteric junction obstruction in a very low birth weight infant: treatment with streptokinase. Pediatr Surg Int 2004;20:804—5. [3] Babut JM, Coeurdacier P, Bawab F, Treguier C, Fremond B. Urinary fungal bezoars in children—report of two cases. Eur J Pediatr Surg 1995;5:248—52. [4] Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, Walsh TJ. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother 2002;46:828—33. [5] Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J. A European perspective on nosocomial urinary tract infections II. Report on incidence, clinical characteristics and outcome (ESGNI-004 study). Clin Microbiol Infect 2001;7:532—42.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
4
H. Garcia et al.
[6] Chitale SV, Shaida N, Burtt G, Burgess N. Endoscopic management of renal candidiasis. J Endourol 2004;18:865—6. [7] Deresinski SC, Stevens DA. Caspofungin. Clin Infect Dis 2003;36:1445—57. [8] Fisher JF, Kavanagh K, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infection: pathogenesis. Clin Infect Dis 2011;52:S437—51. [9] Fisher JF, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infections—treatment. Clin Infect Dis 2011;52:S457—66. [10] Gross M, Winkler H, Pitlik S, Weinberger M. Unexpected candidemia complicating ureteroscopy and urinary stenting. Eur J Clin Microbiol Infect Dis 1998;17:583—6.
[11] Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002;46:1773—80. [12] Safdar N, Slattery WR, Knasinski V, Gangnon RE, Li Z, Pirsch JD, et al. Predictors and outcomes of candiduria in renal transplant recipients. Clin Infect Dis 2005;40:1413—21. [13] Sobel JD, Fisher JF, Kauffman CA, Newman CA. Candida urinary tract infections—epidemiology. Clin Infect Dis 2011;52:S433—6. [14] Vermes A, Guchelaar HJ, Dankert J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother 2000;46:171—9.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
MYCMED-533; No. of Pages 4 Journal de Mycologie Médicale (2015) xxx, xxx—xxx
Available online at
ScienceDirect www.sciencedirect.com
CASE REPORT/CAS CLINIQUE
Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria ´ sistante Traitement d’une candidurie symptomatique re ´ lostomie au fluconazole par irrigation de caspofungine via une pye et flucytosine per-os H. Garcia a, J. Guitard b, J. Peltier a, M. Tligui c, S. Benbouzid c, S. Ait Elhaj a, E. Rondeau a, C. Hennequin b,* a
´ phrologie et transplantation re ´ nale, ho ˆ pitaux universitaires de l’Est-Parisien, Service de ne ˆ pital St-Antoine, 184, rue du Faubourg St-Antoine, 75012 Paris, France ho b ˆ pitaux universitaires de l’Est-Parisien, ho ˆ pital St-Antoine, Service de parasitologie-mycologie, ho 184, rue du Faubourg St-Antoine, 75012 Paris, France c ˆ pitaux universitaires de l’Est-Parisien, ho ˆ pital St-Antoine, 184, Service d’urologie, ho rue du Faubourg St-Antoine, 75012 Paris, France Received 17 November 2014; received in revised form 23 December 2014; accepted 30 December 2014
KEYWORDS Candida; Candiduria; Azole resistance; Caspofungin; Local irrigation
Summary Candiduria may be a marker of serious fungal infections such as pyelonephritis. With the exception of fluconazole and flucytosine, antifungals drugs are not excreted into the urine as active drugs, making the management of infection due to fluconazole-resistant Candida difficult. We report a case of recurrent Candida parapsilosis candiduria in a kidney transplant recipient suffering from chronic ureteral obstruction requiring permanent ureteral catheterization (double-J stent). Attempts to remove the stent led to pyelonephritis episodes during which only Candida was isolated from the urine. Following several courses of azole-based therapy, the causative agent became resistant to fluconazole. Clinical and mycological cure were obtained combining irrigations of caspofungin through a percutaneous calicostomy catheter and oral
* Corresponding author. Service de parasitologie-mycologie, hôpitaux universitaires de l’Est-Parisien, hôpital St-Antoine, 184, rue du Faubourg St-Antoine, 75012 Paris, France. E-mail address: [email protected] (C. Hennequin). http://dx.doi.org/10.1016/j.mycmed.2014.12.003 1156-5233/# 2015 Published by Elsevier Masson SAS.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
2
H. Garcia et al. flucytosine. This strategy may represent an interesting therapeutic alternative in case of fluconazole-resistant symptomatic candiduria. # 2015 Published by Elsevier Masson SAS.
MOTS CLÉS Candida ; Candidurie ; Resistance aux azolés ; Caspofungine ; Irrigation locale
Re ´sume ´ Bien que souvent asymptomatique, la candidurie peut témoigner d’infections sévères comme les pyélonéprites candidosiques. Hormis le fluconazole et la flucytosine, les antifongiques systémiques ne sont pas éliminés sous forme active dans les urines. En cas d’infection à germe fluconazole-résistant, le traitement de ces infections devient alors difficile. Nous rapportons le cas d’une candidurie récurrente à Candida parapsilosis chez un patient transplanté rénal présentant une obstruction urétérale nécessitant un cathétérisme permanent des voies urinaires par sonde double-J. L’ablation répétée du matériel étranger conduisait à des épisodes de pyélonéphrite pour lesquels, seule la levure était isolée des urines. Après plusieurs cures de traitement par dérivés azolés, la souche devenait résistante à ces molécules mais restait sensible aux échinocandines. Un traitement combinant irrigation de caspofungine à travers une pyélostomie et flucytosine per-os permettait une guérison clinique et une éradication mycologique de la levure malgré le maintien de la sonde double-J. Cette stratégie représente une alternative thérapeutique intéressante en cas de candidurie par une souche résistante au fluconazole. # 2015 Publié par Elsevier Masson SAS.
Introduction Candiduria is one of the most common nosocomial infections [13]. Patients with foreign material in urinary tract, notably kidney transplant recipients, are at a particularly high risk [12]. Although most of these infections are asymptomatic, some patients will develop typical clinical features of cystitis. More rarely, candiduria may result in obstruction that may possibly be complicated by urinary sepsis with a possible renal parenchymal involvement and even candidemia [8,5]. In these cases, therapeutic approach, apart from external material withdrawal, is challenging because only fluconazole and flucytosine have activity in the urine [9]. Thus, this condition may represent almost a therapeutic impasse when the causative agent is or becomes resistant to these drugs. We report on the use of local-irrigation of caspofungin in the case of a double-J stent-associated candiduria due to a fluconazole-resistant Candida parapsilosis strain. A 39-year-old male presented in January 2013 to our institution with a 2-day history of dysuria and oliguria. In 2006, he underwent a renal transplantation that further complicated with chronic distal ureter stenosis leading to recurrent obstructive acute kidney injuries or urosepsis requiring multiple double-J catheterizations. A first episode of candiduria due to C. parapsilosis was observed in May 2011 (Table 1). During the following months, he relapsed several times, and following several courses of fluconazole and voriconazole, the strain became resistant to azole derivatives. On admission, his temperature was 36.8 8C, his blood pressure was at 125/80 mmHg. Physical examination only revealed graft tenderness in the right iliac fossa. Laboratory evaluation showed elevated creatinine serum level at 4.54 mg/dL. There was also a mild neutrophilia (8.2 109/L), and an elevated C-reactive protein plasma concentration at 208 mg/L (reference < 4.0 mg/L). Ultrasonography demonstrated hydronephrosis of the kidney graft (renal pelvis 24 mm and ureter 12 mm) despite the correct in situ position of a double-J stent.
The patient was treated empirically with piperacillin/ tazobactam, vancomycin and oral fluconazole at 200 mg per day. C. parapsilosis grew in pure culture from a sample of the renal calix urine. Blood cultures remained negative. Antibiotics were withheld, and fluconazole was changed on day 3 to intravenous caspofungin (70-mg loading dose followed by 50 mg daily). However, urine culture remained positive. Since ultrasonography still showed signs of obstruction, a percutaneous calicostomy was performed on day 12. Double-J stent was changed again on day 17. Because candiduria persisted, an antifungal combination therapy with oral 5-flucytosine (500 mg bid) and continuous irrigation of caspofungin through percutaneous calicostomy catheter (50 mg in 100 mL 0.9% sodium chloride infused during 24 hours) was begun on day 20. Because an ureteroplasty was planned in order to permanently remove any foreign material in the urinary tract and prevent any recurrence of candiduria or urosepsis, the therapy was continued until day 67 when the patient was discharged. On day 23, urine culture turned negative and remained negative. On day 46, an intravenous pyelogram confirmed the persistence of the stenosis of distal ureter. Weekly blood cell count surveillance did not show any sign of toxicity of 5-flucytosine. Creatinine at discharge was stable at 2.2 mg/dL. Ureteroplasty was performed 2 months later. During a 2-year followup, all urine cultures performed routinely remained negative for Candida. Therapeutic management for candiduria depends on the occurrence of clinical manifestations and the presence of underlying predisposing factors for bloodstream dissemination [1]. Immunosuppression, indwelling catheters and ureteral stenosis classified our patient at high risk of dissemination [10]. When antifungal therapy is mandatory, therapeutic options are limited because of the poor urinary diffusion of the active form of most of the antifungal drugs, including the new triazole derivatives and the echinocandins [9,1]. About 20% of amphotericin B administered intravenously is excreted in the urine [4], but renal toxicity limits the use of this drug, particularly in patients with underlying
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
Caspofungin irrigation through percutaneous calicostomy catheter
3
Table 1 Chronology of symptoms, urine culture, antifungal therapy and MICs of the sequential isolates. ˆ mes, des donne ´ es mycologiques (culture urinaire et sensibilite ´ aux antifongiques) et des traitements Chronologie des sympto ´ s. antifongiques administre 2011
2012
May Sep Symptoms + C. parapsilosis urine culture Double-J stent removal/reimplantation x Percutaneous calicostomy Antifungal therapy Fluconazole po
+ + x
Nov
Dec
+
+ + x
2013
Jan Oct Jan +
200 mg/d 25 days
+ + x x
Mar Jul
+
200 mg/d 3 days
Voriconazole po
200 md bid 21 days
Caspofungin iv
50 mg/d 17 days
Caspofungin pci
50 mg/d 47 days 500 mg bid 47 days
Flucytosine po MICs (mg/L) a Amb Flu Vor Cas 5-FC
Feb
ND ND ND ND ND
1 (S) 0.18 (S) 0.006 (S) 0.38 (NA) 0.006 (NA)
0.5 (S) 24 (R) 0.38 (R) 0.5 (NA) 0.032 (NA)
0.750 (S) > 256 (R) 1 (R) 0.750 (NA) 0.016 (NA)
ND ND ND ND ND
0.250 (S) > 256 (R) 4 (R) 0.380 (NA) 0.125 (NA)
0.750 (S) > 256 (R) 2 (R) 0.5 (NA) 0.016 (NA)
In vitro susceptibility tests were performed using the E-test (BioMérieux) method as recommended by the manufacturer. po: oral; iv: intravenous; pci: percutaneous calicostomy irrigation; ND: not determined; NA: non available. a MICs are interpreted according to the breakpoints proposed by the EUCAST (v7.0 2014/08).
renal injury and/or kidney transplant patients, as it was the case of our patient. On the other side, flucytosine monotherapy is not recommended, as the emergence of resistance is common with this molecule [14]. Thus, fluconazole is most often the drug of choice but may be inadequate in case of candiduria due to an organism with fluconazole resistance, either naturally, such as Candida glabrata or Candida krusei, or acquired as seen in our case. There are some reports of irrigations with amphotericin through percutaneous calicostomy device to treat Candida infections of the upper urinary tract [3], but results are inconstant [2,6]. Echinocandins have a wide-spectrum activity against Candida species. In addition, contrary to azole derivatives and conventional amphotericin B, this activity remains intact when yeasts grow in condition of biofilms, as it is the case on the surface of catheter material [11]. This may be important when the withdrawing of the material is impossible, as it was the case for our patient. In addition, caspofungin has been shown to be fungicidal against Candida species [7], and the MIC of caspofungin against the C. parapsilosis isolate of our patient was at 0.5 mg/L, consistent with susceptibility to this drug. In order to achieve efficient concentrations in the urine, we decided to instil caspofungin directly into the urinary tract through the percutaneous calicostomy catheter. In order to guarantee a constant antifungal action, caspofungin was infused in continuous. This treatment, combined with oral flucytosine, was well tolerated, notably no medullar toxicity was noticed, and allowed a rapid
(72 hours) sterilization of the urine culture. No relapse was noted 120 days after the treatment was stopped. This combination therapy may be a valuable alternative in case of symptomatic candiduria with fluconazole-resistant pathogen. Optimization of dosages may be required in the future.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References [1] Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev 2010;23:253—73. [2] Babu R, Hutton KA. Renal fungal balls and pelvi-ureteric junction obstruction in a very low birth weight infant: treatment with streptokinase. Pediatr Surg Int 2004;20:804—5. [3] Babut JM, Coeurdacier P, Bawab F, Treguier C, Fremond B. Urinary fungal bezoars in children—report of two cases. Eur J Pediatr Surg 1995;5:248—52. [4] Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, Walsh TJ. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother 2002;46:828—33. [5] Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J. A European perspective on nosocomial urinary tract infections II. Report on incidence, clinical characteristics and outcome (ESGNI-004 study). Clin Microbiol Infect 2001;7:532—42.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
+ Models
MYCMED-533; No. of Pages 4
4
H. Garcia et al.
[6] Chitale SV, Shaida N, Burtt G, Burgess N. Endoscopic management of renal candidiasis. J Endourol 2004;18:865—6. [7] Deresinski SC, Stevens DA. Caspofungin. Clin Infect Dis 2003;36:1445—57. [8] Fisher JF, Kavanagh K, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infection: pathogenesis. Clin Infect Dis 2011;52:S437—51. [9] Fisher JF, Sobel JD, Kauffman CA, Newman CA. Candida urinary tract infections—treatment. Clin Infect Dis 2011;52:S457—66. [10] Gross M, Winkler H, Pitlik S, Weinberger M. Unexpected candidemia complicating ureteroscopy and urinary stenting. Eur J Clin Microbiol Infect Dis 1998;17:583—6.
[11] Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002;46:1773—80. [12] Safdar N, Slattery WR, Knasinski V, Gangnon RE, Li Z, Pirsch JD, et al. Predictors and outcomes of candiduria in renal transplant recipients. Clin Infect Dis 2005;40:1413—21. [13] Sobel JD, Fisher JF, Kauffman CA, Newman CA. Candida urinary tract infections—epidemiology. Clin Infect Dis 2011;52:S433—6. [14] Vermes A, Guchelaar HJ, Dankert J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother 2000;46:171—9.
Please cite this article in press as: Garcia H, et al. Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria. Journal De Mycologie Médicale (2015), http://dx.doi.org/10.1016/ j.mycmed.2014.12.003
