Imhof, A.

Misselwitz, B.

Schneemann, M.

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Bile Aspiration for Diagnosis of Candida glabrataCholecystitisInfection with Candida species is a common nosocomialproblem in critically ill patients [1–3]. Candidemia isassociated with a high mortality rate; the clinical outcomestrongly depends on timely application of an appropriateantifungal [4]. However, even though many antifungalsare available now, clinical and microbiological failures ofantifungal therapy are encountered frequently [3]. Littleevidence exists to guide the management of this difficultsituation. The change of antifungal therapy to an alter-native agent is often considered. However, failure ofantifungal therapy might also be due to a second fungusmissed at the time of the initial diagnosis. Therefore,continuous search for an infectious focus should be a pri-ority. We report the case of a breakthrough infection dueto Candida glabrata in a patient with Candida albicanscandidemia. C. glabrata cholecystitis was diagnosed withbile aspiration which also at least partially cured theinfectious nidus.A 76-year-old woman was referred to the ICU of ourhospital with severe C. albicans sepsis. The personal his-tory of the patient was remarkable for surgical removal ofthe bladder because of a carcinoma. Local complicationsprompted further operations, including construction of anileocoecal reservoir. On day 4 of the hospitalization anileum conduit was connected to the reservoir. The post-operative course was complicated by peritonitis due to aleaky anastomosis, making an ileostoma necessary on day20. Because of short bowel syndrome parenteral nutritionwas started. The patient slowly improved over the nextweeks.On the 11th week of the hospitalization the patientwas transferred to the ICU with dyspnea and delirium.Computer tomography (CT) of the thorax on day 75showed pulmonary embolism and infiltrates, promptinganticoagulation and antibiotic treatment. Two blood cul-tures (BacTAlert, bioMe´rieux, Marcy l’Etoile, France)grew C. albicans after 5 days. The tip of the centralcatheter also grew C. albicans. CHROMagar Candidaplates (CHROMagar Company, Paris, France) were usedfor primary identification. The diagnosis was confirmedusing API Candida (bioMe´rieux). Antifungal therapy withfluconazole, 400 mg iv once daily, was initiated. Despitepersistently elevated markers for systemic inflammation,further blood cultures were negative.On day 90 the CT-scan demonstrated new peribron-chovascular infiltrates, suggestive of Aspergillus pneu-monia. The antifungal regiment was changed tovoriconazole, 200 mg iv twice daily. Abdominal com-plaints prompted a CT-scan of the abdomen on day 95,demonstrating an enlarged gall bladder with perivesicularfluid, suggestive of acalculous cholecystitis. On day 97,150 ml of slightly turbid gall bladder fluid were aspirated.Semiquantitative cultures grew moderate amounts of C.glabrata (no bacterial growth was observed). The sus-ceptibility testing of C. glabrata revealed intermediatesusceptibility to fluconazole (minimal inhibitory concen-tration, MIC, 16 lg/ml) but susceptibility to voriconazole(MIC 0.25 lg/ml). On day 111 the patient had substan-tially improved and was transferred to a peripheral hos-pital. Within the following weeks, short bowel syndromeprevented complete recovery. Surgery was attempted tocorrect the ileostoma. The patient, however, succumbedto postoperative septic complications. Blood cultures didnot show resurgence of candidemia.Candida species account for 2.9% of bloodstreampathogens in Swiss hospitals [1]. Although Candida spe-cies are considered to be normal commensal organisms,disseminated candidiasis is life threatening. Common riskfactors include colonization, broad-spectrum antibiotics, acentral venous catheter, parenteral nutrition, gastrointes-tinal or cardiac surgery, prolonged hospital or ICU stay,burns, diabetes mellitus, and immunosuppression [3].Most of these conditions favor an overgrowth of yeast inthe bowel, provide an entrance route or can be considereda marker of severe underlying disease. Remarkably, ourpatient fulfilled all these risk factors, except no burninjuries and immunosuppression were present.The most common Candida species involved is C.albicans, accounting for 66% of Candida isolates in Swisshospitals, followed by C. glabrata (15%) and C. tropicalis(2–10%) [1]. Our patient has been at high risk for C.glabrata infection. According to a recent study, certainInfection 2008; 36: 189–190DOI 10.1007/s15010-007-7261-yB. Misselwitz, A. Imhof, M. Schneemann (corresponding author)Dept. of Medicine, University Hospital Zurich, Raemistrasse 100,CH-8091, Zürich, Switzerland; Phone: (+41/44) 255-1111, Fax: -4445,e-mail: markus.schneemann@usz.chReceived: June 11, 2007 Æ Revision accepted: September 19, 2007Published online: March 10, 2008Infection CorrespondenceInfection 36 Æ 2008 Æ No. 2  URBAN & VOGEL 189broad spectrum antibiotics and pretreatment with azole-antifungal agents favor infection with C. glabrata orCandida krusei over C. albicans. The risk was strongestwith two of the antibiotics our patient had been exposedto: piperacillin/tazobactam and vancomycin, which in-crease the risk by a factor of 4.2 or 6.5, respectively [5].The differential diagnosis of an enlarged gall bladderin an ICU patient is challenging. On the one hand, hy-drops frequently develops in patients who cannot be fedorally and resolves without specific treatment. On theother, infectious cholecystitis requires emergent surgicalor percutaneous treatment. In a recent study, commonlyused biochemical or radiological criteria such as ASAT,ALAT, AP, GGT, gall bladder wall enlargement, orpericholecystic fluid failed to predict subsequent isolationof microorganisms in the gall aspirate [6]. Therefore, thesuspicion of infectious cholecystitis largely depends onclinical judgment. In a patient like ours with sepsis and noother focus, a suspicious gall bladder should be furtherevaluated. In our case, unequivocal microbiological evi-dence of gall bladder infection has been provided, since C.glabrata was isolated from the bile aspirate. This is highlyunusual because Candida species are an infrequent gallbladder pathogen with C. albicans responsible for themajority of cases and C. glabrata cholecystitis only anec-dotically reported [7, 8].The first-line empirical antifungal for candidemia inhemodynamically stable, non-neutropenic patients and thefirst-line treatment of C. albicans is fluconazole. As soon asspecies differentiation reveals C. krusei or C. glabratafluconazole needs to be replaced, since virtually all C.krusei and 13–75% of C. glabrata isolates are fluconazoleresistant [3, 9, 10]. The therapeutic options now includeamphothericin B, caspofungin, or voriconazole. While vo-riconazole is clearly more effective than fluconazole againstC. krusei or C. glabrata, its use against both pathogens re-mains controversial [2, 3, 11, 12]. For instance, break-through infections with C. glabrata under voriconazoleprophylaxis were noted; however, the minimal inhibitoryconcentration of the isolates has been consistently abovethe proposed break point of > 1 lg/ml [13]. In our case theminimal inhibitory concentration for voriconazole(0.25 lg/ml) remained well below this break point, makingcontinued treatment with this drug a reasonable option.However, even though several potent antifungals areavailable, success of antifungal treatment is uncertain.Therefore, local therapy might be an attractive option. Inour case percutaneous cholecystostomy not only demon-strated the double yeast infection but also in addition atleast partially cured the local infection. Recently, a studycompared percutaneous cholecystostomy with surgery inhigh-risk patients with acute cholecystitis, demonstratinga low rate of complications [14].In summary, failure of fluconazole to improve a crit-ical state in a patient with C. albicans infection raises thepossibility of another Candida species. A search for apossible focus should be attempted; in our case, aspirationof an enlarged gallbladder identified C. glabrata and atleast partially cured the infectious focus. Gallbladderaspiration seems to be a safe and effective option in pa-tients with suspected biliary candidiasis.References1. Marchetti O, et al. Epidemiology of candidemia in Swiss tertiarycare hospitals: secular trends, 1991–2000. Clin Infect Dis 2004;38: 311–320.2. Fluckiger U, et al. Treatment options of invasive fungal infec-tions in adults. Swiss Med Wkly 2006; 136: 447–463.3. Spellberg BJ, Filler SG, Edwards JE Jr: Current treatment strat-egies for disseminated candidiasis. Clin Infect Dis 2006; 42:244–251.4. Blot SI, et al. Effects of nosocomial candidemia on outcomes ofcritically ill patients. Am J Med 2002; 113: 480–485.5. Lin MY, et al. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: acase–case–control study. Antimicrob Agents Chemother 2005;49: 4555–4560.6. Beardsley SL, et al. Predicting infected bile among patientsundergoing percutaneous cholecystostomy. Cardiovasc Inter-vent Radiol 2005; 28: 319–325.7. Warren GH, Marsh S: Granulomatous Torulopsis glabrata cho-lecystitis in a diabetic. Am J Clin Pathol 1982; 78: 406–410.8. Miller DD: Postoperative acalculous cholecystitis due to Toru-lopsis glabrata. Arch Surg 1976; 111: 1404–1405.9. Drago M, Scaltrito MM, Morace G: In vitro activity of vorico-nazole and other antifungal agents against clinical isolates ofCandida glabrata and Candida krusei. Eur J Clin Microbiol InfectDis 2004; 23: 619–624.10. St-Germain G, et al. Prevalence and antifungal susceptibility of442 Candida isolates from blood and other normally sterilesites: results of a 2-year (1996 to 1998) multicenter surveillancestudy in Quebec, Canada. J Clin Microbiol 2001; 39: 949–953.11. Kullberg BJ, et al. Voriconazole versus a regimen of amphoter-icin B followed by fluconazole for candidaemia in non-neu-tropenic patients: a randomised non-inferiority trial. Lancet2005; 366: 1435–1442.12. Ostrosky-Zeichner L, et al. Voriconazole salvage treatment ofinvasive candidiasis. Eur J Clin Microbiol Infect Dis 2003; 22:651–655.13. Imhof A, et al. Breakthrough fungal infections in stem celltransplant recipients receiving voriconazole. Clin Infect Dis2004; 39: 743–746.14. Hatzidakis AA, et al. Acute cholecystitis in high-risk patients:percutaneous cholecystostomy vs conservative treatment. EurRadiol 2002; 12: 1778–1784.B. Misselwitz, A. Imhof, M. SchneemannB. Misselwitz et al. C. glabrata Cholecystitis190 Infection 36 Æ 2008 Æ No. 2  URBAN & VOGEL

Bile Aspiration for Diagnosis of Candida glabrata Cholecystitis

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Bile Aspiration for Diagnosis of Candida glabrata Cholecystitis

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