Geotrichum capitatum can cause infections in humans and its importance has recently been recognized in patients with immunosuppressive conditions. In this report we present the first Croatian pediatric patient with pneumonia in whom G. capitatum was isolated in three sequential bronchoalveolar lavage and tracheal aspiration specimens.Geotrichum capitatum može uzrokovati infekcije u ljudi i njegov značaj je nedavno prepoznat u imunosuprimiranih bolesnika. U ovom radu prikazujemo prvog hrvatskog pedijatrijskog bolesnika s pneumonijom u kojeg je G. capitatum izoliran u tri uzastopna bronhoalveolarna lavata i aspirata traheje

Branka Polić

Daniela Veljačić

Ivana Goić-Barišić

Joško Markić

Marija Tonkić

Tanja Kovačević

English

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Infektolo{ki glasnik 37:1, 23–26 (2017)Croatian Journal of Infection 37:1, 23–26 (2017)Redni broj ~lanka: 800 ISSN 1331-2820The first Croatian pediatric patient with Geotrichum capitatumrespiratory infectionPrvi hrvatski pedijatrijski bolesnik s Geotrichum capitatumrespiratornom infekcijomJo{ko MARKI]1, 3)Branka POLI]1)Tanja KOVA^EVI]1)Daniela VELJA^I]1)Ivana GOI]-BARI[I]2, 3)Marija TONKI]2, 3)1)University Hospital of Split, Department ofPediatrics, Spinciceva 1, 21000 Split,Croatia2)University Hospital of Split, Department ofClinical Microbiology, Spinciceva 1, 21000Split, Croatia3)University of Split, School of Medicine,Soltanska 2, 21000 Split, Croatia Key wordsGeotrichum capitatumpneumoniatreatmentinvasive fungal infectionKey wordsGeotrichum capitatumpneumonijalije~enjeinvazivna gljivi~na infekcijaPrimljeno: 2016–04–07Received: 2016–04–07Prihva}eno: 2016–05–15Accepted: 2016–05–1523Case reportGeotrichum capitatum can cause infections in humans and its importance hasrecently been recognized in patients with immunosuppressive conditions. Inthis report we present the first Croatian pediatric patient with pneumonia inwhom G. capitatum was isolated in three sequential bronchoalveolar lavage andtracheal aspiration specimens. Prikaz bolesnikaGeotrichum capitatum mo`e uzrokovati infekcije u ljudi i njegov zna~aj je ne-davno prepoznat u imunosuprimiranih bolesnika. U ovom radu prikazujemo pr-vog hrvatskog pedijatrijskog bolesnika s pneumonijom u kojeg je G. capitatumizoliran u tri uzastopna bronhoalveolarna lavata i aspirata traheje.IntroductionGeotrichum capitatum is a filamentous yeast-like fun-gus formerly known as Trichosporon capitatum or Blasto-shizomyces capitatus. Although it can be a part of the nor-mal microbiota it can also cause both superficial and inva-sive infections in humans [1, 2]. It forms creamy, wrinkledcolonies that grow on conventional media such asSabouraud dextrose agar [1]. It is occasionally encoun-tered in clinical laboratories and its importance as sys-temic pathogen has recently been recognized in patientswith immunosuppressive conditions [3]. Studies haveshown that there is a significantly higher frequency of in-fections caused by G. capitatum in Europe, with majorityof them occurring in Italy, Spain, and France [4].  Sincemost cases were located in central and southern Europe, itseems that the epidemiology of G. capitatum infectionscould be influenced by climatic factors. The mortality inpatients with G. capitatum infections is high (60 %) [5].In this report we present, to our knowledge, the firstpediatric patient from Croatia in whom the Geotrichumcapitatum was isolated in three sequential bronchoalveo-lar lavage (BAL) and tracheal aspiration specimens. 24J. MARKI] et al. G. capitatum respiratory infection in a childInfektolo{ki glasnik 37:1, 23–26 (2017)fixime oral suspension was administered. Despite the an-timicrobial therapy he continued to be febrile, drank poorand became less responsive to stimuli. He was brought toour pediatric emergency room and subsequently admittedto the pediatric intensive care unit (PICU) with signs ofshock requiring appropriate fluid resuscitation therapy andinotropic support. Laboratory tests showed mild leukocy-tosis (12.8 × 109/L), anemia (hemoglobin 90 g/L; hemat-ocrit 0.32) and moderately increased CRP (89.7 mg/L).Chest X-ray (Figure 1.) confirmed rightsided broncho-pneumonia with complete atelectasis of the left lung. Hisregular chronic therapy was continued and parenteral an-timicrobial therapy with ceftriaxone was initiated.  Despite the intense inhalational and other symptomatictherapy, his respiratory condition worsened. Therefore, hewas sedated, intubated and mechanical ventilation was ini-tiated. Because of the atelectasis and thick and abundantsecretion in his lower airways, in addition to regular phys-ical respiratory therapy and frequent tracheal aspiration,an aspiration of lower airways with fiberoptic broncho-scope was also done and the first BAL specimen was sentfor microbiology analysis. He was fed by parenteral nutri-tion. The following day, due to further increase of inflam-matory biomarkers (procalcitonin >100 ng/mL), parenter-al meropenem was administered. He was also given ablood transfusion. Three days later, Geotrichum capitatumCase reportA 6-year-old boy was referred to the UniversityHospital of Split with a two and a half week intermittentfever duration. He was born after an uneventful pregnancyand soon after the birth was diagnosed with multimalfor-mation syndrome (frontal bossing, low posterior hairline,dysplastic ears, flat nasal bridge, gingival hyperplasia, ir-regular dentition, high-arched palate) and early epilepticencephalopathy (seizures with delayed psychomotor de-velopment – unable to walk, minimal visual contact, se-vere speech impairment). His previous hospitalization inour Department was a year before due to pneumonia andrespiratory insufficiency. During that hospitalization hewas mechanically ventilated for 9 days. He was dis-charged home with his regular anticonvulsive therapy andthe parents were educated to administer noninvasive ven-tilatory support. His present illness started 17 days prior tohospitalization with fever and upper respiratory tract in-fection symptoms. The boy was examined by his primarycare physician who prescribed amoxicillin oral suspen-sion. After eight days of antimicrobial treatment his con-dition improved. However, three days before the hospitaladmission he became febrile up to 40.0 °C with increasedrespiratory effort. He was clinically reexamined by hisprimary care physician the day later. Laboratory bloodtests were done (L 14.5 G/L, CRP 67.0 mg/L) and ce-Figure 1. Chest x-ray at the time of hospital admissionSlika 1. Radiogram plu}a u vrijeme prijema u bolnicuG. capitatum respiratory infection in a childInfektolo{ki glasnik 37:1, 23–26 (2017) 25J. MARKI] et al.and Candida albicans were confirmed in BAL and flu-conazole was administered. BAL specimens were cul-tured on blood agar, Sabouraud agar (Merck KgaA, Darm-stadt, Germany) and CHROMagar Candida (CHROM-agar Orientation, Paris, France). After 24 hours of incuba-tion on two temperature conditions (25 °C and 36 °C) twotypes of colonies were revealed. The total number ofgrowing colonies was > 105 colony forming units (CFU)/ml of BAL. On the CHROMagar Candida media greencolonies of Candida albicans were positive in germ tubeformation, confirming Candida albicans identification.On the Sabouraud agar diferent type of cream coloureddry and wrinkled colonies were observed. These coloniesshowed no germ tube formation. Microscopic view andmicrocultivations on cornmeal agar (25 °C and 35 °C) re-vealed abundant thin, septate filaments with multiple rec-tangular arthroconidia and the absence of blastoconidiaand chlamydospores. The isolate was identified as G. cap-itatum according to the biochemical patterns obtained bythe VITEK 2 System (bioMerieux, Marcy-l'Etoile, France)using YST card. Gradually, his condition improved andinotropic support was discontinued. Candida albicansand Geotrichum capitatum were again isolated in the sec-ond BAL taken two days later. Therefore, fluconazole wasreplaced with intravenous amphotericin B and voricona-zole. At the same time, coagulase negative Staphylococ-cus sp. was isolated from the blood culture and teicoplaninwas administered as well. The patient's condition contin-ued to improve but we were not able to wean him of themechanical ventilation. By the end of the second week oftreatment he again became hemodynamically unstablewith symptoms and laboratory signs (L 15.7 × 109/L; CRP299.4 mg/L; procalcitonin 3.95 ng/mL) of sepsis requiringinotropic support. Eight days after initiation of ampho-tericin B and voriconazole treatment, G. capitatum wasisolated again, this time from tracheal aspirate specimen.Blood culture was sterile. Amikacin and micafungin wereadded to the treatment regime. However, his conditioncontinued to deteriorate with further increase of inflam-matory biomarkers (CRP 377.1 mg/L, procalcitonin 81.65ng/mL). Despite all intensive treatment and therapy, onthe 18th day, he developed bradycardia leading to asystoleand death.DiscussionIn this report we describe the first Croatian pediatricnon-hematologic patient with pulmonary infection causedby Geotrichum capitatum. Prior to hospitalization the pa-tient was treated with oral antibiotics and admitted toPICU requiring mechanical ventilation and intensivetreatment.Fungi are part of normal microbiota and some of themare considered nonpathogenic. However, they can causesystemic infections in patients that are severely immuno-compromised due to illness or therapy with immunosup-pressive drugs [6]. Most fungal infections are caused byCandida spp., but the frequency of other rare molds andunusual yeasts is increasing. Risk factors for fungal infec-tions include hospitalization in ICU, prolonged therapywith broad-spectrum antibiotics and steroids, central ve-nous catheter, total parenteral nutrition, neutropenia andprevious colonisation [6, 7, 8].Geotrichum capitatum has emerged as a fungal pathogenin recent years. Invasive fungal infections caused by thisagent are often characterized by a multiorgan involvementwith a fatal course despite antifungal therapy. Numerousstudies have shown increased occurrence of Geotrichumcapitatum infection in patients with impaired immune re-sponse to infection [3, 4, 9]. In a study that involved 353immunocompromised patients over a 37 months period,colonisation and infection by G. capitatum was found in3.7% of them [3]. Most of the studies published so farhave described the infection caused by G. capitatum inadult patients, but some of them also described infectionwith this pathogen in immunocompromised children [9,10]. Infection is also possible in immunocompetent pa-tients. Usually it will affect middle to older-aged maleswith underlying lung pathology (chronic obstructive pul-monary disease, tuberculosis) or with risk factors likesmoking or previous transplantation [11].The pulmonary localization is commonly reported inG. capitatum septicemia and the radiological signs resem-ble those found in invasive pulmonary aspergillosis [4].In our patient, laboratory and clinical signs stronglysuggest that G. capitatum and C. albicans were cause of res-piratory tract infection. They were not isolated from bloodcultures. Since the susceptibility testing of G. capitatumhas not yet been established due to the absence of break-points, the treatment of these infections is based on empir-ical terapy according to limited available literature data. Currently, there are no official guidelines concerningthe most effective antifungal therapy for G. capitatum in-fection. The therapy with azoles is widely used as effec-tive in the treatment of yeast infections. It is also suggest-ed that azoles should be used as first-line agents in patientslike ours [11]. However, our initial antimicotic therapywith fluconazole seemed to be inefficient. This may bedue to resistance or decreased susceptibility of G. capita-tum to fluconazole. Therefore, fluconazole was replacedwith voriconazole and amphotericin B combination thera-py. Based on limited clinical data available, amphotericinB and voriconazole are also recommended to be used,alone or in combination. Same authors reported poor sus-ceptibility of some strains to flucytosine, fluconazole anditraconazole [4]. However, in our patient, this combina-tion therapy eradicated C. albicans, but G. capitatum re-mained positive in tracheal aspiration specimen. There-26fore, further studies evaluating optimal treatment, dosageand duration of therapy are warranted. It may be possiblethat failure of antimycotic treatment, combined with otherfactors, such as underlying diseases, hospitalization inPICU and concomitant bacterial sepsis, could be the rea-sons for undiserable outcome.Aretrospective study and review published in 2005 hasshown that the majority of infections caused by G. capita-tum occurred in Europe, mostly in the Mediteranean areato which Croatia belongs [4]. Therefore, physicians prac-ticing in this area have to consider G. capitatum as a possi-ble cause of infection if an immunocompromised or evenimmunocompetent patient shows signs of persistent infec-tion despite the broad spectrum antibacterial therapy.Although this is, to our knowledge, the first describedcase of G. capitatum infection in a pediatric patient fromCroatia, pediatricians should take into consideration thisfilamentous yeast-like fungus as a possible cause of infec-tion as well.Conflict of interestThe authors declare no conflict of interest.References[1] D'Antonio D, Mazzoni A, Iacone A et al. Emergence of flucona-zole-resistant strains of Blastoschizomyces capitatus causing noso-comial infections in cancer patients. J Clin Microbiol 1996; 34:753–755.[2] Radi} M, Goi}-Bari{i} I, Ku{}evi} D, Novak A, Tonki} M, Rubi}@. Geotrichum capitatum respiratory tract infection in a patientwith polytrauma. Infez Med 2015; 3: 270–274.[3] Haupt HM, Merz WG, Beschorner WE, Vaughan WP, Saral R.Colonization and infection with Trichosporon species in the im-munosuppressed host. J Infect Dis 1983; 147: 199–203.[4] Girmenia C, Pagano L, Martino B et al. Invasive Infections Causedby Trichosporon Species and Geotrichum capitatum in Patientswith Hematological Malignancies: a Retrospective MulticenterStudy from Italy and Review of the Literature. J Clin MicrobiolInfect 2005; 43: 1818–1828.[5] Darles C, Pons S, Gaillard T, Roméo E, Brisou P. Infection dissem-inee a Geotrichum capitatum. Med Mal Infect 2012; 42: 574–575.[6] Fridkin SK, Jarvis WR. Epidemiology of nosocomial fungal infec-tions. Clin Microbiol Rev, 1996; 9: 499–511.[7] Nedel WL, Moraes VD, Falci DR, Pasqualotto AC. Geotrichumcapitatum fungaemia: an unusual pathogenin critically-ill-relatedinfections. Anaesth Intensive Care 2013; 41: 685–687.[8] Ersoz G, Otag F, Erturan Z et al. An outbreak of Dipodascus capi-tatus infection in the ICU: Three case reports and review of the lit-erature. Jpn J Infect Dis 2004; 57: 248–252.[9] Yilmaz Karapinara D, Karadaş N, Önder Siviş Z et al. Case report:Rare severe mycotic infections in children receiving empiricalcaspofungin treatment for febrile neutropenia. Braz J Infect Dis2015; 19(5): 549–552.[10] Saghrouni F, Abdeljelil JB, Youssef YB et al. Geotrichum capita-tum septicemia in patients with acute myeloid leukemia. Report ofthree cases. Med Mycol Case Re, 2012; 1: 88–90. [11] Tanabe MB, Patel SA. Blastoschizomyces capitatus pulmonary in-fections in immunocompetent patients: case report, case series andliterature review. Epidemiol Infect 2018; 146: 58–64.J. MARKI] et al. G. capitatum respiratory infection in a childInfektolo{ki glasnik 37:1, 23–26 (2017)

Prvi hrvatski pedijatrijski bolesnik s Geotrichum capitatum respiratornom infekcijom

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