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brazjinfectdis2019;23(6):451–461

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Case

report

Catheter-related

infection

due

to

Papiliotrema

laurentii

in

an

oncologic

patient:

Case

report

and

systematic

review

Marcos

Rech

Londero

a

,

Crisley

Dossin

Zanrosso

a

,

Leandro

Luis

Corso

b

,

Lessandra

Michelin

b

,

Jonathan

Soldera

b,∗

aHospitalVirviRamos(HVR),InternalMedicine,CaxiasdoSul,RS,Brazil

bUniversidadedeCaxiasdoSul(UCS),CaxiasdoSul,RS,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received2June2019 Accepted20October2019

Availableonline16November2019

Keywords: Cryptococcus Papiliotrema Catheter-relatedinfections AmphotericinB Stomachneoplasms.

a

b

s

t

r

a

c

t

Background:Papiliotremalaurentiiisoneofseveralnon-neoformanscryptococcithathave

rarelybeenassociatedwithhumaninfection,sinceitwaspreviouslyconsideredsaprophyte andthoughttobenon-pathogenictohumans.Nevertheless,increasingnumberofreports ofhumaninfectionhaveemergedinrecentyears,mostlyinoncologicpatients.

Aim: Toreportacaseofafemalepatientwithpyloricobstructivecancerwitha catheter-relatedPapiliotremalaurentiibloodstreaminfectionandsystematicallyreviewtheavailable evidenceonP.laurentiiinfectioninhumans.

Methods:RetrievalofstudieswasbasedonMedicalSubjectHeadingsandHealthSciences

Descriptors,whichwerecombinedusingBooleanoperators.Searcheswererunonthe elec-tronicdatabasesScopus,WebofScience,MEDLINE(PubMed),BIREME(BibliotecaRegional deMedicina),LILACS(LatinAmericanandCaribbeanHealthSciencesLiterature),Cochrane LibraryforSystematicReviewsandOpengray.eu.Therewasnolanguageordateof publica-tionrestrictions.Thereferencelistsofthestudiesretrievedweresearchedmanually.

Results:Thesearchstrategyretrieved1703references.Inthefinalanalysis,31references

wereincluded,withthedescriptionof35cases.Everypatientbutonehadaprevious co-morbidity-48.4%ofpatientshadaneoplasm.AmphotericinBwasthemostusedtreatment andonlyasinglecaseofresistancetoitwasreported.Mostpatientswerecuredofthe infection.

Conclusion: P.laurentiiinfectioninhumansisusuallyassociatedtoneoplasiaandmultiple

co-morbidities,andamphotericinBseemstobeareliableagentfortreatment.

©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.Thisis anopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/

licenses/by-nc-nd/4.0/).

Correspondingauthorat:SchoolofMedicine,UniversidadedeCaxiasdoSul(UCS),Av.VereadorMárioPezzi,699/601,CaxiasdoSul

95084-180,Brazil.

E-mailaddress:jonathansoldera@gmail.com(J.Soldera).

https://doi.org/10.1016/j.bjid.2019.10.005

1413-8670/©2019SociedadeBrasileiradeInfectologia.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

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braz j infect dis.2019;23(6):451–461

Introduction

The advancement of Medicine brought new medications, therapeutics, invasive diagnostic methods and surgical approacheshaveindifferentpathologies.However,new obsta-clesemergetodefyourscientificknowledge.Rarepathogens until then unknown take advantage of health fragility in humanstocauseinfectionswithalarmingproportions.

Cryptococcusspp.otherthanC.neoformansandC.gattiiwere

previouslyconsideredtobesaprophytesandnon-pathogenic tohumans;however,opportunisticinfectionsassociatedwith

rareCryptococcusspp.,suchasCryptococcuslaurentiiand

Cryp-tococcusalbidus,haveincreasedoverthepastfourdecades.1

Cryptococcus laurentii belongs to the phylum basidiomycota

ofthefungiandisanencapsulatedsaprobic yeastandcan bewidely isolated from various typesofenvironments.2 It

is widely distributed throughout the world, including the Caribbean,AntarcticandtheHimalayasandcanbeacquired fromair,water,wood,soil,pigeonexcrementsaswellas var-iousfoods, suchas cheese,fruit, porkproducts, bean,and wine.3Since2015,thespeciesnameCryptococcuslaurentiiwas

replacedbyPapiliotremalaurentii.Thisnomenclaturewasbased onphylogenetic analysesbasedonthesequencingofseven genesandregionssuchasITSrRNAgene,theD1/D2domains ofthelargesubunit(LSUor26S)rRNAgene,thesmall sub-unit(SSUor18S)rRNAgene,twosubunitsofRNApolymerase II(RPB1and RPB2), translation elongationfactor1-␣ (TEF1) andcytochromeb(CYTB).

Withincreasingimmunosuppressiondueto antineoplas-tictherapy,organtransplantation,catheterinsertion,dialysis and other invasive diagnostic and therapeutic procedures, systemic fungal infections are observed more frequently.4

Non-neoformans cryptococci have been reported to cause infectioninmanyorgans.Thebloodstreamandcentral ner-voussystemarethemostcommonsitesofnon-neoformans cryptococcal infection.5 Due to the rarity of cases

involv-ing P. laurentii, a standard treatment has not yet been

established.Commonly, amphotericinBwith flucytosine is recommended.6

Theaimofthis paperwas toreporta caseofafemale patientwithpyloricobstructivecancerwithcatheter-related

Papiliotrema laurentii bloodstream infection and

systemati-callyreviewtheavailableevidenceonP.laurentiiinfectionin humans.

Case

report

A 68-year old female patient, previously diagnosed with type 2 diabetes, arterial hypertension, non-alcoholic fatty liverdisease,withaprevioushistoryofbreastcancerwhich was treated with radical mastectomy, radiotherapy and chemotherapyadecadeago,soughtcareduetoweightloss(20 %oftotalbodymass-over40pounds),incoerciblevomiting, weakness,hypoglicemiaandupperabdominalpain.

Shewasadmittedtothehospitalforinvestigation. CAT-scanshowed gastricdistension.Upperdigestive endoscopy showedsubmucosal obstructive pyloricmalignancy(Fig. 1), but superficial biopsies came back negative for cancer.

Fig.1–Infiltrativesubmucosalgastricneoplasminthe

pylorus(circle).

Colonoscopywasincompleteduetoinadequatecolonic prepa-ration - the patient vomited manitol. Magnetic resonance showedapyloric-duodenalmass,suggestiveofsubmucosal pyloriccancer.Atwo-weekparenteralnutrition(PN)was initi-atedwiththepurposeofimprovingnutritionpriortosurgery. PatientgainedfivepoundswhileonPN.Inthe12thdayofPN, thepatientbegantopresentfever.Bloodculturesweredrawn andampicillin-sulbactamwasinitiatedwithlittleresponse.

Five days thereafter, the patient presented with bac-teremia.Catheterandperipheralculturesdrawnduringfever cameback positiveforPapiliotremalaurentii,with antifungi-grampending.Identificationoftheisolatewasperformedon the Vitek 2(YST card- BioMérieux,Marcyl’Etoile,France) automated identification system, whichreported P. lauren-tii.TheconcernregardingmisdiagnosisbyViteksystemswas minimized since the P. laurentii culture had been sent to twodifferentlaboratoriesandregrownfortheantifungigram, which confirmed the first and second P. laurentii diagnosis withthesameresistanceprofile.Theisolatesenttothe sec-ondlabwasagainidentifiedbythesameVitek2(BioMérieux, Marcyl’Etoile,France)yeastidentificationcard withtesting staff blindedtoprevious Vitek2and antifungigramresults. Xiaoetal.citedthatcomparedtothegoldstandard (identifi-cationofITS-internaltranscribedspacer),Vitek2cancorrectly identify81.0%ofP.laurentiiisolates.7Fluconazole,

piperacillin-tazobactamand vancomycin replacedampicillin-sulbactam andthesiteofthecatheterwasswitched.Infivedays,fever subduedandafter5-daynegativecontrolbloodcultures, par-tial gastrectomy withY-en-Roux gastroenteric anastomosis wasperformed(Fig.2).Withanadequateevolution,patient begantoeatorallyandPNwasreducedgradually.

Fivedaysaftersurgery,feverwasagainnotedandcatheter and peripheral cultures were positive for P. laurentii and

Candidaparapsilosis.Thefirstwas susceptibletoflucytosine

(intermediary), fluconazole, amphotericin B, voriconazole, and resistant to micafungin and caspofungin. The latter wassusceptibletoflucytosine,fluconazole,amphotericinB, voriconazole,micafunginandcaspofungin.Transesophageal echocardiogram was negative for infective endocarditis.

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brazj infect dis.2019;23(6):451–461

453

Fig.2–Surgicalresectionofneoplasm(circle).

Fig.3–Post-operativecontrol:gastroentericanastomosis withnolesionorgastricfoodresidue.

Vancomycin and piperacillin-tazobactam were already fin-ished and patient was on monotherapy with fluconazole 800mg once a day. Catheter site was switched again and amphotericinB50mgonceadaywasassociated,with resolu-tionoffever.After14daysofcombinedtherapyandnegative peripheral cultures, patient was discharged with a dosage of 800mg oral fluconazole daily. A post-operative control CAT-scanandanupperdigestiveendoscopywereperformed, showingnosignsofrecurrenceoftheneoplasm(Fig.3).

Materials

and

methods

Thisstudywascarriedoutinaccordancewiththe recommen-dationscontainedinthePreferredReportingItemsfor Sys-tematicReviewsand Meta-Analysis(PRISMA-P)guidelines.8

OursystematicreviewwasregisteredwiththeInternational ProspectiveRegisterofSystematicReviews(PROSPERO), main-tainedbyYorkUniversity,on14January2019[registrationNo. CRD42019122125(www.crd.york.ac.uk/prospero/)].

Datasources

Studieswereretrievedusingtheterm“Cryptococcuslaurentii”.

SearcheswererunontheelectronicdatabasesScopus,Web ofScience,Medline(PubMed),BIREME(BibliotecaRegionalde Medicina),LILACS(LatinAmericanandCaribbeanHealth

Sci-ences Literature),Cochrane Library forSystematic Reviews andOpengray.eu.Therewasnolanguageordateof publica-tion restrictions.Thereferencelistsoftheretrievedstudies weresubmittedtomanualsearch.Databasesweresearched January2019.

Inclusioncriteriaandoutcomes

Casereportorcaseseriesstudieswereeligibleforselection. Iftherewasmorethanonestudypublishedusingthesame case,themostrecentstudywasselectedforanalysis.Studies publishedonlyasabstractswereincluded,aslongasthedata availablemadedatacollectionpossible.Theoutcome mea-suredwascureoftheinfectionordeath.

Studyselectionanddataextraction

Aninitialscreeningoftitlesandabstractswasthefirststage toselectpotentiallyrelevantpapers.Thesecondstepwasthe analysisofthefull-lengthpapers.Twoindependentreviewers extracteddatausingastandardizeddataextractionformafter assessing and reaching consensuson eligible studies.The samereviewersseparatelyassessedeachstudyandextracted data about thecharacteristics ofthe subjects and the out-comesmeasured.Athirdreviewerwasresponsibleforclearing divergencesinstudyselectionanddataextraction.

Statisticalanalysis

Datawassummarizedusingdescriptiveanalysis–frequency andmeans.

Results

Systematicreview

Thesearchstrategyretrieved1703references,767references wereexcludedbecausetheywereduplicates.Afteranalyzing titlesandabstracts,900referenceswereexcluded.Fulltexts wereretrievedfor37references.Inthefinalanalysis,31 ref-erences wereincluded, comprehending35 cases.Flowchart illustrating the search strategy is shown in Fig. 4. Studies includedwereeitheracasereportoracaseseries.

CasesfromIndia,Slovakia,USAand Italywerethemost common(19.3%,12.9%,9.7%and9.7%,respectively).Atotal of35patientswereincluded,correspondingto17maleand12 female(thesexofsixpatientswasnotinformed).Ageranged froma6-day-oldneonateto88yearsold(meanagewas40.3 years).Themostcommonclinicalpresentationwasfever(25 %);16.1%wererelatedtocatheterinfection;67.7%had posi-tivebloodcultures(54.8%)orofcerebrospinalfluid(12.9%).

Only one patient was found to have no previous co-morbidity. Twenty-three patients were immunosuppressed (considering both immunologic disorders and/or use of immunosuppressive agents). Neoplasias were described in 48.4%ofthepatients.

ResistanceprofileofP.laurentiiwasreportedformostcases; onecaseshowedresistancetofluconazoleandflucytosineand anothertoamphotericinB.AmphotericinBwasthefirstchoice

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b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461

Table1–Summaryofsystematicallyreviewedreportedcases. Reference Country Age Sex Clinical

Presenta-tion

Siteof Infection

Co-morbidities ImmunossupressionNeoplasm Resistance Treatment Outcome

Asano9,2014 Japan 32 M Fever Peritoneal

fluid

IgAnephropathyon peritonealdialysis

Yes None Susceptibleto

amphotericin B,flucytosine, fluconazole and voriconazole Voriconazole for3 months Cured Averbuch10, 2002

Israel 16 M Fever Blood

culture

Mestastatic gan-glioneuroblastoma

Yes Yes Resistanceto

fluconazole and 5-fluorocytosine Amphotericin Bfor3 weeks Cured Banerjee11, 2013 India 76 M Fever, shortness ofbreath, heart failure Blood culture Arterial hypertension, coronaryartery disease,previous hemorrhagicstroke

None None Susceptibleto

fluconazole, amphotericin B, voriconazole. Resistanceto flucytosine Amphotericin Bfor2 weeks followed by flu-conazole for2 weeks Cured Bauters12, 2001

Belgium 45 M Fever Oropharinx Erytroleukaemia Yes Yes NR Amphotericin

Bfor18 days

Death

Bhat2,2016 India 26 F Diarrhea Enteritis Hodgkin’s

lymphomawho underwent autologous hematopoeticstem celltransplant

Yes Yes Susceptibleto

amphotericin B, fluconazole, voriconazole, and5 flucytosine Voriconazole for4 weeks Cured Calista13, 2015 Italy 74 M Diarrhea and neu-tropenia Enteritis HepatitisB, colorectalcanceron chemotherapy

Yes Yes None Amphotericin

Bfor10 days

Cured

Cheng14,2015 Taiwan 88 F Fever,

neutrope-niaand abdomi-nal pain Urineand blood culture

DiffuselargeBcell lymphomaon chemotherapy

Yes Yes NR Amphotericin

Band flucyto-sinefor2 weeks

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455

–Table1(Continued)

Reference Country Age Sex Clinical Presenta-tion

Siteof Infection

Co-morbidities ImmunossupressionNeoplasm Resistance Treatment Outcome

Conti15,2015 Italy 47 F Fever

associ-atedwith weakness intheleft lower limb

Lungs Systemiclupus erythematosusand SjogrenSyndrome, treatedwith cyclosporineAand corticoids

Yes None NR Initially

ampho-tericinB, switched to flu-conazole for8 months dueto toxicity Cured

Ding16,2018 Malasya 35 F Fever,

supraclav-icular mass

Blood culture

Hodgkinlymphoma Yes Yes NR Fluconazole

for2 weeks Cured Furman-Kuklinska3, 2009

Polonia 39 NR Fever Blood

culture TypeI membra-noproliferative glomerulonephritis, previoususeof prednisoneand cyclophosphamide

Yes None Susceptibleto

amphotericin B, voriconazole, itraconazole and fluconazole Fluconazole for3 weeks, switched to itra-conazole for4 weeksdue to persis-tenceof fungemia Cured Gupta17,2018 India 6 days M Worsening ofclinic condition Blood culture

Premature,lowbirth weight

None None Susceptibleto

amphotericin Band fluconazole Amphotericin Bfor8 days followed by flu-conazole for24 days Cured

James18,2000 Venezuela69 F Feverand

headache

CNS HIV-negative

idiopathicCD4 deffciency

Yes None NR Amphotericin

Bfollowed by flu-conazole Cured Johnson19, 1997

USA 27 F Feverand

painful cutaneous nodules Blood culture Intravenousdrug use,pelvic inflammatory disease,infectious endocarditisand bipolardisorder

None None NR Fluconazole

for4 weeks

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b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461 –Table1(Continued)

Reference Country Age Sex Clinical Presenta-tion

Siteof Infection

Co-morbidities ImmunossupressionNeoplasm Resistance Treatment Outcome

Johnson19, 1997 USA 27 days M Candiduria, fungus ballsin both kidneys Blood culture Hypoplasticlungs andbilateral hydronephrosisdue toposteriorurethral valves

None None NR Amphotericin

Bfor2 weeks Cured Kamalam20, 1977 India 40 NR Verrucous nodules around theankle andleft foot Skin NR NR NR NR Potassium iodidefor 4months, switched to ampho-tericinB dueto iodism Cured Khawcharo-enporn5, 2006 Thailand 35 M Fever, headache Blood culture andCNS

HIV Yes None NR Amphotercin

Bfor14 days followed by flu-conazole for3 months Cured Kordosis21, 1998 Greece 34 M Dyspnea, drycough, weight loss,fever, headache and diplopia

CNS HIVandKaposi’s sarcoma

Yes Yes NR Amphotericin

Band flucyto-sinefor2 weeks followed by flu-conazole asa main-tenance therapy Cured Krcmery4, 1997

Slovakia 17 NR Fever Blood

culture

Leukemia,recent bonemarrow transplant

Yes Yes NR Fluconazole

for2 weeks Cured Krcmery22, 1998 Slovakia NR M Catheter-related Blood culture

Solidtumor None Yes None Fluconazole

for10 days Cured Krcmery22, 1998 Slovakia NR M Catheter-related Blood culture Non-Hodgkin lymphoma, corticoids

Yes Yes NR Amphotericin

Bfor20 days Death Kunova23, 1999 Slovakia NR NR Fever, catheter-related Blood culture

Neutropenia Yes Yes NR Amphotericin

Bfor14 days

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457

–Table1(Continued)

Reference Country Age Sex Clinical Presenta-tion

Siteof Infection

Co-morbidities ImmunossupressionNeoplasm Resistance Treatment Outcome

Kunova23, 1999 Slovakia NR NR Fever, catheter-related Blood culture

Neutropenia Yes Yes NR Fluconazole

for10 days

Cured

Kunova23,

1999

Slovakia NR NR Fever Blood

culture

Neutropenia Yes Yes NR NR Death

Lynch24,1980 USA 55 F Skinrash

and proximal muscle weakness Lungs Dermatomiosis, chronicuseof corticoids

Yes None Susceptibleto

amphotericin Band flucytosine Amphotericin Bfor6 weeks Cured Manfredi25, 2006

Italy 34 M Feverand

headache

CNS Intravenousdrug user,HIV

Yes None Resistanceto

both amphotericin Band flucytosine Fluconazole for46 days Cured Martinez26, 2016

Mexico 65 M Skinulcer Skin Cutaneous

leishmaniosis

None None NR Itraconazole Cured

Mittal27,2015 India 30 F

Post-partum, headache and drowsi-ness Blood culture RecentC-section duetofetaldistress

None None NR Amphotericin

B Death Molina-leyva28, 2013 Spain 8 F Skin lesionin theright forearm

Skin None None None Susceptibleto

amphotericin Band fluconazole Fluconazole for2 weeks Cured

Neves6,2015 Brazil 42 M Fever

episodes, severe abdomi-nalpain, weakness and respi-ratory distress Blood culture Cervicalcancer treatedwith chemotherapyand radiotherapy1year priortothe hospitalization

None Yes Susceptibleto

amphotericin Band fluconazole Fluconazole for22 weeks Cured

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b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461 –Table1(Continued)

Reference Country Age Sex Clinical Presenta-tion

Siteof Infection

Co-morbidities ImmunossupressionNeoplasm Resistance Treatment Outcome

Park1,2017 Korea 47 F Fever,

erythema-tous papules Blood culture Refractoryacute myeloidleukemia afterallogenic hematopoieticstem celltransplantation, onchemotherapy

Yes Yes NR Amphotericin

Bfor3 weeks Cured Rodriguez29, 2012 Colombia3 months M Bronquiolitis dueto aden-ovirus, catheter-related Blood culture

Prematurebabywith downsyndrome

None None NR Amphotericin

B Death Shankar30, 2006 India 35 F Fever, night sweats, pleuritic chestpain and dyspnea Peritoneal fluid

HIV,diabetes Yes None NR Fluconazole

for5 weeks

Cured

Simon31,2005 Hungary 9 M Enlarged

lymph nodesand hep-atosplenomegaly CNS x-linked hyper-immunoglobulinM syndrome

Yes None Susceptibleto

amphotericin Band fluconazole Fluconazole for9 months with tittering ofdosage Cured Sinnott32, 1989 USA 13 F Abdominal painand fever Peritoneal fluid

Chronicrenalfailure inperitonealdialysis

Yes None NR Flucytosine

and micona-zol, switched to ampho-tericinB for2 months Cured Vlchkova-Lashkoska33, 2004 Slovakia 51 M Skin lesionon theback Skinand CNS

Alcoholism None None Susceptibleto

amphotericin Band flucytosine

NR NR

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459

SCOPUS

768 citations(s) 587 citations(s) 274 citations(s) 26 citations(s) 250 citations(s) 0 citations(s) 1 citations(s)

937 non-duplicate citations scrrened

Inclusion/exclusion criteria applied

900 articles excluded after title/abstract screen

37 articles retrieved

Inclusion/exclusion criteria applied

31 articles included

2 articles excluded after full text screen

(reviews)

4 articles excluded during data extraction (3 due to incomplete data, i due to infection

not by C laurentii) Web of science BIREME LILACS PubMed Cochrane Opengrayue

Fig.4–Studyselectionflowchart.

oftreatmentfor51.6%ofthepatients,followedby flucona-zolein35.5%ofthe cases.Fluconazolewasthe choicefor maintenancetreatmentforalongerperiod.Curewasachieved in82.8%ofthepatientsincludedonthisstudyafterproper treatment.TheseresultsaresummarizedinTable1.

Discussion

P.laurentiihasahighdegreeofinterspeciesheterogeneityand

hasbeendivided intophylogenetic groupsIand II. Physio-logicand biochemical characteristics ofthe speciesin the complex are similar. Nevertheless, the species in phyloge-neticgroupI,suchasCryptococcusflavescensandCryptococcus

aureus,can bedistinguished from phylogenetic groupII by

theircombinationofassimilationpatternsofd-glucosamine,

Nacetyl-d-glucosamine, DL-lactic acid, 1,2-propanediol and

sodiumnitriteandvitaminrequirements.34Cryptococcus

neo-formans and P. laurentii share many common traits and

structures–thehemolyticcapacityofP.laurentiiisan intrin-sic characteristic that optimizes its infective capacity and increasesitsgrowthinblood.35

Thelikelihoodofcryptococcalinfectionishighlyincreased inpatientswithimpairedcell-mediatedimmunity,including lymphoproliferativedisorders,HIVinfection(CD4counts<100 cells/␮l) andhematologicmalignancies.36 Otherriskfactors

are:useofsteroidorchemotherapy,37organtransplantation,

impairedhumoralimmunitysuchashyper-IgMsyndrome,38

non-HIVlymphopenia,39invasivedevices40anddirector

indi-rect exposures topigeon excreta.41 From our analysis, the

presenceofinvasivecatheters,immunosuppressionand neo-plasmsweresignificantriskfactorsassociatedtoP.laurentii

infection.

P.laurentiihasbeenreportedtocauseinfectionsinmany

organsystems.42 Thebloodstreamandcentralnervous

sys-tem were the most common sites of infection, although some other sites such as keratitis43 have been reported.

Fever was the most common clinical finding, present in mostcases.ChoicesanddurationoftreatmentforP.laurentii

infections depended onthe anatomical involvement, host-immunestatus,andseverityofinfection.Recommendations

regardingtreatmentforinfectionsarelimited,duetothesmall numberofempiricallytreatedcasesandtheabsenceof con-trolled trial data.Amphotericin Balone wasusedformost treatments, withahigh rateofcure(80%). Themostused regimenwasaninductionperiodof14daysfollowedby main-tenancefluconazole,withacurerateof75 %.Nonetheless, 10patientsweretreatedwithmonotherapywithfluconazole, withacurerateof90%.

Ajoint clinicalguideline publishedin2013bythe Euro-peanSocietyofClinicalMicrobiologyandInfectiousDiseases Fungal Infection Study Group (ESCMID) and the European Confederation of Medical Mycology (ECMM) for the diag-nosis and management ofrare invasive yeastinfections is theavailableconsensusonhowtomanagetheseinfections.

Fornon-neoformansandnon-gattiiCryptococcusinfectionsitis

recommended the use of amphotericinB with or without flucytosinefortheinductionofCNSandsevereinfectionsor fluconazoleinadoseover400mgdailyifdemonstratedin-vitro

sensitivity.Fornon-CNSandnon-severeinfections,400mgof dailyfluconazolecanbeusedforinductionandmaintenance treatment,reservingamphotericinBforlessazole suscepti-blespecies.Duetointrinsicresistance,echinocandinsarenot recommended.44

Susceptibility testing was reported for only 13 isolates, includingourisolate.Onewasfoundtoberesistantinvitro

to amphotericin Band other to fluconazole. Although our isolate was notresistant in vitroto fluconazole, monother-apyfailed,justifyingaswitchtoamphotericinBfollowedby maintenancetherapywithfluconazole.Clinicalcorrelations betweensusceptibilitytestingresultsandtreatmentoutcome arelacking.19

Thecurerateoftheinfection was82.8%, andthemost effectivedrugwasamphotericinB,usedin44.8%ofthecured cases. Although this infection generally occurs in patients withmultipleco-morbidities,it doesnotappeartobevery severe,withahighresponseratetocommonlyusedtherapy forresistantyeast.22,45

Averyimportantconcernregardingourreportedcasemust bebroughtintoattention:thereisareportofmisdiagnosisby Viteksystems,confoundingcandidaspecies,suchasC.

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braz j infect dis.2019;23(6):451–461

sincetheculturehadtobesenttoadifferentlabandregrown fortheantifungigram,whichconfirmedthefirstandsecond

C.laurentiidiagnosiswiththesameresistanceprofileandthe

C.parapsilosisdiagnosisinadifferentsystem.

In conclusion, P. laurentii, generally considered a non-infectivesaprobe, may cause relevantfungemia and other infections,especiallyinimmunocompromisedandoncologic patients.Centralcathetersseemtobeaparticularriskfactor forfungemiawiththisyeast.Themainclinicalmanifestation isfever,bloodculturesare usefulfordiagnosis,and induc-tiontreatmentwithamphotericinBfollowedbymaintenance fluconazoleseemstoachieveasignificantsuccessrate.

Conflict-of-interest

statement

Allauthorshavenothingtodisclose.

Author

contributions

Allauthorscontributedtostudyconceptanddesign,and draft-ingofthemanuscript;Allauthorscontributedtoacquisition ofdata,analysisandinterpretationofdata;MichelinL con-tributedinrevisingthefinalmanuscript;SolderaJandCorso LLcontributedtostatisticalanalysis;SolderaJcontributedto studysupervision;allauthorscontributedtocriticalrevision ofthemanuscriptforimportantintellectualcontent.

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