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/).
452
braz j infect dis.2019;23(6):451–461Introduction
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.
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
454
b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461Table1–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
b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461
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
456
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
b r a z j i n f e c t d i s . 2 0 1 9; 2 3(6) :451–461
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
458
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
brazj infect dis.2019;23(6):451–461
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.
460
braz j infect dis.2019;23(6):451–461sincetheculturehadtobesenttoadifferentlabandregrown 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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