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evista da Sociedade Brasileira de Medicina Tropical 44(6):745-748, nov-dez, 2011

INTRODUCTION

1. Laboraório de Micologia Médica, Cenro de Ciências Biológicas, Universidade Federal de Pernambuco,ecie, PE. Address to: Dra. Rejane Pereira Neves. Depo de Micologia/CCB/UFPE. Av. Prof. Nelson Chaves s/n,  Cidade Universiária, 50670-420 ecie, PE, Brasil.Phone/Fax: 55 81 2126-8480

e-mail: rejadel@yahoo.com.br; rejadel29@yahoo.com.breceived in 10/04/2011

 Accepted in 01/06/2011

Fungemia in a university hospital: an epidemiological approach

Fungemia em hospial universiário: uma abordagem epidemiológicaFabíola Maria Marques do Couto1, Daniele Patrícia Cerqueira Macedo1 and ejane Pereira Neves1

 ABSTRCT

Introduction: Fungemia corresponds o he isolaion o ungi in he bloodsream and occursmosly in immunosuppressed paiens. Te early diagnosis and reamen o hese inecionsare relevan given he serious hrea o he affeced paiens and possible spread o oher organs,ofen becoming aal. Te growing number o ungemia associaed wih poor prognosis resuledin his research aiming o diagnose and assess he epidemiological aspecs o hemaogenousinecions by ungi. Methods: Te sudy included 58 blood samples colleced wihin a1-year period, rom paiens a he Hospital das Clinicas , Federal Universiy o Pernambuco,

 by venipuncure in vacuum ubes. Blood samples were processed or direc examinaionand culure and idenificaion, conduced by observing he macroscopic and microscopiccharacerisics, as well as physiological characerisics when necessary. esults: Eigh (13.8%)episodes o ungemia were idenified, accouning or he oal sample, and hese pahogens were Candida , Histoplasma , Trichosporon , Cryptococcus,  and a demaiaceous ungus.C. albicans  was he prevalen species, accouning or 37.5% o he cases. Mos affeced paiens were adulmales. Tere was no predominance or any aciviy, and he risk o acquired immunodeficiencysyndrome was he underlying pahology mos ofen cied. Conclusions: Te isolaion o ungiconsidered as emergen species, such asC. membranifaciens and demaiaceous species, highlighshe imporance o epidemiological monioring o cases o ungemia in immunocompromisedpaiens, as he herapy o choice depends on he knowledge o he aehiological agen.

Keywords: Epidemiology. Fungemia. Universiy hospial.

ESUMO

Introdução: Fungemia corresponde ao isolameno de ungos  na correne sanguínea eocorre, sobreudo, em pacienes imunossuprimidos. O diagnósico e raameno precocedesas inecções são relevanes diane da grave ameaça aos pacienes acomeidos e possíveldisseminação via hemaogênica para ouros órgãos, ornando-se muias vezes aal. O crescenenúmero de casos de ungemia associados ao mau prognósico resulou na realização desapesquisa que eve por objeivo diagnosicar e avaliar aspecos epidemiológicos das inecçõeshemaogênicas por ungos. Métodos: O esudo incluiu 58 amosras de sangue coleadas,durane um ano, de pacienes inernados no Hospial das Clínicas da Universidade Federalde Pernambuco, aravés da punção venosa em ubos a vácuo. As amosras de sangue oramprocessadas para exame direo e culura e a idenificação, conduzida aravés da observação dascaracerísicas macroscópicas, microscópicas e quando necessárias fisiológicas. esultados:Oio (13,8%) episódios de ungemia oram idenificados, correspondendo ao oal das amosrase os agenes eiológicos envolvidos oram Candida, Histoplasma, Trichosporon, Cryptococcus eum ungo demáceo. C. albicans oi a espécie prevalene com 37,5% dos casos. A maior pare dospacienes acomeidos perencia ao sexo masculino, na idade adula. Não houve predominância

para nenhuma aividade de risco e a síndrome da imunodeficiência adquirida oi a paologiade base mais ciada. Conclusões: O isolameno de ungos considerados emergenes comoC. membranifaciens e espécies demáceas ressalam a imporância do acompanhamenoepidemiológico dos casos de ungemia em imunocompromeidos, uma vez que a escolhaerapêuica depende do conhecimeno do agene eiológico.

Palavras-chaves: Epidemiologia. Fungemia. Hospial universiário.

In recen years, here was a marked increasein he number o serious inecions caused bypahogenic ungi and hose radiionally considerednon-pahogenic. Inecions caused by hese

organisms usually occur in paiens wih impairedimmune deense, suering rom cancer, wihacquired immunodeiciency syndrome (AIDS),or who received immunosuppressive herapy, haddisrupions o he normal barriers, or experiencedchanges in normal microbioa1.

 Advances in medicine have led o prolongedsurvival o immunocompromised paiens and as wellas he developmen opporunisic ungal inecions. Among hese inecions, ungemia corresponds ohe presence o ungi in he bloodsream, whoseincidence has risen in recen decades. Te presence

o viable microorganisms in he bloodsreamsuggess acive inecion in issues, and he paien'srecovery may depend on early idenificaion andisolaion o he aehiological agen2, 3.

Fungemia or hemaogenous ungal inecionsrepresen a serious healh problem, involvinghospialized paiens wih predisposing condiionsleading o a high moraliy rae4, 5.

he clinical presenaion is nonspeciic, andever is he mos common one2, 6 , which makes hediagnosis o ungemia a challenge, as blood culuresare posiive in less han 50% o cases6, 7. Tus, hediagnosis is usually lae in he course o he inecionor even during necropsy 4.

 Yea ss hav e been incre asingly pre senas aehiological agens o ungemia, includingCandida albicans and oher species such as Candidanon-albicans5. Neverheless, oher ungi, such asHistoplasma capsulatum,  may also be involved.Differenial paterns o species disribuion have no been ully elucidaed and may be closely relaed ohe poenial virulence o hese microorganisms8.

he early diagnosis and reamen o hese

ungemias are relevan given he serious hrea oimmunocompromised paiens and possible spread,hemaogenously, o deeper organs, ofen becoming

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METHODS

RESULTS

Couto FMM et al - Fungemia: an epidemiological approach

TABLE 1 - Distribution of causative agents of fungaemia according to gender, age, underlying

pathology and occupation of the patients.

  Underlying

Fungaemia agent Gender Age pathology Occupation

Candida albicans female 25 malignan umors no occupaion

Candida albicans male 33 AIDS hairdresser

Candida albicans male 55 AIDS bricklayer

Candida membranifaciens female 39 AIDS housewife

Cryptococcus neoformans male 24 AIDS hairdresser

Demaiaceous fungi male 35 diabetes mellitus eacher

Histoplasma capsulatum female 32 lupus eryhemaosus no occupaion

Trichosporon sp. male 48 AIDS ruck driver

 AIDS: acquired immune deficiency syndrome.

aal. An appropriae managemen hrough clinical and laboraorialdiagnosis may be effecive wih a saisacory global healh benefi9.

Te growing number o ungemia associaed wih poor prognosisled o his sudy aiming o diagnose and evaluae he epidemiologicalaspecs o hemaogenous inecions by ungi.

his sudy was conduced in hospialized paiens a heSecor o Inecious and Parasiic Diseases o he Hospital das

Clínicas (Federal Universiy o Pernambuco), and he proceduresperormed are in accordance wih he ehical sandards o hehuman experimenaion commiee o he Cener or HealhSciences, Federal Universiy o Pernambuco, Brazil. Paiens'personal daa were regisered such as age, sex, occupaion, andunderlying disease. Tree venous blood samples were asepicallycolleced in consecuive days by venipuncure ino Vacuainer® ubes using EDA anicoagulan. Tis is an unusual echnique or

deecion o ungemia inroduced o aciliae he diagnosis hroughdirec examinaion, which is no possible o perorm using hesandard mehods. Te samples were processed by usual mehods(direc examinaion and isolaion in culure) or mycologicaldiagnosis a he Medical Mycology Laboraory, Federal Universiyo Pernambuco.

Direc examinaion o clinical specimens was perormed wihou clar iicaion, as well as Giemsa sai ning and Nankin. Aliquos o 2mL o oal blood were plaed in he orm o sriaionson Sabouraud dexrose agar broh and brain hear inusion, bohadded wih chloramphenicol (Dico Laboraories) incubaeda 30°C and 37°C in an aerobic amosphere or 20 days. Pure

culures were ranserred o he surace o Sabouraud dexroseagar plus yeas exrac or he axonomic ideniicaion o heeiologic agens10, 11.

he ideniicaion was conduced on he basis o heirmorphophysiological properies and biochemical ess, includingauxanogram, zimogram, acid, and urease producion according oBarnet12 and De Hoog10. Te idenificaion was also done by heauomaed sysem VIEK 120 (bioMerieux).

In a period o 1 year, 58 blood samples rom inpaiens wihclinical suspicion o ungal blood inecion and wih a compromisedimmune sysem were analyzed. A oal o eigh episodes o ungemia were idenified during his period (March 2009 o March 2010). Afer compleion o he mycological laboraory diagnosis wih direcexaminaion and culure, based on he observaion o macroscopic,microscopic, and physiological characerisics, ungemia aehiologicalagen yeass o he genera Trichosporon, Candida, and Cryptococcus as well as a represenaive dimorphic Histoplasma capsulatum and arepresenaive o demaiaceous filamenous ungi were idenified. Teincidence o paiens wih ungemia was 13.8%, and he aehiologicalagens are shown in Table 1.

Te age o he eigh paiens wih ungemia, ranged rom 24 o55 years (mean: 36.3 years), predominanly (25.8%) in men. Teiroccupaions varied rom being a housewie, bricklayer, hairdresser,ruck driver, and eacher, wih no predominance or any risky aciviy.

From he oal number o paiens analized, 31 (53.4%) hadhuman immunodeficiency virus (HIV), and AIDS was he mosrequen underlying pahology cied among he affeced paiens wih ungemia, corresponding o five (62.5%) cases, ollowed bylupus eryhemaosus, malignan umors, and diabetes mellitus , wihone case each. Among he paiens wih AIDS, wo (40%) wereinjecing drug users, our (80%) were homosexual, and one (20%) was heerosexual.

Based on clinical evaluaion, all paiens wih ungemia wereanemic wih ebrile condiions; one (12.5%) wih pancyopenia;six (75%) wih vomiing, diarrhea, and respiraory problems; andwo (25%) wih cuaneous rash.

 Afer mycological diagnosis, our paiens received amphoericinB (oal dose o 400mg o 2g), which is considered he drug o choiceor he reamen o sysemic mycoses. Tree paiens died even beore saring his reamen. In one o he paien, he reamen was no insiued or abandonmen o monioring. From hose whoreceived he reamen, hree had an iniial good response, receivingmainenance herapy afer sympoms remission, wih amphoericin B(1mg/kg/dose once a week) or iraconazole daily. One paien diedduring hospializaion and reamen.

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ev Soc Bras Med Trop 44(6):745-748, nov-dez, 2011

DISCUSSION

In his group o paiens diagnosed wih ungemia, reamen wassared only afer laboraorial diagnosis. Early deecion o risk acorsor he developmen o ungemia, such as adminisraion o broad-specrum anibioics, use o muliple lumen caheers, mechanical

 venilaion, pareneral nuriion, and colonizaion ungal, has led oempirical reamen o reduce he high moraliy rae associaed wihungal inecions13. Oher acors cied as underlying condiions aremalignan diseases, use o coricoseroids, cancer chemoherapy,radiaion, malnuriion, and advanced age; hey are idenified asadjuvan agens in he onse o ungemia5, 7.

Fungemia generally induces ever, myalgia, and, possibly, askin rash. ess or deecing microorganisms in blood culuresare needed in cases o renal involvemen, oseoaricular lesions,endocardiis, meningiis, hypoension and muliple organ ailureand oher acors 14.

In his sudy, he majoriy o he diagnosed cases o ungemia

had Candida species as he main agen, and such resuls are similaro he findings o oher sudies, suggesing his genus as primarilyresponsible or cases o ungemia in immunossupressed paiens2, 15.

I was esablished ha he genus Candida is principally involvedin he onse o nosocomial inecions, where C. albicans ungemiais cied as he main cause, alhough here are increasing repors o blood inecions caused by oher species o Candida non-albicans and emergen ungi species16, 17. Colombo5 showed he deecion o145 candidemia in six hospials in Brazil he prevalence o C. non-albicans species in 63% o cases, C. parapsilosis and C. tropicalis , hepredominan, alhough he las hree decades in American eachinghospials, C. albicans species has been responsible or more han six-

old increase in he requency o ungemia by his yeas18, 19.In his research, we isolaed C. membranifaciens as he causaive

agen o ungemia. Franci and Pecile20 also repored a case caused byhis species in cancer paiens. C. membranifaciens has radiionally been considered non-pahogenic, and his is he firs repored case osysemic inecion in a paien wih AIDS. Addiionally, he incidenceo demaiaceous ungi isolaed rom blood o paiens wih diabetes

mellitus has rarely been repored.

During he mycological laboraorial diagnosis, i is possibleo deec ungemia caused by C. neoformans , Trichosporon ,H. capsulatum, and demaiaceos ungi. According o he NaionalSD/AIDS o he Minisry o Healh, rom 1980 o 2002, 6% oopporunisic inecions in HIV-posiive paiens were caused byC. neoformans. Considering he opporunisic ungal inecions haaffec paiens wih HIV worldwide, crypococcosis is he second-mos common21.

Te associaion o hisoplasmosis and HIV is requenly ound where he mycosis is endemic, wih prevalence ranging beween 2%and 30%, based on he sudied region. In our research, we observedhe involvemen o H. capsulatum  in homosexual paien, 32 wihHIV. In mos cases, laen oci o hisoplasmosis, may culminaein disseminaed orm. 14, 22. According o Borges22 , 18 cases ohisoplasmosis occurred in immunosuppressed paiens, and 17 had AIDS, mosly males.

 We had a case o Trichosporon ungemia, which is considered anemerging pahogen in disseminaed inecions. Te clinical picure

o inecion by his yeas is nonspecific and very poor prognosis23, 24.In a sudy conduced by Di Bonavenura23 , i was shown ha biofilmormaion by Trichosporon spp explains he persisence o ineciondespie in vitro suscepibiliy o aniungal agens.

I is considered ha early adminisraion o amphoericin Bcan resul in clinical improvemen or ungal inecions. However, when paiens are immunocompromised, here may be resisance

o his drug in vivo , which explains he high raes o moraliy inhis populaion24. In our work, amphoericin B was prescribed wihgood resuls.

In conclusion, our daa show ha he species C. albicans , C. non-albicans ,H. capsulatum, andC. neoformans remain he leading aehiologicagens causing ungemia, alhough oher emergen species may also be involved such as Trichosporon. AIDS remains he mos commonunderlying disease among males. Tus, compleion o he mycologicallaboraory diagnosis in immunossupressed paiens remains essenial inguiding an accurae and early reamen o cure he inecion.

 ACKNOWLEDGMENTS

Te auhors declare ha here is no conflic o ineres.

CONFLICT OF INTEREST

FINANCIAL SUPPORT

REFERENCES

Te auhors hank he Federal Universiy o Pernambuco (UFPE)and he Pos Graduae Program in Biology o Fungi (PPGBF) oha insiuion.

Pro eioria de Pesquisa (POPESQ/UFPE).

1. ibeiro LC, Hahn C, Favalessa OC, adano , Fones CJ. Sysemic mycosis:acors associaed wih deah among paiens ineced wih he humanimmunodeficiency virus, Cuiabá, Sae o Mao Grosso, Brazil, 2005-2008.ev Soc Bras Med rop 2009; 42:698-705.

2. Viudes A, Pemán J, Canón E, Ubeda P, López-ibo JL, Gobernado M.Candidemia a a erciary-Care Hospial: Epidemiology, reamen, ClinicalOucome and isk Facors or Deah. Eur J Clin Microbiol Inec Dis2002; 21:767-774.

3. Zaragora , Perman J. Invasive ungal inecions in criically ill paiens: differenherapeuic opions and a uniorm sraegy. ev Iberoam Micol 2006; 23:59-63.

4. Eggimann P, Garbino J, Pite D. Managemen o Candida species inecions incriically ill paiens. Lance Inec Dis 2003; 3:772-785.

5. Colombo AL, Guimarães . Epidemiologia das inecções hemaogênicas porCandida spp. ev Soc Bras Med rop 2003; 36:599-607.

6. Alonso-Valle H, Acha O, Garcia-Palomo JD, Farinas-Álvarez C, Fernandez-Mazarrasa C, e al. Candidemia in erciary Care Hospial: Epidemiology andFacors Influencing Moaliy. Eur J Clin Microbiol Inec Dis 2003; 22:254-257.

7. Blo SI, Vandewoude KH, Hose EA, Colardyn FA. Effecs o NosocomialCandidemia on Oucomes o Criically ill Paiens. Am J Med 2002; 113:480-485.

8. Chang A, Neoyos D, Horn D. Candidemia in he 21s cenury. Fuure Microbiol 2008; 3:463-472.

9. França JC, ibeiro CEL, Queiroz-elles F. Candidemia in a Brazilian eriary carehospial: incidence, requency o differen species, risk acors and aniungal

suscepibiliy. ev Soc Bras Med rop 2008; 41:23-28.10. De Hoog GS, Guarro J, Gené J, Figueras MJ. Alas o clinical ungi.

2nd ed. Washingon, DC: American Sociey or Microbiology; 2001.

8/20/2019 Artigo Infecto

http://slidepdf.com/reader/full/artigo-infecto 4/4

748

11. Lacaz CS, Poro EM, Cosa JE, Heins-Vaccari EM, Melo N. raado de micologiamédica. 9h ed. São Paulo: Sarvier; 2002.

12. Barnet JA, Payne W, Yarrow D. Yeass: characerisic s and idenificaion.3rd ed. Cambridge Universiy Press: Cambridge; 2000.

13. Velasco E, Tuler LCS, Marins CAS, Nucci M, Dias LMC, Gonçalves VMSC.Epidemiology o Bloodsream Inecions a a Cancer Cener.   S Paulo Med J2000; 118:131-138.

14. Oliveira FM, Fernandes SS, Severo CB, Guazzelli LS, Severo LC. Histoplasma

capsulatum ungaemia in paiens wih acquired immunodeficiency syndrome:deecion by lysis-cenriugaion blood-culuring echnique. ev Ins Med ropS Paulo 2007; 49:135-138.

15. Godoy P, iraboschi IN, Severo LC, Busamane B, Calvo B, Almeida LP, eal. Species disribuion and aniungal suscepibiliy profile o Candida  spp

 bloodsream isolaes rom lain american hospials. Mem Ins Oswaldo Cruz2003; 98:401-405.

16. Girmenia C, Pizzarelli, G, Crisini F, Barchiesi F, Spreghini E, Scalise G, e al.Candida guilliermondii Fungemia in Paiens wih Hemaologic Malignancies.

 J Clin Microb 2006; 44:2458-2464.

17. Colombo AL, Nucci M, Park BJ, Nouér SA, Arhingon-Skaggs B, Mata DA, e al. Epidemiology o candidemia in Brazil: a naion wide seninel surveillance ocandidemia in eleven medical ceners. J Clin Microbiol  2006; 44:2816-2823.

18. Franci , Pecile P. Cenral venous caheer-relaed inecion due o Candida

membranaefaciens , a new opporunisic azole-resisan yeas in a cancer paien:a case repor and a review o lieraure. Mycoses 2005; 48:357-359.

19. Silva P, abelo R, erra AP, eixeira DN. Suscepibiliy o aniungal agensamong Cryptococcus neoformans varieies isolaed rom paiens a a universiyhospial. ev Soc Bras Med rop 2008; 41:158-162.

20. Borges AS, Ferreira MS, Silvesre MA, Nishioka SA, ocha A. Hisoplasmoseem pacienes imunodeprimidos: esudo de 18 casos observados em Uberlândia,MG. ev Soc Bras Med rop 1997; 30:119-124.

21. Di Bonavenura G, Pompilio A, Picciani C, Iezzi M, D’Anonio D, Piccolomini. Biofilm ormaion by he emerging ungal pahogen Trichosporon asahii:developmen, archiecure, and aniungal resisance. Animicrob AgensChemoher 2006; 50:3269-3276.

22. Pereira DN, Nader SS, Nader P, Marins PG, Furlan SP, Henges C. Inecçãodisseminada por Trichosporon  spp em recém-nascido premauro: relao de umcaso. J Pediar 2009; 85:459-561.

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