REVIEW Foha Microbiol 47 (2). 105-112 (2002)
h t t p : / / w w w . b i o m e d , can. cz/mbu/folia/
Causative Agents of Nosocomial Mycoses A. TOM~iKOVA ]nsntute of MtcrobtologT. Faculty of Medtcine, ('harles Universio,. 305 99 Plzeh. Czechta Recetved 24 September 2001
ABSTRACT. In the last few years mycoses have been caused by fungi tbrmerly considered to be harmless for humans. They cause diseases of plants and insects; some of them are also used in the industry. They are now usually called "emerging fungi". We investigated this flora with respect to their potential to cause infections in hospitals. These fungi are present in the air, on medical objects and instrumentation, in the respiratory tract and on the hands of hospital staff; other sources have been identified in the use of iatrogenic methods. Mycotic diseases, their risk factors, their clinical pictures, and spectra of agents were analyzed in 1990-2000; the results were compared with data in the literature. Transplantations were the most frequent risk factors, fungemia and abscess the most frequent clinical picture and filamentous fungi (genera Absidia,
Acremonium, Alternaria, Apophysomyces, Aspergillus, Bipolaris, Cladophialophora, Cunninghamella, Exserohilum, Fusarium, Chaetomium, Chrysosporium, Lecythophora, Ochroconis, Paecilomyces, Pythium, Rhizopus, Scedosporium, Scopulariopsis) were the most frequent agents of nosocomial infections. These filamentous fungi and also some yeasts (genera Candida, Cryptococcus, Trichosporon) bring about different clinical syndromes in both immunocompromised and immunocompetent patients.
CONTFNIS I 2 3 4 5 6
1
Introduction 105 Candidemia 105 Candiduria and funguria Oncohematology 106 Intesive care units 107 Ophthalmology 107
105
7 Urology 107 8 Cardiosurgery 108 9 Dermatovenerology 109 10 Nosocomial mycoses in different clinics in Plzefi References 109
109
INTRODUCTION
Nosocomial infections caused by opportunistic and pathogenic fungi are an important cause of morbidity and mortality among hospitalized patients. They occur especially in patients with severe basic diseases and have no characteristic symptoms. Their epidemiology, transport and pathogenesis are not well known. The development of mycosis depends primarily on the defense mechanism of patients. Clinical pictures of nosocomial mycoses are different (Dorko et al. 2000a,b, 2001 a,b).
2
CANDIDEMIA
Candidemia is the most important and severe nosocomial infection. It can be evoked by a large range of yeasts and yeast-like fungi. The most important are C. albicans (Graningen et al. 1993), C. parapsilosis (Gangneux et al. 1998), C. famata, C. tropicalis, Trichosporon beigelii (Hajjeh et al. 1995) and Saccharomyces boulardi. They are endogenously occurring mostly in the gastrointestinal tract. Besides the yeast-like fungi, bloodstream infections can be caused by a range of filamentous fungi (Bipolaris spicifera, Scedosporium prolificans, Hormonema dermatoides, Phialemonium curvatum and Exophialajeanselmei). The most frequent risk factor is the central catheter.
CANDIDURIA AND FUNGURIA
In the last few years a dramatic increase of urine infection can be noted. The infections are caused mostly by Candida spp., exceptionally by Aspergillus spp. and Fusarium spp. Candiduria and funguria (Mirdha et al. 1998) can signalize different pathological states including invasive kidney disease, fungus ball and superficial infection of the'lower part of the urinary tract (Table 1).
106
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Table I. Causative agents of nosocomial candidemia and limgemia, and of nosocomtal candldurla and funguria Candidemia and fungemta
Candiduna and funguria
Candida albwans fartlata glabrata krusei parapsilosts tropicalts Rhodotorula rubra Saccharomyces boulardii Trtchosporon beigelit
Candida albwans mconspicua krusei parapsilosis pseudotropicalts (C. kefyr) stellatoidea troptcalis Geotrlchum spp.
Btpolar~s sptctfera Exophtala jeanselmei Hormonerna dermato/des Phialemonium curvature Scedosporium prolificans
Aspergtllus spp. Fusarium spp.
Patients with immune defects (e.g., HIV-positive) (Aly et al. 1996) are very sensitive to fungal infections (Coleman et al. 1993). Besides Pneumocystis carinii and Candida spp. a great number of yeasts (De Lalla et al. 1993) and filamentous fungi (Hunderson et al. 1979; Halpern et al. 1992) are less frequently present in the hospital environment and can cause different clinical pictures in these patients (Table 11). Table 11. Causative agents of nosocomial mycoses in AIDS patients Strain
Diagnos~s, syndromes
Pneumocystts carmu
dissemination
Absidta corymblfera Cunntngharaella berthollettae Mucor spp.
cerebral lbrm of mucormycosis
Scedosportum apzospermum prolificans
otttis, sinusitis, keratitis; endophthalmitis. osteoarthntls
Pseudoallescherta boydu
invasive form different forms of aspergiilosis
Aspergtllus fumigatus pneumonia, fungemia; dissemination, chorioretinitis Saccharomyces cerevistae Cryptococcus curvata meningitis neoformans vat. neoformans A,D neoJormans vat gattit B,C invasive ['orm Trtchosporon be~gelii
4
Candida albtcans famota glabrata krzgseI parapsdosls tropicalts
candidosis: oral, oropharyngeal, esophageal, colitis, endocarditis, vaginitis, meningitis, candidemta
Malassezta furfur Trichophyton mentagrophytes rubrum
seborrhoic dermatitis
Eptdermophyton floccosum
white subungual onychomycosis
tinea corporis; tinea cruris, pedis
ONCOHEMATOLOGY
The o c c u r r e n c e o f fungal infections, especially o f candidosis in o n c o h e m a t o l o g y has increased in the last ten years. C. albicans and C. glabrata o c c u r more often in solid tumors ( B o d e y et al. 1992; Andre-
A(i[:N 15 OF NOSOCOMIAL. MYCOSt-S - - revtew
2U02
107
mont et al. 1996), whereas the non-albicans strains are frequent in transplantation units (Table 111) (Hitchckok et al. 1985; Wingard 1995; Gangneux et al. 1998). Table III. Nosocomial nlycoses in oncohematology and in IC[J a
Oncohematology agent b
ICU
diagnosis
Candtda albtcans glabrata gutlliermondu kruset lustlamue parapsdosts tropicahs
candidosis oropharyngeal candtdosis esopharyngeal candidosis disseminated
Candida albicans glabrata
in solid tumors
agent
diagnosis
Candida albicans glabrata lusttantae gutlltermond# pseudotroptcahs thstoplasma spp. Cocctdloldes spp. Mucor spp. Aspergdlus spp.
sepsis
Dermatophytes
alntensive care units.
bNon-albtcans strains occur more often in hematology and transplantation units.
INTESIVE CARE UNITS In intesive care units severe infections are the most frequent causes of death (Pendleburg et al. 1989). Besides C. albicans, many non-albicans species (Solomkin et al. 1985), aspergilli, Histoplasma, Coccidioides and dermatophytes can also cause the infections mentioned above (Table lll; cf. Dorko et al. 2001 c; Yrubenovb. et al. 2001 ).
6
OPHTHALMOLOGY
Nosocomial mycoses in ophthalmology concern endogenous metastatic fungal infections of the inner eye (endophthalmitis) (Montero et al. 1988; Brooks 1989). The most important agent is C. albicans, which causes over 70 % of all nosocomial infections of the eye. In contrary with endophthalmitis, keratitis is mostly exogenous and the agents are Candida, Fusarium and Aspergillus (Table IV; cf. Dorko et al. 2001d). Table IV. Nosocomial mycoses in ophthalmology Agent
Diagnosis
Agent
Diagnosis
Condldo albtcans glabrata parapsilosis tropicalis Cryptococcus spp. Trichosporon betgeht
endophthalmitis
Blastomyces dermatitidis Coccidioides immitis Histop[asma capsulatum Pseudoallescheria boydii Mucor spp. Sporothrix schenckii
endophthalmitis
Aspergdlus spp. Candtda s p p Fusarium spp. Mucor spp.
keratitis
Aspergillus candidus JlavId$ furnigalus roger
7
UROLOGY
Recently an increase of urine contamination by fungal elements in hospitalized patients has appeared. The causative agents belong to facultative pathogens (Jemmi et al. 1992) and are dangerous particularly
108 A. TOMSiKOV,g,
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for patients with damaged function of phagocytes (metabolic damage after corticoid and immunosupressive treatment (Table V) (Wise et al. 1980; Kuntze et al. 1988). Table V. Nosocomialmycoses m urologyand after kidney transplantatiotl Agent
Diagnosis
Agent
urology
Diagnosis urology
Aspergdlusfi~mtgatus flavus niger Cryptococcus spp.
kidneyabscess infarction necrosis kidney, adrenals, prostate
Candtda albtcans troptcahs paraps~losts glabrata
kidney abscess, peritoneal infection, pyelonephritis, cystitis septicemia
Geotrichum s p p . Hansenulafablam
accompanying infections of kidney stones
Paectlomyces spp Paracoccidtoides spp Pttvcomyces spp. Mucor spp.
accompanying infections of kidney stones
after kidney transplantation
Aspergillus sp. Blastomyces dermatttidis Coccidiotdes immitisa Cr),ptococcus spp. Histoplasma capsulaturn
affection of kidney. adrenal glands
aAIsoagent of mycoses of prostate and testicles. 8
CARDIOSURGERY
The most important is the increase o f endocarditis after prosthetic valves (Boden et al. 1983). The agents in 7-20 % are Candida spp., especially C. albicans, C. parapsilosis, C. krusei, less frequently representatives o f the genera Aspergillus, Histoplasma, Cryptococcus, Mucor, Trichosporon, Curvularia, Phialophora, Hormodendrum, Saccharomyces, Paecilomyces and Penicillium. After colonization of the prosthetic valves, Candida spp. form a biofilm (Calderone et al. 1991) on the valves containing a layer of cells in the extracellular polymetric matrix (Table VI). Table VI. Agents ofnosocomial mycoses in surge~,
Agent
Diagnosis
Candlda albicansa prosthetic valve endocarditisb kruseia parapsilosisa Ctyptococcus neoformans Aspergillus sp. Curvularia gentculata Htstoplasma capsulatum Hormodendrum dermatitidis Mucor spp. Paectlomyces spp. Penicdhurn spp. a7-20 %.
bCardiosurgery.
Agent
Diagnosis
Phialophora mutabilis Saccharomyces spp. Trichosporon cutaneum
prosthetic valve endocarditisb
systenucmycosesc Candida albtcans glabrata guilhermondii krusei parapsilosis pseudotropicalis tropicalis
Clnfantsurgery.
Systemic Candida infections with very high mortality are very frequent in premature newborns. These mycoses depend on the course of birth, long-lasting intubation and parenteral nutrition, intravenous catheters (Karabinis et al. 1988; Wey et al. 1989) and immune defects. The most frequent agents are C. albicans, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis, C. pseudotropicalis, C. tropicalis.
2002
9
AGENTS OI: NOSOCOMIAL MYCOSES - - review
'109
DERMATOVENEROLOGY
The skin surface o f humans is resistant to fungal infections depending on fungistatically active free fatty acids and antagonistic bacterial flora. The damage of these factors, moisture, swollen cortical layer and traumas cause and often support the colonization. Pathogenic fungi appear upon changing medium, permitting long-lasting fungal colonization and multiplication of fungal pathogen (Table VII; cf. Jautov:~ et al. 2001). Table VII. Nosocomlal mycoses in dermatovenerology Agent
%a
Diagnosis
Candtda albtcans
95 95
candidosis intertriginosa candidosis genitoglutealis infantum, paronychia candidosa candida vulvovagimtis, candida balanitis, balanopostitis candidosis intertriginosa candidosis intertriginosa, paronychia candidosa candidosis intertriginosa candida vulvovaginitis candidosis in AIDS patients
70 -80 tropicalis parapsilosis guilliermondli glabrata albtcans B troptcalis kruset glabrata Malassezta furfur Cryptococcus spp. ttistop/asma spp. Coccid~oides spp. Aspergillus spp.
95 95 95 70 80 90
pityriasis versicolor nodules abscess abscess nodules
apercentage of occurrence.
10
NOSOCOMIAL
MYCOSES
IN D I F F E R E N T
C L I N I C S IN PLZEIq
We analyzed the nosocomial infections, their risk factors, clinical pictures and agents appearing in different clinics in the years 1990-97. Transplantations were the most frequent cause o f these diseases (Table VIII), and aspergilli were the most frequent agents after kidney, lung, heart and liver transplantations (Table IX). The range o f agents differed year from year (Table X), F u n g e m i a and abscesses were the most frequent clinical picture (Table XI). Besides, 103 cases of candidemia caused by 11 Candida spp. and I species o f Cryptococcus were observed in 1998-2000 (Table XII). REFERENCES
ALY R., BERGER T.: Common superficial fungal infections in patients with AIDS. C/in.Infect.Dis. 22, 128-132 (1996). ANDREMONTA., LANCARR., [.E N.A., 11ATTCt.EOUELJ.M., BARONS., TAVAKOLIT., DANIELM.F.: Secular trends in mortality associated with bloodstream infections in 4268 patients hospitalized in a Cancer Referral Center between 1975 and 1989. Clin. Mwroblol. Infect. I, 160-167 (1996). 13ODENW.E., FISHERA, MEDLITROSA., BENttAMJ., MCENAN','M.T.: Bioprosthetic endocarditis due to Cryptococcus neoformans. J.CardtovascSurg(Torino) 24, 164-166 (1983). BODEY G., BUEt.TMANNB., I)UGUIDW., GIBBS D., HANK H., HOTCttl M.: Fungal infections in cancer patients; an international autopsy survey. Eur d C/in M~crobloLInfect. Dts. I 1, 99-109 (1992). BROOK.SR.G.: Prospective study of Candida endophthalmais in hospitalized patients with candidemia. Archlntern.Med 149, 2226-2228 (1989). CALDERONER A., BRAUN P.C.: Adherence and receptor relationships of Candida albicans. Microbiol Rev. 55, 1-20 (1991). COI.I)ERWODDS.B., SWlNSKIL A, KARCIIMERA.W, WATERNAUXC.M., BUCKLEYM.J.: Risk factors for the development of prosthetic valve endocardltis Circulation 72, 31-37 (1985). COLEMAND.C, BENNETTD.C., SULIVAND J . GALLAOHERP.J., JIENMANM.C., SrtANEEYD.B.. RUSSELR.J.: Oral Candida in HIV inli:chon and AIDS: new perspectives - new approaches. Crtt.Rev.Mtcrobiol. 19, 61-82 (1993). DE I.ALLAF., VAGLIA A., FRANZETTIM., MANFRIN V., PELLIZZERG P., FABRIS P.: Cryptococcal pleural effusion as first indicator of AIDS: a case report Infection 21, 192 (1993). DORKO[-~.,KMETOV,~M., PILIPCINECE.. BRACOKOVAI., DORKOF , I)ANKOJ., ~VICK9E., TKACIKOVAE.: Rare non-albicans Candtda species detected mdtfferent clinical diagnoses Foha MicrobJol. 45, 364-368 (2000a).
110
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A TOMS[K()VA
Table VIII. Risk Ihctors ofnosocomial mycoses m 1990-97 Risk factor
1990
1991
1992
1993
1994
1995
1996
1997
+ +
+ .
+
5-
4-
+
4-
diseases Leukemia Diabetes mellitus AIDS Neutropenia Blood malignity Granulocytopenia Granulomatosis Cancer Ulcus Obstruction of urinary tract
* + +
* 4-
+
4+ +
4+
4.
+
+
+
+
-,other
Transplantation Prosthetic valves 9Peritoneal dialysis Immune defects Immunosuppression Intravenous drugs Burns Eye solution Abdomen surgery Chest surgery Heart surgery Urine catheter Hyperalimentation Intravenous catheter Trauma
+
factors
4-
+
t
4-
+
4-
4-
4-
4-
4-
+
+
+
+
4-
4-
+
4-
4-
4-
4-
4-
4-
+
4-
+ +
+
+
Table iX. Nosocomial mycoses and time of the occurrence of their agents after transplantation in 1990-91 Tissue
%
Tissue
%
Species
Kidney Hea~ Pancreas
15 20 25
Lung laver
30 50
C a n d t d a spp. C r y p t o c o c c u s spp. A s p e r g i l l u s spp.
Months 0-5.5 >6 0.5-6 (>6)
Table X. Occurrence of agents ofnosocomial mycoses in 1990-97 Agent
1990
Candida albicans dubliniensis
1991
1992
+
+
famala glabrata krusei lusitantae parapsilosis rugosa tropicalis utilts
+ +
+ +
1994
1995
1996
1997
+
+ +
~-
+
+ +
+
+ +
+ + + +
+
+ +
4
+
+
Cryptococcus neoformans laurentii
+
+ +
Hansenula anoma[a
+
fohmi Saccharomyces cerevtsiae Trichornonas b e t g e h i
+ +
Blastornyces capttis Rhodotorula rubra
1993
+
+
+ + +
+
A(iENTS OF NOSOCOMIAL MYCOSES - - revtew
2002
"1"11
T a b l e Xl. Clinical syndromes ofnosocomial mycoses in 1990-98 Syndrome mbsdess Candidemia Cholangitis Cholecystitis Colitis Dissemination Endocarditis Endophthalmitis Fasciitis Fungemias Granuloma Lung infiltration Meningitis Meningoencephahtis Mycotic aneurysm Myocarditis Necrotic cellulitis Esophagitis Osteoarthritis Osteomyel~lis Pericarditis Peritonitis Phaeohyphomycosis Pleuritis Pneumonia Prostatitis Sepsis Septic arthritis Septic thrombosis Septicemia Sinusitis Subdural e m p y e m a Tenosynovitis Zygomycosis
1990
1991
1992
t-
t
t
1993
1994
1995
1996
1997
+
,-
t
+
1998
+ + + + + + +
+ +
+ +
*
+
+ +
+
~-
+
+ +
+ +
+
+ + +
+ +
+ +
+
+ +
+
+ + + + + + + * + + +
+
+ +
+ + +
+
+ + + +
+
+ + +
+ +
+
+ +
+ +
+
+
T a b l e XII. Occurrence a and agents o f c a n d i d e m i a in 1 9 9 8 - 2 0 0 0 in Czech Republic Agent
%
Agent
%
Candtda albicans parapsdosts rnelinii troptcalis krusei claussenii
30 23 22
Candida guilliermondtt robusta reukaufif scottn kefyr Cryptococcus diffluens
I0 I0 8 5 3 3
15 15 I0
a 1 9 9 8 : 2 2 cases, 1999: 21, 2000: 60.
DORKO E., KME'I'OVA M., DORKO F., BRACOKOVA I., DANKO J., gVlCK'r E.. I'KACIKOVA E.: Prevalence of Cryptococcus neoformans in clinical specimens. Foha Microbiol. 45, 369 -372 (2000b). DORKO E., JEN(~A A., PILIP~'INEC E., DANKO J., gVICKY E., TK,~,~'IKOVA l~.: Candida-associated denture stomatitis. Folia Microbiol. 46, 443~146 (2001a). DORKO E., ZIBRIN M., JI-N~'A A., PILIP~'INEC E., DANKO J., TKA~'IKOVA L'.: The histopathologica[ characterization of oral Candida leukoplakias. Folia Mtcrobiol. 46, 447-451 (2001b). DORKO E., VIRAGOv,/~ S., JAUTOVA J., PII.IP~'INFC E., DANKO J., ~VlCKY E., TKA~'IKOVA [:.: Electrophoretic karyotyping of Candida albwans stratus isolated from premature m|'ants and hospital personnel in a neonatal intensive care unit. Foha Microbiol. 46, 453-457 (2001c)
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DORKO k., PII.IP('INI-C E.. MAIiEE M., VIRAGOVAS , BRA~'OKOVAl., DORKO F., gVt(TK~?E., DANKOJ., HOLODA E, ONDRA.~OVICM.. TKACIKOVAE.: Yeast-like microorganisms in eye infections. Folia Microbiol. 46. 147-150 (200 Id). (]ANGNEUX J.P., ['tANNEQUINC., I.ABASTIEM.M., DE CHAUVIB F.: ('gtndlda parapsdosts: une cause de plus en plus frequnte de lbngemie nosocomiale La Presse Med. 21. 1104 (1998). QRANINGEN W., PRESTERll. [-., SCHNEEWEISSB., TELEKY B., GEORGOPOULOSA.: Treatment of Candlda albtcans fungaemia with t]uconazole..l.lnJect. 26. 133-146 (1993). HAJJEH R.A., BL.t;MBERG H.M.: Bloodstream infection due to Trichosporon beigeht in a burn patient. Case report and review of therapy. Clin. Infect. Dis. 20, 913-916 (1995). HALPERN m., SZABO S., IiOCHBERG E., ]-IAMME'R(].S., LIN J., GURTMAN A.C., SACKS t1.8., SHAPIROR S , HIRSCHMAN S.Z.: Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome Amer.J.Med. 92, 437-440 (1992). HUNDERSON DK., EDWARDSJ.E., [SttlDA K, GUZI" L B. Experimental hematogenous Candida endophthalmms diagnostic approaches lnfect.hnmun, 23, 858-861 (1979) HITCHCKOK R.J [., PALLETA., HALt. M.A., MOI.ONE P S J : Urinary tract candidiasis in neonates and infants. Rev.lnfect.Dts. 7, 630640 (1985) J A U T O V A J . VIRAGOvAS . ONDRA.~OVL("M, HOLOD,', E. Incidence of Candtda species isolated from human skin and nails: a survey. l-oha Micro&ol. 46, 333 337 (200l). JEMMI M, JEMI-GI.tARBI ]t.. ZORGL'i A., JLIDI R., JEMMI L.: Abscds renal el perirenal et obstructmn du tractus urmaire d'origine lbngique ~i Torulopsts glabrata, a.d'UroL 98, 50-52 (1992). KARABINIS A., ]JILl. C.. [.ECI.ERQ C., TANCREDE C., BAUME D., ANDRE-MONT A.: Risk factor for candidemia in cancer patients: a case-control study, a'.Clin. Mtcrobiol. 26,429-432 (1988). KUNTZEJ.R.. HERMANNM.II., EVANSS.G.: Genitourinary coccidioidomycosis. J. Urol. 140, 370 (1988). MAYER K.H., SC}tOENBAUM S.C.: Evaluation and management of prosthetic valve endocarditis. Progr.Cardiovasc.Dis. 25, 43-54 (1982). MIRDHA B.R., SETHI S.. BAgERJEE N.: Prevalence of fungal species with l't,nguria. Indian .I.Med.Res. 107, 90-93 (1998). MONTERO A.. COtIEN .I.E, FERNANDEZM.A., MAZZOLINI(3., GOMEZC.R., PERUGINIJ.: Cerebral pseudoallescheriasis clue to Pseudoallerscherla boydu as the first manifestation of AIDS. Clin.lnfect.Dts. 26, 1476-1477 (1998). PENDLEBURG W.W., PI-RI_ D.P., MUNOZ D.G.: Multiple microabscesses in the central nervous system: a clinico-pathologic study. .J.NeuropathoL ExpNeurol. 48, 290-300 (1989). SOBEL JD., KAUFFMANC.A., MCKINSEY D., ZERVOS M., VAZQUEZJ.A., KARCtIMER A.W., LEE J., THOMAS C., DISMUKF.SW.E.: Candiduria: a randomized, double-blind study of treatment with t'luconazole and placebo. Clm.lnfect.Dls. 30. 19-24 (2000). SOt.OMKIN J.S., MILS E.L., GIEBING G.S., NE_L_SONR.D., SIMMONS R.L., QUBC P.G.: Phagocytosis of Candtda albicans by human leucocyte: opsonic requirements. J.Infect.Dis. 13"I, 30-37 (1985). TRUBENOVAD., VIRAGOVAS., PILIP~'INECE., DANKOJ., ~V[CK'9 E., I'K,/~r E.: Candidaemia in cancer patients and in children in a neonatal intensive care unit. Fofia Mmrobiol. 46, 161-164 (2001). WE',' S.B., MORI M., PFALLERM.A., WOOLSO~ R.F Hospital acquired candidemia. The attributable mortality and excess length of stay. Arch.lntern.Med. 148. 2642 (1988). WISE G.J., KOZINNP.J., GOLDBERGP.: Flucytosine in the management of genitourinary candidiasis: 5 years of experience. J. Urol. 124, 70-72 (1980). WINGARD J.R.: Importance of Candida species other than C. albicans as pathogens in oncology patients. Clin.lnfect. Dis. 20, 115-125 (1995).