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Increased Incidence of Vulvovaginal Candidiasis Caused

Increased Incidence of Vulvovaginal Candidiasis Caused

Jpn. J. Infect. Dis., 54, 1031107, 2001

Original Article lncreased Incidence of Vulvovaglnal Caused by glabrata in Jordan

Khaled H. Abu-Elteen*

Department of Biological Sciences, Faculo, of Science, Hashemite University, PO.Box 330077- Zarqa 13133, Jordan

(Received May 28, 2001. Accepted July 16, 2001)

SUMMARY: Due to the rislng Importance Of and other non-albicans Candida as prlnCiple human opportunistic , 356 Women with abnormal vaglnal discharge who attended a prlVate Obstetrics and gynecology clinic in Amman, Jordan, between January 1 999 and February 2001 were examined･ The isolation rate of Candida spp･ from high-vaglnal swabs was 44･9%･ CHROMagar Candida and conventional mycologlCal methods identified six isolated Candida spp., including C. albicans, C. glabrata, C. tropicalis, C･ parapsilosis, C･ krusei, and C･ kefyr･ The percentages of C･ albicans, C･ glabrat.a, and C･ tropicalis isolates were 43･1%, 32･5%, and 8･ 1%, respectively･ C･ albicans was isolated in combinatlOn With C･ tropicalis and C･ krusei in two patients･ Statistical analysts Of the present results clearly show an increase in the incidence of vulvovaglnal candidiasis caused by C. glabrata in the two study periods, 199411996 and 1999-2001 (P- 0･0186)･ In contrast, Comparlng the proportions of vulvovaglnal candidiasis caused by C･ albicans in the two periods, there was no slgnificant difference･ These results may have slgniflCant Clinical implications, as C･ glabrata are innately less susceptible to most agents than C･ albicans; these findings support viewing this organism as a major .

(15-18). INTRODUCT10N Several studies have suggested that血e increased丘equency Vaginal candidiasis is a widespread, Common disease ofvulvovaglnal candidiasis is caused by non-albicans Candida affecting a substantial proportion of women of childbearlng spp･ (19-21)･ One such study demonstrated that the propor- age ( 1 )A The pathogenFsis of this frequent clinical problem, tion Ofvulvovaglnal candidiasis cases caused by non-albicans however, remains elusIVe, and its incidence can be expected Candida spp. rose from 9.9% in 1988 to 17･2% in 1995 (20)I to continue rislng, aS risk factors are not diminishing. While Evidence regarding the selectivity of these , especially approximately 75% of women experience a slngle episode of C･ glabrata, comes from HIV-seropositive women receivlng

Candida vaglnitis in their lifetime, a slgni丘cant percentage of fluconazole (4); the yaginalflora in w?men receiving women (5-7%) experience recurrent (2-4)･ Candida fluconazole shifts to an lnCreaSe in absolute Isolation rates of albicans is responsible for 80194% of vulvovaglnal candidi- C. glabrata, but with low attack rates of clinical (22)･ asis (5), the remaining cases being due to other Candida spp･ A number of investlgatOrS have emphasized the role of such as C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, species other than C. albicans as emergent pathogens in and C. keji,r (5). In recent years, the incidence in the human urinary tract candidal infection (23 ,24). A dramatic increase population of infection with human virus in the carriage Of C. glabrata has also been demonstrated in (HIV), organ transplantation, Widespread and increased use dentate individuals over 80 years of age; the proportion of of immunosuppressive therapy together with broad-spectrum individuals with dentures carrylng C. glabrata in one study

antimycotic therapy have血amatically increased the incidence was greater than 50% (25). Because of differences in their of candidiasis caused by C. glabrata and other non-albicans susceptibility agalnSt Certain ant血ngal dmgs, changes in the Candida spp. (6- 10). C. glabrata represents the second-most &equency and distribution of Candida spp･ are of great inter- common Candida spp. causing bloodstream infection (7,9, 1 1 ). est. We, therefore, felt that it would be ofvalue to assess the

It accounts fわr 8% of all cases of candidemia involving frequency of isolation of various Candida spp･from Jordanian patients with cancer (12), 13% of cases involving non- women with abnormal vaginal discharge during the period of neワtrOPenic patients (13,14), and 1 1% of cases involving 1 999-200 1 and to compare these results with those obtained patlentS With candidemia (7). Nosocomial during the period 1994-1996･ caused by C. glabrata have increased substantially, while yeast infections caused by C. albicans have decreased according MATERIALS AND METHODS to a Universlty OHowa Hospltals and Clinics study between the years 1987-1988 and 1993-1994 (9). Moreover, Wingard Study subjects: High-vaglnal swabs were collected from et al. (15) noted an increase in colonization with C･ glabrata 356 women (aged between 1 8-52) attending obstetrics and among bone-marrow transplant recIPlentS glVenfluconazole gynecology clinics in Amman, Jordan with variable degrees as an antifungal prophylactic drug. Furthermore, C･ glabrata of abnormal vaglnal discharge between January 1999 and accounts for 75% offungemia cases among patients receivlng February 2001. After slgnlng an informed consent to carry out the procedure, each patient completed a questionnaire *Co汀eSpOnding author: Fax:+962-6-4 1 28772, E-mail: Salma@ about age, work, use of contraceptlVeS, history of pelvic

hu. edu.j o inflammatory disease, history of , and theuse of topical

loョ antifungal agents and/or . The gynecologlCal history most frequent associations of the vulvovaglnal symptoms

and examination of subjects, noted vulvovaglnal symptoms were leuko汀hea (36.6%), buming sensation (25.3%), and (leukorrhea, buming sensation, itching, dysuria, dyspareu- dysuria (I 9.7%), as presented in Table 3･ The Table also shows nia), and the type (mucous, creamy, lumpy, foamy), as yell that the percentages of patients manifesting one, two, or three as the presence or absence of odor of the vaglnal secretlOnS symptoms ofvulvovaglnitis were 21 ･3%, 27･8%, and 25･2%,

were also reported. respectively. Bumlng Sensation and leuko汀hea were the Isolation and identification of Candida spp.: A sample of vaginal material (posteriPr fomiX) was obtained with the aid of a sterile plain cotton-tlpped swab and was immediately Table 1. Prcvalcncc ofvulvovaglnalinfcctions among women inoculated into Sabouraud dextrose broth (Difco, Detroit, according to age

Mich., USA) Containing 50 mgL~t ofchloramphenicol. Tubes Age (years) No. cxamincd No. infcctcd % infbctcd

were incubated at 300C fわr up to 48 h, and were then cultured lヽJ ltJ I 1 ≦19 68 1 tJ 7 4 2 5 5 42 0 6 L 1 00 00 00 into Sabouraud Dextrose agar (SDA) and CHROM a甲r (CA) 20-29 65

(CHROM agar, Paris, France). Following inoculatlOn, the 30-40 1 25 culture plates were incubated in air at 300C and were inspected ≧41 98 daily fわr a total or 7 days. All yeast isolates observed on CA were identified by colony morphology and pigmentation Tbta1 3 56 according to the manufacturer's instructions and as has been

previously described (26). Isolates from CA and SDA plates Table 2. Proportion ofvulvovaglnal candidiasis caused by diffcrcnt were identified according to their morphologleS On COmmeal Candida spp. during 1994-1996 and I999- 2001 agar (CMA), their formation of germ tube in serum, and, for Number of culture-positive (%) isolates that were chlamydospore negative and/or gem-tube CandL-da spp. 1994-I 996 1 999-2001 negative, the results of conventional biochemical and assimila- tion tests camied out according to established procedures (27). 40 (51.3) 69 (43.1) ln cases where identification was ambiguous, the Apt 20C Candt'da glabrata 14 (17.9) 52 (32.5) system (bioMerieux SA, Lyon, France) was employed. Candida lropicalis 10(12.8) 13 (8.I) Statistical analysis: The slgnificance of differences in 2 (2.6) 6 (3.8) CandL'da kruseL' 5 (6.4) 1 1 (6.9) prevalence rates was evaluated using 2 X 2 contingency tables with the chi-square test; values ofP < 0.05 Were considered Candida kqbr 5 (6.4) 9 (5.6) statistically slgnificant. Candida guilliermondii 2 (2.6) ND

Tbta1 78 (100) 160 (100)

RES UIXS ND- Not detect()d

A total of 356 Women with variable degrees of abnomal vaglnal discharge were examined between January 1 999 and Table 3. Association of symptoms observed in positive cases of February 2001･ Ofthese, 160 women (44･9%) were y?ast- yeast infections culture positive. The prevalence of vulvovaglnal infectlOnS No. of symptoms claimed S ymptoms Pcrc cn ta苦c in the 30-40 years age group was 56.8%, followed by by the patients patients of the 20-29 ye?rs age group (50･8%) (Table 1)･ The Asymptom ati c prevalence of vulvovaglnal infections at ≧40 and ≦ 1 9 years One symptom D 4 0 3 7 5 2 L 3 2 3 4 6 3 L 2 4 3 2 4 3 4 2 7 2 8 4 8 2 2 6 6 9 4 ｣ 2 ｣ ｣ 2 4 6 2 4 was 4 1.8% and 22. 1 %, respectively. Based on statistical analysts Dys of the results, a slgnificant difference between age groups

30-40 and ≦19 and age groups 30-40 and ≧40 in the number L of vulvovaginal infections (P - 0.000 and 0.0266, respec- a tively) was established. Furthermore, there was no significant Two symptoms 1-D difference between age groups 30-40 and 20-29 in the number 1-Dys ofvulvovaginal infections (P - 0.43). トB Distribution of Candida spp.: Using the manufacturer's L-D guidelines fわr CA Candida and published criteria by Odds L-Dys and Bemaerts (26), We were able to identify the following L-I species: C. albicans, C. glabrata, C. tropicalis, C. krusei, and a-L C. parapsilosis on the basis of colony color. However, there D-B was no difference in the sensitivityofCA and SDA. There was Three symptoms D-I-Dys a lOO% correlation between CA and the Apt test for identiflCa- LD-Dys tion of C. albicans, C. tropicalis, and C. krusei, and 88% for L-D-a identification of C. glabrata and C. parapsilosis (confirmed L-D-1 by Apt test)･ A single-ye.a.st species was cultured from 160 L-Dys-1 patients in the culture-posltlVe population. C. albicans was the L_1-B most frequent isolate, accountlng for 43. 1% of all isolates, B-D-I while C. glabrata and C. tropicalis accounted for 32.5% and B-D-Dys

8･ 1% of isolates, respectively (Table 2)･ Furtherヮore, C･ Four symptoms 1-良-D-L 10.5 albicans was isolated in combination with C. krusel and C The data reprcsentthe percentage of total positive cases observed tropicalis in two cases. in the infected women. B: bunllng Sensation, D: dysuria, Dys:

Symptoms associatedwith vulvovaginal infections: The dyspareunia, I: itching, L: leuko汀hea.

104 symptoms most frequently complained of by the patients others (26,32), who felt that further Tethods were required during the clinical examination; they accounted fわr 23% for confirmation of C. glabrata identlty･ of symptoms, followed by itching and leukorrhea (17･6%)･ C. albicans was isolatedfrom 43. 1 % of the culture-positive Asymptomatic cases and cases with more than three symp- patients, followed by C. glabrata 32.5%, and C･ tropicalis toms accounted fわr 15.2% and 10.5%, respectively, of all 8. 1 % patients; these results are consistent with仇ose presented patients (Table 3). previousy (29). The high isolation rate of C･ glabrata from Trends invulvovaginal infections caused by yeast species: high-vaginal swab specimens has been reported by others Table 2 shows the frequency distribution of Candida spp･ ln (7,8,10,20,34). In fact, depending on the site of infection, C. yeast-positive patients during two study periods ( 1 994- 1996 glabrata is often the second or third most common cause of and 1999-2001); C. albicans was the most common species candidiasis after C･ albicans (7)･ Howeyer, more recent among the isolates identified to the species level during the epidemiologlCal studies showed a mycologlCal shift from C･ two study periods. Overall, the proportion ofvulvovaglnal yeast albicans to non-albicans Candida spp. such as C. glabrata, infections caused by C. albicans decreased from 5113% in C. tropicalis, C. parapsilosis and C. krusei (6,9, I 5, 1 7,20,35)･ 1994-1996 to 43.1% in 1999-2001. ln contrast, the occurrence Spinillo et al. (20) showed that the proportion of vulvovaginal of C. glabrata was found to increase from 17･9% in 1994- candidiasis cases caused by non-albicans Candida spp. rose 1996 to 32.5% in 1999-2001. Statistical analyses indicated from 9.9% in 1988 to 17.2% in 1995. All of these studies that in the period 1994-1996 there was a statistically slgnifi- have found that C. glabrata has risen in incidence, and cant difference between the proportion of vulvovaglnal researchers have suggested that the use of nuconazole may candidiasis caused by C. albicans and by C･ glabrata (P - have contributed to the increase in the isolation of C glabrata 0.000). Furthermore, there was no significant difference and the decrease in C. albicans isolation. Vazquez et al. (34) between C. albicans and C. glabrata during the 1999-2001 reported that within 6 months of initiation offluconazole study period (P - 0.05). On the other hand, the proportions prophylaxis, the isolation of C. albicans decreased by 60%, of vulvovaglnal candidiasis caused by C. albicans during while the isolation of C. glabrata was >70% higher in the t.wo study periods (1994-1996 and 1999-2001) showed patients asslgnedfluconazole than in those asslgned placebo･ no slgnificant difference. There was a significant difference; These results are similar to those reported by other investlga- however, in the proportions of vulvovaglnal candidiasis tors (4,9,24). C. glabrata is of special importance because of caused by C･ glabrata in the twp study periods (P - 0101 86), its imate resistance to antifungal agents, specifically to indicatlng a marked increase ln Vulvovaglnal candidiasis (3,7-9,36,37). The specific mechanisms ofantifungal resistance caused by C. glabrata between the periods 199411996 and to the class of antifungal agents are not yetfullyunder- 199912001. The isolation rate of C. krusei remained at stood. In C. glabrata, several mechanisms of azole resistance approximately 6.4%; rates of C. tropicalis isolation were have been identified: increased P-450-dependent ergosteroI 12.8% and 8.1% in the 1994-1996 and 1999-2001 periods, synthesis and an energy-dependent emux pump offluconazole, respectively. Other Candida spp. causlng aS follows: fewer r!ossibly via.a multi-azole cross-resistance (8,34)･ The statis- than 10. 1% ofall vulvovaglnal infections during the two study tlCal analysis Of data obtained in the present study clearly periods were C. parapsilosis, 3.4%; C･ kefyr 5･9%, and C･ shows an increase in血e incidence ofvulvovaglnal candidiasis guilliermondii Ol 8%･ caused by C. glabrata between the periods 1994-1996 and 1999-2001, With the results agreelng Well with those of the above-mentioned studies. DISCUSSION This study has also revealed that the symptoms most During the past two decades, several investlgatOrS have frequently complained of by the majority Of women with a reported that the frequency of yeast infections, especially with positive culture for yeast are leukorrhea, a burnlng Sensa- the Candida spp., has increased dramatically (9, 1 0,29)･ This tion, itching, and dysuria. Willmott (38) found that symptoms, increase has been accompanied by an increase in the number particularly vaglnal irritation, Were reported by over half of of Candida spp. recognized to cause disease (6,7,10,16,23)･ patients having yeast-containlng Vaglnal cultures･ Geiger et In this study, yeast was recovered from 160 (44.9%) of the al. (39) showed that abnomal discharge was less丘equent in 356 patients with variable degrees of abnormal vaglnal women with symptomatic vaglnitis due to C. glabrata than to discharge. These flndings agree with the observations reported C. albicans, which may reflect the effects ofa lack ofhypha by other investlgatOrS that yeast can be recovered in the range fomation by the C. glabrata blastoconidia (8, 1 0)･ Vaginitis of5-53.3% in healthy women (29,30). The highest infection due to C. glabrata was reported to be the main indolent rate (56･8%) was detected among woヤen in the 30-40 age with reduced inflammation and hence less dyspareunia (39). group, which represents the most actlVe Sexual age･ The Moreover, patients with C. glabrata vaglnitis frequently incidence of vulvovaglnal yeast infections decreased in older reported a buming sensation rather than itching (2,8,39)･ age groTps (1,5)･ The results presented indicate that the frequency of C･ ConsIStent With previous findings (26,3 1 -33), there was glabrata vaglnitis has increased from 17･9% in 1994-1996 to no difference in the sensitivlty Of CA and SDA･ We were 32.5% in 1 999-2001. The described increase in the occu汀enCe able to identifyto the species level 100% of the isolates of C. of C･ glabrata and other non-albicans Candida spp･ occurred albicans, C. hlOPicalis,and C. kT7iSei on CA, which confirms the some years after the introduction offluconazole as a prophyl results of other studies (26,3 1 -33). Isolates of C. glabrata, the lactic agents f♭r use by patients with vulvovaglnal candidiasis･ second-most common yeast isolated in our suⅣey, presented more difficulties. Dark pink-purple colonies with a pale edge ACKNOWLEDGMENTS were usually C. glabrata, but 12% (confirmed by API 20C) did not present enough constant definitive colonial features The technical assistance provided by Mr. M. Ghaleb is on CA. The results of this study confirmthe difficulties with greatly appreciated. I would like to thank Dr･ Ali Z･ Elkami C. glabrata identification encountered with CA reported by for critically reading the manuscrlPt･

105 This study was partially supported by the Hashemite Agents Chemother., 37, 1 847-1849.

University Research Council. 1 6. Abi-Said, D., Anaissie, E., Uzun, 0., Ra且d, 1., Pinzcowski, H. and Vartivarian, S. (1997): The epidemiology of hematogenous candidiasis caused by different Candida REFERENCES species. Clin. Infect. Dis., 24, 1 12211 128.

1. Sobel, ∫. D. (1992): Pathogenesis and treatment of 17. Price, M. F., LaRocco, M. T. and Gentry,し. 0.(1994): recurrentvulvovaglnal candidiasis. Clin. Infect･ Dis., 14 Fluconazole susceptibilities of Candida species and (Suppl.), S148-S153. distribution of species recovered from cultures over 2. Giraldo, P., Yon Nowaskonski, A., Gomes, F. A., Linhares, a 5-year period. Antimicrob. Agents Chemother., 38, 1., Neves, N. A. and Witkin, S. S. (2000): Vaginal coloni- 1422-1424. zation by Candida in asymptomatic women with and 18. Rex, J. H., Rinaldi, M. G. and Pfaller, M. A. (1995): without a history of recurrent vulvovaglnal candidiasis. Resistance of Candida species tofluconazole.Antimicrob. Obstet. Gyneco1., 95, 413-416. Agents Chemother., 39, 1-8. 3. Ringdahl, E. N. (2000): Treatment of recurrent vulvovagi- 19. Sinofsky, F. E. (1999): Vulvovaginal candidiasis: topical nal candidiasis. Am. Fan. Phys., 61, 3306-3312. versus oral therapy. The Female Patient, 24, 19-23･

4･ Sobel, J･ D･ (1999)･ Limitatioヮs ofantifungal agents in 20. Spinillo, A., Capuzzo, E., Gulminetti, R･, Marone, P･,

the treatment of Candida vaglnitis: future challenges. Colonna,し. and Piazzi, G. (1997): Prevalence of and Drug Resist. Updates, 2, 148-152. risk factors for fungal vaglnitis caused by non-albicans 5. Odds, F. C. (1988): Candidiasis of the genitalia. p.124- species. Am. ∫. Obstet. Gyneco1., 176, 138-141.

135. J〃 F.C. Odds (ed.), Candida and Candidosis. A 21. Sobel, ∫. D., Faro, S., Force, 良., Foxman, 良., Ledger, W. Review and Bibliography, 2nd ed., Balliere-Tindal, J., Nyirjesy, P. R., Reed, B. D. and Summers, P. R. (1998): London. Vulvovaglnal candidiasis: epidemiologic, diagnosis, and 6. Knoke, M., Schulz, K. and Bernhardt, H. (1997): the therapeutic considerations. Am. J･ Obstet･ Gyneco1., Dynamics of Candida isolationsfrom humansfrom 1 9921 178, 203-211. 1995 in Greifswald, Germany. Mycoses, 40, 105-I 10. 22. Schuman, P., Capps, L and Peng, G. (1997): Weekly 7. Pfaller, M. A. (1996): Nosocomial candidiasis: emerging fluconazole for the treatment of mucosal candidiasis in species, reservoirs, and modes. Clin. Infect. Dis., 22, women with HIV infection. A randomized, double blind, Supp1., 89-94. placebo controlled trial.Ann. Intern. Med., I 26, 689-696. 8. Fidel, P. L., Vazquez, J.A.and Sobel, J. D. (1999): Candida 23. Hazen, K. C., Theisz, G. W. and Howelly, S. A. (1999): glabrata: review of epidemiology, pathogenesis, and Chronic urinary tract infection due to Candida utilis. J. clinical disease with comparison to C. albicans. Clin. Clin. Microbio1., 37, 824-827.

Microbiol. Rev., 12, 80-96. 24. Febre, N., Silva, V, Medeiros, E. A. S., Wey, 良., Colombo, 9. Berrouane, Y. F., Herwaldt, L A. and Pfaller, M. A. (1999): A･ L･ and Fisclman, 0･ (1 999): Microbiological character- Trends in antifungal use and epidemiology ofnosocomial istics of isolated from urinary tracts of intensive yeast infTectionsina universityhospital. J. Clin. Microbiol., care unlt Patients undergolng urinary catheterization. J. 37, 531-537. Clin. Microbio1., 37, 1584-1586. 10. Hazen, K. C. (1995): New and emerging yeast species. 25. Lockhart, S. R., Joly, S., Vargas, K., Swails-Wenger, J., Clin. Microbiol. Rev., 8, 462-478. Enger, L･ and Soll, D･ R･ (I 999)= Natural defenses P!ainst ll. Nguyen, M. H., Peacock, J. E" MomiS,A. J., Tanner, D. Candida colonization breakdown in the oral cavltleS Of

C., Nguyen, M. L., Snydman, D. R., Wagener, M. M., the elderly. ∫. Dent. Res., 78, 857-868. Rinaldi, M. G. and Yu, V. L. (1996): The changing face 26. Odds, F. C. and Bemaerts, R. (1994): CHROMagar of candidemia: emergence of non-Candida albicans Candida, a new differential isolation medium for

species and antifungal resistance.Am. J. Med., 100, 6 I 7- presumptlVe identi丘cation of clinically important Candida 623. species. ∫. Clin. Microbio1., 32, 1923-1929. 12･ Wingard, J･ R. (1995): Importance of Candida species 27. Warren, N. G･ and Hazen, K･ C. (1995): Candida, CTWtO-

other than C. albicans as pathogens in oncology patients. cocc〟∫, and other yeasts of medical importance. p 723- Clin. Infect. Dis., 20, 115-125. 737. In P. R. Murray, E. J. 0. Baron, M. A. Pfaller, F. C.

13･ Rex, J･ H･, Bennett, J. E., Sugar,A. M., Pappas, P. G., van Tenover and 良. H. Yolken (eds), Manual of Clinical der Horst, C. M., Edwards, ∫. E., Washbum, R. G., Scheld, .American SocietyofMicrobiology, Wash- W. M., Karchmer, A. W., Dine, A. P., Levenstein, M. J. ington, D.C. and Webb, C. D. (1994): A randomized trial comparing 28･ Pfaller, M･ A･ (1989): Infection. control: Opportunistic nuconazole with for the treatment of fungal infections-the increasing Importance Of Candida

candidemia in patients without . N. Engl. ∫. species. Infect. Control Hosp. Epidemiol., 1 0, 2701273. Med., 331, 1325-1330. 29. Abu-Elteen, K. H., Abdul-Malek, A. M. M. andAbdul- 14･ Rex, J. H., Pfaller, M. A., Barry,A. L., Nelson, P. W. and Wahid, N･ A･ (1997): Prevalence and susceptibility of Webb, C. D. (1995): Antifungal susceptibility testing of vaglnal yeast isolates in Jordan. Mycoses, 40, 179-185. isolatesfrom a randomized, multicenter trial offluconazole 30. Al-Rawi, N. and Kavanagh, K. (1999): Characterization

versus amphotericin 良 as treatment of non-neutropenic of yeasts implicated in vulvovaglnal candidiasis in Irish patients withcandidemia.Antimicrob. Agents Chemother. , women. Br. ∫. Biomed. S°i., 56, 99-104. 39, 40-44. 31. Houang, E. T. S., Chu, K. C., Koehler,A. P. and Cheng, 15. Wingard, ∫. 良., Merz, W G., Rinaldi, M. G., Miller, C. B., A. F. B. (1997): Use ofCHROMagar Candida for genital

Karp, J･ E･ and Saral, R. (1993):Association of Torulop- specimens in the diagnostic laboratory･ ∫. Clin. Patho1., sis glabrata infections withfluconazole prophylaxis in 50, 563-565. neutropenic bone ma汀OW transplant patients. Antimicrob. 32. Ainscough, S. and Kibbler, C. C. (1998): An evaluation

106 of the cost-effectiveness of using CHROMagar for yeast Intem. Med., 160, 2659-2664. identification in a routine microbiology laboratory. J. 36. Kronvall, G. and Karlsson, 1. (2001): Fluconazole and Med. Microbio1., 47, 623-628. multidisk testlng Of Candida species for 33. Pfaller, M. A., Houston, A. and Coffmann, S. (1996): disk test calibration and MIC estimation. ∫. Clin. Application of CHROMagar Candida for rapid screen- Microbio1., 39, 1422-1428. lng Ofclinical specimens for Candida albicans, Candida 37. Chang, H. C., Chang, J. J., Chan, S. H., Huang,A. H., tropicalis, , and Candida (Torulopsis) Wu, T.し., Liれ, M. C. and C血ang, T. C. (2001): Evalua- glabrata. J. Clin. Microbio1., 34, 58-61. tion of Etest for direct antifungal susceptibility testing 34. Vazquez, ∫. A., Sobel, ∫. D., Peng, G., Steele-Moore,し, ofyeasts in positive blood cultures. ∫. Clin. Microbio1., Schum.an, P･, Holloway, W･ and Neaton, J･ D･ (1999): 39, 1328-1333. EvolutlOn Of vaginal Candida species recovered from 38. Willmott, F. E. (1975): Genital yeasts in female patients

human immunodeficiency virus-infected women receiv- attending a VD clinic. Br. ∫. Vener. Dis., 51, 119-122. lng nuCOnaZOle prophylaxis: the emergence of Candida 39. Geiger,A. M., Foxman, B. and Sobel, ). D. (1995): Chromic glabrata. Clin. Infect. Dis., 28, 1025-1031. vulvovaglnal candidiasis: characteristics of women with 35. Abbas, ∫., Bodey, G. P., Hanna, H. A., Mardani, M., Candida albicans, Candida glabrata, and no Candida. Girgawy, E., Abi-Said, D., Whimbey, E., Hachem, 良. Genitourin. Med., 7 1, 304-307. and Raad, I. (2000): Candida krusei . Arch.

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