Bille, J.

Cajot, A.

Crave, J. P.

Glauser, M. P.

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806The sampleswerethen mounted on aluminum stubs and sputter-coated with gold.For comparison, tissue-culture cellswithout spirochetes weresimilarlyprepared. Also, spirochetesgrownin BSKII alone weregentlydrawn down on a 0.2 um milliporefilter and the filter wasprocessedfor scanningelectronmicroscopyas above (figure lA).In each instance, spirochetes could be seen attached to most(figure IB),but not all, of the cellsgrownin tissueculture.Highermagnification revealed that the spirochetes usually appeared asintertwined pairs at the host cell surface (figure Ie), and theywere easily distinguished from the surface features of culturedcells that were not inoculated with spirochetes (figure ID). Wedid not observethe spirochetesassociated with small round bod-ies on the cell surface as reported with the spirochete-tick cellcultures[7].Wehaveestablishedconditionsthat allowthe B burg-dorferi spirocheteto growand attach to mammalian cellsin vitro.This is the first step in the design of experiments for studyingthe parameters of attachment and the mechanismsof spirochetepathogenicity in mammalian cells.KARIM E. HECHEMY, WILLIAM A. SAMSONOFF,MARY McKEE, JOSEPH M. GUTTMANWadsworth Center for Laboratories and Research,New York State Department of Health. AlbanyReferencesI. Christensen GO, Simpson WA, Beachy EH. Microbial adherence ininfection. In: Mandell GL, Douglas RG, Bennett XX, eds. Princi-Correspondencepies and practices of infectious diseases. New York, John Wiley &Sons, 1985:6-232. SteereAC, Malawista SE, Bartenhagen NH, Spieler PN, Newman JH,Rahn OW, Hutchinson GJ, Green J, Snydman DR, Taylor E. Theclinical spectrum and treatment of Lyme disease. YaleJ Bioi Med1984;57:453-4563. Burgdorfer W, Barbour AG, HayesSF, Benach JL, Grunwaldt E, DavisJP. Lyme disease-a tick-borne spirochetosis? Science 1982;216:1317-13194. Benach JL, Fleit HB, Habicht GS, Coleman JL, Bosler EM, Lane BP.Interactions of phagocytes with the Lyme disease spirochete: roleof the Fc receptor. J Infect Dis 1984;150:497-5075. Fumarola D, Cedola MC, Guanti G, Matsuura A, Uede T, Jirillo E.Adherence of Lymediseasespirochetes to rat lymphocytes. ZentralblBakteriol Mikrobiol Hyg [Aj 1986;263:146-1506. Peterson PK, Clawson CC, LeeDA, Garlich OJ, Quie PG, JohnsonRC. Human phagocyte interactions with the Lymediseasespirochete.Infect Immun 1984;46:608-6117. Kurtti TJ, Munderloh UG, Ahlstrand GG, Johnson RC. Borrelia burg-dorferi in tick cell culture: growth and cellular adherence. J MedEntomol 1988;25:256-2618. Benach JL, Coleman JL, Garcia-Mono JL, Deponte PC. Biologicalactivity of Borrelia burgdorferi antigens. In: Benach JL, Bosler EM,eds. Lyme disease and related disorders. New York: Ann NY AcadSci 1988;539:115-1259. Madin SH, Darby NB Jr. Established kidney cell lines of normal adultbovine and ovine origin. Proc Soc Exp BioI Med 1958;98:574-57610. Barbour AG. Isolation and cultivation of Lyme disease spirochetes.Yale J Bioi Med 1984;57:521-555THE JOURNAL OF INFECTIOUS DISEASES. VOL. 159, NO.4. APRIL 1989© 1989 by The University of Chicago. All rights reserved. 0022-1899/89/5904-0042$01.00Single-Dose Therapy for Oral Candidiasis withFluconazole in HIV-Infected Adults: A Pilot StudyCOLLEAGUES-Oral candidiasis isa commonproblemin neoplasticdiseases, after prolonged antibiotic therapy, or in the aged, de-bilitated patient, but most cases are now seen in human immu-nodeficiencyvirus (HIV)-infected patients [I, 2]. In this setting,the infection is especially difficult to treat: topical antifungalsare unpalatable, only partially effective,and relapsesafter treat-ment are generally observed. Systemic ketoconazole representsan efficient alternative, but hepatic toxicity [3]and the possibil-ity of drug interaction with other medications frequently takenby these patients, like zidovudine, are of concern.Fluconazole, (Pfizer, Zurich) is a novelbis-triazoleantifungalagent exhibitingthe followingfavorable pharmacokinetic prop-erties:(1)goodabsorption after oral administration(85010 bioavail-This study was approved by the Research Ethics Committee of theDepartment of Internal Medicine at the Centre Hospitalier UniversitaireVaudois, Lausanne, and written informed consent was obtained from allsubjects who received fluconazole.Fluconazole was supplied by Pfizer, Fluelastrasse 7, 8048 Zurich, Swit-zerland.Please address requests for reprints to Dr. M. P. Glauser, Division ofInfectious Diseases, Centre Hospitalier Universitaire Vaudois, 1011Lausanne, Switzerland.ability), (2) long plasma half-life (30 h), (3) low-plasma proteinbinding (11 010) with a rapid distribution in tissue fluids such assaliva,and (4) predominantly renal excretion(60010) [4J.Prelimi-nary experience in 95 patients with oropharyngeal candidiasisshowed the drug was effectiveand well tolerated when given asa 50 mg capsule once daily for a median period of 9 d [5]. How-ever, the above-mentioned pharmacokinetic properties suggestthat a single-dosetreatment could be effective. Wetested this hy-pothesisin an open, noncomparativestudy in HIV-infected adultspresenting with oral candidiasis.From I October 1987, all HIV-positive adults presentingat ourinstitution with oral candidiasis wereproposed a singleoral doseof 150mg fluconazole as sole treatment. Patients with mouthsymptoms (pain, burning, and dryness) and characteristic signs(raisedconfluentwhitepatcheson a hyperemic base)were includedif the swab culture of the lesions showed ~1O Candida coloniesafter inoculation on a whole Sabouraud agar plate at bedside.Eligiblepatients took a 150mg fluconazole capsule under di-rect medical supervision and were seen again on days 4, 7, and14-21and then once a month (within the framework of an ongo-ing AIDS cohort study). The culture was repeated on days 7 and14-21.The clinical response was defined by the total disappear-ance of signsand symptoms, and the microbiologic response bythe disappearanceof Candida on culture,or a drop of two gradesor more on a four-grade semiquantitative culture scale (table I).Correspondence 807Table 1. Clinical and microbiological evolution. didiasis. The clinical response persisted in 22 (96070) of 23 pa-tients on day 7, in 16(73070) of 22 on days 14-21,and in 11 (52070)Patient (no. of 21 on day 42;2 patients died from other complications of theirprevious epi- Day 14-21 Day 42 HIV infection. A microbiologic response was documented in 20sodes oral Day 0 Day 7 (87070) of 23 patients on day 7, and persisted in 9 (41070) of 22candidiasis Clinical Clinical on days 14-21 (table I). Among the 10 patients in whom signswithin 6 mo) Culture" Culture" relapse Culture* relapse and symptoms recurred, the free interval after the administra-1 (2) 4 1 no 2 no tion of fluconazole was 6-33 d (median: 18 d).2 4 0 yes 3 ND In this observation, the successrate for a single-dosetreatment3 (6) 3 0 yes 3 ND of oral candidiasis with fluconazole was 100070 at day 4, but signs4 3 0 no 3 no and symptoms recurred in 10 patients during the study period.5 (2) 4 4t ND ND ND Seven had one or more episode of oral candidiasis during the6 4 2 no 2 no previous 6 mo, and six had AIDS. However,all responded again7 (5) 3 0 no 3 no to a second 150mg dose of fluconazole. The drug was welltoler-8 3 0 yes 3 ND ated in all patients, and no hepatic, renal, or hematologic side9 (I) 3 1 no 3 yes effects were observed. Among the 23 patients, 18were enrolled10 3 0 no 0 no in a prospectivezidovudine postmarketing surveillanceprogram,11 4 0 no 3 no and fluconazoledid not appear to be associatedwith suchzidovu-12t 3 0 dine toxicityas granulocytopenia or anemia. As plasma drug levels13 (7) 2 1 yes 3 ND werenot measured, the possibilityof subclinicalinteractioncould14t 3 3 no 3 not be excluded.The correlation betweenthe culture and the clin-15 3 2 no 1 no ical responsewasweakafter day 7: An increasingnumber of Can-16 (1) 3 0 no 0 yes dida upon semiquantitative cultures wasnot predictiveof a clini-17 4 0 no 1 no cal relapse.Culture was helpful only for the initial confirmation18 (3) 3 0 no 2 yes of the clinical diagnosis.19 (3) 3 0 yes 3 ND Single-dose fluconazole oral therapy for oropharyngeal can-20 3 0 no 2 no didiasis was easy to administer, effective, and well tolerated in21 4 1 no I no our limited pilot study. This therapeutic approach might avoid22 3 0 no 0 yes continuous treatment in patients in whom advancedimmunosup-23 3 I no 1 no pression induces frequent relapsesand is of special interest whenketoconazole cannot be used.NOTE. No patients had clinical relapse on day 4. ND = no J. P. CRAVE, A. CAlor, J. BILLE, M. P. GLAUSERanalysis after first relapse. Division of Infectious Diseases, Department of Internal* 0 = no growth, I = 1-9 Candida colonies, 2 = 10-19colo- Medicine and Institute of Microbiology, Centre Hospitaliernies, 3 = ~ 20 colonies, 4 = confluent growth.t Patient 5 had clinical relapse on day 7. Universitaire Vaudois, Lausanne, Switzerlandt Died during study period.ReferencesWedescribe data from the first 31 patients. Three patients re-fused the protocol. One patient was excluded because she hadpruritus and urticaria while receiving ketoconazole for a previ-ous episode,whichrecurredwith a questionableangioedemasoonafter ketoconazole was givenagain; thus she wasconsidered im-idazole intolerant. Four others werelost to follow-up. Among the23 evaluable patients, 15 had AIDS,S had AIDS-related com-plex(ARC), and 3 had no symptom of HIV infection before thisepisode. Nine had suffered one or more episodes of oral candidi-asis within the previous 6 mo.On day 4, no patients had signs and symptoms of oral can-I. Warner LC, Fisher BK. Cutaneous manifestations of the acquired im-munodeficiency syndrome. Int J Dermatol 1986;25:337-3502. Kaslow RA, Phair JP, Friedman HB, Lyter D, Solomon RE, DudleyJ, Polk BF, Blackwelder W. Infection with the human immunodefi-ciency virus: clinical manifestations and their relationship to immunedeficiency. Ann Intern Med 1987;107:474-4803. Tabor E. Hepatotoxicity of ketoconazole in men and in patients under50. N Engl J Med 1987;316:1606-16074. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on newtriazoles. Antimicrob Agents Chemother 1988;32:1-85. Farrow PR, Brammer KW, Feczko JM. Fluconazole: a new treatmentfor oropharyngeal candidiasis in AIDS and malignancy [abstract 949].In: Program and abstracts of the 27th Interscience Conference onAntimicrobial Agents and Chemotherapy. New York: American So-ciety for Microbiology, 1987

Single-Dose Therapy for Oral Candidiasis with Fluconazole in HIV-Infected Adults: A Pilot Study

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