Notes
Efficacy of Oral Fluconazole in the Treatment of AIDS Associated Oesophageal Candidiasis S. D e Wit, D. U r b a i n , E Rahir, D. W e e r t s , N. C l u m e c k *
To assess the efficacy and tolerance offluconazole in the treatment of oesophageal candidiasis, 47 A I D S patients with this infection were enrolled in an open prospective study using fluconazole 100 nag given orally once daily. Clinical cure was obtained in all of 41 evaluable patients, with confirmation o f cure in all of 31 patients who underwent post-treatment oesophagoscopy. Forty patients Were followed up for at least 30 days; n o n e suffered a relapse of oesophagitis but seven had a recurrence of stomatitis which was effectively treated with fluconazole. Flueonazole was well tolerated. Nausea was noted in three patients one of w h o m interrupted therapy: Transient mild elevation of A L T / A S T was noted in five of 41 patients (12 %). Fluconazole appears to be a safe and effective agent for oral therapy of oesophageal candidiasis associated with AIDS.
.Oesophageal candidiasis accounts for 11% of all infections occurring in AIDS patients in the USA. It is one of the most frequent findings among African and Haitian AIDS patients (1-4). There is no universal recommendation concerning treatment of AIDS-associated candida oesophagitis. Ketoconazole and clotrimazole are widely used in AIDS patients but their efficacy has not been extensively studied. Severe cases have been treated With amphotericin B but intravenous administration and serious side effects make this therapy unsatisfactory (5, 6). Fluconazole is a new bis-triazole antifungal drug which differs markedly from other imidazoles in its pharmacokinetic properties. It has been shown to be more active than ketoconazole in the treatment of oropharyngeal candidiasis associated with HIV infection (7, 8).
Divisionof InfectiousDiseases,St. Pierre UniversityHospital, Rue Haute 322, B-1000 Brussels, Belgium.
Vol. 10. No. 6
503
We present here the results of an open prospective study evaluating the efficacy of fluconazole in AIDS patients with candida oesophagitis. Patients and Methods. During an 18-month period, all HIV seropositive adult patients with signs or symptoms suggesting oesophageal candidiasis were evaluated. Patients were eligible for the study if the infection was endoscopically and microscopically confirmed with histological evidence of tissue invasion. They were not enrolled if they were taking any other systemic antifungal drug, had moderate or severe liver disease, or had known sensitivity and/or a previous severe adverse hepatic reaction to imidazoles.
Patients were given 100 mg fluconazole once daily at the same time each day for a minimal duration of two weeks. Signs and symptoms resulting from the oesophageal infection were recorded at entry. In-patients were reviewed daily after the start of treatment while in hospital. Out-patients or patients discharged from hospital while still on treatment were reviewed weekly and at the end of treatment. Signs and symptoms were assessed and recorded as at the pre-treatment assessment. Clinical assessment of the response to treatment was graded as clinical cure, improvement or failure. Clinical cure was defined as complete disappearance of complaints (i.e. dysphagia, odynophagia). Whenever possible, a follow-up oesophagoscopy was performed to confirm disappearance of mucosal lesions. Follow-up visits with clinical assessment took place weekly after completion of therapy. Blood was taken before treatment, and weekly during treatment and follow-up to determine complete blood and platetet counts and serum chemistry values. Side effects were recorded at all examinations, including follow-up. A n y chemically significant abnormalities of laboratory tests were monitored until values returned to normal or until the reason for the abnormality had been determined. Treatment was discontinued if AST or ALT levels increased threefold or more. Results and Discussion. Forty-seven patients were enrolled (30 males; 17 females; 34 Caucasians, 13 blacks; mean age 37 years, range 21-66 years). Oesophageal candidiasis was the first manifestation of AIDS in 13 of the 47 patients. Twentyseven patients had had previous oropharyngeal candidiasis nine of whom had also had oesophageal candidiasis. None of the patients had received corticosteroids during the four weeks before diagnosis. Oesophageal candidiasis was
504
confirmed by oesophagoscopy and microscopy in all patients. Two patients died of other opportunistic infections during fluconazole therapy. Four patients were lost to follow-up. Thus a total of 41 of the 47 patients could be evaluated at the end of treatment. The mean duration of therapy in the 41 patients was 19 days (range 11-28 days). This wide range of duration is due to the fact that the first patients enrolled were treated for four weeks. The duration was shortened in the next patients. Clinical cure was obtained at the end of therapy in all 41 patients (100 %). Ten patients refused to undergo posttreatment oesophagoscopy. Disappearance of the mucosal lesions was confirmed in all other 31 patients. Forty patients could be monitored during a follow-up period of one month. No relapse of oesophageal candidiasis was observed. Seven patients (17.5 %) suffered a recurrence of oropharyngeal candidiasis after a mean period of 25 days (range 13-30 days). All patients were retreated with fluconazole and cured. Fluconazole was well tolerated except in three patients who complained of upper gastrointestinal tract disturbances (nausea, vomiting), leading to interruption of treatment in one patient after 11 days' of therapy. Transient elevation (less than three times baseline values) of ALT/AST levels was noted in five patients (12 %). Oral oesophageal candidiasis is the most common fungal infection in HIV infected patients and is predictive of progressive immunosuppression (5). Despite the high frequency of this manifestation, no universal recommendations for treatment have been made until now. The efficacy of topical antimycotics is considered to be ihsufficient. Oral ketoconazole (200-400 mg per day) or clotrimazole (30-50 mg per day) have generally been successful, although recurrence is frequent. ParenteraI amphotericin has been considered as the most effective treatment but is generally indicated only in refractory cases (5, 6, 9). Treatment failures with ketoconazole have been reported. This could be due to resistance of some Candida albicans strains but has also been linked to drug malabsorption due to reduction of gastric secretion in patients with AIDS. Due to its dibasic structure, ketoconazole absorption is grossly impaired under hypochlorhydric conditions (10-12). Fluconazole is a new orally and intravenously administered antifungal triazole whose pharmacokinetic properties differ markedly from those of other imidazoles, in particular ketoconazole. It is
Eur. J. Clin. Microbiol. Iilfect. Dis.
considerably less lipophilic and more water soluble than other azoles. Oral absorption is rapid and high (> 90 %), and remains unaffected by food. In a prospective double-blind non-crossover study comparing fluconazole (5(I mg orally once daily) with ketoconazole (200 mg orally once daily) in the treatment of oropharyngeal candidiasis in patients with A R C and AIDS, fluconazole was significantly more effective than ketoconazole (8). Fluconazole (100-200 mg daily) has been shown to be effective in the treatment of candideal oesophagitis in H I V patients but these open studies involved small numbers of patients (13; EM. Gritti et al., A. Gil et al., 5th International Conference on AIDS, 1989, Abstracts MBP96 and MCP71). Our study involving 41 evaluable patients confirms that fluconazole is highly effective in treating oesophageal candidiasis associated with AIDS. Recurrence of candidiasis has been shown to be common after ketoconazole or other antifungal treatment. Our results indicate a high rate of relapse of stomatitis after fluconazole (17.5 % during a one month follow-up). This suggests that the deep-seated infection was cured and that oral reinfection probably occurred afterwards. Fluconazole was well tolerated and surveillance did not show any clinically relevant adverse effects except in one patient who stopped treatment because of nausea. This is in accordance with previous findings indicating that minor gastrointestinal signs and symptoms and asymptomatic elevation of hepatic e n z y m e s occur in less than 5 % of fluconazole recipients (14). The mean duration of treatment was 19 days (range 11 to 28 days). Clinical improvement is generally observed after less than five days of treatment, suggesting that the duration of treatment could be shorter than that we used. In fact, fluconazole has been shown to be effective in a single dose of 150 mg for oral thrush and 400 mg for oesophageal candidiasis in a small number of patients (15; J.R Chave et al., 5th International Conference on AIDS, 1989, Abstract ThBP319). Further studies should compare single dose therapy with therapy of one or two weeks' duration.
References
i. Selik RM, Slarcher E'I, Curran JW: Oppor|unistic discases reported in AIDS patients: frequencies, ttssociations, trends. AIDS 1988, 1: 175-182.
Vo1.10,1991
2. De Wit S~ Hermans P, Roth D, Van Laethem Y, Clumeck N: Natural history of HIV infection in African patients. In: Giraldo G, Beth-Giraldo E, Clumeek N, Gharbi RM, Kyalwazi SK, de Thd G (ed): Second International Symposium on AIDS and Associated Cancers in Africa, Naples 1987. Karger, Basel, 1988, p. 114--123. 3. Plot P, Quinn TC, Taehnan H, Feinsod FM, Milangu KB, Wobin O, Mbendi N, Mazebo P, Ndangi K, Stevens W, Kalambayi K , Mitchell S, Bridts C, McCormick JB: Acquired immanodefieicney syndrome in a heterosexual population in Zaire. Lancet 1984, it: 65-69. 4. Pape JW, Liautaud B, Thomas F, Mathurin JR, St. Amand MMA, Boney M, Pean V, Pamphile M, Laroche AC, Dehovitz J, Johnson WD: The acquired immunodeficiency syndrome in Haiti. Annals o[ Internal Medicine 1985, 103: 674-678. 5. Glatt AE, Chirgwin K, Landesman SH: Treatment of infections associated with human immunodcficicncy virus. New England Journal of Medicine 1988, 318: 1439-1448. 6. Young LS: Treatable aspects of infection due to human immunodeficiency virus. Lancet 1987, it: 1503-1506. 7. De Wit S, Clumeck N: Fluconazol¢ ill the treatment of fungal infections associated with AIDS. Infection 1989, 17: 121-123. 8. De Wit S, Weerls D, Goossens H, Clumeck N: Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet 1989, i: 746748. 9. Connolly GM, Hawkins D, ltarcourt-Webster JN, Parsnns PA, Husain OAN, Gazzard BG: Ocsophagcal symptoms, their causes, treatment, and prognosis in patients with the acquired immunodcficicncy syndrome. Gut 1989, 30: 1033-1039. 10. Tavitian A, Raufman JP, Rosenthal LE, Weber J, Webher CA, Dincsoy HP: Ketoconazo[e-resistant candida esophagitis in patients with acquired immunodeficiency syndrome. Gastroenterology 1986, 91): 443-445. 11. Lake-Bakaar G, Quadros E, Beidas S, Elsakr M, Tom W, Wilson DE, Dincsoy HP, Cohen P, Straus EW: Gastric secretory failure in patients with the acquired immunodeficiency syndrome. Annals of Internal Medicine 1988, 109: 502-504. 12. Lake-Bakaar G, Tom W, Lake-Bakaar D, Gupta N, Beidas S, Eisakr M, Straus E: Gastropathy and kctoconazole malabsorption in the acquired immunodeficiency syndrome. Annals of Internal Medicine 1988, 109: 471--473. 13. Ityams KC, Escamilla J, Papadimos T J, Garcia Gonzales P, Lnzada R, Maeareno E, Bonilla N, Diaz Marlinez F: New triazole antifungal agents (fluconazole and itraconazole) in the treatment of HIV-relatcd gastrointestinal candidiasis. Scandinavian Journal of Infectious Diseases 1989, 21: 355-356, 14. Saag MS, Disnmkes WE: Azole antifungal agents: emphasis on new triazolcs. Antimicrobial Agents and Chemotherapy 1988, 32: 1-8. 15. Chave JP, Cajot A, Bille J, Glauser MP: Single-dose therapy for oral candidiasis with fluconazolc in H1Vinfected adults: a pilot study. Journal of Infectious Diseases I989, 159: 806-807.
505
Leuconostoc Species as a Cause of Bacteremia: Two Case Reports and a Literature Review J . C . L . B e r n a l d o d e Q u i r 6 s 1 . , E M u f i o z 1, E . C e r c e n a d o 1, T. H e r n a n d e z S a m p e l a y o 2, S. M o r e n o 1, E. B o u z a 1
Two n e w cases o f significant b a c t e r e m i a c a u s e d by L e u c o n o s t o c spp. are r e p o r t e d and five others d e s c r i b e d ill the literature are reviewed. F o u r o f the s e v e n p a t i e n t s w e r e u n d e r o n e y e a r old a n d p r e s e n t e d with p r o l o n g e d d i a r r h e a r e l a t e d t o gastrointestinal disorders. T h e r e m a i n i n g t h r e e patients w e r e o v e r 50 y e a r s o f a g e and being t r e a t e d in intensive c a r e units. Six p a t i e n t s h a d n o s o c o m i a l l y a c q u i r e d c a t h e t e r - r e l a t e d bacteremia. L e u c o n o s t o c spp. a r e naturally resistant to v a n c o m y c i n , and five patients h a d received this antibiotic for prior b a c t e r e m i a c a u s e d by methicillin-resistant staphylococci. T h e m a j o r i t y o f patients p r e s e n t e d with f e v e r w i t h o u t severe c o m plications. Penicillin is the t r e a t m e n t o f choice and there is no r e p o r t o f any d e a t h directly attributable to infection by these m i c r o o r g a n i s m s . I n f e c t i o n with L e u c o n o s t o c spp. s h o u l d be susp e c t e d i f " v a n c o m y c i n - r e s i s t a n t s t r e p t o c o c c i " are isolated f r o m the b l o o d , a n d r e c o r d e d as a p o t e n tial cause o f b a c t e r e m i a in patients with indwelling i n t r a v e n o u s catheters.
Leuconostoc spp. are g r a m - p o s i t i v e coccobacilli which b e l o n g to the lactic acid b a c t e r i a g r o u p (t). T h e y are used in industrial m i c r o b i o l o g y in the p r o d u c t i o n of wine, dairy p r o d u c t s and d e x t r a n s (2). T h e y are naturally resistant to v a n c o m y c i n since the cell wall fails to p r o v i d e a target for this antibiotic (1). A l t h o u g h they have occasionally b e e n isolated f r o m vaginal and stool samples (3), Leuconostoc spp. are not a regular part of the norreal h u m a n flora. Leuconostoc spp. are not generally c o n s i d e r e d to be a h u m a n p a t h o g e n (4), but s p o r a d i c cases of p n e u m o n i a (5, 6), meningitis (7), infection of peritoneal dyalisis fluid (8), and b a c t e r e m i a (5, 6, lServicio de Mierobiotogfa Clinfca, and 2Servicio de Pcdiatria, Hospital General "Gregorio Marafidn", e/Dl: Esquerdo 46, 28007 Madrid, Spain.
Efficacy of Oral Fluconazole in the Treatment of AIDS Associated Oesophageal Candidiasis S. D e Wit, D. U r b a i n , E Rahir, D. W e e r t s , N. C l u m e c k *
To assess the efficacy and tolerance offluconazole in the treatment of oesophageal candidiasis, 47 A I D S patients with this infection were enrolled in an open prospective study using fluconazole 100 nag given orally once daily. Clinical cure was obtained in all of 41 evaluable patients, with confirmation o f cure in all of 31 patients who underwent post-treatment oesophagoscopy. Forty patients Were followed up for at least 30 days; n o n e suffered a relapse of oesophagitis but seven had a recurrence of stomatitis which was effectively treated with fluconazole. Flueonazole was well tolerated. Nausea was noted in three patients one of w h o m interrupted therapy: Transient mild elevation of A L T / A S T was noted in five of 41 patients (12 %). Fluconazole appears to be a safe and effective agent for oral therapy of oesophageal candidiasis associated with AIDS.
.Oesophageal candidiasis accounts for 11% of all infections occurring in AIDS patients in the USA. It is one of the most frequent findings among African and Haitian AIDS patients (1-4). There is no universal recommendation concerning treatment of AIDS-associated candida oesophagitis. Ketoconazole and clotrimazole are widely used in AIDS patients but their efficacy has not been extensively studied. Severe cases have been treated With amphotericin B but intravenous administration and serious side effects make this therapy unsatisfactory (5, 6). Fluconazole is a new bis-triazole antifungal drug which differs markedly from other imidazoles in its pharmacokinetic properties. It has been shown to be more active than ketoconazole in the treatment of oropharyngeal candidiasis associated with HIV infection (7, 8).
Divisionof InfectiousDiseases,St. Pierre UniversityHospital, Rue Haute 322, B-1000 Brussels, Belgium.
Vol. 10. No. 6
503
We present here the results of an open prospective study evaluating the efficacy of fluconazole in AIDS patients with candida oesophagitis. Patients and Methods. During an 18-month period, all HIV seropositive adult patients with signs or symptoms suggesting oesophageal candidiasis were evaluated. Patients were eligible for the study if the infection was endoscopically and microscopically confirmed with histological evidence of tissue invasion. They were not enrolled if they were taking any other systemic antifungal drug, had moderate or severe liver disease, or had known sensitivity and/or a previous severe adverse hepatic reaction to imidazoles.
Patients were given 100 mg fluconazole once daily at the same time each day for a minimal duration of two weeks. Signs and symptoms resulting from the oesophageal infection were recorded at entry. In-patients were reviewed daily after the start of treatment while in hospital. Out-patients or patients discharged from hospital while still on treatment were reviewed weekly and at the end of treatment. Signs and symptoms were assessed and recorded as at the pre-treatment assessment. Clinical assessment of the response to treatment was graded as clinical cure, improvement or failure. Clinical cure was defined as complete disappearance of complaints (i.e. dysphagia, odynophagia). Whenever possible, a follow-up oesophagoscopy was performed to confirm disappearance of mucosal lesions. Follow-up visits with clinical assessment took place weekly after completion of therapy. Blood was taken before treatment, and weekly during treatment and follow-up to determine complete blood and platetet counts and serum chemistry values. Side effects were recorded at all examinations, including follow-up. A n y chemically significant abnormalities of laboratory tests were monitored until values returned to normal or until the reason for the abnormality had been determined. Treatment was discontinued if AST or ALT levels increased threefold or more. Results and Discussion. Forty-seven patients were enrolled (30 males; 17 females; 34 Caucasians, 13 blacks; mean age 37 years, range 21-66 years). Oesophageal candidiasis was the first manifestation of AIDS in 13 of the 47 patients. Twentyseven patients had had previous oropharyngeal candidiasis nine of whom had also had oesophageal candidiasis. None of the patients had received corticosteroids during the four weeks before diagnosis. Oesophageal candidiasis was
504
confirmed by oesophagoscopy and microscopy in all patients. Two patients died of other opportunistic infections during fluconazole therapy. Four patients were lost to follow-up. Thus a total of 41 of the 47 patients could be evaluated at the end of treatment. The mean duration of therapy in the 41 patients was 19 days (range 11-28 days). This wide range of duration is due to the fact that the first patients enrolled were treated for four weeks. The duration was shortened in the next patients. Clinical cure was obtained at the end of therapy in all 41 patients (100 %). Ten patients refused to undergo posttreatment oesophagoscopy. Disappearance of the mucosal lesions was confirmed in all other 31 patients. Forty patients could be monitored during a follow-up period of one month. No relapse of oesophageal candidiasis was observed. Seven patients (17.5 %) suffered a recurrence of oropharyngeal candidiasis after a mean period of 25 days (range 13-30 days). All patients were retreated with fluconazole and cured. Fluconazole was well tolerated except in three patients who complained of upper gastrointestinal tract disturbances (nausea, vomiting), leading to interruption of treatment in one patient after 11 days' of therapy. Transient elevation (less than three times baseline values) of ALT/AST levels was noted in five patients (12 %). Oral oesophageal candidiasis is the most common fungal infection in HIV infected patients and is predictive of progressive immunosuppression (5). Despite the high frequency of this manifestation, no universal recommendations for treatment have been made until now. The efficacy of topical antimycotics is considered to be ihsufficient. Oral ketoconazole (200-400 mg per day) or clotrimazole (30-50 mg per day) have generally been successful, although recurrence is frequent. ParenteraI amphotericin has been considered as the most effective treatment but is generally indicated only in refractory cases (5, 6, 9). Treatment failures with ketoconazole have been reported. This could be due to resistance of some Candida albicans strains but has also been linked to drug malabsorption due to reduction of gastric secretion in patients with AIDS. Due to its dibasic structure, ketoconazole absorption is grossly impaired under hypochlorhydric conditions (10-12). Fluconazole is a new orally and intravenously administered antifungal triazole whose pharmacokinetic properties differ markedly from those of other imidazoles, in particular ketoconazole. It is
Eur. J. Clin. Microbiol. Iilfect. Dis.
considerably less lipophilic and more water soluble than other azoles. Oral absorption is rapid and high (> 90 %), and remains unaffected by food. In a prospective double-blind non-crossover study comparing fluconazole (5(I mg orally once daily) with ketoconazole (200 mg orally once daily) in the treatment of oropharyngeal candidiasis in patients with A R C and AIDS, fluconazole was significantly more effective than ketoconazole (8). Fluconazole (100-200 mg daily) has been shown to be effective in the treatment of candideal oesophagitis in H I V patients but these open studies involved small numbers of patients (13; EM. Gritti et al., A. Gil et al., 5th International Conference on AIDS, 1989, Abstracts MBP96 and MCP71). Our study involving 41 evaluable patients confirms that fluconazole is highly effective in treating oesophageal candidiasis associated with AIDS. Recurrence of candidiasis has been shown to be common after ketoconazole or other antifungal treatment. Our results indicate a high rate of relapse of stomatitis after fluconazole (17.5 % during a one month follow-up). This suggests that the deep-seated infection was cured and that oral reinfection probably occurred afterwards. Fluconazole was well tolerated and surveillance did not show any clinically relevant adverse effects except in one patient who stopped treatment because of nausea. This is in accordance with previous findings indicating that minor gastrointestinal signs and symptoms and asymptomatic elevation of hepatic e n z y m e s occur in less than 5 % of fluconazole recipients (14). The mean duration of treatment was 19 days (range 11 to 28 days). Clinical improvement is generally observed after less than five days of treatment, suggesting that the duration of treatment could be shorter than that we used. In fact, fluconazole has been shown to be effective in a single dose of 150 mg for oral thrush and 400 mg for oesophageal candidiasis in a small number of patients (15; J.R Chave et al., 5th International Conference on AIDS, 1989, Abstract ThBP319). Further studies should compare single dose therapy with therapy of one or two weeks' duration.
References
i. Selik RM, Slarcher E'I, Curran JW: Oppor|unistic discases reported in AIDS patients: frequencies, ttssociations, trends. AIDS 1988, 1: 175-182.
Vo1.10,1991
2. De Wit S~ Hermans P, Roth D, Van Laethem Y, Clumeck N: Natural history of HIV infection in African patients. In: Giraldo G, Beth-Giraldo E, Clumeek N, Gharbi RM, Kyalwazi SK, de Thd G (ed): Second International Symposium on AIDS and Associated Cancers in Africa, Naples 1987. Karger, Basel, 1988, p. 114--123. 3. Plot P, Quinn TC, Taehnan H, Feinsod FM, Milangu KB, Wobin O, Mbendi N, Mazebo P, Ndangi K, Stevens W, Kalambayi K , Mitchell S, Bridts C, McCormick JB: Acquired immanodefieicney syndrome in a heterosexual population in Zaire. Lancet 1984, it: 65-69. 4. Pape JW, Liautaud B, Thomas F, Mathurin JR, St. Amand MMA, Boney M, Pean V, Pamphile M, Laroche AC, Dehovitz J, Johnson WD: The acquired immunodeficiency syndrome in Haiti. Annals o[ Internal Medicine 1985, 103: 674-678. 5. Glatt AE, Chirgwin K, Landesman SH: Treatment of infections associated with human immunodcficicncy virus. New England Journal of Medicine 1988, 318: 1439-1448. 6. Young LS: Treatable aspects of infection due to human immunodeficiency virus. Lancet 1987, it: 1503-1506. 7. De Wit S, Clumeck N: Fluconazol¢ ill the treatment of fungal infections associated with AIDS. Infection 1989, 17: 121-123. 8. De Wit S, Weerls D, Goossens H, Clumeck N: Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet 1989, i: 746748. 9. Connolly GM, Hawkins D, ltarcourt-Webster JN, Parsnns PA, Husain OAN, Gazzard BG: Ocsophagcal symptoms, their causes, treatment, and prognosis in patients with the acquired immunodcficicncy syndrome. Gut 1989, 30: 1033-1039. 10. Tavitian A, Raufman JP, Rosenthal LE, Weber J, Webher CA, Dincsoy HP: Ketoconazo[e-resistant candida esophagitis in patients with acquired immunodeficiency syndrome. Gastroenterology 1986, 91): 443-445. 11. Lake-Bakaar G, Quadros E, Beidas S, Elsakr M, Tom W, Wilson DE, Dincsoy HP, Cohen P, Straus EW: Gastric secretory failure in patients with the acquired immunodeficiency syndrome. Annals of Internal Medicine 1988, 109: 502-504. 12. Lake-Bakaar G, Tom W, Lake-Bakaar D, Gupta N, Beidas S, Eisakr M, Straus E: Gastropathy and kctoconazole malabsorption in the acquired immunodeficiency syndrome. Annals of Internal Medicine 1988, 109: 471--473. 13. Ityams KC, Escamilla J, Papadimos T J, Garcia Gonzales P, Lnzada R, Maeareno E, Bonilla N, Diaz Marlinez F: New triazole antifungal agents (fluconazole and itraconazole) in the treatment of HIV-relatcd gastrointestinal candidiasis. Scandinavian Journal of Infectious Diseases 1989, 21: 355-356, 14. Saag MS, Disnmkes WE: Azole antifungal agents: emphasis on new triazolcs. Antimicrobial Agents and Chemotherapy 1988, 32: 1-8. 15. Chave JP, Cajot A, Bille J, Glauser MP: Single-dose therapy for oral candidiasis with fluconazolc in H1Vinfected adults: a pilot study. Journal of Infectious Diseases I989, 159: 806-807.
505
Leuconostoc Species as a Cause of Bacteremia: Two Case Reports and a Literature Review J . C . L . B e r n a l d o d e Q u i r 6 s 1 . , E M u f i o z 1, E . C e r c e n a d o 1, T. H e r n a n d e z S a m p e l a y o 2, S. M o r e n o 1, E. B o u z a 1
Two n e w cases o f significant b a c t e r e m i a c a u s e d by L e u c o n o s t o c spp. are r e p o r t e d and five others d e s c r i b e d ill the literature are reviewed. F o u r o f the s e v e n p a t i e n t s w e r e u n d e r o n e y e a r old a n d p r e s e n t e d with p r o l o n g e d d i a r r h e a r e l a t e d t o gastrointestinal disorders. T h e r e m a i n i n g t h r e e patients w e r e o v e r 50 y e a r s o f a g e and being t r e a t e d in intensive c a r e units. Six p a t i e n t s h a d n o s o c o m i a l l y a c q u i r e d c a t h e t e r - r e l a t e d bacteremia. L e u c o n o s t o c spp. a r e naturally resistant to v a n c o m y c i n , and five patients h a d received this antibiotic for prior b a c t e r e m i a c a u s e d by methicillin-resistant staphylococci. T h e m a j o r i t y o f patients p r e s e n t e d with f e v e r w i t h o u t severe c o m plications. Penicillin is the t r e a t m e n t o f choice and there is no r e p o r t o f any d e a t h directly attributable to infection by these m i c r o o r g a n i s m s . I n f e c t i o n with L e u c o n o s t o c spp. s h o u l d be susp e c t e d i f " v a n c o m y c i n - r e s i s t a n t s t r e p t o c o c c i " are isolated f r o m the b l o o d , a n d r e c o r d e d as a p o t e n tial cause o f b a c t e r e m i a in patients with indwelling i n t r a v e n o u s catheters.
Leuconostoc spp. are g r a m - p o s i t i v e coccobacilli which b e l o n g to the lactic acid b a c t e r i a g r o u p (t). T h e y are used in industrial m i c r o b i o l o g y in the p r o d u c t i o n of wine, dairy p r o d u c t s and d e x t r a n s (2). T h e y are naturally resistant to v a n c o m y c i n since the cell wall fails to p r o v i d e a target for this antibiotic (1). A l t h o u g h they have occasionally b e e n isolated f r o m vaginal and stool samples (3), Leuconostoc spp. are not a regular part of the norreal h u m a n flora. Leuconostoc spp. are not generally c o n s i d e r e d to be a h u m a n p a t h o g e n (4), but s p o r a d i c cases of p n e u m o n i a (5, 6), meningitis (7), infection of peritoneal dyalisis fluid (8), and b a c t e r e m i a (5, 6, lServicio de Mierobiotogfa Clinfca, and 2Servicio de Pcdiatria, Hospital General "Gregorio Marafidn", e/Dl: Esquerdo 46, 28007 Madrid, Spain.
