212
Letters to the Editor
among psoriatics mean that the benefits of prophylaxis usually outweigh its risks. 6 Nevertheless, psoriatics should be warned of the risk when considering travel to malarious areas and whenever antimalarials are prescribed. Such drugs should be given to them only when essential. Affected psoriatics should seek dermatological help urgently, since topical treatment usually controls these exacerbations. 1.4 Exacerbation of psoriasis is not among side-effects reported with the new antimalarial mefloquine hydrochloride, but the risks are probably similar to those of other chloroquine-tike drugs.
Department of Dermatology, Level 4, Lauriston Building, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh E H 3 9 Y W , Scotland, U.K.
I. 2. 3. 4. 5. 6.
J . P . Vestey J. A. Savin
References Abel EA, DiCicco LM, Orenberg EK, Fraki JE, Farber EM. Drugs in exacerbation of psoriasis. J Am Acad Dermatol 1986; I5: lOO7-1o22. Ziprkowski L, Haim S, Bank H. Atabrine in psoriasis, zqcta Med Orient 1954; I3: 45-52. Mallett R, Pye R. Risks and benefits of prophylactic antimalarial drugs. Br Med J 1989; 299 : 14oo Kuflik EG. Effect of antimalarial drugs on psoriasis. Curls 198o; 26: 153-155. Katugampola G, Katugampola S. Chloroquine and psoriasis. Int J Dermatol 199o; 29: 153-154. Breckenridge A. Risks and benefits of prophylactic antimalarial drugs. BrMedJI989; 299: I057-IO58.
C o s t i m p l i c a t i o n s o f a l t e r n a t i v e t r e a t m e n t s for A I D S p a t i e n t s w i t h cryptococcal meningitis
Accepted for publication 15 August I99I Sir, T h e article by Buxton et al., 1 is interesting but misleading in one respect. A major distinction should have been drawn in the abstract between the effectiveness of fluconazole for maintenance therapy after amphotericin B primary therapy, and its effectiveness as p r i m a r y therapy. T h e r e is little doubt that fluconazole is a drug of choice for maintenance therapy of cryptococcal meningitis in A I D S , if preceded by amphotericin B (with or without flucytosine)fl' a It is effective, non-toxic and cost effective. T h i s is not necessarily true when fluconazole is used for primary therapy. Buxton et al., failed to reference a randomised study supported by Pfizer in which fluconazole was markedly inferior to amphotericin B (0"7 m g / k g / d a y ) combined with flucytosine (four of 14 fluconazole treated patients died, compared with none of six treated with amphotericin B. 4 I n a large, as yet unpublished study, 5 comparing fluconazole with amphotericin B without flucytosine, the interim results indicated no difference between the treatments, but both regimens were successful in only 40 % of the patients. T h i s is a poor overall result, suggesting that both regimens (fluconazole 200-400 m g daily or amphotericin B 0"5-0"6 m g / k g / d a y without flucytosine) are suboptimal. T i m e to sterilisation of C S F was delayed in the fluconazole group. It is thus misleading to the readership to suggest that fluconazole is ' a t least as effective as amphotericin B ' . It is either as effective or less effective for p r i m a r y therapy.
Letters to the Editor
2][ 3
Various poor prognostic factors in first-episode cryptococcal meningitis in A I D S have been identified. These include a low C S F white cell count ( < 20 × lO3/1), C S F cryptococcal antigen reciprocal titre > 256, a low serum sodium and positive extraneural cultures. These poor prognostic factors have not, however, been consistent from study to study. Nevertheless, more severely ill patients should receive amphotericin B, probably with flucytosine, as primary therapy. Those with a more favourable outlook can be treated with fluconazole initially, but under careful clinical supervision. Incidentally, Coker and Harris 6 in a letter to the Journal in the same issue remark on the failure of fluconazole for cryptococcal meningitis in A I D S despite an inhibitory C S F concentration of the drug. It is now clear that the C S F concentration of an antifungal is an irrelevant measurement. Amphotericin B penetrates the blood-brain barrier poorly ( < IO%) and yet has been the mainstay of therapy for years. Itraconazole is as effective as fluconazole in non-comparative trials for both cryptococcal, 7-9 and coccidioidal 1° meningitis and is undetectable in the CSF. Probably what is important is brain and meningeal drug concentrations as the disease being treated is a meningo-encephalitis, not a ' C S F i t i s '.
University of Manchester, David W. Denning Regional Department of Infectious Diseases and Tropical Medicine, Monsall Hospital, Newton Heath, Manchester M I o 8 W R , U.K. References
1. Buxton MJ, Dubois D J, Turner, RR et al. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin B-based therapies. J Infect I99I; z3: I7-31. 2. Bozzette SA, Larsen RA, Chiu Jet al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med I99I; 324: 580-584. 3- Powderly W, Saag M, Cloud Get al. Fluconazole (FLU) versus amphotericin B (AMB) as maintenance therapy for prevention of relapse of AIDS-associated cryptococcal meningitis (CM). (Abstr.) 3oth Interscience Conference on Antimicrobial Agents and Chemotherapy, 2I-24 October, I99O, Atlanta, GA, p. 280. 4. Larsen RA, Leal MA, Chan LS. Fluconazole compared to amphotericin B plus flucytosine for the treatment of cryptococcal meningitis: a prospective study. Ann Intern Med I99O; II3: 183-187. 5. Dismukes WE, Cloud G, Thompson A et al. Fluconazole versus amphotericin B therapy of acute cryptococcal meningitis. (Abstr.) 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, I7-2o September, i989, Houston, TX, p. 282. 6. Coker RJ, Harris JRW. Failure offluconazole treatment in cryptococcal meningitis despite adequate CSF levels. J Infect i99i ; 23: IOI-IO3. 7. Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. hraconazole therapy of cryptococcal meningitis and cryptococcosis. Arch Intern Med 1989; I49: 23oi-23o8. 8. Denning DW, Tucker RM, Hostetler JS et al. Oral itraconazole therapy of cryptococcal meningitis and cryptococcosis in patients with AIDS. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G, Drouhet E, Dupont B, Van Cutsem J, Eds. Mycoses in A I D S patients. New York: Plenum Press, 199o: 3o5-324. 9. Viviani MA, Tortorano AM, Langer M e t al. Experience with itraconazole in cryptococcosis and aspergillosis. J Infect 1989; I8: I51-I65. IO. Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy of chronic coccidioidal meningitis. Ann Intern Med 199o; I I 2 : IO8-I I2.
Letters to the Editor
among psoriatics mean that the benefits of prophylaxis usually outweigh its risks. 6 Nevertheless, psoriatics should be warned of the risk when considering travel to malarious areas and whenever antimalarials are prescribed. Such drugs should be given to them only when essential. Affected psoriatics should seek dermatological help urgently, since topical treatment usually controls these exacerbations. 1.4 Exacerbation of psoriasis is not among side-effects reported with the new antimalarial mefloquine hydrochloride, but the risks are probably similar to those of other chloroquine-tike drugs.
Department of Dermatology, Level 4, Lauriston Building, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh E H 3 9 Y W , Scotland, U.K.
I. 2. 3. 4. 5. 6.
J . P . Vestey J. A. Savin
References Abel EA, DiCicco LM, Orenberg EK, Fraki JE, Farber EM. Drugs in exacerbation of psoriasis. J Am Acad Dermatol 1986; I5: lOO7-1o22. Ziprkowski L, Haim S, Bank H. Atabrine in psoriasis, zqcta Med Orient 1954; I3: 45-52. Mallett R, Pye R. Risks and benefits of prophylactic antimalarial drugs. Br Med J 1989; 299 : 14oo Kuflik EG. Effect of antimalarial drugs on psoriasis. Curls 198o; 26: 153-155. Katugampola G, Katugampola S. Chloroquine and psoriasis. Int J Dermatol 199o; 29: 153-154. Breckenridge A. Risks and benefits of prophylactic antimalarial drugs. BrMedJI989; 299: I057-IO58.
C o s t i m p l i c a t i o n s o f a l t e r n a t i v e t r e a t m e n t s for A I D S p a t i e n t s w i t h cryptococcal meningitis
Accepted for publication 15 August I99I Sir, T h e article by Buxton et al., 1 is interesting but misleading in one respect. A major distinction should have been drawn in the abstract between the effectiveness of fluconazole for maintenance therapy after amphotericin B primary therapy, and its effectiveness as p r i m a r y therapy. T h e r e is little doubt that fluconazole is a drug of choice for maintenance therapy of cryptococcal meningitis in A I D S , if preceded by amphotericin B (with or without flucytosine)fl' a It is effective, non-toxic and cost effective. T h i s is not necessarily true when fluconazole is used for primary therapy. Buxton et al., failed to reference a randomised study supported by Pfizer in which fluconazole was markedly inferior to amphotericin B (0"7 m g / k g / d a y ) combined with flucytosine (four of 14 fluconazole treated patients died, compared with none of six treated with amphotericin B. 4 I n a large, as yet unpublished study, 5 comparing fluconazole with amphotericin B without flucytosine, the interim results indicated no difference between the treatments, but both regimens were successful in only 40 % of the patients. T h i s is a poor overall result, suggesting that both regimens (fluconazole 200-400 m g daily or amphotericin B 0"5-0"6 m g / k g / d a y without flucytosine) are suboptimal. T i m e to sterilisation of C S F was delayed in the fluconazole group. It is thus misleading to the readership to suggest that fluconazole is ' a t least as effective as amphotericin B ' . It is either as effective or less effective for p r i m a r y therapy.
Letters to the Editor
2][ 3
Various poor prognostic factors in first-episode cryptococcal meningitis in A I D S have been identified. These include a low C S F white cell count ( < 20 × lO3/1), C S F cryptococcal antigen reciprocal titre > 256, a low serum sodium and positive extraneural cultures. These poor prognostic factors have not, however, been consistent from study to study. Nevertheless, more severely ill patients should receive amphotericin B, probably with flucytosine, as primary therapy. Those with a more favourable outlook can be treated with fluconazole initially, but under careful clinical supervision. Incidentally, Coker and Harris 6 in a letter to the Journal in the same issue remark on the failure of fluconazole for cryptococcal meningitis in A I D S despite an inhibitory C S F concentration of the drug. It is now clear that the C S F concentration of an antifungal is an irrelevant measurement. Amphotericin B penetrates the blood-brain barrier poorly ( < IO%) and yet has been the mainstay of therapy for years. Itraconazole is as effective as fluconazole in non-comparative trials for both cryptococcal, 7-9 and coccidioidal 1° meningitis and is undetectable in the CSF. Probably what is important is brain and meningeal drug concentrations as the disease being treated is a meningo-encephalitis, not a ' C S F i t i s '.
University of Manchester, David W. Denning Regional Department of Infectious Diseases and Tropical Medicine, Monsall Hospital, Newton Heath, Manchester M I o 8 W R , U.K. References
1. Buxton MJ, Dubois D J, Turner, RR et al. Cost implications of alternative treatments for AIDS patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin B-based therapies. J Infect I99I; z3: I7-31. 2. Bozzette SA, Larsen RA, Chiu Jet al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. N Engl J Med I99I; 324: 580-584. 3- Powderly W, Saag M, Cloud Get al. Fluconazole (FLU) versus amphotericin B (AMB) as maintenance therapy for prevention of relapse of AIDS-associated cryptococcal meningitis (CM). (Abstr.) 3oth Interscience Conference on Antimicrobial Agents and Chemotherapy, 2I-24 October, I99O, Atlanta, GA, p. 280. 4. Larsen RA, Leal MA, Chan LS. Fluconazole compared to amphotericin B plus flucytosine for the treatment of cryptococcal meningitis: a prospective study. Ann Intern Med I99O; II3: 183-187. 5. Dismukes WE, Cloud G, Thompson A et al. Fluconazole versus amphotericin B therapy of acute cryptococcal meningitis. (Abstr.) 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, I7-2o September, i989, Houston, TX, p. 282. 6. Coker RJ, Harris JRW. Failure offluconazole treatment in cryptococcal meningitis despite adequate CSF levels. J Infect i99i ; 23: IOI-IO3. 7. Denning DW, Tucker RM, Hanson LH, Hamilton JR, Stevens DA. hraconazole therapy of cryptococcal meningitis and cryptococcosis. Arch Intern Med 1989; I49: 23oi-23o8. 8. Denning DW, Tucker RM, Hostetler JS et al. Oral itraconazole therapy of cryptococcal meningitis and cryptococcosis in patients with AIDS. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G, Drouhet E, Dupont B, Van Cutsem J, Eds. Mycoses in A I D S patients. New York: Plenum Press, 199o: 3o5-324. 9. Viviani MA, Tortorano AM, Langer M e t al. Experience with itraconazole in cryptococcosis and aspergillosis. J Infect 1989; I8: I51-I65. IO. Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy of chronic coccidioidal meningitis. Ann Intern Med 199o; I I 2 : IO8-I I2.
