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Rifabutin appears to be a promising agent for combination treatment of AIDS-related toxoplasma encephalitis
352
Letters to the Editor
Ralstonia pickettii Involved in Spinal Osteitis in an Immunocompetent Adult Sir,
Ralstonia pickettii is a non-fermenting, Gram-negative rod that is found in water and soil and on plants, fruits and vegetables. 1 Bacteraemia and pyuria due to this rarely pathogenic organism have been infrequently reported, and then associated with foreign material or contamination of material supposed to be sterile. 2 In 1992 the organism was transferred from the genus Pseudomonas RNA homology group II to the genus Burkholderia. 3 Recently, it was transferred to the new genus Ralstonia. 4 We describe a case of a thoracic vertebral osteitis in an immunocompetent patient, in which R. pickettii was involved. A 40-year-old, previously fit immnnocompetent female was hospitalized for investigation of a suspected vertebral tumour. Eight months previously, back pains had begun after ordinary physical exercise and became more intense with time. Clinical examination revealed circumscribed tenderness over the middle and lower end of the thoracic spine. Isotope bone scanning showed multiple hot spots in T7, Tg, T12, L2 and L3 vertebrae and the sternal end of the right first and second rib. Thoracic spine X-ray showed destruction in the body of T7 and T9 vertebrae. Magnetic resonance imaging (MRI) showed osteitislfl;e changes in T7 and T9 vertebral bodies, combined with surrounding minor soft tissue swelling but no involvement of the intervertebral discs. Laboratory examination revealed a leucocyte count of 11.2 x 109/1 (normal 4 . 0 - 1 1 . 0 x 109/1) with normal differential count. C-reactive protein and alkaline phosphatase were within the normal range, anti-streptolysin O and anti-streptococcal deoxyribonuclease B reactions were normal and rheumatoid factor was negative. Bone m a r r o w cytology was normal. A primary turnout was excluded. An open biopsy of the seventh vertebral body was taken and showed mild osteitis. Ralstonia pickettii was isolated from intraoperative bone material. In the agar disc diffusion test performed on MuellerHinton agar, the organism was susceptible to ampicillin, mezlocillin, piperacillin, cefoxitin, cefotaxime, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Staphylococcus epidermidis was also isolated but only from a swab taken intraoperatively. In addition, Propionibacterium acnes was isolated from intraoperatively obtained bone material. Therapy consisted of a 12-week course of orally administered ciprofloxacin (500 mg twice daily). In addition, the patient was immobilized for 12 weeks followed by a Boston-overlappedbrace for 6 months to reduce pain. After 12 weeks of therapy, leucocytes normalized to 6.7 x 109/I and the patient became free of pain. An MRI scan performed 6 months postoperatively showed significant reduction in the signs of osteititis. Previously, a single case of vertebral osteitis and discitis due to R. piekettii in a 71-year-old black male with chronic renal failure, diabetes mellitus, hypertension, and cirrhosis with ascites, who underwent chronic hemodialysis, has been described. 2 The authors suggested that the patient might have been infected by the haemodialysis machines and catheters, or during a preceding hospitalization w h e n the patient received corticosteroids, had an iv catheter, and a cardiac catheterization was performed. In contrast to that case, the patient described here had no underlying disease and had not received any immunosuppressive therapy.
In this case, besides R. pickettii, S. epidermidis and P, aches were isolated from intraoperative material. Unlike R, pickettii, S, epidermidis and R acnes are part of the physiological resident flora of the skin and usually represent perioperative contamination. However, involvement of these bacteria in this case of osteitis cannot be completely excluded. The clinical and radiological appearance of this vertebral osteitis showed differences to a c o m m o n spondylitis because of the lack of involvement of the intervertebral discs. In addition, radiology revealed other foci at several vertebrae and ribs which suggested a haematogenous infection. The similarity to the previously described case of osteomyelitis is striking. This case demonstrates that R. pickettii may rarely be involved in serious infections in immunocompetent patients. H.-A. Eisner I, G. P. D a h m e n a, R. Laufs 1, D. Mack 1
1Institute of Medical Microbiology and Immunology, Martinistrafle 52, D-20246 Hamburg, 2Orthopaedic University-Hospital, Martinistrafle 52, D-20246 Hamburg, Germany
References 1 Gilligan PH. Pseudomonas and Burkholderia. In: Murray PR, Baron El, Pfaller MA, Tenover FC, Yolken RH, eds. Manual of Clinical Microbiology. Washington, DE: American Society for Microbiology, 1995: 509-519. 2 Wertheim WA, Markovitz DM. Osteomyelitis and intervertebral discitis caused by Pseudomonas pJckettiL J Clin Microbiol 1992; 30: 2506-2508. 3 Yabuuchi E, Kosako Y, Oyaizu H et al. Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. Miclvbiol hnmunol 1992; 36: 1251-1275. 4 Yaabuchi E, Kosako Y, Yano I, Hotta H, Nishiuchi Y. Transfer of two Burkholderia and an Alcaligenes species to Ralstonia gen nov.: proposal of Ralstonia pickettii (Ralston, Palleroni and Doudoroff 1973) comb. nov., Ralstonia solanacearum (Smith 1896) comb. nov. and Ralstonia eutropha (Davis 1969) comb. nov. Microbiol Immunol 1995; 39: 897-904.
Accepted for publication 7 August 1997
Rifabutin Appears to be a Promising Agent for Combination Treatment of AIDS-related Toxoplasma Encephalitis Sir, Toxoplasma encephalitis is an important parasitic disease in AIDS patients. 1 Standard therapy consists of pyrimethamine in combination with sulfadiazine or clindamycin, but these regimens fail in a certain proportion of cases and are associated with a high frequency of adverse events, 2 Although there is little clinical experience so far with alternative treatment regimens using drugs such as atovaquone or a combination of pyrimethamine plus azithromycin, efficacy and tolerance seem to be limited. 3-5 Therefore, there is still a need for novel alternative regimens. We report a patient who has been treated successfully with a combination of pyrimethamine plus rifabutin.
Letters to the Editor A 38-year-old white male homosexual presented in September 1994 with holocranial headache. The patient had not been taking any antiretroviral or prophylactic drugs until then. Physical examination revealed oral thrush and small pharyngeal and cutaneous lesions of Kaposi's sarcoma. Pertinent laboratory parameters were unremarkable, except for a C D 4 + lymphocyte count of 20@1. A cranial computertomography scan (CCT) revealed five contrast-enhanced ringshaped foci of up to 2 cm in diameter, as typically seen in patients with AIDS-related toxoplasma encephalitis. Toxoplasma serology (Sabin-Feldman dye test) showed a reciprocal titre of 256 (equalling 53 IU/ml according to the WHO reference serum). Serum was negative for anti-toxoplasma fgM antibodies, consistent with reactivation of latent infection. As the patient had a history of allergy against various drugs including sulfonamides and clindamycin, and as there was no established alternative regimen for the standard treatment combinations available at the time treatment was started, the patient was treated with an experimental combination of 300 mg rifabutin every 8 h plus 100 m g pyrimethamine once daily. Folinic acid rescue was performed with 15 mg leucovorin daily. All medications were given orally. Prior to starting treatment, the patient's informed consent had been obtained. A distinct improvement of the headache was noted within the first days of treatment. Control CCT on day 7 revealed a visible reduction of focal sizes, with complete radiographic and clinical resolution after 30 days of treatment, which was well tolerated throughout the course. The patient's oral thrush had responded to treatment with topical amphotericin B solution. As a risk of uveitis with long-term use of rifabutin in AIDS patients had been reported, 6 the patient was put on a relapse prophylaxis on discharge with a combination of 500 mg sulfadoxine plus 25 mg pyrimethamine (1 Fansidar ® tablet) twice a week, plus 15 m g leucovorin. 7 As it has also been reported earlier, prophylaxis was well tolerated despite the patient's k n o w n allergy against sulfonamides such as the co-trimoxazole component sulfamethoxazole. 8 The patient remained relapsefree until death 8 months later due to disseminated Kaposi's sarcoma. Rifabutin is a rifamycin derivative, with excellent activity against tachyzoites and cysts of toxoplasma encephalitis in an experimental murine model. 9'~° In combination with pyrimethamine, the efficacy of rifabutin is considerably increased. Both drugs act synergistically. Pyrimethamine is a dihydrofolate reductase inhibitor, whereas rifabutin inhibits protein synthesis on the ribosomal level. ~ Both drugs act synergistically. Until now, clinical data on the efficacy of this drug combination are lacking. To our knowledge, this is the first report indicating its efficacy in the treatment of AIDS-related toxoplasma encephalitis. Common side effects of rifabutin such as abdominal discomfort, nausea and vomiting tend to be mild and transient, and were not seen in our patient. ~2 There was also no evidence of uveitis. Rifabutin is an important drug for the m a n a g e m e n t of AIDS-related Mycobacterium avium complex (MAC) disease; however, its long-term use, particularly in combination with drugs inhibiting the hepatic rifabutin metabolism, may lead to uveitis/''13 The risk of uveitis is dose-dependent. In a recent study, the use of 600 mg rifabutin daily in combination with clarithromycin led to uveitis in 24 of 63 cases (38%) after a median duration of 42 days, with the earliest occurrence on day 25. Clarithromycin leads to an increase of the serum levels of rifabutin of 77% and of the active rifabutin metabolite LM
353
565 of 236%. With a treatment time of 1 m o n t h and without concurrent use of drugs inhibiting rifabutin metabolism, 14 uveitis may not be expected to occur even with a higher dose of rifabutin. Pyrimethamine does not appear to increase the rifabutin serum level. The efficacy and tolerability of the pyrimethamine-rifabutin combination seen in our patient suggests that this regimen may be an alternative therapy for the treatment of toxoplasma encephalitis. D. Schiirmann 1, M. P. Grobusch 1 and B. Ruf2 1Medizinische Klinik (I@ktiologie), Charitd (Campus Virchow-glinikum), Humboldt Universitdt zu Berlin, 13353 Berlin, Germany; '-Klinik ffir hmere Medizin (hffektiologie), Stddtisches Klinikum St. Georg, Delitzscher Strafle 141, 0 4 1 2 9 Leipzig, Germany
References 1 Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin infect Disc 1992: 15: 211-222. 2 Dannemann B, McCutchan A, Israelski D et al. Treatment of toxoplasmic encephalitis in patients with AIDS. Ann Intern Med 1992; 116: 33. 3 Wiselka MJ, Read R, Finch RG. Response to oral and intravenous azithromycin in a patient with toxoplasma encephalitis and AIDS. J Infect 1996; 33: 227-229. 4 Torres RA, Weinberg W, Stansell J e t al. and the Atovaquone/ Toxoplasmic encephalitis Study Group. Aiovaquone for salvage treatment and suppression of toxoplasmic encephalitis in patients with AID's'. Clin Infect Dis 1997; 24: 422-429. 5 Saba J, Morlat P, Raft] H et al. Pyrimethamine plus azithromycin for treatment of acute toxoplasma encephalitis. Eur J Clin Microbiol Infect Dis 1993; 12: 853-856. 6 Havlir D, Torriani F, Dub4 M. Uveitis associated with rifabutin prophylaxis. Ann Intern Med 1994: 121: 510-512. 7 Ruf B, Schtirmann D, Bergmann F et al. Efficacy of pyrimethamine/ sulfadoxine in the prevention of toxoplasmic encephalitis relapses and Pneumocystis carinii pneumonia. Eur J Clin Microbiol Infect Dis 1993; 12: 325-329. 8 Gottlieb MS, Knight S, Mitsuyasu R et al. Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine. Lancet 1984; it: 398-399. 9 Araujo FG, Slifer T, Remington JS. Rifabutin is active in murine models of toxoplasmosis. Antimicrob Agents Chemother 1994; 3: 570 575. 10 Olliaro P, Gorini G, Jabes D et al. In vitro and in vivo activity of rifabutin against Toxoplasma gondii. J Antimicrob Chemotherapy 1994; 34: 649-657. 11 Kunin CM. Antimicrobial activity of rifabutin. Clin Infect Dis 1996; 22(Suppl. 1): $3-13. 12 Nightingale SD, Cameron DW, Gordin FM et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993; 329: 828-833. 13 Shafran SD, Singer J, Zarowny DP et aI. A comparison of two regimens for the treatment of Mycobaeterium avium complex bacteremia in AIDS: rifabutin, ethambutoL and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996; 335: 377-383. 14 Piscitelli SC, Flexner C, Minor JR, Polis MA, Masur H. Drug interactions in patients infected with human immunodeficiency virus. Clin I@ct Dis 1996; 23: 685-693. Accepted for publication 4 September 1997
Letters to the Editor
Ralstonia pickettii Involved in Spinal Osteitis in an Immunocompetent Adult Sir,
Ralstonia pickettii is a non-fermenting, Gram-negative rod that is found in water and soil and on plants, fruits and vegetables. 1 Bacteraemia and pyuria due to this rarely pathogenic organism have been infrequently reported, and then associated with foreign material or contamination of material supposed to be sterile. 2 In 1992 the organism was transferred from the genus Pseudomonas RNA homology group II to the genus Burkholderia. 3 Recently, it was transferred to the new genus Ralstonia. 4 We describe a case of a thoracic vertebral osteitis in an immunocompetent patient, in which R. pickettii was involved. A 40-year-old, previously fit immnnocompetent female was hospitalized for investigation of a suspected vertebral tumour. Eight months previously, back pains had begun after ordinary physical exercise and became more intense with time. Clinical examination revealed circumscribed tenderness over the middle and lower end of the thoracic spine. Isotope bone scanning showed multiple hot spots in T7, Tg, T12, L2 and L3 vertebrae and the sternal end of the right first and second rib. Thoracic spine X-ray showed destruction in the body of T7 and T9 vertebrae. Magnetic resonance imaging (MRI) showed osteitislfl;e changes in T7 and T9 vertebral bodies, combined with surrounding minor soft tissue swelling but no involvement of the intervertebral discs. Laboratory examination revealed a leucocyte count of 11.2 x 109/1 (normal 4 . 0 - 1 1 . 0 x 109/1) with normal differential count. C-reactive protein and alkaline phosphatase were within the normal range, anti-streptolysin O and anti-streptococcal deoxyribonuclease B reactions were normal and rheumatoid factor was negative. Bone m a r r o w cytology was normal. A primary turnout was excluded. An open biopsy of the seventh vertebral body was taken and showed mild osteitis. Ralstonia pickettii was isolated from intraoperative bone material. In the agar disc diffusion test performed on MuellerHinton agar, the organism was susceptible to ampicillin, mezlocillin, piperacillin, cefoxitin, cefotaxime, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Staphylococcus epidermidis was also isolated but only from a swab taken intraoperatively. In addition, Propionibacterium acnes was isolated from intraoperatively obtained bone material. Therapy consisted of a 12-week course of orally administered ciprofloxacin (500 mg twice daily). In addition, the patient was immobilized for 12 weeks followed by a Boston-overlappedbrace for 6 months to reduce pain. After 12 weeks of therapy, leucocytes normalized to 6.7 x 109/I and the patient became free of pain. An MRI scan performed 6 months postoperatively showed significant reduction in the signs of osteititis. Previously, a single case of vertebral osteitis and discitis due to R. piekettii in a 71-year-old black male with chronic renal failure, diabetes mellitus, hypertension, and cirrhosis with ascites, who underwent chronic hemodialysis, has been described. 2 The authors suggested that the patient might have been infected by the haemodialysis machines and catheters, or during a preceding hospitalization w h e n the patient received corticosteroids, had an iv catheter, and a cardiac catheterization was performed. In contrast to that case, the patient described here had no underlying disease and had not received any immunosuppressive therapy.
In this case, besides R. pickettii, S. epidermidis and P, aches were isolated from intraoperative material. Unlike R, pickettii, S, epidermidis and R acnes are part of the physiological resident flora of the skin and usually represent perioperative contamination. However, involvement of these bacteria in this case of osteitis cannot be completely excluded. The clinical and radiological appearance of this vertebral osteitis showed differences to a c o m m o n spondylitis because of the lack of involvement of the intervertebral discs. In addition, radiology revealed other foci at several vertebrae and ribs which suggested a haematogenous infection. The similarity to the previously described case of osteomyelitis is striking. This case demonstrates that R. pickettii may rarely be involved in serious infections in immunocompetent patients. H.-A. Eisner I, G. P. D a h m e n a, R. Laufs 1, D. Mack 1
1Institute of Medical Microbiology and Immunology, Martinistrafle 52, D-20246 Hamburg, 2Orthopaedic University-Hospital, Martinistrafle 52, D-20246 Hamburg, Germany
References 1 Gilligan PH. Pseudomonas and Burkholderia. In: Murray PR, Baron El, Pfaller MA, Tenover FC, Yolken RH, eds. Manual of Clinical Microbiology. Washington, DE: American Society for Microbiology, 1995: 509-519. 2 Wertheim WA, Markovitz DM. Osteomyelitis and intervertebral discitis caused by Pseudomonas pJckettiL J Clin Microbiol 1992; 30: 2506-2508. 3 Yabuuchi E, Kosako Y, Oyaizu H et al. Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov. Miclvbiol hnmunol 1992; 36: 1251-1275. 4 Yaabuchi E, Kosako Y, Yano I, Hotta H, Nishiuchi Y. Transfer of two Burkholderia and an Alcaligenes species to Ralstonia gen nov.: proposal of Ralstonia pickettii (Ralston, Palleroni and Doudoroff 1973) comb. nov., Ralstonia solanacearum (Smith 1896) comb. nov. and Ralstonia eutropha (Davis 1969) comb. nov. Microbiol Immunol 1995; 39: 897-904.
Accepted for publication 7 August 1997
Rifabutin Appears to be a Promising Agent for Combination Treatment of AIDS-related Toxoplasma Encephalitis Sir, Toxoplasma encephalitis is an important parasitic disease in AIDS patients. 1 Standard therapy consists of pyrimethamine in combination with sulfadiazine or clindamycin, but these regimens fail in a certain proportion of cases and are associated with a high frequency of adverse events, 2 Although there is little clinical experience so far with alternative treatment regimens using drugs such as atovaquone or a combination of pyrimethamine plus azithromycin, efficacy and tolerance seem to be limited. 3-5 Therefore, there is still a need for novel alternative regimens. We report a patient who has been treated successfully with a combination of pyrimethamine plus rifabutin.
Letters to the Editor A 38-year-old white male homosexual presented in September 1994 with holocranial headache. The patient had not been taking any antiretroviral or prophylactic drugs until then. Physical examination revealed oral thrush and small pharyngeal and cutaneous lesions of Kaposi's sarcoma. Pertinent laboratory parameters were unremarkable, except for a C D 4 + lymphocyte count of 20@1. A cranial computertomography scan (CCT) revealed five contrast-enhanced ringshaped foci of up to 2 cm in diameter, as typically seen in patients with AIDS-related toxoplasma encephalitis. Toxoplasma serology (Sabin-Feldman dye test) showed a reciprocal titre of 256 (equalling 53 IU/ml according to the WHO reference serum). Serum was negative for anti-toxoplasma fgM antibodies, consistent with reactivation of latent infection. As the patient had a history of allergy against various drugs including sulfonamides and clindamycin, and as there was no established alternative regimen for the standard treatment combinations available at the time treatment was started, the patient was treated with an experimental combination of 300 mg rifabutin every 8 h plus 100 m g pyrimethamine once daily. Folinic acid rescue was performed with 15 mg leucovorin daily. All medications were given orally. Prior to starting treatment, the patient's informed consent had been obtained. A distinct improvement of the headache was noted within the first days of treatment. Control CCT on day 7 revealed a visible reduction of focal sizes, with complete radiographic and clinical resolution after 30 days of treatment, which was well tolerated throughout the course. The patient's oral thrush had responded to treatment with topical amphotericin B solution. As a risk of uveitis with long-term use of rifabutin in AIDS patients had been reported, 6 the patient was put on a relapse prophylaxis on discharge with a combination of 500 mg sulfadoxine plus 25 mg pyrimethamine (1 Fansidar ® tablet) twice a week, plus 15 m g leucovorin. 7 As it has also been reported earlier, prophylaxis was well tolerated despite the patient's k n o w n allergy against sulfonamides such as the co-trimoxazole component sulfamethoxazole. 8 The patient remained relapsefree until death 8 months later due to disseminated Kaposi's sarcoma. Rifabutin is a rifamycin derivative, with excellent activity against tachyzoites and cysts of toxoplasma encephalitis in an experimental murine model. 9'~° In combination with pyrimethamine, the efficacy of rifabutin is considerably increased. Both drugs act synergistically. Pyrimethamine is a dihydrofolate reductase inhibitor, whereas rifabutin inhibits protein synthesis on the ribosomal level. ~ Both drugs act synergistically. Until now, clinical data on the efficacy of this drug combination are lacking. To our knowledge, this is the first report indicating its efficacy in the treatment of AIDS-related toxoplasma encephalitis. Common side effects of rifabutin such as abdominal discomfort, nausea and vomiting tend to be mild and transient, and were not seen in our patient. ~2 There was also no evidence of uveitis. Rifabutin is an important drug for the m a n a g e m e n t of AIDS-related Mycobacterium avium complex (MAC) disease; however, its long-term use, particularly in combination with drugs inhibiting the hepatic rifabutin metabolism, may lead to uveitis/''13 The risk of uveitis is dose-dependent. In a recent study, the use of 600 mg rifabutin daily in combination with clarithromycin led to uveitis in 24 of 63 cases (38%) after a median duration of 42 days, with the earliest occurrence on day 25. Clarithromycin leads to an increase of the serum levels of rifabutin of 77% and of the active rifabutin metabolite LM
353
565 of 236%. With a treatment time of 1 m o n t h and without concurrent use of drugs inhibiting rifabutin metabolism, 14 uveitis may not be expected to occur even with a higher dose of rifabutin. Pyrimethamine does not appear to increase the rifabutin serum level. The efficacy and tolerability of the pyrimethamine-rifabutin combination seen in our patient suggests that this regimen may be an alternative therapy for the treatment of toxoplasma encephalitis. D. Schiirmann 1, M. P. Grobusch 1 and B. Ruf2 1Medizinische Klinik (I@ktiologie), Charitd (Campus Virchow-glinikum), Humboldt Universitdt zu Berlin, 13353 Berlin, Germany; '-Klinik ffir hmere Medizin (hffektiologie), Stddtisches Klinikum St. Georg, Delitzscher Strafle 141, 0 4 1 2 9 Leipzig, Germany
References 1 Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin infect Disc 1992: 15: 211-222. 2 Dannemann B, McCutchan A, Israelski D et al. Treatment of toxoplasmic encephalitis in patients with AIDS. Ann Intern Med 1992; 116: 33. 3 Wiselka MJ, Read R, Finch RG. Response to oral and intravenous azithromycin in a patient with toxoplasma encephalitis and AIDS. J Infect 1996; 33: 227-229. 4 Torres RA, Weinberg W, Stansell J e t al. and the Atovaquone/ Toxoplasmic encephalitis Study Group. Aiovaquone for salvage treatment and suppression of toxoplasmic encephalitis in patients with AID's'. Clin Infect Dis 1997; 24: 422-429. 5 Saba J, Morlat P, Raft] H et al. Pyrimethamine plus azithromycin for treatment of acute toxoplasma encephalitis. Eur J Clin Microbiol Infect Dis 1993; 12: 853-856. 6 Havlir D, Torriani F, Dub4 M. Uveitis associated with rifabutin prophylaxis. Ann Intern Med 1994: 121: 510-512. 7 Ruf B, Schtirmann D, Bergmann F et al. Efficacy of pyrimethamine/ sulfadoxine in the prevention of toxoplasmic encephalitis relapses and Pneumocystis carinii pneumonia. Eur J Clin Microbiol Infect Dis 1993; 12: 325-329. 8 Gottlieb MS, Knight S, Mitsuyasu R et al. Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine. Lancet 1984; it: 398-399. 9 Araujo FG, Slifer T, Remington JS. Rifabutin is active in murine models of toxoplasmosis. Antimicrob Agents Chemother 1994; 3: 570 575. 10 Olliaro P, Gorini G, Jabes D et al. In vitro and in vivo activity of rifabutin against Toxoplasma gondii. J Antimicrob Chemotherapy 1994; 34: 649-657. 11 Kunin CM. Antimicrobial activity of rifabutin. Clin Infect Dis 1996; 22(Suppl. 1): $3-13. 12 Nightingale SD, Cameron DW, Gordin FM et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993; 329: 828-833. 13 Shafran SD, Singer J, Zarowny DP et aI. A comparison of two regimens for the treatment of Mycobaeterium avium complex bacteremia in AIDS: rifabutin, ethambutoL and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med 1996; 335: 377-383. 14 Piscitelli SC, Flexner C, Minor JR, Polis MA, Masur H. Drug interactions in patients infected with human immunodeficiency virus. Clin I@ct Dis 1996; 23: 685-693. Accepted for publication 4 September 1997