1042 Correspondence bronchial secretions with increased antibacte- rial effect, resulting in improved efficacy in cystic fibrosis exacerbations. Future pharma- cokinetic/pharmacodynamic analyses and clinical trials are necessary to document this outcome. One obvious benefit with once-daily administration is a reduction in the number of infusions administered per day. This finding is particularly relevant since selected cystic iibrosis patients can be treated at home with aminoglycosides. Once-daily aminoglycoside therapy results in improved quality of life in home care patients. In conclusion, this pilot study suggests that the pharmacokinetic disposition of tobramycin is unaltered in cystic fibrosis patients regardless of the dose. If, as has been observed in other patient populations, this regimen is docu- mented to be safe and effective, it may result in simplified administration and improved quality of life in these patients. B. JOSEPH GUGLIELMO LORI A. QUAN" MICHAEL S. STULBARG* 'Division of Clinical Pharmacy, School of Pharmacy; ''Adult Cystic Fibrosis Center, Department of Medicine, Clinical Science 152, Box 0622, 521 Parnassus, University of California, San Francisco, CA 94143-0622, USA References deGroot, R. & Smith, A. L. (1987). Antibiotic pharmacokinetics in cystic fibrosis. Clinical Phar- macokinetics 13, 228-53 Gibaldi, M. (1984). Noncompartmental pharmacoki- netics. In Biopharmaceutics and Clinical Pharma- cokinetics 3rdedn. (Gibaldi, M., Ed.), pp 17-28. Lea & Febiger, Philadelphia, PA Matthews. Z., Cistulh, K. & Barnes, D. (1994). Once daily dosing of aminoglycosides. Australia and New Zealand Journal of Medicine 24, 730. Powell, S. H.. Thompson, W. L., Luthe, M. A , Stern, R. C, Grossniklaus. D. A , Bloxham, D. D. et al. (1983). Once-daily vs continuous aminogly- coside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin and tobramycin. Journal of Infectious Diseases 147, 918-32. Preston, S. L. & Briceland, L. L. (1995). Single daily dosing of aminoglycosides Pharmacotherapv 15, 297-316. Smith D. L., Stableforth, D. E. & Geddes, A M (1994). Evaluation of a once-daily netilmicin regimen in the treatment of cystic fibrosis. Journal of Antimicrobial Chemotherapy 33, 191-3. Fluconazole plus allopurinol in treatment of visceral leishmanlasis J Antimicrob Chemother 1996; 37: 1042-1043 Sir, Standard treatments for visceral leishmaniasis (pentavalent antimonials, pentamidine and amphotericin B) pose several problems that can make management of this disease quite difficult, especially in immunocompromised hosts. Primary failure of treatment occurs occasionally but is more common in immuno- compromised patients. Switching to an alterna- tive drug is the usual response and this sometimes can solve the problem (Cook, 1993). Relapse is becoming a particular problem in immunosuppressed subjects. AIDS patients sometimes relapse, even after apparently successful courses of treatment with the three available drugs (Medrano et al., 1992). Toxicity is the third problem. With some patients clinicians can run out of options because of successive adverse effects with the standard drugs. Failure of antimonials or severe toxicity is particularly troublesome in patients with diminished renal function be- cause pentamidine and amphotericin B carry increased risks in this setting. Rescue therapy with gamma interferon (de-Gorgolas, Castrillo & Fernandez-Guerrero, 1993) or monotherapy with allopurinol have offered inconsistent results in immunocompromised patients. Keto- conazole both as monotherapy or combined with allopurinol (Halim et al., 1993) has been used successfully in some cases of visceral leishmaniasis as has itraconazole (Lafeuillade et al., 1992), but experience is scanty. Experience with new lipid formulations of amphotericin B is even more limited, although good renal tolerance to liposomal ampho- tericin B has been reported. Severe antimonial toxicity in a renal transplant patient prompted us to design a regimen with non-nephrotoxic drugs. After a successful experience with fluconazole plus allopurinol we have treated two other patients. Our results are recorded here. Case 1. A woman with a renal transplant had a diagnosis of visceral leishmaniasis made by bone marrow smear (Giemsa) and culture. She developed a severe acute pancreatitis induced by meglumine antimoniate and serum crea- tinine peaked to 3.5 mg/dL. Antimonials were stopped and the patient was treated orally with fluconazole 200 mg od and allopurinal 300 mg od for 3 weeks. Case 2. A 32 year old man with AIDS diagnosed as having visceral leishmaniasis by guest on July 6, 2011 jac.oxfordjournals.org Downloaded from