204

Letters to the Editor References

I. Hay RJ. Fluconazole. J Infect 199o; 21: 1-6. 2. Leen CLS, Dunbar EM, Ellis ME, Mandal BK. Once weekly Fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS-related complex : a double blind placebo-controlled study. J Infect 199o; 21: 55-60. 3. De Wit S, Weerts D, Goosens H, Chunech N. Comparison offluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet 1989; i: 746-747. 4. Warnock DW, Burke J, Cope NJ, Johnson EM, Van Frannhofer NA, Williams EW. Fluconazole resistance in Candida glabrata. Lancet 1988; ii: 131o. 5. Erlich KS, Mills J, Chatis P e t al. Acyclovir resistant Herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 32o: 293-296 • 6. Erice A, Chen S, Buron KK, Stanat SC, Balfour H, Jordan MC. Progressive disease due to gancyclovir resistant cytomegalovirus in immunocompromised patients. N Engl J Med 1989; 32o : 289-292. 7. Holt RJ, Azmi A. Miconazole resistant candida. Lancet 1978; i: 5o-51. 8. Horsburgh CR, Kirkpatrick CH. Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole : experience with twenty one patients. Am ff Med 1983; 74 (Suppl. IB) : 23-29. 9. Kerridge D, Nicholas RO. Drug resistance in the opportunistic pathogens Candida albicans and Candida glabrata, ff Antimicrob Chemother 1986; 18 (Suppl. B): 39-49-

Candida albicans r e s i s t a n c e i n A I D S Accepted for publication 14 November 199o Sir, Oral candidosis is the commonest opportunistic infection seen in patients who are i m m u n o c o m p r o m i s e d as a result of H I V infection. Initially, systemic antifungal therapy with ketoconazole was widely used, but recently this imidazole has been superceded in many centres by the triazoles, fluconazole and itraconazole. Reasons for this include the poor absorption of ketoconazole in the presence of achlorhydria, which is c o m m o n in advanced H I V disease, and the rare association of this drug with fatal hepatotoxicity. However, we now report the isolation of fluconazole-resistant, ketoconazole-sensitive Candida albicans occurring in an A I D S patient with oesophageal candidosis. T h e patient, a 43-year-old homosexual male, developed dysphagia whilst on 50 mg fluconazole daily. H e had been taking this medication continuously over the previous 12 months as prophylaxis against recurrent oral candidosis. A presumptive diagnosis of oesophageal candidosis was made and the fluconazole was increased to 200 mg daily, as it was assumed that serum levels could have been low owing to concurrent treatment with rifampicin. 1 T h e r e was no clinical improvement during the following 4 weeks and the patient therefore underwent endoscopy. This revealed confluent plaques of candida obscuring oesophageal mucosal detail. T h e dosage of fluconazole was further increased to 4oo mg daily with some subsequent clinical improvement. Repeat endoscopy IO days later revealed persistent oesophageal candidosis, with a less florid appearance than before. T h e patient died 2 weeks later of an unrelated cause. T h e serum level of fluconazole measured 2 h after ingestion of a daily dose of 200 mg was 21"3 mg/1 (therapeutic range 1"3-3"4 mg/1). Candida albicans was cultured from material obtained at each oesophagoscopy. T h e sensitivity of each of the isolates to fluconazole, ketoconazole and itraconazole was measured using an agar dilution

Letters to the Editor

205

method. 2 T h e m i n i m u m inhibitory concentration obtained for fluconazole was 5o mg/1 and those for ketoconazole and itraconazole were less than I mg/1. Fluconazole resistance has been described in disseminated C. glabrata infection and in ketoconazole-resistant C. albicans species isolated from patients with chronic mucocutaneous candidosis. 3,4 I n view of the continuing improvement in life expectancy of patients with A I D S , may we expect the emergence of resistant strains of C. albicans in patients on long term antifungal prophylaxis ? We feel that clinicians should be aware that a C. albicans resistant to fluconazole but sensitive to ketoconazole has now been isolated from a patient with A I D S. (We would like to thank Pfizer Central Research for their assistance.)

* Department of GU Medicine, St Mary's Hospital af Department of Mycology, St Mary's Hospital Medical School London W2 I N Y , U.K.

V . S . Kitchen* M. Savaget J. R. W. Harris*

References

i. Mau S, Salamone FR, Muller RJ, Polsky BW. Trimetrexate, gancyclovir, foscarnet and fluconazole-investigational drugs used in the management of AIDS. Hosp Pharm I989; 24 : 209-215. 2. Odds FC, Abbott AB, Pye G, Troke PF. Improved method for the estimation of antifungal inhibitory concentrations against Candida sp. based on azole/antibiotic interactions. J Med Vet Mycol I986; 24: 3o5-3II. 3. Warnock DW, Burke J, Cope NJ, Johnson EM, von Fraunhofer NA, Williams EW. Fluconazole resistance in Candida glabrata. Lancet I988; ii: I3IO. 4. Smith KJ, Warnock DW, Kennedy CTC, Johnson EM. Azole resistance in Candida albicans. J Med Vet Mycol I986; 24: I33-I44.

Cerebrospinal

fluid shunt infection: an unusual case

Accepted for publication 24 July I99O Sir, Cerebrospinal fluid shunt infections are an important cause of morbidity and mortality. A mortality rate of up to 3 1 % has been reported.1 Most shunt infections are caused by coagulase-negative staphylococci, 2 with Staphylococcus aureus as the second most frequent pathogen. We wish to report an unusual case of a shunt infection with

Neisseria gonorrhoeae. A I7-year-old-girl with a ventriculo-peritoneal shunt following an episode of meningitis in infancy presented with I2 h history of acute abdominal pain. On examination the area over the abdominal insertion of the shunt was tender, with an overlying cellulitis extending to mid-sternal level. T h e patient was afebrile and there were no signs of meningitis. T h e peripheral W B C count was raised (I6"I x Iog); all other tested haematological parameters were normal. A diagnosis of shunt infection was made and the shunt was removed in theatre and sent for culture. It was not t h o u g h t necessary to replace it at the time. T h e patient was started empirically on broad-spectrum antibiotic therapy consisting of intravenous penicillin, flucloxacillin, gentamicin and metronidazole, to which she responded rapidly. On the following day a heavy pure growth of N. gonorrhoeae was cultured from the abdominal end of the shunt, with a scanty growth of the same organism from the ventricular end. Because of the POssibility of polymicrobial pelvic infection, antibiotic therapy was changed to

Candida albicans resistance in AIDS.

204 Letters to the Editor References I. Hay RJ. Fluconazole. J Infect 199o; 21: 1-6. 2. Leen CLS, Dunbar EM, Ellis ME, Mandal BK. Once weekly Flucon...
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