Letters to the E d i t o r
345
2. Cook GC. The great malaria problem: where is the light at the end of the tunnel? (Editorial) J Infect 1989; 18: I-IO. 3. Rieckmann KH, Davis DR, Hutton DC. Plasmodium vivax resistance to chloroquine? Lancet 1989, ii: 1183-1184. 4. Whitby M, Wood G, Veenendall JR, Rieckmann K. Chloroquine-resistant Plasmodium vivax. Lancet 1989, ii: 1395. 5. Clyde DF, McCarthy VC. Radical cure of Chesson strain vivax malaria by 7, not 14 days of treatment with primaquine. Am J Trop Med Hyg 1977; 26: 562-563. 6. British National Formulary. Published by British Medical Association and Royal Pharmaceutical Society of Great Britain 199o; 20: 5.4.2zi.
F l u c o n a z o l e r e s i s t a n t c a n d i d a in A I D S
Accepted for publication 28 M a y 1991 Sir, We were interested to read the reports by Fox et al., 1 and Kitchen et al., 2 describing candidosis resistant to fluconazole in A I D S patients, as we have also seen a similar phenomenon. A 32-year-old homosexual male, who had been H I V positive since 1985, was admitted because of a painful perianal ulcer. In the past he had had Pneumocystis carinii pneumonia, Kaposi's sarcoma, cytomegalovirus (CMV) retinitis and recurrent oral and oesophageal candidosis. His C M V maintenance therapy was changed from ganciclovir to foscarnet because of neutropenia (WBC o ' 9 x IO~). Although his ketoconazole dosage was increased from 2oo r a g / d a y to 400 mg twice daily his oral candidosis persisted and this treatment was therefore changed to fluconazole 4 o o m g / d a y . D u r i n g his admission he developed ecthyma gangrenosum and Pseudomonas aeruginosa was cultured from numerous skin sites but not from blood. He recovered slowly during a prolonged hospital stay, but his appetite remained poor and he was grossly wasted. Oral candidosis continued to be a problem and a m o u t h swab taken after 5 weeks therapy with fluconazole grew both Candida albieans and C. glabrata. Their sensitivities are shown in Table I. He became m u c h more debilitated and died 2 weeks later whilst in respite care placement. This case supports the findings of Fox et al., 1 and Kitchen et al., 2 in whose A I D S patients candida became resistant to fluconazole but remained sensitive to ketoconazole and itraconazole. This finding is in many ways surprising, in that all the azole compounds act by selective inhibition of fungal Lanesterol C I 4 Demethylase ~ and it would seem likely that resistance would be to all azoles 4 rather than to one agent. I f
Table I MIC
( ~ g / m l ) o f f u n g a l isolates Candida albicans
Miconazole Ketoconazole Itraconazole Fluconazole Nystatin Amphotericin
I o-I o- i IOO Io IO
Candida glabrata I I I IOO ioo IOO
Letters to the Editor
346
fluconazole resistance becomes a c o m m o n p r o b l e m in patients given continuous therapy, single dose 5 or pulsed therapy may be needed. (We wish to thank Jan Van Cutsem at the Janssen Research Foundation, Beerse, Belgium for his assistance.)
* A I D S Unit and t Department of Microbiology, Westminster Hospital, Horseferry Road, London S.W.I and ~ John Hunter Clinic, Fulham Road, London S W I o 9TH, U.K.
Don Smith* Fiona Boag:~ Jenifer Midgleyt Brian Gazzard*
References I. FOX R, Neal KR, Leen CLS, Ellis ME, Mandal BK. Fluconazole resistant candida in AIDS. J Infect I99I; 22: 2IO-2O4. 2. Kitchen VS, Savage M, Harris JRW. Candida albicans resistance in AIDS. J Infect I99I ; 22" 2 0 4 - 2 0 5 .
3. Vanden Boossche H, Marichal P, Gorrens J e t al. Interaction of azole derivatives with cytochrome P45o isoenzymes in yeast, fungi, plants and mammalian cells. Pestic Sci I987; 2I : 289. 4. Warnock DW, Burke J, Cope NJ, Johnson EM, Von Fraunhofer NA, Williams EW. Fluconazole resistance in Candida glabrata. Lancet 1988; ii: 131o. 5. Chave JP, Francioli P, Hirschel B, Glauser MP. Single dose therapy for esophageal candidiasis with fluconazole. AIDS 199o; 4: IO34-IO35. Septicaemia
a n d s e p t i c a r t h r i t i s d u e to Pseudomonas putida in a neutropenic patient
Accepted for publication I July 1991 Sir, T h e increasing n u m b e r of organisms now regarded as opportunistic pathogens requires that laboratories are able to identify accurately a wider range of bacteria. We describe a fatal case of septicaemia and septic arthritis in an i m m u n o c o m p r o m i s e d patient due to a multiply-resistant Pseudomonas putida. A 66-year-old female was admitted with a confirmed relapse of acute myeloid leukaemia, a central line was inserted and cytotoxic chemotherapy commenced. D u r i n g the next 24 days she was intermittently pyrexial and had an episode of focal seizures and loss of consciousness. Blood cultures remained negative but P. putida was isolated from surveillance faeces on day I7. D u r i n g this time she received intravenous netilmicin and piperacillin, with vancomycin, amphotericin B and erythromycin being added in. On day 24 she developed a swollen, painful left knee. Aspirated joint fluid and blood cultures yielded P. putida. Piperacillin and netilmicin were discontinued and ciprofloxacin commenced. T h e organism was found to be multiplyresistant and only sensitive in vitro to imipenem [ m i n i m u m inhibitory concentration ( M I C ) I m g / I ] and polymyxin. She developed a septic arthritis of her right elbow and spreading septic loci in her skin. I m i p e n e m and amikacin were added followed by polymyxin. A slow i m p r o v e m e n t took place, but on day 42 the patient died following a cardiac arrest. Specimens taken at p o s t , m o r t e m revealed the persistence of P. putida in the knee despite treatment with two antibiotics to which it was sensitive in vitro. Pseudomonas putida is a c o m m o n enviro_nmental inhabitant and can be part of the normal pharyngeal flora.1 T h e significance of its isolation has been questioned I but the
345
2. Cook GC. The great malaria problem: where is the light at the end of the tunnel? (Editorial) J Infect 1989; 18: I-IO. 3. Rieckmann KH, Davis DR, Hutton DC. Plasmodium vivax resistance to chloroquine? Lancet 1989, ii: 1183-1184. 4. Whitby M, Wood G, Veenendall JR, Rieckmann K. Chloroquine-resistant Plasmodium vivax. Lancet 1989, ii: 1395. 5. Clyde DF, McCarthy VC. Radical cure of Chesson strain vivax malaria by 7, not 14 days of treatment with primaquine. Am J Trop Med Hyg 1977; 26: 562-563. 6. British National Formulary. Published by British Medical Association and Royal Pharmaceutical Society of Great Britain 199o; 20: 5.4.2zi.
F l u c o n a z o l e r e s i s t a n t c a n d i d a in A I D S
Accepted for publication 28 M a y 1991 Sir, We were interested to read the reports by Fox et al., 1 and Kitchen et al., 2 describing candidosis resistant to fluconazole in A I D S patients, as we have also seen a similar phenomenon. A 32-year-old homosexual male, who had been H I V positive since 1985, was admitted because of a painful perianal ulcer. In the past he had had Pneumocystis carinii pneumonia, Kaposi's sarcoma, cytomegalovirus (CMV) retinitis and recurrent oral and oesophageal candidosis. His C M V maintenance therapy was changed from ganciclovir to foscarnet because of neutropenia (WBC o ' 9 x IO~). Although his ketoconazole dosage was increased from 2oo r a g / d a y to 400 mg twice daily his oral candidosis persisted and this treatment was therefore changed to fluconazole 4 o o m g / d a y . D u r i n g his admission he developed ecthyma gangrenosum and Pseudomonas aeruginosa was cultured from numerous skin sites but not from blood. He recovered slowly during a prolonged hospital stay, but his appetite remained poor and he was grossly wasted. Oral candidosis continued to be a problem and a m o u t h swab taken after 5 weeks therapy with fluconazole grew both Candida albieans and C. glabrata. Their sensitivities are shown in Table I. He became m u c h more debilitated and died 2 weeks later whilst in respite care placement. This case supports the findings of Fox et al., 1 and Kitchen et al., 2 in whose A I D S patients candida became resistant to fluconazole but remained sensitive to ketoconazole and itraconazole. This finding is in many ways surprising, in that all the azole compounds act by selective inhibition of fungal Lanesterol C I 4 Demethylase ~ and it would seem likely that resistance would be to all azoles 4 rather than to one agent. I f
Table I MIC
( ~ g / m l ) o f f u n g a l isolates Candida albicans
Miconazole Ketoconazole Itraconazole Fluconazole Nystatin Amphotericin
I o-I o- i IOO Io IO
Candida glabrata I I I IOO ioo IOO
Letters to the Editor
346
fluconazole resistance becomes a c o m m o n p r o b l e m in patients given continuous therapy, single dose 5 or pulsed therapy may be needed. (We wish to thank Jan Van Cutsem at the Janssen Research Foundation, Beerse, Belgium for his assistance.)
* A I D S Unit and t Department of Microbiology, Westminster Hospital, Horseferry Road, London S.W.I and ~ John Hunter Clinic, Fulham Road, London S W I o 9TH, U.K.
Don Smith* Fiona Boag:~ Jenifer Midgleyt Brian Gazzard*
References I. FOX R, Neal KR, Leen CLS, Ellis ME, Mandal BK. Fluconazole resistant candida in AIDS. J Infect I99I; 22: 2IO-2O4. 2. Kitchen VS, Savage M, Harris JRW. Candida albicans resistance in AIDS. J Infect I99I ; 22" 2 0 4 - 2 0 5 .
3. Vanden Boossche H, Marichal P, Gorrens J e t al. Interaction of azole derivatives with cytochrome P45o isoenzymes in yeast, fungi, plants and mammalian cells. Pestic Sci I987; 2I : 289. 4. Warnock DW, Burke J, Cope NJ, Johnson EM, Von Fraunhofer NA, Williams EW. Fluconazole resistance in Candida glabrata. Lancet 1988; ii: 131o. 5. Chave JP, Francioli P, Hirschel B, Glauser MP. Single dose therapy for esophageal candidiasis with fluconazole. AIDS 199o; 4: IO34-IO35. Septicaemia
a n d s e p t i c a r t h r i t i s d u e to Pseudomonas putida in a neutropenic patient
Accepted for publication I July 1991 Sir, T h e increasing n u m b e r of organisms now regarded as opportunistic pathogens requires that laboratories are able to identify accurately a wider range of bacteria. We describe a fatal case of septicaemia and septic arthritis in an i m m u n o c o m p r o m i s e d patient due to a multiply-resistant Pseudomonas putida. A 66-year-old female was admitted with a confirmed relapse of acute myeloid leukaemia, a central line was inserted and cytotoxic chemotherapy commenced. D u r i n g the next 24 days she was intermittently pyrexial and had an episode of focal seizures and loss of consciousness. Blood cultures remained negative but P. putida was isolated from surveillance faeces on day I7. D u r i n g this time she received intravenous netilmicin and piperacillin, with vancomycin, amphotericin B and erythromycin being added in. On day 24 she developed a swollen, painful left knee. Aspirated joint fluid and blood cultures yielded P. putida. Piperacillin and netilmicin were discontinued and ciprofloxacin commenced. T h e organism was found to be multiplyresistant and only sensitive in vitro to imipenem [ m i n i m u m inhibitory concentration ( M I C ) I m g / I ] and polymyxin. She developed a septic arthritis of her right elbow and spreading septic loci in her skin. I m i p e n e m and amikacin were added followed by polymyxin. A slow i m p r o v e m e n t took place, but on day 42 the patient died following a cardiac arrest. Specimens taken at p o s t , m o r t e m revealed the persistence of P. putida in the knee despite treatment with two antibiotics to which it was sensitive in vitro. Pseudomonas putida is a c o m m o n enviro_nmental inhabitant and can be part of the normal pharyngeal flora.1 T h e significance of its isolation has been questioned I but the
