326
Letters
to the Editor
Sir,
Fluconazole
and
Candida
krusei
infections
We report the case of a 53-year-old woman who died of Candida krusei infection during consolidation chemotherapy for acute myeloid leukaemia. During three previous chemotherapy courses she had received antimicrobial prophylaxis which included amphotericin suspension 100 mg every 6 hours and fluconazole 50 mg once daily both by mouth. After the final j-day course of consolidation chemotherapy with mitozantrone and cytarabine she became neutropenic on day 8 and pyrexial on day 12, having received amphotericin and fluconazole prophylaxis as during previous Candida krusei was isolated from some superficial swabs (throat admissions. and perineum) and from 10 blood cultures taken over a period of 22 days. She was treated with increasing doses of amphotericin up to 1 mg kg-’ day-’ but she did not respond to treatment and eventually died on day 39 without having recovered from the neutropenia. During her illness she suffered from many of the possible side-effects of systemic amphotericin including nephrotoxicity, hypokalaemia, hypomagnesaemia and cardiac toxicity. On day 36 amphotericin dosage was reduced from 1 mg kg-’ day-’ to 1 mg kg-’ every other day because of the deteriorating renal function (estimated creatinine clearance had fallen to 23 ml min-‘). Fluconazole is a much better tolerated antifungal agent which has been used successfully for the treatment of systemic Candida infections;“2 however, we did not use it because of sensitivity testing results. Sensitivity to antifungals was assessed with a broth dilution method: amphotericin minimum inhibitory concentration (MIC) was 1.25 mg 1-l and fluconazole 2.5 mg 1-l. These results were consistent with those reported by others for C. krusei: these strains are usually slightly less susceptible to amphotericin than Candida albicans strains3’4 and are much less susceptible to fluconazole. 3 Although there is no agreement on MIC cut-off values to define resistance, the use of animal models suggests that C. krusei strains are actually resistant to fluconazole.’ Candida infections with a fluconazoleThe occurrence of systemic resistant strain in a patient receiving fluconazole prophylaxis has prompted us to review our records. In June 1990 we started identifying the species of all our yeast isolates: so far C. krusei accounts for 1.8% of all isolates. Of 22 patients from whom we isolated C. krusei and whose medical records were available, 15 had previously received fluconazole including 14 HIV-infected patients. In HIV-infected patients it has been shown that fluconazole treatment is associated with increased frequency of C. krusei isolation.6 Systemic candidiasis is not a common infection in HIV patients but is a major cause of morbidity and mortality in neutropenic patients. We suggest that the isolation frequency of C. krusei in patients who are given fluconazole prophylaxis should be monitored and that the beneficial
327
Letters to the Editor effects
of this regimen
the risk of selecting
in neutropenic
less susceptible
G. E. Bignardi M. A. Savage R. Coker* S. G. Davis?
patients strains
should
be weighed
against
such as C. izrusei.
Department of Medical Microbiology *Department of Genito- Urinary Medicine and 7 Department of Haematology St Mary’s Hospital London W2 1NY References
1. Jakab K, Kelemen E, Prinz G, T&ok I. Amphotericin-resistant invasive hepatosplenic candidiasis controlled by fluconazole. Lancet 1990; 335: 473474. 2. Conti DJ, Tolkoff-Rubin NE, Baker GP, Doran M, Cosimi AB, Delmonico F et al. Successful treatment of invasive fungal infection with fluconazole in organ transplant recipients. Transplantation 1989; 48: 692-695. 3. Marriott MS, Richardson K. The discovery and mode of action of fluconazole. In: Development and Edaluation of Fromling RA, Ed. Recent Trends in the Discovery, Antifungal Agents. J R Prous Science Publishers 1987; 81-92. 4. Merz WG, Karp JE, Schron D, Sara1 R. Increased incidence of fungemia caused by Candida krusei. 7 Clin Microbial 1986: 24: 581-584. 5. Fisher MA, Sh;eh-Hui S, Haddad J, Tarry WF. Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata and Candida krusei. Antimicrob Agents Chemother 1989; 33: 1443-6. 6. Just G, Steinheimer D, Schnellbach B, Bottinger C, Helm EB, Stille W. Change of causative organisms under antifungal treatment in immunosuppressed patients with HIV-infections. Mycoses 1989; 32 (Suppl 2): 47-51.
Sir,
Slime
production
and adherence by coagulase-negative staphylococci
We read with interest the study of phenotypic characteristics in S. epidermidis by Souto et al.’ and in particular of their attempt to examine the phenomena of adherence and slime production. The fault of most in-vitro assays of slime production by coagulase-negative staphylococci (CNS) is the reliance on initial bacterial adherence for a positive result. As such, strains that may be able to produce slime and yet not adhere to the surface under investigation (see below) are ignored. Souto et al.’ examined slime production by planktonic cells using a lectin (concanavalin A) based assay’ and the same phenomenon by adherent bacteria in the tube test.3 We have similarly found a lack of correlation between these two assays. We also employed three other lectins (Machra pomifera, Pisum sat&urn and poly-L-lysine) but failed to correlate these results with those of S. epidermidis adherence as measured by the tube,3 microtitre tray,4 ATP
Letters
to the Editor
Sir,
Fluconazole
and
Candida
krusei
infections
We report the case of a 53-year-old woman who died of Candida krusei infection during consolidation chemotherapy for acute myeloid leukaemia. During three previous chemotherapy courses she had received antimicrobial prophylaxis which included amphotericin suspension 100 mg every 6 hours and fluconazole 50 mg once daily both by mouth. After the final j-day course of consolidation chemotherapy with mitozantrone and cytarabine she became neutropenic on day 8 and pyrexial on day 12, having received amphotericin and fluconazole prophylaxis as during previous Candida krusei was isolated from some superficial swabs (throat admissions. and perineum) and from 10 blood cultures taken over a period of 22 days. She was treated with increasing doses of amphotericin up to 1 mg kg-’ day-’ but she did not respond to treatment and eventually died on day 39 without having recovered from the neutropenia. During her illness she suffered from many of the possible side-effects of systemic amphotericin including nephrotoxicity, hypokalaemia, hypomagnesaemia and cardiac toxicity. On day 36 amphotericin dosage was reduced from 1 mg kg-’ day-’ to 1 mg kg-’ every other day because of the deteriorating renal function (estimated creatinine clearance had fallen to 23 ml min-‘). Fluconazole is a much better tolerated antifungal agent which has been used successfully for the treatment of systemic Candida infections;“2 however, we did not use it because of sensitivity testing results. Sensitivity to antifungals was assessed with a broth dilution method: amphotericin minimum inhibitory concentration (MIC) was 1.25 mg 1-l and fluconazole 2.5 mg 1-l. These results were consistent with those reported by others for C. krusei: these strains are usually slightly less susceptible to amphotericin than Candida albicans strains3’4 and are much less susceptible to fluconazole. 3 Although there is no agreement on MIC cut-off values to define resistance, the use of animal models suggests that C. krusei strains are actually resistant to fluconazole.’ Candida infections with a fluconazoleThe occurrence of systemic resistant strain in a patient receiving fluconazole prophylaxis has prompted us to review our records. In June 1990 we started identifying the species of all our yeast isolates: so far C. krusei accounts for 1.8% of all isolates. Of 22 patients from whom we isolated C. krusei and whose medical records were available, 15 had previously received fluconazole including 14 HIV-infected patients. In HIV-infected patients it has been shown that fluconazole treatment is associated with increased frequency of C. krusei isolation.6 Systemic candidiasis is not a common infection in HIV patients but is a major cause of morbidity and mortality in neutropenic patients. We suggest that the isolation frequency of C. krusei in patients who are given fluconazole prophylaxis should be monitored and that the beneficial
327
Letters to the Editor effects
of this regimen
the risk of selecting
in neutropenic
less susceptible
G. E. Bignardi M. A. Savage R. Coker* S. G. Davis?
patients strains
should
be weighed
against
such as C. izrusei.
Department of Medical Microbiology *Department of Genito- Urinary Medicine and 7 Department of Haematology St Mary’s Hospital London W2 1NY References
1. Jakab K, Kelemen E, Prinz G, T&ok I. Amphotericin-resistant invasive hepatosplenic candidiasis controlled by fluconazole. Lancet 1990; 335: 473474. 2. Conti DJ, Tolkoff-Rubin NE, Baker GP, Doran M, Cosimi AB, Delmonico F et al. Successful treatment of invasive fungal infection with fluconazole in organ transplant recipients. Transplantation 1989; 48: 692-695. 3. Marriott MS, Richardson K. The discovery and mode of action of fluconazole. In: Development and Edaluation of Fromling RA, Ed. Recent Trends in the Discovery, Antifungal Agents. J R Prous Science Publishers 1987; 81-92. 4. Merz WG, Karp JE, Schron D, Sara1 R. Increased incidence of fungemia caused by Candida krusei. 7 Clin Microbial 1986: 24: 581-584. 5. Fisher MA, Sh;eh-Hui S, Haddad J, Tarry WF. Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata and Candida krusei. Antimicrob Agents Chemother 1989; 33: 1443-6. 6. Just G, Steinheimer D, Schnellbach B, Bottinger C, Helm EB, Stille W. Change of causative organisms under antifungal treatment in immunosuppressed patients with HIV-infections. Mycoses 1989; 32 (Suppl 2): 47-51.
Sir,
Slime
production
and adherence by coagulase-negative staphylococci
We read with interest the study of phenotypic characteristics in S. epidermidis by Souto et al.’ and in particular of their attempt to examine the phenomena of adherence and slime production. The fault of most in-vitro assays of slime production by coagulase-negative staphylococci (CNS) is the reliance on initial bacterial adherence for a positive result. As such, strains that may be able to produce slime and yet not adhere to the surface under investigation (see below) are ignored. Souto et al.’ examined slime production by planktonic cells using a lectin (concanavalin A) based assay’ and the same phenomenon by adherent bacteria in the tube test.3 We have similarly found a lack of correlation between these two assays. We also employed three other lectins (Machra pomifera, Pisum sat&urn and poly-L-lysine) but failed to correlate these results with those of S. epidermidis adherence as measured by the tube,3 microtitre tray,4 ATP
