Vol. 11, t992
Was secondary to bacteremia, since in other cases this was not a manifestation of cellulitis. The treatment of septic thrombophlebitis requires prolonged use of systemic antibiotics along with hgature or resection of the involved venous segment and the collaterals. On the other hand, cellulitis is a very uncommon manifestation of salmonellosis in the absence of Underlyfng disease or previous trauma (3). Salmonella enteriditis, Salmonella typhimurium and Salmonella dublin are found most frequently to be the pathogens. Salmonella serotype give has not been previously reported as a cause of cellulitis or septic thrombophlebitis. On the basis of OUr experience Salmonella group E should be ineluded in the list Of etiological agents causing these entities in patients without underlying disease.
M. Javaloyas* M.D. Garcfa E. Sierra J. D o m i n g o Hospital de Viladecans, 08840 Viladeeans, Barcelona, Spain.
References
1. Hook EW: Salmonella species (including typhoid fever). In: Mandell GL, Douglas RG, Bennet JE: Principles and practice of infectious diseases. Churchill Livingstone, New York, 1990, p. 1700-1716. 2. Navarro M, Almirante B, Bellnmnt J, Jolis L: Fatal septic thrombophlebitis due to Salmonella enteriditis. European Journal of Clinical Microbiology and Infectious Diseases 1989, 8: 82--83. 3. Cohen JI, Bartlett JA, Corey GR: Extra-intestinal manifestations of Sahnonella infections. Medicine 1987, 66: 349-388. 4. KnobelB, Sommer1, MenashesZ: A rare presentation of systemic salmonellosis. Infection 1985, 13: 70-72. 5. Aguado JM, Obeso G, Cahaniilas JJ, Fern~ndezGuerrero M, Al~s J: Pleuropulmonaryinfections due to nontyphoid strains of Salmonella. Archives of Internal Medicine 1990, 150: 54-56.
201
Failure o f F l u c o n a z o l e in Systemic Candidiasis
Fluconazole, an antifungat azole, was recently approved by the US Food and Drug Administration for oral and intravenous (i.v.) treatment of cryptococcal meningitis and various forms of candidiasis (1). It is recommended as a substitute for amphotericin B in cases of failure or severe intolerance. We recently treated a patient with systemic candidiasis who developed septic shock with growth of Candida from blood while on fluconazole therapy. In early 1990 a 43-year-old female with longstanding ulcerative colitis underwent restorative proctocolectomy and laparotomy for small bowel obstruction. In September 1990 the patient was readmitted due to general deterioration and was put on total parenteral nutrition. While on rifampicin and trimethoprim-sulfamethoxazole therapy (for suspected brucellosis), she developed severe thrombophlebitis at the peripheral hyperalimentation infusion site, and her fever spiked to 39 °C. The peripheral line was removed, rifampin and trimethoprim-sulfamethoxazolewere discontinued and amphotericin B therapy was initiated following the repeated isolation of Candida spp. from blood on three separate days. Over the next four days the patient received 40 mg of amphotericin B daily, during which time increasing chills, shivering and high fevers were uncontrolled by i.v. hydrocortisone 100 mg and phenothiazide 25 mg. The total parenteral nutrition was continued concomitantly by means of a central venous line. Due to the severe intolerance of amphotericin B, i,v. fluconazole 200 rag/day was started, followed by 100 mg/day, and was well tolerated. The serum concentration of fluconazole was not determined. The patient did not improve and on day 4 of fluconazole therapy she deteriorated, developing septic shock. After hemodynamic resuscitation, an explorative laparotomy was performed for suspected uncontrolled intra-abdominal focus of infection but did not reveal the cause for sepsis. Intravenous amphotericin B 40 mg was readministered concomitant with hydrocortisone 300 rag/day, resulting in improvement in symptoms and fever. Two blood culture specimens taken on the day of the septic shock grew Candida again. All Candida isolates were later identified as Torulopsis glabrata, Following a four-week course of amphotericin B and slow tapering off of the hydrocortisone, the patient was discharged on oral alimentation and in good condition.
202
There are only a few reports on the clinical use of fluconazole in systemic candidiasis. Six of nine (67 %) non-AIDS patients with severe candidiasis treated with 200 mg/day fluconazole improved or were clinically cured (2). In a larger study conducted by the manufacturer, the success rate was only 61% among 91 non-AIDS patients with invasive or visceral candidiasis (3). There were two failures among nine episodes of candidemia in eight patients (7 with solid tumours and 1 with Crohn's disease) receiving 100-300 mg/day (4). The two failures occurred in patients who had received 200 mg/day, on day 6 and 19 of therapy, respectively. In another study, four patients with deep-seated Candida infections improved clinically with prolonged fluconazote therapy, 100 mg/day (R.D. Diamond et al., Tenth Congress of the International Society of Human and Animal Mycology, Barcelona, 1988, Abstract). A few additional single cases of invasive infection were successfully treated with low-dose oral or i.v. fluconazole (5-7). Our case demonstrates that i.v. fluconazole, given initially at 200 rag/day and later at 100 mg/day, may not achieve fungicidal levels in some patients or for specific isolates (i.e. Torulopsis glabrata). As the patient weighed 60 kg, the 200 rag/day initially administered was in compliance with the recommended loading dose of 3 mg/kg. However, a higher dose of 300-400 rag/day may have been beneficial. In spite of the encouraging data on successful fluconazole therapy in systemic candidiasis, it should be used with caution in lifethreatening infections, and clinical response should be carefully monitored.
Y. Siegman-Igra 1. M.Y. R a b a u 2 1 Infectious Disease Unit, and 2Department of Surgery "C", IchilovHospital,Tel-AvivSouraskyMedicalCenter, TeI-Aviv University, 6 Weizman Street, TeI-Aviv 64239, Israel.
References Fluconazole. Medical Letter on Drugs and Therapeutics 1990, 32: 50--52. 2. Robinson PA, Knirsch AK, Joseph JA: Fluconazole for life-threateningfungal infections in patients who cannot be treated with conventionalantifungalagents. Reviews of Infectious Diseases 1990, 12: 349-363. 1,
Eur. J. Clin. Microbiol. Infect. Dis.
3. Bodey GP: Fungal infections in cancer patients - an overview. Pfizer International, 1990. 4. MeunierF: Fluconazoletreatment of fungal infections in the immune-compromised host. Seminars in Ontology 1990, 17: 19-23. 5. IsalskaBJ, Stanbridge TN: Fluconazole in the treatment of candidal prosthetic valve endocarditis. British Medical Journal 1988, 297: 178-179. 6. Dave Y, Hickey MM, Wilkins EGL: Fluconazole in renal candidosis. Lancet 1989, i: 163-164. 7. Kirk AJB, Gould FK, Freeman R, Corris PA, Dark JH: Fluconazole and candidosis. Lancet 1989, i: 339.
P o s s i b l e Failure o f I t r a c o n a z o l e in P r e v e n t i n g Fungal Infection in a N e u t r o p e n i c L e u k a e m i a Patient
In the treatment of leukaemia patients in our hospital, we use a combination of antimicrobial and antifungal drugs as selective gut decontamination to prevent the development of gramnegative and fungal infections (1). This regimen consists of a combination of norfloxacin 400 mg b.i.d, and itraconazole 200 mg b.i.d., a new antifungal drug (Janssen Pharmaceuticals, Belgium). During the first week, colistin solution, 1 mg per ml as mouthwash, 5 ml four times a day and nystatin suspension 105 IU per ml as mouthwash, 5 ml four times daily are also administered. Recently, we encountered a severe complication in a patient who was treated with itraconazole, which is claimed to be a very active agent againstAspergillus and Candida species in a prophylactic setting (1-3). A 54-year-old male was referred to our hospital for treatment of acute leukaemia, diagnosed elsewhere. Bone marrow aspirate showed 96.4 % Sudan positive and PAS weak positive blast cells. Immunophenotyping of blood and bone marrow revealed a high percentage CD11, CD13, CD33, CDw65, MPO and partial HLA-Dr positive cells. Acute myeloid leukaemia, type M1 (FAB classification), was diagnosed. The first chemotherapy course, daunorubicin 45 mg/m2, days 1-3, combined with cytosine arabinoside 200 mg/m2, days 4-11 (4), was complicated by respiratory tract infections during the neutropenic episode, despite selective gut decontamination. On chest X-ray infiltrates were revealed in the lower left lung segment, later spreading to the upper region and also to the right lung. The lesion
Was secondary to bacteremia, since in other cases this was not a manifestation of cellulitis. The treatment of septic thrombophlebitis requires prolonged use of systemic antibiotics along with hgature or resection of the involved venous segment and the collaterals. On the other hand, cellulitis is a very uncommon manifestation of salmonellosis in the absence of Underlyfng disease or previous trauma (3). Salmonella enteriditis, Salmonella typhimurium and Salmonella dublin are found most frequently to be the pathogens. Salmonella serotype give has not been previously reported as a cause of cellulitis or septic thrombophlebitis. On the basis of OUr experience Salmonella group E should be ineluded in the list Of etiological agents causing these entities in patients without underlying disease.
M. Javaloyas* M.D. Garcfa E. Sierra J. D o m i n g o Hospital de Viladecans, 08840 Viladeeans, Barcelona, Spain.
References
1. Hook EW: Salmonella species (including typhoid fever). In: Mandell GL, Douglas RG, Bennet JE: Principles and practice of infectious diseases. Churchill Livingstone, New York, 1990, p. 1700-1716. 2. Navarro M, Almirante B, Bellnmnt J, Jolis L: Fatal septic thrombophlebitis due to Salmonella enteriditis. European Journal of Clinical Microbiology and Infectious Diseases 1989, 8: 82--83. 3. Cohen JI, Bartlett JA, Corey GR: Extra-intestinal manifestations of Sahnonella infections. Medicine 1987, 66: 349-388. 4. KnobelB, Sommer1, MenashesZ: A rare presentation of systemic salmonellosis. Infection 1985, 13: 70-72. 5. Aguado JM, Obeso G, Cahaniilas JJ, Fern~ndezGuerrero M, Al~s J: Pleuropulmonaryinfections due to nontyphoid strains of Salmonella. Archives of Internal Medicine 1990, 150: 54-56.
201
Failure o f F l u c o n a z o l e in Systemic Candidiasis
Fluconazole, an antifungat azole, was recently approved by the US Food and Drug Administration for oral and intravenous (i.v.) treatment of cryptococcal meningitis and various forms of candidiasis (1). It is recommended as a substitute for amphotericin B in cases of failure or severe intolerance. We recently treated a patient with systemic candidiasis who developed septic shock with growth of Candida from blood while on fluconazole therapy. In early 1990 a 43-year-old female with longstanding ulcerative colitis underwent restorative proctocolectomy and laparotomy for small bowel obstruction. In September 1990 the patient was readmitted due to general deterioration and was put on total parenteral nutrition. While on rifampicin and trimethoprim-sulfamethoxazole therapy (for suspected brucellosis), she developed severe thrombophlebitis at the peripheral hyperalimentation infusion site, and her fever spiked to 39 °C. The peripheral line was removed, rifampin and trimethoprim-sulfamethoxazolewere discontinued and amphotericin B therapy was initiated following the repeated isolation of Candida spp. from blood on three separate days. Over the next four days the patient received 40 mg of amphotericin B daily, during which time increasing chills, shivering and high fevers were uncontrolled by i.v. hydrocortisone 100 mg and phenothiazide 25 mg. The total parenteral nutrition was continued concomitantly by means of a central venous line. Due to the severe intolerance of amphotericin B, i,v. fluconazole 200 rag/day was started, followed by 100 mg/day, and was well tolerated. The serum concentration of fluconazole was not determined. The patient did not improve and on day 4 of fluconazole therapy she deteriorated, developing septic shock. After hemodynamic resuscitation, an explorative laparotomy was performed for suspected uncontrolled intra-abdominal focus of infection but did not reveal the cause for sepsis. Intravenous amphotericin B 40 mg was readministered concomitant with hydrocortisone 300 rag/day, resulting in improvement in symptoms and fever. Two blood culture specimens taken on the day of the septic shock grew Candida again. All Candida isolates were later identified as Torulopsis glabrata, Following a four-week course of amphotericin B and slow tapering off of the hydrocortisone, the patient was discharged on oral alimentation and in good condition.
202
There are only a few reports on the clinical use of fluconazole in systemic candidiasis. Six of nine (67 %) non-AIDS patients with severe candidiasis treated with 200 mg/day fluconazole improved or were clinically cured (2). In a larger study conducted by the manufacturer, the success rate was only 61% among 91 non-AIDS patients with invasive or visceral candidiasis (3). There were two failures among nine episodes of candidemia in eight patients (7 with solid tumours and 1 with Crohn's disease) receiving 100-300 mg/day (4). The two failures occurred in patients who had received 200 mg/day, on day 6 and 19 of therapy, respectively. In another study, four patients with deep-seated Candida infections improved clinically with prolonged fluconazote therapy, 100 mg/day (R.D. Diamond et al., Tenth Congress of the International Society of Human and Animal Mycology, Barcelona, 1988, Abstract). A few additional single cases of invasive infection were successfully treated with low-dose oral or i.v. fluconazole (5-7). Our case demonstrates that i.v. fluconazole, given initially at 200 rag/day and later at 100 mg/day, may not achieve fungicidal levels in some patients or for specific isolates (i.e. Torulopsis glabrata). As the patient weighed 60 kg, the 200 rag/day initially administered was in compliance with the recommended loading dose of 3 mg/kg. However, a higher dose of 300-400 rag/day may have been beneficial. In spite of the encouraging data on successful fluconazole therapy in systemic candidiasis, it should be used with caution in lifethreatening infections, and clinical response should be carefully monitored.
Y. Siegman-Igra 1. M.Y. R a b a u 2 1 Infectious Disease Unit, and 2Department of Surgery "C", IchilovHospital,Tel-AvivSouraskyMedicalCenter, TeI-Aviv University, 6 Weizman Street, TeI-Aviv 64239, Israel.
References Fluconazole. Medical Letter on Drugs and Therapeutics 1990, 32: 50--52. 2. Robinson PA, Knirsch AK, Joseph JA: Fluconazole for life-threateningfungal infections in patients who cannot be treated with conventionalantifungalagents. Reviews of Infectious Diseases 1990, 12: 349-363. 1,
Eur. J. Clin. Microbiol. Infect. Dis.
3. Bodey GP: Fungal infections in cancer patients - an overview. Pfizer International, 1990. 4. MeunierF: Fluconazoletreatment of fungal infections in the immune-compromised host. Seminars in Ontology 1990, 17: 19-23. 5. IsalskaBJ, Stanbridge TN: Fluconazole in the treatment of candidal prosthetic valve endocarditis. British Medical Journal 1988, 297: 178-179. 6. Dave Y, Hickey MM, Wilkins EGL: Fluconazole in renal candidosis. Lancet 1989, i: 163-164. 7. Kirk AJB, Gould FK, Freeman R, Corris PA, Dark JH: Fluconazole and candidosis. Lancet 1989, i: 339.
P o s s i b l e Failure o f I t r a c o n a z o l e in P r e v e n t i n g Fungal Infection in a N e u t r o p e n i c L e u k a e m i a Patient
In the treatment of leukaemia patients in our hospital, we use a combination of antimicrobial and antifungal drugs as selective gut decontamination to prevent the development of gramnegative and fungal infections (1). This regimen consists of a combination of norfloxacin 400 mg b.i.d, and itraconazole 200 mg b.i.d., a new antifungal drug (Janssen Pharmaceuticals, Belgium). During the first week, colistin solution, 1 mg per ml as mouthwash, 5 ml four times a day and nystatin suspension 105 IU per ml as mouthwash, 5 ml four times daily are also administered. Recently, we encountered a severe complication in a patient who was treated with itraconazole, which is claimed to be a very active agent againstAspergillus and Candida species in a prophylactic setting (1-3). A 54-year-old male was referred to our hospital for treatment of acute leukaemia, diagnosed elsewhere. Bone marrow aspirate showed 96.4 % Sudan positive and PAS weak positive blast cells. Immunophenotyping of blood and bone marrow revealed a high percentage CD11, CD13, CD33, CDw65, MPO and partial HLA-Dr positive cells. Acute myeloid leukaemia, type M1 (FAB classification), was diagnosed. The first chemotherapy course, daunorubicin 45 mg/m2, days 1-3, combined with cytosine arabinoside 200 mg/m2, days 4-11 (4), was complicated by respiratory tract infections during the neutropenic episode, despite selective gut decontamination. On chest X-ray infiltrates were revealed in the lower left lung segment, later spreading to the upper region and also to the right lung. The lesion
