JAC Advance Access originally published online on February 9, 2006
Journal of Antimicrobial Chemotherapy 2006 57(4):796-798; doi:10.1093/jac/dkl016
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Correspondence |
Successful voriconazole therapy of disseminated Fusarium verticillioides infection in an immunocompromised patient receiving chemotherapy
1 Clinic of Infectious Diseases, IRCCS San Raffaele, Vita-Salute University, Milan, Italy; 2 Institute of Hygiene and Preventive Medicine, Milan University, Milan, Italy; 3 Department of Surgery, Division of Gastrointestinal Surgery, IRCCS San Raffaele, Vita-Salute University, Milan, Italy; 4 Department of Nuclear Medicine, IRCCS San Raffaele, Milan, Italy
* Corresponding author. Tel: +39-02-2643-7939; Fax: +39-02-2643-7030; E-mail: sagnelli.caterina{at}hsr.it
Keywords: fungal infections , antifungals , azoles , F. verticillioides
Sir,
Fusarium spp. are frequently involved in human cutaneous and ocular infection, but also in disseminated diseases. In immunologically compromised hosts, local infection may spread and cause invasive fusarial infection, which is characterized by persistent fever despite broad-spectrum antibacterials and is frequently associated with skin lesions of the limbs (60–80% of patients) and accompanied by myalgias with multiple organ involvement (lung, liver, spleen, kidney, heart and brain). The mortality rate of fusariosis in immunologically compromised hosts is 50–80%.1
A 47-year-old woman underwent total gastrectomy in April 2002 for gastric cancer (signet ring cell carcinoma; T3, N2 and G3), followed by several cycles of chemotherapy with 5-fluorouracil and folinic acid.
In June 2004 peritoneal nodules with a histological appearance of signet ring cell carcinoma were identified and four cycles of adjuvant chemotherapy with docetaxel were administered through a peritoneal port-cath catheter combined with intravenous (iv) 5-fluorouracil and methotrexate, with the last cycle being given on 15 July 2004.2 The patient never showed neutropenia.
On 25 July 2004, she was admitted to our medical centre because of fever (max. 39°C) lasting 40 days despite the use of various antibiotics. Thoracic computed tomography (CT) performed at the end of July revealed several small nodules (max. diameter 1 cm) with a shared peripheral halo in both lungs; subsequent positron emission tomography (PET) images showed hypermetabolism in the right lung lesions (Figure 1, upper panels).
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Fusarium verticillioides was isolated from the cultures of five sequential blood samples and peritoneal fluid; a bronchoscopic alveolar lavage culture was negative. The in vitro susceptibility of F. verticillioides was tested by broth microdilution following CSLI (formerly NCCLS) guidelines M38-A (2002) and showed that the strain was susceptible to amphotericin B (MIC 0.5 mg/L), itraconazole (MIC 0.25 mg/L) and voriconazole (MIC 0.25 mg/L).
Liposomal amphotericin B was given only once because of the onset of a sharp pain in the right shoulder during the infusion. Voriconazole treatment was started on July 28 at a daily dose of 400 mg twice daily and given iv for 63 days in our medical centre and subsequently orally for 11 days at home.
On 2 August, the patient underwent a right hemicolectomy extended to the transverse colon and partial peritonectomy for metastatic colon stenosis and peritoneal carcinoma. Two days later, she underwent surgery for a neoplastic perforation of the terminal ileum. A thoraco-abdominal CT performed on 6 August showed that the small nodules in both lungs had remained unchanged, the presence of bilateral abundant pleural exudate with atelectasia of the inferior lobes and a large amount of fluid in the abdomen. The patient's clinical condition worsened (development of severe dyspnoea, sharp abdominal pain and high fever); bilateral thoracic and several abdominal drainages were inserted.
Various microorganisms were found: Streptococcus mitis, Pseudomonas aeruginosa and Candida glabrata were isolated from blood cultures and abdominal abscess fluid, and the last two organisms were also isolated from the abdominal drainages (together with Enterococcus gallinarum and Enterobacter cloacae) and the peritoneal port-cath catheter.
Many antibiotic courses were given together with voriconazole: amikacin (500 mg twice daily) for 36 days; amoxicillin/clavulanic acid (500 mg thrice daily) for 12 days; linezolid (600 mg twice daily) for 37 days; meropenem (500 mg thrice daily) for 54 days; metronidazole (500 mg thrice daily) for 21 days; vancomycin (500 mg thrice daily) for 12 days; levofloxacin (500 mg once daily) for 26 days; and ceftazidime (2000 mg twice daily) for 5 days.
The clinical condition of the patient improved with the disappearance of fever and abdominal pain. The complete resolution of the pulmonary and pleural lesions was confirmed by a CT scan recorded on 22 October (Figure 1, lower panels).
The patient was considered to have recovered from F. verticillioides infection and returned to her normal activities on 28 September 2004. She was in good clinical condition at the time she was last seen in October 2005.
This is one of only a few reported cases of a patient with cancer undergoing adjuvant chemotherapy being successfully treated with voriconazole for disseminated fusariosis. Her early intolerance to liposomal amphotericin B forced us to treat her with long-term voriconazole therapy, with a very good prognosis and no adverse events. As far as we know, there are previously published reports of voriconazole being successfully used to treat brain Fusarium solani infection in a neutropenic cancer patient, and disseminated fusariosis in an immunocompromised host with acute myeloid leukaemia unresponsive to liposomal amphotericin B.3
The favourable effect of long-term voriconazole treatment in our case underlines its usefulness in treating disseminated Fusarium infection. It is therefore suggested that voriconazole can be considered a valid choice for the treatment of this aggressive mycotic disease.3–6
Transparency declarations
None to declare.
Supplementary data
Figure 1 is available in colour as online Supplementary data at http://jac.oxfordjournals.org/.
Acknowledgements
We would like to thank the patient for her informed consent to use her clinical documentation for publication. No financial support has been given for this report.
References
1. Rodriguez CA, Lujan-Zilbermann J, Woodard P et al. Successful treatment of disseminated fusariosis. Bone Marrow Transplant 2003; 31: 411–2.[CrossRef][Web of Science][Medline]
2. Yonemura Y, Kawamura T, Bandou E et al. Treatment of peritoneal dissemination from gastric cancer by peritonectomy and chemohyperthermic peritoneal perfusion. Br J Surg 2005; 92: 370–5.[CrossRef][Medline]
3. Vincent AL, Cabrero JE, Greene JN et al. Successful voriconazole therapy of disseminated Fusarium solani in the brain of a neutropenic cancer patient. Cancer Control 2003; 10: 414–9.[Medline]
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Durand-Jolly I, Alfandari S, Benchikh Z et al. Successful outcome of disseminated Fusarium infection with skin localization treatment with voriconazole and amphotericin B-lipid complex in a patient with acute leukemia. J Clin Microbiol 2003; 41: 4898–900.
5. Consigny S, Dhedin N, Datry A et al. Successful voriconazole treatment of disseminated Fusarium infection in an immunocompromised patient. Clin Infect Dis 2003; 37: 311–3.[CrossRef][Web of Science][Medline]
6. Donnelly JP, De Pauw BE. Voriconazole-a new therapeutic agent with an extended spectrum of antifungal activity. Clin Microbiol Infect 2004; 10 Suppl 1: 107–17.
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