Fungal infections in neutropenic patients: a 8-year prospective study

Nucci, Marcio; Pulcheri, Wolmar; Spector, Nelson; Bueno, Ana Paula; Bacha, Paulo Cesar; Caiuby, Maria Julieta; Derossi, Andrea; Costa, Rosane; Morals, José Carlos; Oliveira, Halley Pacheco de

doi:10.1590/S0036-46651995000500004

Abstracts

In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p<0.001), longer duration of profound (<100/mm³) neutropenia (p<0.001), the use of corticosteroids (p<0.001), gram-positive bacteremia (p=0.002) and younger age (p=0.03). In multivariate analysis only recovery of the neutropenia (p<0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p=0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.

Aspergillosis; Fusarium sp. infections; Candidiasis; Trichosporon sp. infections; Opportunistic fungal infections

Com o objetivo de melhor caracterizar incidência, epidemiologia, síndromes específicas, tratamento e prognóstico associado com infecções fúngicas sistêmicas em pacientes neutropênicos foi feito um estudo prospectivo de 8 anos. Durante este período foram diagnosticadas 30 infecções fúngicas em 30 pacientes neutropênicos febris (10%). Houve 15 casos de candidíase, 5 aspergiloses pulmonares, 3 sinusites por Aspergillus fumigatus, 5 infecções por Fusarium sp., uma infecção por Trichosporon sp., e uma infecção por Rhodotorula rubra. As hemoculturas foram positivas em 18 casos (60%). Os fatores de risco para infecção fúngica em análise multivariada foram: presença de cateter venoso central (p<0,001), duração maior de neutropenia <100/mm³ (p<0,001), uso de corticosteróides (p<0,001), bacteremia por germes gram-positivos (p=0,002) e idade menor (p=0.03). Em análise multivariada apenas recuperação da neutropenia (p<0,001) esteve associada com bom prognóstico, enquanto que o diagnóstico de infecção por Fusarium sp. (p=0,006) se correlacionou com um mau prognóstico. A taxa de óbito foi de 43%. Não houve diferença estatisticamente significante nas taxas de óbito em pacientes que receberam (52%) ou não (50%) terapia anti-fúngica. A identificação de grupos de risco, síndromes específicas e fatores prognósticos pode contribuir para a redução na elevada letalidade das infecções fúngicas em pacientes neutropênicos.

MICOLOGY

Fungal infections in neutropenic patients. A 8-year prospective study

Infecções fúngicas em pacientes neutropênicos. Estudo prospectivo de 8 anos

Marcio Nucci^I,II; Wolmar Pulcheri^I; Nelson Spector^I; Ana Paula Bueno^II; Paulo Cesar Bacha^II; Maria Julieta Caiuby^I; Andrea Derossi^II; Rosane Costa^II; José Carlos Morals^I; Halley Pacheco de Oliveira^I

^IServiços de Hematologia, Patologia Clínica e Anatomia Patológica, Hospital Universitário (HUCFF) - Universidade Federal do Rio de Janeiro

^IISeção de Hematologia, Laboratório de Micologia, Hospital Universitário (HUPE) - Universidade do Estado do Rio de Janeiro

^{Correspondence to} Correspondence to: Dr. Marcio Nucci Hospital Universitário Clementino Fraga Filho Av. Brigadeiro Trompovsky s/n 21941-590 Rio de Janeiro, RJ, Brasil

SUMMARY

In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p<0.001), longer duration of profound (<100/mm³) neutropenia (p<0.001), the use of corticosteroids (p<0.001), gram-positive bacteremia (p=0.002) and younger age (p=0.03). In multivariate analysis only recovery of the neutropenia (p<0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p=0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.

Keywords: Aspergillosis; Fusarium sp. infections; Candidiasis; Trichosporon sp. infections; Opportunistic fungal infections.

RESUMO

Com o objetivo de melhor caracterizar incidência, epidemiologia, síndromes específicas, tratamento e prognóstico associado com infecções fúngicas sistêmicas em pacientes neutropênicos foi feito um estudo prospectivo de 8 anos. Durante este período foram diagnosticadas 30 infecções fúngicas em 30 pacientes neutropênicos febris (10%). Houve 15 casos de candidíase, 5 aspergiloses pulmonares, 3 sinusites por Aspergillus fumigatus, 5 infecções por Fusarium sp., uma infecção por Trichosporon sp., e uma infecção por Rhodotorula rubra. As hemoculturas foram positivas em 18 casos (60%). Os fatores de risco para infecção fúngica em análise multivariada foram: presença de cateter venoso central (p<0,001), duração maior de neutropenia <100/mm³ (p<0,001), uso de corticosteróides (p<0,001), bacteremia por germes gram-positivos (p=0,002) e idade menor (p=0.03). Em análise multivariada apenas recuperação da neutropenia (p<0,001) esteve associada com bom prognóstico, enquanto que o diagnóstico de infecção por Fusarium sp. (p=0,006) se correlacionou com um mau prognóstico. A taxa de óbito foi de 43%. Não houve diferença estatisticamente significante nas taxas de óbito em pacientes que receberam (52%) ou não (50%) terapia anti-fúngica. A identificação de grupos de risco, síndromes específicas e fatores prognósticos pode contribuir para a redução na elevada letalidade das infecções fúngicas em pacientes neutropênicos.

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Recebido para publicação em 11/05/1995

Aceito para publicação em 15/09/1995

1. ANAISSIE, E.J. - Opportunistic mycosis in the immunocompromised host: experience at a cancer center and review. Clin. infect. Dis., 14 (suppl. 1): S43-S53, 1992.
2. ANTTILA, V.; RUUTU, P.; BONDESTAM, S. et al. - Hepatosplenic yeast infection in patients with acute leukemia: a diagnostic problem. Clin. infect. Dis., 18: 979-981, 1994.
3. BILLE, J.; STOCKMAN, L.; ROBERTS, G.D.; HORSTMEIER, C.D. & ILSTRUP, D.M. - Evaluation of a lysis-centrifugation system for recovery of yeasts and filamentous fungi from blood. J. clin. Microbiol., 18: 469-471, 1983.
4. BODEY, G.P. - Fungal infection and fever of unknown origin in neutropenic patients. Amer. J. Med., 80 (suppl. 5C): 112-119, 1986.
5. BODEY, G.P. - Fungal infections in cancer patients. Ann. N. Y. Acad. Sci., 544: 431-442, 1988.
6. BODEY, G.P. - Azole antifungal agents. Clin. infect. Dis., 14(suppl. 1): S161-S169, 1992.
7. BODEY, G.P.; ANAISSIE, E.; GUTTERMAN, J. & VADHAN-RAJ, S. - Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for fungal infection in patients with cancer. Clin. infect. Dis., 17: 705-707, 1993.
8. BODEY, G.P.; BUELTMANN, B.; DUGUID, W. et al. - Fungal infections in cancer patients: an international autopsy survey. Europ. J. clin. Microbiol. infect. Dis., 11: 99-109, 1992.
9. DEGREGORIO, M.W.; LEE, W.M.F.; LINKER, C.A.; JACOBS, R.A. & RIES, C.A. - Fungal infections in patients with acute leukemia. Amer. J. Med., 73: 543-548, 1982.
10. GEFTER, W.B.; ALBELDA, S.M.; TALBOT, G.H. et al. - Invasive pulmonary aspergillosis and acute leukemia. Limitations in the diagnostic utility of the air crescent sign. Radiology, 157: 605-610, 1985.
11. GERSON, S.L.; TALBOT, G.H.; HURWITZ, S. et al. - Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann. intern. Med., 100: 345-351, 1984.
12. GERSON S.L.;TALBOT, G.H.; LUSK, E. et al.- Invasive pulmonary aspergillosis in adult acute leukemia; clinical clues to its diagnosis. J. clin. Oncol., 3: 1109-1116, 1985.
13. GROOPMAN, J.E.; MOLINA, J.M. & SCADDEN, D.T. - Hematopoietic growth factors. New Engl. J. Med.,321: 1449-1459, 1989.
14. GUIOT, H.F.L.; FIBBE, W.E. & van't WOUT, J.W. - Risk factors for fungal infection in patients with malignant hematologic disorders: implications for empirical therapy and prophylaxis. Clin. infect. Dis., 18: 525-532, 1994.
15. KUHLMAN, J.E.; FISHMAN, E.K.; BURCH, P.A. et al. - Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest, 92: 95-99, 1987.
16. MAARTENS, G. & WOOD, M.J. - The clinical presentation and diagnosis of invasive fungal infections. J. Antimicrob. Chemother., 28(suppl.A): 13-22, 1991.
17. MARTINO, P.; GASTALDI, R.; RACCAH, R. & GIRMENIA, C. - Clinical patterns of Fusarium infections in immunocompromised patients. J. Infect., 28 (suppl. 1): 7-15, 1994.
18. NUCCI, M.; PULCHERI, W.; SPECTOR, N. et al. - Cutaneous involvement of systemic fungal infections in neutropenic patients. Haematologica, 77: 522-523, 1992.
19. NUCCI, M.; SPECTOR, N.; LUCENA, S. et al. - Three cases of Fusarium species in neutropenic patients. Europ. J. clin. Microbiol. infect. Dis., 11: 1160-1162, 1992.
20. NUCCI, M.; SCHECHTER, M.; SPECTOR, N. et. al. - Antibiotic regimen as an independent risk factor for disseminated fungal infections in neutropenic patients in Brazil. Trans. roy. Soc. trop. Med. Hyg., 89: 107-110, 1995.
21. NUCCI, M.; PULCHERI, W.; BACHA, P.C. et al. - Amphotericin B followed by itraconazole in the treatment of disseminated fungal infections in neutropenic patients. Mycoses, 37: 433-437, 1994.
22. RAAD, I.I. & BODEY, G.P. - Infectious complications of indwelling vascular catheters. Clin. infect. Dis., 15: 197-210, 1992.
23. TALBOT, G.H.; HUANG, A. & PROVENCHER, M. - Invasive aspergillosis rhinosinusitis in patients with acute leukemia. Rev. infect. Dis., 13: 219-232, 1991.
24. THALER, M.; PASTAKIA, B.; SHAWKER, T.H.; O'LEARY, T. & PIZZO, P.A. - Hepatic candidiasis in cancer patients: the evolving picture of a syndrome. Ann. intern. Med., 108: 88-100, 1988.
25. WALSH, T.J. & DIXON, D.M. - Nosocomial aspergillosis: environmental microbiology, hospital epidemiology, diagnosis and treatment. Europ. J. Epidem., 5: 131-142, 1989.

Correspondence to:

Dr. Marcio Nucci

Hospital Universitário Clementino Fraga Filho

Av. Brigadeiro Trompovsky s/n

21941-590 Rio de Janeiro, RJ, Brasil

Publication Dates

Publication in this collection
21 Sept 2006
Date of issue
Oct 1995

History

Accepted
15 Sept 1995
Received
11 May 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ANAISSIE, E.J. - Opportunistic mycosis in the immunocompromised host: experience at a cancer center and review. Clin. infect. Dis., 14 (suppl. 1): S43-S53, 1992.

[2] 2. ANTTILA, V.; RUUTU, P.; BONDESTAM, S. et al. - Hepatosplenic yeast infection in patients with acute leukemia: a diagnostic problem. Clin. infect. Dis., 18: 979-981, 1994.

[3] 3. BILLE, J.; STOCKMAN, L.; ROBERTS, G.D.; HORSTMEIER, C.D. & ILSTRUP, D.M. - Evaluation of a lysis-centrifugation system for recovery of yeasts and filamentous fungi from blood. J. clin. Microbiol., 18: 469-471, 1983.

[4] 4. BODEY, G.P. - Fungal infection and fever of unknown origin in neutropenic patients. Amer. J. Med., 80 (suppl. 5C): 112-119, 1986.

[5] 5. BODEY, G.P. - Fungal infections in cancer patients. Ann. N. Y. Acad. Sci., 544: 431-442, 1988.

[6] 6. BODEY, G.P. - Azole antifungal agents. Clin. infect. Dis., 14(suppl. 1): S161-S169, 1992.

[7] 7. BODEY, G.P.; ANAISSIE, E.; GUTTERMAN, J. & VADHAN-RAJ, S. - Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for fungal infection in patients with cancer. Clin. infect. Dis., 17: 705-707, 1993.

[8] 8. BODEY, G.P.; BUELTMANN, B.; DUGUID, W. et al. - Fungal infections in cancer patients: an international autopsy survey. Europ. J. clin. Microbiol. infect. Dis., 11: 99-109, 1992.

[9] 9. DEGREGORIO, M.W.; LEE, W.M.F.; LINKER, C.A.; JACOBS, R.A. & RIES, C.A. - Fungal infections in patients with acute leukemia. Amer. J. Med., 73: 543-548, 1982.

[10] 10. GEFTER, W.B.; ALBELDA, S.M.; TALBOT, G.H. et al. - Invasive pulmonary aspergillosis and acute leukemia. Limitations in the diagnostic utility of the air crescent sign. Radiology, 157: 605-610, 1985.

[11] 11. GERSON, S.L.; TALBOT, G.H.; HURWITZ, S. et al. - Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann. intern. Med., 100: 345-351, 1984.

[12] 12. GERSON S.L.;TALBOT, G.H.; LUSK, E. et al.- Invasive pulmonary aspergillosis in adult acute leukemia; clinical clues to its diagnosis. J. clin. Oncol., 3: 1109-1116, 1985.

[13] 13. GROOPMAN, J.E.; MOLINA, J.M. & SCADDEN, D.T. - Hematopoietic growth factors. New Engl. J. Med.,321: 1449-1459, 1989.

[14] 14. GUIOT, H.F.L.; FIBBE, W.E. & van't WOUT, J.W. - Risk factors for fungal infection in patients with malignant hematologic disorders: implications for empirical therapy and prophylaxis. Clin. infect. Dis., 18: 525-532, 1994.

[15] 15. KUHLMAN, J.E.; FISHMAN, E.K.; BURCH, P.A. et al. - Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest, 92: 95-99, 1987.

[16] 16. MAARTENS, G. & WOOD, M.J. - The clinical presentation and diagnosis of invasive fungal infections. J. Antimicrob. Chemother., 28(suppl.A): 13-22, 1991.

[17] 17. MARTINO, P.; GASTALDI, R.; RACCAH, R. & GIRMENIA, C. - Clinical patterns of Fusarium infections in immunocompromised patients. J. Infect., 28 (suppl. 1): 7-15, 1994.

[18] 18. NUCCI, M.; PULCHERI, W.; SPECTOR, N. et al. - Cutaneous involvement of systemic fungal infections in neutropenic patients. Haematologica, 77: 522-523, 1992.

[19] 19. NUCCI, M.; SPECTOR, N.; LUCENA, S. et al. - Three cases of Fusarium species in neutropenic patients. Europ. J. clin. Microbiol. infect. Dis., 11: 1160-1162, 1992.

[20] 20. NUCCI, M.; SCHECHTER, M.; SPECTOR, N. et. al. - Antibiotic regimen as an independent risk factor for disseminated fungal infections in neutropenic patients in Brazil. Trans. roy. Soc. trop. Med. Hyg., 89: 107-110, 1995.

[21] 21. NUCCI, M.; PULCHERI, W.; BACHA, P.C. et al. - Amphotericin B followed by itraconazole in the treatment of disseminated fungal infections in neutropenic patients. Mycoses, 37: 433-437, 1994.

[22] 22. RAAD, I.I. & BODEY, G.P. - Infectious complications of indwelling vascular catheters. Clin. infect. Dis., 15: 197-210, 1992.

[23] 23. TALBOT, G.H.; HUANG, A. & PROVENCHER, M. - Invasive aspergillosis rhinosinusitis in patients with acute leukemia. Rev. infect. Dis., 13: 219-232, 1991.

[24] 24. THALER, M.; PASTAKIA, B.; SHAWKER, T.H.; O'LEARY, T. & PIZZO, P.A. - Hepatic candidiasis in cancer patients: the evolving picture of a syndrome. Ann. intern. Med., 108: 88-100, 1988.

[25] 25. WALSH, T.J. & DIXON, D.M. - Nosocomial aspergillosis: environmental microbiology, hospital epidemiology, diagnosis and treatment. Europ. J. Epidem., 5: 131-142, 1989.

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