Article information
El tratamiento antifúngico combinado, simultáneo o secuencial, se ha considerado, con frecuencia, como una alternativa adecuada para mejorar los resultados que se obtienen con la monoterapia. Las equinocandinas, grupo de fármacos al que pertenece la anidulafungina, poseen un mecanismo de acción diferente del de los demás fármacos antifúngicos, lo que aventura cuando menos buenas posibilidades de sinergia con otros grupos. Sin embargo, la mayoría de los datos disponibles sobre la eficacia de las diferentes combinaciones procede de modelos de infección en animales, datos in vitro y comunicación de casos clínicos, mientras son muy escasos los datos procedentes de ensayos clínicos controlados. Los datos disponibles no permiten afirmar que el tratamiento combinado tenga una eficacia significativamente superior a la de la monoterapia; sin embargo, puede ser adecuado para el tratamiento de micosis invasoras graves asociadas a una elevada tasa de mortalidad, tales como las formas de aspergilosis que cursan con afección del sistema nervioso central o afección pulmonar extensa, cavitada o con insuficiencia respiratoria, y las infecciones causadas por hongos multirresistentes.
Palabras clave:
Anidulafungina
Tratamiento combinado
Equinocandina
Combined, simultaneous or sequential antifungal therapy has often been considered an appropriate option to improve the results obtained with monotherapy. Anidulafungin belongs to the echinocandin family, which has a different mechanism of action from the remaining antifungal agents, a characteristic that heralds a good chance of synergy with other groups. However, most of the data available on the efficacy of different combinations comes from animal models of infection, «in vitro» data and case reports, while data from controlled clinical trials are scarce. The available data are insufficient to allow us to conclude that the efficacy of combined therapy is significantly superior to that of monotherapy. However, the efficacy of combined therapy may be adequate for the treatment of severe invasive mycoses associated with high mortality rates, such as forms of aspergillosis that provoke central nervous system involvement, extensive pulmonary involvement, cavitated areas, or respiratory failure and infections caused by multiresistant fungi.
Key words:
Anidulafungin
Combined therapy
Echinocandin
Full text is only aviable in PDF
Bibliografía
[1.]
R. Herbrecht, D.W. Denning, T.F. Patterson, J.E. Bennett, R.E. Greene, J.W. Oestmann, et al.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.
N Engl J Med, 347 (2002), pp. 408-415
[2.]
B. Almirante, D. Rodriguez, B.J. Park, M. Cuenca-Estrella, A.M. Planes, M. Almela, et al.
Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, barcelona, Spain, from 2002 to 2003.
J Clin Microbiol, 43 (2005), pp. 1829-1835
[3.]
J.A. Ribes, C.L. Vanover-Sams, D.J. Baker.
Zygomycetes in human disease.
Clin Microbiol Rev, 13 (2000), pp. 236-301
[4.]
M. Nucci, E. Anaissie.
Fusarium infections in immunocompromised patients.
Clin Microbiol Rev, 20 (2007), pp. 695-704
[5.]
C.M. Van der Horst, M.S. Saag, G.A. Cloud, R.J. Hamill, J.R. Graybill, J.D. Sobel, et al.
Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.
N Engl J Med, 337 (1997), pp. 15-21
[6.]
J.E. Edwards Jr., G.P. Bodey, R.A. Bowden, T. Buchner, B.E. De Pauw, S.G. Filler, et al.
International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections.
Clin Infect Dis, 25 (1997), pp. 43-59
[7.]
D.P. Kontoyiannis, R.E. Lewis.
Toward more effective antifungal therapy: the prospects of combination therapy.
Br J Haematol, 126 (2004), pp. 165-175
[8.]
C. Fohrer, L. Fornecker, Y. Nivoix, C. Cornila, C. Marinescu, R. Herbrecht.
Antifungal combination treatment: a future perspective.
Int J Antimicrob Agents, 27 (2006), pp. 25-30
[9.]
M. Cuenca-Estrella.
Combinations of antifungal agents in therapy —what value are they?.
J Antimicrob Chemother, 54 (2004), pp. 854-869
[10.]
J.A. Karlowsky, D.J. Hoban, G.G. Zhanel, B.P. Goldstein.
In vitro interactions of anidulafungin with azole antifungals, amphotericin B and 5-fluorocytosine against Candida species.
Int J Antimicrob Agents, 27 (2006), pp. 174-177
[11.]
E.E. Roling, M.E. Klepser, A. Wasson, R.E. Lewis, E.J. Ernst, M.A. Pfaller.
Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY 303366) alone and in combination against Candida spp. and Crytococcus neoformans via time-kill methods.
Diagn Microbiol Infect Dis, 43 (2002), pp. 13-17
[12.]
M.A. Hossain, G.H. Reyes, L.A. Long, P.K. Mukherjee, M.A. Ghannoum.
Efficacy of caspofungin combined with amphotericin B against azole-resistant Candida albicans.
J Antimicrob Chemother, 51 (2003), pp. 1427-1429
[13.]
E.R. Oliveira, A.W. Fothergill, W.R. Kirkpatrick, B.J. Coco, T.F. Patterson, S.W. Redding.
In vitro interaction of posaconazole and caspofungin against clinical isolates of Candida glabrata.
Antimicrob Agents Chemother, 49 (2005), pp. 3544-3545
[14.]
P.K. Mukherjee, D.J. Sheehan, C.A. Hitchcock, M.A. Ghannoum.
Combination treatment of invasive fungal infections.
Clin Microbiol Rev, 18 (2005), pp. 163-194
[15.]
M.D. Johnson, C. MacDougall, L. Ostrosky-Zeichner, J.R. Perfect, J.H. Rex.
Combination antifungal therapy.
Antimicrob Agents Chemother, 48 (2004), pp. 693-715
[16.]
M. Marine, C. Serena, J. Pastor, G. Quindos, A.J. Carrillo, J. Guarro.
In vitro activity of micafungin combined with itraconazole against Candida spp.
Int J Antimicrob Agents, 30 (2007), pp. 463-465
[17.]
C. Serena, B. Fernandez-Torres, F.J. Pastor, L. Trilles, S. Lazera Mdos, N. Nolard, et al.
In vitro interactions of micafungin with other antifungal drugs against clinical isolates of four species of Cryptococcus.
Antimicrob Agents Chemother, 49 (2005), pp. 2994-2996
[18.]
C. Serena, M. Marine, F.J. Pastor, N. Nolard, J. Guarro.
In vitro interaction of micafungin with conventional and new antifungals against clinical isolates of Trichosporon, Sporobolomyces and Rhodotorula.
J Antimicrob Chemother, 55 (2005), pp. 1020-1023
[19.]
S. Arikan, M. Lozano-Chiu, V. Paetznick, J.H. Rex.
In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp.
Antimicrob Agents Chemother, 46 (2002), pp. 245-247
[20.]
I. Shalit, Y. Shadkchan, Z. Samra, N. Osherov.
In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points.
Antimicrob Agents Chemother, 47 (2003), pp. 1416-1418
[21.]
S. Perea, G. Gonzalez, A.W. Fothergill, W.R. Kirkpatrick, M.G. Rinaldi, T.F. Patterson.
In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp.
Antimicrob Agents Chemother, 46 (2002), pp. 3039-3041
[22.]
A. Philip, Z. Odabasi, J. Rodriguez, V.L. Paetznick, E. Chen, J.H. Rex, et al.
In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp.
Antimicrob Agents Chemother, 49 (2005), pp. 3572-3574
[23.]
M. Cuenca-Estrella, A. Gomez-Lopez, G. Garcia-Effron, L. Alcazar-Fuoli, E. Mellado, M.J. Buitrago, et al.
Combined activity in vitro of caspofungin, amphotericin B, and azole agents against itraconazole-resistant clinical isolates of Aspergillus fumigatus.
Antimicrob Agents Chemother, 49 (2005), pp. 1232-1235
[24.]
A. Yekutiel, I. Shalit, Y. Shadkchan, N. Osherov.
In vitro activity of caspofungin combined with sulfamethoxazole against clinical isolates of Aspergillus spp.
Antimicrob Agents Chemother, 48 (2004), pp. 3279-3283
[25.]
D.B. White, H.K. Slocum, Y. Brun, C. Wrzosek, W.R. Greco.
A new nonlinear mixture response surface paradigm for the study of synergism: a three drug example.
Curr Drug Metab, 4 (2003), pp. 399-409
[26.]
J. Meletiadis, T. Stergiopoulou, E.M. O'Shaughnessy, J. Peter, T.J. Walsh.
Concentration-dependent synergy and antagonism within a triple antifungal drug combination against Aspergillus species: analysis by a new response surface model.
Antimicrob Agents Chemother, 51 (2007), pp. 2053-2064
[27.]
Y.F. Brun, C.G. Dennis, W.R. Greco, R.J. Bernacki, P.J. Pera, J.J. Bushey, et al.
Modeling the combination of amphotericin B, micafungin, and nikkomycin Z against Aspergillus fumigatus in vitro using a novel response surface paradigm.
Antimicrob Agents Chemother, 51 (2007), pp. 1804-1812
[28.]
C. Yustes, J. Guarro.
In vitro synergistic interaction between amphotericin B and micafungin against Scedosporium spp.
Antimicrob Agents Chemother, 49 (2005), pp. 3498-3500
[29.]
M. Cuenca-Estrella, A. Alastruey-Izquierdo, L. Alcazar-Fuoli, L. Bernal-Martinez, A. Gomez-Lopez, M.J. Buitrago, et al.
In Vitro Activities of 35 Double Combinations of Antifungal Agents against Scedosporium apiospermum and Scedosporium prolificans.
Antimicrob Agents Chemother, 52 (2008), pp. 1136-1139
[30.]
M. Cuenca-Estrella, A. Gomez-Lopez, M.J. Buitrago, E. Mellado, G. Garcia-Effron, J.L. Rodriguez-Tudela.
In vitro activities of 10 combinations of antifungal agents against the multiresistant pathogen Scopulariopsis brevicaulis.
Antimicrob Agents Chemother, 50 (2006), pp. 2248-2250
[31.]
W.R. Kirkpatrick, S. Perea, B.J. Coco, T.F. Patterson.
Efficacy of caspofungin alone and in combination with voriconazole in a Guinea pig model of invasive aspergillosis.
Antimicrob Agents Chemother, 46 (2002), pp. 2564-2568
[32.]
V. Petraitis, R. Petraitiene, A.A. Sarafandi, A.M. Kelaher, C.A. Lyman, H.E. Casler, et al.
Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin.
J Infect Dis, 187 (2003), pp. 1834-1843
[33.]
W.J. Steinbach, D.A. Stevens, D.W. Denning.
Combination and sequential antifungal therapy for invasive aspergillosis: review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001.
Clin Infect Dis, 37 (2003), pp. S188-S224
[34.]
L. Ostrosky-Zeichner, D. Kontoyiannis, J. Raffalli, K.M. Mullane, J. Vazquez, E.J. Anaissie, et al.
International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia.
Eur J Clin Microbiol Infect Dis, 24 (2005), pp. 654-661
[35.]
J.W. Baddley, P.G. Pappas.
Combination antifungal therapy for the treatment of invasive yeast and mold infections.
Curr Infect Dis Rep, 9 (2007), pp. 448-456
[36.]
K.A. Marr, M. Boeckh, R.A. Carter, H.W. Kim, L. Corey.
Combination antifungal therapy for invasive aspergillosis.
Clin Infect Dis, 39 (2004), pp. 797-802
[37.]
D.W. Denning, K.A. Marr, W.M. Lau, D.P. Facklam, V. Ratanatharathorn, C. Becker, et al.
Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis.
J Infect, 53 (2006), pp. 337-349
[38.]
S.C. Metcalf, D.H. Dockrell.
Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts.
J Infect, 55 (2007), pp. 287-299
[39.]
N. Singh, K.J. Pursell.
Combination therapeutic approaches for the management of invasive aspergillosis in organ transplant recipients.
Mycoses, 51 (2008), pp. 99-108
[40.]
T.B. Aliff, P.G. Maslak, J.G. Jurcic, M.L. Heaney, K.N. Cathcart, K.A. Sepkowitz, et al.
Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin.
Cancer, 97 (2003), pp. 1025-1032
[41.]
J. Maertens, A. Glasmacher, R. Herbrecht, A. Thiebaut, C. Cordonnier, B.H. Segal, et al.
Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis.
Cancer, 107 (2006), pp. 2888-2897
[42.]
N. Singh, A.P. Limaye, G. Forrest, N. Safdar, P. Munoz, K. Pursell, et al.
Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.
Transplantation, 81 (2006), pp. 320-326
[43.]
D.P. Kontoyiannis, R. Hachem, R.E. Lewis, G.A. Rivero, H.A. Torres, J. Thornby, et al.
Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies.
Cancer, 98 (2003), pp. 292-299
[44.]
D. Caillot, A. Thiebaut, R. Herbrecht, S. De Botton, A. Pigneux, F. Bernard, et al.
Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial).
Cancer, 110 (2007), pp. 2740-2746
[45.]
G. Damaj, V. Ivanov, B. Le Brigand, E. D’Incan, M.F. Doglio, K. Bilger, et al.
Rapid improvement of disseminated aspergillosis with caspofungin/voriconazole combination in an adult leukemic patient.
Ann Hematol, 83 (2004), pp. 390-393
[46.]
C. Tascini, E. Tagliaferri, R. Iapoce, A. Leonildi, F. Menichetti.
Caspofungin in combination with itraconazole and amphotericin B for the treatment of invasive Aspergillosis in humans, with a method to test ex vivo synergism.
Clin Microbiol Infect, 9 (2003), pp. 901-902
[47.]
J.M. Vagace, C. Sanz-Rodriguez, M.S. Casado, N. Alonso, M. Garcia-Dominguez, F.G. De la Llana, et al.
Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report.
BMC Infect Dis, 7 (2007), pp. 40
[48.]
Y. Nivoix, A. Zamfir, P. Lutun, F. Kara, V. Remy, B. Lioure, et al.
Combination of caspofungin and an azole or an amphotericin B formulation in invasive fungal infections.
J Infect, 52 (2006), pp. 67-74
[49.]
W.J. Steinbach, W.A. Schell, J.L. Miller, J.R. Perfect.
Scedosporium prolificans osteomyelitis in an immunocompetent child treated with voriconazole and caspofungin, as well as locally applied polyhexamethylene biguanide.
J Clin Microbiol, 41 (2003), pp. 3981-3985
[50.]
A. Safdar.
Progressive cutaneous hyalohyphomycosis due to Paecilomyces lilacinus: rapid response to treatment with caspofungin and itraconazole.
Clin Infect Dis, 34 (2002), pp. 1415-1417
Copyright © 2008. Elsevier España S.L.. Todos los derechos reservados
