PROFILAXIS CON FLUOROQUINOLONAS EN PACIENTES NEUTROPENICOS





PROFILAXIS CON FLUOROQUINOLONAS EN PACIENTES NEUTROPENICOS

(especial para SIIC © Derechos reservados)
La profilaxis con quinolonas, siempre y cuando la resistencia lo permita, debe ser propuesta como uso de rutina en los pacientes neutropénicos.
cruciani9.jpg Autor:
Mario Cruciani
Columnista Experto de SIIC

Institución:
Center of Preventive Medicine & HIV Outpatient Clinic


Artículos publicados por Mario Cruciani
Recepción del artículo
15 de Febrero, 2006
Aprobación
1 de Marzo, 2006
Primera edición
6 de Julio, 2006
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Las fluoroquinolonas han sido extensamente estudiadas como profilaxis en los pacientes oncológicos con neutropenia. Su eficacia se revisó en diversos metaanálisis. Hasta el momento, no hay dudas acerca de que la profilaxis con fluoroquinolonas produjo una disminución en la aparición de infecciones gramnegativas en los individuos neutropénicos. Por el contrario, los beneficios de la profilaxis con fluoroquinolonas sobre otros parámetros de la morbimortalidad secundaria a la infección no fueron evidentes. En parte, la efectividad global limitada de la profilaxis con fluoroquinolonas se relaciona con la cobertura inadecuada de las bacterias grampositivas. Los resultados de un metaanálisis no avalaron el uso rutinario de cobertura frente a las bacterias grampositivas en combinación con la profilaxis con fluoroquinolonas en pacientes neutropénicos. Sin embargo, la utilización de cobertura frente a gérmenes grampositivos puede considerarse en subgrupos especiales, como las personas con neutropenia grave, mucositis oral, trasplante de médula ósea y tratamiento con altas dosis de arabinósido de citosina. Recientemente, ensayos clínicos grandes, bien realizados, confirmaron la eficacia a largo plazo de la profilaxis con fluoroquinolonas. También hay pruebas de que la profilaxis con fluoroquinolonas constituye una intervención costo-efectiva. Además, se demostró una reducción de la mortalidad en un metaanálisis reciente y en informes provenientes de los centros oncológicos de Europa se comprobó un rebote importante de las bacteriemias por patógenos gramnegativos después de la interrupción de la profilaxis con fluoroquinolonas. En vista de estos hallazgos, la profilaxis con quinolonas durante la granulocitopenia, siempre y cuando la resistencia lo permita, aún es apropiada.

Palabras clave
granulocitopenia, profilaxis antibiótica, quinolonas, cáncer


Artículo completo

(castellano)
Extensión:  +/-12.46 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Fluoroquinolones have been studied extensively as prophylaxis in neutropenic cancer patients. Their efficacy has been reviewed in several meta-analyses. As yet, there is no question that prophylaxis with fluoroquinolones has led to a decrease in the occurrence of gram-negative infections in neutropenic patients. By contrast, the benefits of fluoroquinolone prophylaxis on other parameters of infection-related morbidity and on the occurrence of infection-related mortality are not evident. Part of the limited overall effectiveness of fluoroquinolone prophylaxis is related to the inadequate coverage for gram-positive bacteria. The results of a meta-analysis do not support the routine use of gram-positive coverage in combination with quinolone prophylaxis in neutropenic patients; however, the use gram-positive coverage can be considered in particular subgroups of neutropenic patients, such as those with more severe neutropenia, oral mucositis, bone marrow transplantation, and receiving high-dose cytosine arabinoside. Recent well conducted, large clinical trials confirm the long lasting efficacy of fluoroquinolones prophylaxis. There is also evidence that fluoroquinolones prophylaxis is a cost-effective intervention. Moreover, a reduction in mortality has been demonstated in a recent meta-analysis, and reports from cancer centers in Europe have shown a striking rebound of gram-negative bacteremias after discontinuation in the use of prophylaxis with fluoroquinolones. In light of the these findings, prophylaxis with a quinolone during granulocytopenia, where resistance permits, is still appropriate.

Riassunto
Negli ultimi 20 anni la profilassi delle infezioni batteriche nel paziente granulocitopenico mediante l'utilizzo di fluorchinoloni è stata ampiamente studiata. L'efficacia di tale applicazione è stata inoltre oggetto di diverse meta-analisi. Di certo si puo' affermare che l'efficacia dei fluorchinoloni nel ridurre le infezioni da gram-negativi nel paziente neutropenico è ben documentata: Per contro, i benefici della profilassi con fluorchinoloni su altri parametri di morbidita' e sulla mortalita' legata ad infezione è incerta. Parte della limitata efficacia dei fluorchinoloni in profilassi è legata all'inadeguata copertura nei confronti dei batteri gram-positivi. I risultati di una meta-analisi al riguardo non supportano l'impiego routinario dei fluorchinoloni in associazione a farmaci attivi nei confronti di gram-positivi per la profilassi del paziente granulocitopenico; tuttavia l'associazione con tali farmaci potrebbe essere presa in considerazione in alcuni sottogruppi di pazienti ad alto rischio (neutropenia particolarmente grave, trapiantati di midollo, chemioterapia con alte dosi di cytosine arabinoside). Recenti studi di ampio respiro hanno confermato l'efficacia a lungo termine della profilassi con fluorchinoloni. Vi è inoltre l'evidenza che la profilassi con fluorchinoloni nel neutropenico è un intervento costo-efficace. Inoltre, una recente meta-analisi ha evidenziato una riduzione della mortalità per infezione nei pazienti profilassati, mentre varie segnalazioni da centri Europei per la terapia del cancro evidenziano una netta ripresa delle batteriemie da gram-negativi dopo l'interruzione dell'impiego in profilassi dei fluorchinoloni. Globalmente, tutti questi dati supportano il concetto che l'impiego della profilassi con fluorchinoloni nei pazienti granulocitopenici, qualora non sussistano problemi di resistenza, è ancora attuale ed appropriato.

Key words
granulocytopenia, antibiotic prophylaxis, quinolones, cancer


Full text
(english)
para suscriptores/ assinantes

Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Infectología
Relacionadas: Atención Primaria, Farmacología, Hematología, Medicina Interna



Comprar este artículo
Extensión: 12.46 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Mario Cruciani, Center of Preventive Medicine & HIV Outpatient Clinic, 37135, V. Germania 20, Verona, Italia
Bibliografía del artículo
1. Pizzo PA. Considerations for the prevention of infectious complications in patient with cancer. Rev Infect Dis 1989; 11 (Suppl. 7):S1551-63.
2. Zinner SH. Treatment and prevention of infections in immunocompromised hosts. In: Gorbach SL, Bartlett JG, Blacklow NR, editors. Infectious Diseases, 2nd edition. WB Saunders Company, Philadelphia.
3. Cruciani M. Antibacterial prophylaxis. Int J Antimicrob Agents 2000; 16:123-5.
4. Kerr KG. The prophylaxis of bacterial infections in neutropenic patients. J Antimicrob Chemother 1999; 44:587-91.
5. Van der Waaij D, Berghuis-de Vries JM, Lekkerker-van der Wees JEC. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J Hyg 1971; 69:405-11.
6. EORTC International Antimicrobial Therapy Project Group: Cotrimoxazole in the prevention of infection in neutropenic patients. J Infect Dis 1984; 150:372-9.
7. Cruciani M, Rampazzo R, Malena M et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis 1996; 23:795-805.
8. Rotstein C, Mandell LA, Goldberg N. Fluoroquinolone prophylaxis for profoundly neutropenic cancer patients: a meta-analysis. Current Oncology 1997; 4 suppl 2:2-7.
9. Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol. 1998;16:1179-87.
10. Cruciani M, Malena M, Bosco O, Nardi S, Serpelloni G, Mengoli C. Reappraisal with meta-analysis of the addition of Gram-positive prophylaxis to fluoroquinolone in neutropenic patients. J Clin Oncol 2003; 21:4127-37.
11. Klastersky J. Science and pragmatism in the treatment and prevention of neutropenic infection. J Antimicrob Chemother 1998; 41 (Suppl. D):13-24.
12. Oppheneim BA, Hartley JE, Lee W et al. Outbreak of coagulase-negative staphylococcus highly resistant to ciprofloxacin in a leukemia unit. Br Med J 1989; 299:294-7.
13. Kotilainen P, Nikoskelainen J, Huovinen P. Emergence of ciprofloxacin-resistant coagulase-negative staphylococcal skin flora in immunocompromised patients receiving ciprofloxacin. J Infect Dis 1990; 161:41-4.
14. Bochud PY, Eggiman Ph, Calandra Th. et al. Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis 1994; 18:25-31.
15. Tunkel AR, Sepkowitz KA. Infections caused by viridans streptococci in patients with neutropenia. Clin Infect Dis 2002; 34:1524-9.
16. O'Grady NP, Alexander M, Dellinger EP et al. Guidelines for the prevention of intravascular catheter-related infections Clin Infect Dis 2002; 35:1281-307.
17. Razonable RR, Litzow MR, Khaliq Y et al. Bacteremia due to viridans group streptococci with diminished susceptibility to levofloxacin among neutropenic patients receiving levofloxacin prophylaxis. Clin Infect Dis 2002; 34:1469-74.
18. Guglielmo BJ, Graff L, Linker C et al. Emergence of fluoroquinolone-resistant viridans streptococci associated with levofloxacin prophylaxis in neutropenic cancer patients. Abstracts of the Infectious Diseases Society of America 40th annual meeting. Chicago, October 24-27, 2002 (Abstr. 19).
19. Jones RN, Pfaller MA. Potencies of newer fluoroquinolones against Viridans group Streptococci isolated in 637 cases of bloodstream infection in the SENTRY Antimicrobial Surveillance Program (1997 to 1999): beyond Canada! Antimicrob Agents Chemother 2000; 44:2922-3.
20. Kaneko A, Sasaki J, Shimadzu M et al. Comparison of gyrA and parC mutations and resistance levels among fluoroquinolone-resistant isolates and laboratory-derived mutants of oral streptococci. J Antimicrob Chemother 2000; 45:771-5.
21. Hooper DC. Mechanisms of action of antimicrobials: focus on fluoroquinolones. Clin Infect Dis 2001 ; 32 (suppl. 1):S9-15.
22. Prabhu RM, Elliott MA, Patel R . Apparent failure of moxifloxacin to prevent ciprofloxacin- and levofloxacin-susceptible Pseudomonas aeruginosa bacteremia in neutropenic patients undergoing peripheral blood stem cell transplantation. Clin Infect Dis 2004; 38:1043-1045.
23. Reuter S, Sigge A, Bommer M et al. Moxifloxacin-prophylaxis during neutropenia in patients with hemato-oncological malignancies. Abst. K-1540. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, December 16-19, 2005.
24. Minenko SV, Dmitrieva NV, Sokolova EN, Zhukov NV, Ptushkin VV. Efficacy of moxifloxacin (Avelox) in prophylaxis of infection in patients with profound neutropenia. Antibiot Khimioter 2004;49:26-31.
25. Kern WV, Andrioff E, Oethinger M et al. Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrob Agents Chemother 1994 ; 36:681-7.
26. Cometta A, Calandra T, Bille J et al. Escherichia coli resistant to fluoroquinolones in patients with cancer and neutropenia. N Engl J Med 1994; 330:1240-1 (letter).
27. Carratalá J, Fernández Sevilla A, Tubau F. Emergence of quinolone-resistant Escherichia coli in neutropenic patients with cancer who have received prophylactic norfloxacin. Clin Infect Dis 1995; 20:557-60.
28. Kern WV, Klose K, Jellen-Ritter AS, et al. Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia. Eur J Clin Microbiol Infect Dis 2005; 24:111-8.
29. Martino R, Subira M, Altes A et al. Effect of discontinuing prophylaxis with norfloxacin in patients with hematologic malignancies and severe neutropenia. A matched case-control study of the effect on infectious morbidity. Acta Haematol 1998; 99:206-11.
30. Nucci M. Resistant bacteria in stem cell transplant recipients. Rev Bras Hematol Hemoter 2002; 24:220-227.
31. Gómez L, Garau J, Estrada C, et al . Ciprofloxacin prophylaxis in patients with acute leukemia and granulocytopenia in an area with a high prevalence of ciprofloxacin-resistant Escherichia coli. Cancer 2003; 97:419-24.
32. Delarive P, Baumgarter JD, Glauser MP et al. Evaluation de la prophylaxie antibiotique chez les patients neutropeniques avec hemopathie maligne. Scweizerische Medizinische Wonchenschrift 2000; 130:1837-44.
33. De Bock R, Cometta A, Kern W et al. Incidence of single agent gram-negative bacteremias in neutropenic cancer patients in EORTC-IATG trials of empirical therapy for febrile neutropenia. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, December 2001 (Abstr. L-773).
34. Reuter S, Kern WV, Sigge A, Dohner H, Marre R, Kern P, Von Baum H. Impact of fluoroquinolone prophylaxis on reduced infection-related mortality among patients with neutropenia and hematologic malignancies. Clin Infect Dis 2005; 40:1087-93.
35. Cruciani M. Malena M, Rampazzo R et al. A cost-effectiveness analysis of prophylaxis in granulocytopenic patients. 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, September 15-18, 1996 (abs. N22).
36. The GIMEMA infection Program. Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. Ann Intern Med 1991; 115:7-12.30.
37. Messori A, Trippoli S, Tendi E. Related G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation. J Clin Pharm Ther 1996; 21:57-63.
38. Bucaneve G, Micozzi A, Menichetti F, et al. Levofloxacin to prevent bacterial infection in patients with cancer. N Engl J Med. 2005; 353:977-987.
39. Cullen M, Steven N, Billingham L, et al. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 2005; 353:988-998.
40. Baden LR. Prophylactic antimicrobial agents and the importance of fitness. N Engl J Med 2005; 353:1052-1054.
41. Gilbert DN, Kohlhepp SJ, Slama KA, et al. Phenotypic resistance of Staphylococcus aureus, selected Enterobacteriaceae and Pseudomonas aeruginosa after single and multiple in vitro exposures to ciprofloxacin, levofloxacin and trovafloxacin. Antimicrob Agents Chemother 2001; 45:883-92.
42. Polk RE, Johnson CK, McClish D, Wenzel RP, Edmond MB. Predicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities. Clin Infect Dis 2004; 15:39:497-503.
43. Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 2005; 142:979-95.
44. Karp JE, Merz WG, Hendricksen C, et al. Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1987; 106:1-7.
45 Hughes WT, Armstrong D, Bodey GP et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002; 34:730-51.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618