Abstract
The aim of the present study was to investigate the epidemiologic evolution of fluoroquinolone resistance of E. coli clinical isolates from patients admitted to a hematology-oncology service where fluoroquinolone prophylaxis during neutropenia was recommended as the standard of care for many years but was then discontinued in a trial conducted in patients with acute leukemia. Fluoroquinolones had been shown to decrease the incidence of gram-negative bacteremia in cancer patients with neutropenia, yet it was thought that the emergence of resistance in Escherichia coli and other gram-negative bacteria may have caused a progressive lack of efficacy of fluoroquinolone prophylaxis. Epidemiologic surveillance of fluoroquinolone resistance of E. coli clinical isolates at our cancer center since 1992 showed a continuing influx of new clones not previously observed in the population of cancer patients, an increase in the number of cancer patients per year colonized and/or infected by fluoroquinolone-resistant E. coli (1992–1994, 10–16 patients; 1995–1997, 24–27 patients), and a resistance rate of >50% among E. coli bloodstream isolates of hematology-oncology patients. A 6-month fluoroquinolone prophylaxis discontinuation intervention trial in 1998 suggested that despite increasing resistance among E. coli isolates, fluoroquinolone prophylaxis in acute leukemia patients was still effective in the prevention of gram-negative bacteremia (incidence rates, 8% during the pre-intervention period vs. 20% after discontinuation; p<0.01). The resumption of fluoroquinolone prophylaxis in acute leukemia patients thereafter decreased the incidence of gram-negative bacteremia to the pre-intervention level (9%; p=0.03), while the proportion of in vitro fluoroquinolone resistance in E. coli bacteremia isolates again increased (from 15% during the intervention period to >50% in the post-intervention period). Relative rates of resistance thus were a poor indicator of the potential clinical benefits associated with fluoroquinolone prophylaxis in cancer patients.
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References
Bodey GP (1988) Antimicrobial prophylaxis for infection in neutropenic patients. Curr Clin Topics Infect Dis 9:1–43
Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KVI, Shenep JL, Young LS (2002) 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730–751
Kern WV (2001) Current epidemiology of infections in neutropenic cancer patients. In: Rolston KVI, Rubenstein EB (eds) Febrile neutropenia. Martin Dunitz, London, pp 57–90
Zinner SH(1999) Changing epidemiology of infections in patients with neutropenia and cancer: emphasis on gram-positive and resistant bacteria. Clin Infect Dis 29:490–494
Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, Concia E (1996) Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis 23:795–805
Engels E, Lau J, Barza M (1998) Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol 16:1179–1187
Rotstein C, Mandell LA, Goldberg N (1997) Fluoroquinolone prophylaxis for profoundly neutropenic cancer patients: a meta-analysis. Curr Opin Oncol 4(Suppl 2):S2–S7
Kern WV, Kurrle E (1991) Ofloxacin versus trimethoprim-sulfamethoxazole for infection prevention in acute leukemia. Infection 19:73–80
Kern WV (1998) Epidemiology of fluoroquinolone-resistant Escherichia coli among neutropenic cancer patients. Clin Infect Dis 27:235–237
Liang RH, Yung RW, Chan TK, Chau PY, Lam WK, So SY, Todd D (1990) Ofloxacin versus cotrimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy. Antimicrob Agents Chemother 34:215–218
Talbot GH, Cassileth PA, Paradiso L, Correa-Coronas R, Bond L (1993) Oral enoxacin for infection prevention in adults with acute non-lymphocytic leukemia. Antimicrob Agents Chemother 37:474–482
Ball P (1995) Is resistant Escherichia coli bacteremia an inevitable outcome for neutropenic patients receiving a fluoroquinolone as prophylaxis? Clin Infect Dis 20:561–563
Murphy M, Brown AE, Sepkowitz KA, Bernard EM, Kiehn TE, Armstrong D (1997) Fluoroquinolone prophylaxis for the prevention of bacterial infection in patients with cancer—is it justified? Clin Infect Dis 25:346–347
Nucci M, Pulcheri W, Spector N, Bueno AP, Silveira S, Marangoni D, Ferreira R, Pacheco de Oliveira H (1994) Quinolone prophylaxis in neutropenic patients: efficacy versus resistance. Oncol Reports 1:1101–1105
Young LS (1988) Antimicrobial prophylaxis in the neutropenic host: lessons from the past and perspectives for the future. Eur J Clin Microbiol Infect Dis 7:93–97
Carratala J, Fernandez-Sevilla A, Tubau F, Dominguez MA, Gudiol F (1996) Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis. Antimicrob Agents Chemother 40:503–505
Carratala J, Fernandez-Sevilla A, Tubau F, Callis M, Gudiol F (1995) Emergence of quinolone-resistant Escherichia coli bacteremia in neutropenic patients with cancer who have received prophylactic norfloxacin. Clin Infect Dis 20:557–560
Cometta A, Calandra T, Bille J, Glauser MP (1994) E. coli resistant to fluoroquinolones in patients with cancer and neutropenia. New Engl J Med 330:1240–1241
Kern WV, Andriof E, Oethinger M, Kern P, Hacker J, Marre R (1994) Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrob Agents Chemother 38:681–687
Lang A, de Fina G, Meyer R, Aschbacher R, Rizza F, Mayr O, Casini M (2001) Comparison of antimicrobial use and resistance of bacterial isolates in a haematology ward and an intensive care unit. Eur J Clin Microbiol Infect Dis 20:657–660
Perea S, Hidalgo M, Arcediano A, Ramos MJ, Gomez C, Hornedo J, Lumbreras C, Folgueira D, Cortes-Funes H, Rodriguez-Noriega A (1999) Incidence and clinical impact of fluoroquinolone-resistant Escherichia coli in the faecal flora of cancer patients treated with high dose chemotherapy and ciprofloxacin prophylaxis. J Antimicrob Chemother 44:117–120
Somolinos N, Arranz R, del Rey MC, Jimenez ML (1992) Superinfections by Escherichia coli resistant to fluoroquinolones in immunocompromised patients. J Antimicrob Chemother 30:730–731
van Belkum A, Goessens W, van der Schee C, Lemmens-den Toom N, Vos MC, Cornelissen J, Lugtenburg E, de Marie S, Verbrugh H, Lowenberg B, Endtz H (2001) Rapid emergence of ciprofloxacin-esistant enterobacteriaceae containing multiple gentamicin resistance associated integrons in a Dutch hospital. Emerg Infect Dis 7:862–871
van Kraaij MGJ, Dekker AW, Peters E, Fluit A, Verdonck LF, Rozenberg-Arska M (1998) Emergence and infectious complications of ciprofloxacin-resistant Escherichia coli in haematological cancer patients. Eur J Clin Microbiol Infect Dis 17:591–592
von Baum H, Franz U, Geiss HK (2000) Prevalence of ciprofloxacin-resistant Escherichia coli in hematologic-oncologic patients. Infection 28:278–281
Zaidi Y, Hastings M, Murray J, Hassan R, Kurshid M, Mahendra P (2001) Quinolone resistance in neutropenic patients: the effect of prescribing policy in the UK and Pakistan. Clin Lab Haematol 23:39–42
Delarive P, Baumgartner JD, Glauser MP, Cometta A (2000) Evaluation de la prophylaxie antibiotique chez les patients neutropéniques avec hémopathie maligne. Schweiz Med Wochenschr 130:1837–1844
Donnelly JP, Maschmeyer G, Daenen S, for the EORTC Gnotobiotic Project Group (1992) Selective oral antimicrobial prophylaxis for the prevention of infection in acute leukemia—ciprofloxacin versus co-trimoxazole plus colistin. Eur J Cancer 28A:873–878
Gomez L, Garau J, Estrada C, Marquez M, Dalmau D, Xercavins M, Marti JM, Estany C (2003) Ciprofloxacin prophylaxis in patients with acute leukemia and granulocytopenia in an area with a high prevalence of ciprofloxacin-resistant Escherichia coli. Cancer 97:419–424
Mannan P, Kibbler CC, Noone P (1988). Activity of ciprofloxacin and colistin against Pseudomonas aeruginosa isolates from neutropenic patients: a possible approach to prophylaxis. J Antimicrob Chemother 22:953–954
Martino R, Subira M, Altes A, Lopez R, Sureda A, Domingo-Albos A, Pericas R, Brunet S (1998) 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 99:206–211
de Bock R, Cometta A, Kern WV, Aoun M, Caballero D, Engelhard D, Schaffner A, Galazzo M, Paesmans M, Vandenbergh M, Viscoli C (2001) Incidence of single agent gram-negative bacteremia in neutropenic cancer patients in EORTC-IATG trials of empirical therapy for febrile neutropenia. Program and abstracts of the 41st Interscience Conference of Antimicrobial Agents and Chemotherapy. Abstract no. L773
Krüger WH, Hornung RJ, Hertenstein B, Kern WV, Kröger N, Ljungman P, Zander AR, and the EBMT (2001) Practices of infectious disease prevention and management during hematopoietic stem cell transplantation: a survey from the European group for blood and marrow transplantation. J Hematother Stem Cell Res 10:895–903
Gracia Escudero A, Gonzalez MM, Gimenez Garrido F, Clavero Farre C, Garcia Perez MJ, Alvarez Corral G, Reyes Bertos A, Villegas Maldonado G, Rodriguez Cuartero A (2003) Estudio prospectivo y controlado, no aleatorizado de tres cohortes sobre la efectividad de dos pautas antibioticas, levofloxacino y contrimoxazol, en profilaxis antibacteriana de pacientes neutropenicos. Med Clin (Barcelona) 120:321–325
Kern WV, Hay B, Kern P, Marre R, Arnold R (1994) A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis. Antimicrob Agents Chemother 38:465–472
National Committee for Clinical Laboratory Standards (1997) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 3rd edn. Approved standard M100-S7. NCLLS, Wayne, PA
Blackwood RA, Rode CK, Pierson CL, Bloch CA (1997) Pulsed-field gel electrophoresis genomic fingerprinting of hospital Escherichia coli bacteraemia isolates. J Med Microbiol 46:506–510
Oethinger M, Conrad S, Kaifel K, Cometta A, Bille J, Klotz G, Glauser MP, Marre R, the EORTC International Antimicrobial Therapy Cooperative Group, Kern WV (1996) Molecular epidemiology of fluoroquinolone-resistant Escherichia coli bloodstream isolates from patients admitted to European cancer centers. Antimicrob Agents Chemother 40:387–392
Oethinger M, Jellen-Ritter AS, Conrad S, Marre R, Kern WV (1998) Colonization and infection with fluoroquinolone-resistant Escherichia coli among cancer patients: clonal analysis. Infection 26:379–384
Tascini C, Menichetti F, Bozza S, Fedele M, Preziosi R, Allegrucci M, del Favero A, Micozzi A, Martino P, Bistoni F (1999) Molecular typing of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolated from blood of neutropenic cancer patients in a single center. Clin Microbiol Infect 5:457–461
Mandal P, Kapil A, Goswami K, Das B, Dwivedi SN (2001) Uropathogenic Escherichia coli causing urinary tract infections. Indian J Med Res 114:207–211
Threlfall EJ, Cheasty T, Graham A, Rowe B (1997) High-level resistance to ciprofloxacin in Escherichia coli. Lancet 349:403
Contrepois M, Bertin Y, Pohl P, Picard B, Girardeau JP (1998) A study of relationships among F17a producing enterotoxigenic and non-enterotoxigenic Escherichia coli strains isolated from diarrheic calves. Vet Microbiol 64:75–81
Dekker AW, Rozenberg-Arska M, Verhoef J (1987) Infection prophylaxis in acute leukaemia: a comparison of ciprofloxacin with trimethoprim-sulfamethoxazole and colistin. Ann Intern Med 106:7–12
Yeh SP, Hsueh EJ, Yu MS, Wu H, Wang YC (1999) Oral ciprofloxacin as antibacterial prophylaxis after allo-BMT: a reappraisal. Bone Marrow Transplant 24:1207–1211
Munoz L, Martino R, Subira M, Brunet S, Sureda A, Sierra J (1999) Intensified prophylaxis of febrile neutropenia with ofloxacin plus rifampin during severe short-duration neutropenia in patients with lymphoma. Leuk Lymphoma 34:585–589
Gomez-Martin C, Sola C, Hornedo J, Perea S, Lumbreras C, Valenti V, Arcediano A, Rodriguez M, Salazar R, Cortes-Funes H, Hidalgo M (2000) Rifampin does not improve the efficacy of quinolone antibacterial prophylaxis in neutropenic cancer patients: results of a randomized clinical trial. J Clin Oncol 18:2126–2134
Palau J, Picon I, Angel Climent M, Marti R, Aznar E, Sanjuan MC, Maiquez J (2001) [Infection in patients with neutropenia that undergo an autologous peripheral blood stem cell transplant due to breast cancer]. Enferm Infecc Microbiol Clin 19:422–427
Salazar R, Sola C, Maroto P, Tabernero JM, Brunet J, Verger G, Valenti V, Cancelas JA, Ojeda B, Mendoza L, Rodriguez M, Montesinos J, Lopez-Lopez JJ (1999) Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 23:27–33
Bow EJ, Loewen R, Vaughan D (1995) Reduced requirement for antibiotic therapy targeting gram-negative organisms in febrile, neutropenic patients with cancer who are receiving antibacterial chemoprophylaxis with oral quinolones. Clin Infect Dis 20:907–912
Gilbert C, Meisenberg B, Vredenburgh J, Ross M, Hussein A, Perfect J, Peters WP (1994) Sequential prophylactic oral and empiric once-daily parenteral antibiotics for neutropenia and fever after high-dose chemotherapy and autologous bone marrow support. J Clin Oncol 12:1005–1011
Lew MA, Kehoe K, Ritz J, Antman KH, Nadler L, Kalish LA, Finberg R (1991) Prophylaxis of bacterial infections with ciprofloxacin in patients undergoing bone marrow transplantation. Transplantation 51:630–636
Lopez A, Soler JA, Julia A, Novo A, Bueno J (1994) [Prophylaxis with ciprofloxacin in postchemotherapy neutropenia in acute myeloid leukemia] Med Clin (Barcelona) 102:81–85
Nagatomo A, Watanabe K, Kunikane H, Okamoto H, Kunitoh H (1998) A randomized controlled trial of sulfamethoxazole/trimethoprim plus norfloxacin versus sulfamethoxazole/trimethoprim alone for the prophylaxis of bacterial infection during chemotherapy for lung cancer. Lung Cancer 19:121–125
Prentice HG, Hann IM, Nazareth B, Paterson P, Bhamra A, Kibbler CC (2001) Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance. Br J Haematol 115:46–52
Schroeder M, Schadeck-Gressel A, Selbach J, Westerhausen M (1992) Antibiotic prophylaxis with gyrase inhibitors during cytostatically induced granulocytopenia in patients with solid tumors: a double-blind prospective randomized study. Onkologie 15:476–479
Tjan-Heijnen VC, Postmus PE, Ardizzoni A, Manegold CH, Burghouts J, van Meerbeeck J, Gans S, Mollers M, Buchholz E, Biesma B, Legrand C, Debruyne C, Giaccone G, for the EORTC Lung Cancer Group (2001) Reduction of chemotherapy-induced febrile leukopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study. Ann Oncol 12:1359–1368
Yamada T, Dan K, Nomura T (1993) Prevention of bacterial and fungal infections in acute leukemia patients: a new and potent combination of oral norfloxacin and amphotericin B. Intern Med 32:710–715
Yoo JH, Huh DH, Choi JH, Shin WS, Kang MW, Kim CC, Kim DJ (1997) Molecular epidemiological analysis of quinolone-resistant Escherichia coli causing bacteremia in neutropenic patients with leukemia in Korea. Clin Infect Dis 25:1385–1391
Bochud PY, Calandra T, Francioli P (1994) Bacteremia due to viridans streptococci in neutropenic patients: a review. Am J Med 97:256–264
Bow EJ, Mandell LA, Louie TJ, Feld R, Palmer M, Zee B, Pater J (1996) Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group. Ann Intern Med 125:183–190
Timmers GJ, Dijstelbloem Y, Simoons-Smit AM, van Winkelhoff AJ, Touw DJ, Vandenbroucke-Grauls CM, Huijgens PC (2004) Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies. Bone Marrow Transplant 33:847–853
Razonable RR, Litzow MR, Khaliq Y, Piper KE, Rouse MS, Patel R (2002) Bacteremia due to viridans group streptococci with diminished susceptibility to levofloxacin among neutropenic patients receiving levofloxacin prophylaxis. Clin Infect Dis 34:1469–1474
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Kern, W.V., Klose, K., Jellen-Ritter, A.S. 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 24, 111–118 (2005). https://doi.org/10.1007/s10096-005-1278-x
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DOI: https://doi.org/10.1007/s10096-005-1278-x