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Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis

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Abstract

In neutropenic patients receiving quinolone prophylaxis, bacteremia with viridans group streptococci resistant to quinolones is a known complication. The frequency of occurrence of quinolone-resistant organisms colonizing the oropharynx during antibacterial prophylaxis with a quinolone is not well defined. In 48 patients undergoing hematopoietic stem cell transplantation, the prevalence of quinolone resistance in viridans group streptococci colonizing the oropharynx before and during antibacterial prophylaxis with gatifloxacin or moxifloxacin (most with concomitant penicillin) was determined. For quinolone-resistant isolates, mutations in the genes gyrA and parC, which confer resistance to quinolones, were analyzed. Seventy-four isolates before and 27 isolates during quinolone use were recovered from patients' oropharynxes. The numbers of susceptible isolates recovered before versus during quinolone use were as follows: 52 (70%) versus three (11%) for ciprofloxacin, 66 (89%) versus eight (30%) for levofloxacin, 66 (89%) versus ten (37%) for gatifloxacin, and 67 (91%) versus 11 (41%) for moxifloxacin (p<0.0001). Mutations in gyrA and/or parC were detected in quinolone-resistant isolates. Quinolone-resistant viridans group streptococci are frequently found in the oropharynx of neutropenic patients after a brief (median, 8 days) exposure to gatifloxacin or moxifloxacin.

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References

  1. Anonymous (1994) Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. A trial of oral penicillin V or placebo combined with pefloxacin. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. JAMA 272:1183–1189

    Article  Google Scholar 

  2. 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

    PubMed  CAS  Google Scholar 

  3. Haahr V, Peterslund NA, Moller JK (1997) The influence of antimicrobial prophylaxis on the microbial and clinical findings in patients after autologous bone marrow transplantation. Scand J Infect Dis 29:623–626

    Article  PubMed  CAS  Google Scholar 

  4. Patrick CC (1997) Use of fluoroquinolones as prophylactic agents in patients with neutropenia. Pediatr Infect Dis J 16:135–139; discussion 160–162

    Article  PubMed  CAS  Google Scholar 

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Yeh SP, Hsueh EJ, Yu MS, Wu H, Wang YC (1999) Oral ciprofloxacin as antibacterial prophylaxis after allogeneic bone marrow transplantation: a reappraisal. Bone Marrow Transplant 24:1207–1211

    Article  PubMed  CAS  Google Scholar 

  7. Warren RE, Wimperis JZ, Baglin TP, Constantine CE, Marcus R (1990) Prevention of infection by ciprofloxacin in neutropenia. J Antimicrob Chemother 26:109–123

    PubMed  Google Scholar 

  8. Kern W, Kurrle E (1991) Ofloxacin versus trimethoprim-sulfamethoxazole for prevention of infection in patients with acute leukemia and granulocytopenia. Infection 19:73–80

    Article  PubMed  CAS  Google Scholar 

  9. Anonymous (1991) Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. The GIMEMA Infection Program. Ann Intern Med 115:7–12

    Google Scholar 

  10. Bochud PY, Eggiman P, Calandra T, Van Melle G, Saghafi L, Francioli P (1994) Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis 18:25–31

    PubMed  CAS  Google Scholar 

  11. Schots R, Trullemans F, Van Riet I, Kaufman L, Hafsia A, Meddeb B, Hadj Ali ZB, Ben Abid H, Lauwers S, Van Camp B (2000) The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation. Transplantation 69:1511–1514

    Article  PubMed  CAS  Google Scholar 

  12. Persson L, Vikerfors T, Sjoberg L, Engervall P, Tidefelt U (2000) Increased incidence of bacteraemia due to viridans streptococci in an unselected population of patients with acute myeloid leukaemia. Scand J Infect Dis 32:615–621

    Article  PubMed  CAS  Google Scholar 

  13. Yuen KY, Woo PC, Liang RH, Chiu EK, Chen FF, Wong SS, Lau YL, Ha SY, Peiris JS, Siau H, Chan TK (1998) Clinical significance of alimentary tract microbes in bone marrow transplant recipients. Diagn Microbiol Infect Dis 30:75–81

    Article  PubMed  CAS  Google Scholar 

  14. Kennedy HF, Morrison D, Kaufmann ME, Jackson MS, Bagg J, Gibson BE, Gemmell CG, Michie JR (2000) Origins of Staphylococcus epidermidis and Streptococcus oralis causing bacteraemia in a bone marrow transplant patient. J Med Microbiol 49:367–370

    PubMed  CAS  Google Scholar 

  15. Bochud PY, Calandra T, Francioli P (1994) Bacteremia due to viridans streptococci in neutropenic patients: a review. Am J Med 97:256–264

    Article  PubMed  CAS  Google Scholar 

  16. Broun ER, Wheat JL, Kneebone PH, Sundblad K, Hromas RA, Tricot G (1994) Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation. Antimicrob Agents Chemother 38:576–579

    PubMed  CAS  Google Scholar 

  17. Classen DC, Burke JP, Ford CD, Evershed S, Aloia MR, Wilfahrt JK, Elliott JA (1990) Streptococcus mitis sepsis in bone marrow transplant patients receiving oral antimicrobial prophylaxis. Am J Med 89:441–446

    Article  PubMed  CAS  Google Scholar 

  18. Marron A, Carratala J, Gonzalez-Barca E, Fernandez-Sevilla A, Alcaide F, Gudiol F (2000) Serious complications of bacteremia caused by viridans streptococci in neutropenic patients with cancer. Clin Infect Dis 31:1126–1130

    Article  PubMed  CAS  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. Elting LS, Bodey GP, Keefe BH (1992) Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clin Infect Dis 14:1201–1207

    PubMed  CAS  Google Scholar 

  21. Spanik S, Trupl J, Kunova A, Botek R, Sorkovska D, Grey E, Studena M, Lacka J, Oravcova E, Krchnakova A, Rusnakova V, Svec J, Krupova I, Grausova S, Stopkova K, Koren P, Krcmery V Jr (1997) Viridans streptococcal bacteraemia due to penicillin-resistant and penicillin-sensitive streptococci: analysis of risk factors and outcome in 60 patients from a single cancer centre before and after penicillin is used for prophylaxis. Scand J Infect Dis 29:245–249

    Article  PubMed  CAS  Google Scholar 

  22. Diekema DJ, Beach ML, Pfaller MA, Jones RN, Group SP (2001) Antimicrobial resistance in viridans group streptococci among patients with and without the diagnosis of cancer in the USA, Canada and Latin America. Clin Microbiol Infect 7:152–157

    Article  PubMed  CAS  Google Scholar 

  23. Gordon KA, Beach ML, Biedenbach DJ, Jones RN, Rhomberg PR, Mutnick AH (2002) Antimicrobial susceptibility patterns of beta-hemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997–2000). Diagn Microbiol Infect Dis 43:157–162

    Article  PubMed  CAS  Google Scholar 

  24. Bassetti M, Dembry LM, Farrel PA, Callan DA, Andriole VT (2001) Comparative antimicrobial activity of gatifloxacin with ciprofloxacin and beta-lactams against gram-positive bacteria. Diagn Microbiol Infect Dis 41:143–148

    Article  PubMed  CAS  Google Scholar 

  25. de Azavedo JC, Trpeski L, Pong-Porter S, Matsumura S, Low DE (1999) In vitro activities of fluoroquinolones against antibiotic-resistant blood culture isolates of viridans group streptococci from across Canada. Antimicrob Agents Chemother 43:2299–2301

    PubMed  Google Scholar 

  26. Andriole VT (ed) (2000) The quinolones. Academic, San Diego

  27. Ferrandiz MJ, Oteo J, Aracil B, Gomez-Garces JL, De La Campa AG (1999) Drug efflux and parC mutations are involved in fluoroquinolone resistance in viridans group streptococci. Antimicrob Agents Chemother 43:2520–2523

    PubMed  CAS  Google Scholar 

  28. Kaneko A, Sasaki J, Shimadzu M, Kanayama A, Saika T, Kobayashi I (2000) Comparison of gyrA and parC mutations and resistance levels among fluoroquinolone-resistant isolates and laboratory-derived mutants of oral streptococci. J Antimicrob Chemother 45:771–775

    Article  PubMed  CAS  Google Scholar 

  29. Facklam R (2002) What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin Microbiol Rev 15:613–630

    Article  PubMed  Google Scholar 

  30. National Committee for Clinical Laboratory Standards (2001) Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute (formerly NCCLS), Wayne, PA

  31. National Committee for Clinical Laboratory Standards (2003) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Clinical and Laboratory Standards Institute (formerly NCCLS), Wayne, PA

  32. Hall L, Doerr KA, Wohlfiel SL, Roberts GD (2003) Evaluation of the MicroSeq System for identification of mycobacteria by 16S ribosomal DNA sequencing and its integration into a routine clinical mycobacteriology laboratory. J Clin Microbiol 41:1447–1453

    Article  PubMed  CAS  Google Scholar 

  33. Janoir C, Zeller V, Kitzis MD, Moreau NJ, Gutmann L (1996) High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA. Antimicrob Agents Chemother 40:2760–2764

    PubMed  CAS  Google Scholar 

  34. Gonzalez I, Georgiou M, Alcaide F, Balas D, Linares J, de la Campa AG (1998) Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci. Antimicrob Agents Chemother 42:2792–2798

    PubMed  CAS  Google Scholar 

  35. Timmers GJ, Dijstelbloem Y, Simoons-Smit AM, van Winkelhoff AJ, Touw DJ, Vandenbroucke-Graul CMJE, 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

    Article  PubMed  CAS  Google Scholar 

  36. Schmitz FJ, Fisher A, Boos M, Mayer S, Milatovic D, Fluit AC (2001) Quinolone-resistance mechanisms and in vitro susceptibility patterns among European isolates of Streptococcus mitis, Streptococcus sanguis, and Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis 20:219–222

    Article  PubMed  CAS  Google Scholar 

  37. Janoir C, Podglajen I, Kitzis MD, Poyart C, Gutmann L (1999) In vitro exchange of fluoroquinolone resistance determinants between Streptococcus pneumoniae and viridans streptococci and genomic organization of the parEparC region in S. mitis. J Infect Dis 180:555–558

    Article  PubMed  CAS  Google Scholar 

  38. Schmitz FJ, Milatovic D, Boos M, Mayer S, Fluit AC (2002) In vitro activity of the novel des-F(6) quinolone BMS-284756 against genetically characterized clinical streptococcal isolates, including isolates with reduced quinolone susceptibility. J Antimicrob Chemother 49:698–701

    Article  PubMed  CAS  Google Scholar 

  39. Erickson PR, Herzberg MC (1999) Emergence of antibiotic-resistant Streptococcus sanguis in dental plaque of children after frequent antibiotic therapy. Pediatr Dent 21:181–185

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the bone marrow transplant coordinators R.A. Goodew, T.S. Jahns, M.M. Knudsvig, P.A. McLean, and J.M. Theuer for helping with patient recruitment, T.L. Hoskin from the Center for Patient Oriented Research for statistical assistance, and Dr. A. Trampuz for critical review of the manuscript. Financial support was received from the Mayo Foundation.

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Correspondence to R. Patel.

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Prabhu, R.M., Piper, K.E., Litzow, M.R. et al. Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis. Eur J Clin Microbiol Infect Dis 24, 832–838 (2005). https://doi.org/10.1007/s10096-005-0037-3

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