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Tigecycline in febrile neutropenic patients with haematological malignancies: a retrospective case documentation in four university hospitals

  • Clinical and Epidemiological Study
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Abstract

Objectives

Tigecycline (TGC) is a first-in-class glycylcycline with an expanded spectrum of activity. Although TGC has not been prospectively studied in febrile neutropenia (FN), we observed that occasionally critically ill neutropenic patients unresponsive to other antibiotics were treated with TGC in our departments. The aim of our study was to analyse effectiveness and toxicity of TGC in FN.

Methods

Data of infectious episodes treated with TGC were retrospectively collected. Baseline data of patients, haematological malignancy, infection and adverse events were documented. Success was defined as defervescence (≥7 days) in the absence of any sign of persistent infection.

Results

Data of 35 patients with haematological malignancies and FN were evaluated. Median duration of neutropenia was 25 days (range 6–69 days). The type of infection was pneumonia in 24 patients, four microbiologically documented infections, three clinically documented infections and four with fever of unknown origin. The TGC was administered after a median of two (range 1–5) prior antibiotic regimens. Treatment was successful in 15 (43 %) patients. In patients with prolonged neutropenia (≥28 days), response was significantly lower (13 vs. 79 %; p = 0.001). Eight (23 %) patients died during the fever episode. Grade 3–4 toxicity occurred in five (14 %) patients.

Conclusion

Our results showed promising response rates to TGC and very low toxicity rates compared to the generally low response rate of third-line antibiotic therapies, indicating that TGC may be a successful alternative for salvage treatment of febrile neutropenia, but further study is needed.

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References

  1. Chastre J. Evolving problems with resistant pathogens. Review. Clin Microbiol Infect. 2008;14:3–14.

    Article  CAS  PubMed  Google Scholar 

  2. Carmeli Y. Strategies for managing today’s infections. Review. Clin Microbiol Infect. 2008;14:22–31.

    Article  PubMed  Google Scholar 

  3. Sader HS, Streit JM, Fritsche TR, Jones RN. Antimicrobial susceptibility of gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002–2004). Clin Microbiol Infect. 2006;12:844–52.

    Article  CAS  PubMed  Google Scholar 

  4. Mendes C, Kiffer CR, Blosser-Middleton RS, Jones ME, Karlowsky JA, Barth A, Rossi F, Andrade S, Sader HS, Thornsberry C, Sahm DF. Antimicrobial susceptibility to levofloxacin and other antibacterial agents among common respiratory pathogens-a Brazilian perspective from the GLOBAL Surveillance Initiative 2001–2002. Clin Microbiol Infect. 2004;10:521–6.

    Article  CAS  PubMed  Google Scholar 

  5. Slama TG. Gram-negative antibiotic resistance: there is a price to pay. Crit Care. 2008;12(Suppl 4):S4.

    Article  PubMed  Google Scholar 

  6. Guner R, Hasanoglu I, Keske S, Kalem AK, Tasyaran MA. Outcomes in patients infected with carbapenem-resistant Acinetobacter baumannii and treated with tigecycline alone or in combination therapy. Infection. 2011;39:515–8.

    Article  CAS  PubMed  Google Scholar 

  7. Florescu I, Beuran M, Dimov R, Razbadauskas A, Bochan M, Fichev G, Dukart G, Babinchak T, Cooper CA, Ellis-Grosse EJ, Dartois N, Gandjini H. Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study. J Antimicrob Chemother. 2008;62(Suppl 1):i17–28.

    Article  CAS  PubMed  Google Scholar 

  8. Sacchidanand S, Penn RL, Embil JM, Campos ME, Curcio D, Ellis-Grosse E, Loh E, Rose G. Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: results from a phase 3, randomized, double-blind trial. Int J Infect Dis. 2005;9:251–61.

    Article  CAS  PubMed  Google Scholar 

  9. Babinchak T, Ellis-Grosse E, Dartois N, Rose GM, Loh E. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis. 2005;41(Suppl 5):S354–67.

    Article  CAS  PubMed  Google Scholar 

  10. Oliva ME, Rekha A, Yellin A, Pasternak J, Campos M, Rose GM, Babinchak T, Ellis-Grosse EJ, Loh E. A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: nCT00081744]. BMC Infect Dis. 2005;5:88.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis. 2005;41(Suppl 5):S341–53.

    Article  CAS  PubMed  Google Scholar 

  12. Fomin P, Koalov S, Cooper A, Babinchak T, Dartois N, De Vane N, Castaing N, Tellado J. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections—the European experience. J Chemother. 2008;20(Suppl 1):12–9.

    Article  CAS  PubMed  Google Scholar 

  13. Meagher AK, Passarell JA, Cirincione BB, Van Wart SA, Liolios K, Babinchak T, Ellis-Grosse EJ, Ambrose PG. Exposure-response analyses of tigecycline efficacy in patients with complicated skin and skin-structure infections. Antimicrob Agents Chemother. 2007;51:1939–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Bradford PA, Weaver-Sands DT, Petersen PJ. In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis. 2005;41(Suppl 5):S315–32.

    Article  CAS  PubMed  Google Scholar 

  15. Pankey GA. Tigecycline. J Antimicrob Chemother. 2005;56:470–80.

    Article  CAS  PubMed  Google Scholar 

  16. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Infectious Diseases Society of America: clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2011;52:e56–93.

    Article  PubMed  Google Scholar 

  17. Glasmacher A, Lilienfeld-Toal M, Schulte S, Hahn C, Schmidt-Wolf IG, Prentice A. An evidence-based evaluation of important aspects of empirical antibiotic therapy in febrile neutropenic patients. Clin Microbiol Infect. 2005;11(Suppl 5):17–23.

    Article  CAS  PubMed  Google Scholar 

  18. Schiel X, Link H, Maschmeyer G, Glass B, Cornely OA, Buchheidt D, Wilhelm M, Silling G, Helmerking M, Hiddemann W, Ostermann H, Hentrich M. A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II. Infection. 2006;34:118–26.

    Article  CAS  PubMed  Google Scholar 

  19. Hiddemann W, Maschmeyer G, Link H, Helmerking M, Adam D. Therapy of infections in patients with acute leukemia. Med Klin (Munich). 1997;92:406–9.

    Article  CAS  Google Scholar 

  20. Link H, Bohme A, Cornely OA, Hoffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW. Antimicrobial therapy of unexplained fever in neutropenic patients–guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol. 2003;82(Suppl 2):S105–17.

    Article  CAS  PubMed  Google Scholar 

  21. Chemaly RF, Hanmod SS, Jiang Y, Rathod DB, Mulanovich V, Adachi JA, Rolston KV, Raad II, Hachem RY. Tigecycline use in cancer patients with serious infections: a report on 110 cases from a single institution. Medicine (Baltimore). 2009;88:211–20.

    Article  Google Scholar 

  22. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14.

    Article  CAS  PubMed  Google Scholar 

  23. Tygacil T. Tygacil (tigecycline IV) prescribing information (package insert). Philadelphia: Wyeth Pharmaceuticals; 2009.

    Google Scholar 

  24. Sbrana F, Malacarne P, Viaggi B, Costanzo S, Leonetti P, Leonildi A, Casini B, Tascini C, Menichetti F. Carbapenem-Sparing Antibiotic Regimens for Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Intensive Care Unit. Clin Infect Dis. 2013;56:697–700.

    Article  CAS  PubMed  Google Scholar 

  25. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. A randomized phase 2 trial to evaluate the clinical efficacy of two high tigecycline dosage regimens versus imipenem/cilastatin in hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013;57:1756–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tanaseanu C, Milutinovic S, Calistru PI, Strausz J, Zolubas M, Chernyak V, Dartois N, Castaing N, Gandjini H, Cooper CA. Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia. BMC Pulm Med. 2009;9:44.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Bergallo C, Jasovich A, Teglia O, Oliva ME, Lentnek A, de Wouters L, Zlocowski JC, Dukart G, Cooper A, Mallick R. Safety and efficacy of intravenous tigecycline in treatment of community-acquired pneumonia: results from a double-blind randomized phase 3 comparison study with levofloxacin. Diagn Microbiol Infect Dis. 2009;63:52–61.

    Article  CAS  PubMed  Google Scholar 

  28. Bassetti M, Nicolini L, Repetto E, Righi E, Del Bono V, Viscoli C. Tigecycline use in serious nosocomial infections: a drug use evaluation. BMC Infect Dis. 2010;10:287.

    PubMed Central  PubMed  Google Scholar 

  29. Hahn-Ast C, Glasmacher A, Arns A, Muhling A, Orlopp K, Marklein G, Lilienfeld-Toal M. An audit of efficacy and toxicity of teicoplanin versus vancomycin in febrile neutropenia: is the different toxicity profile clinically relevant? Infection. 2008;36:54–8.

    Article  CAS  PubMed  Google Scholar 

  30. Matsuoka H, Tsukamoto A, Shirahashi A, Koga S, Suzushima H, Shibata K, Uozumi K, Yamashita K, Okamura S, Kawano F, Tamura K. Efficacy of intravenous ciprofloxacin in patients with febrile neutropenia refractory to initial therapy. Leuk Lymphoma. 2006;47:1618–23.

    Article  CAS  PubMed  Google Scholar 

  31. Vazquez L, Encinas MP, Morin LS, Vilches P, Gutierrez N, Garcia-Sanz R, Caballero D, Hurle AD. Randomized prospective study comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients. Haematologica. 1999;84:231–6.

    CAS  PubMed  Google Scholar 

  32. Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fatkenheuer G, Wisplinghoff H, Seifert H, Vehreschild MJ. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection. 2012;40:613–9.

    Article  CAS  PubMed  Google Scholar 

  33. Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis. 2008;46:567–70.

    Article  PubMed  Google Scholar 

  34. Peleg AY. Optimizing therapy for Acinetobacter baumannii. Semin Respir Crit Care Med. 2007;28:662–71.

    Article  PubMed  Google Scholar 

  35. Gardiner D, Dukart G, Cooper A, Babinchak T. Safety and efficacy of intravenous tigecycline in subjects with secondary bacteremia: pooled results from 8 phase III clinical trials. Clin Infect Dis. 2010;50:229–38.

    Article  PubMed  Google Scholar 

  36. Conte JE Jr, Golden JA, Kelly MG, Zurlinden E. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int J Antimicrob Agents. 2005;25:523–9.

    Article  CAS  PubMed  Google Scholar 

  37. Rodvold KA, Gotfried MH, Cwik M, Korth-Bradley JM, Dukart G, Ellis-Grosse EJ. Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose. J Antimicrob Chemother. 2006;58:1221–9.

    Article  CAS  PubMed  Google Scholar 

  38. FDA. FDA Drug Safety Communication: increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections. http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm 2010.

  39. Yahav D, Lador A, Paul M, Leibovici L. Efficacy and safety of tigecycline: a systematic review and meta-analysis—authors’ responses. J Antimicrob Chemother. 2011;66:2895–6.

    Article  CAS  Google Scholar 

  40. Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R, Pizzo P, Rolston KV, Shenep JL, Young LS. 1997 Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 1997;25:551–73.

    Article  CAS  PubMed  Google Scholar 

  41. Dale DC, Guerry D, Wewerka JR, Bull JM, Chusid MJ. Chronic neutropenia. Medicine (Baltimore). 1979;58:128–44.

    Article  CAS  Google Scholar 

  42. Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64:328–40.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

This study was supported by a research grant from Wyeth Pfizer pharma GmbH, Münster, Germany.

Author information

Authors and Affiliations

  1. Department of Internal Medicine III, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    K. S. Schwab, C. Hahn-Ast, A. Glasmacher, C. Leyendecker, C. M. Nellessen & P. Brossart

  2. Department of Internal Medicine II, University of Wuerzburg Medical Center, Wuerzburg, Germany

    W. J. Heinz

  3. Department of Internal Medicine, University of Duesseldorf, Duesseldorf, Germany

    U. Germing

  4. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    G. Egerer

  5. Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany

    G. Marklein

  6. Department of Hematology and Oncology, Jena University Hospital, Jena, Germany

    M. von Lilienfeld-Toal

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  1. K. S. Schwab
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  2. C. Hahn-Ast
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  3. W. J. Heinz
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  11. M. von Lilienfeld-Toal
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Correspondence to K. S. Schwab.

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K.S. Schwab and C. Hahn-Ast contributed equally.

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Schwab, K.S., Hahn-Ast, C., Heinz, W.J. et al. Tigecycline in febrile neutropenic patients with haematological malignancies: a retrospective case documentation in four university hospitals. Infection 42, 97–104 (2014). https://doi.org/10.1007/s15010-013-0524-x

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  • DOI: https://doi.org/10.1007/s15010-013-0524-x

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