Skip to main content

Advertisement

SpringerLink
Log in

Tigecycline-associated hypofibrinogenemia in a real-world setting

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Tigecycline is a broad-spectrum antibiotic used to treat infections that do not respond to first-line treatments. High-doses and extended treatments are common; therefore, adverse events might be more frequent and severe than those observed in clinical trials. Several case-reports have referred hypofibrinogenemia in patients who received tigecycline. Objective To analyse the impact of tigecycline use on coagulation parameters, and identify which variables could be related with this. Setting The study was performed at Hospital Universitari Vall Hebron, in Barcelona, Spain. Method Observational, retrospective study. All patients older than 18, who received tigecycline for > 72 h from January 2016 to March 2018 were included. Clinical and laboratory data from before, during and at the end of tigecycline treatment were retrospectively collected. Differences between means were analyzed using the paired-sample Student’s t-test. Binary logistic regression was performed to identify risk factors for hypofibrinogenemia. Main outcome measure Mean difference in fibrinogen plasma concentration and INR, before and at the end of tigecycline treatment. Results 78 patients (mean age 65; SD ± 15.5 years) were identified. The most common indications for tigecycline treatment were abdominal (66%), respiratory tract (16%) and skin&soft tissue (10%) infections. High-dose tigecycline was used in 62% of cases and the median duration of treatment was 12 days. Hypofibrinogenemia occurred in 12 patients, 5 bleeding events were observed and 4 of them required fibrinogen administration. Tigecycline caused significant alterations in fibrinogen plasma concentration (mean decrease 1.76 g/L; IC 95% 1.36 to 2.15) as well as INR (mean increase 0.11; IC 95% 0.05 to 0.17). Both were recovered after treatment cessation. We identified duration of treatment > 4 weeks (OR = 6.6), high-dose tigecycline (OR = 4.75) and high protein C levels (OR = 4.2) as independent variables associated with fibrinogen decrease, but not renal impairment. Conclusions Tigecycline administration has been related with hypofibrinogenemia, especially when high-doses of tigecycline are used. Health professionals should be aware of the potentially severe tigecycline-associated hypofibrinogenemia and monitor coagulation during treatment, especially when high-doses of tigecycline are used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

References

  1. European Medicines Agency. Tygacil®. European Medicines Agency, 2015. https://www.ema.europe.eu/docs/en/documents/overview/tygacil-epar-summary-public_en.pdf. Accessed Dec 2019.

  2. Food and Drugs Administration. Tygacil®. FDA, 2005. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf. Accessed Dec 2019.

  3. 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(12):2895–6.

    Article  CAS  Google Scholar 

  4. Falagas M, Vardakas K, Tsiveriotis K, Triarides N, Tansarli G. Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections. Int J Antimicrob Agents. 2014;44(1):1–7.

    Article  CAS  Google Scholar 

  5. Food and Drugs Administration. FDA Drug Safety Communication: Increased risk of death with Tygacil (tigecycline) compared to other antibiotics used to treat similar infections. FDA, 2010. https://www.fda.gov/Drugs/drug-safety-and-availability/fda-drug-safety-communication-increased-risk-death-tygacil-tigecycline-compared-other-antibiotics. Accessed Dec 2019.

  6. Shen F, Han Q, Xie D, Fang M, Zeng H, Deng Y. Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. Int J Infect Dis. 2015;30:67–73.

    Article  Google Scholar 

  7. Pieringer H, Schmekal B, Biesenbach G, Pohanka E. Severe coagulation disorder with hypofibrinogenemia associated with the use of tigecycline. Ann Hematol. 2010;89(10):1063–4.

    Article  Google Scholar 

  8. Wu X, Zhao P, Dong L, Zhang X. A case report of patient with severe acute cholangitis with tigecycline treatment causing coagulopathy and hypofibrinogenemia. Medicine. 2017;96(49):e9124.

    Article  Google Scholar 

  9. Sabanis N, Paschou E, Gavriilaki E, Kalaitzoglou A, Varileiou S. Hypofibrinogenemia induced by tigecycline: a potentially life-threatening coagulation disorder. Infect Dis. 2015;47(10):743–6.

    Article  Google Scholar 

  10. Zhang Q, Zhou S, Zhou J. Tigecycline treatment causes a decrease in fibrinogen levels. Antimicrob Agents Chemother. 2014;59(3):1650–5.

    Article  Google Scholar 

  11. Routsi C, Kokkoris S, Douka E, Ekonomidou F, Karaiskos I, Giamarellou H. High-dose tigecycline-associated alterations in coagulation parameters in critically ill patients with severe infections. Int J Antimicrob Agents. 2015;45(1):90–3.

    Article  CAS  Google Scholar 

  12. Conde-Estévez D, Grau S, Horcajada J, Luque S. Off-label prescription of tigecycline: clinical and microbiological characteristics and outcomes. Int J Antimicrob Agents. 2010;36(5):471–2.

    Article  Google Scholar 

  13. De Pascale G, Montini L, Pennisi M, Bernini V, Maviglia R, Bello G, et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18(3):R90.

    Article  Google Scholar 

  14. Postier R, Green S, Klein S, Ellis-Grosse E, Loh E. Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients. Clin Ther. 2004;26(5):704–14.

    Article  CAS  Google Scholar 

  15. Ellis-Grosse E, 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 Infecti Dis. 2005;41(s5):S341–S353353.

    Article  CAS  Google Scholar 

  16. Oliva M, Rekha A, Yellin A, Pasternak J, Campos M, Rose G, et al. 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 Infec Dis. 3074A;5(1):88.

    Article  Google Scholar 

  17. Rhodes A, Evans L, Alhazzani W, Levy M, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486–552.

    Article  Google Scholar 

  18. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014. https://doi.org/10.1111/trf.12431.

    Article  PubMed  Google Scholar 

  19. Hemostasia y trombosis. In: Provan D, Baglin T, Dokal I, de Vos J. Manual de Hematología Clínica. Barcelona: 2017. pp 453–543. eBook ISBN: 9788491131816.

  20. Wu P, Wu C. Tigecycline-associated hypofibrinogenemia: a case report and review of the literature. IDCases. 2018;11:56–7.

    Article  Google Scholar 

  21. Vasse M, Paysant J, Soria J, Mirshahi S, Vannier J, Soria C. Down-regulation of fibrinogen biosynthesis by IL-4, IL-10 and IL-13. Br J Haematol. 1996;93(4):955–61.

    Article  CAS  Google Scholar 

  22. Fuller G. The effects of hepatocyte stimulating factor on fibrinogen biosynthesis in hepatocyte monolayers. J Cell Biol. 1985;101(4):1481–6.

    Article  CAS  Google Scholar 

Download references

Funding

This is an independent research study. No grants nor other fundings has been received to carry on this study.

Conflicts of interest

None of the authors declare a conflict of interests in relation to the content of this study.

Author information

Authors and Affiliations

  1. Clinical Pharmacist in Pharmacy Department, Hospital Universitari Vall Hebron, Barcelona, Spain

    David Campany-Herrero, Pilar Lalueza-Broto & Lucas Rivera-Sánchez

  2. Resident in Hospital Pharmacy in Pharmacy Department, Hospital Universitari Vall, Barcelona, Spain

    Maria Larrosa-Garcia

  3. Infectious Diseases Department, Hospital Universitari Vall Hebron, Barcelona, Spain

    Juan Espinosa-Pereiro & Carles Pigrau-Serrallach

  4. Internal Medicine, Hospital Universitari Vall Hebron, Barcelona, Spain

    Jaume Mestre-Torres

  5. Servei de Farmàcia, Vall d’Hebron Hospital Campus, Paseo Valle de Hebrón, 119-129, 08035, Barcelona, Spain

    David Campany-Herrero

Authors
  1. David Campany-Herrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Larrosa-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pilar Lalueza-Broto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucas Rivera-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan Espinosa-Pereiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jaume Mestre-Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carles Pigrau-Serrallach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Campany-Herrero.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 kb)

Supplementary file2 (XLSX 289 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Campany-Herrero, D., Larrosa-Garcia, M., Lalueza-Broto, P. et al. Tigecycline-associated hypofibrinogenemia in a real-world setting. Int J Clin Pharm 42, 1184–1189 (2020). https://doi.org/10.1007/s11096-020-01072-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-020-01072-7

Search

Navigation