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Tigecycline use in critically ill patients: a multicentre prospective observational study in the intensive care settingOpen access

Philippe Montravers| Hervé Dupont| Jean-Pierre Bedos| Philippe Bret
Original
Volume 40, Issue 7 / July , 2014

Pages 988 - 997

Abstract

Purpose

This prospective observational study aimed at describing prescription patterns of tigecycline and patient outcomes in 26 French intensive care units (ICU).

Methods

Data of consecutive cases of adult patients treated with tigecycline were collected from the initiation until 7 days after the end of treatment. Response to treatment was classified as success, failure or undetermined and analyses were presented according to severity (SOFA score <7 or ≥7). Survival was recorded at 28 days.

Results

A total of 156 patients were included (64 % male, age 60 ± 15 years). At inclusion, 53 % had a SOFA score ≥7; 93 % had received prior anti-infective agents. Tigecycline was given as first-line treatment in 47 % of patients, mostly in combination (67 %), for intra-abdominal (IAI 56 %), skin and soft tissue (SSTI 19 %) or other infections. A total of 76 % of the treated infections were hospital-acquired. Bacteraemia was reported in 12 % of patients. Median treatment duration was 9 days. Tigecycline was prematurely stopped in 42 % patients. The global success rate was 60 % at the end of treatment, and significantly higher with treatment duration more than 9 days (76 vs. 47 %, P < 0.001). Success rate was 65 % for patients alive at the end of treatment. Success rates tended to decrease with illness severity, immunosuppression, bacteraemia and obesity. Survival rate at day 28 was 85 % in the whole cohort and significantly higher in the less severely ill patients (P < 0.001).

Conclusions

Tigecycline success rates appear comparable to those reported in clinical studies in ICU with severe infections. Tigecycline could be an alternative in ICU patients.

Keywords

References

  1. Breedt J, Teras J, Gardovskis J, Maritz FJ, Vaasna T, Ross DP, Gioud-Paquet M, Dartois N, Ellis-Grosse EJ, Loh E et al (2005) Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase 3 comparison study with vancomycin-aztreonam. Antimicrob Agents Chemother 49:4658–4666. doi:10.1128/AAC.49.11.4658-4666.2005
    • View reference on PubMed
    • View reference on publisher's website
  2. Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E et al (2005) 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 41(Suppl 5):S341–S353. doi:10.1086/431675
    • View reference on PubMed
    • View reference on publisher's website
  3. Sacchidanand S, Penn RL, Embil JM, Campos ME, Curcio D, Ellis-Grosse E, Loh E, Rose G (2005) 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 9:251–261. doi:10.1016/j.ijid.2005.05.003
    • View reference on PubMed
    • View reference on publisher's website
  4. Babinchak T, Ellis-Grosse E, Dartois N, Rose GM, Loh E et al (2005) The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis 41(Suppl 5):S354–S367. doi:10.1086/431676
    • View reference on PubMed
    • View reference on publisher's website
  5. Fomin P, Beuran M, Gradauskas A, Barauskas G, Datsenko A, Dartois N, Ellis-Grosse E, Loh E et al (2005) Tigecycline is efficacious in the treatment of complicated intra-abdominal infections. Int J Surg 3:35–47. doi:10.1016/j.ijsu.2005.03.011
    • View reference on PubMed
    • View reference on publisher's website
  6. Oliva ME, Rekha A, Yellin A, Pasternak J, Campos M, Rose GM, Babinchak T, Ellis-Grosse EJ, Loh E et al (2005) 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 5:88. doi:10.1186/1471-2334-5-88
    • View reference on PubMed
    • View reference on publisher's website
  7. Towfigh S, Pasternak J, Poirier A, Leister H, Babinchak T (2010) A multicentre, open-label, randomized comparative study of tigecycline versus ceftriaxone sodium plus metronidazole for the treatment of hospitalized subjects with complicated intra-abdominal infections. Clin Microbiol Infect 16:1274–1281. doi:10.1111/j.1469-0691.2010.03122.x
    • View reference on PubMed
    • View reference on publisher's website
  8. Bergallo C, Jasovich A, Teglia O, Oliva ME, Lentnek A, de Wouters L, Zlocowski JC, Dukart G, Cooper A, Mallick R et al (2009) 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 63:52–61. doi:10.1016/j.diagmicrobio.2008.09.001
    • View reference on PubMed
    • View reference on publisher's website
  9. Freire AT, Melnyk V, Kim MJ, Datsenko O, Dzyublik O, Glumcher F, Chuang YC, Maroko RT, Dukart G, Cooper CA, Korth-Bradley JM, Dartois N, Gandjini H et al (2010) Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 68:140–151. doi:10.1016/j.diagmicrobio.2010.05.012
    • View reference on PubMed
    • View reference on publisher's website
  10. Tanaseanu C, Bergallo C, Teglia O, Jasovich A, Oliva ME, Dukart G, Dartois N, Cooper CA, Gandjini H, Mallick R et al (2008) Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn Microbiol Infect Dis 61:329–338. doi:10.1016/j.diagmicrobio.2008.04.009
    • View reference on PubMed
    • View reference on publisher's website
  11. 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 et al (2008) 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 62(Suppl 1):i17–i28. doi:10.1093/jac/dkn250
    • View reference on PubMed
    • View reference on publisher's website
  12. Vasilev K, Reshedko G, Orasan R, Sanchez M, Teras J, Babinchak T, Dukart G, Cooper A, Dartois N, Gandjini H, Orrico R, Ellis-Grosse E et al (2008) A phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae. J Antimicrob Chemother 62(Suppl 1):i29–i40. doi:10.1093/jac/dkn249
    • View reference on PubMed
    • View reference on publisher's website
  13. Bassetti M, Nicolini L, Repetto E, Righi E, Del Bono V, Viscoli C (2010) Tigecycline use in serious nosocomial infections: a drug use evaluation. BMC Infect Dis 10:287. doi:10.1186/1471-2334-10-287
    • View reference on PubMed
  14. Curcio D, Fernandez F, Cane A, Barcelona L, Stamboulian D (2008) Indications of a new antibiotic in clinical practice: results of the tigecycline initial use registry. Braz J Infect Dis 12:198–201
    • View reference on PubMed
    • View reference on publisher's website
  15. Swoboda S, Ober M, Hainer C, Lichtenstern C, Seiler C, Wendt C, Hoppe-Tichy T, Buchler M, Weigand MA (2008) Tigecycline for the treatment of patients with severe sepsis or septic shock: a drug use evaluation in a surgical intensive care unit. J Antimicrob Chemother 61:729–733. doi:10.1093/jac/dkm541
    • View reference on PubMed
    • View reference on publisher's website
  16. Gardiner D, Dukart G, Cooper A, Babinchak T (2010) Safety and efficacy of intravenous tigecycline in subjects with secondary bacteremia: pooled results from 8 phase III clinical trials. Clin Infect Dis 50:229–238. doi:10.1086/648720
    • View reference on PubMed
    • View reference on publisher's website
  17. Bassetti M, Eckmann C, Bodmann KF, Dupont H, Heizmann WR, Montravers P, Guirao X, Capparella MR, Simoneau D, Sanchez Garcia M (2013) Prescription behaviours for tigecycline in real-life clinical practice from five European observational studies. J Antimicrob Chemother 68(Suppl 2):ii5–ii14. doi:10.1093/jac/dkt140
    • View reference on PubMed
  18. Eckmann C, Montravers P, Bassetti M, Bodmann KF, Heizmann WR, Sanchez Garcia M, Guirao X, Capparella MR, Simoneau D, Dupont H (2013) Efficacy of tigecycline for the treatment of complicated intra-abdominal infections in real-life clinical practice from five European observational studies. J Antimicrob Chemother 68(Suppl 2):ii25–ii35. doi:10.1093/jac/dkt142
    • View reference on PubMed
  19. Montravers P, Bassetti M, Dupont H, Eckmann C, Heizmann WR, Guirao X, Garcia MS, Capparella MR, Simoneau D, Bodmann KF (2013) Efficacy of tigecycline for the treatment of complicated skin and soft-tissue infections in real-life clinical practice from five European observational studies. J Antimicrob Chemother 68(Suppl 2):ii15–ii24. doi:10.1093/jac/dkt141
    • View reference on PubMed
  20. Heizmann WR, Dupont H, Montravers P, Guirao X, Eckmann C, Bassetti M, Garcia MS, Capparella MR, Simoneau D, Bodmann KF (2013) Resistance mechanisms and epidemiology of multiresistant pathogens in Europe and efficacy of tigecycline in observational studies. J Antimicrob Chemother 68(Suppl 2):ii45–ii55. doi:10.1093/jac/dkt144
    • View reference on PubMed
  21. Guirao X, Sanchez Garcia M, Bassetti M, Bodmann KF, Dupont H, Montravers P, Heizmann WR, Capparella MR, Simoneau D, Eckmann C (2013) Safety and tolerability of tigecycline for the treatment of complicated skin and soft-tissue and intra-abdominal infections: an analysis based on five European observational studies. J Antimicrob Chemother 68(Suppl 2):ii37–ii44. doi:10.1093/jac/dkt143
    • View reference on PubMed
  22. McCabe W, Jackson G (1962) Gram-negative bacteremia: I Etiology and ecology. Arch Intern Med 110:847–855
    • View reference on publisher's website
  23. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60:646–649
    • View reference on PubMed
    • View reference on publisher's website
  24. Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963
    • View reference on PubMed
    • View reference on publisher's website
  25. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710
  26. Jaeschke R, Guyatt G, Sackett DL (1994) Users’ guides to the medical literature. III. How to use an article about a diagnostic test. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 271:389–391
    • View reference on PubMed
    • View reference on publisher's website
  27. Chen Z, Wu J, Zhang Y, Wei J, Leng X, Bi J, Li R, Yan L, Quan Z, Chen X, Yu Y, Wu Z, Liu D, Ma X, Maroko R, Cooper A (2010) Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial. BMC Infect Dis 10:217. doi:10.1186/1471-2334-10-217
    • View reference on PubMed
    • View reference on publisher's website
  28. Cai Y, Wang R, Liang B, Bai N, Liu Y (2011) Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother 55:1162–1172. doi:10.1128/AAC.01402-10
    • View reference on PubMed
    • View reference on publisher's website
  29. Tasina E, Haidich AB, Kokkali S, Arvanitidou M (2011) Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis 11:834–844. doi:10.1016/S1473-3099(11)70177-3
    • View reference on PubMed
    • View reference on publisher's website
  30. Vardakas KZ, Rafailidis PI, Falagas ME (2012) Effectiveness and safety of tigecycline: focus on use for approved indications. Clin Infect Dis 54:1672–1674. doi:10.1093/cid/cis239
    • View reference on PubMed
    • View reference on publisher's website
  31. FDA (2010) http://www.fda.gov/drugs/drugsafety/ucm224370.htm. Accessed 1 Jan 2014
  32. EMA (2011) http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/human/000644/WC500102228.pdf. Accessed 1 Jan 2014
  33. EMA (2012) http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000644/WC500044509.pdf. Accessed 1 Jan 2014
  34. Prasad P, Sun J, Danner RL, Natanson C (2012) Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 54:1699–1709. doi:10.1093/cid/cis270
    • View reference on PubMed
    • View reference on publisher's website
  35. Yahav D, Lador A, Paul M, Leibovici L (2011) Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother 66:1963–1971. doi:10.1093/jac/dkr242
    • View reference on PubMed
    • View reference on publisher's website
  36. Chastre J, Wunderink R, Prokocimer P, Lee M, Kaniga K, Friedland I (2008) Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med 36:1089–1096. doi:10.1097/CCM.0b013e3181691b99
    • View reference on PubMed
    • View reference on publisher's website
  37. Pletz MW, Lipman J (2013) Clinical measures for increased creatinine clearances and suboptimal antibiotic dosing. Intensive Care Med 39:1322–1324. doi:10.1007/s00134-013-2918-8
  38. Falagas ME, Vardakas KZ, Tsiveriotis KP, Triarides NA, Tansarli GS (2014) Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2014.01.006
    • View reference on PubMed
  39. Paiva JA (2013) Adding risk factors for potentially resistant pathogens, increasing antibiotic pressure and risk creating the “untreatable bacteria”: time to change direction. Intensive Care Med 39:779–781. doi:10.1007/s00134-012-2811-x
  40. Pankey GA, Sabath LD (2004) Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections. Clin Infect Dis 38:864–870. doi:10.1086/381972
    • View reference on PubMed
    • View reference on publisher's website
  41. Curcio D, Vargas SW, Ugarte Ubiergo S, Varon F, Rojas Suarez J, Paz Chavez C, Curiale A et al (2011) Tigecycline treatment of critically ill patients: the LatinUser experience. Curr Clin Pharmacol 6:18–25
    • View reference on PubMed
    • View reference on publisher's website
  42. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R et al (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228. doi:10.1007/s00134-012-2769-8
  43. Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, Pennisi MA, Bello G, Antonelli M (2013) Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med 39:682–692. doi:10.1007/s00134-013-2828-9

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