Effectiveness and Safety of High Dose Tigecycline for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis.
Carbapenem resistance
Gram-negative bacteria
Infectious disease
Multidrug resistance
Tigecycline
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
08
12
2019
pubmed:
2
2
2020
medline:
21
10
2020
entrez:
2
2
2020
Statut:
ppublish
Résumé
Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial. To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections. Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed. Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30-0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09-5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44-3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22-0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06-0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07-0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80-5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44-2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09-0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias. High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics.
Sections du résumé
BACKGROUND
Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial.
OBJECTIVES
To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections.
METHODS
Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed.
RESULTS
Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30-0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09-5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44-3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22-0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06-0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07-0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80-5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44-2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09-0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias.
CONCLUSIONS
High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics.
Identifiants
pubmed: 32006240
doi: 10.1007/s12325-020-01235-y
pii: 10.1007/s12325-020-01235-y
pmc: PMC7223407
doi:
Substances chimiques
Anti-Bacterial Agents
0
Tigecycline
70JE2N95KR
Banques de données
figshare
['10.6084/m9.figshare.11591916']
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Pagination
1049-1064Subventions
Organisme : Conch Hospital
ID : F20190301
Pays : International
Références
Arthur C, Awa Marie CS, Bent HI, et al. Antimicrobial resistance: a priority for global health action. Bull World Health Organ. 2015;93(7):439.
Thabit AK, Crandon JL, Nicolau DP. Antimicrobial resistance: impact on clinical and economic outcomes and the need for new antimicrobials. Expert Opin Pharmacother. 2015;16(2):159–77.
pubmed: 25496207
Mauldin PD, Salgado CD, Hansen IS, Durup DT, Bosso JA. Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant Gram-negative bacteria. Antimicrob Agents Chemother. 2010;54(1):109–15.
pubmed: 19841152
Peleg AY, Hooper DC. Hospital-acquired infections due to Gram-negative bacteria. N Engl J Med. 2010;362(19):1804–13.
pubmed: 20463340
pmcid: 3107499
Hawkey P. Multidrug-resistant Gram-negative bacteria: a product of globalization. J Hosp Infect. 2015;89(4):241–7.
pubmed: 25737092
Hawkey PM, Warren RE, Livermore DM, et al. Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother. 2018;73(suppl_3):iii2–78.
pubmed: 29514274
Bedenić B, Plečko V, Sardelić S, Uzunović S, Godič Torkar K. Carbapenemases in Gram-negative bacteria: laboratory detection and clinical significance. BioMed Res Int. 2014;2014:841951.
Tal-Jasper R, Katz DE, Amrami N, et al. Clinical and epidemiological significance of carbapenem resistance in Acinetobacter baumannii infections. Antimicrob Agents Chemother. 2016;60(5):3127–31.
pubmed: 26883694
pmcid: 4862462
Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13(9):785–96.
pubmed: 23969216
pmcid: 4673667
Duin DV, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8(4):1–10.
Horcajada JP, Montero M, Oliver A, et al. Epidemiology and treatment of multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections. Clin Microbiol Rev. 2019;32(4):e00031–19.
Kaye KS, Pogue JM. Infections caused by resistant Gram-negative bacteria: epidemiology and management. Pharmacotherapy. 2015;35(10):949–62.
pubmed: 26497481
Nowak J, Zander E, Stefanik D, et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother. 2017;72(12):3277–82.
pubmed: 28961773
pmcid: 5890771
Pérez A, Gato E, Pérez-Llarena J, et al. High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother. 2019;74(5):1244–52.
pubmed: 30753505
Cassir N, Rolain J-M, Brouqui P. A new strategy to fight antimicrobial resistance: the revival of old antibiotics. Front Microbiol. 2014;5:551.
pubmed: 25368610
pmcid: 4202707
Falagas ME, Kopterides P. Old antibiotics for infections in critically ill patients. Curr Opin Crit Care. 2007;13(5):592–7.
pubmed: 17762241
Kaewpoowat Q, Ostrosky-Zeichner L. Tigecycline: a critical safety review. Expert Opin Drug Saf. 2015;14(2):335–42.
pubmed: 25539800
Livermore DM. Tigecycline: what is it, and where should it be used? J Antimicrob Chemother. 2005;56(4):611–4.
pubmed: 16120626
Pankey GA. Tigecycline. J Antimicrob Chemother. 2005;56(3):470–80.
pubmed: 16040625
Kuti JL, Kim A, Cloutier DJ, Nicolau DP. Evaluation of plazomicin, tigecycline, and meropenem pharmacodynamic exposure against carbapenem-resistant Enterobacteriaceae in patients with bloodstream infection or hospital-acquired/ventilator-associated pneumonia from the CARE Study (ACHN-490-007). Infect Dis Ther. 2019;8(3):383–96.
pubmed: 31254273
pmcid: 6702525
Wang J, Pan Y, Shen J, Xu Y. The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob. 2017;16(1):24.
pubmed: 28381268
pmcid: 5382384
Xu L, Wang Y-L, Du S, Chen L, Long L-H, Wu Y. Efficacy and safety of tigecycline for patients with hospital-acquired pneumonia. Chemotherapy. 2016;61(6):323–30.
pubmed: 27144279
Tasina E, Haidich A-B, Kokkali S, Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis. 2011;11(11):834–44.
pubmed: 21784708
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;39:25–33.
pubmed: 26283551
Prasad P, Sun J, Danner RL, Natanson C. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis. 2012;54(12):1699–709.
pubmed: 22467668
pmcid: 3404716
Giamarellou H, Poulakou G. Pharmacokinetic and pharmacodynamic evaluation of tigecycline. Expert Opin Drug Metab Toxicol. 2011;7(11):1459–70.
pubmed: 21958044
Falagas ME, Vardakas KZ, Tsiveriotis KP, Triarides NA, Tansarli GS. 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.
pubmed: 24602499
Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777.
pubmed: 26030634
Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2011.
Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.
pubmed: 27733354
pmcid: 5062054
Higgins JP, Altman DG, Gøtzsche PC, al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
pubmed: 3196245
pmcid: 3196245
Higgins TJP. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.
pubmed: 12958120
pmcid: 12958120
Thorlund K, Anema A, Mills E. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals. Clin Epidemiol. 2010;2:57.
pubmed: 20865104
pmcid: 2943189
Balandin Moreno B, Fernandez Simon I, Pintado Garcia V, et al. Tigecycline therapy for infections due to carbapenemase-producing Klebsiella pneumoniae in critically ill patients. Scand J Infect Dis. 2014;46(3):175–80.
pubmed: 24354959
Chen Z, Shi X. Adverse events of high-dose tigecycline in the treatment of ventilator-associated pneumonia due to multidrug-resistant pathogens. Medicine. 2018;97(38):e12467.
pubmed: 30235740
pmcid: 6160260
De Pascale G, Montini L, Pennisi M, et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18(3):R90.
Geng TT, Xu X, Huang M. High-dose tigecycline for the treatment of nosocomial carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a retrospective cohort study. Medicine (Baltimore). 2018;97(8):e9961.
pubmed: 29465589
pmcid: 5841956
Ibrahim MM, Abuelmatty AM, Mohamed GH, et al. Best tigecycline dosing for treatment of infections caused by multidrug-resistant pathogens in critically ill patients with different body weights. Drug Des Dev Ther. 2018;12:4171–9.
Maseda E, Suárez-de-la-Rica A, Anillo V, et al. A practice-based observational study identifying factors associated with the use of high-dose tigecycline in the treatment of secondary peritonitis in severely ill patients. Rev Esp Quimioter. 2015;28(1):47–53.
pubmed: 25690145
Vardakas KZ, Matthaiou DK, Falagas ME, Antypa E, Koteli A, Antoniadou E. Tigecycline for carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. Infect Dis. 2015;47(10):751–3.
Wu X, Zhu Y, Chen Q, et al. Tigecycline therapy for nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria in critically ill patients who received inappropriate initial antibiotic treatment: a retrospective case study. BioMed Res Int. 2016;2016:8395268.
Di Carlo P, Gulotta G, Casuccio A, et al. KPC-3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiol. 2013;13(1):13.
Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013;57(4):1756–62.
pubmed: 23357775
pmcid: 3623336
Draghi DC, Tench S, Dowzicky MJ, Sahm DF. Baseline in vitro activity of tigecycline among key bacterial pathogens exhibiting multidrug resistance. Chemotherapy. 2008;54(2):91–100.
pubmed: 18303257
Rizek C, Ferraz JR, van der Heijden IM, et al. In vitro activity of potential old and new drugs against multidrug-resistant Gram-negatives. J Infect Chemother. 2015;21(2):114–7.
pubmed: 25456893
Yahav D, Lador A, Paul M, Leibovici L. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother. 2011;66(9):1963–71.
pubmed: 21685488
Ni W, Han Y, Liu J, et al. Tigecycline treatment for carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(11):e3126.
pubmed: 26986165
pmcid: 4839946
Vardakas KZ, Matthaiou DK, Falagas ME, Antypa E, Koteli A, Antoniadou E. Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. J Infect. 2015;70(6):592–9.
pubmed: 25447713
Siwakoti S, Subedi A, Sharma A, Baral R, Bhattarai NR, Khanal B. Incidence and outcomes of multidrug-resistant Gram-negative bacteria infections in intensive care unit from Nepal-a prospective cohort study. Antimicrob Resist Infect Control. 2018;7(1):114.
pubmed: 30275945
pmcid: 6158849
Liu Q, Li X, Li W, et al. Influence of carbapenem resistance on mortality of patients with Pseudomonas aeruginosa infection: a meta-analysis. Sci Rep. 2015;5:11715.
pubmed: 26108476
pmcid: 4479982
Morata L, Cobos-Trigueros N, Martínez JA, et al. Influence of multidrug resistance and appropriate empirical therapy on the 30-day mortality rate of Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother. 2012;56(9):4833–7.
pubmed: 22751533
pmcid: 3421866
Mei H, Yang T, Wang J, Wang R, Cai Y. Efficacy and safety of tigecycline in treatment of pneumonia caused by MDR Acinetobacter baumannii: a systematic review and meta-analysis. J Antimicrob Chemother. 2019;74(12):3423–31.
pubmed: 31377765