A retrospective observational study of the impact of Tigecycline in treating multidrug resistant pneumonia
Keywords:Hospital acquired, Pneumonia, Resistant, Tigecycline
Background: Few antimicrobials are currently active to treat extensively drug resistant (XDR) gram-negative bacilli infections. This represents a serious global public health concern. Critically ill patients face the brunt of majority of these infections. Tigecycline has coverage for a majority of these XDR infections (with the exception of Pseudomonas aeruginosa), but is not currently approved for hospital-acquired pneumonia. Nevertheless it is being commonly used for this indication though many meta-analysis have suggested an increased risk of death in patients receiving this antibiotic.
Methods: In this retrospective analysis we compared the mortality rates between a Tigecycline based and a non Tigecycline based therapy for XDR infections in the critically ill over a period of 12 months. A total of 93 patients were included in the study.
Results: Tigecycline group had significantly increased risk for in hospital mortality with an odds ratio of 6.0 and 95% CI of 1.37 to 26.12 with a p value of 0.01. But such a difference was not evident in 14 day mortality.
Conclusions: Initiation of Tigecycline for multidrug resistant, pneumonia needs to be re-thought. Only a small percentage of patients with pneumonia with in-vitro sensitivity having low minimum inhibitory concentration (MIC) would benefit from the drug. Even in this group the risk of increased mortality needs to be carefully considered before Initiation of therapy.
Tripodi MF, Durante-Mangoni E, Fortunato R, Utili R, Zarrilli R. Comparative activities of Colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases.Int J Antimicrob Agents. 2007;30:537–40.
Principe L, D’Arezzo S, Capone A,Petrosillo N, Visca P. In vitro activity of Tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumannii. Ann Clin Microbiol Antimicrob. 2009;8:18.
Ni W, Shao X, Di X, Cui J, Wang R, Liu Y. In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii A systematic review and meta-analysis. Int J Antimicrob Agents. 2015;45:8-18.
Chopra I, Roberts M. Tetracycline antibiotics mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65:232–60.
Meagher AK, Ambrose PG, Grasela TH, Ellis-Grosse EJ. Pharmacokinetic/pharmacodynamics profile for Tigecycline - a new glycylcycline antimicrobial agent. Diagn Microbiol Infect Dis. 2005;52:165–71.
Kim NH, Hwang JH, Song KH, Choe PG, Kim ES, Park SW, et al. Tigecycline in carbapenem-resistant Acinetobacter baumannii bacteraemia:susceptibility and clinical outcome. Scand J Infect Dis. 2013;45:315–9.
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268-81.
Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T. Tigecycline possibly under dosed for the treatment of pneumonia:a pharmacokinetic viewpoint. Int J Antimicrob Agents. 2009;34:101–2.
Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37:840–51.
Meagher AK, Passarell JA, Cirincione BB, Van Wart SA, Liolios K, Babinchak T, et al. Exposure response analyses of Tigecycline efficacy in patients with complicated skin and skin structure infections. Antimicrob. Agents Chemother. 2007;51:1939–45.
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;57:1756–62.
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;18:90.
Grandesso S, Sapino B, Amici G, Mazzucato S, Solinas M, Gion M. Are Etest and Vitek2 good choices for Tigecycline susceptibility testing when comparing broth microdilution for MDR and XDR Acinetobacter baumannii? New Microbiol. 2014;37:503-8.