High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria
Tóm tắt
The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses. We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated. Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure. TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria.
Tài liệu tham khảo
Rampton JE, Curran MP, Tygacil® prescribing information (2010): Tigecycline. Drugs 2005, 65: 2623-2635. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf 10.2165/00003495-200565180-00008
Food and Drug Administration: FDA drugsafety 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
Cai Y, Chai D, Wang R, Liang B, Bai N: Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother 2012, 67: 1607-1615. 10.1093/jac/dks084
Barbour A, Schmidt S, Ma B, Schiefelbein L, Rand KH, Burkhardt O, Derendorf H: Clinical pharmacokinetics and pharmacodynamics of tigecycline. Clin Pharmacokinet 2009, 48: 575-584. 10.2165/11317100-000000000-00000
Cunha BA: Multidrug-resistant Gram-negative bacilli causing urinary tract infections clinical considerations. J Chemother 2011, 23: 171-174. 10.1179/joc.2011.23.3.171
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: 1756-1762. 10.1128/AAC.01232-12
File TM Jr: Recommendations for treatment of hospital-acquired and ventilator-associated pneumonia: review of recent international guidelines. Clin Infect Dis 2010, 51: 42-47. 10.1086/653112
Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG: Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010, 50: 133-164. 10.1086/649554
Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL, Montoya JG, Wade JC: Infectious diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005, 41: 1373-1406. 10.1086/497143
Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK: Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009. Update by the Infectious Diseases Society of America. Clin Infect Dis 2009, 49: 1-45. 10.1086/599376
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008, 34: 17-60. 10.1007/s00134-007-0934-2
Department of Health and Human Services. Cancer therapy evaluation program, common terminology criteria for adverse events, v.3.0. August 9, 2006 http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pd
Niederman MS, Chastre J, Corkery K, Fink JB, Luyt CE, García MS: BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med 2012, 38: 263-271. 10.1007/s00134-011-2420-0
Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing; 22nd informational supplement. Clinical and Laboratory Standards Institute document M100–S20. Wayne PA: Clinical and Laboratory Standards Institute; 2012.
Sader HS, Farrell DJ, Jones RN: Tigecycline activity tested against multidrug-resistant Enterobacteriaceae and Acinetobacter spp. isolated in US medical centers (2005–2009). Diagn Microbiol Infect Dis 2011, 69: 223-227. 10.1016/j.diagmicrobio.2010.10.020
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL: Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbio Infect 2012, 18: 268-281. 10.1111/j.1469-0691.2011.03570.x
Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J: Emergence of carbapenem-resistant Klebsiella species possessing the class Acarbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin Infect Dis 2004, 39: 55-60. 10.1086/421495
Rasheed JK, Cockerill F, Tenover FC: Detection and characterization of antimicrobial resistance genes in pathogenic bacteria. In Manual of clinical microbiology, Volume 1. 9th edition. Edited by: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA. Washington, DC: American Society of Microbiology; 2007:1248-1267.
Vicari G, Bauer SR, Neuner EA, Lam SW: Association between colistin dose and microbiologic outcomes in patients with multidrug-resistant gram-negative bacteremia. Clin Infect Dis 2013, 56: 398-404. 10.1093/cid/cis909
Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M: Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniea carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 2012, 55: 943-950. 10.1093/cid/cis588
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 pneumonia carbapenemase-producing K. pneumoniae in intensive care unit. Clin Infect Dis 2013, 56: 697-700. 10.1093/cid/cis969
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, 311 study group: Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010, 68: 140-151. 10.1016/j.diagmicrobio.2010.05.012
Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T: Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint. Int J Antimicrob Agents 2009, 34: 101-102. 10.1016/j.ijantimicag.2009.01.015
Purdy J, Jouve S, Yan JL, Balter I, Dartois N, Cooper CA, Korth-Bradley J: Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study. Clin Ther 2012, 34: 496-507. 10.1016/j.clinthera.2011.12.010
Cunha BA: Pharmacokinetic considerations regarding tigecycline for multidrug-resistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis. J Clin Microbiol 2009, 47: 1613. 10.1128/JCM.00404-09
Humphries RM, Kelesidis T, Dien Bard J, Ward KW, Bhattacharya D, Lewinski MA: Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high-dose tigecycline and colistin. J Med Microbiol 2010, 59: 1383-1386. 10.1099/jmm.0.023010-0
Stein GE, Craig WA: Tigecycline: a critical analysis. Clin Infect Dis 2006, 43: 518-524. 10.1086/505494
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.
Tasina E, Haidich AB, Kokkali S, Arvanitidou M: Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis 2011, 11: 834-844. 10.1016/S1473-3099(11)70177-3
Yahav D, Lador A, Paul M, Leibovici L: Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother 2011, 66: 1963-1971. 10.1093/jac/dkr242
Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y: Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 2012, 56: 2108-2113. 10.1128/AAC.06268-11
Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, Pennisi MA, Bello G, Antonelli M: Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med 2013, 39: 682-692. 10.1007/s00134-013-2828-9