In Vitro Activity of Tigecycline Against Acinetobacter baumannii: Global Epidemiology and Resistance Mechanisms

  • Spyros Pournaras
  • Vasiliki Koumaki
  • Vasiliki Gennimata
  • Evangelia Kouskouni
  • Athanassios TsakrisEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 897)


Acinetobacter baumannii is a pathogen of increasing concern, commonly causing outbreaks in the hospital environment. Of particular concern, A. baumannii strains exhibiting resistance to carbapenems, which were previously considered the treatment of choice for infected patients, have dramatically increased worldwide, leaving a few antibacterial choices. Tigecycline, a broad-spectrum modified minocycline derivative, isconsidered as a last resort drug against multidrug-resistant A. baumannii. Though, resistance to tigecycline has emerged and is growing notably following increasing tigecycline usage. Comparative evaluation of the tigecycline resistance rates reported worldwide is challenging due to the absence of official interpretative criteria for in vitro susceptibility testing and the discrepancies among the different susceptibility methodologies used, with broth microdilution being considered the reference method. Tigecycline resistance is mainly associated with resistance-nodulation-cell division (RND)-type transporters, mainly the AdeABC, AdeFGH and AdeIJK efflux pumps, but other resistance mechanisms have also been implicated. Tigecycline is still an attractive choice for A. baumannii, but further investigations are warranted so that treatment of MDR Α. baumannii could be guided by validated in vitro data.


Tigecycline Acinetobacter baumannii Resistance MIC Resistance mechanisms Susceptibility methods 



No institutional and/or corporate funds have been received by authors for the achievement of the results reported in the manuscript.


  1. Al-Sweih NA, Al-Hubail MA, Rotimi VO (2011) Emergence of tigecycline and colistin resistance in Acinetobacter species isolated from patients in Kuwait hospitals. J Chemother 23(1):13–16. doi: 10.1179/joc.2011.23.1.13 CrossRefPubMedGoogle Scholar
  2. Ahmed NH, Baba K, Clay C, Lekalakala R, Hoosen AA (2012) In vitro activity of tigecycline against clinical isolates of carbapenem resistant Acinetobacter baumannii complex in Pretoria, South Africa. BMC Res Notes 3(5):215. doi: 10.1186/1756-0500-5-215
  3. Amin IM, Richmond GE, Sen P, Koh TH, Piddock LJ, Chua KL (2013) A method for generating marker-less gene deletions in multidrug-resistant Acinetobacter baumannii. BMC Microbiol 13:158. doi: 10.1186/1471-2180-13-158 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E (2008) Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis 46(4):567–570. doi: 10.1086/526775 CrossRefPubMedGoogle Scholar
  5. Araj GF, Ibrahim GY (2008) Tigecycline in vitro activity against commonly encountered multidrug-resistant gram-negative pathogens in a Middle Eastern country. Diagn Microbiol Infect Dis 62(4):411–415. doi: 10.1016/j.diagmicrobio.2008.08.011 CrossRefPubMedGoogle Scholar
  6. Baadani AM, Thawadi SI, El-Khizzi NA, Omrani AS (2013) Prevalence of colistin and tigecycline resistance in Acinetobacter baumannii clinical isolates from 2 hospitals in Riyadh Region over a 2-year period. Saudi Med J 34(3):248–253. PMID: 23475088Google Scholar
  7. Balode A, Punda-Polic V, Dowzicky MJ (2013) Antimicrobial susceptibility of gram-negative and gram-positive bacteria collected from countries in Eastern Europe: results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2004–2010. Int J Antimicrob Agents 41(6):527–535. doi: 10.1016/j.ijantimicag.2013.02.022 CrossRefPubMedGoogle Scholar
  8. Behera B, Das A, Mathur P, Kapil A, Gadepalli R, Dhawan B (2009) Tigecycline susceptibility report from an Indian tertiary care hospital. Indian J Med Res 129(4):446–450. PMID: 19535842Google Scholar
  9. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J (2009) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48(1):1–12. doi: 10.1086/595011 CrossRefPubMedGoogle Scholar
  10. Bradford PA, Petersen PJ, Young M, Jones CH, Tischler M, O’Connell J (2005) Tigecycline MIC testing by broth dilution requires use of fresh medium or addition of the biocatalytic oxygen-reducing reagent oxyrase to standardize the test method. Antimicrob Agents Chemother 49(9):3903–3909. doi: 10.1128/AAC.49.9.3903-3909.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bratu S, Landman D, Martin DA, Georgescu C, Quale J (2008) Correlation of antimicrobial resistance with beta-lactamases, the OmpA-like porin, and efflux pumps in clinical isolates of Acinetobacter baumannii endemic to New York City. Antimicrob Agents Chemother 52(9):2999–3005. doi: 10.1128/AAC.01684-07 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Brink AJ, Bizos D, Boffard KD, Feldman C, Grolman DC, Pretorius J, Richards GA, Senekal M, Steyn E, Welkovic N, Association of Surgeons of South A, Critical Care Society of Southern A, Federation of Infectious Diseases Societies of Southern A, South African Thoracic S, Trauma Society of South A (2010) Guideline: appropriate use of tigecycline. S Afr Med J = Suid-Afrikaanse tydskrif vir geneeskunde 100(6 Pt 2):388–394Google Scholar
  13. BSAC (2015) Susceptibility testing method. Breakpoint tables version 14 Jan 2015. Accessed 10 Apr 2015
  14. Buccoliero G, Morelli E, Lonero G, Romanelli C, Resta F, Pisconti S (2012) Rapid spread of multiresistant Acinetobacter baumannii isolates in intensive care units (ICUs) and in vitro activity of colistin and tigecycline. Infez Med 20(4):296–298PubMedGoogle Scholar
  15. Canigia LF, Bantar C (2008) Susceptibility testing of tigecycline against Acinetobacter spp. by disc diffusion method: withdrawing a therapeutic option by varying the Mueller-Hinton agar? J Antimicrob Chemother 62(6):1463–1464. doi: 10.1093/jac/dkn389 CrossRefPubMedGoogle Scholar
  16. Capone A, D’Arezzo S, Visca P, Petrosillo N, Gruppo Romano Acinetobacter b (2008) In vitro activity of tigecycline against multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 62(2):422–423. doi: 10.1093/jac/dkn172 CrossRefPubMedGoogle Scholar
  17. Casal M, Rodriguez F, Johnson B, Garduno E, Tubau F, de Lejarazu RO, Tenorio A, Gimenez MJ, Bartolome R, Garcia-Rey C, Aguilar L, Garcia-Escribano N (2009) Influence of testing methodology on the tigecycline activity profile against presumably tigecycline-non-susceptible Acinetobacter spp. J Antimicrob Chemother 64(1):69–72. doi: 10.1093/jac/dkp169 CrossRefPubMedGoogle Scholar
  18. Cattoir V, Dowzicky MJ (2014) A longitudinal assessment of antimicrobial susceptibility among important pathogens collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) in France between 2004 and 2012. Antimicrob Resist Infect Control 3(1):36. doi: 10.1186/2047-2994-3-36. eCollection 2014.
  19. Chan MC, Chiu SK, Hsueh PR, Wang NC, Wang CC, Fang CT (2014) Risk factors for healthcare-associated extensively drug-resistant Acinetobacter baumannii infections: a case-control study. PLoS One 9(1):e85973. doi: 10.1371/journal.pone.0085973 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chang KC, Lin MF, Lin NT, Wu WJ, Kuo HY, Lin TY, Yang TL, Chen YC, Liou ML (2012) Clonal spread of multidrug-resistant Acinetobacter baumannii in eastern Taiwan. J Microbiol Immunol Infect = Wei mian yu gan ran za zhi 45(1):37–42. doi: 10.1016/j.jmii.2011.09.019
  21. Chen Q, Li X, Zhou H, Jiang Y, Chen Y, Hua X, Yu Y (2014) Decreased susceptibility to tigecycline in Acinetobacter baumannii mediated by a mutation in trm encoding SAM-dependent methyltransferase. J Antimicrob Chemother 69(1):72–76. doi: 10.1093/jac/dkt319 CrossRefPubMedGoogle Scholar
  22. Chuang YC, Sheng WH, Li SY, Lin YC, Wang JT, Chen YC, Chang SC (2011) Influence of genospecies of Acinetobacter baumannii complex on clinical outcomes of patients with acinetobacter bacteremia. Clin Infect Dis 52(3):352–360. doi: 10.1093/cid/ciq154 CrossRefPubMedGoogle Scholar
  23. Chuang YC, Cheng CY, Sheng WH, Sun HY, Wang JT, Chen YC, Chang SC (2014) Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis 14:102. doi: 10.1186/1471-2334-14-102 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Coyne S, Guigon G, Courvalin P, Perichon B (2010a) Screening and quantification of the expression of antibiotic resistance genes in Acinetobacter baumannii with a microarray. Antimicrob Agents Chemother 54(1):333–340. doi: 10.1128/AAC.01037-09 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Coyne S, Rosenfeld N, Lambert T, Courvalin P, Perichon B (2010b) Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 54(10):4389–4393. doi: 10.1128/AAC.00155-10 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Coyne S, Courvalin P, Perichon B (2011) Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 55(3):947–953. doi: 10.1128/AAC.01388-10 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Damier-Piolle L, Magnet S, Bremont S, Lambert T, Courvalin P (2008) AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrob Agents Chemother 52(2):557–562. doi: 10.1128/AAC.00732-07 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Deng M, Zhu MH, Li JJ, Bi S, Sheng ZK, Hu FS, Zhang JJ, Chen W, Xue XW, Sheng JF, Li LJ (2014) Molecular epidemiology and mechanisms of tigecycline resistance in clinical isolates of Acinetobacter baumannii from a Chinese university hospital. Antimicrob Agents Chemother 58(1):297–303. doi: 10.1128/AAC.01727-13 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Denys GA, Callister SM, Dowzicky MJ (2013) Antimicrobial susceptibility among gram-negative isolates collected in the USA between 2005 and 2011 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Ann Clin Microbiol Antimicrob 12:24. doi: 10.1186/1476-0711-12-24 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Dizbay M, Altuncekic A, Sezer BE, Ozdemir K, Arman D (2008) Colistin and tigecycline susceptibility among multidrug-resistant Acinetobacter baumannii isolated from ventilator-associated pneumonia. Int J Antimicrob Agents 32(1):29–32. doi: 10.1016/j.ijantimicag.2008.02.016 CrossRefPubMedGoogle Scholar
  31. Doi Y, Murray GL, Peleg AY (2015) Acinetobacter baumannii: evolution of antimicrobial resistance-treatment options. Semin Respir Crit Care Med 36(1):85–98. doi: 10.1055/s-0034-1398388 CrossRefPubMedPubMedCentralGoogle Scholar
  32. ECDC (2013) Antimicrobial resistance surveillance in Europe. Annual report of the European Antimicrobial Resistance Surveillance network. Stockholm: ECDCGoogle Scholar
  33. Espinal P, Seifert H, Dijkshoorn L, Vila J, Roca I (2012) Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS. Clin Microbiol Infect 18(11):1097–1103. doi: 10.1111/j.1469-0691.2011.03696.x CrossRefPubMedGoogle Scholar
  34. Farrell DJ, Turnidge JD, Bell J, Sader HS, Jones RN (2010) The in vitro evaluation of tigecycline tested against pathogens isolated in eight countries in the Asia-Western Pacific region (2008). J Infect 60(6):440–451. doi: 10.1016/j.jinf.2010.03.024 CrossRefPubMedGoogle Scholar
  35. FDA (2013) Tygacil (tigecycline): drug safety communication – increased risk of death. Accessed 10 Apr 2015
  36. Fernandez-Mazarrasa C, Mazarrasa O, Calvo J, del Arco A, Martinez-Martinez L (2009) High concentrations of manganese in Mueller-Hinton agar increase MICs of tigecycline determined by Etest. J Clin Microbiol 47(3):827–829. doi: 10.1128/JCM.02464-08 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Fluit AC, Florijn A, Verhoef J, Milatovic D (2005) Presence of tetracycline resistance determinants and susceptibility to tigecycline and minocycline. Antimicrob Agents Chemother 49(4):1636–1638. doi: 10.1128/AAC.49.4.1636-1638.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Garcia CP, Juliet LC, Fernandez VA, San Martin SM, Cifuentes DM, Porte TL, Braun JS, Castillo DL, Vechiola HM, Tapia PC, Sakurada ZA, Chanqueo CL, Lam EM, Espinoza PM, Curcio FD (2009) Multicenter study on the monitoring of in vitro susceptibility to tigeeyeline in Santiago, Chile. Rev Chilena Infectol 26(3):220–226. doi:/S0716-10182009000400003Google Scholar
  39. Garza-Gonzalez E, Llaca-Diaz JM, Bosques-Padilla FJ, Gonzalez GM (2010) Prevalence of multidrug-resistant bacteria at a tertiary-care teaching hospital in Mexico: special focus on Acinetobacter baumannii. Chemotherapy 56(4):275–279. doi: 10.1159/000319903 CrossRefPubMedGoogle Scholar
  40. Gordon NC, Wareham DW (2009) A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacter baumannii with tigecycline. J Antimicrob Chemother 63(4):775–780. doi: 10.1093/jac/dkn555 CrossRefPubMedGoogle Scholar
  41. Grandesso S, Sapino B, Amici G, Mazzucato S, Solinas M, Gion M (2014) Are E-test and Vitek2 good choices for tigecycline susceptibility testing when comparing broth microdilution for MDR and XDR Acinetobacter baumannii? New Microbiol 37(4):503–508PubMedGoogle Scholar
  42. Guven T, Yilmaz G, Guner HR, Kaya Kalem A, Eser F, Tasyaran MA (2014) Increasing resistance of nosocomial Acinetobacter baumannii: are we going to be defeated? Turk J Med Sci 44(1):73–78CrossRefPubMedGoogle Scholar
  43. Higgins PG, Wisplinghoff H, Krut O, Seifert H (2007) A PCR-based method to differentiate between Acinetobacter baumannii and Acinetobacter genomic species 13TU. Clin Microbiol Infect 13(12): 1199–1201. doi: 10.1111/j.1469-0691.2007.01819.x CrossRefPubMedGoogle Scholar
  44. Higgins PG, Schneiders T, Hamprecht A, Seifert H (2010) In vivo selection of a missense mutation in adeR and conversion of the novel blaOXA-164 gene into blaOXA-58 in carbapenem-resistant Acinetobacter baumannii isolates from a hospitalized patient. Antimicrob Agents Chemother 54(12):5021–5027. doi: 10.1128/AAC.00598-10 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Hope R, Warner M, Mushtaq S, Ward ME, Parsons T, Livermore DM (2005) Effect of medium type, age and aeration on the MICs of tigecycline and classical tetracyclines. J Antimicrob Chemother 56(6):1042–1046. doi: 10.1093/jac/dki386 CrossRefPubMedGoogle Scholar
  46. Hornsey M, Ellington MJ, Doumith M, Thomas CP, Gordon NC, Wareham DW, Quinn J, Lolans K, Livermore DM, Woodford N (2010) AdeABC-mediated efflux and tigecycline MICs for epidemic clones of Acinetobacter baumannii. J Antimicrob Chemother 65(8):1589–1593. doi: 10.1093/jac/dkq218 CrossRefPubMedGoogle Scholar
  47. Hornsey M, Loman N, Wareham DW, Ellington MJ, Pallen MJ, Turton JF, Underwood A, Gaulton T, Thomas CP, Doumith M, Livermore DM, Woodford N (2011) Whole-genome comparison of two Acinetobacter baumannii isolates from a single patient, where resistance developed during tigecycline therapy. J Antimicrob Chemother 66(7):1499–1503. doi: 10.1093/jac/dkr168 CrossRefPubMedGoogle Scholar
  48. Hua X, Zhou H, Jiang Y, Feng Y, Chen Q, Ruan Z, Yu Y (2012) Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline. J Bacteriol 194(24):6979–6980. doi: 10.1128/JB.01887-12 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Insa R, Cercenado E, Goyanes MJ, Morente A, Bouza E (2007) In vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia. J Antimicrob Chemother 59(3):583–585. doi: 10.1093/jac/dkl496 CrossRefPubMedGoogle Scholar
  50. Jiang M, Zhang Z, Zhao S (2014) Epidemiological characteristics and drug resistance analysis of multidrug-resistant Acinetobacter baumannii in a China hospital at a certain time. Pol J Microbiol/Polskie Towarzystwo Mikrobiologow = The Polish Society of Microbiologists 63(3):275–281Google Scholar
  51. Jones RN, Ferraro MJ, Reller LB, Schreckenberger PC, Swenson JM, Sader HS (2007) Multicenter studies of tigecycline disk diffusion susceptibility results for Acinetobacter spp. J Clin Microbiol 45(1):227–230. doi: 10.1128/JCM.01588-06 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Karageorgopoulos DE, Kelesidis T, Kelesidis I, Falagas ME (2008) Tigecycline for the treatment of multidrug-resistant (including carbapenem-resistant) Acinetobacter infections: a review of the scientific evidence. J Antimicrob Chemother 62(1):45–55. doi: 10.1093/jac/dkn165 CrossRefPubMedGoogle Scholar
  53. Kim CK, Lee Y, Lee H, Woo GJ, Song W, Kim MN, Lee WG, Jeong SH, Lee K, Chong Y (2010) Prevalence and diversity of carbapenemases among imipenem-nonsusceptible Acinetobacter isolates in Korea: emergence of a novel OXA-182. Diagn Microbiol Infect Dis 68(4):432–438. doi: 10.1016/j.diagmicrobio.2010.07.014 CrossRefPubMedGoogle Scholar
  54. Kulah C, Celebi G, Aktas E, Mengeloglu Z, Comert F, Ankarali H (2009) Unexpected tigecycline resistance among Acinetobacter baumannii Isolates: high minor error rate by Etest. J Chemother 21(4):390–395. doi: 10.1179/joc.2009.21.4.390 CrossRefPubMedGoogle Scholar
  55. Leal Castro AL, Buitrago Gutierrez G, Ovalle V, Cortes JA, Alvarez CA, Colombian Tigecycline Susceptibility Surveillance G (2010) Comparing in vitro activity of tigecycline by using the disk diffusion test, the manual microdilution method, and the VITEK 2 automated system. Rev Argent Microbiol 42(3):208–211PubMedGoogle Scholar
  56. Lee YT, Tsao SM, Hsueh PR (2013) Clinical outcomes of tigecycline alone or in combination with other antimicrobial agents for the treatment of patients with healthcare-associated multidrug-resistant Acinetobacter baumannii infections. Eur J Clin Microbiol Infect Dis 32(9):1211–1220. doi: 10.1007/s10096-013-1870-4 CrossRefPubMedGoogle Scholar
  57. Li X, Liu L, Ji J, Chen Q, Hua X, Jiang Y, Feng Y, Yu Y (2015) Tigecycline resistance in Acinetobacter baumannii mediated by frameshift mutation in plsC, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase. Eur J Clin Microbiol Infect Dis 34(3):625–631. doi: 10.1007/s10096-014-2272-y CrossRefPubMedGoogle Scholar
  58. Liao CH, Kung HC, Hsu GJ, Lu PL, Liu YC, Chen CM, Lee CM, Sun W, Jang TN, Chiang PC, Cheng YJ, Lin HC, Shi ZY, Wang LS, Chuang YC, Tsao SM, Lu CT, Liu JW, Huang CH, Hsueh PR (2008) In-vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii in Taiwan determined by the broth microdilution and disk diffusion methods. Int J Antimicrob Agents 32(Suppl 3):S192–S196. doi: 10.1016/S0924-8579(08)70027-X CrossRefPubMedGoogle Scholar
  59. Lin MF, Lan CY (2014) Antimicrobial resistance in Acinetobacter baumannii: from bench to bedside. World J Clin Cases 2(12):787–814. doi: 10.12998/wjcc.v2.i12.787 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Lin MF, Lin YY, Yeh HW, Lan CY (2014) Role of the BaeSR two-component system in the regulation of Acinetobacter baumannii adeAB genes and its correlation with tigecycline susceptibility. BMC Microbiol 14:119. doi: 10.1186/1471-2180-14-119 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Liu JW, Wang LS, Cheng YJ, Hsu GJ, Lu PL, Liu YC, Chen CM, Lee CM, Sun W, Jang TN, Chiang PC, Chuang YC, Lin HC, Shi ZY, Kung HC, Huang CH, Tsao SM, Lu CT, Liao CH, Hsueh PR (2008) In-vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii in Taiwan. Int J Antimicrob Agents 32(Suppl 3):S188–S191. doi: 10.1016/S0924-8579(08)70026-8 CrossRefPubMedGoogle Scholar
  62. Magnet S, Courvalin P, Lambert T (2001) Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 45(12):3375–3380. doi: 10.1128/AAC.45.12.3375-3380.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Marchand I, Damier-Piolle L, Courvalin P, Lambert T (2004) Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 48(9):3298–3304. doi: 10.1128/AAC.48.9.3298-3304.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Mendes RE, Farrell DJ, Sader HS, Jones RN (2010) Comprehensive assessment of tigecycline activity tested against a worldwide collection of Acinetobacter spp. (2005–2009). Diagn Microbiol Infect Dis 68(3): 307–311. doi: 10.1016/j.diagmicrobio.2010.07.003 CrossRefPubMedGoogle Scholar
  65. Moore IF, Hughes DW, Wright GD (2005) Tigecycline is modified by the flavin-dependent monooxygenase TetX. Biochemistry 44(35):11829–11835. doi: 10.1021/bi0506066 CrossRefPubMedGoogle Scholar
  66. Navon-Venezia S, Leavitt A, Carmeli Y (2007) High tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 59(4):772–774. doi: 10.1093/jac/dkm018 CrossRefPubMedGoogle Scholar
  67. Nemec A, Krizova L, Maixnerova M, van der Reijden TJ, Deschaght P, Passet V, Vaneechoutte M, Brisse S, Dijkshoorn L (2011) Genotypic and phenotypic characterization of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex with the proposal of Acinetobacter pittii sp. nov. (formerly Acinetobacter genomic species 3) and Acinetobacter nosocomialis sp. nov. (formerly Acinetobacter genomic species 13TU). Res Microbiol 162(4):393–404. doi: 10.1016/j.resmic.2011.02.006 CrossRefPubMedGoogle Scholar
  68. Nigro SJ, Hall RM (2012) Antibiotic resistance islands in A320 (RUH134), the reference strain for Acinetobacter baumannii global clone 2. J Antimicrob Chemother 67(2):335–338. doi: 10.1093/jac/dkr447 CrossRefPubMedGoogle Scholar
  69. Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C, Llanos AC, Pachon J (2004) Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother 48(11):4479–4481. doi: 10.1128/AAC.48.11.4479-4481.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Papaparaskevas J, Tzouvelekis LS, Tsakris A, Pittaras TE, Legakis NJ, Hellenic Tigecycline Study Group (2010) In vitro activity of tigecycline against 2423 clinical isolates and comparison of the available interpretation breakpoints. Diagn Microbiol Infect Dis 66(2):187–194. doi: 10.1016/j.diagmicrobio.2009.09.012 CrossRefPubMedGoogle Scholar
  71. Paulsen IT (2003) Multidrug efflux pumps and resistance: regulation and evolution. Curr Opin Microbiol 6(5): 446–451. PMID: 14572535Google Scholar
  72. Peleg AY, Adams J, Paterson DL (2007) Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother 51(6):2065–2069. doi: 10.1128/AAC.01198-06 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Petersen PJ, Jacobus NV, Weiss WJ, Sum PE, Testa RT (1999) In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob Agents Chemother 43(4):738–744PubMedPubMedCentralGoogle Scholar
  74. Piewngam P, Kiratisin P (2014) Comparative assessment of antimicrobial susceptibility testing for tigecycline and colistin against Acinetobacter baumannii clinical isolates, including multidrug-resistant isolates. Int J Antimicrob Agents 44(5):396–401. doi: 10.1016/j.ijantimicag.2014.06.014 CrossRefPubMedGoogle Scholar
  75. Pillar CM, Draghi DC, Dowzicky MJ, Sahm DF (2008) In vitro activity of tigecycline against gram-positive and gram-negative pathogens as evaluated by broth microdilution and Etest. J Clin Microbiol 46(9):2862–2867. doi: 10.1128/JCM.00637-08 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Ricciardi R, Ricciardi AM, Danzi G (2009) In vitro activity of tigecycline against multidrug-resistant Acinetobacter baumannii clinical isolates. Le infezioni in medicina: rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive 17(4):236–239Google Scholar
  77. Rizek C, Ferraz JR, van der Heijden IM, Giudice M, Mostachio AK, Paez J, Carrilho C, Levin AS, Costa SF (2015) In vitro activity of potential old and new drugs against multidrug-resistant gram-negatives. J Infect Chemother 21(2):114–117. doi: 10.1016/j.jiac.2014.10.009 CrossRefPubMedGoogle Scholar
  78. Rosenfeld N, Bouchier C, Courvalin P, Perichon B (2012) Expression of the resistance-nodulation-cell division pump AdeIJK in Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator. Antimicrob Agents Chemother 56(5):2504–2510. doi: 10.1128/AAC.06422-11 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Rumbo C, Gato E, Lopez M, Ruiz de Alegria C, Fernandez-Cuenca F, Martinez-Martinez L, Vila J, Pachon J, Cisneros JM, Rodriguez-Bano J, Pascual A, Bou G, Tomas M, Spanish Group of Nosocomial I, Mechanisms of A, Resistance to A, Spanish Society of Clinical M, Infectious D, Spanish Network for Research in Infectious D (2013) Contribution of efflux pumps, porins, and beta-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 57(11):5247–5257. doi: 10.1128/AAC.00730-13 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Ruzin A, Keeney D, Bradford PA (2007) AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticus-Acinetobacter baumannii complex. J Antimicrob Chemother 59(5):1001–1004. doi: 10.1093/jac/dkm058 CrossRefPubMedGoogle Scholar
  81. Ruzin A, Immermann FW, Bradford PA (2010) RT-PCR and statistical analyses of adeABC expression in clinical isolates of Acinetobacter calcoaceticus-Acinetobacter baumannii complex. Microb Drug Resist 16(2):87–89. doi: 10.1089/mdr.2009.0131 CrossRefPubMedGoogle Scholar
  82. Sader HS, Jones RN, Stilwell MG, Dowzicky MJ, Fritsche TR (2005) Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents. Diagn Microbiol Infect Dis 52(3):181–186. doi: 10.1016/j.diagmicrobio.2005.05.005 CrossRefPubMedGoogle Scholar
  83. Sader HS, Farrell DJ, Flamm RK, Jones RN (2014) Variation in potency and spectrum of tigecycline activity against bacterial strains from U.S. medical centers since its approval for clinical use (2006 to 2012). Antimicrob Agents Chemother 58(4):2274–2280. doi: 10.1128/AAC.02684-13 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Scheetz MH, Qi C, Warren JR, Postelnick MJ, Zembower T, Obias A, Noskin GA (2007) In vitro activities of various antimicrobials alone and in combination with tigecycline against carbapenem-intermediate or -resistant Acinetobacter baumannii. Antimicrob Agents Chemother 51(5):1621–1626. doi: 10.1128/AAC.01099-06 CrossRefPubMedPubMedCentralGoogle Scholar
  85. Seifert H, Stefanik D, Wisplinghoff H (2006) Comparative in vitro activities of tigecycline and 11 other antimicrobial agents against 215 epidemiologically defined multidrug-resistant Acinetobacter baumannii isolates. J Antimicrob Chemother 58(5):1099–1100. doi: 10.1093/jac/dkl383 CrossRefPubMedGoogle Scholar
  86. Spiliopoulou A, Jelastopulu E, Vamvakopoulou S, Bartzavali C, Kolonitsiou F, Anastassiou ED, Christofidou M (2014) In vitro activity of tigecycline and colistin against A. baumannii clinical bloodstream isolates during an 8-year period. J Chemother. doi: 10.1179/1973947814Y.0000000193
  87. Srinivasan VB, Vaidyanathan V, Rajamohan G (2015) AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob Agents Chemother 59(2):1236–1245. doi: 10.1128/AAC.03626-14 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Stein GE, Babinchak T (2013) Tigecycline: an update. Diagn Microbiol Infect Dis 75(4):331–336. doi: 10.1016/j.diagmicrobio.2012.12.004 CrossRefPubMedGoogle Scholar
  89. Sun JR, Chan MC, Chang TY, Wang WY, Chiueh TS (2010) Overexpression of the adeB gene in clinical isolates of tigecycline-nonsusceptible Acinetobacter baumannii without insertion mutations in adeRS. Antimicrob Agents Chemother 54(11):4934–4938. doi: 10.1128/AAC.00414-10 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Sun JR, Perng CL, Chan MC, Morita Y, Lin JC, Su CM, Wang WY, Chang TY, Chiueh TS (2012) A truncated AdeS kinase protein generated by ISAba1 insertion correlates with tigecycline resistance in Acinetobacter baumannii. PLoS One 7(11):e49534. doi: 10.1371/journal.pone.0049534 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Sun Y, Cai Y, Liu X, Bai N, Liang B, Wang R (2013) The emergence of clinical resistance to tigecycline. Int J Antimicrob Agents 41(2):110–116. doi: 10.1016/j.ijantimicag.2012.09.005 CrossRefPubMedGoogle Scholar
  92. Sun JR, Perng CL, Lin JC, Yang YS, Chan MC, Chang TY, Lin FM, Chiueh TS (2014) AdeRS combination codes differentiate the response to efflux pump inhibitors in tigecycline-resistant isolates of extensively drug-resistant Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 33(12):2141–2147. doi: 10.1007/s10096-014-2179-7 CrossRefPubMedGoogle Scholar
  93. Tan TY, Ng LS (2007) Susceptibility of multi-resistant Gram-negative bacilli in Singapore to tigecycline as tested by agar dilution. Ann Acad Med Singap 36(10):807–810. PMID: 17987230Google Scholar
  94. Taneja N, Singh G, Singh M, Sharma M (2011) Emergence of tigecycline & colistin resistant Acinetobacter baumanii in patients with complicated urinary tract infections in north India. Indian J Med Res 133:681–684PubMedPubMedCentralGoogle Scholar
  95. Teng SO, Yen MY, Ou TY, Chen FL, Yu FL, Lee WS (2014) Comparison of pneumonia- and non-pneumonia-related Acinetobacter baumannii bacteremia: impact on empiric therapy and antibiotic resistance. J Microbiol Immunol Infect = Wei mian yu gan ran za zhi. doi: 10.1016/j.jmii.2014.06.011
  96. Thamlikitkul V, Tiengrim S (2008) Effect of different Mueller-Hinton agars on tigecycline disc diffusion susceptibility for Acinetobacter spp. J Antimicrob Chemother 62(4):847–848. doi: 10.1093/jac/dkn267 CrossRefPubMedPubMedCentralGoogle Scholar
  97. Thamlikitkul V, Tiengrim S, Tribuddharat C (2007) Comment on: high tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 60(1):177–178. doi: 10.1093/jac/dkm142
  98. Towner KJ (2009) Acinetobacter: an old friend, but a new enemy. J Hosp Infect 73(4):355–363. doi: 10.1016/j.jhin.2009.03.032 CrossRefPubMedGoogle Scholar
  99. Van TD, Dinh QD, Vu PD, Nguyen TV, Pham CV, Dao TT, Phung CD, Hoang HT, Tang NT, Do NT, Nguyen KV, Wertheim H (2014) Antibiotic susceptibility and molecular epidemiology of complex strains isolated from a referral hospital in northern Vietnam. J Glob Antimicrob Resist 2(4):318–321. doi: 10.1016/j.jgar.2014.05.003 CrossRefPubMedPubMedCentralGoogle Scholar
  100. Yahav D, Lador A, Paul M, Leibovici L (2011) Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother 66(9): 1963–1971. doi: 10.1093/jac/dkr242 CrossRefPubMedGoogle Scholar
  101. Yoon EJ, Courvalin P, Grillot-Courvalin C (2013) RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother 57(7):2989–2995. doi: 10.1128/AAC.02556-12 CrossRefPubMedPubMedCentralGoogle Scholar
  102. Zarate MS, Serruto G, Smayevsky J (2010) The susceptibility to tigecycline of Acinetobacter spp. may vary depending on the methodology used. Int J Infect Dis 14(Suppl 3):e351–e352. doi: 10.1016/j.ijid.2009.08.015 CrossRefPubMedGoogle Scholar
  103. Zarkotou O, Pournaras S, Altouvas G, Pitiriga V, Tziraki M, Mamali V, Themeli-Digalaki K, Tsakris A (2012) Comparative evaluation of tigecycline susceptibility testing methods for expanded-spectrum cephalosporin- and carbapenem-resistant gram-negative pathogens. J Clin Microbiol 50(11):3747–3750. doi: 10.1128/JCM.02037-12 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Spyros Pournaras
    • 1
    • 2
  • Vasiliki Koumaki
    • 1
  • Vasiliki Gennimata
    • 1
  • Evangelia Kouskouni
    • 2
  • Athanassios Tsakris
    • 1
    Email author
  1. 1.Department of Microbiology, Medical SchoolUniversity of AthensAthensGreece
  2. 2.Department of Biopathology, Aretaieio HospitalUniversity of AthensAthensGreece

Personalised recommendations