Skip to main content
SpringerLink
Log in

Antimicrobial Resistance in Stenotrophomonas maltophilia: Mechanisms and Clinical Implications

  • Chapter
  • First Online:
Antimicrobial Drug Resistance

Abstract

Stenotrophomonas maltophilia, a global opportunistic pathogen, persists in various environments and displays high-level intrinsic resistance to a wide range of antimicrobial drugs including β-lactams, aminoglycosides, fluoroquinolones, macrolides, and tetracyclines. Acquired multidrug resistance can be readily derived after exposure of S. maltophilia to different antimicrobials and is rapidly emerging in clinical isolates. This species possesses various molecular and biochemical mechanisms of resistance, which include the production of class A and B β-lactamases, several aminoglycoside-modifying enzymes, Qnr quinolone target protection proteins, and multidrug efflux transporters. Together with virulence factors, the multidrug resistance phenotype poses as a major hurdle for therapeutic development. Trimethoprim-sulfamethoxazole and other antimicrobial combination regimes remain as the dominant therapeutics within the limited drugs against S. maltophilia. However, in addition to a global emergence of resistance to trimethoprim-sulfonamides, the remaining options for combination therapies are often only based on in vitro antimicrobial synergy testing and/or case reports. This chapter provides an overview of the features, mechanisms, and clinical implications of antimicrobial resistance in S. maltophilia with an emphasis on the genetic and biochemical mechanisms of resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hugh R, Ryschenkow E. Pseudomonas maltophilia, an alcaligenes-like species. J Gen Microbiol. 1961;26:123–32. doi:10.1099/00221287-26-1-123.

    Article  CAS  PubMed  Google Scholar 

  2. Swings J, De Vos P, Van Den Mooter M, De Ley J. Transfer of Pseudomonas maltophilia Hugh 1981 to the genus Xanthomonas as Xanthomonas maltophilia (Hugh 1981) comb. nov. Int J Syst Bacteriol. 1983;33(2):409–13. doi:10.1099/00207713-33-2-409.

    Article  Google Scholar 

  3. Palleroni NJ, Bradbury JF. Stenotrophomonas, a new bacterial genus for Xanthomonas maltophilia (Hugh 1980) Swings et al. 1983. Int J Syst Bacteriol. 1993;43(3):606–9. doi:10.1099/00207713-43-3-606.

    Article  CAS  PubMed  Google Scholar 

  4. Ryan RP, Monchy S, Cardinale M, Taghavi S, Crossman L, Avison MB, Berg G, van der Lelie D, Dow JM. The versatility and adaptation of bacteria from the genus Stenotrophomonas. Nat Rev Microbiol. 2009;7(7):514–25. doi:10.1038/nrmicro2163.

    Article  CAS  PubMed  Google Scholar 

  5. Marshall WF, Keating MR, Anhalt JP, Steckelberg JM. Xanthomonas maltophilia: an emerging nosocomial pathogen. Mayo Clin Proc. 1989;64(9):1097–104. doi:10.1016/S0025-6196(12)64979-9.

    Article  CAS  PubMed  Google Scholar 

  6. Spencer RC. The emergence of epidemic, multiple-antibiotic-resistant Stenotrophomonas (Xanthomonas) maltophilia and Burkholderia (Pseudomonas) cepacia. J Hosp Infect. 1995;30(Suppl):453–64. doi:10.1016/0195-6701(95)90049-7.

    Article  PubMed  Google Scholar 

  7. Denton M, Kerr KG. Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia. Clin Microbiol Rev. 1998;11(1):57–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Micozzi A, Venditti M, Monaco M, Friedrich A, Taglietti F, Santilli S, Martino P. Bacteremia due to Stenotrophomonas maltophilia in patients with hematologic malignancies. Clin Infect Dis. 2000;31(3):705–11. doi:10.1086/314043.

    Article  CAS  PubMed  Google Scholar 

  9. Safdar A, Rolston KV. Stenotrophomonas maltophilia: changing spectrum of a serious bacterial pathogen in patients with cancer. Clin Infect Dis. 2007;45(12):1602–9. doi:10.1086/522998.

    Article  PubMed  Google Scholar 

  10. Looney WJ, Narita M, Muhlemann K. Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis. 2009;9(5):312–23. doi:10.1016/S1473-3099(09)70083-0.

    Article  CAS  PubMed  Google Scholar 

  11. Mori M, Tsunemine H, Imada K, Ito K, Kodaka T, Takahashi T. Life-threatening hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in the treatment of hematologic diseases. Ann Hematol. 2014;93(6):901–11. doi:10.1007/s00277-014-2028-x.

    Article  CAS  PubMed  Google Scholar 

  12. Berg G, Roskot N, Smalla K. Genotypic and phenotypic relationships between clinical and environmental isolates of Stenotrophomonas maltophilia. J Clin Microbiol. 1999;37(11):3594–600.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Garrison MW, Anderson DE, Campbell DM, Carroll KC, Malone CL, Anderson JD, Hollis RJ, Pfaller MA. Stenotrophomonas maltophilia: emergence of multidrug-resistant strains during therapy and in an in vitropharmacodynamic chamber model. Antimicrob Agents Chemother. 1996;40(12):2859–64.

    Google Scholar 

  14. Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev. 2012;25(1):2–41. doi:10.1128/CMR.00019-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Falagas ME, Kastoris AC, Vouloumanou EK, Dimopoulos G. Community-acquired Stenotrophomonas maltophilia infections: a systematic review. Eur J Clin Microbiol Infect Dis. 2009;28(7):719–30. doi:10.1007/s10096-009-0709-5.

    Article  CAS  PubMed  Google Scholar 

  16. De Mauri A, Torreggiani M, Chiarinotti D, Andreoni S, Molinari G, De Leo M. Stenotrophomonas maltophilia: an emerging pathogen in dialysis units. J Med Microbiol. 2014;63(Pt 11):1407–10. doi:10.1099/jmm.0.076513-0.

    Article  PubMed  Google Scholar 

  17. Denton M, Todd NJ, Littlewood JM. Role of anti-pseudomonal antibiotics in the emergence of Stenotrophomonas maltophilia in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis. 1996;15(5):402–5. doi:10.1007/BF01690098.

  18. Hotta G, Matsumura Y, Kato K, Nakano S, Yunoki T, Yamamoto M, Nagao M, Ito Y, Takakura S, Ichiyama S. Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: a comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter species. PLoS One. 2014;9(11): e112208. doi:10.1371/journal.pone.0112208.

  19. Stanojevic S, Ratjen F, Stephens D, Lu A, Yau Y, Tullis E, Waters V. Factors influencing the acquisition of Stenotrophomonas maltophilia infection in cystic fibrosis patients. J Cyst Fibros. 2013;12(6):575–83. doi:10.1016/j.jcf.2013.05.009.

    Article  PubMed  Google Scholar 

  20. Trecarichi EM, Tumbarello M. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact. Curr Opin Infect Dis. 2014;27(2):200–10. doi:10.1097/QCO.0000000000000038.

    Article  CAS  PubMed  Google Scholar 

  21. Abbott IJ, Slavin MA, Turnidge JD, Thursky KA, Worth LJ. Stenotrophomonas maltophilia: emerging disease patterns and challenges for treatment. Expert Rev Anti Infect Ther. 2011;9(4):471–88. doi:10.1586/eri.11.24.

    Article  PubMed  Google Scholar 

  22. Falagas ME, Kastoris AC, Vouloumanou EK, Rafailidis PI, Kapaskelis AM, Dimopoulos G. Attributable mortality of Stenotrophomonas maltophilia infections: a systematic review of the literature. Future Microbiol. 2009;4(9):1103–9. doi:10.2217/fmb.09.84.

    Article  PubMed  Google Scholar 

  23. Lockhart SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, Quinn JP, Doern GV. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol. 2007;45(10):3352–9. doi:10.1128/JCM.01284-07.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalised with pneumonia in US and European hospitals: results from the SENTRY Antimicrobial Surveillance Program, 2009–2012. Int J Antimicrob Agents. 2014;43(4):328–34. doi:10.1016/j.ijantimicag.2014.01.007.

    Article  CAS  PubMed  Google Scholar 

  25. Tan CK, Liaw SJ, Yu CJ, Teng LJ, Hsueh PR. Extensively drug-resistant Stenotrophomonas maltophilia in a tertiary care hospital in Taiwan: microbiologic characteristics, clinical features, and outcomes. Diagn Microbiol Infect Dis. 2008;60(2):205–10. doi:10.1016/j.diagmicrobio.2007.09.007.

    Article  CAS  PubMed  Google Scholar 

  26. Di Bonaventura G, Spedicato I, D’Antonio D, Robuffo I, Piccolomini R. Biofilm formation by Stenotrophomonas maltophilia: modulation by quinolones, trimethoprim-sulfamethoxazole, and ceftazidime. Antimicrob Agents Chemother. 2004;48(1):151–60. doi:10.1128/AAC.48.1.151-160.2004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Pompilio A, Pomponio S, Crocetta V, Gherardi G, Verginelli F, Fiscarelli E, Dicuonzo G, Savini V, D’Antonio D, Di Bonaventura G. Phenotypic and genotypic characterization of Stenotrophomonas maltophilia isolates from patients with cystic fibrosis: genome diversity, biofilm formation, and virulence. BMC Microbiol. 2011;11:159. doi:10.1186/1471-2180-11-159.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sánchez P, Alonso A, Campanario E, Alos I, Martiinez JL. Accumulation and efflux of quinolones by clinical isolates of Stenotrophomonas maltophilia. Rev Esp Quimioter. 2000;13(2):176–81.

    PubMed  Google Scholar 

  29. Li X-Z, Zhang L, McKay GA, Poole K. Role of the acetyltransferase AAC(6')-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2003;51(4):803–11. doi:10.1093/jac/dkg148.

    Article  CAS  PubMed  Google Scholar 

  30. Pankuch GA, Jacobs MR, Rittenhouse SF, Appelbaum PC. Susceptibilities of 123 strains of Xanthomonas maltophilia to eight β-lactams (including β-lactam-β-lactamase inhibitor combinations) and ciprofloxacin tested by five methods. Antimicrob Agents Chemother. 1994;38(10):2317–22. doi:10.1128/AAC.38.10.2317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pankuch GA, Jacobs MR, Appelbaum PC. Susceptibilities of 123 Xanthomonas maltophilia strains to clinafloxacin, PD 131628, PD 138312, PD 140248, ciprofloxacin, and ofloxacin. Antimicrob Agents Chemother. 1994;38(2):369–70. doi:10.1128/AAC.38.2.369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang L, Li X-Z, Poole K. Multiple antibiotic resistance in Stenotrophomonas maltophilia: involvement of a multidrug efflux system. Antimicrob Agents Chemother. 2000;44(2):287–93. doi:10.1128/AAC.44.2.287-293.2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tripodi MF, Andreana A, Sarnataro G, Ragone E, Adinolfi LE, Utili R. Comparative activities of isepamicin, amikacin, cefepime, and ciprofloxacin alone or in combination with other antibiotics against Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis. 2001;20(1):73–5. doi:10.1007/PL00011239.

    Google Scholar 

  34. Chow AW, Wong J, Bartlett KH. Synergistic interactions of ciprofloxacin and extended-spectrum β-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia. Antimicrob Agents Chemother. 1988;32(5):782–4. doi:10.1128/AAC.32.5.782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang L, Li X-Z, Poole K. Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia. J Antimicrob Chemother. 2001;48(4):549–52. doi:10.1093/jac/48.4.549.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang L, Li X-Z, Poole K. SmeDEF multidrug efflux pump contributes to intrinsic multidrug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2001;45(12):3497–503. doi:10.1128/AAC.45.12.3497-3503.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. CLSI. Performance standards for antimicrobial susceptibility testing; Twenty-fifth informational supplement, M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.

    Google Scholar 

  38. Felici A, Amicosante G, Oratore A, Strom R, Ledent P, Joris B, Fanuel L, Frere JM. An overview of the kinetic parameters of class B β-lactamases. Biochem J. 1993;291(Pt 1):151–5.doi:10.1042/bj2910151.

    Google Scholar 

  39. Felici A, Amicosante G. Kinetic analysis of extension of substrate specificity with Xanthomonas maltophilia, Aeromonas hydrophila, and Bacillus cereus metallo-β-lactamases. Antimicrob Agents Chemother. 1995;39(1):192–9. doi:10.1128/AAC.39.1.192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Payne DJ, Bateson JH, Gasson BC, Proctor D, Khushi T, Farmer TH, Tolson DA, Bell D, Skett PW, Marshall AC, Reid R, Ghosez L, Combret Y, Marchand-Brynaert J. Inhibition of metallo-β-lactamases by a series of mercaptoacetic acid thiol ester derivatives. Antimicrob Agents Chemother. 1997;41(1):135–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Alonso A, Martínez JL. Multiple antibiotic resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1997;41(5):1140–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ba BB, Feghali H, Arpin C, Saux MC, Quentin C. Activities of ciprofloxacin and moxifloxacin against Stenotrophomonas maltophilia and emergence of resistant mutants in an in vitro pharmacokinetic-pharmacodynamic model. Antimicrob Agents Chemother. 2004;48(3):946–53. doi:10.1128/AAC.48.3.946-953.2004.

  43. Cho SY, Kang CI, Kim J, Ha YE, Chung DR, Lee NY, Peck KR, Song JH. Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia bacteremia? Antimicrob Agents Chemother. 2014;58(1):581–3. doi:10.1128/AAC.01682-13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Wang YL, Scipione MR, Dubrovskaya Y, Papadopoulos J. Monotherapy with fluoroquinolone or trimethoprim-sulfamethoxazole for treatment of Stenotrophomonas maltophilia infections. Antimicrob Agents Chemother. 2014;58(1):176–82. doi:10.1128/AAC.01324-13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Al-Jasser AM. Stenotrophomonas maltophilia resistant to trimethoprim-sulfamethoxazole: an increasing problem. Ann Clin Microbiol Antimicrob. 2006;5:23. doi:10.1186/1476-0711-5-23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Toleman MA, Bennett PM, Bennett DM, Jones RN, Walsh TR. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis. 2007;13(4):559–65. doi:10.3201/eid1304.061378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kaur P, Gautam V, Tewari R. Distribution of class 1 integrons, sul1 and sul2 genes among clinical isolates of Stenotrophomonas maltophilia from a tertiary care hospital in North India. Microb Drug Resist. 2015. doi:10.1089/mdr.2014.0176.

  48. Chung HS, Kim K, Hong SS, Hong SG, Lee K, Chong Y. The sul1 gene in Stenotrophomonas maltophilia with high-level resistance to trimethoprim/sulfamethoxazole. Ann Lab Med. 2015;35(2):246–9. doi:10.3343/alm.2015.35.2.246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang R, Sun Q, Hu YJ, Yu H, Li Y, Shen Q, Li GX, Cao JM, Yang W, Wang Q, Zhou HW, Hu YY, Chen GX. Detection of the Smqnr quinolone protection gene and its prevalence in clinical isolates of Stenotrophomonas maltophilia in China. J Med Microbiol. 2012;61(Pt 4):535–9. doi:10.1099/jmm.0.037309-0.

    Article  PubMed  CAS  Google Scholar 

  50. Gales AC, Jones RN, Forward KR, Linares J, Sader HS, Verhoef J. Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997–1999). Clin Infect Dis. 2001;32 Suppl 2:S104–13. doi:10.1086/320183.

    Article  CAS  PubMed  Google Scholar 

  51. Vidigal PG, Dittmer S, Steinmann E, Buer J, Rath PM, Steinmann J. Adaptation of Stenotrophomonas maltophilia in cystic fibrosis: molecular diversity, mutation frequency and antibiotic resistance. Int J Med Microbiol. 2014;304(5–6):613–9. doi:10.1016/j.ijmm.2014.04.002.

    Article  CAS  PubMed  Google Scholar 

  52. Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez FJ, Barrero-Almodovar AE, Garcia-Garmendia JL, Bernabeu-Wittel IM, Gallego-Lara SL, Madrazo-Osuna J. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis. 2003;36(9):1111–8. doi:10.1086/374337.

  53. Giamarellou H, Poulakou G. Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs. 2009;69(14):1879–901. doi:10.2165/11315690-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  54. Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Hoiby N, Molin S. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol. 2012;10(12):841–51. doi:10.1038/nrmicro2907.

    Article  CAS  PubMed  Google Scholar 

  55. Kollef MH, Chastre J, Fagon JY, Francois B, Niederman MS, Rello J, Torres A, Vincent JL, Wunderink RG, Go KW, Rehm C. Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due to Pseudomonas aeruginosa. Crit Care Med. 2014;42(10):2178–87. doi:10.1097/CCM.0000000000000510.

    Article  PubMed  Google Scholar 

  56. Hawkey PM, Livermore DM. Carbapenem antibiotics for serious infections. Br Med J. 2012;344:e3236. doi:10.1136/bmj.e3236.

    Article  CAS  Google Scholar 

  57. Apisarnthanarak A, Kiratisin P, Apisarnthanarak P, Mundy LM. Gastrointestinal selective capacity of doripenem, meropenem, and imipenem for carbapenem-resistant Gram-negative bacilli in treated patients with pneumonia. Infect Control Hosp Epidemiol. 2011;32(4):410–1. doi:10.1086/659252.

    Article  PubMed  Google Scholar 

  58. Sivakumar M, Hisham M, Nandakumar V, Gopinathan T. Emergence of isolates that are intrinsically resistant to colistin in critically ill patients: are we selecting them out? Crit Care. 2015;19 Suppl 1:95. doi:10.1186/cc14175.

    Article  Google Scholar 

  59. Crossman LC, Gould VC, Dow JM, Vernikos GS, Okazaki A, Sebaihia M, Saunders D, Arrowsmith C, Carver T, Peters N, Adlem E, Kerhornou A, Lord A, Murphy L, Seeger K, Squares R, Rutter S, Quail MA, Rajandream MA, Harris D, Churcher C, Bentley SD, Parkhill J, Thomson NR, Avison MB. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol. 2008;9(4):R74. doi:10.1186/gb-2008-9-4-r74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000;406(6799):959–64. doi:10.1038/35023079.

  61. Fournier PE, Richet H. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis. 2006;42(5):692–9. doi:10.1086/500202.

    Article  PubMed  Google Scholar 

  62. Lira F, Hernández A, Belda E, Sánchez MB, Moya A, Silva FJ, Martínez JL. Whole-genome sequence of Stenotrophomonas maltophilia D457, a clinical isolate and a model strain. J Bacteriol. 2012;194(13):3563–4. doi:10.1128/JB.00602-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Song S, Yuan X, Liu S, Zhang N, Wang Y, Ke Y, Xu J, Huang L, Chen Z, Li Y. Genome sequence of Stenotrophomonas maltophilia S028, an isolate harboring the AmpR-L2 resistance module. J Bacteriol. 2012;194(23):6696. doi:10.1128/JB.01809-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Alavi P, Starcher MR, Thallinger GG, Zachow C, Muller H, Berg G. Stenotrophomonas comparative genomics reveals genes and functions that differentiate beneficial and pathogenic bacteria. BMC Genomics. 2014;15:482. doi:10.1186/1471-2164-15-482.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Zhao Y, Niu W, Sun Y, Hao H, Yu D, Xu G, Shang X, Tang X, Lu S, Yue J, Li Y. Identification and characterization of a serious multidrug resistant Stenotrophomonas maltophilia strain in China. BioMed Res Int. 2015;2015:580240. doi:10.1155/2015/580240.

    PubMed  PubMed Central  Google Scholar 

  66. Rocco F, De Gregorio E, Colonna B, Di Nocera PP. Stenotrophomonas maltophilia genomes: a start-up comparison. Int J Med Microbiol. 2009;299(8):535–46. doi:10.1016/j.ijmm.2009.05.004.

    Article  CAS  PubMed  Google Scholar 

  67. Sanschagrin F, Dufresne J, Levesque RC. Molecular heterogeneity of the L-1 metallo-β-lactamase family from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1998;42(5):1245–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Sánchez MB, Hernández A, Rodriguez-Martínez JM, Martínez-Martínez L, Martínez JL. Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants. BMC Microbiol. 2008;8:148. doi:10.1186/1471-2180-8-148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Li X-Z. Quinolone resistance in bacteria: emphasis on plasmid-mediated mechanisms. Int J Antimicrob Agents. 2005;25(6):453–63. doi:10.1016/j.ijantimicag.2005.04.002.

    Article  CAS  PubMed  Google Scholar 

  70. Jacoby GA, Strahilevitz J, Hooper DC. Plasmid-mediated quinolone resistance. Microbiol Spectr. 2014;2(2). doi: 10.1128/microbiolspec.PLAS-0006-2013.

  71. Chang LL, Chen HF, Chang CY, Lee TM, Wu WJ. Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2004;53(3):518–21. doi:10.1093/jac/dkh094.

    Article  CAS  PubMed  Google Scholar 

  72. Wu K, Wang F, Sun J, Wang Q, Chen Q, Yu S, Rui Y. Class 1 integron gene cassettes in multidrug-resistant Gram-negative bacteria in southern China. Int J Antimicrob Agents. 2012;40(3):264–7. doi:10.1016/j.ijantimicag.2012.05.017.

    Article  CAS  PubMed  Google Scholar 

  73. Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, Richet H, Robert C, Mangenot S, Abergel C, Nordmann P, Weissenbach J, Raoult D, Claverie JM. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet. 2006;2(1): e7. doi:10.1371/journal.pgen.0020007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Li X-Z. Antimicrobial resistance in Salmonella: features and mechanisms. In: Giordano LS, Moretti MA, editors. Salmonella infections: new research. Hauppauge, NY: Nova Scienence Publishers; 2008. p. 1–43.

    Google Scholar 

  75. He T, Shen J, Schwarz S, Wu C, Wang Y. Characterization of a genomic island in Stenotrophomonas maltophilia that carries a novel floR gene variant. J Antimicrob Chemother. 2015;70(4):1031–6. doi:10.1093/jac/dku491.

    CAS  PubMed  Google Scholar 

  76. Adamek M, Linke B, Schwartz T. Virulence genes in clinical and environmental Stenotrophomonas maltophilia isolates: a genome sequencing and gene expression approach. Microb Pathog. 2014;67–68:20–30. doi:10.1016/j.micpath.2014.02.001.

    Article  PubMed  CAS  Google Scholar 

  77. Toleman MA, Bennett PM, Walsh TR. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev. 2006;70(2):296–316. doi:10.1128/MMBR.00048-05.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39(6):1211–33. doi:10.1128/AAC.39.6.1211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bush K, Fisher JF. Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from Gram-negative bacteria. Annu Rev Microbiol. 2011;65:455–78. doi:10.1146/annurev-micro-090110-102911.

    Article  CAS  PubMed  Google Scholar 

  80. Saino Y, Kobayashi F, Inoue M, Mitsuhashi S. Purification and properties of inducible penicillin β-lactamase isolated from Pseudomonas maltophilia. Antimicrob Agents Chemother. 1982;22(4):564–70. doi:10.1128/AAC.39.6.1211.

  81. Akova M, Bonfiglio G, Livermore DM. Susceptibility to β-lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 β-lactamases. J Med Microbiol. 1991;35(4):208–13. doi:10.1099/00222615-35-4-208.

    Article  CAS  PubMed  Google Scholar 

  82. Paton R, Miles RS, Amyes SG. Biochemical properties of inducible β-lactamases produced from Xanthomonas maltophilia. Antimicrob Agents Chemother. 1994;38(9):2143–9. doi:10.1128/AAC.38.9.2143.

  83. Yang Z, Liu W, Cui Q, Niu W, Li H, Zhao X, Wei X, Wang X, Huang S, Dong D, Lu S, Bai C, Li Y, Huang L, Yuan J. Prevalence and detection of Stenotrophomonas maltophilia carrying metallo-β-lactamase blaL1 in Beijing, China. Front Microbiol. 2014;5:692. doi:10.3389/fmicb.2014.00692.

    PubMed  PubMed Central  Google Scholar 

  84. Lecso-Bornet M, Bergogne-Berezin E. Susceptibility of 100 strains of Stenotrophomonas maltophilia to three β-lactams and five β-lactam-β-lactamase inhibitor combinations. J Antimicrob Chemother. 1997;40(5):717–20. doi:10.1093/jac/40.5.717.

    Article  CAS  PubMed  Google Scholar 

  85. Mercuri PS, Ishii Y, Ma L, Rossolini GM, Luzzaro F, Amicosante G, Franceschini N, Frere JM, Galleni M. Clonal diversity and metallo-β-lactamase production in clinical isolates of Stenotrophomonas maltophilia. Microb Drug Resist. 2002;8(3):193–200. doi:10.1089/107662902760326904.

    Article  CAS  PubMed  Google Scholar 

  86. Gould VC, Okazaki A, Avison MB. β-Lactam resistance and β-lactamase expression in clinical Stenotrophomonas maltophilia isolates having defined phylogenetic relationships. J Antimicrob Chemother. 2006;57(2):199–203. doi:10.1093/jac/dki453.

    Article  CAS  PubMed  Google Scholar 

  87. Avison MB, Higgins CS, von Heldreich CJ, Bennett PM, Walsh TR. Plasmid location and molecular heterogeneity of the L1 and L2 β-lactamase genes of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2001;45(2):413–9. doi:10.1128/AAC.45.2.413-419.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mett H, Rosta S, Schacher B, Frei R. Outer membrane permeability and β-lactamase content in Pseudomonas maltophilia clinical isolates and laboratory mutants. Rev Infect Dis. 1988;10(4):765–9. doi:10.1093/clinids/10.4.765.

    Article  CAS  PubMed  Google Scholar 

  89. Li X-Z, Zhang L, Poole K. SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2002;46(2):333–43. doi:10.1128/AAC.46.2.333-343.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dufresne J, Vezina G, Levesque RC. Cloning and expression of the imipenem-hydrolyzing β-lactamase operon from Pseudomonas maltophilia in Escherichia coli. Antimicrob Agents Chemother. 1988;32(6):819–26. doi:10.1128/AAC.32.6.819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Rasmussen BA, Bush K. Carbapenem-hydrolyzing β-lactamases. Antimicrob Agents Chemother. 1997;41(2):223–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Garrity JD, Carenbauer AL, Herron LR, Crowder MW. Metal binding Asp-120 in metallo-β-lactamase L1 from Stenotrophomonas maltophilia plays a crucial role in catalysis. J Biol Chem. 2004;279(2):920–7. doi:10.1074/jbc.M309852200.

    Article  CAS  PubMed  Google Scholar 

  93. Crowder MW, Walsh TR, Banovic L, Pettit M, Spencer J. Overexpression, purification, and characterization of the cloned metallo-β-lactamase L1 from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1998;42(4):921–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Concha NO, Rasmussen BA, Bush K, Herzberg O. Crystal structure of the wide-spectrum binuclear zinc β-lactamase from Bacteroides fragilis. Structure. 1996;4(7):823–36. doi:10.1016/S0969-2126(96)00089-5.

    Google Scholar 

  95. Ullah JH, Walsh TR, Taylor IA, Emery DC, Verma CS, Gamblin SJ, Spencer J. The crystal structure of the L1 metallo-β-lactamase from Stenotrophomonas maltophilia at 1.7 Å resolution. J Mol Biol. 1998;284(1):125–36. doi:10.1006/jmbi.1998.2148.

    Article  CAS  PubMed  Google Scholar 

  96. Payne DJ, Bateson JH, Gasson BC, Khushi T, Proctor D, Pearson SC, Reid R. Inhibition of metallo-β-lactamases by a series of thiol ester derivatives of mercaptophenylacetic acid. FEMS Microbiol Lett. 1997;157(1):171–5. doi:10.1111/j.1574-6968.1997.tb12769.x.

    Article  CAS  PubMed  Google Scholar 

  97. Yang KW, Crowder MW. Inhibition studies on the metallo-β-lactamase L1 from Stenotrophomonas maltophilia. Arch Biochem Biophys. 1999;368(1):1–6. doi:10.1006/abbi.1999.1293.

    Google Scholar 

  98. Payne DJ, Hueso-Rodriguez JA, Boyd H, Concha NO, Janson CA, Gilpin M, Bateson JH, Cheever C, Niconovich NL, Pearson S, Rittenhouse S, Tew D, Diez E, Perez P, De La Fuente J, Rees M, Rivera-Sagredo A. Identification of a series of tricyclic natural products as potent broad-spectrum inhibitors of metallo-β-lactamases. Antimicrob Agents Chemother. 2002;46(6):1880–6. doi:10.1128/AAC.46.6.1880-1886.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Nagano R, Adachi Y, Imamura H, Yamada K, Hashizume T, Morishima H. Carbapenem derivatives as potential inhibitors of various β-lactamases, including class B metallo-β-lactamases. Antimicrob Agents Chemother. 1999;43(10):2497–503.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Nagano R, Adachi Y, Hashizume T, Morishima H. In vitro antibacterial activity and mechanism of action of J-111,225, a novel 1β-methylcarbapenem, against transferable IMP-1 metallo-β-lactamase producers. J Antimicrob Chemother. 2000;45(3):271–6. doi:10.1093/jac/45.3.271.

  101. Denny BJ, Lambert PA, West PW. The flavonoid galangin inhibits the L1 metallo-β-lactamase from Stenotrophomonas maltophilia. FEMS Microbiol Lett. 2002;208(1):21–4. doi:10.1111/j.1574-6968.2002.tb11054.x.

    CAS  PubMed  Google Scholar 

  102. Sanschagrin F, Levesque RC. A specific peptide inhibitor of the class B metallo-β-lactamase L-1 from Stenotrophomonas maltophilia identified using phage display. J Antimicrob Chemother. 2005;55(2):252–5. doi:10.1093/jac/dkh550.

    Article  CAS  PubMed  Google Scholar 

  103. Saino Y, Inoue M, Mitsuhashi S. Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873. Antimicrob Agents Chemother. 1984;25(3):362–5. doi:10.1111/j.1574-6968.2002.tb11054.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Walsh TR, MacGowan AP, Bennett PM. Sequence analysis and enzyme kinetics of the L2 serine β-lactamase from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1997;41(7):1460–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Pradhananga SL, Rowling PJ, Simpson IN, Payne DJ. Sensitivity of L-2 type β-lactamases from Stenotrophomonas maltophilia to serine active site β-lactamase inhibitors. J Antimicrob Chemother. 1996;37(2):394–6. doi:10.1093/jac/37.2.394.

    Article  CAS  PubMed  Google Scholar 

  106. Vartivarian S, Anaissie E, Bodey G, Sprigg H, Rolston K. A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy. Antimicrob Agents Chemother. 1994;38(3):624–7. doi:10.1128/AAC.38.3.624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Normark S. β-Lactamase induction in Gram-negative bacteria is intimately linked to peptidoglycan recycling. Microb Drug Resist. 1995;1(2):111–4. doi:10.1089/mdr.1995.1.111.

    Article  CAS  PubMed  Google Scholar 

  108. Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev. 2009;22(4):582–610. doi:10.1128/CMR.00040-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Hu RM, Huang KJ, Wu LT, Hsiao YJ, Yang TC. Induction of L1 and L2 β-lactamases of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2008;52(3):1198–200. doi:10.1128/AAC.00682-07.

    Article  CAS  PubMed  Google Scholar 

  110. Avison MB, Higgins CS, Ford PJ, von Heldreich CJ, Walsh TR, Bennett PM. Differential regulation of L1 and L2 β-lactamase expression in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2002;49(2):387–9. doi:10.1093/jac/49.2.387.

    Article  CAS  PubMed  Google Scholar 

  111. Okazaki A, Avison MB. Induction of L1 and L2 β-lactamase production in Stenotrophomonas maltophiliais dependent on an AmpR-type regulator. Antimicrob Agents Chemother. 2008;52(4):1525–8. doi:10.1128/AAC.01485-07.

  112. Yang TC, Huang YW, Hu RM, Huang SC, Lin YT. AmpDI is involved in expression of the chromosomal L1 and L2 β-lactamases of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2009;53(7):2902–7. doi:10.1128/AAC.01513-08.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Huang YW, Lin CW, Hu RM, Lin YT, Chung TC, Yang TC. AmpN-AmpG operon is essential for expression of L1 and L2 β-lactamases in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2010;54(6):2583–9. doi:10.1128/AAC.01283-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lin CW, Lin HC, Huang YW, Chung TC, Yang TC. Inactivation of mrcA gene derepresses the basal-level expression of L1 and L2 β-lactamases in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2011;66(9):2033–7. doi:10.1093/jac/dkr276.

    Article  CAS  PubMed  Google Scholar 

  115. Huang YW, Hu RM, Lin CW, Chung TC, Yang TC. NagZ-dependent and NagZ-independent mechanisms for β-lactamase expression in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2012;56(4):1936–41. doi:10.1128/AAC.05645-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Talfan A, Mounsey O, Charman M, Townsend E, Avison MB. Involvement of mutation in ampD I, mrcA, and at least one additional gene in β-lactamase hyperproduction in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2013;57(11):5486–91. doi:10.1128/AAC.01446-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Cullmann W, Dick W. Heterogeneity of β-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen. Chemotherapy. 1990;36(2):117–26. doi:10.1159/000238757.

  118. Avison MB, von Heldreich CJ, Higgins CS, Bennett PM, Walsh TR. A TEM-2 β-lactamase encoded on an active Tn 1-like transposon in the genome of a clinical isolate of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2000;46(6):879–84. doi:10.1093/jac/46.6.879.

  119. al Naiemi N, Duim B, Bart A. A CTX-M extended-spectrum β-lactamase in Pseudomonas aeruginosa and Stenotrophomonas maltophilia. J Med Microbiol. 2006;55(Pt 11):1607–8. doi:10.1099/jmm.0.46704-0.

  120. Maravic A, Skocibusic M, Fredotovic Z, Cvjetan S, Samanic I, Puizina J. Characterization of environmental CTX-M-15-producing Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2014;58(10):6333–4. doi:10.1128/AAC.03601-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Liu W, Zou D, Wang X, Li X, Zhu L, Yin Z, Yang Z, Wei X, Han L, Wang Y, Shao C, Wang S, He X, Liu D, Liu F, Wang J, Huang L, Yuan J. Proteomic analysis of clinical isolate of Stenotrophomonas maltophilia with blaNDM-1, blaL1 and blaL2 β-lactamase genes under imipenem treatment. J Proteome Res. 2012;11(8):4024–33. doi:10.1021/pr300062v.

    Article  CAS  PubMed  Google Scholar 

  122. King BA, Shannon KP, Phillips I. Aminoglycoside 6'-N acetyltransferase production by an isolate of Pseudomonas maltophilia. J Antimicrob Chemother. 1978;4(5):467–8. doi:10.1093/jac/4.5.467-a.

    Article  CAS  PubMed  Google Scholar 

  123. Shaw KJ, Rather PN, Hare RS, Miller GH. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev. 1993;57(1):138–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005;49(2):479–87. doi:10.1128/AAC.49.2.479-487.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Lambert T, Ploy MC, Denis F, Courvalin P. Characterization of the chromosomal aac(6')-Iz gene of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1999;43(10):2366–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Tada T, Miyoshi-Akiyama T, Dahal RK, Mishra SK, Shimada K, Ohara H, Kirikae T, Pokhrel BM. Identification of a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iak, from a multidrug-resistant clinical isolate of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2014;58(10):6324–7. doi:10.1128/AAC.03354-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Okazaki A, Avison MB. Aph(3')-IIc, an aminoglycoside resistance determinant from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2007;51(1):359–60. doi:10.1128/AAC.00795-06.

    Article  CAS  PubMed  Google Scholar 

  128. Vanhoof R, Sonck P, Hannecart-Pokorni E. The role of lipopolysaccharide anionic binding sites in aminoglycoside uptake in Stenotrophomonas (Xanthomonas) maltophilia. J Antimicrob Chemother. 1995;35(1):167–71. doi:10.1093/jac/35.1.167.

    Article  CAS  PubMed  Google Scholar 

  129. Wilcox MH, Winstanley TG, Spencer RC. Outer membrane protein profiles of Xanthomonas maltophilia isolates displaying temperature-dependent susceptibility to gentamicin. J Antimicrob Chemother. 1994;33(3):663–6. doi:10.1093/jac/33.3.663.

    Article  CAS  PubMed  Google Scholar 

  130. Rahmati-Bahram A, Magee JT, Jackson SK. Growth temperature-dependent variation of cell envelope lipids and antibiotic susceptibility in Stenotrophomonas (Xanthomonas) maltophilia. J Antimicrob Chemother. 1995;36(2):317–26. doi:10.1093/jac/36.2.317.

    Article  CAS  PubMed  Google Scholar 

  131. Rahmati-Bahram A, Magee JT, Jackson SK. Temperature-dependent aminoglycoside resistance in Stenotrophomonas (Xanthomonas) maltophilia; alterations in protein and lipopolysaccharide with growth temperature. J Antimicrob Chemother. 1996;37(4):665–76. doi:10.1093/jac/37.4.665.

    Article  CAS  PubMed  Google Scholar 

  132. Mooney L, Kerr KG, Denton M. Survival of Stenotrophomonas maltophilia following exposure to concentrations of tobramycin used in aerosolized therapy for cystic fibrosis patients. Int J Antimicrob Agents. 2001;17(1):63–6. doi:10.1016/S0924-8579(00)00307-1.

    Article  CAS  PubMed  Google Scholar 

  133. McKay GA, Woods DE, MacDonald KL, Poole K. Role of phosphoglucomutase of Stenotrophomonas maltophilia in lipopolysaccharide biosynthesis, virulence, and antibiotic resistance. Infect Immun. 2003;71(6):3068–75. doi:10.1128/IAI.71.6.3068-3075.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Gould VC, Okazaki A, Avison MB. Coordinate hyperproduction of SmeZ and SmeJK efflux pumps extends drug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2013;57(1):655–7. doi:10.1128/AAC.01020-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Lin YT, Huang YW, Liou RS, Chang YC, Yang TC. MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. J Antimicrob Chemother. 2014;69(12):3221–6. doi:10.1093/jac/dku317.

    Article  CAS  PubMed  Google Scholar 

  136. Lin CW, Huang YW, Hu RM, Yang TC. SmeOP-TolCsm efflux pump contributes to the multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2014;58(4):2405–8. doi:10.1128/AAC.01974-13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Lin YT, Huang YW, Chen SJ, Chang CW, Yang TC. The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice. Antimicrob Agents Chemother. 2015;59(7):4067–73. doi:10.1128/AAC.00372-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Valdezate S, Vindel A, Echeita A, Baquero F, Canto R. Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility. Antimicrob Agents Chemother. 2002;46(3):665–71. doi:10.1128/AAC.46.3.665-671.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Ribera A, Domenech-Sánchez A, Ruiz J, Benedi VJ, Jimenez de Anta MT, Vila J. Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in epidemiological unrelated Stenotrophomonas maltophilia clinical isolates. Microb Drug Resist. 2002;8(4):245–51. doi:10.1089/10766290260469499.

    Article  CAS  PubMed  Google Scholar 

  140. Valdezate S, Vindel A, Saez-Nieto JA, Baquero F, Canton R. Preservation of topoisomerase genetic sequences during in vivo and in vitro development of high-level resistance to ciprofloxacin in isogenic Stenotrophomonas maltophilia strains. J Antimicrob Chemother. 2005;56(1):220–3. doi:10.1093/jac/dki182.

  141. Chen CH, Huang CC, Chung TC, Hu RM, Huang YW, Yang TC. Contribution of resistance-nodulation-division efflux pump operon smeU1-V-W-U2-X to multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2011;55(12):5826–33. doi:10.1128/AAC.00317-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Garcia-Leon G, Ruiz de Alegria Puig C, Garcia de la Fuente C, Martínez-Martínez L, Martínez JL, Sánchez MB. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates. Clin Microbiol Infect. 2015;21(5):464–7. doi:10.1016/j.cmi.2015.01.007.

    Article  CAS  PubMed  Google Scholar 

  143. Garcia-Leon G, Salgado F, Oliveros JC, Sánchez MB, Martínez JL. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia. Environ Microbiol. 2014;16(5):1282–96. doi:10.1111/1462-2920.12408.

    Article  CAS  PubMed  Google Scholar 

  144. Shimizu K, Kikuchi K, Sasaki T, Takahashi N, Ohtsuka M, Ono Y, Hiramatsu K. Smqnr, a new chromosome-carried quinolone resistance gene in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2008;52(10):3823–5. doi:10.1128/AAC.00026-08.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Sánchez MB, Martínez JL. SmQnr contributes to intrinsic resistance to quinolones in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2010;54(1):580–1. doi:10.1128/AAC.00496-09.

    Article  PubMed  CAS  Google Scholar 

  146. Gordon NC, Wareham DW. Novel variants of the Smqnr family of quinolone resistance genes in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2010;65(3):483–9. doi:10.1093/jac/dkp476.

    Article  CAS  PubMed  Google Scholar 

  147. Wareham DW, Gordon NC, Shimizu K. Two new variants of and creation of a repository for Stenotrophomonas maltophilia quinolone protection protein (Smqnr) genes. Int J Antimicrob Agents. 2011;37(1):89–90. doi:10.1016/j.ijantimicag.2010.10.002.

    Article  CAS  PubMed  Google Scholar 

  148. Kanamori H, Yano H, Tanouchi A, Kakuta R, Endo S, Ichimura S, Ogawa M, Shimojima M, Inomata S, Ozawa D, Aoyagi T, Weber DJ, Kaku M. Prevalence of Smqnr and plasmid-mediated quinolone resistance determinants in clinical isolates of Stenotrophomonas maltophilia from Japan: novel variants of Smqnr. New Microbes New Infect. 2015;7:8–14. doi:10.1016/j.nmni.2015.04.009.

  149. Sánchez MB, Martínez JL. Differential epigenetic compatibility of qnr antibiotic resistance determinants with the chromosome of Escherichia coli. PLoS One. 2012;7(5): e35149. doi:10.1371/journal.pone.0035149.

  150. Gracia-Paez JI, Ferraz JR, Silva IA, Rossi F, Levin AS, Costa SF. Smqnr variants in clinical isolates of Stenotrophomonas maltophilia in Brazil. Rev Inst Med Trop Sao Paulo. 2013;55(6):417–20. doi:10.1590/S0036-46652013000600008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Chang YC, Tsai MJ, Huang YW, Chung TC, Yang TC. SmQnrR, a DeoR-type transcriptional regulator, negatively regulates the expression of Smqnr and SmtcrA in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2011;66(5):1024–8. doi:10.1093/jac/dkr049.

    Article  CAS  PubMed  Google Scholar 

  152. Retsema J, Girard A, Schelkly W, Manousos M, Anderson M, Bright G, Borovoy R, Brennan L, Mason R. Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against Gram-negative organisms. Antimicrob Agents Chemother. 1987;31(12):1939–47. doi:10.1128/AAC.31.12.1939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Li X-Z, Plésiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev. 2015;28(2):337–418. doi:10.1128/CMR.00117-14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67(4):593–656. doi:10.1128/MMBR.67.4.593-656.2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Vaara M. Agents that increase the permeability of the outer membrane. Microbiol Rev. 1992;56(3):395–411.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Fernandez L, Breidenstein EB, Hancock RE. Creeping baselines and adaptive resistance to antibiotics. Drug Resist Updat. 2011;14(1):1–21. doi:10.1016/j.drup.2011.01.001.

    Article  CAS  PubMed  Google Scholar 

  157. Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol. 2014;5:643. doi:10.3389/fmicb.2014.00643.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Fernandez L, Hancock RE. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012;25(4):661–81. doi:10.1128/CMR.00043-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Moffatt JH, Harper M, Harrison P, Hale JD, Vinogradov E, Seemann T, Henry R, Crane B, St Michael F, Cox AD, Adler B, Nation RL, Li J, Boyce JD. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother. 2010;54(12):4971–7. doi:10.1128/AAC.00834-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65(2):232–60. doi:10.1128/MMBR.65.2.232-260.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Petersen PJ, Jacobus NV, Weiss WJ, Sum PE, Testa RT. In vitroand in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob Agents Chemother. 1999;43(4):738–44.

    Google Scholar 

  162. Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis. 2001;32(11):1608–14. doi:10.1086/320532.

    Article  CAS  PubMed  Google Scholar 

  163. Barbolla R, Catalano M, Orman BE, Famiglietti A, Vay C, Smayevsky J, Centron D, Pineiro SA. Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia isolates. Antimicrob Agents Chemother. 2004;48(2):666–9. doi:10.1128/AAC.48.2.666-669.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Hu LF, Chang X, Ye Y, Wang ZX, Shao YB, Shi W, Li X, Li JB. Stenotrophomonas maltophilia resistance to trimethoprim/sulfamethoxazole mediated by acquisition of sul and dfrA genes in a plasmid-mediated class 1 integron. Int J Antimicrob Agents. 2011;37(3):230–4. doi:10.1016/j.ijantimicag.2010.10.025.

    Article  CAS  PubMed  Google Scholar 

  165. Navarro-Martínez MD, Navarro-Peran E, Cabezas-Herrera J, Ruiz-Gomez J, Garcia-Canovas F, Rodriguez-Lopez JN. Antifolate activity of epigallocatechin gallate against Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2005;49(7):2914–20. doi:10.1128/AAC.49.7.2914-2920.2005.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Sánchez MB, Martínez JL. The efflux pump SmeDEF contributes to trimethoprim-sulfamethoxazole resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2015;59(7):4347–8. doi:10.1128/AAC.00714-15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Köhler T, Kok M, Michea-Hamzehpour M, Plésiat P, Gotoh N, Nishino T, Curty LK, Pechere JC. Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1996;40(10):2288–90.

    PubMed  PubMed Central  Google Scholar 

  168. Munoz JL, Garcia MI, Munoz S, Leal S, Fajardo M, Garcia-Rodriguez JA. Activity of trimethoprim/sulfamethoxazole plus polymyxin B against multiresistant Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis. 1996;15(11):879–82.doi:10.1007/BF01691222.

  169. Qamruddin AO, Alkawash MA, Soothill JS. Antibiotic susceptibility of Stenotrophomonas maltophilia in the presence of lactoferrin. Antimicrob Agents Chemother. 2005;49(10):4425–6. doi:10.1128/AAC.49.10.4425-4426.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Maisetta G, Mangoni ML, Esin S, Pichierri G, Capria AL, Brancatisano FL, Di Luca M, Barnini S, Barra D, Campa M, Batoni G. In vitro bactericidal activity of the N-terminal fragment of the frog peptide esculentin-1b (Esc 1-18) in combination with conventional antibiotics against Stenotrophomonas maltophilia. Peptides. 2009;30(9):1622–6. doi:10.1016/j.peptides.2009.06.004.

  171. Lecso-Bornet M, Pierre J, Sarkis-Karam D, Lubera S, Bergogne-Berezin E. Susceptibility of Xanthomonas maltophilia to six quinolones and study of outer membrane proteins in resistant mutants selected in vitro. Antimicrob Agents Chemother. 1992;36(3):669–71. doi:10.1128/AAC.36.3.669.

  172. Sánchez P, Moreno E, Martínez JL. The biocide triclosan selects Stenotrophomonas maltophilia mutants that overproduce the SmeDEF multidrug efflux pump. Antimicrob Agents Chemother. 2005;49(2):781–2. doi:10.1128/AAC.49.2.781-782.2005.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. García-León G, Sánchez MB, Martínez JL. The inactivation of intrinsic antibiotic resistance determinants widens the mutant selection window for quinolones in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2012;56(12):6397–9. doi:10.1128/AAC.01558-12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Cho HH, Sung JY, Kwon KC, Koo SH. Expression of Sme efflux pumps and multilocus sequence typing in clinical isolates of Stenotrophomonas maltophilia. Ann Lab Med. 2012;32(1):38–43. doi:10.3343/alm.2012.32.1.38.

    Article  CAS  PubMed  Google Scholar 

  175. Alonso A, Martínez JL. Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2001;45(6):1879–81. doi:10.1128/AAC.45.6.1879-1881.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Gould VC, Avison MB. SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships. J Antimicrob Chemother. 2006;57(6):1070–6. doi:10.1093/jac/dkl106.

    Article  CAS  PubMed  Google Scholar 

  177. Sánchez P, Le U, Martínez JL. The efflux pump inhibitor Phe-Arg-β-naphthylamide does not abolish the activity of the Stenotrophomonas maltophilia SmeDEF multidrug efflux pump. J Antimicrob Chemother. 2003;51(4):1042–5. doi:10.1093/jac/dkg181.

    Article  PubMed  CAS  Google Scholar 

  178. Hu RM, Liao ST, Huang CC, Huang YW, Yang TC. An inducible fusaric acid tripartite efflux pump contributes to the fusaric acid resistance in Stenotrophomonas maltophilia. PLoS One. 2012;7(12): e51053. doi:10.1371/journal.pone.0051053.

  179. Al-Hamad A, Upton M, Burnie J. Molecular cloning and characterization of SmrA, a novel ABC multidrug efflux pump from Stenotrophomonas maltophilia. J Antimicrob Chemother. 2009;64(4):731–4. doi:10.1093/jac/dkp271.

    Article  CAS  PubMed  Google Scholar 

  180. Huang YW, Hu RM, Chu FY, Lin HR, Yang TC. Characterization of a major facilitator superfamily (MFS) tripartite efflux pump EmrCABsm from Stenotrophomonas maltophilia. J Antimicrob Chemother. 2013;68(11):2498–505. doi:10.1093/jac/dkt250.

    Article  CAS  PubMed  Google Scholar 

  181. Srijaruskul K, Charoenlap N, Namchaiw P, Chattrakarn S, Giengkam S, Mongkolsuk S, Vattanaviboon P. Regulation by SoxR of mfsA, which encodes a major facilitator protein involved in paraquat resistance in Stenotrophomonas maltophilia. PLoS One. 2015;10(4):e0123699. doi:10.1371/journal.pone.0123699.

  182. García-León G, Hernández A, Hernando-Amado S, Alavi P, Berg G, Martínez JL. A function of the major quinolone resistance determinant of Stenotrophomonas maltophilia SmeDEF is the colonization of the roots of the plants. Appl Environ Microbiol. 2014;80(15):4559–65. doi:10.1128/AEM.01058-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Alonso A, Morales G, Escalante R, Campanario E, Sastre L, Martínez JL. Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology. J Antimicrob Chemother. 2004;53(3):432–4. doi:10.1093/jac/dkh074.

    Article  CAS  PubMed  Google Scholar 

  184. Huang YW, Liou RS, Lin YT, Huang HH, Yang TC. A linkage between SmeIJK efflux pump, cell envelope integrity, and σE-mediated envelope stress response in Stenotrophomonas maltophilia. PLoS ONE. 2014;9(11):e111784. doi:10.1371/journal.pone.0111784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  185. Cuthbertson L, Nodwell JR. The TetR family of regulators. Microbiol Mol Biol Rev. 2013;77(3):440–75. doi:10.1128/MMBR.00018-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Sánchez P, Alonso A, Martínez JL. Cloning and characterization of SmeT, a repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. Antimicrob Agents Chemother. 2002;46(11):3386–93. doi:10.1128/AAC.46.11.3386-3393.2002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Hernández A, Mate MJ, Sánchez-Diaz PC, Romero A, Rojo F, Martínez JL. Structural and functional analysis of SmeT, the repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. J Biol Chem. 2009;284(21):14428–38. doi:10.1074/jbc.M809221200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Huang HI, Shih HY, Lee CM, Yang TC, Lay JJ, Lin YE. In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii: implications for on-site disinfection for hospital infection control. Water Res. 2008;42(1–2):73–80. doi:10.1016/j.watres.2007.07.003.

  189. Morones-Ramirez JR, Winkler JA, Spina CS, Collins JJ. Silver enhances antibiotic activity against Gram-negative bacteria. Sci Transl Mede. 2013;5(190):190ra181. doi: 10.1126/scitranslmed.3006276.

  190. Alonso A, Sánchez P, Martínez JL. Stenotrophomonas maltophilia D457R contains a cluster of genes from Gram-positive bacteria involved in antibiotic and heavy metal resistance. Antimicrob Agents Chemother. 2000;44(7):1778–82. doi:10.1128/AAC.44.7.1778-1782.2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Pages D, Rose J, Conrod S, Cuine S, Carrier P, Heulin T, Achouak W. Heavy metal tolerance in Stenotrophomonas maltophilia. PLoS ONE. 2008;3(2): e1539. doi:10.1371/journal.pone.0001539.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Li X-Z, Nikaido H, Williams KE. Silver-resistant mutants of Escherichia coli display active efflux of Ag+ and are deficient in porins. J Bacteriol. 1997;179(19):6127–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Livermore DM, Mushtaq S, Warner M, Woodford N. Comparative in vitro activity of sulfametrole/trimethoprim and sulfamethoxazole/trimethoprim and other agents against multiresistant Gram-negative bacteria. J Antimicrob Chemother. 2014;69(4):1050–6. doi:10.1093/jac/dkt455.

  194. Nicodemo AC, Paez JI. Antimicrobial therapy for Stenotrophomonas maltophilia infections. Eur J Clin Microbiol Infect Dis. 2007;26(4):229–37. doi:10.1007/s10096-007-0279-3.

    Article  CAS  PubMed  Google Scholar 

  195. Abbott IJ, Peleg AY. Stenotrophomonas, Achromobacter, and nonmelioid Burkholderia species: antimicrobial resistance and therapeutic strategies. Semin Respir Crit Care Med. 2015;36(1):99–110. doi:10.1055/s-0034-1396929.

    Article  PubMed  Google Scholar 

  196. Rojas P, Garcia E, Calderon GM, Ferreira F, Rosso M. Successful treatment of Stenotrophomonas maltophilia meningitis in a preterm baby boy: a case report. J Med Case Reps. 2009;3:7389. doi:10.4076/1752-1947-3-7389.

    Article  Google Scholar 

  197. Farrell DJ, Sader HS, Flamm RK, Jones RN. Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012). Int J Antimicrob Agents. 2014;43(6):533–9. doi:10.1016/j.ijantimicag.2014.01.032.

    Article  CAS  PubMed  Google Scholar 

  198. Lakatos B, Jakopp B, Widmer A, Frei R, Pargger H, Elzi L, Battegay M. Evaluation of treatment outcomes for Stenotrophomonas maltophilia bacteraemia. Infection. 2014;42(3):553–8. doi:10.1007/s15010-014-0607-3.

    Article  CAS  PubMed  Google Scholar 

  199. Pompilio A, Catavitello C, Picciani C, Confalone P, Piccolomini R, Savini V, Fiscarelli E, D’Antonio D, Di Bonaventura G. Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm formation of Stenotrophomonas maltophilia from cystic fibrosis. J Med Microbiol. 2010;59(Pt 1):76–81. doi:10.1099/jmm.0.011981-0.

    Article  CAS  PubMed  Google Scholar 

  200. Insa R, Cercenado E, Goyanes MJ, Morente A, Bouza E. In vitro activity of tigecycline against clinical isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia. J Antimicrob Chemother. 2007;59(3):583–5. doi:10.1093/jac/dkl496.

  201. Farrell DJ, Sader HS, Jones RN. Antimicrobial susceptibilities of a worldwide collection of Stenotrophomonas maltophilia isolates tested against tigecycline and agents commonly used for S. maltophilia infections. Antimicrob Agents Chemother. 2010;54(6):2735–7. doi:10.1128/AAC.01774-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Chen YH, Lu PL, Huang CH, Liao CH, Lu CT, Chuang YC, Tsao SM, Chen YS, Liu YC, Chen WY, Jang TN, Lin HC, Chen CM, Shi ZY, Pan SC, Yang JL, Kung HC, Liu CE, Cheng YJ, Liu JW, Sun W, Wang LS, Ko WC, Yu KW, Chiang PC, Lee MH, Lee CM, Hsu GJ, Hsueh PR. Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006–2010. Antimicrob Agents Chemother. 2012;56(3):1452–7. doi:10.1128/AAC.06053-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Jacquier H, Le Monnier A, Carbonnelle E, Corvec S, Illiaquer M, Bille E, Zahar JR, Jaureguy F, Fihman V, Tankovic J, Cattoir V, Gmc Study Group. In vitro antimicrobial activity of “last-resort” antibiotics against unusual nonfermenting Gram-negative bacilli clinical isolates. Microb Drug Resist. 2012;18(4):396–401. doi:10.1089/mdr.2011.0195.

  204. Tekce YT, Erbay A, Cabadak H, Sen S. Tigecycline as a therapeutic option in Stenotrophomonas maltophilia infections. J Chemother. 2012;24(3):150–4. doi:10.1179/1120009X12Z.00000000022.

    Article  CAS  PubMed  Google Scholar 

  205. Wu Y, Shao Z. High-dosage tigecycline for Stenotrophomonas maltophilia bacteremia. Chin Med J. 2014;127(17):3199. doi:10.3760/cma.j.issn.0366-6999.20140364.

    PubMed  Google Scholar 

  206. Falagas ME, Valkimadi PE, Huang YT, Matthaiou DK, Hsueh PR. Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review. J Antimicrob Chemother. 2008;62(5):889–94. doi:10.1093/jac/dkn301.

    Article  CAS  PubMed  Google Scholar 

  207. Milne KE, Gould IM. Combination antimicrobial susceptibility testing of multidrug-resistant Stenotrophomonas maltophilia from cystic fibrosis patients. Antimicrob Agents Chemother. 2012;56(8):4071–7. doi:10.1128/AAC.00072-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Savini V, Catavitello C, D’Aloisio M, Balbinot A, Astolfi D, Masciarelli G, Pompilio A, Di Bonaventura G, D’Antonio D. Chloramphenicol and rifampin may be the only options against Stenotrophomonas maltophilia. A tale of a colonized bladder device in a patient with myelofibrosis. Infez Med. 2010;18(3):193–7.

    PubMed  Google Scholar 

  209. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin Infect Dis. 2005;40(9):1333–41. doi:10.1086/429323.

    Article  CAS  PubMed  Google Scholar 

  210. Tan TY, Ng SY. The in-vitro activity of colistin in Gram-negative bacteria. Singapore Med J. 2006;47(7):621–4.

    Google Scholar 

  211. Leung C, Drew P, Azzopardi EA. Extended multidrug-resistant Stenotrophomonas maltophilia septicemia in a severely burnt patient. J Burn Care Res. 2010;31(6):966. doi:10.1097/BCR.0b013e3181f93b46.

    Article  PubMed  Google Scholar 

  212. Betts JW, Phee LM, Woodford N, Wareham DW. Activity of colistin in combination with tigecycline or rifampicin against multidrug-resistant Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis. 2014;33(9):1565–72. doi:10.1007/s10096-014-2101-3.

    Article  CAS  PubMed  Google Scholar 

  213. Pintado V, San Miguel LG, Grill F, Mejia B, Cobo J, Fortun J, Martin-Davila P, Moreno S. Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant Gram-negative bacteria. J Infect. 2008;56(3):185–90. doi:10.1016/j.jinf.2008.01.003.

    Article  PubMed  Google Scholar 

  214. Falagas ME, Rafailidis PI, Ioannidou E, Alexiou VG, Matthaiou DK, Karageorgopoulos DE, Kapaskelis A, Nikita D, Michalopoulos A. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents. 2010;35(2):194–9. doi:10.1016/j.ijantimicag.2009.10.005.

    Article  CAS  PubMed  Google Scholar 

  215. Samonis G, Karageorgopoulos DE, Maraki S, Levis P, Dimopoulou D, Spernovasilis NA, Kofteridis DP, Falagas ME. Stenotrophomonas maltophilia infections in a general hospital: patient characteristics, antimicrobial susceptibility, and treatment outcome. PLoS ONE. 2012;7(5), e37375. doi:10.1371/journal.pone.0037375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Wood GC, Underwood EL, Croce MA, Swanson JM, Fabian TC. Treatment of recurrent Stenotrophomonas maltophilia ventilator-associated pneumonia with doxycycline and aerosolized colistin. Ann Pharmacother. 2010;44(10):1665–8. doi:10.1345/aph.1P217.

    Article  PubMed  Google Scholar 

  217. Johnson DM, Jones RN, Pfaller MA. Antimicrobial interactions of trovafloxacin and extended-spectrum cephalosporins or azithromycin tested against clinical isolates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. J Antimicrob Chemother. 1998;42(4):557–9. doi:10.1093/jac/42.4.557.

    Article  CAS  PubMed  Google Scholar 

  218. Saiman L, Chen Y, Gabriel PS, Knirsch C. Synergistic activities of macrolide antibiotics against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans isolated from patients with cystic fibrosis. Antimicrob Agents Chemother. 2002;46(4):1105–7. doi:10.1128/AAC.46.4.1105-1107.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Hornsey M, Longshaw C, Phee L, Wareham DW. In vitro activity of telavancin in combination with colistin versus Gram-negative bacterial pathogens. Antimicrob Agents Chemother. 2012;56(6):3080–5. doi:10.1128/AAC.05870-11.

  220. Page MG, Dantier C, Desarbre E, Gaucher B, Gebhardt K, Schmitt-Hoffmann A. In vitro and in vivoproperties of BAL30376, a β-lactam and dual β-lactamase inhibitor combination with enhanced activity against Gram-negative bacilli that express multiple β-lactamases. Antimicrob Agents Chemother. 2011;55(4):1510–9. doi:10.1128/AAC.01370-10.

  221. Leclercq R, Canton R, Brown DF, Giske CG, Heisig P, MacGowan AP, Mouton JW, Nordmann P, Rodloff AC, Rossolini GM, Soussy CJ, Steinbakk M, Winstanley TG, Kahlmeter G. EUCAST expert rules in antimicrobial susceptibility testing. Clin Microbiol Infect. 2013;19(2):141–60. doi:10.1111/j.1469-0691.2011.03703.x.

    Article  CAS  PubMed  Google Scholar 

  222. Rizek C, Ferraz JR, van der Heijden IM, Giudice M, Mostachio AK, Paez J, Carrilho C, Levin AS, Costa SF. In vitro activity of potential old and new drugs against multidrug-resistant Gram-negatives. J Infect Chemother. 2015;21(2):114–7. doi:10.1016/j.jiac.2014.10.009.

  223. Devos S, Stremersch S, Raemdonck K, Braeckmans K, Devreese B. Intra- and interspecies effects of outer membrane vesicles from Stenotrophomonas maltophilia on β-lactam resistance. Antimicrob Agents Chemother. 2016;60(4):2516–8. doi:10.1128/AAC.02171-15.

  224. Sánchez MB, Martínez JL. Regulation of Smqnrexpression by SmQnrR is strain-specific in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2015;70(10):2913–4. doi:10.1093/jac/dkv196.

  225. Wu CJ, Huang YW, Lin YT, Ning HC, Yang TC. Inactivation of SmeSyRy two-component regulatory system inversely regulates the expression of SmeYZ and SmeDEF efflux pumps in Stenotrophomonas maltophilia. PLoS One. 2016;11(8): e0160943. doi:10.1371/journal.pone.0160943.

  226. Liu MC, Tsai YL, Huang YW, Chen HY, Hsueh PR, Lai SY, Chen LC, Chou YH, Lin WY, Liaw SJ. Stenotrophomonas maltophiliaPhoP, a two-component response regulator, involved in antimicrobial susceptibilities. PLoS One. 2016;11(5): e0153753. doi:10.1371/journal.pone.0153753.

  227. Dulyayangkul P, Charoenlap N, Srijaruskul K, Mongkolsuk S, Vattanaviboon P. Major facilitator superfamily MfsA contributes to multidrug resistance in emerging nosocomial pathogen Stenotrophomonas maltophilia. J Antimicrob Chemother. 2016;71(10): 2990–1. doi:10.1093/jac/dkw233.

  228. Hu LF, Chen GS, Kong QX, Gao LP, Chen X, Ye Y, Li JB. Increase in the prevalence of resistance determinants to trimethoprim/sulfamethoxazole in clinical Stenotrophomonas maltophilia isolates in China. PLoS One. 2016;11(6):e0157693. doi:10.1371/journal.pone.0157693.

  229. Zhao J, Xing Y, Liu W, Ni W, Wei C, Wang R, Liu Y, Liu Y. Surveillance of dihydropteroate synthase genes in Stenotrophomonas maltophilia by LAMP: implications for infection control and initial therapy. Front Microbiol. 2016;7:1723. doi:10.3389/fmicb.2016.01723.

  230. Mojica MF, Ouellette CP, Leber A, Becknell MB, Ardura MI, Perez F, Shimamura M, Bonomo RA, Aitken SL, Shelburne SA. Successful treatment of bloodstream infection due to metallo-β-lactamase-producing Stenotrophomonas maltophiliain a renal transplant patient. Antimicrob Agents Chemother. 2016;60(9): 5130–4. doi:10.1128/AAC.00264-16.

Download references

Acknowledgments

The views in this chapter do not necessarily reflect those of Xian-Zhi Li’s affiliation, Health Canada.

Author information

Authors and Affiliations

  1. Human Safety Division, Veterinary Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada

    Xian-Zhi Li M.D., Ph.D.

  2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Jennifer Li B.Sc.(Hons)

Authors
  1. Xian-Zhi Li M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Li B.Sc.(Hons)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xian-Zhi Li M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Treiber Therapeutics, Cambridge, Massachusetts, USA

    Douglas L. Mayers

  2. Wayne State University School of Medicine, Detroit Medical Center, Detroit, Michigan, USA

    Jack D. Sobel

  3. Canada Research Chair in Antimicrobial Resistance, Centre de recherche en Infectiologie, University of Laval, Quebec City, Canada

    Marc Ouellette

  4. Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Keith S. Kaye

  5. Infection Control and Prevention Unit of Infectious Diseases, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Dror Marchaim

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Li, XZ., Li, J. (2017). Antimicrobial Resistance in Stenotrophomonas maltophilia: Mechanisms and Clinical Implications. In: Mayers, D., Sobel, J., Ouellette, M., Kaye, K., Marchaim, D. (eds) Antimicrobial Drug Resistance. Springer, Cham. https://doi.org/10.1007/978-3-319-47266-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation