Chapter 10 : Global Spread of Multidrug-Resistant Gram-Negative Bacilli

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Global Spread of Multidrug-Resistant Gram-Negative Bacilli, Page 1 of 2

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This chapter describes three emerging issues with multiply resistant gram-negative bacilli, each of which has worldwide importance. First, community-onset infections with CTX-M-15-producing threaten to permanently alter empiric antibiotic choices for urinary tract infection (UTI). Second, producing the carbapenemase (KPC) are now spreading from their epicenter in New York City to multiple parts of the globe and are complicating management of infections in hospitals and nursing homes. Finally, global dissemination of carbapenem-resistant underscores the epidemic potential of successful bacterial lineages. The antibiotic resistance phenotype of the ST131-positive is that the organisms are typically resistant to ceftriaxone, cefotaxime, fluoroquinolones, trimethoprim, trimethoprim-sulfamethoxazole, penicillin/beta-lactamase inhibitor combinations, and tetracyclines. Resistance to aminoglycosides is variable. The clone confers multidrug resistance by the presence of multiple antibiotic resistance genes. As can be expected by the resistance profile of ST131 , treatment options are limited. The isolates are often susceptible to nitrofurantoin, pivmecillinam, and fosfomycin. Interspecies spread of the KPC gene has been documented in a single patient with , , and . The most important mechanism of antibiotic resistance in is production of beta-lactamases. and isolates with resistance to polymyxins and sometimes all antibiotic options have now been detected. If these strains were to spread widely, it is likely that significant mortality would be observed.

Citation: Paterson D, Sidjabat H, Doi Y. 2010. Global Spread of Multidrug-Resistant Gram-Negative Bacilli, p 213-222. In Scheld W, Grayson M, Hughes J (ed), Emerging Infections 9. ASM Press, Washington, DC. doi: 10.1128/9781555816803.ch10

Key Concept Ranking

Outer Membrane Proteins
beta-Lactam Antibiotics
beta-Lactamase Inhibitors
Urinary Tract Infections
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1. Adams-Haduch, J. M.,, B. A. Potoski,, H. E. Sidjabat,, D. L. Paterson, and, Y. Doi. 2009. Activity of temocillin against KPC-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob. Agents Chemother. 53:27002701.
2. Biancofiore, G.,, C. Tascini,, M. Bisa,, G. Gemignani,, M. L. Bindi,, A. Leonildi,, G. Giannotti, and, F. Menichetti. 2007. Colistin, meropenem and rifampin in a combination therapy for multi-drug-resistant Acinetobacter baumannii multifocal infection. A case report. Minerva Anestesiol. 73:181185.
3. Blanco, M.,, M. P. Alonso,, M. H. Nicolas-Chanoine,, G. Dahbi,, A. Mora,, J. E. Blanco,, C. Lopez,, P. Cortes,, M. Llagostera,, V. Leflon-Guibout,, B. Puentes,, R. Mamani,, A. Herrera,, M. A. Coira,, F. Garcia-Garrote,, J. M. Pita, and, J. Blanco. 2009. Molecular epidemiology of Escherichia coli producing extended-spectrum beta-lactamases in Lugo (Spain): dissemination of clone O25b:H4-ST131 producing CTX-M-15. J. Antimicrob. Chemother. 63:11351141.
4. Bogaerts, P.,, T. Naas,, I. Wybo,, C. Bauraing,, O. Soetens,, D. Pierard,, P. Nordmann, and, Y. Glupczynski. 2006. Outbreak of infection by carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-58 in Belgium. J. Clin. Microbiol. 44:41894192.
5. Boucher, H. W.,, G. H. Talbot,, J. S. Bradley,, J. E. Edwards,, D. Gilbert,, L. B. Rice,, M. Scheld,, B. Spellberg, and, J. Bartlett. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:112.
6. Bratu, S.,, D. Landman,, R. Haag,, R. Recco,, A. Eramo,, M. Alam, and, J. Quale. 2005. Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: a new threat to our antibiotic armamentarium. Arch. Intern. Med. 165:14301435.
7. Chua, A. P.,, and K. H. Lee. 2006. Fatal bacteraemic pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus. Singapore Med. J. 47:546548.
8. Clermont, O.,, H. Dhanji,, M. Upton,, T. Gibreel,, A. Fox,, D. Boyd,, M. R. Mulvey,, P. Nordmann,, E. Ruppe,, J. L. Sarthou,, T. Frank,, S. Vimont,, G. Arlet,, C. Branger,, N. Woodford, and, E. Denamur. 2009. Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains. J. Antimicrob. Chemother. 64:274277.
9. Coque, T. M.,, A. Novais,, A. Carattoli,, L. Poirel,, J. Pitout,, L. Peixe,, F. Baquero,, R. Canton, and, P. Nordmann. 2008. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta-lactamase CTX-M-15. Emerg. Infect. Dis. 14:195200.
10. Doi, Y.,, J. M. Adams,, K. Yamane, and, D. L. Paterson. 2007. Identification of 16S rRNA methylase-producing Acinetobacter baumannii clinical strains in North America. Antimicrob. Agents Chemother. 51:42094210.
11. Doi, Y.,, and Y. Arakawa. 2007. 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin. Infect. Dis. 45:8894.
12. Doi, Y.,, S. Husain,, B. A. Potoski,, K. R. McCurry, and, D. L. Paterson. 2009. Extensively drug-resistant Acinetobacter baumannii. Emerg. Infect. Dis. 15:980982.
13. Doi, Y.,, B. A. Potoski,, J. M. Adams-Haduch,, H. E. Sidjabat,, A. W. Pasculle, and, D. L. Paterson. 2008. Simple disk-based method for detection of Klebsiella pneumoniae carbapenemase-type beta-lactamase by use of a boronic acid compound. J. Clin. Microbiol. 46:40834086.
14. Dortet, L.,, I. Radu,, V. Gautier,, F. Blot,, E. Chachaty, and, G. Arlet. 2008. Intercontinental travels of patients and dissemination of plasmid-mediated carbapenemase KPC-3 associated with OXA-9 and TEM-1. J. Antimicrob. Chemother. 61:455457.
15. Ender, P. T.,, D. Gajanana,, B. Johnston,, C. Clabots,, F. J. Tamarkin, and, J. R. Johnson. 2009. Transmission of an extended-spectrum-beta-lactamase-producing Escherichia coli (sequence type ST131) strain between a father and daughter resulting in septic shock and emphysematous pyelonephritis. J. Clin. Microbiol. 47:37803782.
16. Endimiani, A.,, J. M. Depasquale,, S. Forero,, F. Perez,, A. M. Hujer,, D. Roberts-Pollack,, P. D. Fiorella,, N. Pickens,, B. Kitchel,, A. E. Casiano-Colon,, F. C. Tenover, and, R. A. Bonomo. 2009. Emergence of blaKPC-containing Klebsiella pneumoniae in a long-term acute care hospital: a new challenge to our healthcare system. J. Antimicrob. Chemother. 64:11021110.
17. Endimiani, A.,, A. M. Hujer,, F. Perez,, C. R. Bethel,, K. M. Hujer,, J. Kroeger,, M. Oethinger,, D. L. Paterson,, M. D. Adams,, M. R. Jacobs,, D. J. Diekema,, G. S. Hall,, S. G. Jenkins,, L. B. Rice,, F. C. Tenover, and, R. A. Bonomo. 2009. Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA. J. Antimicrob. Chemother. 63:427437.
18. Freeman, J. T.,, S. J. McBride,, H. Heffernan,, T. Bathgate,, C. Pope, and, R. B. Ellis-Pegler. 2008. Community-onset genitourinary tract infection due to CTX-M-15-producing Escherichia coli among travelers to the Indian subcontinent in New Zealand. Clin. Infect. Dis. 47:689692.
19. Gaynes, R.,, and J. R. Edwards. 2005. Overview of nosocomial infections caused by gram-negative bacilli. Clin. Infect. Dis. 41:848854.
20. Gilbert, D. N.,, R. C. Moellering, Jr.,, G. M. Eliopoulos,, H. F. Chambers, and, M. S. Saag. 2009. The Sanford Guide to Antimicrobial Therapy 2009. Antimicrobial Therapy, Inc., Sperryville, VA.
21. Hawser, S. P.,, S. K. Bouchillon,, D. J. Hoban,, R. E. Badal,, P. R. Hsueh, and, D. L. Paterson. 2009. Emergence of high levels of extended-spectrum-beta-lactamase-producing gram-negative bacilli in the Asia-Pacific region: data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob. Agents Chemother. 53:32803284.
22. Higgins, P. G.,, C. Dammhayn,, M. Hackel, and, H. Seifert. Global spread of carbapenem-resistant Acinetobacter baumannii. J. Antimicrob. Chemother. 65:233238.
23. Hujer, K. M.,, A. M. Hujer,, E. A. Hulten,, S. Bajaksouzian,, J. M. Adams,, C. J. Donskey,, D. J. Ecker,, C. Massire,, M. W. Eshoo,, R. Sampath,, J. M. Thomson,, P. N. Rather,, D. W. Craft,, J. T. Fishbain,, A. J. Ewell,, M. R. Jacobs,, D. L. Paterson, and, R. A. Bonomo. 2006. Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp. isolates from military and civilian patients treated at the Walter Reed Army Medical Center. Antimicrob. Agents Chemother. 50:41144123.
24. Kim, B. N.,, A. Y. Peleg,, T. P. Lodise,, J. Lipman,, J. Li,, R. Nation, and, D. L. Paterson. 2009. Management of meningitis due to antibiotic-resistant Acinetobacter species. Lancet Infect. Dis. 9:245255.
25. Kitchel, B.,, J. K. Rasheed,, J. B. Patel,, A. Srinivasan,, S. Navon-Venezia,, Y. Carmeli,, A. Brolund, and, C. G. Giske. 2009. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob. Agents Chemother. 53:33653370.
26. Kitchel, B.,, D. R. Sundin, and, J. B. Patel. 2009. Regional dissemination of KPC-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 53:45114513.
27. Lau, S. H.,, J. Cheesborough,, M. E. Kaufmann,, N. Woodford,, A. R. Dodgson,, K. J. Dodgson,, E. J. Bolton,, A. J. Fox, and, M. Upton. 2009. Rapid identification of uropathogenic Escherichia coli of the O25:H4-ST131 clonal lineage using the DiversiLab repetitive sequence-based PCR system. Clin. Microbiol. Infect. 16:232237.
28. Lee, J.,, G. Patel,, S. Huprikar,, D. P. Calfee, and, S. G. Jenkins. 2009. Decreased susceptibility to polymyxin B during treatment for carbapenem-resistant Klebsiella pneumoniae infection. J. Clin. Microbiol. 47:16111612.
29. Li, J.,, R. L. Nation,, J. D. Turnidge,, R. W. Milne,, K. Coulthard,, C. R. Rayner, and, D. L. Paterson. 2006. Colistin: the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect. Dis. 6:589601.
30. Liu, W.,, L. Chen,, H. Li,, H. Duan,, Y. Zhang,, X. Liang,, X. Li,, M. Zou,, L. Xu, and, P. M. Hawkey. 2009. Novel CTX-M beta-lactamase genotype distribution and spread into multiple species of Enterobacteriaceae in Changsha, Southern China. J. Antimicrob. Chemother. 63:895900.
31. Livermore, D. M. 2005. Tigecycline: what is it, and where should it be used? J. Antimicrob. Chemother. 56:611614.
32. Manges, A. R.,, J. R. Johnson,, B. Foxman,, T. T. O’Bryan,, K. E. Fullerton, and, L. W. Riley. 2001. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. N. Engl. J. Med. 345:10071013.
33. Monteiro, J.,, A. F. Santos,, M. D. Asensi,, G. Peirano, and, A. C. Gales. 2009. First report of KPC-2-producing Klebsiella pneumoniae strains in Brazil. Antimicrob. Agents Chemother. 53:333334.
34. Naas, T.,, P. Nordmann, and, A. Heidt. 2007. Intercountry transfer of PER-1 extended-spectrum beta-lactamase-producing Acinetobacter baumannii from Romania. Int. J. Antimicrob. Agents 29:226228.
35. Navon-Venezia, S.,, A. Leavitt,, M. J. Schwaber,, J. K. Rasheed,, A. Srinivasan,, J. B. Patel, and, Y. Carmeli. 2009. First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States. Antimicrob. Agents Chemother. 53:818820.
36. Nicolas-Chanoine, M. H.,, J. Blanco,, V. Leflon-Guibout,, R. Demarty,, M. P. Alonso,, M. M. Canica,, Y. J. Park,, J. P. Lavigne,, J. Pitout, and, J. R. Johnson. 2008. Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15. J. Antimicrob. Chemother. 61:273281.
37. Nordmann, P.,, G. Cuzon, and, T. Naas. 2009. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect. Dis. 9:228236.
38. Papp-Wallace, K. M.,, C. R. Bethel,, A. M. Distler,, C. Kasuboski,, M. Taracila, and, R. A. Bonomo. 2010. Inhibitor resistance in the KPC-2 beta-lactamase, a preeminent property of this class A beta-lactamase. Antimicrob. Agents Chemother. 54:890897.
39. Paterson, D. L. 2006. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin. Infect. Dis. 43(Suppl. 2):S43S48.
40. Paterson, D. L.,, and Y. Doi. 2007. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin. Infect. Dis. 45:11791181.
41. Peleg, A. Y.,, J. Adams, and, D. L. Paterson. 2007. Tigecycline efflux as a mechanism for nonsusceptibility in Acinetobacter baumannii. Antimicrob. Agents Chemother. 51:20652069.
42. Peleg, A. Y.,, J. M. Bell,, A. Hofmeyr, and, P. Wiese. 2006. Inter-country transfer of gram-negative organisms carrying the VIM-4 and OXA-58 carbapenem-hydrolysing enzymes. J. Antimicrob. Chemother. 57:794795.
43. Peleg, A. Y.,, B. A. Potoski,, R. Rea,, J. Adams,, J. Sethi,, B. Capitano,, S. Husain,, E. J. Kwak,, S. V. Bhat, and, D. L. Paterson. 2007. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J. Antimicrob. Chemother. 59:128131.
44. Peleg, A. Y.,, H. Seifert, and, D. L. Paterson. 2008. Acinetobacter baumannii: emergence of a successful pathogen. Clin. Microbiol. Rev. 21:538582.
45. Perez, F.,, A. M. Hujer,, K. M. Hujer,, B. K. Decker,, P. N. Rather, and, R. A. Bonomo. 2007. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51:34713484.
46. Pitout, J. D.,, L. Campbell,, D. L. Church,, D. B. Gregson, and, K. B. Laupland. 2009. Molecular characteristics of travel-related extended-spectrum-beta-lactamase-producing Escherichia coli isolates from the Calgary health region. Antimicrob. Agents Chemother. 53:25392543.
47. Pitout, J. D.,, L. Campbell,, D. L. Church,, P. W. Wang,, D. S. Guttman, and, D. B. Gregson. 2009. Using a commercial DiversiLab semiautomated repetitive sequence-based PCR typing technique for identification of Escherichia coli clone ST131 producing CTX-M-15. J. Clin. Microbiol. 47:12121215.
48. Pitout, J. D.,, D. B. Gregson,, L. Campbell, and, K. B. Laupland. 2009. Molecular characteristics of extended-spectrum-beta-lactamase-producing Escherichia coli isolates causing bacteremia in the Calgary health region from 2000 to 2007: emergence of clone ST131 as a cause of community-acquired infections. Antimicrob. Agents Chemother. 53:28462851.
49. Pope, J.,, J. Adams,, Y. Doi,, D. Szabo, and, D. L. Paterson. 2006. KPC type beta-lactamase, rural Pennsylvania. Emerg. Infect. Dis. 12:16131614.
50. Pournaras, S.,, E. Protonotariou,, E. Voulgari,, I. Kristo,, E. Dimitroulia,, D. Vitti,, M. Tsalidou,, A. N. Maniatis,, A. Tsakris, and, D. Sofianou. 2009. Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece. J. Antimicrob. Chemother. 64:348352.
51. Prats, G.,, F. Navarro,, B. Mirelis,, D. Dalmau,, N. Margall,, P. Coll,, A. Stell, and, J. R. Johnson. 2000. Escherichia coli serotype O15:K52:H1 as a uropathogenic clone. J. Clin. Microbiol. 38:201209.
52. Sidjabat, H. E.,, D. L. Paterson,, J. M. Adams-Haduch,, L. Ewan,, A. W. Pasculle,, C. A. Muto,, G. B. Tian, and, Y. Doi. 2009. Molecular epidemiology of CTX-M-producing Escherichia coli isolates at a tertiary medical center in western Pennsylvania. Antimicrob. Agents Chemother. 53:47334739.
53. Sidjabat, H. E.,, F. P. Silveira,, B. A. Potoski,, K. M. Abu-Elmagd,, J. M. Adams-Haduch,, D. L. Paterson, and, Y. Doi. 2009. Interspecies spread of Klebsiella pneumoniae carbapenemase gene in a single patient. Clin. Infect. Dis. 49:17361738.
54. Urban, C.,, P. A. Bradford,, M. Tuckman,, S. Segal-Maurer,, W. Wehbeh,, L. Grenner,, R. Colon-Urban,, N. Mariano, and, J. J. Rahal. 2008. Carbapenem-resistant Escherichia coli harboring Klebsiella pneumoniae carbapenemase beta-lactamases associated with long-term care facilities. Clin. Infect. Dis. 46:e127e130.
55. van Dessel, H.,, L. Dijkshoorn,, T. van der Reijden,, N. Bakker,, A. Paauw,, P. van den Broek,, J. Verhoef, and, S. Brisse. 2004. Identification of a new geographically widespread multiresistant Acinetobacter baumannii clone from European hospitals. Res. Microbiol. 155:105112.
56. Villers, D.,, E. Espaze,, M. Coste-Burel,, F. Giauffret,, E. Ninin,, F. Nicolas, and, H. Richet. 1998. Nosocomial Acinetobacter baumannii infections: microbiological and clinical epidemiology. Ann. Intern. Med. 129:182189.
57. White, A. C.,, Jr., R. L. Atmar,, J. Wilson,, T. R. Cate,, C. E. Stager, and, S. B. Greenberg. 1997. Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes. Clin. Infect. Dis. 25:230239.
58. Woodford, N.,, A. Carattoli,, E. Karisik,, A. Underwood,, M. J. Ellington, and, D. M. Livermore. 2009. Complete nucleotide sequences of plasmids pEK204, pEK499, and pEK516, encoding CTX-M enzymes in three major Escherichia coli lineages from the United Kingdom, all belonging to the international O25:H4-ST131 clone. Antimicrob. Agents Chemother. 53:44724482.
59. Woodford, N.,, J. Zhang,, M. Warner,, M. E. Kaufmann,, J. Matos,, A. Macdonald,, D. Brudney,, D. Sompolinsky,, S. Navon-Venezia, and, D. M. Livermore. 2008. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J. Antimicrob. Chemother. 62:12611264.
60. Yamane, K.,, J. Wachino,, Y. Doi,, H. Kurokawa, and, Y. Arakawa. 2005. Global spread of multiple aminoglycoside resistance genes. Emerg. Infect. Dis. 11:951953.
61. Yigit, H.,, A. M. Queenan,, G. J. Anderson,, A. Domenech-Sanchez,, J. W. Biddle,, C. D. Steward,, S. Alberti,, K. Bush, and, F. C. Tenover. 2001. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45:11511161.
62. Yong, D.,, M. A. Toleman,, C. G. Giske,, H. S. Cho,, K. Sundman,, K. Lee, and, T. R. Walsh. 2009. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob. Agents Chemother. 53:50465054.


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Table 1.

Common and emerging antibiotic resistance issues in gram-negative bacilli

Citation: Paterson D, Sidjabat H, Doi Y. 2010. Global Spread of Multidrug-Resistant Gram-Negative Bacilli, p 213-222. In Scheld W, Grayson M, Hughes J (ed), Emerging Infections 9. ASM Press, Washington, DC. doi: 10.1128/9781555816803.ch10

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