Management of infections caused by extended-spectrum β–lactamase-producing Enterobacteriaceae: current evidence and future prospects

Expert Review of Anti-Infective Therapy

Volumn 16, Issue 3, 2018, Pages 205-218

  Sheu, Chau Chyun ^a,b   Lin, Shang Yi ^a,b   Chang, Ya Ting ^a,b   Lee, Chun Yuan ^a,b   Chen, Yen Hsu ^a,b,c   Hsueh, Po Ren ^d  

^a KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^b KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

^c NATIONAL CHIAO TUNG UNIVERSITY   (Taiwan)

^d NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

Antibiotic resistance; extended spectrum lactamase producing Enterobacteriaceae; treatment outcomes; lactam lactamase inhibitor combinations; lactamase

Indexed keywords

AMOXICILLIN PLUS CLAVULANIC ACID; AVIBACTAM PLUS CEFTAZIDIME; AZTREONAM; BETA LACTAMASE INHIBITOR; CARBAPENEM; CARBAPENEM DERIVATIVE; CEFEPIME; CEFMETAZOLE; CEFOPERAZONE PLUS SULBACTAM; CEFTAZIDIME; CEFTOLOZANE PLUS TAZOBACTAM; CEFTRIAXONE; CEPHALOSPORIN DERIVATIVE; CEPHAMYCIN; CLOXACILLIN; DORIPENEM; FLOMOXEF; FOSFOMYCIN; LEVOFLOXACIN; MEROPENEM; METRONIDAZOLE; PENICILLIN DERIVATIVE; PIPERACILLIN PLUS TAZOBACTAM; ANTIINFECTIVE AGENT; BETA LACTAMASE;

ABDOMINAL INFECTION; ACUTE PYELONEPHRITIS; ANTIBIOTIC SENSITIVITY; ANTIBIOTIC THERAPY; BACTEREMIA; BACTERIAL CLEARANCE; BACTERIAL GENE; BACTERIAL STRAIN; BACTERICIDAL ACTIVITY; BACTERIUM ISOLATION; BLASHV 1 GENE; BLATEM 1 GENE; CONCENTRATION RESPONSE; DISEASE SEVERITY; DRUG APPROVAL; DRUG EFFICACY; DRUG TREATMENT FAILURE; ENTEROBACTERIACEAE INFECTION; ESCHERICHIA COLI; EXTENDED SPECTRUM BETA LACTAMASE PRODUCING ENTEROBACTERIACEAE; GRAM NEGATIVE INFECTION; HOSPITAL INFECTION; HUMAN; IN VITRO STUDY; INFECTION; KLEBSIELLA PNEUMONIAE; KLEBSIELLA PNEUMONIAE INFECTION; MINIMUM INHIBITORY CONCENTRATION; MULTIDRUG RESISTANCE; NONHUMAN; PHENOTYPE; PNEUMONIA; POINT MUTATION; PREVALENCE; REVIEW; SEPTIC SHOCK; SURVIVAL RATE; URINARY TRACT INFECTION; ANIMAL; BETA-LACTAM RESISTANCE; DRUG EFFECT; ENTEROBACTERIACEAE; ISOLATION AND PURIFICATION; METABOLISM; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY;

ANIMALS; ANTI-BACTERIAL AGENTS; BETA-LACTAM RESISTANCE; BETA-LACTAMASE INHIBITORS; BETA-LACTAMASES; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ENTEROBACTERIACEAE; ENTEROBACTERIACEAE INFECTIONS; HUMANS; MICROBIAL SENSITIVITY TESTS;

EID: 85042927592     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1080/14787210.2018.1436966     Document Type: Review

References (155)

1. Bassetti M, Poulakou G, Ruppe E, et al. Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach. Intensive Care Med. 2017;43:1464–1475.
2. Medina E, Pieper DH., Tackling threats and future problems of multidrug-resistant bacteria. Curr Top Microbiol Immunol. 2016;398:3–33.
3. Kliebe C, Nies BA, Meyer JF, et al. Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrob Agents Chemother. 1985;28:302–307.
4. Ghafourian S, Sadeghifard N, Soheili S, et al. Extended spectrum beta-lactamases: definition, classification and epidemiology. Curr Issues Mol Biol. 2015;17:11–21.
5. Li Y, Zheng B, Xue F, et al. Changes in minimum inhibitory concentration of levofloxacin for Escherichia coli strains isolated from urine samples in mainland China, 2004 to 2014. J Microbiol Immunol Infect. 2017;50:390–392.
6. Villa L, Pezzella C, Tosini F, et al. Multiple-antibiotic resistance mediated by structurally related IncL/M plasmids carrying an extended-spectrum beta-lactamase gene and a class 1 integron. Antimicrob Agents Chemother. 2000;44:2911–2914.
7. Bradford PA., Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14: 933–951. table of contents.
8. Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008;8:159–166.
9. Chang YT, Coombs G, Ling T, et al. Epidemiology and trends in the antibiotic susceptibilities of Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region, 2010–2013. Int J Antimicrob Agents. 2017;49:734–739.
10. Lee CM, Lai CC, Chiang HT, et al. Presence of multidrug-resistant organisms in the residents and environments of long-term care facilities in Taiwan. J Microbiol Immunol Infect. 2017;50:133–144.
11. Lee CC, Lee CH, Hong MY, et al. Propensity-matched analysis of the impact of extended-spectrum beta-lactamase production on adults with community-onset Escherichia coli, Klebsiella species, and Proteus mirabilis bacteremia. J Microbiol Immunol Infect. 2017. doi: 10.1016/j.jmii.2017.05.006.
12. Jean SS, Lee WS, Bai KJ, et al. Carbapenem susceptibility among Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates obtained from patients in intensive care units in Taiwan in 2005, 2007, and 2009. Diagn Microbiol Infect Dis. 2015;81:290–295.
13. Malloy AM, Campos JM. Extended-spectrum beta-lactamases: a brief clinical update. Pediatr Infect Dis J. 2011;30:1092–1093.
14. Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev. 2005;18:657–686.
15. Boyle DP, Zembower TR. Epidemiology and management of emerging drug-resistant gram-negative bacteria: extended-spectrum beta-lactamases and beyond. Urol Clin North Am. 2015;42:493–505.
16. Kang CI, Song JH, Chung DR, et al. Risk factors and treatment outcomes of community-onset bacteraemia caused by extended-spectrum beta-lactamase-producing Escherichia coli. Int J Antimicrob Agents. 2010;36:284–287.
17. Rottier WC, Ammerlaan HS, Bonten MJ. Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis. J Antimicrob Chemother. 2012;67:1311–1320.
18. Van Aken S, Lund N, Ahl J, et al. Risk factors, outcome and impact of empirical antimicrobial treatment in extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia. Scand J Infect Dis. 2014;46:753–762.
19. Esteve-Palau E, Solande G, Sánchez F, et al. Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: a matched cohort study. J Infect. 2015;71:667–674.
20. Hawser SP, Bouchillon SK, Hoban DJ, et al. 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. 2009;53:3280–3284.
21. Paterson DL, Rossi F, Baquero F, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother. 2005;55:965–973.
22. Gray KJ, Wilson LK, Phiri A, et al. Identification and characterization of ceftriaxone resistance and extended-spectrum beta-lactamases in Malawian bacteraemic Enterobacteriaceae. J Antimicrob Chemother. 2006;57:661–665.
23. Mshana SE, Hain T, Domann E, et al. Predominance of Klebsiella pneumoniae ST14 carrying CTX-M-15 causing neonatal sepsis in Tanzania. BMC Infect Dis. 2013;13:466.
24. El-Khizzi NA, Bakheshwain SM. Prevalence of extended-spectrum beta-lactamases among Enterobacteriaceae isolated from blood culture in a tertiary care hospital. Saudi Med J. 2006;27:37–40.
25. Oh MM, Chae JY, Kim JW, et al. Positive culture for extended-spectrum beta-lactamase during acute prostatitis after prostate biopsy is a risk factor for progression to chronic prostatitis. Urology. 2013;81:1209–1212.
26. Horner C, Fawley W, Morris K, et al. Escherichia coli bacteraemia: 2 years of prospective regional surveillance (2010–12). J Antimicrob Chemother. 2014;69:91–100.
27. Trecarichi EM, Tumbarello M, Spanu T, et al. Incidence and clinical impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies. J Infect. 2009;58:299–307.
28. Horcajada JP, Shaw E, Padilla B, et al. Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance. Clin Microbiol Infect. 2013;19:962–968.
29. Lee JC, Lee NY, Lee HC, et al. Clinical characteristics of urosepsis caused by extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae and their emergence in the community. J Microbiol Immunol Infect. 2012;45:127–133.
30. Ben-Ami R, Rodriguez-Bano J, Arslan H, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009;49:682–690.
31. Calbo E, Romani V, Xercavins M, et al. Risk factors for community-onset urinary tract infections due to Escherichia coli harbouring extended-spectrum beta-lactamases. J Antimicrob Chemother. 2006;57:780–783.
32. Abraham EPEC. An enzyme from bacteria able to destroy penicillin. Nature. 1940;146:837.
33. Bush K. Characterization of β-lactamases. Antimicrob Agents Chemother. 1989;33:259–263.
34. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995;39:1211–1233.
35. Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54:969–976.
36. Sader HS, Hsiung A, Fritsche TR, et al. Comparative activities of cefepime and piperacillin/tazobactam tested against a global collection of Escherichia coli and Klebsiella spp. with an ESBL phenotype. Diagn Microbiol Infect Dis. 2007;57:341–344.
37. Naas T, Poirel L, Nordmann P. Minor extended-spectrum beta-lactamases. Clin Microbiol Infect. 2008;14(Suppl 1):42–52.
38. Pfaller MA, Segreti J. Overview of the epidemiological profile and laboratory detection of extended-spectrum beta-lactamases. Clin Infect Dis. 2006;42(Suppl 4):S153–163.
39. Bonnet R. Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother. 2004;48:1–14.
40. Tzouvelekis LS, Tzelepi E, Tassios PT, et al. CTX-M-type beta-lactamases: an emerging group of extended-spectrum enzymes. Int J Antimicrob Agents. 2000;14:137–142.
41. Rossolini GM, D’Andrea MM, Mugnaioli C. The spread of CTX-M-type extended-spectrum beta-lactamases. Clin Microbiol Infect. 2008;14(Suppl 1):33–41.
42. Woodford N, Ward ME, Kaufmann ME, et al. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK. J Antimicrob Chemother. 2004;54:735–743.
43. Evans BA, Amyes SG. OXA beta-lactamases. Clin Microbiol Rev. 2014;27:241–263.
44. Danel F, Hall LM, Gur D, et al. OXA-14, another extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995;39:1881–1884.
45. Danel F, Hall LM, Gur D, et al. OXA-16, a further extended-spectrum variant of OXA-10 beta-lactamase, from two Pseudomonas aeruginosa isolates. Antimicrob Agents Chemother. 1998;42:3117–3122.
46. Danel F, Hall LM, Duke B, et al. OXA-17, a further extended-spectrum variant of OXA-10 beta-lactamase, isolated from Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1999;43:1362–1366.
47. Mugnier P, Casin I, Bouthors AT, et al. Novel OXA-10-derived extended-spectrum beta-lactamases selected in vivo or in vitro. Antimicrob Agents Chemother. 1998;42:3113–3116.
48. Poirel L, Girlich D, Naas T, et al. OXA-28, an extended-spectrum variant of OXA-10 beta-lactamase from Pseudomonas aeruginosa and its plasmid- and integron-located gene. Antimicrob Agents Chemother. 2001;45:447–453.
49. Al-Bayssari C, Dabboussi F, Hamze M, et al. Detection of expanded-spectrum beta-lactamases in Gram-negative bacteria in the 21st century. Expert Rev Anti Infect Ther. 2015;13:1139–1158.
50. CLSI. Performance standards for antimicrobial susceptibility testing: 20th informational supplement, CLSI document M100-S20. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.
51. CLSI. Performance standards for antimicrobial susceptibility testing: 24th informational supplement, CLSI document M100-S24. Wayne (PA): Clinical and Laboratory Standards Institute; 2014.
52. CLSI. Performance standards for antimicrobial susceptibility testing: 19th informational supplement, CLSI document M100-S19. Wayne (PA): Clinical and Laboratory Standards Institute; 2009.
53. CLSI. Performance standards for antimicrobial susceptibility testing: 23rd informational supplement, CLSI document M100-S23. Wayne (PA): Clinical and Laboratory Standards Institute; 2013.
54. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 1.1, 2010. http://www.eucast.org
55. Livermore DM, Yuan M. Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe. J Antimicrob Chemother. 1996;38:409–424.
56. Paterson DL, Ko WC, Von Gottberg A, et al. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol. 2001;39:2206–2212.
57. Kim YK, Pai H, Lee HJ, et al. Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother. 2002;46:1481–1491.
58. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26: 1–10. quiz 11-12.
59. Maglio D, Ong C, Banevicius MA, et al. Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula. Antimicrob Agents Chemother. 2004;48:1941–1947.
60. Andes D, Craig WA. Treatment of infections with ESBL-producing organisms: pharmacokinetic and pharmacodynamic considerations. Clin Microbiol Infect. 2005;11(Suppl 6):10–17.
61. Lee SY, Kuti JL, Nicolau DP. Cefepime pharmacodynamics in patients with extended spectrum beta-lactamase (ESBL) and non-ESBL infections. J Infect. 2007;54:463–468.
62. Kahlmeter G. Breakpoints for intravenously used cephalosporins in Enterobacteriaceae-EUCAST and CLSI breakpoints. Clin Microbiol Infect. 2008;14(Suppl 1):169–174.
63. Curello J, MacDougall C. Beyond susceptible and resistant, part II: treatment of infections due to Gram-negative organisms producing extended-spectrum beta-lactamases. J Pediatr Pharmacol Ther. 2014;19:156–164.
64. Heil EL, Johnson JK. Impact of CLSI breakpoint changes on microbiology laboratories and antimicrobial stewardship programs. J Clin Microbiol. 2016;54:840–844.
65. Livermore DM, Andrews JM, Hawkey PM, et al. Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly? J Antimicrob Chemother. 2012;67:1569–1577.
66. Kristo I, Pitiriga V, Poulou A, et al. Susceptibility patterns to extended-spectrum cephalosporins among Enterobacteriaceae harbouring extended-spectrum beta-lactamases using the updated clinical and laboratory standards institute interpretive criteria. Int J Antimicrob Agents. 2013;41:383–387.
67. Wang P, Hu F, Xiong Z, et al. Susceptibility of extended-spectrum-beta-lactamase-producing Enterobacteriaceae according to the new CLSI breakpoints. J Clin Microbiol. 2011;49:3127–3131.
68. Hombach M, Mouttet B, Bloemberg GV. Consequences of revised CLSI and EUCAST guidelines for antibiotic susceptibility patterns of ESBL- and AmpC beta-lactamase-producing clinical Enterobacteriaceae isolates. J Antimicrob Chemother. 2013;68:2092–2098.
69. Ku NS, Chung HS, Choi JY, et al. Clinical usefulness of the 2010 clinical and laboratory standards institute revised breakpoints for cephalosporin use in the treatment of bacteremia caused by Escherichia coli or Klebsiella spp. Biomed Res Int. 2015;2015:831074.
70. Seo YB, Lee J, Kim YK, et al. Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli. BMC Infect Dis. 2017;17:404.
71. Paterson DL. “Collateral damage” from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis. 2004;38(Suppl 4):S341–345.
72. Ng TM, Khong WX, Harris PN, et al. Empiric piperacillin-tazobactam versus carbapenems in the treatment of bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae. PLoS One. 2016;11:e0153696.
73. Ofer-Friedman H, Shefler C, Sharma S, et al. Carbapenems versus piperacillin-tazobactam for bloodstream infections of nonurinary source caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Infect Control Hosp Epidemiol. 2015;36:981–985.
74. Tamma PD, Han JH, Rock C, et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum beta-lactamase bacteremia. Clin Infect Dis. 2015;60:1319–1325.
75. Tsai HY, Chen YH, Tang HJ, et al. Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Proteus mirabilis. Diagn Microbiol Infect Dis. 2014;80:222–226.
76. Retamar P, Lopez-Cerero L, Muniain MA, et al. Impact of the MIC of piperacillin-tazobactam on the outcome of patients with bacteremia due to extended-spectrum-beta-lactamase-producing Escherichia coli. Antimicrob Agents Chemother. 2013;57:3402–3404.
77. Yoon YK, Kim JH, Sohn JW, et al. Role of piperacillin/tazobactam as a carbapenem-sparing antibiotic for treatment of acute pyelonephritis due to extended-spectrum beta-lactamase-producing Escherichia coli. Int J Antimicrob Agents. 2017;49:410–415.
78. Kang CI, Park SY, Chung DR, et al. Piperacillin-tazobactam as an initial empirical therapy of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. J Infect. 2012;64:533–534.
79. Rodriguez-Bano J, Navarro MD, Retamar P, et al. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012;54:167–174.
80. Lee NY, Lee CC, Huang WH, et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis. 2013;56:488–495.
81. Wang R, Cosgrove SE, Tschudin-Sutter S, et al. Cefepime therapy for cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia. Open Forum Infect Dis. 2016;3:ofw132.
82. Lee NY, Lee CC, Li CW, et al. Cefepime therapy for monomicrobial Enterobacter cloacae bacteremia: unfavorable outcomes in patients infected by cefepime-susceptible dose-dependent isolates. Antimicrob Agents Chemother. 2015;59:7558–7563.
83. Chopra T, Marchaim D, Veltman J, et al. Impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother. 2012;56:3936–3942.
84. Trivedi M, Patel V, Soman R, et al. The outcome of treating ESBL infections with carbapenems vs. non carbapenem antimicrobials. J Assoc Physicians India. 2012;60:28–30.
85. Park SH, Choi SM, Chang YK, et al. The efficacy of non-carbapenem antibiotics for the treatment of community-onset acute pyelonephritis due to extended-spectrum beta-lactamase-producing Escherichia coli. J Antimicrob Chemother. 2014;69:2848–2856.
86. Ramphal R, Ambrose PG. Extended-spectrum beta-lactamases and clinical outcomes: current data. Clin Infect Dis. 2006;42(Suppl 4):S164–172.
87. Rice LB, Yao JD, Klimm K, et al. Efficacy of different beta-lactams against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. Antimicrob Agents Chemother. 1991;35:1243–1244.
88. Kang CI, Pai H, Kim SH, et al. Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing plasmid-mediated AmpC-type beta-lactamase. J Antimicrob Chemother. 2004;54:1130–1133.
89. Du B, Long Y, Liu H, et al. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome. Intensive Care Med. 2002;28:1718–1723.
90. Paterson DL, Ko WC, Von Gottberg A, et al. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis. 2004;39:31–37.
91. Collins VL, Marchaim D, Pogue JM, et al. Efficacy of ertapenem for treatment of bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2012;56:2173–2177.
92. Vardakas KZ, Tansarli GS, Rafailidis PI, et al. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum beta-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother. 2012;67:2793–2803.
93. Wu UI, Chen WC, Yang CS, et al. Ertapenem in the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli: a propensity score analysis. Int J Infect Dis. 2012;16:e47–52.
94. Berg ML, Crank CW, Philbrick AH, et al. Efficacy of ertapenem for consolidation therapy of extended-spectrum beta-lactamase-producing gram-negative infections: a case series report. Ann Pharmacother. 2008;42:207–212.
95. Bazaz R, Chapman AL, Winstanley TG. Ertapenem administered as outpatient parenteral antibiotic therapy for urinary tract infections caused by extended-spectrum-beta-lactamase-producing Gram-negative organisms. J Antimicrob Chemother. 2010;65:1510–1513.
96. Lee NY, Lee CC, Huang WH, et al. Carbapenem therapy for bacteremia due to extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility. Antimicrob Agents Chemother. 2012;56:2888–2893.
97. Gutierrez-Gutierrez B, Bonomo RA, Carmeli Y, et al. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study. J Antimicrob Chemother. 2016;71:1672–1680.
98. Fong JJ, Rose L, Radigan EA. Clinical outcomes with ertapenem as a first-line treatment option of infections caused by extended-spectrum beta-lactamase producing gram-negative bacteria. Ann Pharmacother. 2012;46:347–352.
99. Bassetti M, Righi E, Fasce R, et al. Efficacy of ertapenem in the treatment of early ventilator-associated pneumonia caused by extended-spectrum beta-lactamase-producing organisms in an intensive care unit. J Antimicrob Chemother. 2007;60:433–435.
100. Lartigue MF, Poirel L, Poyart C, et al. Ertapenem resistance of Escherichia coli. Emerg Infect Dis. 2007;13:315–317.
101. Rattanaumpawan P, Werarak P, Jitmuang A, et al. Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial. BMC Infect Dis. 2017;17:183.
102. DeRyke CA, Banevicius MA, Fan HW, et al. Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. Antimicrob Agents Chemother. 2007;51:1481–1486.
103. Kaniga K, Flamm R, Tong SY, et al. Worldwide experience with the use of doripenem against extended-spectrum-beta-lactamase-producing and ciprofloxacin-resistant Enterobacteriaceae: analysis of six phase 3 clinical studies. Antimicrob Agents Chemother. 2010;54:2119–2124.
104. Hauck C, Cober E, Richter SS, et al. Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections. Clin Microbiol Infect. 2016;22:513–519.
105. Tumbarello M, Viale P, Viscoli C, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012;55:943–950.
106. Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597–602.
107. Gutierrez-Gutierrez B, Perez-Galera S, Salamanca E, et al. A multinational, preregistered cohort study of beta-lactam/beta-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016;60:4159–4169.
108. Shiber S, Yahav D, Avni T, et al. Beta-Lactam/beta-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2015;70:41–47.
109. Pagani L, Migliavacca R, Luzzaro F, et al. Comparative activity of piperacillin/tazobactam against clinical isolates of extended-spectrum beta-lactamase-producing Enterobacteriaceae. Chemotherapy. 1998;44:377–384.
110. D’Angelo RG, Johnson JK, Bork JT, et al. Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. Expert Opin Pharmacother. 2016;17:953–967.
111. Tamma PD, Rodriguez-Bano J. The use of noncarbapenem β-lactams for the treatment of extended-spectrum β-lactamase infections. Clin Infect Dis. 2017;64:972–980.
112. Burgess DS, Hall RG, 2nd. In vitro killing of parenteral beta-lactams against standard and high inocula of extended-spectrum beta-lactamase and non-ESBL producing Klebsiella pneumoniae. Diagn Microbiol Infect Dis. 2004;49:41–46.
113. Gavin PJ, Suseno MT, Thomson RB, Jr., et al. Clinical correlation of the CLSI susceptibility breakpoint for piperacillin- tazobactam against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella species. Antimicrob Agents Chemother. 2006;50:2244–2247.
114. Perez F, Bonomo RA. Editorial commentary: bloodstream infection caused by extended-spectrum beta-lactamase-producing Gram-negative bacteria: how to define the best treatment regimen? Clin Infect Dis. 2015;60:1326–1329.
115. Reese AM, Frei CR, Burgess DS. Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms. Int J Antimicrob Agents. 2005;26:114–119.
116. Ambrose PG, Bhavnani SM, Jones RN. Pharmacokinetics-pharmacodynamics of cefepime and piperacillin-tazobactam against Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: report from the ARREST program. Antimicrob Agents Chemother. 2003;47:1643–1646.
117. Lodise TP, Jr., Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007;44:357–363.
118. Falagas ME, Tansarli GS, Ikawa K, et al. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013;56:272–282.
119. Harris PN, Tambyah PA, Paterson DL. β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infect Dis. 2015;15:475–485.
120. López-Cerero L, Picón E, Morillo C, et al. Comparative assessment of inoculum effects on the antimicrobial activity of amoxycillin-clavulanate and piperacillin-tazobactam with extended-spectrum beta-lactamase-producing and extended-spectrum beta-lactamase-non-producing Escherichia coli isolates. Clin Microbiol Infect. 2010;16:132–136.
121. Docobo-Pérez F, López-Cerero L, López-Rojas R, et al. Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model. Antimicrob Agents Chemother. 2013;57:2109–2113.
122. Rodríguez-Baño J, Picón E, Navarro MD, et al. Impact of changes in CLSI and EUCAST breakpoints for susceptibility in bloodstream infections due to extended-spectrum β-lactamase-producing Escherichia coli. Clin Microbiol Infect. 2012;18:894–900.
123. Denisuik AJ, Lagacé-Wiens PR, Pitout JD, et al. Molecular epidemiology of extended-spectrum β-lactamase-, AmpC β-lactamase- and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolated from Canadian hospitals over a 5 year period: CANWARD 2007–11. J Antimicrob Chemother. 2013;68:57–65.
124. Lagacé-Wiens PR, Nichol KA, Nicolle LE, et al. Treatment of lower urinary tract infection caused by multidrug-resistant extended-spectrum-β-lactamase-producing Escherichia coli with amoxicillin/clavulanate: case report and characterization of the isolate. J Antimicrob Chemother. 2006;57:1262–1263.
125. Rodríguez-Baño J, Alcalá JC, Cisneros JM, et al. Community infections caused by extended-spectrum β-lactamase-producing Escherichia coli. Arch Intern Med. 2008;168:1897–1902.
126. Akova M. Sulbactam-containing beta-lactamase inhibitor combinations. Clin Microbiol Infect. 2008;14(Suppl 1):185–188.
127. Bin C, Hui W, Renyuan Z, et al. Outcome of cephalosporin treatment of bacteremia due to CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli. Diagn Microbiol Infect Dis. 2006;56:351–357.
128. Levin AS. Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem. Clin Microbiol Infect. 2002;8:144–153.
129. Jones RN, Flonta M, Gurler N, et al. Resistance surveillance program report for selected European nations (2011). Diagn Microbiol Infect Dis. 2014;78:429–436.
130. Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin Microbiol Rev. 2010;23:160–201.
131. Kohner PC, Robberts FJ, Cockerill FR, 3rd, et al. Cephalosporin MIC distribution of extended-spectrum-{beta}-lactamase- and pAmpC-producing Escherichia coli and Klebsiella species. J Clin Microbiol. 2009;47:2419–2425.
132. Kang CI, Cha MK, Kim SH, et al. Extended-spectrum cephalosporins and the inoculum effect in tests with CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria. Int J Antimicrob Agents. 2014;43:456–459.
133. Harada S, Ishii Y, Yamaguchi K. Extended-spectrum beta-lactamases: implications for the clinical laboratory and therapy. Korean J Lab Med. 2008;28:401–412.
134. Doi A, Shimada T, Harada S, et al. The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Int J Infect Dis. 2013;17:e159–163.
135. Fukuchi T, Iwata K, Kobayashi S, et al. Cefmetazole for bacteremia caused by ESBL-producing Enterobacteriaceae comparing with carbapenems. BMC Infect Dis. 2016;16:427.
136. Lee CH, Su LH, Chen FJ, et al. Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study. Int J Antimicrob Agents. 2015;46:610–615.
137. Lee CH, Su LH, Chen FJ, et al. Clinical and microbiologic characteristics of adult patients with recurrent bacteraemia caused by extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae. Clin Microbiol Infect. 2015;21(1105):e1101–1108.
138. Neuner EA, Sekeres J, Hall GS, et al. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012;56:5744–5748.
139. Meier S, Weber R, Zbinden R, et al. Extended-spectrum beta-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections: an increasing challenge for antimicrobial therapy. Infection. 2011;39:333–340.
140. Linsenmeyer K, Strymish J, Weir S, et al. Activity of fosfomycin against extended-spectrum-beta-lactamase-producing uropathogens in patients in the community and hospitalized patients. Antimicrob Agents Chemother. 2016;60:1134–1136.
141. Senol S, Tasbakan M, Pullukcu H, et al. Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother. 2010;22:355–357.
142. Zhanel GG, Chung P, Adam H, et al. Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014;74:31–51.
143. Cho JC, Fiorenza MA, Estrada SJ. Ceftolozane/Tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination. Pharmacotherapy. 2015;35:701–715.
144. Scott LJ. Ceftolozane/Tazobactam: a review in complicated intra-abdominal and urinary tract infections. Drugs. 2016;76:231–242.
145. Solomkin J, Hershberger E, Miller B, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis. 2015;60:1462–1471.
146. Wagenlehner FM, Umeh O, Steenbergen J, et al. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet. 2015;385:1949–1956.
147. Popejoy MW, Paterson DL, Cloutier D, et al. Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of phase 3 clinical trials. J Antimicrob Chemother. 2017;72:268–272.
148. Huntington JA, Sakoulas G, Umeh O, et al. Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. J Antimicrob Chemother. 2016;71:2014–2021.
149. Wong D, van Duin D. Novel beta-lactamase inhibitors: unlocking their potential in therapy. Drugs. 2017;77:615–628.
150. Syue LS, Chen YH, Ko WC, et al. New drugs for the treatment of complicated intra-abdominal infections in the era of increasing antimicrobial resistance. Int J Antimicrob Agents. 2016;47:250–258.
151. Falcone M, Paterson D. Spotlight on ceftazidime/avibactam: a new option for MDR Gram-negative infections. J Antimicrob Chemother. 2016;71:2713–2722.
152. Mazuski JE, Gasink LB, Armstrong J, et al. Efficacy and safety of ceftazidime-avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infection: results from a randomized, controlled, double-blind, phase 3 program. Clin Infect Dis. 2016;62:1380–1389.
153. Wagenlehner FM, Sobel JD, Newell P, et al. Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: RECAPTURE, a phase 3 randomized trial program. Clin Infect Dis. 2016;63:754–762.
154. Carmeli Y, Armstrong J, Laud PJ, et al. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016;16:661–673.
155. Torres A, Zhong N, Pachl J, et al. Phase 3, randomized, multicentre study of ceftazidime-avibactam versus meropenem in adults with nosocomial pneumonia including ventilator-associated pneumonia (REPROVE). Paper presented at: 27th European Congress of Clinical Microbiology and Infectious Diseases; 2017 April 22–25; Vienna, Austria.