Treatment of infections caused by extended-spectrum-beta-lactamase-, ampC-, and carbapenemase-producing enterobacteriaceae

Clinical Microbiology Reviews

Volumn 31, Issue 2, 2018, Pages

  Rodríguez Baño, Jesús ^a   Gutiérrez Gutiérrez, Belén ^a   Machuca, Isabel ^b   Pascual, Alvaro ^a  

^a HOSPITAL UNIVERSITARIO VIRGEN MACARENA   (Spain)

^b HOSPITAL UNIVERSITARIO REINA SOFÍA   (Spain)

Author keywords

Antimicrobial therapy; Bloodstream infections; Carbapenemases; Extended spectrum lactamases; Mortality; Multidrug resistance

Indexed keywords

AMINOGLYCOSIDE; AVIBACTAM; AVIBACTAM PLUS CEFTAZIDIME; AZTREONAM; BETA LACTAMASE AMPC; CARBAPENEM DERIVATIVE; CEFEPIME; CEFIDEROCOL; CEPHAMYCIN; CEPHAMYCIN DERIVATIVE; COTRIMOXAZOLE; ERAVACYCLINE; FOSFOMYCIN; IMIPENEM; MEROPENEM PLUS VABORBACTAM; NEW DRUG; PLAZOMICIN; POLYMYXIN; QUINOLONE DERIVATIVE; RELEBACTAM; TEMOCILLIN; TIGECYCLINE; AMPC BETA-LACTAMASES; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; BETA LACTAMASE;

ANTIBIOTIC SENSITIVITY; BACTERIAL INFECTION; BLOODSTREAM INFECTION; BROTH DILUTION; CARBAPENEMASE PRODUCING ENTEROBACTERIACEAE; CRITICALLY ILL PATIENT; DISEASE SEVERITY; ENTEROBACTERIACEAE INFECTION; EXTENDED SPECTRUM BETA LACTAMASE PRODUCING ENTEROBACTERIACEAE; HIGH RISK PATIENT; INFECTION; MORTALITY RATE; MULTIDRUG RESISTANCE; NONHUMAN; PNEUMONIA; POST HOC ANALYSIS; REVIEW; RISK ASSESSMENT; SEPSIS; SEPTIC SHOCK; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; DRUG EFFECT; HUMAN; METABOLISM; MICROBIOLOGY;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; BETA-LACTAMASES; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ENTEROBACTERIACEAE INFECTIONS; HUMANS;

EID: 85042153859     PISSN: 08938512     EISSN: 10986618     Source Type: Journal    
DOI: 10.1128/CMR.00079-17     Document Type: Review

References (398)

1. ECDC/EMEA. 2009. ECDC/EMEA joint technical report. The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. European Centre for Disease Prevention and Control, Stockholm, Sweden. https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time _to_React.pdf.
2. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. 2012. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x.
3. Paterson DL, Bonomo R. 2005. Extended-spectrum β-lactamase: a clinical update. Clin Microbiol Rev 18:657–686. https://doi.org/10.1128/CMR.18.4.657-686.2005.
4. Pitout JD, Laupland KB. 2008. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 8:159–166. https://doi.org/10.1016/S1473-3099(08) 70041-0.
5. Jacoby GA. 2009. AmpC beta-lactamases. Clin Microbiol Rev 22: 161–182. https://doi.org/10.1128/CMR.00036-08.
6. Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas ME. 2012. 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 67: 2793–2803. https://doi.org/10.1093/jac/dks301.
7. Lee B, Kang SY, Kang HM, Yang NR, Kang HG, Ha IS, Cheong HI, Lee HJ, Choi EH. 2013. Outcome of antimicrobial therapy of pediatric urinary tract infections caused by extended-spectrum β-lactamase-producing Enterobacteriaceae. Infect Chemother 45:415–421. https://doi.org/10.3947/ic.2013.45.4.415.
8. Harris PN, Wei JY, Shen AW, Abdile AA, Paynter S, Huxley RR, Pandeya N, Doi Y, Huh K, O’Neal CS, Talbot TR, Paterson DL. 2016. Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis. J Antimicrob Chemother 71:296–306. https://doi.org/10.1093/jac/dkv346.
9. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R. 2014. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis 14: 742–750. https://doi.org/10.1016/S1473-3099(14)70780-7.
10. Rodríguez-Baño J, Pascual A. 2008. Clinical significance of extended-spectrum β-lactamases. Expert Rev Anti Infect Ther 6:671–683. https://doi.org/10.1586/14787210.6.5.671.
11. Kaniga K, Flamm R, Tong SY, Lee M, Friedland I, Redman R. 2010. 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 54:2119–2124. https://doi.org/10.1128/AAC.01450-09.
12. Nicolau DP, Carmeli Y, Crank CW, Goff DA, Graber CJ, Lima AL, Goldstein EJ. 2012. Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems. A review of the evidence. Int J Antimicrob Agents 39:11–15. https://doi.org/10.1016/j.ijantimicag.2011.08.018.
13. Lim CL, Lee W, Lee AL, Liew LT, Nah SC, Wan CN, Chlebicki MP, Kwa AL. 2013. Evaluation of ertapenem use with impact assessment on extended-spectrum beta-lactamases (ESBL) production and gram-negative resistance in Singapore General Hospital (SGH). BMC Infect Dis 13:523. https://doi.org/10.1186/1471-2334-13-523.
14. Lee NY, Huang WH, Tsui KC, Hsueh PR, Ko WC. 2011. Carbapenem therapy for bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae. Diagn Microbiol Infect Dis 70:150–153. https://doi.org/10.1016/j.diagmicrobio.2010.12.008.
15. Wu UI, Chen WC, Yang CS, Wang JL, Hu FC, Chang SC, Chen YC. 2012. Ertapenem in the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli: a propensity score analysis. Int J Infect Dis 16:e47–e52. https://doi.org/10.1016/j.ijid.2011.09.019.
16. Collins VL, Marchaim D, Pogue JM, Moshos J, Bheemreddy S, Sunkara B, Shallal A, Chugh N, Eiseler S, Bhargava P, Blunden C, Lephart PR, Memon BI, Hayakawa K, Abreu-Lanfranco O, Chopra T, Munoz-Price LS, Carmeli Y, Kaye KS. 2012. Efficacy of ertapenem for treatment of bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 56: 2173–2177. https://doi.org/10.1128/AAC.05913-11.
17. Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC. 2012. Carbapenem therapy for bacteremia due to extended-spectrum-beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: implications of ertapenem susceptibility. Antimicrob Agents Chemother 56: 2888–2893. https://doi.org/10.1128/AAC.06301-11.
18. Gutiérrez-Gutiérrez B, Bonomo RA, Carmeli Y, Paterson DL, Almirante B, Martínez-Martínez L, Oliver A, Calbo E, Peña C, Akova M, Pitout J, Origüen J, Pintado V, García-Vázquez E, Gasch O, Hamprecht A, Prim N, Tumbarello M, Bou G, Viale P, Tacconelli E, Almela M, Pérez F, Giamarellou H, Cisneros JM, Schwaber MJ, Venditti M, Lowman W, Bermejo J, Hsueh PR, Mora-Rillo M, Gracia-Ahulfinger I, Pascual A, Rodríguez-Baño J. 2016. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study. J Antimicrob Chemother 71:1672–1680. https://doi.org/10.1093/jac/dkv502.
19. Burkhardt O, Kumar V, Katterwe D, Majcher-Peszynska J, Drewelow B, Derendorf H, Welte T. 2007. Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration. J Antimicrob Chemother 59:277–284. https://doi.org/10.1093/jac/dkl485.
20. Bassetti M, Righi E, Fasce R, Molinari MP, Rosso R, Di Biagio A, Mussap M, Pallavicini FB, Viscoli C. 2007. 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 60:433–435. https://doi.org/10.1093/jac/dkm180.
21. Rattanaumpawan P, Werarak P, Jitmuang A, Kiratisin P, Thamlikitkul V. 2017. Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial. BMC Infect Dis 17:183. https://doi.org/10.1186/s12879-017-2284-1.
22. Dalgic N, Sancar M, Bayraktar B, Dincer E, Pelit S. 2011. Ertapenem for the treatment of urinary tract infections caused by extended-spectrum β-lactamase-producing bacteria in children. Scand J Infect Dis 43: 339–343. https://doi.org/10.3109/00365548.2011.553241.
23. Karaaslan A, Kadayifci EK, Atici S, Akkoc G, Yakut N, Öcal Demir S, Soysal A, Bakir M. 2015. The clinical efficacy and safety of ertapenem for the treatment of complicated urinary tract infections caused by ESBL-producing bacteria in children. Int J Nephrol 2015:595840. https://doi.org/10.1155/2015/595840.
24. Bazaz R, Chapman AL, Winstanley TG. 2010. Ertapenem administered as outpatient parenteral antibiotic therapy for urinary tract infections caused by extended-spectrum-beta-lactamase-producing Gram-negative organisms. J Antimicrob Chemother 65:1510–1513. https://doi.org/10.1093/jac/dkq152.
25. Forestier E, Gros S, Peynaud D, Levast M, Boisseau D, Ferry-Blanco C, Labe A, Lecomte C, Rogeaux O. 2012. Ertapenem intraveineux ou sous-cutane pour le traitement des infections urinaires a enterobacte-rie secretrice de BLSE. Med Mal Infect 42:440–443. https://doi.org/10.1016/j.medmal.2012.07.005.
26. Song S, Kim C, Lim D. 2014. Clinical efficacy of ertapenem for recurrent cystitis caused by multidrug-resistant extended-spectrum β-lactamase-producing Escherichia coli in female outpatients. Korean J Urol 55: 270–275. https://doi.org/10.4111/kju.2014.55.4.270.
27. Trad MA, Zhong LH, Llorin RM, Tan SY, Chan M, Archuleta S, Sulaiman Z, Tam VH, Lye DC, Fisher DA. 2017. Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections. J Chemother 29:25–29. https://doi.org/10.1080/1120009X.2016.1158937.
28. Veve MP, Wagner JL, Kenney RM, Grunwald JL, Davis SL. 2016. Comparison of fosfomycin to ertapenem for outpatient or step-down therapy of extended-spectrum β-lactamase urinary tract infections. Int J Antimicrob Agents 48:56–60. https://doi.org/10.1016/j.ijantimicag.2016.04.014.
29. Zhanel GG, Denisuik A, Vashisht S, Yachison C, Adam HJ, Hoban DJ. 2014. Pharmacodynamic activity of ertapenem versus genotypically characterized extended-spectrum β-lactamase (ESBL)-, KPC- or NDM-producing Escherichia coli with reduced susceptibility or resistance to ertapenem using an in vitro model. J Antimicrob Chemother 69: 2448–2452. https://doi.org/10.1093/jac/dku149.
30. Ungphakorn W, Tängdén T, Sandegren L, Nielsen EI. 2016. A pharmacokinetic-pharmacodynamic model characterizing the emergence of resistant Escherichia coli subpopulations during ertapenem exposure. J Antimicrob Chemother 71:2521–2533. https://doi.org/10.1093/jac/dkw205.
31. Elliott E, Brink AJ, van Greune J, Els Z, Woodford N, Turton J, Warner M, Livermore DM. 2006. In vivo development of ertapenem resistance in a patient with pneumonia caused by Klebsiella pneumoniae with an extended-spectrum beta-lactamase. Clin Infect Dis 42:e95–e98. https:// doi.org/10.1086/503264.
32. Oteo J, Delgado-Iribarren A, Vega D, Bautista V, Rodríguez MC, Velasco M, Saavedra JM, Pérez-Vázquez M, García-Cobos S, Martínez-Martínez L, Campos J. 2008. Emergence of imipenem resistance in clinical Escherichia coli during therapy. Int J Antimicrob Agents 32:534–537. https://doi.org/10.1016/j.ijantimicag.2008.06.012.
33. Skurnik D, Lasocki S, Bremont S, Muller-Serieys C, Kitzis MD, Courvalin P, Andremont A, Montravers P. 2010. Development of ertapenem resistance in a patient with mediastinitis caused by Klebsiella pneumoniae producing an extended-spectrum beta-lactamase. J Med Microbiol 59:115–119. https://doi.org/10.1099/jmm.0.012468-0.
34. Mena A, Plasencia V, García L, Hidalgo O, Ayestarán JI, Alberti S, Borrell N, Pérez JL, Oliver A. 2006. Characterization of a large outbreak by CTX-M-1-producing Klebsiella pneumoniae and mechanisms leading to in vivo carbapenem resistance development. J Clin Microbiol 44: 2831–2837. https://doi.org/10.1128/JCM.00418-06.
35. Pérez F, Bonomo RA. 2012. Can we really use β-lactam/β-lactam inhibitor combinations for the treatment of infections caused by extended-spectrum β-lactamase-producing bacteria? Clin Infect Dis 54:175–177. https://doi.org/10.1093/cid/cir793.
36. Karlowsky JA, Hoban DJ, Hackel MA, Lob S, Sahm DF. 2017. Antimicrobial susceptibility of Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Asia-Pacific countries: SMART 2013–2015. J Med Microbiol 66:61–69. https://doi.org/10.1099/jmm.0.000421.
37. Pitout JD, Gregson DB, Campbell L, Laupland KB. 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: 2846–2851. https://doi.org/10.1128/AAC.00247-09.
38. Pitout JD, Le P, Church DL, Gregson DB, Laupland KB. 2008. Antimicrobial susceptibility of well-characterised multiresistant CTX-M-producing Escherichia coli: failure of automated systems to detect resistance to piperacillin/tazobactam. Int J Antimicrob Agents 32:333–338. https://doi.org/10.1016/j.ijantimicag.2008.04.023.
39. López-Cerero L, Picón E, Morillo C, Hernández JR, Docobo F, Pachón J, Rodríguez-Baño J, Pascual A. 2010. 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 16:132–136. https://doi.org/10.1111/j.1469-0691.2009.02893.x.
40. Rice LB, Carias LL, Shlaes DM. 1994. In vivo efficacies of β-lactam-β-lactamase inhibitor combinations against a TEM-26-producing strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 38:2663–2664. https://doi.org/10.1128/AAC.38.11.2663.
41. Thauvin-Eliopoulos C, Tripodi MF, Moellering RC Jr, Eliopoulos GM. 1997. Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 41:1053–1057.
42. Ambrose PG, Bhavnani SM, Jones RN. 2003. 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 47:1643–1646. https://doi.org/10.1128/AAC.47.5.1643-1646.2003.
43. Docobo-Pérez F, López-Cerero L, López-Rojas R, Egea P, Domínguez-Herrera J, Rodríguez-Baño J, Pascual A, Pachón J. 2013. 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 57:2109–2113. https://doi.org/10.1128/AAC.02190-12.
44. Harada Y, Morinaga Y, Kaku N, Nakamura S, Uno N, Hasegawa H, Izumikawa K, Kohno S, Yanagihara K. 2014. In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. Clin Microbiol Infect 20: O831–O839. https://doi.org/10.1111/1469-0691.12677.
45. Zimhony O, Chmelnitsky I, Bardenstein R, Goland S, Hammer Muntz O, Navon Venezia S, Carmeli Y. 2006. Endocarditis caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae: emergence of resistance to ciprofloxacin and piperacillin-tazobactam during treatment despite initial susceptibility. Antimicrob Agents Chemother 50: 3179–3182. https://doi.org/10.1128/AAC.00218-06.
46. Rodríguez-Baño J, Navarro MD, Retamar P, Picón E, Pascual Á. 2012. β-Lactam/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis 54: 167–174. https://doi.org/10.1093/cid/cir790.
47. Shiber S, Yahav D, Avni T, Leibovici L, Paul M. 2015. β-Lactam/β-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 70:41–47. https://doi.org/10.1093/jac/dku351.
48. Tamma PD, Han JH, Rock C, Harris AD, Lautenbach E, Hsu AJ, Avdic E, Cosgrove SE. 2015. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. Clin Infect Dis 60: 1319–1325. https://doi.org/10.1093/cid/civ003.
49. Tsai HY, Chen YH, Tang HJ, Huang CC, Liao CH, Chu FY, Chuang YC, Sheng WH, Ko WC, Hsueh PR. 2014. Carbapenems and piperacillin/ tazobactam for the treatment of bacteremia caused by extended-spectrum β-lactamase-producing Proteus mirabilis. Diagn Microbiol Infect Dis 80:222–226. https://doi.org/10.1016/j.diagmicrobio.2014.07.006.
50. Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter Paterson DL, Tambyah PA. 2015. Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae. Antimicrob Resist Infect Control 4:14. https://doi.org/10.1186/s13756-015-0055-6.
51. Gutiérrez-Gutiérrez B, Pérez-Galera S, Salamanca E, de Cueto M, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martínez-Martínez L, Pitout J, Akova M, Peña C, Molina J, Hernández A, Venditti M, Prim N, Origüen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Mora-Rillo M, Natera C, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodríguez-Baño J. 2016. A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 60: 4159–4169. https://doi.org/10.1128/AAC.00365-16.
52. Ng TM, Khong WX, Harris PN, De PP, Chow A, Tambyah PA, Lye DC. 2016. Empiric piperacillin-tazobactam versus carbapenems in the treat- ment of bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae. PLoS One 11:e0153696. https://doi.org/10.1371/journal.pone.0153696.
53. Gudiol C, Royo-Cebrecos C, Abdala E, Akova M, Álvarez R, Maestro-de la Calle G, Cano A, Cervera C, Clemente WT, Martín-Dávila P, Freifeld A, Gómez L, Gottlieb T, Gurguí M, Herrera F, Manzur A, Maschmeyer G, Meije Y, Montejo M, Peghin M, Rodríguez-Baño J, Ruiz-Camps I, Suki-ennik TC, Tebe C, Carratalà J. 2017. Efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum-β-lactamase-producing Enterobacteriaceae in hematological patients with neutropenia. Antimicrob Agents Chemother 61:e00164-17. https://doi.org/10.1128/AAC.00164-17.
54. Dizbay M, Özger HS, Karaşahin Ö, Karaşahin EF. 2016. Treatment efficacy and superinfection rates in complicated urinary tract infections treated with ertapenem or piperacillin tazobactam. Turk J Med Sci 46:1760–1764. https://doi.org/10.3906/sag-1506-157.
55. Yoon YK, Kim JH, Sohn JW, Yang KS, Kim MJ. 2017. Role of piperacillin/ tazobactam as a carbapenem-sparing antibiotic for treatment of acute pyelonephritis due to extended-spectrum β-lactamase-producing Escherichia coli. Int J Antimicrob Agents 49:410–415. https://doi.org/10.1016/j.ijantimicag.2016.12.017.
56. Seo YB, Lee J, Kim YK, Lee SS, Lee JA, Kim HY, Uh Y, Kim HS, Song W. 2017. 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 17:404. https://doi.org/10.1186/s12879-017-2502-x.
57. Retamar P, López-Cerero L, Muniain MA, Pascual Á, Rodríguez-Baño J. 2013. Impact of the MIC of piperacillin-tazobactam on the outcome of patients with bacteremia due to extended-spectrum-β-lactamase-producing Escherichia coli. Antimicrob Agents Chemother 57: 3402–3404. https://doi.org/10.1128/AAC.00135-13.
58. Harris PN, Peleg AY, Iredell J, Ingram PR, Miyakis S, Stewardson AJ, Rogers BA, McBryde ES, Roberts JA, Lipman J, Athan E, Paul SK, Baker P, Harris-Brown T, Paterson DL. 2015. Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial. Trials 16:24. https://doi.org/10.1186/s13063-014-0541-9.
59. Yang H, Zhang C, Zhou Q, Wang Y, Chen L. 2015. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PLoS One 10:e0116769. https://doi.org/10.1371/journal.pone.0116769.
60. Cheng L, Nelson BC, Mehta M, Seval N, Park S, Giddins MJ, Shi Q, Whittier S, Gomez-Simmonds A, Uhlemann AC. 2017. Piperacillin-tazobactam versus other antibacterial agents for treatment of bloodstream infections due to AmpC β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 61:e00276-17. https://doi.org/10.1128/AAC.00276-17.
61. van Duin D, Bonomo RA. 2016. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations. Clin Infect Dis 63:234–241. https://doi.org/10.1093/cid/ciw243.
62. Popejoy MW, Paterson DL, Cloutier D, Huntington JA, Miller B, Bliss CA, Steenbergen JN, Hershberger E, Umeh O, Kaye KS. 2017. 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 72:268–272. https://doi.org/10.1093/jac/dkw374.
63. Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, Yates K, Gasink LB. 2016. 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 63:754–762. https://doi.org/10.1093/cid/ciw378.
64. Mazuski JE, Gasink LB, Armstrong J, Broadhurst H, Stone GG, Rank D, Llorens L, Newell P, Pachl J. 2016. 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 62:1380–1389. https://doi.org/10.1093/cid/ciw133.
65. Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, Gasink LB. 2016. 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 16:661–673. https://doi.org/10.1016/S1473-3099(16)30004-4.
66. European Committee on Antimicrobial Susceptibility Testing. 2017. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.0. http://www.eucast.org.
67. Clinical and Laboratory Standards Institute (CLSI). 2017. Performance standards for antimicrobial susceptibility testing, 27th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, Wayne, PA.
68. Rodríguez-Baño J, Picón E, Navarro MD, López-Cerero L, Pascual A. 2012. 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 18: 894–900. https://doi.org/10.1111/j.1469-0691.2011.03673.x.
69. Huang CC, Chen YS, Toh HS, Lee YL, Liu YM, Ho CM, Lu PL, Liu CE, Chen YH, Wang JH, Tang HJ, Yu KW, Liu YC, Chuang YC, Xu Y, Ni Y, Ko WC, Hsueh PR. 2012. Impact of revised CLSI breakpoints for susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2002–2010. Int J Antimicrob Agents 40(Suppl):S4–S10. https://doi.org/10.1016/S0924-8579(12)70003-1.
70. Park KH, Chong YP, Kim SH, Lee SO, Lee MS, Sung H, Kim MN, Kim YS, Woo JH, Choi SH. 2017. Impact of revised broad-spectrum cephalosporin Clinical and Laboratory Standards Institute breakpoints on susceptibility in Enterobacteriaceae producing AmpC β-lactamase. Infect Chemother 49:62–67. https://doi.org/10.3947/ic.2017.49.1.62.
71. Paterson DL, Ko WC, Von Gottberg A, Casellas JM, Mulazimoglu L, Klugman KP, Bonomo RA, Rice LB, McCormack JG, Yu VL. 2001. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum β-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol 39:2206–2212. https://doi.org/10.1128/JCM.39.6.2206 -2212.2001.
72. Lee SY, Kuti JL, Nicolau DP. 2007. Cefepime pharmacodynamics in patients with extended spectrum beta-lactamase (ESBL) and non-ESBL infections. J Infect 54:463–468. https://doi.org/10.1016/j.jinf.2006.09.004.
73. McGowan A. 2008. Breakpoints for extended-spectrum beta-lactamase-producing Enterobacteriaceae: pharmacokinetic/pharmacodynamic considerations. Clin Microbiol Infect 14(Suppl 1):S166–S168.
74. Goethaert K, Van Looveren M, Lammens C, Jansens H, Baraniak A, Gniadkowski M, Van Herck K, Jorens PG, Demey HE, Ieven M, Bossaert L, Goossens H. 2006. High-dose cefepime as an alternative treatment for infections causedby TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients. Clin Microbiol Infect 12:56–62. https://doi.org/10.1111/j.1469-0691.2005.01290.x.
75. Bin C, Hui W, Renyuan Z, Yongzhong N, Xiuli X, Yingchun X, Yuanjue Z, Minjun C. 2006. Outcome of cephalosporin treatment of bacteremia due to CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli. Diagn Microbiol Infect Dis 56:351–357. https://doi.org/10.1016/j.diagmicrobio.2006.06.015.
76. Chopra T, Marchaim D, Veltman J, Johnson P, Zhao JJ, Tansek R, Hatahet D, Chaudhry K, Pogue JM, Rahbar H, Chen TY, Truong T, Rodriguez V, Ellsworth J, Bernabela L, Bhargava A, Yousuf A, Alangaden G, Kaye KS. 2012. 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 56:3936–3942. https://doi.org/10.1128/AAC.05419-11.
77. Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC. 2013. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 56:488–495. https://doi.org/10.1093/cid/cis916.
78. Wang R, Cosgrove SE, Tschudin-Sutter S, Han JH, Turnbull AE, Hsu AJ, Avdic E, Carroll KC, Tamma PD. 2016. Cefepime therapy for cefepime-susceptible extended-spectrum β-lactamase-producing Enterobacteriaceae bacteremia. Open Forum Infect Dis 3:ofw132. https://doi.org/10.1093/ofid/ofw132.
79. Lee NY, Lee CC, Li CW, Li MC, Chen PL, Chang CM, Ko WC. 2015. Cefepime therapy for monomicrobial Enterobacter cloacae bacteremia: unfavorable outcomes in patients infected by cefepime-susceptible dose-dependent isolates. Antimicrob Agents Chemother 59: 7558–7563. https://doi.org/10.1128/AAC.01477-15.
80. Hsieh CC, Lee CH, Li MC, Hong MY, Chi CH, Lee CC. 2016. Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: impact of revised CLSI breakpoints. Int J Antimicrob Agents 47:297–303. https://doi.org/10.1016/j.ijantimicag.2016.01.010.
81. Bedenić B, Beader N, Zagar Z. 2001. Effect of inoculum size on the antibacterial activity of cefpirome and cefepime against Klebsiella pneumoniae strains producing SHV extended-spectrum beta-lactamases. Clin Microbiol Infect 7:626–635. https://doi.org/10.1046/j.1198-743x.2001.x.
82. Thomson KS, Moland ES. 2001. Cefepime, piperacillin-tazobactam, and the inoculum effect in tests with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 45: 3548–3554. https://doi.org/10.1128/AAC.45.12.3548-3554.2001.
83. Wu N, Chen BY, Tian SF, Chu YZ. 2014. The inoculum effect of antibiotics against CTX-M-extended-spectrum β-lactamase-producing Escherichia coli. Ann Clin Microbiol Antimicrob 13:45. https://doi.org/10.1186/s12941-014-0045-1.
84. Costa Ramos JM, Stein C, Pfeifer Y, Brandt C, Pletz MW, Makarewicz O. 2015. Mutagenesis of the CTX-M-type ESBL—is MIC-guided treatment according to the new EUCAST recommendations a safe approach? J Antimicrob Chemother 70:2528–2535. https://doi.org/10.1093/jac/dkv153.
85. Tamma PD, Girdwood SC, Gopaul R, Tekle T, Roberts AA, Harris AD, Cosgrove SE, Carroll KC. 2013. The use of cefepime for treating AmpC β-lactamase-producing Enterobacteriaceae. Clin Infect Dis 57:781–788. https://doi.org/10.1093/cid/cit395.
86. Kang CI, Pai H, Kim SH, Kim HB, Kim EC, Oh MD, Choe KW. 2004. Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing plasmid-mediated AmpC-type beta-lactamase. J Antimicrob Chemother 54:1130–1133. https://doi.org/10.1093/jac/dkh462.
87. Pichardo C, Rodríguez-Martínez JM, Pachón-Ibañez ME, Conejo C, Ibáñez-Martínez J, Martínez-Martínez L, Pachón J, Pascual A. 2005. Efficacy of cefepime and imipenem in experimental murine pneumonia caused by porin-deficient Klebsiella pneumoniae producing CMY-2 beta-lactamase. Antimicrob Agents Chemother 49:3311–3316. https://doi.org/10.1128/AAC.49.8.3311-3316.2005.
88. Betriu C, Salso S, Sánchez A, Culebras E, Gómez M, Rodríguez-Avial I, Picazo JJ. 2006. Comparative in vitro activity and the inoculum effect of ertapenem against Enterobacteriaceae resistant to extended-spectrum cephalosporins. Int J Antimicrob Agents 28:1–5.
89. Pangon B, Bizet C, Buré AA, Pichon F, Philippon A, Regnier B, Gutmann L. 1989. In vivo selection of a cephamycin-resistant, porin-deficient mutant of Klebsiella pneumoniae producing a TEM-3 beta-lactamase. J Infect Dis 159:1005–1006. https://doi.org/10.1093/infdis/159.5.1005.
90. Siu LK, Lu PL, Hsueh PR, Lin FM, Chang SC, Luh KT, Ho M, Lee CY. 1999. Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric oncology ward: clinical features and identification of different plasmids carrying both SHV-5 and TEM-1 genes. J Clin Microbiol 37:4020–4027.
91. Lee CH, Su LH, Tang YF, Liu JW. 2006. Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: a retrospective study and laboratory analysis of the isolates. J Antimicrob Chemother 58:1074–1077. https://doi.org/10.1093/jac/dkl381.
92. Yang CC, Li SH, Chuang FR, Chen CH, Lee CH, Chen JB, Wu CH, Lee CT. 2012. Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing Klebsiella pneumoniae in patients on maintenance hemodialysis. BMC Infect Dis 12:206. https://doi.org/10.1186/1471-2334-12-206.
93. Doi A, Shimada T, Harada S, Iwata K, Kamiya T. 2013. The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Int J Infect Dis 17: e159–e163. https://doi.org/10.1016/j.ijid.2012.09.010.
94. Pilmis B, Parize P, Zahar JR, Lortholary O. 2014. Alternatives to carbapenems for infections caused by ESBL-producing Enterobacteriaceae. Eur J Clin Microbiol Infect Dis 33:1263–1265. https://doi.org/10.1007/s10096-014-2094-y.
95. Matsumura Y, Yamamoto M, Nagao M, Komori T, Fujita N, Hayashi A, Shimizu T, Watanabe H, Doi S, Tanaka M, Takakura S, Ichiyama S. 2015. Multicenter retrospective study of cefmetazole and flomoxef for treatment of extended-spectrum-β-lactamase-producing Escherichia coli bacteremia. Antimicrob Agents Chemother 59:5107–5113. https://doi.org/10.1128/AAC.00701-15.
96. Lee CH, Su LH, Chen FJ, Tang YF, Li CC, Chien CC, Liu JW. 2015. Comparative effectiveness of flomoxef versus carbapenems in the treatment of bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: a retrospective study. Int J Antimicrob Agents 46:610–615. https://doi.org/10.1016/j.ijantimicag.2015.07.020.
97. Fukuchi T, Iwata K, Kobayashi S, Nakamura T, Ohji G. 2016. Cefmetazole for bacteremia caused by ESBL-producing Enterobacteriaceae comparing with carbapenems. BMC Infect Dis 16:427. https://doi.org/10.1186/s12879-016-1770-1.
98. Livermore DM, Hope R, Fagan EJ, Warner M, Woodford N, Potz N. 2006. Activity of temocillin against prevalent ESBL- and AmpC-producing Enterobacteriaceae from South-East England. J Antimicrob Chemother 57:1012–1014. https://doi.org/10.1093/jac/dkl043.
99. Giamarellou H. 2006. Treatment options for multi drug-resistant bacteria. Expert Rev Anti Infect Ther 4:601–618. https://doi.org/10.1586/14787210.4.4.601.
100. Soubirou JF, Rossi B, Couffignal C, Ruppé E, Chau F, Massias L, Lepeule R, Mentre F, Fantin B. 2015. Activity of temocillin in a murine model of urinary tract infection due to Escherichia coli producing or not producing the ESBL CTX-M-15. J Antimicrob Chemother 70:1466–1472. https://doi.org/10.1093/jac/dku542.
101. Balakrishnan I, Awad-El-Kariem FM, Aali A, Kumari P, Mulla R, Tan B, Brudney D, Ladenheim D, Ghazy A, Khan I, Virgincar N, Iyer S, Carryn S, Van de Velde S. 2011. Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC beta-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother 66:2628–2631. https://doi.org/10.1093/jac/dkr317.
102. Laterre PF, Wittebole X, Van de Velde S, Muller AE, Mouton JW, Carryn S, Tulkens PM, Dugernier T. 2015. Temocillin (6 g daily) in critically ill patients: continuous infusion versus three times daily administration. J Antimicrob Chemother 70:891–898. https://doi.org/10.1093/jac/dku465.
103. Vidal L, Gafter-Vili Borok S, Fraser A, Leibovici L, Paul M. 2007. Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 60:247–257. https://doi.org/10.1093/jac/dkm193.
104. Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. 2014. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014: CD003344. https://doi.org/10.1002/14651858.CD003344.pub3.
105. Ong DSY, Frencken JF, Klein Klouwenberg PMC, Juffermans N, van der Poll T, Bonten MJM, Cremer OL. 2017. Short-course adjunctive gentamicin as empirical therapy in patients with severe sepsis and septic shock: a prospective observational cohort study. Clin Infect Dis 64: 1731–1736. https://doi.org/10.1093/cid/cix186.
106. Palacios-Baena ZR, Gutiérrez-Gutiérrez B, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martínez-Martínez L, Pitout J, Akova M, Peña C, Molina Gil-Bermejo J, Hernández A, Venditti M, Prim N, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Paño-Pardo JR, Torre-Cisneros J, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodríguez-Baño J. 2017. Empiric therapy with carbapenem-sparing regimens for bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: results from the INCREMENT cohort. Clin Infect Dis 65:1615–1623. https://doi.org/10.1093/cid/cix606.
107. Gudiol C, Calatayud L, Garcia-Vidal C, Lora-Tamayo J, Cisnal M, Duarte R, Arnan M, Marin M, Carratalà J, Gudiol F. 2010. Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother 65:333–341. https://doi.org/10.1093/jac/dkp411.
108. Han SB, Jung SW, Bae EY, Lee JW, Lee DG, Chung NG, Jeong DC, Cho B, Kang JH, Kim HK, Park YJ. 2015. Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in febrile neutropenic children. Microb Drug Resist 21:244–251. https://doi.org/10.1089/mdr.2014.0092.
109. Zavascki AP, Klee BO, Bulitta JB. 2017. Aminoglycosides against carbapenem-resistant Enterobacteriaceae in the critically ill: the pitfalls of aminoglycoside susceptibility. Expert Rev Anti Infect Ther 15: 519–526. https://doi.org/10.1080/14787210.2017.1316193.
110. Jean SS, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, Kim MJ, Rajasekaram DG, Mendoza M, Tan TY, Kiratisin P, Ni Y, Weinman B, Xu Y, Hsueh PR. 2016. Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2010–2013. Int J Antimicrob Agents 47:328–334. https://doi.org/10.1016/j.ijantimicag.2016.01.008.
111. Haidar G, Alkroud A, Cheng S, Churilla TM, Churilla BM, Shields RK, Doi Y, Clancy CJ, Nguyen MH. 2016. Association between the presence of aminoglycoside-modifying enzymes and in vitro activity of gentamicin, tobramycin, amikacin, and plazomicin against Klebsiella pneumoniae carbapenemase- and extended-spectrum-β-lactamase-producing Enterobacter species. Antimicrob Agents Chemother 60:5208–5214. https://doi.org/10.1128/AAC.00869-16.
112. López-Diaz MD, Culebras E, Rodríguez-Avial I, Rios E, Viñuela-Prieto JM, Picazo JJ, Rodríguez-Avial C. 2017. Plazomicin activity against 346 extended-spectrum-β-lactamase/AmpC-producing Escherichia coli urinary isolates in relation to aminoglycoside-modifying enzymes. Antimicrob Agents Chemother 61:e02454-16. https://doi.org/10.1128/AAC.02454-16.
113. Peterson LR. 2008. A review of tigecycline—the first glycylcycline. Int J Antimicrob Agents 32(Suppl 4):S215–S222. https://doi.org/10.1016/S0924-8579(09)70005-6.
114. Tasina E, Haidich AB, Kokkali S, Arvanitidou M. 2011. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis 11:834–844. https://doi.org/10.1016/S1473-3099(11) 70177-3.
115. Yahav D, Lador A, Paul M, Leibovici L. 2011. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother 66:1963–1971. https://doi.org/10.1093/jac/dkr242.
116. Cai Y, Wang R, Liang B, Bai N, Liu Y. 2011. Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother 55: 1162–1172. https://doi.org/10.1128/AAC.01402-10.
117. Shen F, Han Q, Xie D, Fang M, Zeng H, Deng Y. 2015. Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. Int J Infect Dis 39:25–33. https://doi.org/10.1016/j.ijid.2015.08.009.
118. Vasilev K, Reshedko G, Orasan R, Sanchez M, Teras J, Babinchak T, Dukart G, Cooper A, Dartois N, Gandjini H, Orrico R, Ellis-Grosse E. 2008. A phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae. J Antimicrob Chemother 62(Suppl 1):i29–i40. https://doi.org/10.1093/jac/dkn249.
119. Poulakou G, Kontopidou FV, Paramythiotou E, Kompoti M, Katsiari M, Mainas E, Nicolaou C, Yphantis D, Antoniadou A, Trikka-Graphakos E, Roussou Z, Clouva P, Maguina N, Kanellakopoulou K, Armaganidis A, Giamarellou H. 2009. Tigecycline in the treatment of infections from multi-drug resistant gram-negative pathogens. J Infect 58:273–284. https://doi.org/10.1016/j.jinf.2009.02.009.
120. Eckmann C, Heizmann WR, Leitner E, von Eiff C, Bodmann KF. 2011. Prospective, non-interventional, multicentre trial of tigecycline in the treatment of severely ill patients with complicated infections: new insights into clinical results and treatment practice. Chemotherapy 57:275–284. https://doi.org/10.1159/000329406.
121. Falagas ME, Maraki S, Karageorgopoulos DE, Katoris AC, Mavromano-lakis E, Samonis G. 2010. Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin. Int J Antimicrob Agents 35:240–243. https://doi.org/10.1016/j.ijantimicag.2009.10.019.
122. Vardakas KZ, Legakis NJ, Triarides N, Falagas ME. 2016. Susceptibility of contemporary isolates to fosfomycin: a systematic review of the literature. Int J Antimicrob Agents 47:269–285. https://doi.org/10.1016/j.ijantimicag.2016.02.001.
123. Pullukcu H, Tasbakan M, Sipahi OR, Yamazhan T, Aydemir S, Ulusoy S. 2007. Fosfomycin in the treatment of extended spectrum beta-lactamase-producing Escherichia coli-related lower urinary tract infections. Int J Antimicrob Agents 29:62–65. https://doi.org/10.1016/j.ijantimicag.2006.08.039.
124. Rodríguez-Baño J, Alcalá JC, Cisneros JM, Grill F, Oliver A, Horcajada JP, Tórtola T, Mirelis B, Navarro G, Cuenca M, Esteve M, Peña C, Llanos AC, Cantón R, Pascual A. 2008. Community infections caused by extended- spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med 168:1897–1902. https://doi.org/10.1001/archinte.168.17.1897.
125. Senol S, Tasbakan M, Pullukcu H, Sipahi OR, Sipahi H, Yamazhan T, Arda B, Ulusoy S. 2010. Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother 22:355–357. https://doi.org/10.1179/joc.2010.22.5.355.
126. Falagas ME, Kastoris AC, Kapaskelis AM, Karagoergopoulos DE. 2010. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 10:43–50. https://doi.org/10.1016/S1473-3099(09)70325-1.
127. Grabein B, Graninger W, Rodríguez Baño J, Dinh A, Liesenfeld DB. 2017. Intravenous fosfomycin—back to the future. Systematic review and meta-analysis of the clinical literature. Clin Microbiol Infect 23:363–372. https://doi.org/10.1016/j.cmi.2016.12.005.
128. Karageorgopoulos DE, Wang R, Yu XY, Falagas ME. 2012. Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. J Antimicrob Chemother 67:255–268. https://doi.org/10.1093/jac/dkr466.
129. Docobo-Pérez F, Drusano GL, Johnson A, Goodwin J, Whalley S, Ramos-Martín V, Ballestero-Tellez M, Rodriguez-Martinez JM, Conejo MC, van Guilder M, Rodríguez-Baño J, Pascual A, Hope WW. 2015. Pharmacodynamics of fosfomycin: insights into clinical use for antimicrobial resistance. Antimicrob Agents Chemother 59:5602–5610. https://doi.org/10.1128/AAC.00752-15.
130. VanScoy BD, McCauley J, Ellis-Grosse EJ, Okusanya OO, Bhavnani SM, Forrest A, Ambrose PG. 2015. Exploration of the pharmacokinetic-pharmacodynamic relationships for fosfomycin efficacy using an in vitro infection model. Antimicrob Agents Chemother 59:7170–7177. https://doi.org/10.1128/AAC.04955-14.
131. Kaye KS, Rice LB, Dane A, Stus V, Sagan O, Fedosiuk E, Das A, Skarinsky D, Eckburg PB, Ellis-Grosse EJ. 2017. Intravenous fosfomycin (ZTI-01) for the treatment of complicated urinary tract infections (cUTI) including acute pyelonephritis (AP): results from a multi-center, randomized, double-blind phase 2/3 study in hospitalized adults (ZEUS), abstr 1845. IDWeek.
132. Rosso-Fernández C, Sojo-Dorado J, Barriga A, Lavín-Alconero L, Palacios Z, López-Hernández I, Merino V, Camean M, Pascual A, Rodríguez-Baño J. 2015. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ Open 5:e007363. https://doi.org/10.1136/bmjopen-2014-007363.
133. Rodríguez-Martínez JM, Machuca J, Cano ME, Calvo J, Martínez-Martínez L, Pascual A. 2016. Plasmid-mediated quinolone resistance: two decades on. Drug Resist Updat 29:13–29. https://doi.org/10.1016/j.drup.2016.09.001.
134. Tumbarello M, Sanguinetti M, Montuori E, Trecarichi EM, Posteraro B, Fiori B, Citton R, D’Inzeo T, Fadda G, Cauda R, Spanu T. 2007. Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment. Antimicrob Agents Chemother 51:1987–1994. https://doi.org/10.1128/AAC.01509-06.
135. Endimiani A, Luzzaro F, Perilli M, Lombardi G, Colì A, Tamborini A, Amicosante G, Toniolo A. 2004. Bacteremia due to Klebsiella pneumoniae isolates producing the TEM-52 extended-spectrum beta-lactamase: treatment outcome of patients receiving imipenem or ciprofloxacin. Clin Infect Dis 38:243–251. https://doi.org/10.1086/380645.
136. Rodríguez-Martínez JM, Pichardo C, García I, Pachón-Ibañez ME, Docobo-Pérez F, Pascual A, Pachón J, Martínez-Martínez L. 2008. Activity of ciprofloxacin and levofloxacin in experimental pneumonia caused by Klebsiella pneumoniae deficient in porins, expressing active efflux and producing QnrA1. Clin Microbiol Infect 14:691–697. https://doi.org/10.1111/j.1469-0691.2008.02020.x.
137. Allou N, Cambau E, Massias L, Chau F, Fantin B. 2009. Impact of low-level resistance to fluoroquinolones due to qnrA1 and qnrS1 genes or a gyrA mutation on ciprofloxacin bactericidal activity in a murine model of Escherichia coli urinary tract infection. Antimicrob Agents Chemother 53:4292–4297. https://doi.org/10.1128/AAC.01664-08.
138. Briales A, Rodríguez-Martínez JM, Velasco C, Díaz de Alba P, Domínguez-Herrera J, Pachón J, Pascual A. 2011. In vitro effect of qnrA1, qnrB1, and qnrS1 genes on fluoroquinolone activity against isogenic Escherichia coli isolates with mutations in gyrA and parC. Antimicrob Agents Chemother 55:1266–1269. https://doi.org/10.1128/AAC.00927-10.
139. Jakobsen L, Cattoir V, Jensen KS, Hammerum AM, Nordmann P, Frimodt-Møller N. 2012. Impact of low-level fluoroquinolone resistance genes qnrA1, qnrB19 and qnrS1 on ciprofloxacin treatment of isogenic Escherichia coli strains in a murine urinary tract infection model. J Antimicrob Chemother 67:2438–2444. https://doi.org/10.1093/jac/dks224.
140. Domínguez-Herrera J, Velasco C, Docobo-Pérez F, Rodríguez-Martínez JM, López-Rojas R, Briales A, Pichardo C, Díaz-de-Alba P, Rodríguez-Baño J, Pascual A, Pachón J. 2013. Impact of qnrA1, qnrB1 and qnrS1 on the efficacy of ciprofloxacin and levofloxacin in an experimental pneumonia model caused by Escherichia coli with or without the GyrA mutation Ser83Leu. J Antimicrob Chemother 68:1609–1615. https://doi.org/10.1093/jac/dkt063.
141. Daoud Z, Sokhn ES, Azar E, Masri K, Doron S. 2014. Mutant prevention concentrations of ciprofloxacin against urinary isolates of Escherichia coli and Klebsiella pneumoniae. J Infect Dev Ctries 8:154–159. https://doi.org/10.3855/jidc.3164.
142. Liao CH, Hsueh PR, Jacoby GA, Hooper DC. 2013. Risk factors and clinical characteristics of patients with qnr-positive Klebsiella pneumoniae bacteraemia. J Antimicrob Chemother 68:2907–2914. https://doi.org/10.1093/jac/dkt295.
143. Lee CC, Lui G, Ip M, Ling TK, Lee N. 2012. Frequent detection of plasmid-mediated quinolone resistance (qnr) genes in multidrug-resistant Enterobacteriaceae blood isolates, Hong Kong. Eur J Clin Microbiol Infect Dis 31:3183–3189. https://doi.org/10.1007/s10096-012 -1683-x.
144. Chong YP, Choi SH, Kim ES, Song EH, Lee EJ, Park KH, Cho OH, Kim SH, Lee SO, Kim MN, Jeong JY, Woo JH, Kim YS. 2010. Bloodstream infections caused by qnr-positive Enterobacteriaceae: clinical and microbiologic characteristics and outcomes. Diagn Microbiol Infect Dis 67: 70–77. https://doi.org/10.1016/j.diagmicrobio.2009.12.003.
145. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. 2012. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 25:682–707. https://doi.org/10.1128/CMR.05035-11.
146. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K, Livermore DM, Maya JJ, Nordmann P, Patel JB, Paterson DL, Pitout J, Villegas MV, Wang H, Woodford N, Quinn JP. 2013. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13:785–796. https://doi.org/10.1016/S1473-3099(13)70190-7.
147. Pitout JD, Nordmann P, Poirel L. 2015. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 59:5873–5884. https://doi.org/10.1128/AAC.01019-15.
148. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. 2016. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context treatment options, and detection methods. Front Microbiol 7:895. https://doi.org/10.3389/fmicb.2016.00895.
149. Rodríguez-Baño J, Cisneros JM, Gudiol C, Martínez JA. 2014. Treatment of infections caused by carbapenemase-producing Enterobacteriaceae. Enferm Infecc Microbiol Clin 32(Suppl 4):S49–S55. https://doi.org/10.1016/S0213-005X(14)70174-0.
150. Delgado-Valverde M, Sojo-Dorado J, Pascual A, Rodríguez-Baño J. 2013. Clinical management of infections caused by multidrug-resistant Enterobacteriaceae. Ther Adv Infect Dis 1:49–69. https://doi.org/10.1177/2049936113476284.
151. Morrill HJ, Pogue JM, Kaye KS, LaPlante KL. 2015. Treatment options for carbapenem-resistant Enterobacteriaceae infections. Open Forum Infect Dis 2:ofv050. https://doi.org/10.1093/ofid/ofv050.
152. Falagas ME, Karageorgopoulos DE, Nordmann P. 2011. Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes. Future Microbiol 6:653–666. https://doi.org/10.2217/fmb.11.49.
153. Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. 2011. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 37:415–419. https://doi.org/10.1016/j.ijantimicag.2011.01.012.
154. Ahn C, Syed A, Hu F, O’Hara JA, Rivera JI, Doi Y. 2014. Microbiological features of KPC-producing Enterobacter isolates identified in a U.S. hospital system. Diagn Microbiol Infect Dis 80:154–158. https://doi.org/10.1016/j.diagmicrobio.2014.06.010.
155. NDM-5, causing a complicated urinary tract infection in a patient from the United States. mBio 7:e01191-16. https://doi.org/10.1128/mBio.01191-16.
156. Murri R, Fiori B, Spanu T, Mastrorosa I, Giovannenze F, Taccari F, Palazzolo C, Scoppettuolo G, Ventura G, Sanguinetti M, Cauda R, Fan-toni M. 2017. Trimethoprim-sulfamethoxazole therapy for patients with carbapenemase-producing Klebsiella pneumoniae infections: retrospective single-center case series. Infection 45:209–213. https://doi.org/10.1007/s15010-016-0968-x.
157. Perez F, El Chakhtoura NG, Papp-Wallace KM, Wilson BM, Bonomo RA. 2016. Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply “precision medicine” to antimicrobial chemotherapy? Expert Opin Pharmacother 17:761–781. https://doi.org/10.1517/14656566.2016.1145658.
158. Cobo J, Morosini MI, Pintado V, Tato M, Samaranch N, Baquero F, Cantón R. 2008. Use of tigecycline for the treatment of prolonged bacteremia due to a multiresistant VIM-1 and SHV-12 beta-lactamase-producing Klebsiella pneumoniae epidemic clone. Diagn Microbiol Infect Dis 60:319–322. https://doi.org/10.1016/j.diagmicrobio.2007.09.017.
159. Tascini C, Urbani L, Biancofiore G, Rossolini GM, Leonildi A, Gemignani G, Bindi ML, Mugnaioli C, Filipponi F, Menichetti F. 2008. Colistin in combination with rifampin and imipenem for treating a blaVIM-1 metallo-beta-lactamase-producing Enterobacter cloacae disseminated infection in a liver transplant patient. Minerva Anestesiol 74:47–49.
160. Souli M, Rekatsina PD, Chryssouli Z, Galani I, Giamarellou H, Kanellakopoulou K. 2009. Does the activity of the combination of imipenem and colistin in vitro exceed the problem of resistance in metallo-beta-lactamase-producing Klebsiella pneumoniae isolates? Antimicrob Agents Chemother 53:2133–2135. https://doi.org/10.1128/AAC.01271-08.
161. Souli M, Galani I, Boukovalas S, Gourgoulis MG, Chryssouli Z, Kanellakopoulou K, Panagea T, Giamarellou H. 2011. In vitro interactions of antimicrobial combinations with fosfomycin against KPC-2-producing Klebsiella pneumoniae and protection of resistance development. Antimicrob Agents Chemother 55:2395–2397. https://doi.org/10.1128/AAC.01086-10.
162. Wiskirchen DE, Koomanachai P, Nicasio AM, Nicolau DP, Kuti JL. 2011. In vitro pharmacodynamics of simulated pulmonary exposures of tigecycline alone and in combination against Klebsiella pneumoniae isolates producing a KPC carbapenemase. Antimicrob Agents Chemother 55: 1420–1427. https://doi.org/10.1128/AAC.01253-10.
163. Elemam A, Rahimian J, Doymaz M. 2010. In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase-producing Klebsiella pneumoniae. J Clin Microbiol 48:3558–3562. https://doi.org/10.1128/JCM.01106-10.
164. Bulik CC, Nicolau DP. 2010. In vivo efficacy of simulated human dosing regimens of prolonged-infusion doripenem against carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 54: 4112–4115. https://doi.org/10.1128/AAC.00026-10.
165. Le J, McKee B, Srisupha-Olarn W, Burgess DS. 2011. In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae. J Clin Med Res 3:106–110. https://doi.org/10.4021/jocmr551w.
166. Berçot B, Poirel L, Dortet L, Nordmann P. 2011. In vitro evaluation of antibiotic synergy for NDM-1-producing Enterobacteriaceae. J Antimicrob Chemother 66:2295–2297. https://doi.org/10.1093/jac/dkr296.
167. Samonis G, Maraki S, Karageorgopoulos DE, Vouloumanou EK, Falagas ME. 2012. Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis 31:695–701. https://doi.org/10.1007/s10096-011 -1360-5.
168. Pankey GA, Ashcraft DS. 2011. Detection of synergy using the combination of polymyxin B with either meropenem or rifampin against carbapenemase-producing Klebsiella pneumoniae. Diagn Microbiol Infect Dis 70:561–564. https://doi.org/10.1016/j.diagmicrobio.2011.05.003.
169. Jernigan MG, Press EG, Nguyen MH, Clancy CJ, Shields RK. 2012. The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneu- moniae. Antimicrob Agents Chemother 56:3395–3398. https://doi.org/10.1128/AAC.06364-11.
170. Hirsch EB, Guo B, Chang KT, Cao H, Ledesma KR, Singh M, Tam VH. 2013. Assessment of antimicrobial combinations for Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. J Infect Dis 207: 786–793. https://doi.org/10.1093/infdis/jis766.
171. Tascini C, Tagliaferri E, Giani T, Leonildi A, Flammini S, Casini B, Lewis R, Ferranti S, Rossolini GM, Menichetti F. 2013. Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 57:3990–3993. https://doi.org/10.1128/AAC.00179-13.
172. Lee GC, Burgess DS. 2013. Polymyxins and doripenem combination against KPC-producing Klebsiella pneumoniae. J Clin Med Res 5:97–100. https://doi.org/10.4021/jocmr1220w.
173. Hong JH, Clancy CJ, Cheng S, Shields RK, Chen L, Doi Y, Zhao Y, Perlin DS, Kreiswirth BN, Nguyen MH. 2013. Characterization of porin expression in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae identifies isolates most susceptible to the combination of colistin and carbapenems. Antimicrob Agents Chemother 57: 2147–2153. https://doi.org/10.1128/AAC.02411-12.
174. Nastro M, Rodríguez CH, Monge R, Zintgraff J, Neira L, Rebollo M, Vay C, Famiglietti A. 2014. Activity of the colistin-rifampicin combination against colistin-resistant, carbapenemase-producing Gram-negative bacteria. J Chemother 26:211–216. https://doi.org/10.1179/1973947813Y.0000000136.
175. Demiraslan H, Dinc G, Ahmed SS, Elmali F, Metan G, Alp E, Doganay M. 2014. Carbapenem-resistant Klebsiella pneumoniae sepsis in corticoste-roid receipt mice: tigecycline or colistin monotherapy versus tigecycline/colistin combination. J Chemother 26:276–281. https://doi.org/10.1179/1973947813Y.0000000143.
176. Michail G, Labrou M, Pitiriga V, Manousaka S, Sakellaridis N, Tsakris A, Pournaras S. 2013. Activity of tigecycline in combination with colistin, meropenem, rifampin, or gentamicin against KPC-producing Enterobacteriaceae in a murine thigh infection model. Antimicrob Agents Chemother 57:6028–6033. https://doi.org/10.1128/AAC.00891-13.
177. Gaibani P, Lombardo D, Lewis RE, Mercuri M, Bonora S, Landini MP, Ambretti S. 2014. In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates. J Antimicrob Chemother 69:1856–1865. https://doi.org/10.1093/jac/dku065.
178. Clancy CJ, Hao B, Shields RK, Chen L, Perlin DS, Kreiswirth BN, Nguyen MH. 2014. Doripenem, gentamicin, and colistin, alone and in combinations, against gentamicin-susceptible, KPC-producing Klebsiella pneumoniae strains with various ompK36 genotypes. Antimicrob Agents Chemother 58:3521–3525. https://doi.org/10.1128/AAC.01949-13.
179. Tängdén T, Hickman RA, Forsberg P, Lagerbäck P, Giske CG, Cars O. 2014. Evaluation of double- and triple-antibiotic combinations for VIM-and NDM-producing Klebsiella pneumoniae by in vitro time-kill experiments. Antimicrob Agents Chemother 58:1757–1762. https://doi.org/10.1128/AAC.00741-13.
180. Chua NG, Zhou YP, Tan TT, Lingegowda PB, Lee W, Lim TP, Teo J, Cai Y, Kwa AL. 2015. Polymyxin B with dual carbapenem combination therapy against carbapenemase-producing Klebsiella pneumoniae. J Infect 70:309–311. https://doi.org/10.1016/j.jinf.2014.10.001.
181. Maraki S, Papadakis IS. 2015. Evaluation of antimicrobial combinations against colistin-resistant carbapenemase (KPC)-producing Klebsiella pneumoniae. J Chemother 27:348–352. https://doi.org/10.1179/1973947814Y.0000000218.
182. Toledo PV, Tuon FF, Arend L, Aranha AA, Jr. 2014. Efficacy of tigecycline, polymyxin, gentamicin, meropenem and associations in experimental Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae non-lethal sepsis. Braz J Infect Dis 18:574–575. https://doi.org/10.1016/j.bjid.2014.05.003.
183. Krishnappa LG, Marie MA, Al Sheikh YA. 2015. Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and in vitro synergy of the colistin-meropenem combination. J Chemother 27:277–282. https://doi.org/10.1179/1973947814Y.0000000197.
184. Oliva A, Mascellino MT, Cipolla A, D’Abramo A, De Rosa A, Savinelli S, Ciardi MR, Mastroianni CM, Vullo V. 2015. Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe infections: short-course treatment with colistin increases the in vivo and in vitro activity of double carbapenem regimen. Int J Infect Dis 33:132–134. https://doi.org/10.1016/j.ijid.2015.01.011.
185. Shields RK, Nguyen MH, Potoski BA, Press EG, Chen L, Kreiswirth BN, Clarke LG, Eschenauer GA, Clancy CJ. 2015. Doripenem MICs and ompK36 porin genotypes of sequence type 258, KPC-producing Klebsiella pneumoniae may predict responses to carbapenem-colistin combination therapy among patients with bacteremia. Antimicrob Agents Chemother 59:1797–1801. https://doi.org/10.1128/AAC.03894-14.
186. Ji S, Lv F, Du X, Wei Z, Fu Y, Mu X, Jiang Y, Yu Y. 2015. Cefepime combined with amoxicillin/clavulanic acid: a new choice for the KPC-producing K. pneumoniae infection. Int J Infect Dis 38:108–114. https://doi.org/10.1016/j.ijid.2015.07.024.
187. Stein C, Makarewicz O, Bohnert JA, Pfeifer Y, Kesselmeier M, Hagel S, Pletz MW. 2015. Three dimensional checkerboard synergy analysis of colistin, meropenem, tigecycline against multidrug-resistant clinical Klebsiella pneumoniae isolates. PLoS One 10:e0126479. https://doi.org/10.1371/journal.pone.0126479.
188. Nakamura I, Sakamoto N, Ida Y, Imai R, Aoki K, Ando R, Yamaguchi T, Matsumura H, Matsumoto T. 2015. Combination therapy against poly-microbial infection, including by NDM-1-producing Enterobacteriaceae resistant to colistin. Antimicrob Agents Chemother 59:5092–5093. https://doi.org/10.1128/AAC.00746-15.
189. Abdul Rahim N, Cheah SE, Johnson MD, Yu H, Sidjabat HE, Boyce J, Butler MS, Cooper MA, Fu J, Paterson DL, Nation RL, Bergen PJ, Velkov T, Li J. 2015. Synergistic killing of NDM-producing MDR Klebsiella pneumoniae by two ‘old’ antibiotics—polymyxin B and chloramphenicol. J Antimicrob Chemother 70:2589–2597. https://doi.org/10.1093/jac/dkv135.
190. Salloum NA, Kissoyan KA, Fadlallah S, Cheaito K, Araj GF, Wakim R, Kanj S, Kanafani Z, Dbaibo G, Matar GM. 2015. Assessment of combination therapy in BALB/c mice injected with carbapenem-resistant Enterobacteriaceae strains. Front Microbiol 6:999. https://doi.org/10.3389/fmicb.2015.00999.
191. Rodríguez-Avial I, Pena I, Picazo JJ, Rodríguez-Avial C, Culebras E. 2015. In vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline against carbapenemase-producing Enterobacteriaceae strains. Int J Antimicrob Agents 46:616–621. https://doi.org/10.1016/j.ijantimicag.2015.07.021.
192. Albur MS, Noel A, Bowker K, MacGowan A. 2015. The combination of colistin and fosfomycin is synergistic against NDM-1-producing Enterobacteriaceae in vitro pharmacokinetic/pharmacodynamic model experiments. Int J Antimicrob Agents 46:560–567. https://doi.org/10.1016/j.ijantimicag.2015.07.019.
193. Gagetti P, Pasteran F, Martinez MP, Fatouraei M, Gu J, Fernandez R, Paz L, Rose WE, Corso A, Rosato AE. 2016. Modeling meropenem treatment, alone and in combination with daptomycin, for KPC-producing Klebsiella pneumoniae strains with unusually low carbapenem MICs. Antimicrob Agents Chemother 60:5047–5050. https://doi.org/10.1128/AAC.00168-16.
194. Albiero J, Sy SK, Mazucheli J, Caparroz-Assef SM, Costa BB, Alves JL, Gales AC, Tognim MC. 2016. Pharmacodynamic evaluation of the potential clinical utility of fosfomycin and meropenem in combination therapy against KPC-2-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 60:4128–4139. https://doi.org/10.1128/AAC.03099-15.
195. Ni W, Wei C, Zhou C, Zhao J, Liang B, Cui J, Wang R, Liu Y. 2016. Tigecycline-amikacin combination effectively suppresses the selection of resistance in clinical isolates of KPC-producing Klebsiella pneumoniae. Front Microbiol 7:1304. https://doi.org/10.3389/fmicb.2016.01304.
196. Laishram S, Anandan S, Devi BY, Elakkiya M, Priyanka B, Bhuvaneshwari T, Peter JV, Subramani K, Balaji V. 2016. Determination of synergy between sulbactam, meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance. J Chemother 28: 297–303. https://doi.org/10.1080/1120009X.2016.1143261.
197. Lagerbäck P, Khine WW, Giske CG, Tängdén T. 2016. Evaluation of antibacterial activities of colistin, rifampicin and meropenem combinations against NDM-1-producing Klebsiella pneumoniae in 24 h in vitro time-kill experiments. J Antimicrob Chemother 71:2321–2325. https://doi.org/10.1093/jac/dkw213.
198. Sharma R, Patel S, Abboud C, Diep J, Ly NS, Pogue JM, Kaye KS, Li J, Rao GG. 2017. Polymyxin B in combination with meropenem against carbapenemase-producing Klebsiella pneumoniae: pharmacodynamics and morphological changes. Int J Antimicrob Agents 49:224–232. https://doi.org/10.1016/j.ijantimicag.2016.10.025.
199. de Maio Carrillho CM, Gaudereto JJ, Martins RC, de Castro Lima VA, de Oliveira LM, Urbano MR, Perozin JS, Levin AS, Costa SF. 2017. Colistin-resistant Enterobacteriaceae infections: clinical and molecular characterization and analysis of in vitro synergy. Diagn Microbiol Infect Dis 87:253–257. https://doi.org/10.1016/j.diagmicrobio.2016.11.007.
200. Diep JK, Jacobs DM, Sharma R, Covelli J, Bowers DR, Russo TA, Rao GG. 2017. Polymyxin B in combination with rifampin and meropenem against polymyxin B-resistant KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 61:e02121-16. https://doi.org/10.1128/AAC.02456-16.
201. Ozbek B, Mataracı-Kara E, Er S, Ozdamar M, Yilmaz M. 2015. In vitro activities of colistin, tigecycline and tobramycin, alone or in combination, against carbapenem-resistant Enterobacteriaceae strains. J Glob Antimicrob Resist 3:278–282. https://doi.org/10.1016/j.jgar.2015.09.001.
202. Huang D, Yu B, Diep JK, Sharma R, Dudley M, Monteiro J, Kaye KS, Pogue JM, Abboud CS, Rao GG. 2017. In vitro assessment of combined polymyxin B and minocycline therapy against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Antimicrob Agents Chemother 61:e00073-17. https://doi.org/10.1128/AAC.00073-17.
203. Oliva A, Scorzolini L, Cipolla A, Mascellino MT, Cancelli F, Castaldi D, D’Abramo A, D’Agostino C, Russo G, Ciardi MR, Mastroianni CM, Vullo V. 2017. In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: the activity of the double-carbapenem regimen is related to meropenem MIC value. J Antimicrob Chemother 72:1981–1984. https://doi.org/10.1093/jac/dkx084.
204. Zhou YF, Tao MT, Feng Y, Yang RS, Liao XP, Liu YH, Sun J. 2017. Increased activity of colistin in combination with amikacin against Escherichia coli co-producing NDM-5 and MCR-1. J Antimicrob Chemother 72:1723–1730. https://doi.org/10.1093/jac/dkx038.
205. Tseng SP, Wang SF, Ma L, Wang TY, Yang TY, Siu LK, Chuang YC, Lee PS, Wang JT, Wu TL, Lin JC, Lu PL. 2017. The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan. J Microbiol Immunol Infect 50:653–661. https://doi.org/10.1016/j.jmii.2017.03.003.
206. Yu W, Zhou K, Guo L, Ji J, Niu T, Xiao T, Shen P, Xiao Y. 2017. In vitro pharmacokinetics/pharmacodynamics evaluation of fosfomycin combined with amikacin or colistin against KPC2-producing Klebsiella pneumoniae. Front Cell Infect Microbiol 7:246. https://doi.org/10.3389/fcimb.2017.00246.
207. Yu W, Shen P, Bao Z, Zhou K, Zheng B, Ji J, Guo L, Huang C, Xiao Y. 2017. In vitro antibacterial activity of fosfomycin combined with other antimicrobials against KPC-producing Klebsiella pneumoniae. Int J Antimicrob Agents 50:237–241. https://doi.org/10.1016/j.ijantimicag.2017.03.011.
208. Wenzler E, Deraedt MF, Harrington AT, Danizger LH. 2017. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. Diagn Microbiol Infect Dis 88:352–354. https://doi.org/10.1016/j.diagmicrobio.2017.05.009.
209. Fredborg M, Sondergaard TE, Wang M. 2017. Synergistic activities of meropenem double and triple combinations against carbapenemase-producing Enterobacteriaceae. Diagn Microbiol Infect Dis 88:355–360. https://doi.org/10.1016/j.diagmicrobio.2017.04.015.
210. Zhao M, Bulman ZP, Lenhard JR, Satlin MJ, Kreiswirth BN, Walsh TJ, Marrocco A, Bergen PJ, Nation RL, Li J, Zhang J, Tsuji BT. 2017. Pharmacodynamics of colistin and fosfomycin: a ‘treasure trove’ combination combats KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother 72:1985–1990. https://doi.org/10.1093/jac/dkx070.
211. Zusman O, Avni T, Leibovici L, Adler A, Friberg L, Stergiopoulou T, Carmeli Y, Paul M. 2013. Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems. Antimicrob Agents Chemother 57:5104–5111. https://doi.org/10.1128/AAC.01230-13.
212. Balkan II, Aygün G, Aydın S, Mutcalı SI, Kara Z, Kuşkucu M, Midilli K, Şemen V, Aras S, Yemişen M, Mete B, Özaras R, Saltoğlu N, Tabak F, Öztürk R. 2014. Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival. Int J Infect Dis 26:51–56. https://doi.org/10.1016/j.ijid.2014.05.012.
213. Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M, Venditti M, Bordi E, Capozzi D, Balice MP, Tarasi A, Parisi G, Lappa A, Carattoli A, Petrosillo N, SEERBIO-GRAB Network. 2013. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect 19:E23–E30. https://doi.org/10.1111/1469-0691.12070.
214. Daikos GL, Tsaousi S, Tzouvelekis LS, Anyfantis I, Psichogiou M, Argy-ropoulou A, Stefanou I, Sypsa V, Miriagou V, Nepka M, Georgiadou S, Markogiannakis A, Goukos D, Skoutelis A. 2014. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 58:2322–2328. https://doi.org/10.1128/AAC.02166-13.
215. de Oliveira MS, de Assis DB, Freire MP, Boas do Prado GV, Machado AS, Abdala E, Pierrotti LC, Mangini C, Campos L, Caiaffa Filho HH, Levin AS. 2015. Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins. Clin Microbiol Infect 21:179.e1–179.e7. https://doi.org/10.1016/j.cmi.2014.07.010.
216. Gomez-Simmonds A, Nelson B, Eiras DP, Loo A, Jenkins SG, Whittier S, Calfee DP, Satlin MJ, Kubin CJ, Furuya EY. 2016. Combination regimens for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 60:3601–3607. https://doi.org/10.1128/AAC.03007-15.
217. Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, Venditti M, Tumbarello M, Daikos G, Cantón R, Doi Y, Tuon FF, Karaiskos I, Pérez-Nadales E, Schwaber MJ, Azap Ö, Souli KM, Roilides E, Pournaras S, Akova M, Pérez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodríguez-Baño J, REIPI/ESGBIS/INCREMENT Investigators. 2017. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis 17:726–734. https://doi.org/10.1016/S1473-3099(17)30228-1.
218. Machuca I, Gutiérrez-Gutiérrez B, Gracia-Ahufinger I, Rivera Espinar F, Cano Á, Guzmán-Puche J, Pérez-Nadales E, Natera C, Rodríguez M, León R, Castón JJ, Rodríguez-López F, Rodríguez-Baño J, Torre-Cisneros J. 2017. Mortality associated with bacteremia due to colistin-resistant Klebsiella pneumoniae with high-level meropenem resistance: importance of combination therapy without colistin and carbapenems. Antimicrob Agents Chemother 61:e00406-17. https://doi.org/10.1128/AAC.00406-17.
219. Nabarro LEB, Shankar C, Pragasam AK, Mathew G, Jeyaseelan V, Veera-raghavan B, Verghese VP. 2017. Clinical and bacterial risk factors for mortality in children with carbapenem-resistant Enterobacteriaceae bloodstream infections in India. Pediatr Infect Dis J 36:161–166. https://doi.org/10.1097/INF.0000000000001499.
220. Navarro-San Francisco C, Mora-Rillo M, Romero-Gómez MP, Moreno-Ramos F, Rico-Nieto A, Ruiz-Carrascoso G, Gómez-Gil R, Arribas-López JR, Mingorance J, Paño-Pardo JR. 2013. Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge. Clin Microbiol Infect 19:E72–E79. https://doi.org/10.1111/1469 -0691.12091.
221. Papadimitriou-Olivgeris M, Fligou F, Bartzavali C, Zotou A, Spyropoulou A, Koutsileou K, Vamvakopoulou S, Sioulas N, Karamouzos V, Anastas-siou ED, Spiliopoulou I, Christofidou M, Marangos M. 2017. Carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients: risk factors and predictors of mortality. Eur J Clin Microbiol Infect Dis 36:1125–1131. https://doi.org/10.1007/s10096-017-2899-6.
222. Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y. 2012. Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens. Antimicrob Agents Chemother 56:2108–2113. https://doi.org/10.1128/AAC.06268-11.
223. Satlin MJ, Chen L, Patel G, Gomez-Simmonds A, Weston G, Kim AC, Seo SK, Rosenthal ME, Sperber SJ, Jenkins SG, Hamula CL, Uhlemann AC, Levi MH, Fries BC, Tang YW, Juretschko S, Rojtman AD, Hong T, Mathema B, Jacobs MR, Walsh TJ, Bonomo RA, Kreiswirth BN. 2017. Multicenter clinical and molecular epidemiological analysis of bacteremia due to carbapenem-resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States. Antimicrob Agents Chemother 61: e02349-16. https://doi.org/10.1128/AAC.02349-16.
224. Tofas P, Skiada A, Angelopoulou M, Sipsas N, Pavlopoulou I, Tsaousi S, Pagoni M, Kotsopoulou M, Perlorentzou S, Antoniadou A, Pirou-naki M, Skoutelis A, Daikos GL. 2016. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: anal- ysis of 50 cases. Int J Antimicrob Agents 47:335–339. https://doi.org/10.1016/j.ijantimicag.2016.01.011.
225. Trecarichi EM, Pagano L, Martino B, Candoni A, Di Blasi R, Nadali G, Fianchi L, Delia M, Sica S, Perriello V, Busca A, Aversa F, Fanci R, Melillo L, Lessi F, Del Principe MI, Cattaneo C, Tumbarello M, Haematologic Malignancies Associated Bloodstream Infections Surveillance (HEMA-BIS) Registry-Sorveglianza Epidemiologica Infezioni Funginein Emopa-tie Maligne (SEIFEM) Group, Italy. 2016. Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol 91:1076–1081. https://doi.org/10.1002/ajh.24489.
226. Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M. 2012. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 55:943–950. https://doi.org/10.1093/cid/cis588.
227. Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, Losito AR, Bartoletti M, Del Bono V, Corcione S, Maiuro G, Tedeschi S, Celani L, Cardellino CS, Spanu T, Marchese A, Ambretti S, Cauda R, Viscoli C, Viale P, ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva). 2015. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 70: 2133–2143. https://doi.org/10.1093/jac/dkv086.
228. Villegas MV, Pallares CJ, Escandón-Vargas K, Hernández-Gómez C, Cor-rea A, Álvarez C, Rosso F, Matta L, Luna C, Zurita J, Mejía-Villatoro C, Rodríguez-Noriega E, Seas C, Cortesía M, Guzmán-Suárez A, Guzmán-Blanco M. 2016. Characterization and clinical impact of bloodstream infection caused by carbapenemase-producing Enterobacteriaceae in seven Latin American countries. PLoS One 11:e0154092. https://doi.org/10.1371/journal.pone.0154092.
229. Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, Prekates A, Themeli-Digalaki K, Tsakris A. 2011. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect 17:1798–1803. https://doi.org/10.1111/j.1469-0691.2011.03514.x.
230. Chang YY, Chuang YC, Siu LK, Wu TL, Lin JC, Lu PL, Wang JT, Wang LS, Lin YT, Huang LJ, Fung CP. 2015. Clinical features of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in intensive care units: a nationwide multicenter study in Taiwan. J Microbiol Immunol Infect 48:219–225. https://doi.org/10.1016/j.jmii.2014.05.010.
231. de Maio Carrilho CM, de Oliveira LM, Gaudereto J, Perozin JS, Urbano MR, Camargo CH, Grion CM, Levin AS, Costa SF. 2016. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome. BMC Infect Dis 16:629. https://doi.org/10.1186/s12879-016-1979-z.
232. Díaz A, Ortiz DC, Trujillo M, Garcés C, Jaimes F, Restrepo AV. 2016. Clinical characteristics of carbapenem-resistant Klebsiella pneumoniae infections in ill and colonized children in Colombia. Pediatr Infect Dis J 35:237–241. https://doi.org/10.1097/INF.0000000000000987.
233. Freire MP, Pierrotti LC, Filho HH, Ibrahim KY, Magri AS, Bonazzi PR, Hajar L, Diz MP, Pereira J, Hoff PM, Abdala E. 2015. Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in cancer patients. Eur J Clin Microbiol Infect Dis 34:277–286. https://doi.org/10.1007/s10096-014-2233-5.
234. Katsiari M, Panagiota G, Likousi S, Roussou Z, Polemis M, Alkiviadis Vatopoulos C, Evangelia Platsouka D, Maguina A. 2015. Carbapenem-resistant Klebsiella pneumoniae infections in a Greek intensive care unit: molecular characterisation and treatment challenges. J Glob Antimicrob Resist 3:123–127. https://doi.org/10.1016/j.jgar.2015.01.006.
235. Lowman W, Schleicher G. 2015. Antimicrobial treatment and outcomes of critically ill patients with OXA-48like carbapenemase-producing Enterobacteriaceae infections. Diagn Microbiol Infect Dis 81:138–140. https://doi.org/10.1016/j.diagmicrobio.2014.09.023.
236. Tuon FF, Graf ME, Merlini A, Rocha JL, Stallbaum S, Arend LN, Pecoit-Filho R. 2017. Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae. Braz J Infect Dis 21:1–6. https://doi.org/10.1016/j.bjid.2016.09.008.
237. Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. 2014. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother 58:654–663. https://doi.org/10.1128/AAC.01222-13.
238. Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M. 2017. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother 72:29–39. https://doi.org/10.1093/jac/dkw377.
239. Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, Venditti M, Tumbarello M, Daikos G, Pintado V, Doi Y, Tuon FF, Karaiskos I, Machuca I, Schwaber MJ, Azap Ö, Souli KM, Roilides E, Pournaras S, Akova M, Pérez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodríguez-Baño J, REIPI/ESGBIS/INCREMENT Investigators. 2016. A predictive model of mortality in patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae. Mayo Clin Proc 91:1362–1371. https://doi.org/10.1016/j.mayocp.2016.06.024.
240. Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R. 2013. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis 57:349–358. https://doi.org/10.1093/cid/cit253.
241. Cuzon G, Naas T, Truong H, Villegas MV, Wisell KT, Carmeli Y, Gales AC, Venezia SN, Quinn JP, Nordmann P. 2010. Worldwide diversity of Klebsiella pneumoniae that produce beta-lactamase blaKPC-2 gene. Emerg Infect Dis 16:1349–1356. https://doi.org/10.3201/eid1609.091389.
242. Dautzenberg MJ, Ossewaarde JM, de Kraker ME, van der Zee A, van Burgh S, de Greeff SC, Bijlmer HA, Grundmann H, Cohen Stuart JW, Fluit AC, Troelstra A, Bonten MJ. 2014. Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011. Euro Surveill 19:20723. https://doi.org/10.2807/1560 -7917.ES2014.19.9.20723.
243. Kuti JL, Dandekar PK, Nightingale CH, Nicolau DP. 2003. Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem. J Clin Pharmacol 43:1116–1123. https://doi.org/10.1177/0091270003257225.
244. Daikos GL, Markogiannakis A. 2011. Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems? Clin Microbiol Infect 17:1135–1141. https://doi.org/10.1111/j.1469-0691.2011.03553.x.
245. Giannella M, Trecarichi EM, Giacobbe DR, De FG, Bassetti M, Bartoloni A, Bartoletti M, Losito AR, Del Bono V, Corcione S, Tedeschi S, Raffaelli F, Saffioti C, Spanu T, Rossolini GM, Marchese A, Ambretti S, Cauda R, Viscoli C, Lewis RE, Viale P, Tumbarello M, Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva (ISGRI-SITA). 2017. Effect of combination therapy containing a high dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection. Int J Antimicrob Agents 2017:S0924-8579(17)30311-4. https://doi.org/10.1016/j.ijantimicag.2017.08.019.
246. Wiskirchen DE, Nordmann P, Crandon JL, Nicolau DP. 2013. Efficacy of humanized carbapenem exposures against New Delhi metallo-β-lactamase (NDM-1)-producing Enterobacteriaceae in a murine infection model. Antimicrob Agents Chemother 57:3936–3940. https://doi.org/10.1128/AAC.00708-13.
247. Hagihara M, Crandon JL, Urban C, Nicolau DP. 2013. Efficacy of doripenem and ertapenem against KPC-2-producing and non-KPC-producing Klebsiella pneumoniae with similar MICs. J Antimicrob Chemother 68:1616–1618. https://doi.org/10.1093/jac/dkt056.
248. Anderson KF, Lonsway DR, Rasheed JK, Biddle J, Jensen B, McDougal LK, Carey RB, Thompson A, Stocker S, Limbago B, Patel JB. 2007. Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in Enterobacteriaceae. J Clin Microbiol 45:2723–2725. https://doi.org/10.1128/JCM.00015-07.
249. Bulik CC, Nicolau DP. 2011. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 55:3002–3004. https://doi.org/10.1128/AAC.01420-10.
250. Oliva A, D’Abramo A, D’Agostino C, Iannetta M, Mascellino MT, Gallinelli C, Mastroianni CM, Vullo V. 2014. Synergistic activity and effectiveness of a double-carbapenem regimen in pandrug-resistant Klebsiella pneumoniae bloodstream infections. J Antimicrob Chemother 69: 1718–1720. https://doi.org/10.1093/jac/dku027.
251. Oliva A, Gizzi F, Mascellino MT, Cipolla A, D’Abramo A, D’Agostino C, Trinchieri V, Russo G, Tierno F, Iannetta M, Mastroianni CM, Vullo V. 2016. Bactericidal and synergistic activity of double-carbapenem regimen for infections caused by carbapenemase-producing Klebsiella pneumoniae. Clin Microbiol Infect 22:147–153. https://doi.org/10.1016/j.cmi.2015.09.014.
252. Cprek JB, Gallagher JC. 2015. Ertapenem-containing double-carbapenem therapy for treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother 60:669–673. https://doi.org/10.1128/AAC.01569-15.
253. Souli M, Karaiskos I, Masgala A, Galani L, Barmpouti E, Giamarellou H. 2017. Double-carbapenem combination as salvage therapy for untreat-able infections by KPC-2-producing Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis 36:1305–1315. https://doi.org/10.1007/s10096-017 -2936-5.
254. De Pascale G, Martucci G, Montini L, Panarello G, Cutuli SL, Di Carlo D, Di Gravio V, Di Stefano R, Capitanio G, Vallecoccia MS, Polidori P, Spanu T, Arcadipane A, Antonelli M. 2017. Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case-control study. Crit Care 21:173. https://doi.org/10.1186/s13054-017-1769-z.
255. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL. 2006. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 6:589–601. https://doi.org/10.1016/S1473-3099(06)70580-1.
256. Zavascki AP, Goldani LZ, Li J, Nation RL. 2007. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60:1206–1215. https://doi.org/10.1093/jac/dkm357.
257. Landman D, Georgescu C, Martin DA, Quale J. 2008. Polymyxins revisited. Clin Microbiol Rev 21:449–465. https://doi.org/10.1128/CMR.00006-08.
258. Yahav D, Farbman L, Leibovici L, Paul M. 2012. Colistin: new lessons on an old antibiotic. Clin Microbiol Infect 18:18–29. https://doi.org/10.1111/j.1469-0691.2011.03734.x.
259. Rosso-Fernández C, Garnacho-Montero J, Antonelli M, Dimopoulos G, Cisneros JM, MagicBullet Study Group. 2015. Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics: study protocol for a randomized controlled trial. Trials 16:102. https://doi.org/10.1186/s13063-015-0614-4.
260. Hirsch EB, Tam VH. 2010. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J Antimicrob Chemother 65:1119–1125. https://doi.org/10.1093/jac/dkq108.
261. Dickstein Y, Leibovici L, Yahav D, Eliakim-Raz N, Daikos GL, Skiada A, Antoniadou A, Carmeli Y, Nutman A, Levi I, Adler A, Durante-Mangoni E, Andini R, Cavezza G, Mouton JW, Wijma RA, Theuretzbacher U, Friberg LE, Kristoffersson AN, Zusman O, Koppel F, Dishon Benattar Y, Altunin S, Paul M, AIDA Consortium. 2016. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol. BMJ Open 6:e009956. https://doi.org/10.1136/bmjopen-2015-009956.
262. Bergen PJ, Li J, Nation RL. 2011. Dosing of colistin—back to basic PK/PD. Curr Opin Pharmacol 11:464–469. https://doi.org/10.1016/j.coph.2011.07.004.
263. Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A, Cars O, Giamarellou H. 2009. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother 53:3430–3436. https://doi.org/10.1128/AAC.01361-08.
264. Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL. 2011. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 55:3284–3294. https://doi.org/10.1128/AAC.01733-10.
265. Mohamed AF, Karaiskos I, Plachouras D, Karvanen M, Pontikis K, Jans-son B, Papadomichelakis E, Antoniadou A, Giamarellou H, Armaganidis A, Cars O, Friberg LE. 2012. Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill. Antimicrob Agents Chemother 56:4241–4249. https://doi.org/10.1128/AAC.06426-11.
266. Karaiskos I, Friberg LE, Pontikis K, Ioannidis K, Tsagkari V, Galani L, Kostakou E, Baziaka F, Paskalis C, Koutsoukou A, Giamarellou H. 2015. Colistin population pharmacokinetics after application of a loading dose of 9 MU colistin methanesulfonate in critically ill patients. Antimicrob Agents Chemother 59:7240–7248. https://doi.org/10.1128/AAC.00554-15.
267. EMA. 2017. European Medicines Agency completes review of polymyxin-based medicines. Recommendations issued for safe use in patients with serious infections resistant to standard antibiotics. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals _document/Polymyxin_31/WC500176333.pdf.
268. FDA. 2017. Approved drug products. Label and approval history for Coly-Mycin M, NDA 050108. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050108s030lbl.pdf.
269. Deryke CA, Crawford AJ, Uddin N, Wallace MR. 2010. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother 54:4503–4505. https://doi.org/10.1128/AAC.01707-09.
270. Gibson GA, Bauer SR, Neuner EA, Bass SN, Lam SW. 2015. Influence of colistin dose on global cure in patients with bacteremia due to carbapenem-resistant Gram-negative bacilli. Antimicrob Agents Chemother 60:431–436. https://doi.org/10.1128/AAC.01414-15.
271. Elefritz JL, Bauer KA, Jones C, Mangino JE, Porter K, Murphy CV. 2017. Efficacy and safety of a colistin loading dose, high-dose maintenance regimen in critically ill patients with multidrug-resistant Gram-negative pneumonia. J Intensive Care Med 32:487–493. https://doi.org/10.1177/0885066616646551.
272. Benattar YD, Omar M, Zusman O, Yahav D, Zak-Doron Y, Altunin S, Elbaz M, Daitch V, Granot M, Leibovici L, Paul M. 2016. The effectiveness and safety of high-dose colistin: prospective cohort study. Clin Infect Dis 63:1605–1612. https://doi.org/10.1093/cid/ciw684.
273. Dalfino L, Puntillo F, Ondok MJ, Mosca A, Monno R, Coppolecchia S, Spada ML, Bruno F, Brienza N. 2015. Colistin-associated acute kidney injury in severely ill patients: a step toward a better renal care? A prospective cohort study. Clin Infect Dis 61:1771–1777. https://doi.org/10.1093/cid/civ717.
274. Lee YJ, Wi YM, Kwon YJ, Kim SR, Chang SH, Cho S. 2015. Association between colistin dose and development of nephrotoxicity. Crit Care Med 43:1187–1193. https://doi.org/10.1097/CCM.0000000000000931.
275. Omrani AS, Alfahad WA, Shoukri MM, Baadani AM, Aldalbahi S, Almit-wazi AA, Albarrak AM. 2015. High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia. Ann Clin Microbiol Antimicrob 14:3. https://doi.org/10.1186/s12941-015-0062-8.
276. Vicari G, Bauer SR, Neuner EA, Lam SW. 2013. Association between colistin dose and microbiologic outcomes in patients with multidrug-resistant gram-negative bacteremia. Clin Infect Dis 56:398–404. https://doi.org/10.1093/cid/cis909.
277. Ordooei Javan A, Shokouhi S, Sahraei Z, Salamzadeh J, Azad Armaki S. 2017. Nephrotoxicity of high and conventional dosing regimens of colistin: a randomized clinical trial. Iran J Pharm Res 16:781–790.
278. Nelson BC, Eiras DP, Gomez-Simmonds A, Loo AS, Satlin MJ, Jenkins SG, Whittier S, Calfee DP, Furuya EY, Kubin CJ. 2015. Clinical outcomes associated with polymyxin B dose in patients with bloodstream infections due to carbapenem-resistant Gram-negative rods. Antimicrob Agents Chemother 59:7000–7006. https://doi.org/10.1128/AAC.00844-15.
279. Sandri AM, Landersdorfer CB, Jacob J, Boniatti MM, Dalarosa MG, Falci DR, Behle TF, Bordinhão RC, Wang J, Forrest A, Nation RL, Li J, Zavascki AP. 2013. Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis 57:524–531. https://doi.org/10.1093/cid/cit334.
280. Zavascki AP, Nation RL. 2017. Nephrotoxicity of polymyxins: is there any difference between colistimethate and polymyxin B? Antimicrob Agents Chemother 61:e02319-16. https://doi.org/10.1128/AAC.02319-16.
281. Vardakas KZ, Falagas ME. 2017. Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. Int J Antimicrob Agents 49:233–238. https://doi.org/10.1016/j.ijantimicag.2016.07.023.
282. Kassamali Z, Danziger L. 2015. To B or not to B, that is the question: is it time to replace colistin with polymyxin B? Pharmacotherapy 35: 17–21. https://doi.org/10.1002/phar.1510.
283. Abdelraouf K, He J, Ledesma KR, Hu M, Tam VH. 2012. Pharmacoki- netics and renal disposition of polymyxin B in an animal model. Antimicrob Agents Chemother 56:5724–5727. https://doi.org/10.1128/AAC.01333-12.
284. Thamlikitkul V, Dubrovskaya Y, Manchandani P, Ngamprasertchai T, Boonyasiri A, Babic JT, Tam VH. 2017. Dosing and pharmacokinetics of polymyxin B in patients with renal insufficiency. Antimicrob Agents Chemother 61:e01337-16. https://doi.org/10.1128/AAC.01337-16.
285. López-Cerero L, Egea P, Gracia-Ahufinger I, González-Padilla M, Rodríguez-López F, Rodríguez-Baño J, Pascual A. 2014. Characterisation of the first ongoing outbreak due to KPC-3-producing Klebsiella pneumoniae (ST512) in Spain. Int J Antimicrob Agents 44:538–540. https://doi.org/10.1016/j.ijantimicag.2014.08.006.
286. Rossi Gonçalves I, Ferreira ML, Araujo BF, Campos PA, Royer S, Batistão DW, Souza LP, Brito CS, Urzedo JE, Gontijo-Filho PP, Ribas RM. 2016. Outbreaks of colistin-resistant and colistin-susceptible KPC-producing Klebsiella pneumoniae in a Brazilian intensive care unit. J Hosp Infect 94:322–329. https://doi.org/10.1016/j.jhin.2016.08.019.
287. Mavroidi A, Katsiari M, Likousi S, Palla E, Roussou Z, Nikolaou C, Maguina A, Platsouka ED. 2016. Characterization of ST258 colistin-resistant, blaKPC-producing Klebsiella pneumoniae in a Greek hospital. Microb Drug Resist 22:392–398. https://doi.org/10.1089/mdr.2015.0282.
288. Giacobbe DR, Del Bono V, Trecarichi EM, De Rosa FG, Giannella M, Bassetti M, Bartoloni A, Losito AR, Corcione S, Bartoletti M, Mantengoli E, Saffioti C, Pagani N, Tedeschi S, Spanu T, Rossolini GM, Marchese A, Ambretti S, Cauda R, Viale P, Viscoli C, Tumbarello M, ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva). 2015. Risk factors for bloodstream infections due to colistin-resistant KPC-producing Klebsiella pneumoniae: results from a multicenter case-control-control study. Clin Microbiol Infect 21: 1106.e1–1106.e8. https://doi.org/10.1016/j.cmi.2015.08.001.
289. Weterings V, Zhou K, Rossen JW, van Stenis D, Thewessen E, Kluytmans J, Veenemans J. 2015. An outbreak of colistin-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the Netherlands (July to December 2013), with inter-institutional spread. Eur J Clin Microbiol Infect Dis 34:1647–1655. https://doi.org/10.1007/s10096 -015-2401-2.
290. Falcone M, Russo A, Iacovelli A, Restuccia G, Ceccarelli G, Giordano A, Farcomeni A, Morelli A, Venditti M. 2016. Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Microbiol Infect 22: 444–450. https://doi.org/10.1016/j.cmi.2016.01.016.
291. Rojas LJ, Salim M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Marshall S, Rudin SD, Domitrovic TN, Hujer AM, Hujer KM, Doi Y, Kaye KS, Evans S, Fowler VG, Jr, Bonomo RA, van Duin D, Antibacterial Resistance Leadership Group. 2017. Colistin resistance in carbapenem-resistant Klebsiella pneumoniae: laboratory detection and impact on mortality. Clin Infect Dis 64:711–718. https://doi.org/10.1093/cid/ciw805.
292. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. 2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168. https://doi.org/10.1016/S1473-3099(15)00424-7.
293. Di Pilato V, Arena F, Tascini C, Cannatelli A, Henrici De Angelis L, Fortunato S, Giani T, Menichetti F, Rossolini GM. 2016. mcr-1.2, a new mcr variant carried on a transferable plasmid from a colistin-resistant KPC carbapenemase-producing Klebsiella pneumoniae strain of sequence type 512. Antimicrob Agents Chemother 60: 5612–5615. https://doi.org/10.1128/AAC.01075-16.
294. NDM-1 in Escherichia coli from Venezuela. Antimicrob Agents Chemother 60:6356–6358. https://doi.org/10.1128/AAC.01319-16.
295. NDM-5, causing a complicated urinary tract infection in a patient from the United States. mBio 7:e1191-16. https://doi.org/10.1128/mBio.01191-16.
296. Zhang R, Liu L, Zhou H, Chan EW, Li J, Fang Y, Li Y, Liao K, Chen S. 2017. Nationwide surveillance of clinical carbapenem-resistant Enterobacteriaceae (CRE) strains in China. EBioMedicine 19:98–106. https://doi.org/10.1016/j.ebiom.2017.04.032.
297. Beyrouthy R, Robin F, Lessene A, Lacombat I, Dortet L, Naas T, Ponties V, Bonnet R. 2017. MCR-1 and OXA-48 in vivo acquisition in KPC-producing Escherichia coli after colistin treatment. Antimicrob Agents Chemother 61:e02540-16. https://doi.org/10.1128/AAC.02540-16.
298. Huang TD, Bogaerts P, Berhin C, Hoebeke M, Bauraing C, Glupczynski Y. 2017. Increasing proportion of carbapenemase-producing Enterobacteriaceae and emergence of a MCR-1 producer through a multicentric study among hospital-based and private laboratories in Belgium from September to November 2015. Euro Surveill 22:30530. https://doi.org/10.2807/1560-7917.ES.2017.22.19.30530.
299. Ni W, Han Y, Liu J, Wei C, Zhao J, Cui J, Wang R, Liu Y. 2016. Tigecycline treatment for carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis. Medicine (Baltimore, MD) 95: e3126. https://doi.org/10.1097/MD.0000000000003126.
300. Burkhardt O, Rauch K, Kaever V, Hadem J, Kielstein JT, Welte T. 2009. Tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint. Int J Antimicrob Agents 34:101–102. https://doi.org/10.1016/j.ijantimicag.2009.01.015.
301. Wang J, Pan Y, Shen J, Xu Y. 2017. The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 16:24. https://doi.org/10.1186/s12941-017-0199-8.
302. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. 2013. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother 57:1756–1762. https://doi.org/10.1128/AAC.01232-12.
303. Falagas ME, Vardakas KZ, Tsiveriotis KP, Triarides NA, Tansarli GS. 2014. Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections. Int J Antimicrob Agents 44:1–7. https://doi.org/10.1016/j.ijantimicag.2014.01.006.
304. Di Carlo P, Gulotta G, Casuccio A, Pantuso G, Raineri M, Farulla CA, Bonventre S, Guadagnino G, Ingrassia D, Cocorullo G, Mammina C, Giarratano A. 2013. KPC-3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients. BMC Anesthesiol 13:13. https://doi.org/10.1186/1471-2253-13-13.
305. De Pascale G, Montini L, Pennisi M, Bernini V, Maviglia R, Bello G, Spanu T, Tumbarello M, Antonelli M. 2014. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care 18:R90. https://doi.org/10.1186/cc13858.
306. Balandin Moreno B, Fernández Simón I, Pintado García V, Sánchez Romero I, Isidoro Fernández B, Romera Ortega MA, Alcántara Carmona S, Pérez Redondo M, Galdos Anuncibay P. 2014. Tigecycline therapy for infections due to carbapenemase-producing Klebsiella pneumoniae in critically ill patients. Scand J Infect Dis 46:175–180. https://doi.org/10.3109/00365548.2013.861608.
307. Routsi C, Kokkoris S, Douka E, Ekonomidou F, Karaiskos I, Giamarellou H. 2015. High-dose tigecycline-associated alterations in coagulation parameters in critically ill patients with severe infections. Int J Antimicrob Agents 45:90–93. https://doi.org/10.1016/j.ijantimicag.2014.07.014.
308. Palacios-Baena ZR, Oteo J, Conejo C, Larrosa MN, Bou G, Fernández-Martínez M, González-López JJ, Pintado V, Martínez-Martínez L, Merino M, Pomar V, Mora-Rillo M, Rivera MA, Oliver A, Ruiz-Carrascoso G, Ruiz-Garbajosa P, Zamorano L, Bautista V, Ortega A, Morales I, Pascual Á, Campos J, Rodríguez-Baño J, GEIH-GEMARA (SEIMC) and REIPI Group for CPE. 2016. Comprehensive clinical and epidemiological assessment of colonisation and infection due to carbapenemase-producing Enterobacteriaceae in Spain. J Infect 72:152–160. https://doi.org/10.1016/j.jinf.2015.10.008.
309. Brust K, Evans A, Plemmons R. 2014. Tigecycline in treatment of multidrug-resistant Gram-negative bacillus urinary tract infections: a systematic review. J Antimicrob Chemother 69:2606–2610. https://doi.org/10.1093/jac/dku189.
310. Satlin MJ, Kubin CJ, Blumenthal JS, Cohen AB, Furuya EY, Wilson SJ, Jenkins SG, Calfee DP. 2011. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Antimicrob Agents Chemother 55:5893–5899. https://doi.org/10.1128/AAC.00387-11.
311. van Duin D, Cober E, Richter SS, Perez F, Kalayjian RC, Salata RA, Evans S, Fowler VG, Jr, Kaye KS, Bonomo RA. 2015. Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae. J Antimicrob Chemother 70:1203–1211. https://doi.org/10.1093/jac/dku495.
312. Doi Y, Wachino JI, Arakawa Y. 2016. Aminoglycoside resistance: the emergence of acquired 16S ribosomal RNA methyltransferases. Infect Dis Clin North Am 30:523–537. https://doi.org/10.1016/j.idc.2016.02.011.
313. Li JJ, Sheng ZK, Deng M, Bi S, Hu FS, Miao HF, Ji ZK, Sheng JF, Li LJ. 2012. Epidemic of Klebsiella pneumoniae ST11 clone coproducing KPC-2 and 16S rRNA methylase RmtB in a Chinese university hospital. BMC Infect Dis 12:373. https://doi.org/10.1186/1471-2334-12-373.
314. Mezzatesta ML, Gona F, Caio C, Adembri C, Dell’utri P, Santagati M, Stefani S. 2013. Emergence of an extensively drug-resistant ArmA- and KPC-2-producing ST101 Klebsiella pneumoniae clone in Italy. J Antimicrob Chemother 68:1932–1934. https://doi.org/10.1093/jac/dkt116.
315. Gonzalez-Padilla M, Torre-Cisneros J, Rivera-Espinar F, Pontes-Moreno A, López-Cerero L, Pascual A, Natera C, Rodríguez M, Salcedo I, Rodríguez-López F, Rivero A, Rodríguez-Baño J. 2015. Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae. J Antimicrob Chemother 70:905–913. https://doi.org/10.1093/jac/dku432.
316. Taccone FS, Laterre PF, Spapen H, Dugernier T, Delattre I, Layeux B, De Backer D, Wittebole X, Wallemacq P, Vincent JL, Jacobs F. 2010. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care 14:R53. https://doi.org/10.1186/cc8945.
317. Kato H, Hagihara M, Hirai J, Sakanashi D, Suematsu H, Nishiyama N, Koizumi Y, Yamagishi Y, Matsuura K, Mikamo H. 2017. Evaluation of amikacin pharmacokinetics and pharmacodynamics for optimal initial dosing regimen. Drugs R D 17:177–187. https://doi.org/10.1007/s40268 -016-0165-5.
318. Drusano GL, Louie A. 2011. Optimization of aminoglycoside therapy. Antimicrob Agents Chemother 55:2528–2531. https://doi.org/10.1128/AAC.01314-10.
319. White BP, Lomaestro B, Pai MP. 2015. Optimizing the initial amikacin dosage in adults. Antimicrob Agents Chemother 59:7094–7096. https://doi.org/10.1128/AAC.01032-15.
320. Zazo H, Martín-Suárez A, Lanao JM. 2013. Evaluating amikacin dosage regimens in intensive care unit patients: a pharmacokinetic/ pharmacodynamic analysis using Monte Carlo simulation. Int J Antimicrob Agents 42:155–160. https://doi.org/10.1016/j.ijantimicag.2013.04.021.
321. Brasseur A, Hites M, Roisin S, Cotton F, Vincent JL, De Backer D, Jacobs F, Taccone FS. 2016. A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens: a proof-of-concept study. J Antimicrob Chemother 71:1386–1394. https://doi.org/10.1093/jac/dkv491.
322. Allou N, Bouteau A, Allyn J, Snauwaert A, Valance D, Jabot J, Bouchet B, Galliot R, Corradi L, Montravers P, Augustin P. 2016. Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock. Ann Intensive Care 6:106. https://doi.org/10.1186/s13613-016-0211-z.
323. Choudhury S, Yeng JL, Krishnan PU. 2015. In vitro susceptibilities of clinical isolates of carbapenemase-producing Enterobacteriaceae to fosfomycin and tigecycline. Clin Microbiol Infect 21:e75–e76. https://doi.org/10.1016/j.cmi.2015.06.005.
324. Karageorgopoulos DE, Miriagou V, Tzouvelekis LS, Spyridopoulou K, Daikos GL. 2012. Emergence of resistance to fosfomycin used as adjunct therapy in KPC Klebsiella pneumoniae bacteraemia: report of three cases. J Antimicrob Chemother 67:2777–2779. https://doi.org/10.1093/jac/dks270.
325. Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M, Oikonomou A, Poulakou G, Roilides E, Giamarellou H. 2014. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents 43:52–59. https://doi.org/10.1016/j.ijantimicag.2013.09.010.
326. Adams-Haduch JM, Potoski BA, Sidjabat HE, Paterson DL, Doi Y. 2009. Activity of temocillin against KPC-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother 53:2700–2701. https://doi.org/10.1128/AAC.00290-09.
327. Alexandre K, Chau F, Guérin F, Massias L, Lefort A, Cattoir V, Fantin B. 2016. Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli. J Antimicrob Chemother 71:1899–1904. https://doi.org/10.1093/jac/dkw066.
328. van Dijk K, Voets GM, Scharringa J, Voskuil S, Fluit AC, Rottier WC, Leverstein-Van Hall MA, Cohen Stuart JW. 2014. A disc diffusion assay for detection of class A, B and OXA-48 carbapenemases in Enterobacteriaceae using phenyl boronic acid, dipicolinic acid and temocillin. Clin Microbiol Infect 20:345–349. https://doi.org/10.1111/1469-0691.12322.
329. Woodford N, Pike R, Meunier D, Loy R, Hill R, Hopkins KL. 2014. In vitro activity of temocillin against multidrug-resistant clinical isolates of Escherichia coli, Klebsiella spp. and Enterobacter spp., and evaluation of high-level temocillin resistance as a diagnostic marker for OXA-48 carbapenemase. J Antimicrob Chemother 69:564–567. https://doi.org/10.1093/jac/dkt383.
330. Panagiotakopoulou A, Daikos GL, Miriagou V, Loli A, Tzelepi E, Tzouvelekis LS. 2007. Comparative in vitro killing of carbapenems and aztreonam against Klebsiella pneumoniae producing VIM-1 metallo-beta-lactamase. Int J Antimicrob Agents 29:360–362. https://doi.org/10.1016/j.ijantimicag.2006.11.004.
331. Souli M, Konstantinidou E, Tzepi I, Tsaganos T, Pefanis A, Chryssouli Z, Galani I, Giamarellos-Bourboulis E, Giamarellou H. 2011. Efficacy of carbapenems against a metallo-β-lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model. J Antimicrob Chemother 66:611–617. https://doi.org/10.1093/jac/dkq470.
332. Crandon JL, Nicolau DP. 2013. Human simulated studies of aztreonam and aztreonam-avibactam to evaluate activity against challenging gram-negative organisms, including metallo-β-lactamase producers. Antimicrob Agents Chemother 57:3299–3306. https://doi.org/10.1128/AAC.01989-12.
333. Psichogiou M, Tassios PT, Avlamis A, Stefanou I, Kosmidis C, Platsouka E, Paniara O, Xanthaki A, Toutouza M, Daikos GL, Tzouvelekis LS. 2008. Ongoing epidemic of blaVIM-1-positive Klebsiella pneumoniae in Athens, Greece: a prospective survey. J Antimicrob Chemother 61:59–63. https://doi.org/10.1093/jac/dkm443.
334. Poirel L, Héritier C, Tolün V, Nordmann P. 2004. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 48:15–22. https://doi.org/10.1128/AAC.48.1.15-22.2004.
335. Paño-Pardo JR, Ruiz-Carrascoso G, Navarro-San Francisco C, Gómez-Gil R, Mora-Rillo M, Romero-Gómez MP, Fernández-Romero N, García-Rodríguez J, Pérez-Blanco V, Moreno-Ramos F, Mingorance J. 2013. Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak. J Antimicrob Chemother 68:89–96. https://doi.org/10.1093/jac/dks364.
336. Mimoz O, Grégoire N, Poirel L, Marliat M, Couet W, Nordmann P. 2012. Broad-spectrum β-lactam antibiotics for treating experimental peritonitis in mice due to Klebsiella pneumoniae producing the carbapenemase OXA-48. Antimicrob Agents Chemother 56:2759–2760. https://doi.org/10.1128/AAC.06069-11.
337. Wiskirchen DE, Nordmann P, Crandon JL, Nicolau DP. 2014. Efficacy of humanized carbapenem and ceftazidime regimens against Enterobacteriaceae producing OXA-48 carbapenemase in a murine infection model. Antimicrob Agents Chemother 58:1678–1683. https://doi.org/10.1128/AAC.01947-13.
338. Livermore DM, Mushtaq S, Warner M, Miossec C, Woodford N. 2008. NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum beta-lactamases and carbapenemases. J Antimicrob Chemother 62:1053–1056. https://doi.org/10.1093/jac/dkn320.
339. Stachyra T, Levasseur P, Péchereau MC, Girard AM, Claudon M, Miossec C, Black MT. 2009. In vitro activity of the beta-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother 64:326–329. https://doi.org/10.1093/jac/dkp197.
340. Endimiani A, Choudhary Y, Bonomo RA. 2009. In vitro activity of NXL104 in combination with beta-lactams against Klebsiella pneumoniae isolates producing KPC carbapenemases. Antimicrob Agents Chemother 53:3599–3601. https://doi.org/10.1128/AAC.00641-09.
341. Livermore DM, Mushtaq S, Warner M, Zhang J, Maharjan S, Doumith M, Woodford N. 2011. Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 55:390–394. https://doi.org/10.1128/AAC.00756-10.
342. Aktaş Z, Kayacan C, Oncul O. 2012. In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents 39:86–89. https://doi.org/10.1016/j.ijantimicag.2011.09.012.
343. Endimiani A, Hujer KM, Hujer AM, Pulse ME, Weiss WJ, Bonomo RA. 2011. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 55:82–85. https://doi.org/10.1128/AAC.01198-10.
344. MacVane SH, Crandon JL, Nichols WW, Nicolau DP. 2014. In vivo efficacy of humanized exposures of ceftazidime-avibactam in comparison with ceftazidime against contemporary Enterobacteriaceae isolates. Antimicrob Agents Chemother 58:6913–6919. https://doi.org/10.1128/AAC.03267-14.
345. MacVane SH, Crandon JL, Nichols WW, Nicolau DP. 2014. Unexpected in vivo activity of ceftazidime alone and in combination with avibactam against New Delhi metallo-β-lactamase-producing Enterobacteriaceae in a murine thigh infection model. Antimicrob Agents Chemother 58:7007–7009. https://doi.org/10.1128/AAC.02662-14.
346. Monogue ML, Abbo LM, Rosa R, Camargo JF, Martinez O, Bonomo RA, Nicolau DP. 2017. In vitro discordance with in vivo activity: humanized exposures of ceftazidime-avibactam, aztreonam, and tigecycline alone and in combination against New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae in a murine lung infection model. Antimicrob Agents Chemother 61:e00486-17. https://doi.org/10.1128/AAC.00486-17.
347. Castón JJ, Lacort-Peralta I, Martín-Dávila P, Loeches B, Tabares S, Temkin L, Torre-Cisneros J, Paño-Pardo JR. 2017. Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients. Int J Infect Dis 59:118–123. https://doi.org/10.1016/j.ijid.2017.03.021.
348. Shields RK, Nguyen MH, Chen L, Press EG, Potoski BA, Marini RV, Doi Y, Kreiswirth BN, Clancy CJ. 2017. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother 61:e00883-17. https://doi.org/10.1128/AAC.00883-17.
349. Shields RK, Potoski BA, Haidar G, Hao B, Doi Y, Chen L, Press EG, Kreiswirth BN, Clancy CJ, Nguyen MH. 2016. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis 63:1615–1618. https://doi.org/10.1093/cid/ciw636.
350. Krapp F, Grant JL, Sutton SH, Ozer EA, Barr VO. 2017. Treating complicated carbapenem-resistant Enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation. Int J Antimicrob Agents 49:770–773. https://doi.org/10.1016/j.ijantimicag.2017.01.018.
351. Temkin E, Torre-Cisneros J, Beovic B, Benito N, Giannella M, Gilarranz R, Jeremiah C, Loeches B, Machuca I, Jiménez-Martín MJ, Martínez JA, Mora-Rillo M, Navas E, Osthoff M, Pozo JC, Ramos Ramos JC, Rodriguez M, Sánchez-García M, Viale P, Wolff M, Carmeli Y. 2017. Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms. Antimicrob Agents Chemother 61:e01964-16. https://doi.org/10.1128/AAC.01964-16.
352. King M, Heil E, Kuriakose S, Bias T, Huang V, El-Beyrouty C, McCoy D, Hiles J, Richards L, Gardner J, Harrington N, Biason K, Gallagher JC. 2017. Multicenter study of outcomes with ceftazidime-avibactam in patients with carbapenem-resistant Enterobacteriaceae infections. Antimicrob Agents Chemother 61:e00449-17. https://doi.org/10.1128/AAC.00449-17.
353. van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG, Jr, Paterson DL, Bonomo RA, Evans S, Antibacterial Resistance Leadership Group. 2018. Colistin vs. ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis 66:163–171. https://doi.org/10.1093/cid/cix783.
354. KPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother 61:e02097-16. https://doi.org/10.1128/AAC.02097-16.
355. Shields RK, Nguyen MH, Press EG, Chen L, Kreiswirth BN, Clancy CJ. 2017. Emergence of ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: a case report and review of literature. Open Forum Infect Dis 4:ofx101. https://doi.org/10.1093/ofid/ofx101.
356. Both A, Büttner H, Huang J, Perbandt M, Belmar Campos C, Christner M, Maurer FP, Kluge S, König C, Aepfelbacher M, Wichmann D, Rohde H. 2017. Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J Antimicrob Chemother https://doi.org/10.1093/jac/dkx179.
357. Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG, Jr, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA. 2017. Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae? Antimicrob Agents Chemother 61:e02243-16. https://doi.org/10.1128/AAC.02243-16.
358. Castanheira M, Rhomberg PR, Flamm RK, Jones RN. 2016. Effect of the β-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 60:5454–5458. https://doi.org/10.1128/AAC.00711-16.
359. Castanheira M, Huband MD, Mendes RE, Flamm RK. 2017. Meropenem-vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother 61:e00567-17. https://doi.org/10.1128/AAC.00567-17.
360. Kaye K, Vazquez J, Mathers A, Daikos G, Alexander E, Loutit J, Zhang S, Dudley M, Cornely O. 2017. Clinical outcomes of serious infections due to carbapenem-resistant Enterobacteriaceae (CRE) in TANGO II, a phase 3, randomized, multi-national, open-label trial of meropenem-vaborbactam (M-V) versus best available therapy (BAT), poster 1862. IDWeek.
361. Livermore DM, Mushtaq S, Warner M, Zhang JC, Maharjan S, Doumith M, Woodford N. 2011. Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 66:48–53. https://doi.org/10.1093/jac/dkq408.
362. Zhanel GG, Lawson CD, Zelenitsky S, Findlay B, Schweizer F, Adam H, Walkty A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP, Karlowsky JA. 2012. Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther 10: 459–473. https://doi.org/10.1586/eri.12.25.
363. Almaghrabi R, Clancy CJ, Doi Y, Hao B, Chen L, Shields RK, Press EG, Iovine NM, Townsend BM, Wagener MM, Kreiswirth B, Nguyen MH. 2014. Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and other agents. Antimicrob Agents Chemother 58:4443–4451. https://doi.org/10.1128/AAC.00099-14.
364. Cloutier D, Miller L, Komirenko A, Cebrik D, Krause K, Keepers T, Connolly L, Wagenlehner F. 2017. Plazomicin versus meropenem for the treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP): results of the EPIC Study, abstr OS0250E. Abstr 27th Eur Congr Clin Microbiol Infect Dis. https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=43219.
365. Connolly L, Jubb A, O’Keeffe B, Serio A, Smith A, Gall J, Riddle V, Krause K, Mckinnell J, Zakynthinos E, Daikos GL. 2017. Plazomicin (PLZ) associated with improved survival and safety compared to colistin (CST) in serious carbapenem-resistant Enterobacteriaceae (CRE) infections: results of the CARE Study, abstr OS0250F. Abstr 27th Eur Congr Clin Microbiol Infect Dis. https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=43221.
366. Sutcliffe JA, O’Brien W, Fyfe C, Grossman TH. 2013. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother 57:5548–5558. https://doi.org/10.1128/AAC.01288-13.
367. Livermore DM, Mushtaq S, Warner M, Woodford N. 2016. In vitro activity of eravacycline against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii. Antimicrob Agents Chemother 260: 3840–3844. https://doi.org/10.1128/AAC.00436-16.
368. Zhang Y, Lin X, Bush K. 2016. In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J Antibiot (Tokyo) 69:600–604. https://doi.org/10.1038/ja.2016.73.
369. Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, Sutcliffe JA, Horn P. 2017. Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg 152:224–232. https://doi.org/10.1001/jamasurg.2016.4237.
370. Kohira N, West J, Ito A, Ito-Horiyama T, Nakamura R, Sato T, Rittenhouse S, Tsuji M, Yamano Y. 2016. In vitro antimicrobial activity of a sidero- phore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother 60:729–734. https://doi.org/10.1128/AAC.01695-15.
371. Ito-Horiyama T, Ishii Y, Ito A, Sato T, Nakamura R, Fukuhara N, Tsuji M, Yamano Y, Yamaguchi K, Tateda K. 2016. Stability of novel siderophore cephalosporin S-649266 against clinically relevant carbapenemases. Antimicrob Agents Chemother 60:4384–4386. https://doi.org/10.1128/AAC.03098-15.
372. Falagas ME, Skalidis T, Vardakas KZ, Legakis NJ, Hellenic Cefiderocol Study Group. 2017. Activity of cefiderocol (S-649266) against carbapenem-resistant Gram-negative bacteria collected from inpatients in Greek hospitals. J Antimicrob Chemother 72:1704–1708. https://doi.org/10.1093/jac/dkx049.
373. Kanazawa S, Sato T, Kohira N, Ito-Horiyama T, Tsuji M, Yamano Y. 2017. Susceptibility of imipenem-susceptible but meropenem-resistant bla(IMP-6)-carrying Enterobacteriaceae to various antibacterials, including the siderophore cephalosporin cefiderocol. Antimicrob Agents Chemother 61:e00576-17. https://doi.org/10.1128/AAC.00576-17.
374. Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. 2017. In vitro activity of the siderophore cephalosporin, cefiderocol, against a recent collection of clinically relevant Gram-negative bacilli from North America and Europe, including carbapenem-nonsusceptible isolates (SIDERO-WT-2014 Study). Antimicrob Agents Chemother 61:e00093-17. https://doi.org/10.1128/AAC.00093-17.
375. Dobias J, Dénervaud-Tendon V, Poirel L, Nordmann P. 2017. Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens. Eur J Clin Microbiol Infect Dis 36:2319–2327. https://doi.org/10.1007/s10096-017-3063-z.
376. Katsube T, Wajima T, Ishibashi T, Arjona Ferreira JC, Echols R. 2017. Pharmacokinetic/pharmacodynamic modeling and simulation of cefiderocol, a parenteral siderophore cephalosporin, for dose adjustment based on renal function. Antimicrob Agents Chemother 61: e01381-16. https://doi.org/10.1128/AAC.01381-16.
377. Matsumoto S, Singley CM, Hoover J, Nakamura R, Echols R, Rittenhouse S, Tsuji M, Yamano Y. 2017. Efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli in immunocompetent rat respiratory tract infection models recreating human plasma pharmacokinetics. Antimicrob Agents Chemother 61:e00700-17. https://doi.org/10.1128/AAC.00700-17.
378. Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Arjona Ferreira JC, Ariyasu M, Nagata T. 2017. Cefiderocol compared with imipenem/cirastatin in the treatment of adults with complicated urinary tract infections with or without pyelonephritis or acute uncomplicated pyelonephritis: results from a multicenter, double-blind, randomized study, abstr OS0250D. Abstr 27th Eur Congr Clin Microbiol Infect Dis. https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=43213.
379. Wang X, Zhang F, Zhao C, Wang Z, Nichols WW, Testa R, Li H, Chen H, He W, Wang Q, Wang H. 2014. In vitro activities of ceftazidime-avibactam and aztreonam-avibactam against 372 Gram-negative bacilli collected in 2011 and 2012 from 11 teaching hospitals in China. Antimicrob Agents Chemother 58:1774–1778. https://doi.org/10.1128/AAC.02123-13.
380. Yoshizumi A, Ishii Y, Aoki K, Testa R, Nichols WW, Tateda K. 2015. In vitro susceptibility of characterized β-lactamase-producing Gram-negative bacteria isolated in Japan to ceftazidime-, ceftaroline-, and aztreonam-avibactam combinations. J Infect Chemother 21:148–151. https://doi.org/10.1016/j.jiac.2014.08.028.
381. Li H, Estabrook M, Jacoby GA, Nichols WW, Testa RT, Bush K. 2015. In vitro susceptibility of characterized β-lactamase-producing strains tested with avibactam combinations. Antimicrob Agents Chemother 59:1789–1793. https://doi.org/10.1128/AAC.04191-14.
382. Papp-Wallace KM, Bajaksouzian S, Abdelhamed AM, Foster AN, Winkler ML, Gatta JA, Nichols WW, Testa R, Bonomo RA, Jacobs MR. 2015. Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases. Diagn Microbiol Infect Dis 82:65–69. https://doi.org/10.1016/j.diagmicrobio.2015.02.003.
383. Biedenbach DJ, Kazmierczak K, Bouchillon SK, Sahm DF, Bradford PA. 2015. In vitro activity of aztreonam-avibactam against a global collection of Gram-negative pathogens from 2012 and 2013. Antimicrob Agents Chemother 59:4239–4248. https://doi.org/10.1128/AAC.00206-15.
384. Vasoo S, Cunningham SA, Cole NC, Kohner PC, Menon SR, Krause KM, Harris KA, De PP, Koh TH, Patel R. 2015. In vitro activities of ceftazidime-avibactam, aztreonam-avibactam, and a panel of older and contemporary antimicrobial agents against carbapenemase-producing Gram-negative bacilli. Antimicrob Agents Chemother 59:7842–7846. https:// doi.org/10.1128/AAC.02019-15.
385. Dupont H, Gaillot O, Goetgheluck AS, Plassart C, Emond JP, Lecuru M, Gaillard N, Derdouri S, Lemaire B, Girard de Courtilles M, Cattoir V, Mammeri H. 2015. Molecular characterization of carbapenem-nonsusceptible enterobacterial isolates collected during a prospective interregional survey in France and susceptibility to the novel ceftazidime-avibactam and aztreonam-avibactam combinations. Antimicrob Agents Chemother 60:215–221. https://doi.org/10.1128/AAC.01559-15.
386. Sy SK, Beaudoin ME, Zhuang L, Löblein KI, Lux C, Kissel M, Tremmel R, Frank C, Strasser S, Heuberger JA, Mulder MB, Schuck VJ, Derendorf H. 2016. In vitro pharmacokinetics/pharmacodynamics of the combination of avibactam and aztreonam against MDR organisms. J Antimicrob Chemother 71:1866–1880. https://doi.org/10.1093/jac/dkw082.
387. KPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother 60:4490–4500. https://doi.org/10.1128/AAC.00107-16.
388. Mischnik A, Baumert P, Hamprecht A, Rohde A, Peter S, Feihl S, Knob-loch J, Gölz H, Kola A, Obermann B, Querbach C, Willmann M, Gebhardt F, Tacconelli E, Gastmeier P, Seifert H, Kern WV, DZIF-ATHOS Study Group. 2017. Susceptibility to cephalosporin combinations and aztreonam/avibactam among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission. Int J Antimicrob Agents 49:239–242. https://doi.org/10.1016/j.ijantimicag.2016.10.013.
389. Hirsch EB, Ledesma KR, Chang KT, Schwartz MS, Motyl MR, Tam VH. 2012. In vitro activity of MK-7655, a novel β-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria. Antimicrob Agents Chemother 56:3753–3757. https://doi.org/10.1128/AAC.05927-11.
390. Livermore DM, Warner M, Mushtaq S. 2013. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 68:2286–2290. https://doi.org/10.1093/jac/dkt178.
391. Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, Quale J. 2015. Activity of imipenem with relebactam against Gram- negative pathogens from New York City. Antimicrob Agents Chemother 59:5029–5031. https://doi.org/10.1128/AAC.00830-15.
392. Lob SH, Hackel MA, Kazmierczak KM, Hoban DJ, Young K, Motyl MR, Karlowsky JA, Sahm DF. 2017. In vitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015—results from the SMART global surveillance program. Diagn Microbiol Infect Dis 88: 171–176. https://doi.org/10.1016/j.diagmicrobio.2017.02.018.
393. Lob SH, Hackel MA, Kazmierczak KM, Young K, Motyl MR, Karlowsky JA, Sahm DF. 2017. In vitro activity of imipenem-relebactam against Gram-negative ESKAPE pathogens isolated by clinical laboratories in the United States in 2015 (results from the SMART global surveillance program). Antimicrob Agents Chemother 61:e02209-16. https://doi.org/10.1128/AAC.02209-16.
394. Haidar G, Clancy CJ, Chen L, Samanta P, Shields RK, Kreiswirth BN, Nguyen MH. 2017. Identifying spectra of activity and therapeutic niches for ceftazidime-avibactam and imipenem-relebactam against carbapenem-resistant Enterobacteriaceae. Antimicrob Agents Chemother 61:e00642-17. https://doi.org/10.1128/AAC.00642-17.
395. Hecker SJ, Reddy KR, Totrov M, Hirst GC, Lomovskaya O, Griffith DC, King P, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Clifton MC, Atkins K, Raymond A, Potts KT, Abendroth J, Boyer SH, Loutit JS, Morgan EE, Durso S, Dudley MN. 2015. Discovery of a cyclic boronic acid β-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem 58:3682–3692. https://doi.org/10.1021/acs.jmedchem.5b00127.
396. Giamarellou H, Poulakou G. 2011. Pharmacokinetic and pharmacodynamic evaluation of tigecycline. Expert Opin Drug Metab Toxicol 7:1459–1470. https://doi.org/10.1517/17425255.2011.623126.
397. Davido B, Fellous L, Lawrence C, Maxime V, Rottman M, Dinh A. 2017. Ceftazidime-avibactam and aztreonam an interesting strategy to overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 61:e01008-17. https://doi.org/10.1128/AAC.01008-17.
398. Bidair M, Zervos M, Sagan O, Zaitsev V, Loutit JS, Dudley MN, Vazquez J. 2017. Clinical outcomes in adults with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP) in TANGO 1, a phase 3 randomized, double-blind, double-dummy trial comparing meropenem-vaborbactam (M-V) with piperacillin-tazobactam (P-T), abstr P1289. Abstr 27th Eur Congr Clin Microbiol Infect Dis. https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid= 40121.