An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

Erlangga Yusuf, Hannelore I Bax, Nelianne J Verkaik, Mireille van Westreenen, Erlangga Yusuf, Hannelore I Bax, Nelianne J Verkaik, Mireille van Westreenen

Abstract

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

Keywords: CPE; ESBL; gram-negative bacteria; new antibiotics.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Vincent J.-L., Rello J., Reinhart K., Marshall J.K., Silva E., Anzueto A., Martin C.D., Moreno R., Lipman J., EPIC II Group of Investigators et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–2329. doi: 10.1001/jama.2009.1754.
    1. Tacconelli E., Carrara E., Savoldi A., Harbarth S., Mendelson M., Monnet D.L., Pulcini C., Kahlmeter G., Kluytmans J., Carmeli Y., et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 2018;18:318–327. doi: 10.1016/S1473-3099(17)30753-3.
    1. Bush K. Past and present perspectives on β-lactamases. Antimicrob. Agents Chemother. 2018;62:01076-18. doi: 10.1128/AAC.01076-18.
    1. Walsh T.R., Toleman M.A., Poirel L., Nordmann P. Metallo-β-lactamases: The quiet before the storm? Clin. Microbiol. Rev. 2005;18:306–325. doi: 10.1128/CMR.18.2.306-325.2005.
    1. Munoz-Price L.S., Poirel L.A., Bonomo R., Schwaber M.J., Daikos G.L., Cormican M., Cornaglia G., Garau J., Gniadkowski M., Hayden M.K., et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect. Dis. 2013;13:785–796. doi: 10.1016/S1473-3099(13)70190-7.
    1. Poirel L., Potron A., Nordmann P. OXA-48-like carbapenemases: The phantom menace. J. Antimicrob. Chemother. 2012;67:1597–1606. doi: 10.1093/jac/dks121.
    1. Glasner C., Albiger B., Buist G., Tambić A.A., Canton R., Carmeli Y. Carbapenemase-producing Enterobacte-riaceae in Europe: A survey among national experts from 39 countries, February 2013. Eurosurveillance. 2013;18:20525. doi: 10.2807/1560-7917.ES2013.18.28.20525.
    1. Wang R., Van Dorp L., Shaw L.P., Bradley P., Wang Q., Wang X., Jin L., Zhang Q., Liu Y., Rieux A., et al. The global distribution and spread of the mobilized colistin resistance gene mcr-1. Nat. Commun. 2018;9:1–9. doi: 10.1038/s41467-018-03205-z.
    1. Shaeer K.M., Zmarlicka M.T., Chahine E.B., Piccicacco N., Cho J.C. Plazomicin: A next-generation aminoglycoside. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2019;39:77–93. doi: 10.1002/phar.2203.
    1. Eljaaly K., Alharbi A., AlShehri S., Ortwine J.K., Pogue J.M. Plazomicin: A novel aminoglycoside for the treatment of resistant gram-negative bacterial infections. Drugs. 2019;79:243–269. doi: 10.1007/s40265-019-1054-3.
    1. Tang H.-J., Lai C.-C. Plazomicin-associated nephrotoxicity. Clin. Infect. Dis. 2019;71:1130–1131. doi: 10.1093/cid/ciz1064.
    1. Castanheira M., Deshpande L.M., Woosley L.N., Serio A.W., Krause K.M., Flamm R.K. Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes and other resistance mechanisms. J. Antimicrob. Chemother. 2018;73:3346–3354. doi: 10.1093/jac/dky344.
    1. Zhanel G.G., Adam H.J., Baxter M.R., Fuller J.A., Nichol K., Denisuik A.J., Golden A.R., Hink R., Lagacé-Wiens P.R.S., Walkty A., et al. 42936 pathogens from Canadian hospitals: 10 years of results (2007–16) from the CANWARD surveillance study. J. Antimicrob. Chemother. 2019;74:iv5–iv21. doi: 10.1093/jac/dkz283.
    1. Jacobs M.R., Good C.E., Patel R., Arias C.A., Kreiswirth B.N., Rojas L.J., D’Souza R., White R.C., Brinkac L.M., Nguyen K., et al. Argonaut II study of the in vitro activity of plazomicin against carbapenemase-producing klebsiella pneumoniae. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.00012-20.
    1. Castanheira M., Sader H.S., Mendes R.E., Jones R.N. Activity of plazomicin tested against enterobacterales isolates collected from U.S. Hospitals in 2016–2017: Effect of different breakpoint criteria on susceptibility rates among aminoglycosides. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.02418-19.
    1. Cox G., Ejim L., Wright G.D., Stogios P.J., Koteva K., Bordeleau E., Evdokimova E., Sieron A.O., Savchenko A., Serio A.W., et al. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect. Dis. 2018;4:980–987. doi: 10.1021/acsinfecdis.8b00001.
    1. Denervaud-Tendon V., Poirel L.E., Connolly L., Krause K.M., Nordmann P. Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates. J. Antimicrob. Chemother. 2017;72:2787–2791. doi: 10.1093/jac/dkx239.
    1. Wagenlehner F.M.E., Cloutier D.J., Komirenko A.S., Cebrik D.S., Krause K.M., Keepers T.R., Connolly E., Miller L.G., Friedland I., Dwyer J.P., et al. Once-daily plazomicin for com-plicated urinary tract infections. N. Engl. J. Med. 2019;380:729–740. doi: 10.1056/NEJMoa1801467.
    1. Connolly L.E., Riddle V., Cebrik D., Armstrong E.S., Miller L.G. A multicenter, randomized, double-blind, phase 2 study of the efficacy and safety of plazomicin compared with levofloxacin in the treatment of complicated urinary tract infection and acute pyelonephritis. Antimicrob. Agents Chemother. 2018;62 doi: 10.1128/AAC.01989-17.
    1. McKinnell J.A., Dwyer J.P., Talbot G.H., Connolly L.E., Friedland I., Smith A., Jubb A.M., Serio A.W., Klause K.M., Daikos G.L. Plazomicin for infections caused by car-bapenem-resistant Enterobacteriaceae. N. Engl. J. Med. 2019;380:791–793. doi: 10.1056/NEJMc1807634.
    1. Portsmouth S., van Veenhuyzen D., Echols R., Machida M., Ferreira J.C.A., Ariyasu M., Tenke P., Nagata T.D. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: A phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect. Dis. 2018;18:1319–1328. doi: 10.1016/S1473-3099(18)30554-1.
    1. Carmeli Y., Armstrong J., Laud P.J., Newell P., Stone G., Wardman A., Gasink L.B. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): A randomised, pathogen-directed, phase 3 study. Lancet Infect. Dis. 2016;16:661–673. doi: 10.1016/s1473-3099(16)30004-4.
    1. Wagenlehner F.M., Sobel J.D., Newell P., Armstrong J., Huang X., Stone G.G., Yates K., Gasink L.B. Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: Recapture, a phase 3 randomized trial program. Clin. Infect. Dis. 2016;63:754–762. doi: 10.1093/cid/ciw378.
    1. Popejoy M.W., Paterson D.L., Cloutier D., Huntington J.A., Miller B., Bliss C.A., Steenbergen J.N., Hershberger E., Umeh O., Kaye K.S. 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. 2016;72:268–272. doi: 10.1093/jac/dkw374.
    1. Wagenlehner F.M., Umeh O., Steenbergen J., Yuan G., Darouiche R.O. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: A randomised, double-blind, phase 3 trial (ASPECT-cUTI) Lancet. 2015;385:1949–1956. doi: 10.1016/S0140-6736(14)62220-0.
    1. Kaye K.S., Bhowmick T., Metallidis S., Bleasdale S.C., Sagan O.S., Stus V., Vasquez J., Zaitsev V., Bidair M., Giamarellos-Bourboulis E.J., et al. Effect of meropenem-vaborbactam vs piperacil-lin-Tazobactam on clinical cure or improvement and microbial eradication in complicated urinary tract infection the TANGO I randomized clinical trial. JAMA J. Am. Med. Assoc. 2018;319:788–789. doi: 10.1001/jama.2018.0438.
    1. Wunderink R.G., Giamarellos-Bourboulis E.J., Rahav G., Mathers A.J., Bassetti M., Vazquez J., Cornely O.A., Solomkin J., Bhowmick T., Kaye K.S., et al. Effect and Safety of Meropenem–Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial. Infect Dis Ther. 2018;7:439–455. doi: 10.1007/s40121-018-0214-1.
    1. Motsch J., De Oliveira C.M., Du J., Joeng H.-K., Tipping R.W., Aggrey A., Young K., Kartsonis N.A., Butterton J.R., Paschke A., et al. Restore-imi 1: A multicenter, randomized, double-blind trial comparing efficacy and safety of imipenem/Relebactam vs colistin plus imipenem in patients with imipenem-nonsusceptible bacterial infections. Clin. Infect. Dis. 2020;70:1799–1808. doi: 10.1093/cid/ciz530.
    1. Heaney M., Mahoney M.V., Gallagher J.C. Eravacycline: The tetracyclines strike back. Ann. Pharmacother. 2019;53:1124–1135. doi: 10.1177/1060028019850173.
    1. Zhanel G.G., Baxter M.R., Adam H.J., Sutcliffe J., Karlowsky J.A. In vitro activity of eravacycline against 2213 Gram-negative and 2424 Gram-positive bacterial pathogens isolated in Canadian hospital laboratories: CANWARD surveillance study 2014–2015. Diagn. Microbiol. Infect. Dis. 2018;91:55–62. doi: 10.1016/j.diagmicrobio.2017.12.013.
    1. Livermore D.M., Mushtaq B.S., Warner A.M., Woodforda A.N. In vitro activity of eravacycline against carbapenem-Resistant enterobacteriaceae and acinetobacter baumannii. Antimicrob. Agents Chemother. 2016;60:3840–3844. doi: 10.1128/AAC.00436-16.
    1. Johnston B.D., Thuras P., Porter S.B., Anacker M., VonBank B., Vagnone P.S., Witwer M., Castanheira M., Johnsonet J.R. Activity of cefiderocol, ceftazidime-avibactam, and eravacycline against carbapenem-resistant escherichia coli isolates from the united states and international sites in re-lation to clonal background, resistance genes, coresistance, and region. Antimicrob. Agents Chemother. 2020;64:e00797-20. doi: 10.1128/AAC.00797-20.
    1. Fyfe C., LeBlanc G., Close B., Nordmann P., Dumas J., Grossman T.H. Eravacycline is active against bacterial isolates expressing the polymyxin resistance gene mcr-1. Antimicrob. Agents Chemother. 2016;60:6989–6990. doi: 10.1128/AAC.01646-16.
    1. Solomkin J.S., Gardovskis J., Lawrence K., Montravers P., Sway A., Evans D., Tsai L. Ignite4: Results of a phase 3, randomized, multicenter, prospective trial of eravacycline vs meropenem in the treatment of complicated intraabdominal infections. Clin. Infect. Dis. 2018;69:921–929. doi: 10.1093/cid/ciy1029.
    1. Solomkin J., Evans D., Slepavicius A., Lee P., Marsh A., Tsai L., Sutcliffe J.A., Horn A. Assessing the efficacy and safety of Eravacycline vs Ertapenem in complicated intra-abdominal infections in the investigating gram-negative infections treated with erava-cycline (IGNITE 1) trial a randomized clinical trial. JAMA Surg. 2017;152:224–232. doi: 10.1001/jamasurg.2016.4237.
    1. Alosaimy S., Molina K.C., Claeys K.C., Andrade J., Truong J., King M.A., Pullinger M.B., Huang G., Morrisette T., Lagnf A.M., et al. Early experience with eravacycline for complicated infections. Open For. Infect. Dis. 2020;7:ofaa071. doi: 10.1093/ofid/ofaa071.
    1. Qin X., Tran B.G., Kim M.J., Wang L., Nguyen D.A., Chen Q., Song J., Laud P.J., Store G.G., Chow J.W. A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia. Int. J. Antimicrob. Agents. 2017;49:579–588. doi: 10.1016/j.ijantimicag.2017.01.010.
    1. Mazuski J.E., Gasink L.B., Armstrong J., Broadhurst H., Stone G.G., Rank D., Llorens L., Newell P., Pachl J. Efficacy and safety of ceftazidime-avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infection: Results from a randomized, controlled, double-blind, phase 3 program. Clin. Infect. Dis. 2016;62:1380–1389. doi: 10.1093/cid/ciw133.
    1. Lucasti C., Hershberger E., Miller B., Yankelev S., Steenbergen J., Friedland I., Solomkin J. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrob. Agents Chemother. 2014;58:5350–5357. doi: 10.1128/AAC.00049-14.
    1. Miller B., Popejoy M.W., Hershberger E., Steenbergen J.N., Alverdy J. Characteristics and outcomes of complicated in-tra-abdominal infections involving Pseudomonas aeruginosa from a randomized, double-blind, phase 3 ceftolozane-tazobactam study. Antimicrob. Agents Chemother. 2016;60:4387–4390. doi: 10.1128/AAC.03074-15.
    1. Solomkin J., Hershberger E., Eckmann C., Miller B., Popejoy M., Friedland I., Steenbergen J., Yoon M., Collins S., Yuan G., et al. Ceftolozane/Tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: Results from a randomized, double-blind, phase 3 trial (Aspect-ciai) Clin. Infect. Dis. 2015;60:1462–1471. doi: 10.1093/cid/civ097.
    1. Livermore D.M., Tulkens P.M. Temocillin revived. J. Antimicrob. Chemother. 2008;63:243–245. doi: 10.1093/jac/dkn511.
    1. Balakrishnan I., Awad-El-Kariem F.M., Aali A., Kumari P., Mulla R., Tan B., Brudney D., Ladenheim D., Ghazy A., Khan I., et al. Temocillin use in England: Clinical and mi-crobiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC β-lactamase-producing En-terobacteriaceae. J. Antimicrob. Chemother. 2011;66:2628–2631. doi: 10.1093/jac/dkr317.
    1. Adams-Haduch J.M., Paterson D.L., Doi Y., Potoski B.A., Sidjabat H.E. Activity of Temocillin against KPC-Producing Klebsiella pneumoniae and Escherichia coli. Antimicrob. Agents Chemother. 2009;53:2700–2701. doi: 10.1128/AAC.00290-09.
    1. Tsakris A., Koumaki V., Politi L., Balakrishnan I., Tsakris A. Activity of temocillin against KPC-producing Enterobacteriaceae clinical isolates. Int. J. Antimicrob. Agents. 2020;55:105843. doi: 10.1016/j.ijantimicag.2019.10.024.
    1. Zhanel G.G., Golden A.R., Lagacé-Wiens P.R.S., Walkty A.J., Noreddin A., Iii J.P.L., Karlowsky J.A., Zelenitsky S., Wiebe K., Lawrence C.K., et al. Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant gram-negative bacilli. Drugs. 2019;79:271–289. doi: 10.1007/s40265-019-1055-2.
    1. Bassetti M., Echols R., Matsunaga Y., Ariyasu M., Doi Y., Ferrer R., Lodise T.P., Naas T., Niki Y., Paterson D.L., et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): A randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect. Dis. 2021;21:226–240. doi: 10.1016/S1473-3099(20)30796-9.
    1. Jacobs M.R., Abdelhamed A.M., Kreiswirth B.N., Greco C., Fouts D.E., Bonomo R.A., Good C.E., Rhoads D.D., Hujer K.M., Hujer A.M., et al. Argonaut-I: Activity of cefiderocol (S-649266), a siderophore cephalosporin, against gram-negative bacteria, including carbapenem-resistant nonfermenters and enterobacteriaceae with defined extended-spectrum β-lactamases and carbapenemases. Antimicrob. Agents Chemother. 2018;63 doi: 10.1128/AAC.01801-18.
    1. Kresken M., Korte-Berwanger M., Gatermann S.G., Pfeifer Y., Pfennigwerth N., Seifert H., Werner G. In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany. Int. J. Antimicrob. Agents. 2020;56:106128. doi: 10.1016/j.ijantimicag.2020.106128.
    1. Kresken M., Körber-Irrgang B., Pfeifer Y., Werner G. Activity of temocillin against CTX-M-producing Escherichia coli and Klebsiella pneumoniae from Germany. Int. J. Antimicrob. Agents. 2018;51:159–160. doi: 10.1016/j.ijantimicag.2017.06.014.
    1. Wunderink R.G., Matsunaga Y., Ariyasu M., Clevenbergh P., Echols R., Kaye K.S., Kollef M., Menon A., Pogue J.M., Nagata T.D., et al. Cefiderocol versus high-dose, extend-ed-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): A randomised, dou-ble-blind, phase 3, non-inferiority trial. Lancet. Infect. Dis. 2021;21:213–225. doi: 10.1016/S1473-3099(20)30731-3.
    1. Falcone M., Tiseo G., Menichetti F., Nicastro M., Leonildi A., Vecchione A., Casella C., Forfori F., Malacarne P., Guarracino F., et al. Cefiderocol as rescue therapy for acinetobacter baumannii and other carbapenem-resistant gram-negative infections in intensive care unit patients. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa1410.
    1. van Duin D., Bonomo R.A. Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-lactamase inhibitor combinations. Clin. Infect. Dis. 2016;63:234–241. doi: 10.1093/cid/ciw243.
    1. Wong D., van Duin D. Novel beta-lactamase inhibitors: Unlocking their potential in therapy. Drugs. 2017;77:615–628. doi: 10.1007/s40265-017-0725-1.
    1. Sader H.S., Flamm R.K., Carvalhaes C.G., Castanheira M. Comparison of ceftazidime-avibactam and ceftolozane-tazobactam in vitro activities when tested against gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2017–2018) Diagn. Microbiol. Infect. Dis. 2020;96:114833. doi: 10.1016/j.diagmicrobio.2019.05.005.
    1. Zhanel G.G., Lawrence C.K., Adam H., Schweizer F., Zelenitsky S., Zhanel M., Lagacé-Wiens R.S., Walkty A., Denisuik A., Golden A., et al. Imipenem–relebactam and meropenem–vaborbactam: Two novel carbapenem-β-lactamase inhibitor combinations. Drugs. 2018;78:65–98. doi: 10.1007/s40265-017-0851-9.
    1. Sader H.S., Carvalhaes C.G., Streit J.M., Doyle T.B., Castanheira M. Antimicrobial activity of ceftazidime-avibactam, ceftolozane-tazobactam and comparators tested against pseudomonas aeruginosa and klebsiella pneumoniae isolates from united states medical centers in 2016–2018. Microb. Drug Resist. 2020 doi: 10.1089/mdr.2020.0217.
    1. Mirza H.C., Hortaç E., Koçak A.A., Demirkaya M.H., Yayla B., Güçlü A.Ü., Başustaoğlu A. In vitro activity of ceftolozane–tazobactam and ceftazidime–avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study. J. Glob. Antimicrob. Resist. 2020;20:334–338. doi: 10.1016/j.jgar.2019.09.016.
    1. Torres A., Zhong N., Pachl J., Timsit J.-F., Kollef M., Chen Z., Song J., Taylor D., Laud P.J., Stone G.G., et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): A randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect. Dis. 2018;18:285–295. doi: 10.1016/S1473-3099(17)30747-8.
    1. Zhong H., Zhao X.-Y., Zhang Z.-L., Gu Z.-C., Zhang C., Gao Y., Cui M. Evaluation of the efficacy and safety of ceftazidime/avibactam in the treatment of Gram-negative bacterial infections: A systematic review and meta-analysis. Int. J. Antimicrob. Agents. 2018;52:443–450. doi: 10.1016/j.ijantimicag.2018.07.004.
    1. Stone G.G., Newell P., Gasink L.B., Broadhurst H., Wardman A., Yates K., Chen Z., Song J., Chow J.W. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: Pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J. Antimicrob. Chemother. 2018;73:2519–2523. doi: 10.1093/jac/dky204.
    1. Kollef M.H., Nováček M., Kivistik Ü., Réa-Neto Á., Shime N., Martin-Loeches I., Timsit J.-F., Wunderink R.G., Burno C.J., Rhee E.G., et al. Ceftolozane–tazobactam versus mero-penem for treatment of nosocomial pneumonia (ASPECT-NP): A randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect. Dis. 2019;19:1299–1311. doi: 10.1016/S1473-3099(19)30403-7.
    1. Titov I., Wunderink R.G., Roquilly A., Rodríguez Gonzalez D., David-Wang A., Boucher. H.W., Kaye K.S., Losada M.C., Du J., Tipping R., et al. A randomized, double-blind, multicenter trial comparing efficacy and safety of imipenem/Cilastatin/Relebactam versus piperacil-lin/Tazobactam in adults with hospital-acquired or ventilator-associated bacterial pneumonia (Restore-imi 2 study) Clin. Infect. Dis. 2020:ciaa803. doi: 10.1093/cid/ciaa803.
    1. Shortridge D., Castanheira M., Pfaller M.A., Flamm R.K. Ceftolozane-tazobactam activity against pseudomonas aeruginosa clinical isolates from U.S. Hospitals: Report from the pacts antimicrobial surveillance program, 2012 to 2015. Antimicrob. Agents Chemother. 2017;61:e00465-17. doi: 10.1128/AAC.00465-17.
    1. Kuo S.-C., Liu C.-E., Lu P.-L., Chen Y.-S., Lu M.-C., Ko W.-C., Hsueh P.-R., Chuang Y.-C., Wang F.-D. Activity of ceftolozane-tazobactam against Gram-negative pathogens isolated from lower respiratory tract infections in the Asia-Pacific region: SMART 2015–2016. Int. J. Antimicrob. Agents. 2020;55:105883. doi: 10.1016/j.ijantimicag.2020.105883.
    1. Karlowsky J.A., Hackel M.A., Bouchillon S.K., Sahm D.F. In vitro activity of WCK 5222 (Cefepime-zidebactam) against worldwide collected gram-negative bacilli not susceptible to carbapenems. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.01432-20.
    1. Sader H.S., Carvalhaes C.G., Duncan L.R., Flamm R.K., Shortridge D. Susceptibility trends of ceftolozane/tazobactam and comparators when tested against European Gram-negative bacterial surveillance isolates collected during 2012–18. J. Antimicrob. Chemother. 2020;75:2907–2913. doi: 10.1093/jac/dkaa278.
    1. Pogue J.M., Kaye K.S., Veve M.P., Patel T.S., Gerlach A.T., Davis S.L., Puzniak L.A., File T.M., Olson S., Perez F., et al. Ceftolozane/tazobactam vs polymyxin or aminogly-coside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa. Clin. Infect. Dis. 2020;71:304–310. doi: 10.1093/cid/ciz816.
    1. Castón J.J., Gallo M., García M., Cano A., Escribano A., Machuca I., Gracia-Aufinger I., Guzman-Puche J., Pérez-Nadales E., Recio M., et al. Ceftazidime-avibactam in the treatment of infections caused by KPC-producing Klebsiella pneumoniae: Factors associated with clinical efficacy in a single-center cohort. Int. J. Antimicrob. Agents. 2020;56:106075. doi: 10.1016/j.ijantimicag.2020.106075.
    1. Gallagher J.C., Satlin M.J., Claeys K.C., Hiles J., Vyas N.M., Bland C.M., Suh J., Biason K., McCoy D., A King M., et al. Ceftolozane-tazobactam for the treatment of multidrug-resistant pseudomonas aeruginosa infections: A multicenter study. Open Forum Infect. Dis. 2018;5:ofy280. doi: 10.1093/ofid/ofy280.
    1. Sheffield M., Nelson D., O’Neal M., Gould A.P., Bouchard J., Nicolau D., Bookstaver P.B. Use of continuous-infusion ceftolozane/tazobactam for resistant Gram-negative bacterial infections: A retrospective analysis and brief review of the literature. Int. J. Antimicrob. Agents. 2020;56:106158. doi: 10.1016/j.ijantimicag.2020.106158.
    1. Bassetti M., Vena A., Giacobbe D.R., Falcone M., Tiseo G., Giannella M., Pascale R., Meschiari M., DiGaetano M., Oliva A., et al. Ceftolozane/Tazobactam for treatment of severe ESBL-producing enterobacterales infections: A multicenter nationwide clinical experience (CEFTABUSE II Study) Open Forum Infect. Dis. 2020;7:ofaa139. doi: 10.1093/ofid/ofaa139.
    1. Arakawa S., Kawahara K., Kawahara M., Yasuda M., Fujimoto G., Sato A., Yokokawa R., Yoshinari T., Rhee E.G., Aoyama N. The efficacy and safety of tazobac-tam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. J. Infect. Chemother. 2019;25:104–110. doi: 10.1016/j.jiac.2018.10.009.
    1. Ackley R., Roshdy D., Meredith J., Minor S., Anderson W.E., Capraro G.A., Polk C. Meropenem-vaborbactam versus ceftazidime-avibactam for treatment of carbapenem-resistant enterobacteriaceae infections. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.02313-19.
    1. Alosaimy S., Jorgensen S.C.J., Athans V., Saw S., Yost C.N., Davis S.L., Rybak M.J., Lagnf A.M., Melvin S., Mynatt R.P., et al. Real-world multicenter analysis of clinical outcomes and safety of meropenem-vaborbactam in patients treated for serious gram-negative bacterial infections. Open Forum Infect. Dis. 2020;7:ofaa051. doi: 10.1093/ofid/ofaa051.
    1. Shields R.K., McCreary E.K., Nguyen M.H., Marini R.V., Kline E.G., Jones E.C., Hao B., Chen L., Kreiswirth B.N., Doi Y., et al. Early experience with meropenem-vaborbactam for treatment of carbapenem-resistant enterobacteriaceae infections. Clin. Infect. Dis. 2020;71:667–671. doi: 10.1093/cid/ciz1131.
    1. Castanheira M., Doyle T.B., Kantro V., Mendes R.E., Shortridge D. Meropenem-vaborbactam activity against car-bapenem-resistant enterobacterales isolates collected in U.S. Hospitals during 2016 to 2018. Antimicrob. Agents Chemother. 2020;64:e01951-19.
    1. Lapuebla A., Abdallah M., Olafisoye O., Cortes C., Urban C., Landman D., Quale J. Activity of imipenem with relebactam against gram-negative pathogens from New York city. Antimicrob. Agents Chemother. 2015;59:5029–5031. doi: 10.1128/AAC.00830-15.
    1. Lob S.H., Hackel M.A., Kazmierczak K.M., Hoban D.J., Young K., Motyl M.R., Karlowsky J.A., Sahm D.F. 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. 2017;88:171–176. doi: 10.1016/j.diagmicrobio.2017.02.018.
    1. Canver M.C., Satlin M.J., Westblade L.F., Kreiswirth B.N., Chen L., Robertson A., Fauntleroy K., La Spina M., Callan K., Jenkins S.G. Activity of imipenem-relebactam and comparator agents against genetically characterized isolates of carbapenem-resistant enterobacteriaceae. Antimicrob. Agents Chemother. 2019;63 doi: 10.1128/AAC.00672-19.
    1. Kaye K.S., Boucher H.W., Paschke A., Brown M.L., Aggrey A., Khan I., Joeng H.-K., Tipping R.W., Du J., Young K., et al. Comparison of treatment outcomes between analysis populations in the restore-imi 1 phase 3 trial of imipenem-cilastatin-relebactam versus colistin plus imipenem-cilastatin in patients with imipenem-nonsusceptible bacterial infections. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.02203-19.
    1. Livermore D.M., Mushtaq S., Meunier D., Hopkins K.L., Hill R., Adkin R., Chaudhry A., Pike R., Staves S., Woodford N., et al. Activity of ceftolozane/tazobactam against surveillance and “problem” Enterobacteriaceae, Pseudomonas Aeruginosa and non-fermenters from the British Isles. J. Antimicrob. Chemother. 2017;72:2278–2289. doi: 10.1093/jac/dkx136.
    1. Mushtaq S., Meunier D., Vickers A., Woodford N., Livermore D.M. Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases. J. Antimicrob. Chemother. 2020 doi: 10.1093/jac/dkaa456.
    1. Simner P.J., Patel R. Cefiderocol antimicrobial susceptibility testing considerations: The Achilles’ Heel of the Trojan Horse? J. Clin. Microbiol. 2020;59 doi: 10.1128/JCM.00951-20.
    1. Palzkill T. Metallo-β-lactamase structure and function. Ann. N. Y. Acad. Sci. 2013;1277:91–104. doi: 10.1111/j.1749-6632.2012.06796.x.
    1. Karlowsky J.A., Kazmierczak K.M., De Jonge B.L.M., Hackel M.A., Sahm D.F., Bradford P.A. In vitro activity of aztreonam-avibactam against enterobacteriaceae and pseudomonas aeruginosa isolated by clinical laboratories in 40 countries from 2012 to 2015. Antimicrob Agents Chemother. 2017;61 doi: 10.1128/AAC.00472-17.

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