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European Journal of Clinical Microbiology & Infectious Diseases
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 10/2021

24.06.2021 | Review

Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions

verfasst von: Kathleen Tompkins, David van Duin

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 10/2021

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Abstract

Carbapenem-resistant Enterobacterales (CRE) are a growing threat to human health worldwide. CRE often carry multiple resistance genes that limit treatment options and require longer durations of therapy, are more costly to treat, and necessitate therapies with increased toxicities when compared with carbapenem-susceptible strains. Here, we provide an overview of the mechanisms of resistance in CRE, the epidemiology of CRE infections worldwide, and available treatment options for CRE. We review recentlyapproved agents for the treatment of CRE, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and novel aminoglycosides and tetracyclines. We also discuss recent advances in phage therapy and antibiotics that are currently in development targeted to CRE. The potential for the development of resistance to these therapies remains high, and enhanced antimicrobial stewardship is imperative both to reduce the spread of CRE worldwide and to ensure continued access to efficacious treatment options.
Literatur
1.
2.
3.
4.
van Duin D, Doi Y (2017) The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 8:460–469PubMedCrossRef
5.
Nordmann P, Poirel L (2014) The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect 20:821–830PubMedCrossRef
6.
7.
Bonomo RA et al (2018) Carbapenemase-Producing Organisms: A Global Scourge. Clin Infect Dis 66:1290–1297PubMedCrossRef
8.
Kelly AM, Mathema B, Larson EL (2017) Carbapenem-resistant Enterobacteriaceae in the community: a scoping review. Int J Antimicrob Agents 50:127–134PubMedPubMedCentralCrossRef
9.
Barbadoro P et al (2021) Carriage of Carbapenem-Resistant Enterobacterales in Adult Patients Admitted to a University Hospital in Italy. Antibiotics (Basel) 10:61CrossRef
10.
Hu H et al (2020) Clinical and microbiological characteristics of community-onset Carbapenem-resistant Enterobacteriaceae isolates. Infect Drug Resist 13:3131–3143PubMedPubMedCentralCrossRef
11.
12.
Taggar G, Attiq Rheman M, Boerlin P, Diarra MS (2020) Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals Food and the Environment. Antibiotics (Basel) 9:693CrossRef
13.
Martin A, Fahrbach K, Zhao Q, Lodise T (2018) Association Between Carbapenem Resistance and Mortality Among Adult, Hospitalized Patients With Serious Infections Due to Enterobacteriaceae: Results of a Systematic Literature Review and Meta-analysis. Open Forum Infect Dis 5:ofy150PubMedPubMedCentralCrossRef
14.
Kohler PP et al (2017) Carbapenem resistance, initial antibiotic therapy, and mortality in Klebsiella pneumoniae bacteremia: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 38:1319–1328PubMedCrossRef
15.
Zilberberg MD, Nathanson BH, Sulham K, Fan W, Shorr AF (2017) Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis 17:279PubMedPubMedCentralCrossRef
16.
Bartsch SM et al (2017) Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Clin Microbiol Infect 23(48):e9-48.e16
17.
Igbinosa O, Dogho P, Osadiaye N (2020) Carbapenem-resistant Enterobacteriaceae: A retrospective review of treatment and outcomes in a long-term acute care hospital. Am J Infect Control 48:7–12PubMedCrossRef
18.
Adar A et al (2021) Clinical and Demographic Characteristics of Patients With a New Diagnosis of Carriage or Clinical Infection With Carbapenemase-Producing Enterobacterales: A Retrospective Study. Front Public Health 9:616793PubMedPubMedCentralCrossRef
19.
Voor In’t Holt AF, Severin JA, Lesaffre EMEH, Vos MC (2014) A systematic review and meta-analyses show that carbapenem use and medical devices are the leading risk factors for carbapenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 58:2626–2637CrossRef
20.
Tamma PD et al (2020) Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis doi:https://​doi.​org/​10.​1093/​cid/​ciaa1478
21.
Ruppé É, Woerther P-L, Barbier F (2015) Mechanisms of antimicrobial resistance in Gram-negative bacilli. Ann Intensive Care 5:61PubMedCrossRef
22.
23.
24.
Bush K, Bradford PA (2020) Epidemiology of β-Lactamase-Producing Pathogens. Clin Microbio Rev 33:e00047-19
25.
26.
van Duin D et al (2020) Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis 20:731–741PubMedPubMedCentralCrossRef
27.
Nordmann P, Poirel L (2002) Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 8:321–331PubMedCrossRef
28.
Palzkill T (2018) Structural and Mechanistic Basis for Extended-Spectrum Drug-Resistance Mutations in Altering the Specificity of TEM, CTX-M, and KPC β-lactamases. Front Mol Biosci 5:16PubMedPubMedCentralCrossRef
29.
Walther-Rasmussen J, Høiby N (2007) Class A carbapenemases. J Antimicrob Chemother 60:470–482PubMedCrossRef
30.
31.
Yigit H et al (2001) Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 45:1151–1161PubMedPubMedCentralCrossRef
32.
Deshpande LM, Jones RN, Fritsche TR, Sader HS (2006) Occurrence and Characterization of Carbapenemase-Producing Enterobacteriaceae: Report from the SENTRY Antimicrobial Surveillance Program (2000–2004). Microb Drug Resist 12:223–230PubMedCrossRef
33.
Castanheira M, Farrell SE, Deshpande LM, Mendes RE, Jones RN (2013) Prevalence of β-lactamase-encoding genes among Enterobacteriaceae bacteremia isolates collected in 26 U.S. hospitals: report from the SENTRY Antimicrobial Surveillance Program (2010). Antimicrob Agents Chemother 57:3012–3020PubMedPubMedCentralCrossRef
34.
Villegas MV et al (2006) First detection of the plasmid-mediated class A carbapenemase KPC-2 in clinical isolates of Klebsiella pneumoniae from South America. Antimicrob Agents Chemother 50:2880–2882PubMedCrossRef
35.
Rada AM et al (2020) Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity. Antimicrob Agents Chemother 64:e01743-20PubMedPubMedCentralCrossRef
36.
Navon-Venezia S et al (2009) First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States. Antimicrob Agents Chemother 53:818–820PubMedCrossRef
37.
Karampatakis T, Antachopoulos C, Iosifidis E, Tsakris A, Roilides E (2016) Molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Greece. Future Microbiol 11:809–823PubMedCrossRef
38.
Gartzonika K et al (2018) Identification of a KPC-9-producing Klebsiella pneumoniae ST258 cluster among KPC-2-producing isolates of an ongoing outbreak in Northwestern Greece: a retrospective study. Clin Microbiol Infect 24:558–560PubMedCrossRef
39.
Vubil D et al (2017) Outbreak of KPC-3-producing ST15 and ST348 Klebsiella pneumoniae in a Portuguese hospital. Epidemiol Infect 145:595–599PubMedCrossRef
40.
Baraniak A et al (2017) Multiregional dissemination of KPC-producing Klebsiella pneumoniae ST258/ST512 genotypes in Poland, 2010–14. J Antimicrob Chemother 72:1610–1616PubMedCrossRef
41.
42.
43.
44.
Walsh TR (2005) The emergence and implications of metallo-β-lactamases in Gram-negative bacteria. Clin Microbiol Infect 11:2–9PubMedCrossRef
45.
46.
Watanabe M, Iyobe S, Inoue M, Mitsuhashi S (1991) Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 35:147–151PubMedPubMedCentralCrossRef
47.
Malchione MD, Torres LM, Hartley DM, Koch M, Goodman JL (2019) Carbapenem and colistin resistance in Enterobacteriaceae in Southeast Asia: Review and mapping of emerging and overlapping challenges. Int J Antimicrob Agents 54:381–399PubMedCrossRef
48.
Matsumura Y et al (2017) Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae. Antimicrob Agents Chemother 61:e02729-16PubMedPubMedCentral
49.
Lauretti L et al (1999) Cloning and characterization of blaVIM, a new integron-borne metallo-beta-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob Agents Chemother 43:1584–1590PubMedPubMedCentralCrossRef
50.
51.
Yong D et al (2009) Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53:5046–5054PubMedPubMedCentralCrossRef
52.
Mairi A, Pantel A, Sotto A, Lavigne J-P, Touati A (2018) OXA-48-like carbapenemases producing Enterobacteriaceae in different niches. Eur J Clin Microbiol Infect Dis 37:587–604PubMedCrossRef
53.
Poirel L, Potron A, Nordmann P (2012) OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 67:1597–1606PubMedCrossRef
54.
Pitout JDD, Peirano G, Kock MM, Strydom K-A, Matsumura Y (2019) The Global Ascendency of OXA-48-Type Carbapenemases. Clin Microbiol Rev 33:e00102-19PubMedPubMedCentralCrossRef
55.
Walther-Rasmussen J, Høiby N (2006) OXA-type carbapenemases. J Antimicrob Chemother 57:373–383PubMedCrossRef
56.
Nordmann P, Dortet L, Poirel L (2012) Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med 18:263–272PubMedCrossRef
57.
Guzmán-Puche J et al (2021) Characterization of OXA-48-producing Klebsiella oxytoca isolates from a hospital outbreak in Tunisia. J Glob Antimicrob Resist 24:306–310PubMedCrossRef
58.
Heireman L et al (2020) Toilet drain water as a potential source of hospital room-to-room transmission of carbapenemase-producing Klebsiella pneumoniae. J Hosp Infect 106:232–239PubMedCrossRef
59.
Shaidullina E et al (2020) Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak. Antibiotics (Basel) 9:862CrossRef
60.
Lyman M et al (2015) Notes from the Field: Carbapenem-resistant Enterobacteriaceae Producing OXA-48-like Carbapenemases-United States, 2010–2015. MMWR Morb Mortal Wkly Rep 64:1315–1316PubMedCrossRef
61.
Jean S-S et al (2015) Carbapenemase-producing Gram-negative bacteria: current epidemics, antimicrobial susceptibility and treatment options. Future Microbiol 10:407–425PubMedCrossRef
62.
Ract P et al (2019) Synergistic in vitro activity between aztreonam and amoxicillin-clavulanate against Enterobacteriaceae-producing class B and/or class D carbapenemases with or without extended-spectrum β-lactamases. J Med Microbiol 68:1292–1298PubMedCrossRef
63.
Biswas S, Brunel J-M, Dubus J-C, Reynaud-Gaubert M, Rolain J-M (2012) Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther 10:917–934PubMedCrossRef
64.
Capone A et al (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–E30PubMedCrossRef
65.
Giacobbe DR et al (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):e1-8
66.
Kai J, Wang S (2020) Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design. Int Microbiol 23:355–366PubMedCrossRef
67.
Band VI et al (2021) Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States. MBio 12:e02881-20PubMedPubMedCentralCrossRef
68.
Seo J, Wi YM, Kim JM, Kim Y-J, Ko KS (2021) Detection of colistin-resistant populations prior to antibiotic exposure in KPC-2-producing Klebsiella pneumoniae clinical isolates. J Microbiol 59:590–597PubMedCrossRef
69.
Motsch J et al (2020) 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 70:1799–1808PubMedCrossRef
70.
Wunderink RG et al (2018) 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 7:439–455PubMedPubMedCentralCrossRef
71.
van Duin D et al (2018) Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis 66:163–171PubMedCrossRef
72.
73.
74.
75.
76.
77.
78.
79.
Huang L et al (2021) Prevalence and mechanisms of fosfomycin resistance among KPC-producing Klebsiella pneumoniae clinical isolates in China. Int J Antimicrob Agents 57:106226PubMedCrossRef
80.
Michalopoulos AS, Livaditis IG, Gougoutas V (2011) The revival of fosfomycin. Int J Infect Dis 15:e732–e739PubMedCrossRef
81.
Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI (2008) Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 46:1069–1077PubMedCrossRef
82.
Michalopoulos A et al (2010) Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin Microbiol Infect 16:184–186PubMedCrossRef
83.
Pontikis K et al (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 43:52–59PubMedCrossRef
84.
85.
86.
Seifert H, Blondeau J, Dowzicky MJ (2018) In vitro activity of tigecycline and comparators (2014-2016) among key WHO ‘priority pathogens’ and longitudinal assessment (2014-2016) of antimicrobial resistance: a report from the T.E.S.T. study. Int J Antimicrob Agents 52:474–484PubMedCrossRef
87.
Ni W et al (2016) Tigecycline Treatment for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review and Meta-Analysis. Medicine 95:e3126PubMedPubMedCentralCrossRef
88.
Sbrana F et al (2013) Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit. Clin Infect Dis 56:697–700PubMedCrossRef
89.
importance of combination therapy (2012) Tumbarello, M. et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Infect Dis 55:943–950CrossRef
90.
Pournaras S, Koumaki V, Spanakis N, Gennimata V, Tsakris A (2016) Current perspectives on tigecycline resistance in Enterobacteriaceae: susceptibility testing issues and mechanisms of resistance. Int J Antimicrob Agents 48:11–18PubMedCrossRef
91.
Yoon EJ, Oh Y, Jeong SH (2020) Development of Tigecycline Resistance in Carbapenemase-Producing Klebsiella pneumoniae Sequence Type 147 via AcrAB Overproduction Mediated by Replacement of the ramA Promoter. Ann Lab Med 40:15–20PubMedCrossRef
92.
93.
He T et al (2019) Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans. Nat Microbiol 4:1450–1456PubMedCrossRef
94.
95.
96.
97.
Ng SMS et al (2018) Repurposing Zidovudine in combination with Tigecycline for treating carbapenem-resistant Enterobacteriaceae infections. Eur J Clin Microbiol Infect Dis 37:141–148PubMedCrossRef
98.
Cebrero-Cangueiro T et al (2018) In vitro Activity of Pentamidine Alone and in Combination With Aminoglycosides, Tigecycline, Rifampicin, and Doripenem Against Clinical Strains of Carbapenemase-Producing and/or Colistin-Resistant Enterobacteriaceae. Front Cell Infect Microbiol 8:363PubMedPubMedCentralCrossRef
99.
Otto RG et al (2019) An alternative strategy for combination therapy: Interactions between polymyxin B and non-antibiotics. Int J Antimicrob Agents 53:34–39PubMedCrossRef
100.
Zhanel GG et al (2013) Ceftazidime-Avibactam: a Novel Cephalosporin/b-lactamase Inhibitor Combination. Drugs; Auckland 73:159–177CrossRef
101.
102.
Sousa A et al (2018) Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother 73:3170–3175PubMedCrossRef
103.
De la Calle C et al (2019) Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam. Int J Antimicrob Agents 53:520–524PubMedCrossRef
104.
Shields RK et al (2017) Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia. Antimicrob Agents Chemother 61:e00883-17PubMedPubMedCentral
105.
106.
Wilson GM et al (2021) Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug-Resistant Gram-Negative Infections. Open Forum Infect Dis 8:ofaa651PubMedPubMedCentralCrossRef
107.
108.
Mazuski JE et al (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 62:1380–1389PubMedPubMedCentralCrossRef
109.
Wagenlehner FM et al (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 63:754–762PubMedPubMedCentralCrossRef
110.
Torres A et al (2018) Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis 18:285–295PubMedCrossRef
111.
de Jonge BLM et al (2016) In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014). Antimicrob Agents Chemother 60:3163–3169PubMedPubMedCentralCrossRef
112.
Spiliopoulou I, Kazmierczak K, Stone GG (2020) In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015–17). J Antimicrob Chemother 75:384–391PubMedCrossRef
113.
Nelson K et al (2017) Resistance to Ceftazidime-Avibactam Is Due to Transposition of KPC in a Porin-Deficient Strain of Klebsiella pneumoniae with Increased Efflux Activity. Antimicrob Agents Chemother 61:e00989-17PubMedPubMedCentralCrossRef
114.
Humphries RM, Hemarajata P (2017) Resistance to Ceftazidime-Avibactam in Klebsiella pneumoniae Due to Porin Mutations and the Increased Expression of KPC-3. Antimicrob Agents Chemother 61:e00537-17PubMedPubMedCentral
115.
Humphries RM et al (2015) First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate. Antimicrob Agents Chemother 59:6605–6607PubMedPubMedCentralCrossRef
116.
Shields RK et al (2017) Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections. Antimicrob Agents Chemother 61:e02097-16PubMedPubMedCentral
117.
Poirel L et al (2020) KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity. Antimicrob Agents Chemother 64:e00321-20PubMedPubMedCentral
118.
Winkler ML, Papp-Wallace KM, Bonomo RA (2015) Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop. J Antimicrob Chemother 70:2279–2286PubMedPubMedCentralCrossRef
119.
Shields RK et al (2016) Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections. Clin Infect Dis 63:1615–1618PubMedPubMedCentralCrossRef
120.
Zhang Y, Kashikar A, Brown CA, Denys G, Bush K (2017) Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam. Antimicrob Agents Chemother 61:e00389-17PubMedPubMedCentral
121.
122.
Shields RK, Doi Y (2020) Aztreonam Combination Therapy: An Answer to Metallo-β-Lactamase-Producing Gram-Negative Bacteria? Clin Infect Dis 71:1099–1101PubMedCrossRef
123.
Karlowsky JA et al (2017) 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 61:e00472-17PubMedPubMedCentralCrossRef
124.
Shaw E et al (2018) Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection. J Antimicrob Chemother 73:1104–1106PubMedCrossRef
125.
126.
Alghoribi MF et al (2021) Successful treatment of infective endocarditis due to pandrug-resistant Klebsiella pneumoniae with ceftazidime-avibactam and aztreonam. Sci Rep 11:9684PubMedPubMedCentralCrossRef
127.
128.
Cornely OA et al (2020) Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study. J Antimicrob Chemother 75:618–627PubMedCrossRef
129.
130.
131.
Cho JC, Zmarlicka MT, Shaeer KM, Pardo J (2018) Meropenem/Vaborbactam, the First Carbapenem/β-Lactamase Inhibitor Combination. Ann Pharmacother 52:769–779PubMedCrossRef
132.
Hecker SJ et al (2015) Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases. J Med Chem 58:3682–3692PubMedCrossRef
133.
Lomovskaya O et al (2017) Vaborbactam: Spectrum of Beta-Lactamase Inhibition and Impact of Resistance Mechanisms on Activity in Enterobacteriaceae. Antimicrob Agents Chemother 61:e01443-17PubMedPubMedCentralCrossRef
134.
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:e00567-17PubMedPubMedCentral
135.
Kaye KS et al (2018) Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial. JAMA 319:788–799PubMedPubMedCentralCrossRef
136.
Sun D, Rubio-Aparicio D, Nelson K, Dudley MN, Lomovskaya O (2017) Meropenem-Vaborbactam Resistance Selection, Resistance Prevention, and Molecular Mechanisms in Mutants of KPC-Producing Klebsiella pneumoniae. Antimicrob Agents Chemother 61:e01694-17PubMedPubMedCentral
137.
Wilson WR, Kline EG, Jones CE, Morder KT, Mettus RT, Doi Y et al (2019) Effects of KPC Variant and porin genotype on the in vitro activity of meropenem-vaborbactam against carbapenem-resistant enterobacteriaceae. Antimicrob Agents Chemother 63. https://​doi.​org/​10.​1128/​AAC.​02048-18
138.
Dulyayangkul P, Wan Nur Ismah WAK, Douglas EJA, Avison MB (2020) Mutation of kvrA Causes OmpK35 and OmpK36 Porin Downregulation and Reduced Meropenem-Vaborbactam Susceptibility in KPC-Producing Klebsiella pneumoniae. Antimicrob Agents Chemother 64:e02208-19PubMedPubMedCentral
139.
Olsen I (2015) New promising β-lactamase inhibitors for clinical use. Eur J Clin Microbiol Infect Dis 34:1303–1308PubMedCrossRef
140.
Zhanel GG et al (2018) Imipenem-Relebactam and Meropenem–Vaborbactam: Two Novel Carbapenem-ß-Lactamase Inhibitor Combinations. Drugs; Auckland 78:65–98CrossRef
141.
Campanella TA, Gallagher JC (2020) A Clinical Review and Critical Evaluation of Imipenem-Relebactam: Evidence to Date. Infect Drug Resist 13:4297–4308PubMedPubMedCentralCrossRef
142.
Lob SH et al (2020) In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance Europe 2015–2017. J Med Microbiol 69:207–217PubMedCrossRef
143.
144.
Smith JR, Rybak JM, Claeys KC (2020) Imipenem-Cilastatin-Relebactam: A Novel β-Lactam-β-Lactamase Inhibitor Combination for the Treatment of Multidrug-Resistant Gram-Negative Infections. Pharmacotherapy 40:343–356PubMedCrossRef
145.
146.
van Duin D, Bonomo RA (2016) Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-Lactamase Inhibitor Combinations. Clin Infect Dis 63:234–241PubMedPubMedCentralCrossRef
147.
Armstrong ES, Miller GH (2010) Combating evolution with intelligent design: the neoglycoside ACHN-490. Curr Opin Microbiol 13:565–573PubMedCrossRef
148.
Livermore DM et al (2011) Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 66:48–53PubMedCrossRef
149.
Eljaaly K, Alharbi A, Alshehri S, Ortwine JK, Pogue JM (2019) Plazomicin: A Novel Aminoglycoside for the Treatment of Resistant Gram-Negative Bacterial Infections. Drugs 79:243–269PubMedCrossRef
150.
Walkty A et al (2014) In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011–2012. Antimicrob Agents Chemother 58:2554–2563PubMedPubMedCentralCrossRef
151.
152.
Wagenlehner FME et al (2019) Once-Daily Plazomicin for Complicated Urinary Tract Infections. N Engl J Med 380:729–740PubMedCrossRef
153.
McKinnell JA et al (2019) Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae. N Engl J Med 380:791–793PubMedCrossRef
154.
Theuretzbacher U, Paul M (2018) Developing a new antibiotic for extensively drug-resistant pathogens: the case of plazomicin. Clin Microbiol Infect 24:1231–1233PubMedCrossRef
155.
156.
Mullard A (2019) Achaogen bankruptcy highlights antibacterial development woes. Nat Rev Drug Discov 18:411PubMed
157.
Shaeer KM, Zmarlicka MT, Chahine EB, Piccicacco N, Cho J (2019) C. Plazomicin: A Next-Generation Aminoglycoside. Pharmacotherapy 39:77–93PubMedCrossRef
158.
Zhanel GG et al (2012) Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther 10:459–473PubMedCrossRef
159.
Roch M et al (2020) Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae. J Glob Antimicrob Resist 24:183–189PubMedCrossRef
160.
Xiao X-Y et al (2012) Fluorocyclines 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent. J Med Chem 55:597–605PubMedCrossRef
161.
Zhanel GG et al (2016) Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent. Drugs 76:567–588PubMedCrossRef
162.
Zhang Y, Lin X, Bush K (2016) In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J Antibiot 69:600–604CrossRef
163.
Livermore DM, Mushtaq S, Warner M, Woodford N (2016) In Vitro Activity of Eravacycline against Carbapenem-Resistant Enterobacteriaceae and Acinetobacter baumannii. Antimicrob Agents Chemother 60:3840–3844PubMedPubMedCentralCrossRef
164.
Clark JA, Kulengowski B, Burgess DS (2020) In vitro activity of eravacycline compared with tigecycline against carbapenem-resistant Enterobacteriaceae. Int. J Antimicrob Agents 56:106178PubMedCrossRef
165.
Solomkin JS et al (2019) Eravacycline: a new treatment option for complicated intra-abdominal infections in the age of multidrug resistance. Future Microbiol 14:1293–1308PubMedCrossRef
166.
167.
168.
Grossman TH, O’Brien W, Kerstein KO, Sutcliffe JA (2015) Eravacycline (TP-434) is active in vitro against biofilms formed by uropathogenic Escherichia coli. Antimicrob Agents Chemother 59:2446–2449PubMedPubMedCentralCrossRef
169.
170.
Heaney M, Mahoney MV, Gallagher JC (2019) Eravacycline: The Tetracyclines Strike Back. Ann Pharmacother 53:1124–1135PubMedCrossRef
171.
Grossman TH et al (2012) Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother 56:2559–2564PubMedPubMedCentralCrossRef
172.
173.
Ding Y et al (2020) Emergence of tigecycline- and eravacycline-resistant Tet(X4)-producing Enterobacteriaceae in the gut microbiota of healthy Singaporeans. J Antimicrob Chemother 75:3480–3484PubMedCrossRef
174.
Honeyman L et al (2015) Structure-activity relationship of the aminomethylcyclines and the discovery of omadacycline. Antimicrob Agents Chemother 59:7044–7053PubMedPubMedCentralCrossRef
175.
Zhanel GG et al (2020) Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent. Drugs 80:285–313PubMedCrossRef
176.
O’Riordan W et al (2019) Omadacycline for Acute Bacterial Skin and Skin-Structure Infections. N Engl J Med 380:528–538PubMedCrossRef
177.
Stets R et al (2019) Omadacycline for Community-Acquired Bacterial Pneumonia. N Engl J Med 380:517–527PubMedCrossRef
178.
O’Riordan W et al (2019) Once-daily oral omadacycline versus twice-daily oral linezolid for acute bacterial skin and skin structure infections (OASIS-2): a phase 3, double-blind, multicentre, randomised, controlled, non-inferiority trial. Lancet Infect Dis 19:1080–1090PubMedCrossRef
179.
180.
181.
Lutgring JD et al (2020) Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018. Antimicrob. Agents Chemother 64:e00499-20PubMedPubMedCentralCrossRef
182.
Möllmann U, Heinisch L, Bauernfeind A, Köhler T, Ankel-Fuchs D (2009) Siderophores as drug delivery agents: application of the ‘Trojan Horse’ strategy. Biometals 22:615–624PubMedCrossRef
183.
El-Lababidi RM, Rizk JG (2020) Cefiderocol: A Siderophore Cephalosporin. Ann Pharmacother 54:1215–1231PubMedCrossRef
184.
Ito-Horiyama T et al (2016) Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases. Antimicrob Agents Chemother 60:4384–4386PubMedPubMedCentralCrossRef
185.
Poirel L, Kieffer N, Nordmann P (2018) Stability of cefiderocol against clinically significant broad-spectrum oxacillinases. Int J Antimicrob Agents 52:866–867PubMedCrossRef
186.
Katsube T, Echols R, Wajima T (2019) Pharmacokinetic and Pharmacodynamic Profiles of Cefiderocol, a Novel Siderophore Cephalosporin. Clin Infect Dis 69:S552–S558PubMedPubMedCentralCrossRef
187.
Kohira N et al (2016) In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates Including Carbapenem-Resistant Strains. Antimicrob Agents Chemother 60:729–734PubMedPubMedCentralCrossRef
188.
Zhanel GG et al (2019) Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli. Drugs 79:271–289PubMedCrossRef
189.
190.
Portsmouth S et al (2018) 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 18:1319–1328PubMedCrossRef
191.
Wunderink RG et al (2021) Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 21:213–225PubMedCrossRef
192.
193.
Bassetti M et al (2021) 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 21:226–240PubMedCrossRef
194.
Yamano Y (2019) In Vitro Activity of Cefiderocol Against a Broad Range of Clinically Important Gram-negative Bacteria. Clin Infect Dis 69:S544–S551PubMedPubMedCentralCrossRef
195.
Hackel MA et al (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:e00093-17PubMedPubMedCentralCrossRef
196.
Hackel MA et al (2018) In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014 to 2016. Antimicrob Agents Chemother 62:e01968-17PubMedPubMedCentral
197.
Kohira N et al (2020) Reduced susceptibility mechanism to cefiderocol, a siderophore cephalosporin, among clinical isolates from a global surveillance programme (SIDERO-WT-2014). J Glob Antimicrob Resist 22:738–741PubMedCrossRef
198.
Kortright KE, Chan BK, Koff JL, Turner PE (2019) Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria. Cell Host Microbe 25:219–232PubMedCrossRef
199.
Dedrick RM et al (2019) Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med 25:730–733PubMedPubMedCentralCrossRef
200.
201.
Rehman S, Ali Z, Khan M, Bostan N, Naseem S (2019) The dawn of phage therapy. Rev Med Virol 29:e2041PubMedCrossRef
202.
Reindel R, Fiore CR (2017) Phage therapy: considerations and challenges for development. Clin Infect Dis 64:1589–1590
203.
204.
Chanishvili N (2012) Phage therapy–history from Twort and d’Herelle through Soviet experience to current approaches. Adv Virus Res 83:3–40PubMedCrossRef
205.
Jault P et al (2019) Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis 19:35–45PubMedCrossRef
206.
Aslam S et al (2020) Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States. Open Forum Infect Dis 7:ofaa389PubMedPubMedCentralCrossRef
207.
Amarillas L et al (2017) Isolation and Characterization of phiLLS, a Novel Phage with Potential Biocontrol Agent against Multidrug-Resistant Escherichia coli. Front Microbiol 8:1355PubMedPubMedCentralCrossRef
208.
Oliveira H et al (2016) Characterization and genome sequencing of a Citrobacter freundii phage CfP1 harboring a lysin active against multidrug-resistant isolates. Appl Microbiol Biotechnol 100:10543–10553PubMedCrossRef
209.
Li M et al (2020) Characterization and genome analysis of Klebsiella phage P509, with lytic activity against clinical carbapenem-resistant Klebsiella pneumoniae of the KL64 capsular type. Arch Virol 165:2799–2806PubMedCrossRef
210.
Li M et al (2020) Isolation and Characterization of Novel Lytic Bacteriophages Infecting Epidemic Carbapenem-Resistant Klebsiella pneumoniae Strains. Front Microbiol 11:1554PubMedPubMedCentralCrossRef
211.
Horváth M et al (2020) Identification of a newly isolated lytic bacteriophage against K24 capsular type, carbapenem resistant Klebsiella pneumoniae isolates. Sci Rep 10:5891PubMedPubMedCentralCrossRef
212.
Ciacci N et al (2018) Characterization of vB_Kpn_F48, a Newly Discovered Lytic Bacteriophage for Klebsiella pneumoniae of Sequence Type 101. Viruses 10:482PubMedCentralCrossRef
213.
Anand T et al (2020) Phage therapy for treatment of virulent Klebsiella pneumoniae infection in a mouse model. J Glob Antimicrob Resist 21:34–41PubMedCrossRef
214.
Labrie SJ, Samson JE, Moineau S (2010) Bacteriophage resistance mechanisms. Nat Rev Microbiol 8:317–327PubMedCrossRef
215.
Guo D et al (2021) Genetic and Chemical Engineering of Phages for Controlling Multidrug-Resistant Bacteria. Antibiotics (Basel) 10:202CrossRef
216.
217.
Livermore DM, Mushtaq S, Warner M, Vickers A, Woodford N (2017) In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria. J Antimicrob Chemother 72:1373–1385PubMedCrossRef
218.
Thomson KS, AbdelGhani S, Snyder JW, Thomson GK (2019) Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens. Antibiotics (Basel) 8:32CrossRef
219.
Sader HS, Castanheira M, Huband M, Jones RN, Flamm RK (2017) WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015. Antimicrob Agents Chemother 61:e00072-17PubMedPubMedCentral
220.
Rodvold KA et al (2018) Plasma and Intrapulmonary Concentrations of Cefepime and Zidebactam following Intravenous Administration of WCK 5222 to Healthy Adult Subjects. Antimicrob Agents Chemother 62:e00682-18PubMedPubMedCentral
221.
Preston RA et al (2019) Single-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal Impairment. Antimicrob Agents Chemother 63:e01484-18PubMed
222.
Liu B et al (2020) Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections. J Med Chem 63:2789–2801PubMedCrossRef
223.
224.
Hamrick JC et al (2020) VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa. Antimicrob Agents Chemother 64:e01963-19PubMedPubMedCentralCrossRef
225.
Abdelraouf K, Almarzoky Abuhussain S, Nicolau DP (2020) In vivo pharmacodynamics of new-generation β-lactamase inhibitor taniborbactam (formerly VNRX-5133) in combination with cefepime against serine-β-lactamase-producing Gram-negative bacteria. J Antimicrob Chemother 75:3601–3610PubMedPubMedCentralCrossRef
226.
Reck F et al (2018) Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228. Bioorg Med Chem Lett 28:748–755PubMedCrossRef
227.
Blais J et al (2018) In Vitro Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-Resistant Enterobacteriaceae. Antimicrob Agents Chemother 62:e00552-18PubMedPubMedCentralCrossRef
228.
Dean CR et al (2018) Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother 62:e01200-18PubMedPubMedCentralCrossRef
229.
Osborn M et al (2019) A First-in-Human Study To Assess the Safety and Pharmacokinetics of LYS228, a Novel Intravenous Monobactam Antibiotic in Healthy Volunteers. Antimicrob Agents Chemother 63:e02592-18PubMedPubMedCentralCrossRef
230.
231.
Barnes MD et al (2019) Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC. Antimicrob Agents Chemother 63:e00432-19PubMedPubMedCentral
232.
Davies DT et al (2020) Discovery of ANT3310, a Novel Broad-Spectrum Serine β-Lactamase Inhibitor of the Diazabicyclooctane Class, Which Strongly Potentiates Meropenem Activity against Carbapenem-Resistant Enterobacterales and Acinetobacter baumannii. J Med Chem 63:15802–15820PubMedCrossRef
233.
Mushtaq S, Vickers A, Woodford N, Haldimann A, Livermore DM (2019) Activity of nacubactam (RG6080/OP0595) combinations against MBL-producing Enterobacteriaceae. J Antimicrob Chemother 74:953–960PubMedCrossRef
234.
Mallalieu NL et al (2020) Safety and Pharmacokinetic Characterization of Nacubactam, a Novel β-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers. Antimicrob Agents Chemother 64:e02229-19PubMedPubMedCentralCrossRef
Metadaten
Titel
Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions
verfasst von
Kathleen Tompkins
David van Duin
Publikationsdatum
24.06.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 10/2021
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-021-04296-1

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