Antibacterial agents active against Gram Negative Bacilli in phase I, II, or III clinical trials

References

• GBD 2019. Antimicrobial resistance collaborators. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the global burden of disease study 2019. Lancet. 2022;400:2221–2248.
   PubMed Web of Science ®Google Scholar
• Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399:629–655.
   PubMed Web of Science ®Google Scholar
• Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA. 2018;320(10):984. doi: 10.1001/jama.2018.12163
   PubMed Web of Science ®Google Scholar
• De Oliveira DMP, Forde BM, Kidd TJ, et al. Antimicrobial resistance in ESKAPE pathogens. Clin Microbiol Rev. 2020;33(3). doi: 10.1128/CMR.00181-19
   PubMed Web of Science ®Google Scholar
• Butler MS, Henderson IR, Capon RJ, et al. Antibiotics in the clinical pipeline as of December 2022. J Antibiot (Tokyo). 2023;76(8):431–473.
   PubMed Web of Science ®Google Scholar
• Timsit JF, Paul M, Shields RK, et al. Cefiderocol for the treatment of infections due to metallo-B-lactamase–producing pathogens in the CREDIBLE-CR and APEKS-NP phase 3 randomized studies. Clin Infect Dis. 2022;75(6):1081–1084. doi: 10.1093/cid/ciac078
   PubMed Web of Science ®Google Scholar
• Livermore DM, Mushtaq S, Vickers A, et al. Activity of aztreonam/avibactam against metallo-β-lactamase-producing enterobacterales from the UK: impact of penicillin-binding protein-3 inserts and CMY-42 β-lactamase in Escherichia coli. Int J Antimicrob Agents. 2023;61(5):106776. doi: 10.1016/j.ijantimicag.2023.106776
   PubMed Web of Science ®Google Scholar
• Le Terrier C, Nordmann P, Sadek M, et al. In vitro activity of cefepime/zidebactam and cefepime/taniborbactam against aztreonam/avibactam-resistant NDM-like-producing escherichia coli clinical isolates. J Antimicrob Chemother. 2023;78(5):1191–1194. doi: 10.1093/jac/dkad061
   PubMed Web of Science ®Google Scholar
• Zhang Y, Kashikar A, Brown CA, et al. 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. 2017;61(8). doi: 10.1128/AAC.00389-17
   Web of Science ®Google Scholar
• Findlay J, Poirel L, Bouvier M, et al. In vitro activity of sulbactam-durlobactam against carbapenem-resistant acinetobacter baumannii and mechanisms of resistance. J Glob Antimicrob Resist. 2022;30:445–450. doi: 10.1016/j.jgar.2022.05.011
   PubMed Web of Science ®Google Scholar
• Le Terrier C, Gruenig V, Fournier C, et al. NDM-9 resistance to taniborbactam. Lancet Infect Dis. 2023;23(4):401–402. doi: 10.1016/S1473-3099(23)00069-5
   PubMed Web of Science ®Google Scholar
• Duffy EM, Buurman ET, Chiang SL, et al. The CARB-X portfolio of nontraditional antibacterial products. ACS Infect Dis. 2021;7(8):2043–2049.
   PubMed Web of Science ®Google Scholar
• Morinaka A, Tsutsumi Y, Yamada M, et al. OP0595, a new diazabicyclooctane: mode of action as a serine β-lactamase inhibitor, antibiotic and β-lactam ‘enhancer’. J Antimicrob Chemother. 2015;70(10):2779–2786. doi: 10.1093/jac/dkv166
   PubMed Web of Science ®Google Scholar
• Livermore DM, Mushtaq S, Warner M, et al. Activity of OP0595/β-lactam combinations against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing β-lactamases. J Antimicrob Chemother. 2015;70(11):3032–3041. doi: 10.1093/jac/dkv239
   PubMed Web of Science ®Google Scholar
• Mallalieu NL, Winter E, Fettner S, et al. Safety and pharmacokinetic characterization of nacubactam, a novel β-lactamase inhibitor, alone and in combination with meropenem, in healthy volunteers. Antimicrob Agents Chemother. 2020;64(5). doi: 10.1128/AAC.02229-19
   PubMed Web of Science ®Google Scholar
• Papp-Wallace KM, Nguyen NQ, Jacobs MR, et al. Strategic approaches to overcome resistance against Gram-negative pathogens using β-lactamase inhibitors and β-lactam enhancers: activity of three novel diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234. J Med Chem. 2018;61(9):4067–4086. doi: 10.1021/acs.jmedchem.8b00091
   PubMed Web of Science ®Google Scholar
• Moya B, Barcelo IM, Cabot G, et al. In vitro and in vivo activities of β-lactams in combination with the Novel β-lactam enhancers zidebactam and WCK 5153 against multidrug-resistant metallo-β-lactamase-producing klebsiella pneumoniae. Antimicrob Agents Chemother. 2019;63(5). doi: 10.1128/AAC.00128-19
   Web of Science ®Google Scholar
• Hujer AM, Marshall SH, Mack AR, et al. Transcending the challenge of evolving resistance mechanisms in pseudomonas aeruginosa through β-lactam-enhancer-mechanism-based cefepime/zidebactam. MBio. 2023;14(6). doi: 10.1128/mbio.01118-23
   PubMed Web of Science ®Google Scholar
• Moya B, Barcelo IM, Bhagwat S, et al. WCK 5107 (zidebactam) and WCK 5153 are novel inhibitors of PBP2 showing potent “β-lactam enhancer” activity against pseudomonas aeruginosa, including multidrug-resistant metallo-β-lactamase-producing high-risk clones. Antimicrob Agents Chemother. 2017;61(6). doi: 10.1128/AAC.02529-16
   Web of Science ®Google Scholar
• Moya B, Bhagwat S, Cabot G, et al. Effective inhibition of PBPs by cefepime and zidebactam in the presence of VIM-1 drives potent bactericidal activity against MBL-expressing pseudomonas aeruginosa. J Antimicrob Chemother. 2020;75(6):1474–1478. doi: 10.1093/jac/dkaa036
   PubMed Web of Science ®Google Scholar
• Barceló I, Cabot G, Palwe S, et al. In vitro evolution of cefepime/zidebactam (WCK 5222) resistance in pseudomonas aeruginosa: dynamics, mechanisms, fitness trade-off and impact on in vivo efficacy. J Antimicrob Chemother. 2021;76(10):2546–2557. doi: 10.1093/jac/dkab213
   PubMed Web of Science ®Google Scholar
• Moya B, Barcelo IM, Bhagwat S, et al. Potent β-lactam enhancer activity of zidebactam and WCK 5153 against acinetobacter baumannii, including carbapenemase-producing clinical isolates. Antimicrob Agents Chemother. 2017;61(11). doi: 10.1128/AAC.01238-17
   Web of Science ®Google Scholar
• Rodvold KA, Gotfried MH, Chugh R, et al. Plasma and intrapulmonary concentrations of cefepime and zidebactam following intravenous administration of WCK 5222 to healthy adult subjects. Antimicrob Agents Chemother. 2018;62(8). doi: 10.1128/AAC.00682-18
   Web of Science ®Google Scholar
• Preston RA, Mamikonyan G, DeGraff S, et al. Single-center evaluation of the pharmacokinetics of WCK 5222 (cefepime-zidebactam combination) in subjects with renal impairment. Antimicrob Agents Chemother. 2019;63(1). doi: 10.1128/AAC.01484-18
   Web of Science ®Google Scholar
• Tirlangi PK, Wanve BS, Dubbudu RR, et al. Successful use of cefepime-zidebactam (WCK 5222) as a salvage therapy for the treatment of disseminated extensively drug-resistant New Delhi metallo-β-lactamase-producing pseudomonas aeruginosa infection in an adult patient with acute T-cell leukemia. Antimicrob Agents Chemother. 2023;67(8). doi: 10.1128/aac.00500-23
   PubMed Web of Science ®Google Scholar
• Dubey D, Roy M, Shah TH, et al. Compassionate use of a novel β-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report. Ann Clin Microbiol Antimicrob. 2023;22(1). doi: 10.1186/s12941-023-00606-x
   PubMed Web of Science ®Google Scholar
• Mushtaq S, Garello P, Vickers A, et al. Activity of ertapenem/zidebactam (WCK 6777) against problem enterobacterales. J Antimicrob Chemother. 2022;77(10):2772–2778. doi: 10.1093/jac/dkac280
   PubMed Web of Science ®Google Scholar
• Gethers M, Chen I, Abdelraouf K, et al. In vivo efficacy of WCK 6777 (ertapenem/zidebactam) against carbapenemase-producing klebsiella pneumoniae in the neutropenic murine pneumonia model. J Antimicrob Chemother. 2022;77(7):1931–1937. doi: 10.1093/jac/dkac110
   PubMed Web of Science ®Google Scholar
• Lomovskaya O, Castanheira M, Lindley J, et al. In vitro potency of xeruborbactam in combination with multiple β-lactam antibiotics in comparison with other β-lactam/β-lactamase inhibitor (BLI) combinations against carbapenem-resistant and extended-spectrum β-lactamase-producing enterobacterales. Antimicrob Agents Chemother. 2023;67(11). doi: 10.1128/aac.00440-23
   Google Scholar
• Sun D, Tsivkovski R, Pogliano J, et al. Intrinsic antibacterial activity of xeruborbactam in vitro: assessing spectrum and mode of action. Antimicrob Agents Chemother. 2022;66(10). doi: 10.1128/aac.00879-22
   Web of Science ®Google Scholar
• [cited 2024 Jan 2]. Available from: www.shionogi.com/us/en/news/2023/06
   Google Scholar
• Davies DT, Leiris S, Zalacain M, et al. 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. 2020;63(24):15802–15820. doi: 10.1021/acs.jmedchem.0c01535
   PubMed Web of Science ®Google Scholar
• Durand-Réville TF, Guler S, Comita-Prevoir J, et al. ETX2514 is a broad-spectrum β-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including acinetobacter baumannii. Nat Microbiol. 2017;2(9). doi: 10.1038/nmicrobiol.2017.104
   PubMed Web of Science ®Google Scholar
• McLeod SM, Shapiro AB, Moussa SH, et al. Frequency and mechanism of spontaneous resistance to sulbactam combined with the novel β-lactamase inhibitor ETX2514 in clinical isolates of acinetobacter baumannii. Antimicrob Agents Chemother. 2018;62(2). doi: 10.1128/AAC.01576-17
   PubMed Web of Science ®Google Scholar
• Zalacain M, Achard P, Llanos A, et al. Meropenem-ANT3310, a unique β-lactam-β-lactamase inhibitor combination with expanded antibacterial spectrum against Gram-negative pathogens including carbapenem-resistant acinetobacter baumannii. Antimicrob Agents Chemother. 2024. doi:10.1128/aac.01120-23.
   PubMed Web of Science ®Google Scholar
• Fratoni AJ, Berry AV, Liu X, et al. Imipenem/Funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing gram-negative bacteria: a novel modelling approach for time-dependent killing. J Antimicrob Chemother. 2023;78(9):2343–2353. doi: 10.1093/jac/dkad242
   PubMed Web of Science ®Google Scholar
• Li Y, Yan M, Xue F, et al. In vitro and in vivo activities of a novel β-lactamase inhibitor combination imipenem/XNW4107 against recent clinical Gram-negative bacilli from China. J Glob Antimicrob Resist. 2022;31:1–9. doi: 10.1016/j.jgar.2022.07.006
   PubMed Web of Science ®Google Scholar
• Dansky H. Safety, tolerability, and pharmacokinetics of KSP-1007 after single and multiple ascending doses alone or in combination with meropenem in healthy subjects. ASM Microbe; Houston. 2023.
   Google Scholar
• Sader HS, Carvalhaes CG, Mendes RE, et al. Antimicrobial activity of high-dose cefepime-tazobactam (WCK 4282) against a large collection of gram-negative organisms collected worldwide in 2018 and 2019. Int J Infect Dis. 2022;116:306–312. doi: 10.1016/j.ijid.2022.01.029
   PubMed Web of Science ®Google Scholar
• Samuelsen Ø, Åstrand OAH, Fröhlich C, et al. ZN148 is a modular synthetic metallo-β-lactamase inhibitor that reverses carbapenem resistance in gram-negative pathogens in vivo. Antimicrob Agents Chemother. 2020;64(6). doi: 10.1128/AAC.02415-19
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 2]. Available from: www.adjutecpharma.com/news
   Google Scholar
• Li J, Nation RL, Turnidge JD, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006;6(9):589–601. doi: 10.1016/S1473-3099(06)70580-1
   PubMed Web of Science ®Google Scholar
• Roberts KD, Zhu Y, Azad MAK, et al. A synthetic lipopeptide targeting top-priority multidrug-resistant gram-negative pathogens. Nat Commun. 2022;13(1). doi: 10.1038/s41467-022-29234-3.
   Web of Science ®Google Scholar
• Brown P, Abbott E, Abdulle O, et al. Design of next generation polymyxins with lower toxicity: the discovery of SPR206. ACS Infect Dis. 2019;5(10):1645–1656. doi: 10.1021/acsinfecdis.9b00217
   PubMed Web of Science ®Google Scholar
• Akhoundsadegh N, Belanger CR, Hancock REW. Outer membrane interaction kinetics of new polymyxin B analogs in gram-negative bacilli. Antimicrob Agents Chemother. 2019;63(10). doi: 10.1128/AAC.00935-19
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhao C, Wang Q, et al. Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant gram-negative bacilli. J Antimicrob Chemother. 2020;75(9):2609–2615. doi: 10.1093/jac/dkaa217
   PubMed Web of Science ®Google Scholar
• Bruss J, Lister T, Gupta VK, et al. Single- and multiple-ascending-dose study of the safety, tolerability, and pharmacokinetics of the polymyxin derivative SPR206. Antimicrob Agents Chemother. 2021;65(10). doi: 10.1128/AAC.00739-21
   PubMed Web of Science ®Google Scholar
• Rodvold KA, Bader J, Bruss JB, et al. Pharmacokinetics of SPR206 in plasma, pulmonary epithelial lining fluid, and Alveolar Macrophages following intravenous administration to healthy adult subjects. Antimicrob Agents Chemother. 2023;67(7). doi: 10.1128/aac.00426-23
   PubMed Web of Science ®Google Scholar
• Bruss JB, Bader J, Hamed KA, et al. Safety and pharmacokinetics of SPR206 in subjects with varying degrees of renal impairment. Antimicrob Agents Chemother. 2023;67(11). doi: 10.1128/aac.00505-23
   Google Scholar
• Duncan LR, Wang W, Sader HS. In vitro potency and spectrum of the novel polymyxin MRX-8 tested against clinical isolates of gram-negative bacteria. Antimicrob Agents Chemother. 2022;66(5). doi: 10.1128/aac.00139-22
   Web of Science ®Google Scholar
• Wu S, Yin D, Zhi P, et al. In vitro activity of MRX-8 and comparators against clinical isolated gram-negative bacilli in China. Front Cell Infect Microbiol. 2022;12. doi: 10.3389/fcimb.2022.829592
   Web of Science ®Google Scholar
• Lepak AJ, Wang W, Andes DR. Pharmacodynamic evaluation of MRX-8, a novel polymyxin, in the neutropenic mouse thigh and lung infection models against gram-negative pathogens. Antimicrob Agents Chemother. 2020;64(11). doi: 10.1128/AAC.01517-20
   Web of Science ®Google Scholar
• [cited 2024 Jan 2]. Available from: www.micurxchina.com/news
   Google Scholar
• Hameed S, Sharma S, Nandishaiah R. BWC0977, a novel dual target topoisomerase inhibitor: antimicrobial potency, spectrum and mechanism of action. ECCMID; Amsterdam. 2019.
   Google Scholar
• Huband M, Lindley J, Watters A, et al. In vitro activity of BWC0977 (a novel bacterial topoisomerase inhibitor) and comparators against recent clinical and molecularly characterized enterobacteriaceae and non-fermenter isolates from the United states and Europe. ECCMID; Amsterdam. 2019.
   Google Scholar
• [cited 2024 Feb 4]. Available from: www.bugworksresearch.com/pipeline
   Google Scholar
• [cited 2024 Feb 2]. Available from: www.recce.com.au/company-announcements/
   Google Scholar
• Hallal Ferreira Raro O, Poirel L, Tocco M, et al. Impact of veterinary antibiotics on plasmid-encoded antibiotic resistance transfer. J Antimicrob Chemother. 2023;78(9):2209–2216. doi: 10.1093/jac/dkad226
   PubMed Web of Science ®Google Scholar
• Caméléna F, Liberge M, Rezzoug I, et al. In vitro activity of apramycin against 16S-RMTase-producing gram-negative isolates. J Glob Antimicrob Resist. 2023;33:21–25. doi: 10.1016/j.jgar.2023.02.005
   PubMed Web of Science ®Google Scholar
• Galani I, Papoutsaki V, Karaiskos I, et al. In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020–2021: a multicenter study. Eur J Clin Microbiol Infect Dis. 2023;42(7):843–852. doi: 10.1007/s10096-023-04616-7
   PubMed Web of Science ®Google Scholar
• Gysin M, Hon PY, Tan P, et al. Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in Southeast Asia. Int J Antimicrob Agents. 2022;60(4):106659. doi: 10.1016/j.ijantimicag.2022.106659
   PubMed Web of Science ®Google Scholar
• Rzhepishevska O, Ekstrand-Hammarström B, Popp M, et al. The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source. Antimicrob Agents Chemother. 2011;55(12):5568–5580. doi: 10.1128/AAC.00386-11
   PubMed Web of Science ®Google Scholar
• Goss CH, Kaneko Y, Khuu L, et al. Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections. Sci Transl Med. 2018;10(460). doi: 10.1126/scitranslmed.aat7520
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 2]. Available from: www.aridispharma.com/ar-501/
   Google Scholar
• Millard J Broad-spectrum, potent activity of pravibismane versus comparators against diabetic foot ulcer infection patient isolates collected in a phase ib study. 9th International Symposium on the Diabetic Foot; Amsterdam. 2023.
   Google Scholar
• [cited 2023 Dec 17]. Available from: www.microbioncorp.com/pipeline
   Google Scholar
• Antraygues K, Maingot M, Schellhorn B, et al. Design and synthesis of water-soluble prodrugs of rifabutin for intravenous administration. Eur J Med Chem. 2022;238:114515. doi: 10.1016/j.ejmech.2022.114515
   PubMed Web of Science ®Google Scholar
• Trebosc V, Kemmer C, Lociuro S, et al. Rifabutin for infusion (BV100) for the treatment of severe carbapenem-resistant Acinetobacter baumannii infections. Drug Discov Today. 2021;26(9):2099–2104.
   PubMed Web of Science ®Google Scholar
• Trebosc V, Schellhorn B, Schill J, et al. In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms. J Antimicrob Chemother. 2020;75(12):3552–3562. doi: 10.1093/jac/dkaa370
   PubMed Web of Science ®Google Scholar
• Luna B, Trebosc V, Lee B, et al. A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii. Nat Microbiol. 2020;5(9):1134–1143. doi: 10.1038/s41564-020-0737-6
   PubMed Web of Science ®Google Scholar
• Cheng J, Yan J, Reyna Z, et al. Synergistic Rifabutin and colistin reduce emergence of resistance when treating Acinetobacter baumannii. Antimicrob Agents Chemother. 2021;65(4). doi: 10.1128/AAC.02204-20
   Web of Science ®Google Scholar
• Zampaloni C, Mattei P, Bleicher K, et al. A novel antibiotic class targeting the lipopolysaccharide transporter. Nature. 2024;625(7995):566–571. doi: 10.1038/s41586-023-06873-0.
   PubMed Web of Science ®Google Scholar
• Guenther A, Millar L, Messer A, et al. 2126. Safety, tolerability, and pharmacokinetics (PK) in Healthy Participants Following Single Dose Administration of Zosurabalpin, a Novel Pathogen-Specific Antibiotic for the treatment of serious Acinetobacter infections. Open Forum Infect Dis. 2023;10(Supplement_2). doi: 10.1093/ofid/ofad500.1749
   Google Scholar
• He P, Huang S, Wang R, et al. Novel nitroxoline derivative combating resistant bacterial infections through outer membrane disruption and competitive NDM-1 inhibition. Emerg Microbes Infect. 2023;13(1). doi: 10.1080/22221751.2023.2294854
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 1]. Available from: www.asieris.com/pipeline
   Google Scholar
• Ji XW, Xue F, Kang ZS, et al. Model-informed drug development, Pharmacokinetic/Pharmacodynamic cutoff value determination, and antibacterial efficacy of benapenem against enterobacteriaceae. Antimicrob Agents Chemother. 2020;64(3). doi: 10.1128/AAC.01751-19
   Web of Science ®Google Scholar
• Zhao CY, Lv Y, Zhu Y, et al. A first-in-human safety, tolerability, and pharmacokinetics study of Benapenem in healthy Chinese volunteers. Antimicrob Agents Chemother. 2019;63(3). doi: 10.1128/AAC.02188-18
   Web of Science ®Google Scholar
• Yang H, Zhang M, Chen Y, et al. Pharmacokinetics of benapenem for injection in subjects with mild to moderate renal impairment. Eur J Clin Pharmacol. 2022;78(7):1079–1086. doi: 10.1007/s00228-022-03317-y
   PubMed Web of Science ®Google Scholar
• Dalbey RE, Lively MO, Bron S, et al. The chemistry and enzymology of the type I signal peptidases. Protein Sci Publ Protein Soc. 1997;6(6):1129–1138. doi: 10.1002/pro.5560060601
   PubMed Web of Science ®Google Scholar
• Ranasinghe A, Henderson A, Cottrell K, et al. Determining the in vitro susceptibility of tebipenem, an oral carbapenem, against third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolated from bloodstream infections. JAC-Antimicrob Resist. 2022;4(5). doi: 10.1093/jacamr/dlac105
   PubMedGoogle Scholar
• Eckburg PB, Muir L, Critchley IA, et al. Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. N Engl J Med. 2022;386(14):1327–1338. doi: 10.1056/NEJMoa2105462
   PubMed Web of Science ®Google Scholar
• Trout RE, Zulli A, Mesaros E, et al. Discovery of VNRX-7145 (VNRX-5236 etzadroxil): an orally bioavailable β-lactamase inhibitor for Enterobacterales Expressing Ambler class A, C, and D enzymes. J Med Chem. 2021;64(14):10155–10166. doi: 10.1021/acs.jmedchem.1c00437
   PubMed Web of Science ®Google Scholar
• Chatwin CL, Hamrick JC, Trout REL, et al. Microbiological Characterization of VNRX-5236, a Broad-Spectrum β-Lactamase Inhibitor for Rescue of the Orally Bioavailable Cephalosporin Ceftibuten as a Carbapenem-Sparing Agent against Strains of Enterobacterales Expressing Extended-Spectrum β-Lactamases and Serine Carbapenemases. Antimicrob Agents Chemother. 2021;65:e0055221.
   PubMed Web of Science ®Google Scholar
• Karlowsky JA, Wise MG, Hackel MA, et al. Ceftibuten-Ledaborbactam Activity against Multidrug-Resistant and Extended-Spectrum-β-Lactamase-Positive Clinical Isolates of Enterobacterales from a 2018–2020 Global Surveillance Collection. Antimicrob Agents Chemother. 2022;66(11). doi: 10.1128/aac.00934-22
   Web of Science ®Google Scholar
• Karlowsky JA, Hackel MA, Sahm DF. In vitro activity of Ceftibuten/VNRX-5236 against urinary tract infection isolates of Antimicrobial-Resistant Enterobacterales. Antimicrob Agents Chemother. 2022;66(1). doi: 10.1128/AAC.01304-21
   Web of Science ®Google Scholar
• Mendes RE, Rhomberg PR, Watters AA, et al. In vitro activity of the orally bioavailable ceftibuten/VNRX-7145 (VNRX-5236 etzadroxil) combination against a challenge set of enterobacterales pathogens carrying molecularly characterized β-lactamase genes. J Antimicrob Chemother. 2022;77(3):689–694. doi: 10.1093/jac/dkab425
   PubMed Web of Science ®Google Scholar
• Sader HS, Carvalhaes CG, Huband MD, et al. Antimicrobial activity of ceftibuten-avibactam against a global collection of enterobacterales from patients with urinary tract infections (2021). Eur J Clin Microbiol Infect Dis. 2023;2023(4):453–459. doi: 10.1007/s10096-023-04562-4
   Google Scholar
• [cited 2024 Jan 1]. Available from: www.armatapharma.com/pipeline
   Google Scholar
• Rappo U, Kahan-Hanum M, Ussery X A phase 1b/2a randomized, double-blind, placebo-controlled, multicenter study evaluating nebulized phage therapy in Cystic Fibrosis Subjects with chronic Pseudomonas aeruginosa pulmonary infection. North American Cystic Fibrosis Conference 2023; Toronto.
   Google Scholar
• [cited 2023 Nov 29]. Available from: www.biomx.com/our-pipeline/
   Google Scholar
• Tamma PD, Souli M, Billard M, et al. Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial. Trials. 2022;23(1). doi: 10.1186/s13063-022-07047-5.
   PubMed Web of Science ®Google Scholar
• Gencay YE, Jasinskytė D, Robert C, et al. Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice. Nat Biotechnol. 2023;42(2):265–274. doi: 10.1038/s41587-023-01759-y
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 23]. Available from: www.sniprbiome.com/pipeline
   Google Scholar
• Ghose C, Euler CW. Gram-negative bacterial Lysins. Antibiotics. 2020;9(2):74. doi: 10.3390/antibiotics9020074
   Web of Science ®Google Scholar
• Lehoux D In vivo efficacy of CF-370 alone and in addition to amikacin in the rabbit acute pneumonia model caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa. ECCMID 2022.
   Google Scholar
• Deslouches B, Phadke SM, Lazarevic V, et al. De Novo generation of cationic antimicrobial peptides: influence of length and tryptophan substitution on antimicrobial activity. Antimicrob Agents Chemother. 2005;49(1):316–322. doi: 10.1128/AAC.49.1.316-322.2005
   PubMed Web of Science ®Google Scholar
• Deslouches B, Steckbeck JD, Craigo JK, et al. Rational design of engineered cationic antimicrobial peptides consisting exclusively of arginine and tryptophan, and their activity against multidrug-resistant pathogens. Antimicrob Agents Chemother. 2013;57(6):2511–2521. doi: 10.1128/AAC.02218-12
   PubMed Web of Science ®Google Scholar
• Huang DB, Brothers KM, Mandell JB, et al. Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class. PloS One. 2022;17(9):e0274815. doi: 10.1371/journal.pone.0274815
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 15]. Available from: www.peptilogics.com/pipeline
   Google Scholar
• Huang D, Dobbins D, Ghahramani P, et al. A phase 1 study of the safety, tolerability, and pharmacokinetics of single ascending doses of a First-in-Human Engineered Cationic Peptide, PLG0206, intravenously administered in healthy subjects. Antimicrob Agents Chemother. 2022;66(1). doi: 10.1128/AAC.01441-21
   Web of Science ®Google Scholar
• Mandel S, Michaeli J, Nur N, et al. OMN6 a novel bioengineered peptide for the treatment of multidrug resistant gram negative bacteria. Sci Rep. 2021;11(1). doi: 10.1038/s41598-021-86155-9
   PubMed Web of Science ®Google Scholar
• Michaeli J, Mandel S, Maximov S, et al. In vitro and In vivo antimicrobial activity of the novel peptide OMN6 against multidrug-resistant acinetobacter baumannii. Antibiot Basel Switz. 2022;11(9):1201. doi: 10.3390/antibiotics11091201
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 16]. Available from: www.omnixmedical.com/pipeline/
   Google Scholar
• Martin-Loeches I, Dale GE, Torres A. Murepavadin: a new antibiotic class in the pipeline. Expert Rev Anti Infect Ther. 2018;16(4):259–268. doi: 10.1080/14787210.2018.1441024
   PubMed Web of Science ®Google Scholar
• Díez-Aguilar M, Hernández-García M, Morosini MI, et al. Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates. J Antimicrob Chemother. 2021;76(4):984–992. doi: 10.1093/jac/dkaa529
   PubMed Web of Science ®Google Scholar
• Ekkelenkamp MB, Cantón R, Díez-Aguilar M, et al. Susceptibility of pseudomonas aeruginosa recovered from cystic fibrosis patients to murepavadin and 13 comparator antibiotics. Antimicrob Agents Chemother. 2020;64(2). doi: 10.1128/AAC.01541-19
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 13]. Available from: www.spexisbio.com/pipeline
   Google Scholar
• Fraser-Pitt DJ, Dolan SK, Toledo-Aparicio D, et al. Cysteamine inhibits glycine utilisation and disrupts virulence in pseudomonas aeruginosa. Front Cell Infect Microbiol. 2021;11. doi: 10.3389/fcimb.2021.718213
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 1]. Available from: www.novabiotics.co.uk/pipeline
   Google Scholar
• Savitskii MV, Moskaleva NE, Brito A, et al. Pharmacokinetics, quorum-sensing signal molecules and tryptophan-related metabolomics of the novel anti-virulence drug fluorothiazinon in a Pseudomonas aeruginosa-induced pneumonia murine model. J Pharm Biomed Anal. 2023;236:115739. doi: 10.1016/j.jpba.2023.115739
   PubMed Web of Science ®Google Scholar
• Laterre PF, Colin G, Dequin PF, et al. CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2019;19(6):620–630. doi: 10.1016/S1473-3099(18)30805-3
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 1]. Available from: www.eagleus.com/pipeline
   Google Scholar
• DiNubile MJ, Levinson SL, Stossel TP, et al. Recombinant Human Plasma Gelsolin Improves Survival and Attenuates Lung Injury in a Murine Model of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia. Open Forum Infect Dis. 2020;7(8). doi: 10.1093/ofid/ofaa236
   PubMed Web of Science ®Google Scholar
• Rogers JV, Hall VL, McOsker CC. Crumbling the castle: targeting DNABII proteins for collapsing bacterial biofilms as a therapeutic approach to treat disease and combat antimicrobial resistance. Antibiot Basel Switz. 2022;11(1):104. doi: 10.3390/antibiotics11010104
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 6]. Available from: www.clarametyx.com/pipeline
   Google Scholar
• Selim H, Radwan TEE, Reyad AM. Regulation of T3SS synthesis, assembly and secretion in Pseudomonas aeruginosa. Arch Microbiol. 2022;204(8). doi: 10.1007/s00203-022-03068-5
   PubMed Web of Science ®Google Scholar
• [cited 2023 Dec 6]. Available from: www.infextx.com/pipeline
   Google Scholar
• Que YA, Lazar H, Wolff M, et al. Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia. Eur J Clin Microbiol Infect Dis. 2014;33(10):1861–1867. doi: 10.1007/s10096-014-2156-1
   PubMed Web of Science ®Google Scholar
• Soliman C, Walduck AK, Yuriev E, et al. Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine. J Biol Chem. 2018;293(14):5079–5089. doi: 10.1074/jbc.RA117.001170
   PubMed Web of Science ®Google Scholar
• [cited 2024 Jan 1]. Available from: www.alopexx.com/pipeline
   Google Scholar
• Prasad NK, Seiple IB, Cirz RT, et al. Leaks in the pipeline: a Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020. Antimicrob Agents Chemother. 2022;66(5). doi: 10.1128/aac.00054-22.
   Web of Science ®Google Scholar
• Kaye KS, Shorr AF, Wunderink RG, et al. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect Dis. 2023;23:1072–1084.
   PubMed Web of Science ®Google Scholar
• Iovleva A, McElheny CL, Fowler EL, et al. In vitro activity of sulbactam-durlobactam against colistin-resistant and/or cefiderocol-non-susceptible, carbapenem-resistant Acinetobacter baumannii collected in U.S. hospitals. Antimicrob Agents Chemother. 2024. doi:10.1128/aac.01258-23.
   PubMed Web of Science ®Google Scholar
• Ehrmann S, Barbier F, Demiselle J, et al. Inhaled amikacin to prevent ventilator-associated pneumonia. N Engl J Med. 2023;389(22):2052–2062. doi: 10.1056/NEJMoa2310307
   PubMed Web of Science ®Google Scholar
• Tamma PD, Bonomo RA, Mathers AJ. Infectious diseases society of america 2023 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. 2023.
   Google Scholar
• Mushtaq S, Vickers A, Woodford N, et al. Activity of aztreonam/avibactam and ceftazidime/avibactam against Enterobacterales with carbapenemase-independent carbapenem resistance. Int J Antimicrob Agents. 2024;63(3):107081. doi: 10.1016/j.ijantimicag.2023.107081
   PubMed Web of Science ®Google Scholar
• Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: a randomized clinical trial. JAMA. 2018;319(17):1781–9. doi: 10.1001/jama.2018.3627
   PubMed Web of Science ®Google Scholar
• Parmar K, Komarow L, Ellison DW, et al. Interlaboratory comparison of Pseudomonas aeruginosa phage susceptibility testing. J Clin Microbiol. 2023;61(12). doi: 10.1128/jcm.00614-23
   PubMed Web of Science ®Google Scholar
• Oh JT, Ambler JE, Cassino C, et al. Development of a broth microdilution method for exebacase susceptibility testing. Antimicrob Agents Chemother. 2021;65:e0258720.
   PubMed Web of Science ®Google Scholar