Novel investigational treatments for ventilator-associated pneumonia and critically ill patients in the intensive care unit

References

• Craven TH, Wojcik, G, McCoubrey, J, Brooks, O et al, . Ventilator-associated pneumonia surveillance using two methods. J Hosp Infect. 2020 Apr;104(4):522–528.
   PubMed Web of Science ®Google Scholar
• Steen J, Vansteelandt, S, De Bus, L, Depuydt, P et al, . Attributable mortality of ventilator-associated pneumonia. replicating findings, revisiting methods. Ann Am Thorac Soc. 2021 May;18(5):830–837.
   PubMed Web of Science ®Google Scholar
• Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol. 2012 Mar;33(3):250–256.
   PubMed Web of Science ®Google Scholar
• Vincent JL, Bihari, D J, Suter, P M, Bruining, H A, White, J, Nicholas-Chanoin, M H et al, . The prevalence of nosocomial infection in intensive care units in Europe. results of the European Prevalence of Infection in Intensive Care (EPIC) study. EPIC International Advisory Committee. JAMA. 1995 Aug;274(8):639–644.
   PubMed Web of Science ®Google Scholar
• Keneally RJ, Peterson TJ, Benjamin JR, et al. Making ventilator associated pneumonia rate a meaningful quality marker. J Intensive Care Med. 2020 Sep;885066620952763. https://doi.org/10.1177/0885066620952763
   Google Scholar
• Weber DJ, Sickbert-Bennett EE, Brown V, et al. Completeness of surveillance data reported by the National Healthcare Safety Network: an analysis of healthcare-associated infections ascertained in a tertiary care hospital, 2010. Infect Control Hosp Epidemiol. 2012 Jan;33(1):94–96.
   PubMed Web of Science ®Google Scholar
• Klein EY, Van Boekel, TP, Martinez, EM, Pant, S, Gandra, S et al, . Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci. 2018 Apr;115(15):E3463–E3470.
   PubMed Web of Science ®Google Scholar
• Luyt C-E, Combes A, Trouillet J-L, et al. Biomarkers to optimize antibiotic therapy for pneumonia due to multidrug-resistant pathogens. Clin Chest Med. 2011 Sep;32(3):431–438.
   PubMed Web of Science ®Google Scholar
• Martin-Loeches I, Povoa, P, Rodriguez, A, Curcio, D et al, . Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015 Nov;3(11):pp. 859–868.
   PubMed Web of Science ®Google Scholar
• Boucher HW, Talbot, GH, Bradley, JS, Edwards, JE, Gilbert, D et al, . Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009 Jan;48(1):1–12.
   PubMed Web of Science ®Google Scholar
• European Centre for Disease Prevention and Control and European Medicines Agency, The bacterial challenge: time to react: a call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. LU: publications office, 2009. cited 2021 Sep 22 [Online]. Available: https://data.europa.eu/doi/10.2900/2518
   Google Scholar
• Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 2008 Apr;197(8):1079–1081.
   PubMed Web of Science ®Google Scholar
• Zilahi G, Artigas A, Martin-Loeches I. What’s new in multidrug-resistant pathogens in the ICU? Ann Intensive Care. 2016 Oct;6(1):96.
   PubMed Web of Science ®Google Scholar
• Kostyanev T, Bonten, MJM, O'Brien, S, Steel, H, Ross, S, Francois, B, et al. The innovative medicines initiative’s new drugs for bad bugs programme: European public-private partnerships for the development of new strategies to tackle antibiotic resistance. J Antimicrob Chemother. 2016 Feb;71(2):290–295.
   PubMed Web of Science ®Google Scholar
• Luyt C-E, Bréchot N, Trouillet J-L, et al. Antibiotic stewardship in the intensive care unit. Crit Care Lond Engl. 2014 Aug;18(5):480.
   PubMed Web of Science ®Google Scholar
• Ribeir Oda Cunha B, Fonseca LP, Calado CRC. Antibiotic discovery: where have we come from, where do we go? Antibiotics. 2019 Apr;8(2):45.
   Google Scholar
• Renwick MJ, Brogan DM, Mossialos E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J Antibiot (Tokyo). 2016 Feb;69(2):73–88.
   PubMed Web of Science ®Google Scholar
• European Centre for Disease Prevention and Control (ECDC), E. F. S. Authority (EFSA), and E. M. Agency (EMA). ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals. EFSA J. 2017;15(7): 04872.
   Web of Science ®Google Scholar
• Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis. 2019 Apr;6(2):109–119.
   PubMed Web of Science ®Google Scholar
• Gajdács M. The continuing threat of methicillin-resistant staphylococcus aureus. Antibiot. Basel Switz 2019 May;8(2):p. E52.
   PubMed Web of Science ®Google Scholar
• Yusuf E, Bax HI, Verkaik NJ, et al. An update on eight “new” antibiotics against multidrug-resistant gram-negative bacteria. J Clin Med. 2021 Mar;10(5):1068.
   PubMed Web of Science ®Google Scholar
• Boucher HW. Bad bugs, no drugs 2002–2020: progress, challenges, and call to action. Trans. Am. Clin. Climatol. Assoc., 2020 131 ;65–71.
   PubMedGoogle Scholar
• Tacconelli E, Carrara, E, Savoldi, A, Harbarth, S, Mendelson, M, Monnet, DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318–327.
   PubMed Web of Science ®Google Scholar
• Motsch J, de Oliveira, CM, Stus, V, Koksal, I, Lyulko, O, Boucher , H, 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 Off Publ Infect Dis Soc Am. 2020 Apr;70(9):1799–1808.
   PubMed Web of Science ®Google Scholar
• Martin-Loeches I, Rodriguez AH, Torres A. New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe. Curr Opin Crit Care. 2018 Oct;24(5):347–352.
   PubMed Web of Science ®Google Scholar
• ‘zavicefta-epar-product-information_en.pdf’ zavicefta-epar-product-information_en.pdf’ . Accessed: Aug. 19, 2021 Accessed 19 08 2021. Accessed https://www.ema.europa.eu/en/documents/product-information/zavicefta-epar-product-information_en.pdf
   Google Scholar
• Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of gram-negative bacterial infections. Core Evid 2014;9:13–25.
   PubMedGoogle Scholar
• Krapp F, Grant JL, Sutton SH, et al. Treating complicated carbapenem-resistant Enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation. Int J Antimicrob Agents. 2017 Jun;49(6):770–773.
   PubMed Web of Science ®Google Scholar
• Soriano A, Carmeli Y, Omrani AS, et al. Ceftazidime-avibactam for the treatment of serious gram-negative infections with limited treatment options: a systematic literature review. Infect. Dis. Ther. 2021 Aug;10(4):1989–2034.
   PubMed Web of Science ®Google Scholar
• Sader HS, Castanheira M, Flamm RK, et al. Ceftazidime/avibactam tested against gram-negative bacteria from intensive care unit (ICU) and non-ICU patients, including those with ventilator-associated pneumonia. Int J Antimicrob Agents. 2015 Jul;46(1):53–59.
   PubMed Web of Science ®Google Scholar
• ‘International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia | European Respiratory Society.’ https://erj.ersjournals.com/content/50/3/1700582 (cited Aug. 19, 2021).
   Google Scholar
• ‘Overview | pneumonia (hospital-acquired): antimicrobial prescribing | guidance | NICE.’ https://www.nice.org.uk/guidance/ng139 (cited Aug. 19, 2021).
   Google Scholar
• Sartelli M, Chichom-Mefire, A, Labricciosa, FM, Hardcastle, T, Abu-Zidan, FM, Adesunkanmi, AK, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J. Emerg. Surg. WJES. 2017Jul;12:29.
   PubMed Web of Science ®Google Scholar
• Kalil AC, Metersky, ML, Klompas, M, Muscedere, J, Sweeney, DA, Palmer, LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society. Clin Infect Dis Off Publ Infect Dis Soc Am. 2016 Sep;63(5):e61–e111.
   PubMed Web of Science ®Google Scholar
• Anonymous, ‘Zerbaxa,’ European Medicines Agency, Sep. 17, 2018. [Online]. Available: https://www.ema.europa.eu/en/medicines/human/EPAR/zerbaxa (cited 2021 Aug. 30
   Google Scholar
• ‘Drug approval package: brand name (generic name) NDA #’. [Online]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000TOC.cfm (cited 2021 Aug 30).
   Google Scholar
• Cuba GT, Rocha-Santos, G, Cayo, R, Streling, AP, Nodari, CS, et al. In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa. J Antimicrob Chemother. 2020 Jul;75(7):1874–1878.
   PubMed Web of Science ®Google Scholar
• Goodlet KJ, Nicolau DP, Nailor MD. In vitro comparison of ceftolozane-tazobactam to traditional beta-lactams and ceftolozane-tazobactam as an alternative to combination antimicrobial therapy for pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017 Dec;61(12):e01350–17.
   PubMed Web of Science ®Google Scholar
• Kollef MH, Nováček, M, Kivistik, U, et al. Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2019 Dec;19(12):1299–1311.
   PubMed Web of Science ®Google Scholar
• Zaragoza R, Vidal-Cortes, P, Aguilar, G, Borges, M, Diaz, E, et al. Update of the treatment of nosocomial pneumonia in the ICU. Crit Care. 2020 Jun;24(1):383.
   PubMed Web of Science ®Google Scholar
• Talbot GH, Das, A, Cush, S, Dane, A, Wible, M, Echols, R, et al. Evidence-based study design for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. J Infect Dis. 2019 Apr;219(10):1536–1544.
   PubMed Web of Science ®Google Scholar
• Zhanel GG, Lawrence, CK, Adam, H, Schweizer, F, Zelenitsky, S, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-β-lactamase inhibitor combinations. Drugs. 2018 Jan;78(1):65–98.
   PubMed Web of Science ®Google Scholar
• Lob SH, Hackel, MA, Kazmierczak, KM, Hoban, DJ, et al. 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 Jun;88(2):171–176.
   PubMed Web of Science ®Google Scholar
• Francisco EM, ‘Recarbrio’, European Medicines Agency, Dec. 10, 2019. [Online]. Available: https://www.ema.europa.eu/en/medicines/human/EPAR/recarbrio (cited 2021 Sep. 02
   Google Scholar
• ‘recarbrio-epar-product-information_en.pdf’. Accessed: Sep. 02, 2021 Accessed 2 9 2021. Accessed: https://www.ema.europa.eu/en/documents/product-information/recarbrio-epar-product-information_en.pdf
   Google Scholar
• Kaye KS, Bhowmick, T, Metallidis, S, Bleasdale, SC, Sagan, OS, et al. 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. 2018 Feb;319(8):788–799.
   PubMed Web of Science ®Google Scholar
• Pfaller MA, Huband MD, Mendes RE, et al. In vitro activity of meropenem/vaborbactam and characterisation of carbapenem resistance mechanisms among carbapenem-resistant Enterobacteriaceae from the 2015 meropenem/vaborbactam surveillance programme. Int J Antimicrob Agents. 2018 Aug;52(2):144–150.
   PubMed Web of Science ®Google Scholar
• Wunderink RG, Giamarellos-Bourboulis, EJ, Rahav, Galia, Mathers, AJ, Bassetti, M, 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 Dec;7(4):4.
   Web of Science ®Google Scholar
• Bhowmick T, ‘clinical outcomes of patient subgroups in theStudy’ TANGOII. Infect Dis Ther. Mar 2021;10(1):35–46
   PubMed Web of Science ®Google Scholar
• Oueslati S, Nordmann P, Poirel L. Heterogeneous hydrolytic features for OXA-48-like -lactamases. J Antimicrob Chemother. 2015 Jan;dku524. DOI:https://doi.org/10.1093/jac/dku524
   Google Scholar
• Chew KL, Tay MKL, Cheng B, et al. Aztreonam-avibactam combination restores susceptibility of aztreonam in dual-carbapenemase-producing enterobacteriaceae. Antimicrob Agents Chemother. 2018 Jul;62(8):e00414–18.
   PubMed Web of Science ®Google Scholar
• Esposito S, Stone GG, Papaparaskevas J. In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. J Glob Antimicrob Resist. 2021Mar;24:14–22.
   PubMed Web of Science ®Google Scholar
• Vasoo S, Cunningham, SA, Cole, NC, Kohner, PC, Menon, SR, Krause, KM, Harris, KA, De, PP, Koh, TH, Patel, R, et al. In vitro activities of ceftazidime-avibactam, aztreonam-avibactam, and a panel of older and contemporary antimicrobial agents against carbapenemase-producing gram-negative bacilli. Antimicrob Agents Chemother. 2015 Dec;59(12):7842–7846.
   PubMed Web of Science ®Google Scholar
• Isler B, Harris P, Stewart AG, et al. An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR enterobacterales and Pseudomonas aeruginosa. J Antimicrob Chemother. 2021 Feb;76(3):550–560.
   PubMed Web of Science ®Google Scholar
• Karlowsky JA, Hackel MA, Bouchillon SK, et al. In vitro activity of WCK 5222 (cefepime-zidebactam) against worldwide collected gram-negative bacilli not susceptible to carbapenems. Antimicrob Agents Chemother. 2020 Nov;64(12):e01432–20.
   PubMed Web of Science ®Google Scholar
• Livermore DM, Mushtaq S, Warner M, et al. In vitro activity of cefepime/zidebactam (WCK 5222) against gram-negative bacteria. J Antimicrob Chemother. 2017 May;72(5):1373–1385.
   PubMed Web of Science ®Google Scholar
• Mushtaq S, Garello P, Vickers A, et al. Activity of cefepime/zidebactam (WCK 5222) against “problem” antibiotic-resistant gram-negative bacteria sent to a national reference laboratory. J Antimicrob Chemother. 2021 May;76(6):1511–1522.
   PubMed Web of Science ®Google Scholar
• Bhagwat SS, Periasamy H, Takalkar SS, et al. The novel β-lactam enhancer zidebactam augments the in vivo pharmacodynamic activity of cefepime in a neutropenic mouse lung Acinetobacter baumannii infection model. Antimicrob Agents Chemother. 2019 Mar;63(4):e02146–18.
   PubMed 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 Jan;63(1):e01484–18.
   PubMed Web of Science ®Google Scholar
• Thomson KS, AbdelGhani S, Snyder JW, et al. Activity of cefepime-zidebactam against multidrug-resistant (MDR) gram-negative pathogens. Antibiotics. 2019 Mar;8(1):32.
   Google Scholar
• Venatorx Pharmaceuticals, Inc., ‘A phase 3, randomized, double-blind, active controlled noninferiority study evaluating the efficacy, safety, and tolerability of cefepime/VNRX-5133 in adults with complicated urinary tract infections (cUTI), including acute pyelonephritis’, clinicaltrials.gov, clinical trial registration NCT03840148, Jun. 2021. cited 2021 Sep 21. [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT03840148
   Google Scholar
• Das S, Fitzgerald, R, Ullah, A, et al. Intrapulmonary pharmacokinetics of cefepime and enmetazobactam in healthy volunteers: towards new treatments for nosocomial pneumonia. Antimicrob Agents Chemother. 2020 Dec;65(1):e01468–20.
   PubMed Web of Science ®Google Scholar
• Allecra, ‘A Phase 3, Randomized, Double-blind, study to evaluate the efficacy and safety of cefepime-AAI101 compared to piperacillin/tazobactam in the treatment of complicated urinary tract infections, including acute pyelonephritis.,’ clinicaltrials.gov, Clinical trial registration NCT03687255, Mar. 2020.cited 2021 Sep 21. [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT03687255
   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 Oct;70(10):2779–2786.
   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. Antimicrobial Agents and Chemotherapy. 2020 Apr;64(5):e02229–19.
   PubMed Web of Science ®Google Scholar
• Hagihara M, Kato, H, Sugano , T et al, . Pharmacodynamic evaluation of meropenem, cefepime, or aztreonam combined with a novel β-lactamase inhibitor, nacubactam, against carbapenem-resistant and/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model. Int J Antimicrob Agents. 2021 May;57(5):106330.
   PubMed Web of Science ®Google Scholar
• Monogue ML, Giovagnoli S, Bissantz C, et al. In vivo efficacy of meropenem with a novel non-β-lactam–β-lactamase inhibitor, nacubactam, against gram-negative organisms exhibiting various resistance mechanisms in a murine complicated urinary tract infection model. Antimicrob Agents Chemother. 2018 Aug;62(9):e02596–17.
   PubMed Web of Science ®Google Scholar
• Monogue ML, Nicolau DP. Translational efficacy of humanized exposures of cefepime, ertapenem, and levofloxacin against extended-spectrum-β-lactamase-producing Escherichia coli in a murine model of complicated urinary tract infection. Antimicrob. Agents Chemother. 2017;61(11):e01329–17.
   PubMed Web of Science ®Google Scholar
• Giacobbe DR, De Rosa, FG, Del Bono, V, Grossi, PA et al, . Ceftobiprole: drug evaluation and place in therapy. Expert Rev Anti Infect Ther. 2019 Sep;17(9):689–698.
   PubMed Web of Science ®Google Scholar
• Campanile F, Bongiorno D, Mongelli G, et al. Bactericidal activity of ceftobiprole combined with different antibiotics against selected Gram-positive isolates. Diagn Microbiol Infect Dis. 2019 Jan;93(1):77–81.
   PubMed Web of Science ®Google Scholar
• Torres A, Mouton JW, Pea F. Pharmacokinetics and dosing of ceftobiprole medocaril for the treatment of hospital- and community-acquired pneumonia in different patient populations. Clin Pharmacokinet. 2016 Dec;55(12):1507–1520.
   PubMed Web of Science ®Google Scholar
• Nicholson SC, Welte, T, File Jr, TM, Strauss, RS et al, . A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation. Int J Antimicrob Agents. 2012 Mar;39(3):240–246.
   PubMed Web of Science ®Google Scholar
• Awad SS, Rodriguez, AH, Chuang, YC, Marjanek, Z et al, . A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia. Clin. Infect. Dis. Off. Publ. Infect Dis. Soc. Am 2014 Jul;59(1):51–61.
   PubMed Web of Science ®Google Scholar
• Lupia T, Pallotto C, Corcione S, et al. Ceftobiprole perspective: current and potential future indications. Antibiotics. 2021 Feb;10(2):170.
   Web of Science ®Google Scholar
• Overcash JS, Kim, C, Keech, R, Gumenchuk, I et al, . Ceftobiprole compared with vancomycin plus aztreonam in the treatment of acute bacterial skin and skin structure infections: results of a phase 3, randomized, double-blind trial (TARGET). Clin Infect Dis Off Publ Infect Dis Soc Am. 2020 Sep p. ciaa974. DOI:https://doi.org/10.1093/cid/ciaa974
   Google Scholar
• Sotgiu G, Aliberti, S, Gramegna, A, Mantero, M et al, . Efficacy and effectiveness of Ceftaroline Fosamil in patients with pneumonia: a systematic review and meta-analysis. Respir Res. 2018 Oct;19(1):205.
   PubMedGoogle Scholar
• File TM, Low, DE, Eckburg, PB et al, . FOCUS 1: a randomized, double-blinded, multicentre, phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66(3):iii19–32.
   PubMedGoogle Scholar
• Low DE, File, TM, Eckburg, PB et al, . FOCUS 2: a randomized, double-blinded, multicentre, phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66(3):iii33–44.
   PubMedGoogle Scholar
• Riccobene TA, Pushkin R, Jandourek A, et al. Penetration of ceftaroline into the epithelial lining fluid of healthy adult subjects. Antimicrob Agents Chemother. 2016 Sep;60,(10):5849–5857.
   PubMed Web of Science ®Google Scholar
• Welte T, Kantecki M, Stone GG, et al. Ceftaroline fosamil as a potential treatment option for staphylococcus aureus community-acquired pneumonia in adults. Int J Antimicrob Agents. 2019 Oct;54(4):410–422.
   PubMed Web of Science ®Google Scholar
• Kaye KS, Udeani G, Cole P, et al. Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia. Hosp. Pract 2015 Jul;43(3):144–149.
   PubMedGoogle Scholar
• Hackel MA, Tsuji M, Yamano Y, et al. 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. 2017 Aug;61(9):e00093–17.
   PubMed Web of Science ®Google Scholar
• Dimitrova EK, ‘Fetcroja’, European Medicines Agency, Feb. 24, 2020. [Online]. Available: https://www.ema.europa.eu/en/medicines/human/EPAR/fetcroja (cited 2021 Sep. 14
   Google Scholar
• Bassetti M, Echols, R, Matsunaga, Y 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 Feb;21(2):226–240.
   PubMed Web of Science ®Google Scholar
• Wunderink RG, Matsunaga, Y, Ariyasu, M et al, . 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. 2021 Feb;21(2):213–225.
   PubMed Web of Science ®Google Scholar
• Falcone M, Tiseo, Giusy, Nicastro, M et al, . Cefiderocol as rescue therapy for Acinetobacter baumannii and other carbapenem-resistant gram-negative infections in intensive care unit patients. Clin Infect Dis. 2021 Jun;72(11):2021–2024.
   PubMed Web of Science ®Google Scholar
• ‘Summary review plazomicin FDA approval’. cited 2021 Sep 16. [Online]. Available: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000SumR.pdf
   Google Scholar
• Aggen JB, Armstrong, ES, Goldblum, AA et al, . Synthesis and spectrum of the neoglycoside ACHN-490. Antimicrob Agents Chemother. 2010 Nov;54(11):4636–4642.
   PubMed Web of Science ®Google Scholar
• Almaghrabi R, Clancy, CJ, Doi, Y et al, . Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and other agents. Antimicrob Agents Chemother. 2014 Aug;58(8):4443–4451.
   PubMed Web of Science ®Google Scholar
• Connolly LE, Riddle V, Cebrik D, et al. 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 Apr;62(4):e01989–17.
   PubMed Web of Science ®Google Scholar
• Wagenlehner FME, Cloutier, DJ, Komirenko, AS et al, . Once-daily plazomicin for complicated urinary tract infections. N Engl J Med. 2019 Feb;380(8):729–740.
   PubMed Web of Science ®Google Scholar
• McKinnell JA, Dwyer, JP, Talbot, GH et al, . Plazomicin for infections caused by carbapenem-resistant enterobacteriaceae. N. Engl. J. Med. 2019 Feb;380(8):791–793.
   PubMed Web of Science ®Google Scholar
• Matsumoto T. Arbekacin: another novel agent for treating infections due to methicillin-resistant staphylococcus aureus and multidrug-resistant gram-negative pathogens. Clin. Pharmacol. Adv. Appl 2014Sep;6:139–148.
   PubMedGoogle Scholar
• Parajuli NP, Mandava CS, Pavlov MY, et al. Mechanistic insights into translation inhibition by aminoglycoside antibiotic arbekacin. Nucleic Acids Res. 2021 Jun;49(12):6880–6892.
   PubMed Web of Science ®Google Scholar
• Watanabe A, Yanagihara, K, Matsumoto, T et al, . Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese society of chemotherapy, Japanese association for infectious diseases, and Japanese society for clinical microbiology in 2009: general view of the pathogens’ antibacterial susceptibility’. J. Infect. Chemother. Off. J. Jpn. Soc. Chemother 2012 Oct;18(5):609–620.
   PubMed Web of Science ®Google Scholar
• Hwang J-H, Lee J-H, Moon M-K, et al. The efficacy and safety of arbekacin and vancomycin for the treatment in skin and soft tissue MRSA infection: preliminary study. Infect Chemother. 2013 Mar;45(1):62–68.
   PubMedGoogle Scholar
• Araoka H, Baba, M, Takagi, S et al, . Monobactam and aminoglycoside combination therapy against metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa screened using a “break-point checkerboard plate.” Scand J. Infect. Dis 2010 Mar;42(3):231–233.
   PubMed Web of Science ®Google Scholar
• Sutcliffe JA, O’Brien W, Fyfe C, et al. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother. 2013 Nov;57(11):5548–5558.
   PubMed Web of Science ®Google Scholar
• Livermore DM, Mushtaq S, Warner M, et al. In vitro activity of eravacycline against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii. Antimicrob Agents Chemother. 2016 May;60(6):3840–3844.
   PubMed Web of Science ®Google Scholar
• Connors KP, Housman, ST, Pope, JS et al, . Phase I, Open-Label, Safety and Pharmacokinetic Study To Assess Bronchopulmonary Disposition of Intravenous Eravacycline in Healthy Men and Women’.Antimicrob Agents Chemother 2014 Apr;58(4):2113–2118.
   PubMed Web of Science ®Google Scholar
• Solomkin J, Evans, D, Slepavicius, A et al, . Assessing the efficacy and safety of eravacycline vs ertapenem in complicated intra-abdominal infections in the investigating gram-negative infections treated with eravacycline (IGNITE 1) trial: a randomized clinical trial. JAMA Surg. 2017 Mar;152(3):224.
   PubMed Web of Science ®Google Scholar
• Solomkin JS, Evans, D, Slepavicius, A et al, . IGNITE4: results of a phase 3, randomized, multicenter, prospective trial of eravacycline vs meropenem in the treatment of complicated intraabdominal infections. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019 Sep;69(6):921–929.
   PubMed Web of Science ®Google Scholar
• Alosaimy S, Molina, KC, Claeys, KC et al, . Early experience with eravacycline for complicated infections. Open Forum Infect Dis. 2020 May;7(5):ofaa071.
   PubMed Web of Science ®Google Scholar
• Zhanel GG, Love, R, Adam, H et al, . Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens. Drugs. 2015 Feb;75(3):253–270.
   PubMed Web of Science ®Google Scholar
• Anonymous, ‘Sivextro,’ European Medicines Agency, Sep. 17, 2018. [Online]. Available: https://www.ema.europa.eu/en/medicines/human/EPAR/sivextro (cited 2021 Sep. 17
   Google Scholar
• Bensaci M, Sahm D. Surveillance of tedizolid activity and resistance: in vitro susceptibility of Gram-positive pathogens collected over 5 years from the United States and Europe. Diagn Microbiol Infect Dis. 2017 Feb;87(2):133–138.
   PubMed Web of Science ®Google Scholar
• Shorr AF, Lodise, TP, Corey, GR et al, . Analysis of the phase 3 ESTABLISH trials of tedizolid versus linezolid in acute bacterial skin and skin structure infections’. Antimicrob Agents Chemother. 2015 Feb;59(2):864–871.
   PubMed Web of Science ®Google Scholar
• Wunderink RG, Roquilly, A, Croce, M, Rodriguez Gonzalez, D et al, . A phase 3, randomized, double-blind study comparing tedizolid phosphate and linezolid for treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia. Clin Infect Dis Off Publ Infect Dis Soc Am. 2021 Mar;73(3):e710–e718.
   PubMed Web of Science ®Google Scholar
• Bouza E, Muñoz P, Burillo A. The role of tedizolid in skin and soft tissue infections. Curr Opin Infect Dis. 2018 Apr;31(2):131–140.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wang, Y, Van Driel, ML et al, . Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia. Antimicrob Resist Infect Control. 2019 May;8(1):72.
   PubMedGoogle Scholar
• Kutateladze M. Experience of the Eliava Institute in bacteriophage therapy. Virol Sin. 2015 Feb;30(1):80–81.
   PubMed Web of Science ®Google Scholar
• Hesse S, Adhya S. Phage therapy in the twenty-first century: facing the decline of the antibiotic era; is it finally time for the age of the phage?’. Annu Rev Microbiol. 2019 Sep;73(1):155–174.
   PubMedGoogle Scholar
• Hesse S, Rajaure, M, Wall, E et al, . Phage resistance in multidrug-resistant Klebsiella pneumoniae ST258 evolves via diverse mutations that culminate in impaired adsorption. mBio. 2020 Jan;11(1):e02530–19.
   PubMed Web of Science ®Google Scholar
• Hampton HG, Watson BNJ, Fineran PC. The arms race between bacteria and their phage foes. Nature. 2020 Jan;577(7790):327–336.
   PubMed Web of Science ®Google Scholar
• Burmeister AR, Fortier, A, Roush, C et al, . Pleiotropy complicates a trade-off between phage resistance and antibiotic resistance. Proc Natl Acad Sci. 2020 May;117(21):11207–11216.
   PubMed Web of Science ®Google Scholar
• Adaptive Phage Therapeutics, Inc., ‘Expanded access study of phage treatment in Covid-19 patients on anti-microbials for pneumonia or bacteremia/septicemia due to a. baumannii, p. aeruginosa or s. aureus’, clinicaltrials.gov, clinical trial registration NCT04636554, Feb. 2021. Accessed: 2021 Sep 20 .[Online]. Available: https://clinicaltrials.gov/ct2/show/NCT04636554
   Google Scholar
• Maddocks S, Fabijan, AP, Ho, J et al, . Bacteriophage therapy of ventilator-associated pneumonia and empyema caused by pseudomonas aeruginosa. Am J Respir Crit Care Med. 2019 Nov;200(9):1179–1181.
   PubMed Web of Science ®Google Scholar
• Bagińska N, Pichlak A, Górski A, et al. Specific and selective bacteriophages in the fight against multidrug-resistant Acinetobacter baumannii. Virol Sin. 2019 Aug;34(4):347–357.
   PubMed Web of Science ®Google Scholar
• Debarbieux L, LeDuc, D, Maura, D et al, . Bacteriophages can treat and prevent pseudomonas aeruginosa lung infections. J Infect Dis. 2010 Apr;201(7):1096–1104.
   PubMed Web of Science ®Google Scholar
• Comeau AM, Tétart F, Trojet SN, et al. Phage-antibiotic synergy (PAS): β-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE. 2007 Aug;2(8):e799.
   PubMed Web of Science ®Google Scholar
• Kebriaei R, Lev, K, Morrisette, T et al, . Bacteriophage-antibiotic combination strategy: an alternative against methicillin-resistant phenotypes of staphylococcus aureus. Antimicrob Agents Chemother. 2020 Jun;64(7):e00461–20.
   PubMed Web of Science ®Google Scholar
• Gu Liu C, Green, SI, Min , L et al, . Phage-antibiotic synergy is driven by a unique combination of antibacterial mechanism of action and stoichiometry. mBio. 2020 Aug;11(4):e01462–20.
   PubMed Web of Science ®Google Scholar
• Wu N, Dai, J, Mingquan, G et al, . Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients. Emerg Microbes Infect. 2021 Dec;10(1):612–618.
   PubMed Web of Science ®Google Scholar
• Lin Y, Kyung Chang RY, Britton WJ, et al. Synergy of nebulized phage PEV20 and ciprofloxacin combination against Pseudomonas aeruginosa. Int J Pharm. 2018 Nov;551(1–2):158–165.
   PubMedGoogle Scholar
• Li M, Chang RYK, Lin Y, et al. Phage cocktail powder for Pseudomonas aeruginosa respiratory infections. Int J Pharm. 2021Mar;596:120200.
   PubMedGoogle Scholar
• Monserrat-Martinez A, Gambin Y, Sierecki E. Thinking outside the bug: molecular targets and strategies to overcome antibiotic resistance. Int J Mol Sci. 2019 Mar;20(6):E1255.
   PubMed Web of Science ®Google Scholar
• Falcó V, Burgos J, Papiol E, et al. Investigational drugs in phase I and phase II clinical trials for the treatment of hospital-acquired pneumonia. Expert Opin Investig Drugs. 2016 Jun;25(6):653–665.
   PubMed Web of Science ®Google Scholar
• Horn MP, Zuercher, AW, Imboden, MA et al, . Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11. Antimicrob Agents Chemother. 2010 Jun;54(6):2338–2344.
   PubMed Web of Science ®Google Scholar
• Que Y-A, 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 Oct;33(10):1861–1867.
   PubMed Web of Science ®Google Scholar
• Hua L, Hilliard, JJ, Shi, Y et al, . Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob Agents Chemother. 2014;58(2):1108–1117.
   PubMed Web of Science ®Google Scholar
• Sakagami M. In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv Drug Deliv Rev. 2006 Oct;58(9–10):1030–1060.
   PubMed Web of Science ®Google Scholar
• Rouby -J-J, Monsel A. Nebulized Antibiotics. Anesthesiology. 2019 Aug;131(2):229–232.
   PubMedGoogle Scholar
• Rello J, Sole-Lleonart, C, Rouby, JJ et al, . Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect. 2017 Sep;23(9):629–639.
   PubMed Web of Science ®Google Scholar
• Solé-Lleonart C, Rouby, JJ, Blot, S et al, . Nebulization of antiinfective agents in invasively mechanically ventilated adults. Anesthesiology. 2017 May;126(5):890–908.
   PubMed Web of Science ®Google Scholar
• Solé-Lleonart C, Roberts, JA, Chastre, J et al, . Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines. Clin Microbiol Infect. 2016 Apr;22(4):359–364.
   PubMed Web of Science ®Google Scholar
• Rello J, Rouby, JJ, Sole-Lleonart, C et al, . Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect. 2017 Sep;23(9):640–646.
   PubMed Web of Science ®Google Scholar
• Rouby JJ, Sole-Lleonart C, Rello J. Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin. Intensive Care Med. 2020;46(4):766–770.
   PubMed Web of Science ®Google Scholar
• Niederman MS, Alder, J, Bassetti, M et al, . Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial. Lancet Infect Dis. 2020 Mar;20(3):330–340.
   PubMed Web of Science ®Google Scholar
• Dhanani JA, Diab, Sara, Chaudhary, J et al, . Lung pharmacokinetics of tobramycin by intravenous and nebulized dosing in a mechanically ventilated healthy ovine model. Anesthesiology. 2019 Aug;131(2):344–355.
   PubMed Web of Science ®Google Scholar
• Tang R, Luo R, Wu B, et al. Effectiveness and safety of adjunctive inhaled antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. J Crit Care. 2021Jun;65:133–139.
   PubMed Web of Science ®Google Scholar
• Blanchard JD, Elias V, Cipolla D, et al. Effective treatment of mycobacterium avium subsp. hominissuis and mycobacterium abscessus species infections in macrophages, biofilm, and mice by using liposomal ciprofloxacin’. Antimicrob Agents Chemother. 2018 Sep;62(10):e00440–18.
   PubMed Web of Science ®Google Scholar
• Bassetti M, Vena A, Russo A, et al. Inhaled liposomal antimicrobial delivery in lung infections. Drugs. 2020 Sep;80(13):1309–1318.
   PubMed Web of Science ®Google Scholar
• Haworth CS, Bilton, D, Chalmers, JD, Davis, AM et al, . Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Lancet Respir Med. 2019 Mar;7(3):213–226.
   PubMed Web of Science ®Google Scholar
• Zakharkina T, Martin-Loeches, I, Matamoros, S et al, . The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia. Thorax. 2017;72(9):1–8.
   PubMed Web of Science ®Google Scholar
• Rouzé A, Martin-Loeches, I, Povoa, P et al, . Correction to: relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med. 2021 Nov. DOI:https://doi.org/10.1007/s00134-021-06588-8.
   Google Scholar
• Shafiq N, Pandey , AK, Malhotra, S et al, . Shortage of essential antimicrobials: a major challenge to global health security. BMJ Glob Health. 2021 Nov;6(11):e006961.
   PubMed Web of Science ®Google Scholar
• Garduno A, Martín-Loeches I. Efficacy and appropriateness of novel antibiotics in response to antimicrobial-resistant gram-negative bacteria in patients with sepsis in the ICU. Expert Rev Anti Infect Ther. 2021 Dec;1–19. DOI:https://doi.org/10.1080/14787210.2022.1999804
   Google Scholar