In Vitro and In Vivo Antimicrobial Activity of the Novel Peptide OMN6 against Multidrug-Resistant Acinetobacter baumannii

The rapid worldwide spread of antimicrobial resistance highlights the significant need for the development of innovative treatments to fight multidrug-resistant bacteria. This study describes the potent antimicrobial activity of the novel peptide OMN6 against a wide array of drug-resistant Acinetobacter baumannii clinical isolates. OMN6 prevented the growth of all tested isolates, regardless of any pre-existing resistance mechanisms. Moreover, in vitro serial-passaging studies demonstrated that no resistance developed against OMN6. Importantly, OMN6 was highly efficacious in treating animal models of lung and blood infections caused by multidrug-resistant A. baumannii. Taken together, these results point to OMN6 as a novel antimicrobial agent with the potential to treat life-threatening infections caused by multidrug-resistant A. baumannii avoiding resistance.

[1]  O. Rosenberg,et al.  Leaks in the Pipeline: a Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020 , 2022, Antimicrobial agents and chemotherapy.

[2]  L. Czaplewski,et al.  Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed , 2022, Antimicrobial agents and chemotherapy.

[3]  Alan D. Lopez,et al.  Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis , 2022, The Lancet.

[4]  C. Casals,et al.  Synergistic Action of Antimicrobial Lung Proteins against Klebsiella pneumoniae , 2021, International journal of molecular sciences.

[5]  H. Petković,et al.  Towards the sustainable discovery and development of new antibiotics , 2021, Nature Reviews Chemistry.

[6]  L. Ferrari,et al.  OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria , 2021, Scientific Reports.

[7]  M. Antonelli,et al.  Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial , 2019, Critical Care.

[8]  A. Oliver,et al.  Challenging Antimicrobial Susceptibility and Evolution of Resistance (OXA-681) during Treatment of a Long-Term Nosocomial Infection Caused by a Pseudomonas aeruginosa ST175 Clone , 2019, Antimicrobial Agents and Chemotherapy.

[9]  M. Ouellette,et al.  Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. , 2017, The Lancet. Infectious diseases.

[10]  Z. Iqbal,et al.  The global distribution and spread of the mobilized colistin resistance gene mcr-1 , 2017, bioRxiv.

[11]  J. Jacob,et al.  Comparison of 30- and 90-Day Mortality Rates in Patients with Cultures Positive for Carbapenem-resistant Enterobacteriaceae and Acinetobacter in Atlanta, 2011–2015 , 2017, Open Forum Infectious Diseases.

[12]  R. Wunderink,et al.  International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia , 2017, European Respiratory Journal.

[13]  Peggy Cruse,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. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  Alan P. Johnson,et al.  Transferable resistance to colistin: a new but old threat. , 2016, The Journal of antimicrobial chemotherapy.

[15]  I. Henderson,et al.  Alternatives to antibiotics-a pipeline portfolio review. , 2016, The Lancet. Infectious diseases.

[16]  Jianzhong Shen,et al.  Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. , 2015, The Lancet. Infectious diseases.

[17]  A. Sáenz,et al.  Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN , 2015, The Journal of Immunology.

[18]  Ronald N. Jones,et al.  Ceftolozane/tazobactam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012). , 2014, International journal of antimicrobial agents.

[19]  Z. Erdoğan-Yildirim,et al.  Effect of Pulmonary Surfactant on Antimicrobial Activity In Vitro , 2013, Antimicrobial Agents and Chemotherapy.

[20]  J. Quinn,et al.  Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40 , 2006, Antimicrobial Agents and Chemotherapy.

[21]  D. Pittet,et al.  Clean Care is Safer Care: a worldwide priority , 2005, The Lancet.

[22]  L. Mortin,et al.  Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. , 2005, The Journal of infectious diseases.

[23]  E. Caldwell,et al.  Influence of a Pulmonary Surfactant on the In Vitro Activity of Tobramycin against Pseudomonas aeruginosa , 1999, Antimicrobial Agents and Chemotherapy.

[24]  D. Gommers,et al.  Influence of pulmonary surfactant on in vitro bactericidal activities of amoxicillin, ceftazidime, and tobramycin , 1995, Antimicrobial agents and chemotherapy.

[25]  M. Khrestchatisky,et al.  Synthetic therapeutic peptides: science and market. , 2010, Drug discovery today.

[26]  J. Waitz Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically , 1990 .