Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients

Author:

Marner Michael12ORCID,Kolberg Laura3ORCID,Horst Julia345,Böhringer Nils26,Hübner Johannes37,Kresna I Dewa M.2,Liu Yang2,Mettal Ute2,Wang Lei2,Meyer-Bühn Melanie3,Mihajlovic Sanja1,Kappler Matthias3,Schäberle Till F.126ORCID,von Both Ulrich357ORCID

Affiliation:

1. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch for Bioresources, Giessen, Germany

2. Justus-Liebig-University of Giessen, Giessen, Germany

3. Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany

4. Institute for Medical Information Processing, Biometry, and Epidemiology – IBE, LMU Munich, Munich, Germany

5. Pettenkofer School of Public Health, Munich, Germany

6. German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Giessen, Germany

7. German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany

Abstract

Antimicrobial resistance (AMR) represents an ever increasing threat to the health care system. Even recently licensed drugs are often not efficient for the treatment of infections caused by Gram-negative bacteria, like Pseudomonas aeruginosa , a causative agent of lung infections. To address this unmet medical need, innovative antibiotics, which possess a new mode of action, need to be developed. Here, the antibiogram of clinical isolates derived from cystic fibrosis patients was generated and new bicyclic heptapeptides, which inhibit the outer membrane protein BamA, exhibited strong activity, also against multidrug-resistant isolates.

Funder

Bundesministerium für Bildung und Forschung

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

Reference45 articles.

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2. World Health Organization. 2014. Antimicrobial resistance: global report on surveillance. World Health Organization, Geneva, Switzerland.

3. World Health Organization. 2015. Global action plan on antimicrobial resistance. WHO Report 2015. World Health Organization, Geneva, Switzerland.

4. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

5. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

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