New antibiotics are needed to counter multidrug-resistant Gram-negative infections such as those commonly seen in cystic fibrosis, German researchers argued in Microbiology Spectrum.
Antibiotics have been a defining line of defense against microbial infection since their discovery a century ago. However, improper and excessive use of them has given rise to a new generation of pathogens that are resistant to some, if not all, currently available antibiotic therapy.
Scientists across the globe recognize this problem; antimicrobial resistance has been listed as a top 10 threat to world health. As a result, the World Health Organization has encouraged a concerted effort to develop novel antibiotics against top-priority Gram-negative pathogens, including Pseudomonas aeruginosa, which is particularly life-threatening to patients with cystic fibrosis.
The authors of this study sought to investigate the merits of 5 drugs against Pseudomonas aeurginosa isolates derived from respiratory fluids obtained from patients with cystic fibrosis. The 5 drugs included 3 that were recently licensed: ceftazidime-avibactam, ceftolozane-tazobactam, and cefiderocol; the other 2 were antibiotics that were still at the preclinical stage of development: darobactin B and darobactin B9.
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All 3 of the newly licensed antibiotics were found to be ineffective against P auerignosa; the authors of the study reported high levels of resistance to all of these drugs. The research team hypothesized that this was because they all had the same mechanism of action: inhibiting the transpeptidase activity of penicillin-biding proteins.
However, both darobactin B and darobactin B9 demonstrated promising antimicrobial activity; they were found to perform with the same efficacy or better than currently licensed antimicrobial therapy against P aeruginosa infection in patients with cystic fibrosis.
“Thus, speeding up the process for clinical trials and eventual licensing of these novel antibiotic compounds should be a priority, since clinicians worldwide will soon be left without any choice for treating multidrug-resistant Pseudomonas infections,” the authors of the study concluded.
Marner M, Kolberg L, Horst J, et al. 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. Microbiol Spectr. 2023;e0443722. doi:10.1128/spectrum.04437-22