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Updated: Jun 5, 2025
Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions
Xenia Kostoulias1,2,3, Ying Fu1,4, Faye C Morris1,3
1Infection Program, Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
Background:
Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P. aeruginosa biofilms.
Methods:
We evaluated the efficacy of ceftolozane/tazobactam against clinical P. aeruginosa isolates, the laboratory isolate PAO1 and its isogenic mutS-deficient hypermutator derivative (PAOMS) grown under static and dynamic biofilm conditions. The clinical isolate collection included strains with mucoid and hypermutable phenotypes.
Results:
Ceftolozane/tazobactam exposure led to a bactericidal (≥3 log cfu/cm2) biofilm reduction in 15/18 (83%) clinical isolates grown under static conditions, irrespective of carbapenem susceptibility or mucoid phenotype, with greater activity compared with colistin (P < 0.05). Dynamically grown biofilms were less susceptible to ceftolozane/tazobactam with active biofilm reduction (≥1 log cfu/cm2) observed in 2/3 isolates. Hypermutability did not affect the antibiofilm efficacy of ceftolozane/tazobactam in either static or dynamic conditions when comparing PAO1 and PAOMS. Consistent with the activity of ceftolozane/tazobactam as a potent inhibitor of PBP3, dramatic impacts on P. aeruginosa morphology were observed.
Conclusions:
Our data demonstrate that ceftolozane/tazobactam has encouraging properties in the treatment of P. aeruginosa biofilm infections, and its activity is not diminished against mucoid or hypermutable variants at the timepoints examined.
Insights
Ceftolozane/tazobactam effectively reduces Pseudomonas aeruginosa biofilms, even in persistent mucoid or hypermutable forms. This new combination therapy shows promise against challenging biofilm infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pseudomonas aeruginosa biofilms present significant challenges to current antibacterial therapies.
- The presence of mucoid and hypermutable phenotypes further complicates biofilm treatment.
- Limited data exists on the efficacy of ceftolozane/tazobactam against P. aeruginosa biofilms.
Purpose of the Study:
- To evaluate the efficacy of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa with biofilm-forming capabilities.
- To assess the impact of mucoid and hypermutable phenotypes on the antibiofilm activity of ceftolozane/tazobactam.
- To compare the efficacy of ceftolozane/tazobactam with colistin against P. aeruginosa biofilms.
Main Methods:
- Tested ceftolozane/tazobactam against clinical P. aeruginosa isolates and laboratory strains (PAO1, PAOMS) under static and dynamic biofilm conditions.
- Included clinical isolates with mucoid and hypermutable phenotypes.
- Assessed biofilm reduction and morphological changes post-treatment.
Main Results:
- Ceftolozane/tazobactam achieved bactericidal biofilm reduction in 83% of static clinical isolates, outperforming colistin.
- Activity was consistent regardless of carbapenem susceptibility or mucoid phenotype.
- Dynamically grown biofilms showed reduced susceptibility, with active reduction in 2/3 isolates.
- Hypermutability did not impact antibiofilm efficacy.
- Significant morphological alterations in P. aeruginosa were observed, consistent with PBP3 inhibition.
Conclusions:
- Ceftolozane/tazobactam demonstrates promising activity against Pseudomonas aeruginosa biofilm infections.
- The drug's efficacy is maintained against mucoid and hypermutable variants.
- Further investigation into ceftolozane/tazobactam for biofilm infections is warranted.
