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Combining SNAPs with antibiotics shows enhanced synergistic efficacy against S. aureus and P. aeruginosa biofilms.

ABSTRACT: Biofilm infections are associated with a high mortality risk for patients. Antibiotics perform poorly against biofilm communities, so high doses and prolonged treatments are often used in clinical settings. We investigated the pairwise interactions of two synthetic nano-engineered antimicrobial polymers (SNAPs). The g-D50 copolymer was synergistic with penicillin and silver sulfadiazine against planktonic Staphylococcus aureus USA300 in synthetic wound fluid. Furthermore, the combination of g-D50 and silver sulfadiazine showed a potent synergistic antibiofilm activity against S. aureus USA300 using in vitro and ex vivo wound biofilm models. The a-T50 copolymer was synergistic with colistin against planktonic Pseudomonas aeruginosa in synthetic cystic fibrosis medium, and this pair showed a potent synergistic antibiofilm activity against P. aeruginosa in an ex vivo cystic fibrosis lung model. SNAPs thus have the potential for increased antibiofilm performance in combination with certain antibiotics to shorten prolonged treatments and reduce dosages against biofilm infection.

SUBMITTER: Maset RG

PROVIDER: S-EPMC10250483 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Combining SNAPs with antibiotics shows enhanced synergistic efficacy against S. aureus and P. aeruginosa biofilms.

Maset Ramón Garcia RG Hapeshi Alexia A Lapage John J Harrington Niamh N Littler Jenny J Perrier Sébastien S Harrison Freya F

NPJ biofilms and microbiomes 20230608 1

Biofilm infections are associated with a high mortality risk for patients. Antibiotics perform poorly against biofilm communities, so high doses and prolonged treatments are often used in clinical settings. We investigated the pairwise interactions of two synthetic nano-engineered antimicrobial polymers (SNAPs). The g-D50 copolymer was synergistic with penicillin and silver sulfadiazine against planktonic Staphylococcus aureus USA300 in synthetic wound fluid. Furthermore, the combination of g-D5 ...[more]

PMID: 37291132

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Project description:Resistance to ?-lactam antibiotics is a frequent problem in Pseudomonas aeruginosa lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded ?-lactamase and biofilm formation. The purpose of this study was to investigate the role of ?-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on P. aeruginosa biofilms. P. aeruginosa PAO1 and its corresponding ?-lactamase-overproducing mutant, PA?DDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers, microtiter plates, and on alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on the biofilms was investigated in vitro by time-kill methods. Time-dependent killing of ceftazidime was observed in PAO1 biofilms, but concentration-dependent killing activity of ceftazidime was observed for ?-lactamase-overproducing biofilms of P. aeruginosa in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PA?DDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of ?-lactamase, which can hydrolyze the ?-lactam antibiotics. The PK/PD indices of the AUC/MBIC and C(max)/MBIC (AUC is the area under concentration-time curve, MBIC is the minimal biofilm-inhibitory concentration, and C(max) is the maximum concentration of drug in serum) are probably the best parameters to describe the effect of ceftazidime in ?-lactamase-overproducing P. aeruginosa biofilms. Meanwhile, imipenem showed time-dependent killing on both PAO1 and PA?DDh2Dh3 biofilms. An inoculum effect of ?-lactams was found for both planktonic and biofilm P. aeruginosa cells. The inoculum effect of ceftazidime for the ?-lactamase-overproducing mutant PA?DDh2Dh3 biofilms was more obvious than for PAO1 biofilms, with a requirement of higher antibiotic concentration and a longer period of treatment.

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Combining SNAPs with antibiotics shows enhanced synergistic efficacy against S. aureus and P. aeruginosa biofilms.

Publications

Combining SNAPs with antibiotics shows enhanced synergistic efficacy against S. aureus and P. aeruginosa biofilms.

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