{"doi":"10.3389/fphar.2024.1339858","title":"Influence of β-lactam pharmacodynamics on the systems microbiology of gram-positive and gram-negative polymicrobial communities","abstract":"Objectives We sought to evaluate the pharmacodynamics of β-lactam antibacterials against polymicrobial communities of clinically relevant gram-positive and gram-negative pathogens. Methods Two Enterococcus faecalis isolates, two Staphylococcus aureus isolates, and three Escherichia coli isolates with varying β-lactamase production were evaluated in static time-killing experiments. Each gram-positive isolate was exposed to a concentration array of ampicillin ( E. faecalis ) or cefazolin ( S. aureus ) alone and during co-culture with an E. coli isolate that was β-lactamase-deficient, produced TEM-1, or produced KPC-3/TEM-1B. The results of the time-killing experiments were summarized using an integrated pharmacokinetic/pharmacodynamics analysis as well as mathematical modelling to fully characterize the antibacterial pharmacodynamics. Results In the integrated analysis, the maximum killing of ampicillin (E max ) against both E. faecalis isolates was ≥ 4.11 during monoculture experiments or co-culture with β-lactamase-deficient E. coli , whereas the E max was reduced to ≤ 1.54 during co-culture with β-lactamase-producing E. coli . In comparison to monoculture experiments, culturing S. aureus with KPC-producing E. coli resulted in reductions of the cefazolin E max from 3.25 and 3.71 down to 2.02 and 2.98, respectively. Two mathematical models were created to describe the interactions between E. coli and either E. faecalis or S. aureus . When in co-culture with E. coli , S. aureus experienced a reduction in its cefazolin K max by 24.8% (23.1%RSE). Similarly, β-lactamase-producing E. coli preferentially protected the ampicillin-resistant E. faecalis subpopulation, reducing K max,r by 90.1% (14%RSE). Discussion β-lactamase-producing E. coli were capable of protecting S. aureus and E. faecalis from exposure to β-lactam antibacterials.","journal":"Frontiers in Pharmacology","year":2024,"id":498206,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1344768,"name":"Harpreet Kaur","orcid":"0000-0002-0047-7146","position":1,"is_corresponding":false},{"id":1344769,"name":"Ravneet Kaur","orcid":"0000-0003-2603-9125","position":2,"is_corresponding":false},{"id":1345037,"name":"Trisha Minoza","orcid":null,"position":3,"is_corresponding":false},{"id":347041,"name":"Michael L. Kent","orcid":"0000-0001-7968-5142","position":4,"is_corresponding":false},{"id":741433,"name":"Ayeh Barekat","orcid":null,"position":5,"is_corresponding":false},{"id":350708,"name":"Justin R. Lenhard","orcid":"0000-0002-2570-7593","position":6,"is_corresponding":false},{"id":350707,"name":"Nicholas M. Smith","orcid":"0000-0002-0212-2787","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:09:38.543544Z","pmid":"38895629","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}