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However, such categorization has proven challenging in clinical practice, as these definitions only apply under specific laboratory conditions, which may differ from clinical settings. Several factors, such as the specific bacteria or infectious medium, can affect the action of antibiotics, with many antibacterials exerting both activities. These definitions have also led to the belief that bactericidal antibacterials are superior to bacteriostatic, especially in more severe cases, such as endocarditis, neutropenia and bacteraemia. Additionally, current dogma dictates against the combination of bactericidal and bacteriostatic antibacterials in clinical practice, due to potential antagonism. This review aimed to assess the differences in antibacterial activity of bactericidal and bacteriostatic antibacterials based on in vitro and in vivo studies and examine their antagonistic or synergistic effects. Our findings show that specific bacteriostatic agents, such as linezolid and tigecycline, are clinically non-inferior to bactericidals in multiple infections, including pneumonia, intra-abdominal infections, and skin and soft tissue infections. Studies also support using several bacteriostatic agents as salvage therapies in severe infections, such as neutropenic fever and endocarditis. Additionally, not all combinations of bacteriostatic and bactericidal agents appear to be antagonistic, with many combinations, such as linezolid and rifampicin, already being used. The findings should be interpreted with caution, as most evidence is from observational studies and there is a need for randomized controlled trials to assess their effectiveness and combinations, especially within the context of rising antimicrobial resistance.<\/jats:p>","DOI":"10.1093\/jac\/dkae380","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T15:31:08Z","timestamp":1728487868000},"page":"1-17","source":"Crossref","is-referenced-by-count":156,"title":["Bactericidal versus bacteriostatic antibacterials: clinical significance, differences and synergistic potential in clinical practice"],"prefix":"10.1093","volume":"80","author":[{"given":"Angela","family":"Ishak","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, 48202 Henry Ford Hospital , Detroit, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Mazonakis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Thoracic Diseases General Hospital Sotiria , 11527 Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-8535","authenticated-orcid":false,"given":"Nikolaos","family":"Spernovasilis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, German Oncology Centre , 4108 Limassol ,","place":["Cyprus"]},{"name":"School of Medicine, University of Crete , 71500 Heraklion ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Akinosoglou","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras , 26504 Rio ,","place":["Greece"]},{"name":"Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras , 26504 Rio ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Tsioutis","sequence":"additional","affiliation":[{"name":"School of Medicine, European University Cyprus , 6 Diogenes str, Nicosia 2404 ,","place":["Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"2025010309471902200_dkae380-B1","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1086\/381972","article-title":"Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections","volume":"38","author":"Pankey","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2025010309471902200_dkae380-B2","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1093\/cid\/cix1127","article-title":"Busting the myth of \u2018static vs cidal\u2019: a systemic literature 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