{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:59:46Z","timestamp":1790135986455,"version":"4.0.1"},"reference-count":51,"publisher":"Scientific Scholar","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Resistance against nearly all antibiotics used clinically have been documented in bacteria. There is an ever-increasing danger caused by multidrug-resistant Gram-negative bacteria in both hospital and community settings. In Gram-negative bacteria, intrinsic resistance to currently available antibiotics is mainly due to overexpressed efflux pumps which are constitutively present and also presence of protective outer membrane. Combination therapy,\n                      <jats:italic toggle=\"yes\">i.e.<\/jats:italic>\n                      , use of two or more antibiotics, was thought to be an effective strategy because it took advantage of the additive effects of multiple antimicrobial mechanisms, lower risk of resistance development and lower mortality and improved clinical outcome. However, none of the benefits were seen in\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      studies. Antibiotic hybrids are being used to challenge the growing drug resistance threat and increase the usefulness of current antibiotic arsenal. Antibiotic hybrids are synthetic constructs of two molecules which are covalently linked. These could be two antibiotics or antibiotic with an adjuvant (efflux pump inhibitor, siderophore,\n                      <jats:italic toggle=\"yes\">etc.<\/jats:italic>\n                      ) which increases the access of the antibiotics to the target. The concepts, developments and challenges in the future use of antibiotic hybrids are discussed here. Majority of the studies have been conducted on fluoroquinolones and aminoglycosides molecules. The antibiotic tobramycin has the property to enhance the action of antimicrobial agents against which the multidrug-resistant Gram-negative bacteria were earlier resistant, and thus potentiating the action of legacy antibiotics. Antibiotic hybrids may have a role as the silver bullet in Gram-negative bacteria to overcome drug resistance as well as extend the spectrum of existing antibiotics\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijmr.ijmr_755_18","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T03:30:52Z","timestamp":1559532652000},"page":"97-106","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":139,"title":["Next-generation strategy for treating drug resistant bacteria"],"prefix":"10.25259","volume":"149","author":[{"given":"Varsha","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","reference":[{"key":"R1-3-20241212","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1172\/JCI18535","article-title":"Antimicrobial resistance: The example of Staphylococcus aureus","volume":"111","author":"Lowy","year":"2003","journal-title":"J Clin Invest"},{"key":"R2-3-20241212","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1271\/bbb.70.1060","article-title":"Antibiotic resistance in bacteria and its future for novel antibiotic development","volume":"70","author":"Yoneyama","year":"2006","journal-title":"Biosci Biotechnol Biochem"},{"key":"R3-3-20241212","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/QCO.0b013e32833f0d3e","article-title":"Multiresistant Gram-negative infections: A global perspective","volume":"23","author":"Ho","year":"2010","journal-title":"Curr Opin Infect Dis"},{"key":"R5-3-20241212","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1093\/cid\/cit152","article-title":"10 x \u201820 progress-development of new drugs active against Gram-negative bacilli: An update from the infectious diseases society of America","volume":"56","author":"Boucher","year":"2013","journal-title":"Clin Infect Dis"},{"key":"R6-3-20241212","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejcb.2009.10.011","article-title":"Impact of the glycostructure of amphiphilic membrane components on the function of the outer membrane of Gram-negative bacteria as a matrix for incorporated channels and a target for antimicrobial peptides or proteins","volume":"89","author":"Gutsmann","year":"2010","journal-title":"Eur J Cell Biol"},{"key":"R7-3-20241212","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0005-2736(90)90218-D","article-title":"Partitioning of hydrophobic probes into lipopolysaccharide bilayers","volume":"1024","author":"Vaara","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"R8-3-20241212","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrmicro3047","article-title":"Fortifying the barrier: The impact of lipid A remodelling on bacterial pathogenesis","volume":"11","author":"Needham","year":"2013","journal-title":"Nat Rev Microbiol"},{"key":"R10-3-20241212","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bbapap.2008.11.005","article-title":"Outer membrane permeability and antibiotic resistance","volume":"1794","author":"Delcour","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"R11-3-20241212","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.tim.2011.04.005","article-title":"Pseudomonas aeruginosa: All roads lead to resistance","volume":"19","author":"Breidenstein","year":"2011","journal-title":"Trends Microbiol"},{"key":"R12-3-20241212","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"R13-3-20241212","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bcp.2017.01.003","article-title":"What is an \u201cideal\u201d antibiotic? 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