Antibacterial Resistance Leadership Group: Open for Business

Chambers, Henry F.; Bartlett, John G.; Chiou, Christine C.; Cosgrove, Sara E.; Cross, H. R.; Daum, Robert S.; Downing, Michele; Evans, Scott; Knisely, Jane M.; Kreiswirth, Barry N; Lautenbach, Ebbing; Mickley, Brenda; Patel, Robin; Pettigrew, Melinda M.; Rodvold, Keith A.; Spellberg, Brad; Fowler, Vance G.

doi:10.1093/cid/ciu132

Cited by 22 publications

(15 citation statements)

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“…Such informed decision-making, especially when it relates to empiric therapy, could potentially have important clinical impact by improving patient outcomes and by reducing the emergence of resistance, the risk of unnecessary toxicity, and healthcare costs [3,15].…”

Section: Discussionmentioning

confidence: 99%

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Evans¹,

Hujer²,

Jiang³

et al. 2015

Clin Infect Dis.

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Background. Rapid molecular diagnostic (RMD) platforms may lead to better antibiotic use. Our objective was to develop analytical strategies to enhance the interpretation of RMDs for clinicians.Methods. We compared the performance characteristics of 4 RMD platforms for detecting resistance against β-lactams in 72 highly resistant isolates of Escherichia coli and Klebsiella pneumoniae (PRIMERS I). Subsequently, 2 platforms were used in a blinded study in which a heterogeneous collection of 196 isolates of E. coli and K. pneumoniae (PRIMERS II) were examined. We evaluated the genotypic results as predictors of resistance or susceptibility against β-lactam antibiotics. We designed analytical strategies and graphical representations of platform performance, including discrimination summary plots and susceptibility and resistance predictive values, that are readily interpretable by practitioners to inform decision-making.Results. In PRIMERS I, the 4 RMD platforms detected β-lactamase (bla) genes and identified susceptibility or resistance in >95% of cases. In PRIMERS II, the 2 platforms identified susceptibility against extended-spectrum cephalosporins and carbapenems in >90% of cases; however, against piperacillin/tazobactam, susceptibility was identified in <80% of cases. Applying the analytical strategies to a population with 15% prevalence of ceftazidime-resistance and 5% imipenem-resistance, RMD platforms predicted susceptibility in >95% of cases, while prediction of resistance was 69%-73% for ceftazidime and 41%-50% for imipenem.Conclusions. RMD platforms can help inform empiric β-lactam therapy in cases where bla genes are not detected and the prevalence of resistance is known. Our analysis is a first step in bridging the gap between RMDs and empiric treatment decisions.

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Section: Discussionmentioning

confidence: 99%

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Evans¹,

Hujer²,

Jiang³

et al. 2015

Clin Infect Dis.

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“…The three-Atlrepeat domain, R 1-3 (17,18), was expressed with a N-terminal His 6 tag in Escherichia coli M15 using the isopropyl-␤-D-thiogalactopyranoside (IPTG)-inducible plasmid pEQ30Atl R [1][2][3] (19,20). Cells were cultivated in 2ϫ yeast extract-tryptone broth (YT) to an OD of 0.5 at 37°C and then induced with 0.5 mM IPTG for 4 h at 20°C.…”

Section: Methodsmentioning

confidence: 99%

“…The majority of antibiotics in use today are derivatives of molecules discovered in the early to midtwentieth century. The lack of novel compounds, coupled with the emergence and spread of antibiotic resistance, has resulted in an increasingly dangerous situation (2)(3)(4).…”

mentioning

confidence: 99%

Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis

Homma

Nuxoll

Gandt

et al. 2016

Antimicrob Agents Chemother

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Teixobactin represents the first member of a newly discovered class of antibiotics that act through inhibition of cell wall synthesis. Teixobactin binds multiple bactoprenol-coupled cell wall precursors, inhibiting both peptidoglycan and teichoic acid synthesis. Here, we show that the impressive bactericidal activity of teixobactin is due to the synergistic inhibition of both targets, resulting in cell wall damage, delocalization of autolysins, and subsequent cell lysis. We also find that teixobactin does not bind mature peptidoglycan, further increasing its activity at high cell densities and against vancomycin-intermediate Staphylococcus aureus (VISA) isolates with thickened peptidoglycan layers. These findings add to the attractiveness of teixobactin as a potential therapeutic agent for the treatment of infection caused by antibiotic-resistant Gram-positive pathogens.

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“…The Antibacterial Resistance Leadership Group (ARLG) has recently formed, and is providing grants to contribute to antibiotic development at smaller institutions. 31 There is also the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)…”

Section: Policymentioning

confidence: 99%

Incentivizing Antibiotic Research and Development

Scandlen-Finken¹,

Wertheimer²

2015

Innov Pharm

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; and most significantly Professor Albert Wertheimer, PhD, who had a seemingly endless store of inspiration and encouragement.In some parts of this manuscript, we include screenshots of information publicly available on the Internet. We include these under fair use guidelines in which we reproduce them for purposes such as criticism, comment, reporting, teaching, scholarship and research. Abstract This paper explores the current situation regarding antibiotic resistance and its casualties, as well as the mechanisms being employed to overcome the increase in resistance, and decrease in antibiotic effectiveness. Through analysis of antibiotic research, development, and regulation, this paper adds to the discussion by filling in the current gaps regarding the procurement of sustainable funding via an insurance model framework. By incentivizing the pharmaceutical industry to invest in antibiotic research, and by guaranteeing returns on investment, a global solution to the current antibiotic resistance problem can be contained. IntroductionWe are on the dawn of an international crisis. Infections are getting harder to treat, treatments are becoming more frequent, more expensive, and more people are dying.1,2 Multi-drug resistant organisms (MDRO) are being found all over the world. 3 Many fear

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Antibacterial Resistance Leadership Group: Open for Business

Cited by 22 publications

References 0 publications

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II

Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis

Incentivizing Antibiotic Research and Development

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