TY - JOUR A1 - Kannan, Krishna A1 - Kanabar, Pinal A1 - Schryer, David A1 - Florin, Tanja A1 - Oh, Eugene A1 - Bahroos, Neil A1 - Tenson, Tanel A1 - Weissman, Jonathan S. A1 - Mankin, Alexander S. T1 - The general mode of translation inhibition by macrolide antibiotics JF - Proceedings of the National Academy of Sciences of the United States of America KW - ribosome KW - antibiotics KW - macrolides KW - translation KW - peptidyl transferase Y1 - 2014 U6 - https://doi.org/10.1073/pnas.1417334111 SN - 0027-8424 VL - 111 IS - 45 SP - 15958 EP - 15963 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Sengupta, Saswati A1 - Chattopadhyay, Madhab K. A1 - Grossart, Hans-Peter T1 - The multifaceted roles of antibiotics and antibiotic resistance in nature JF - Frontiers in microbiology N2 - Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host-parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics in nature. KW - antibiotics KW - sub-inhibitory concentration KW - quorum sensing KW - virulence KW - stress response KW - antibiotic resistance KW - antibiotic paradox Y1 - 2013 U6 - https://doi.org/10.3389/fmicb.2013.00047 SN - 1664-302X VL - 4 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Weinelt, Ferdinand Anton A1 - Stegemann, Miriam Songa A1 - Theloe, Anja A1 - Pfäfflin, Frieder A1 - Achterberg, Stephan A1 - Weber, Franz A1 - Dübel, Lucas A1 - Mikolajewska, Agata A1 - Uhrig, Alexander A1 - Kiessling, Peggy A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Hennig, Stefanie A1 - Kloft, Charlotte T1 - Evaluation of a meropenem and piperacillin monitoring program in intensive care unit patients calls for the regular assessment of empirical targets and easy-to-use dosing decision tools JF - Antibiotics : open access journal N2 - The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1-5 x MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8-40 mg/L and 16-80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing. KW - meropenem KW - piperacillin/tazobactam KW - antimicrobial stewardship KW - critically ill KW - antibiotics KW - pharmacokinetic/pharmacodynamic Y1 - 2022 U6 - https://doi.org/10.3390/antibiotics11060758 SN - 2079-6382 VL - 11 IS - 6 PB - MDPI CY - Basel ER -