Antibiotics in the clinical pipeline at the end of 2015
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.72
Authors: Mark S Butler, Mark AT Blaskovich & Matthew A Cooper
In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.73
Authors: Yunliang Zhang, Xiaoyan Lin & Karen Bush
Antibacterial fatty acids destabilize hydrophobic and multicellular aggregates of biofilm in S. aureus
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.76
Authors: Zulfiqar Ali Mirani, Shagufta Naz, Fouzia Khan, Mubashir Aziz, Asadullah, Muhammad Naseem Khan & Seema Ismat Khan
Isolation and anti-HIV-1 integrase activity of lentzeosides A–F from extremotolerant lentzea sp. H45, a strain isolated from a high-altitude Atacama Desert soil
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.78
Authors: Dominik Wichner, Hamidah Idris, Wael E Houssen, Andrew R McEwan, Alan T Bull, Juan A Asenjo, Michael Goodfellow, Marcel Jaspars, Rainer Ebel & Mostafa E Rateb
Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.79
Authors: Hyun Bong Park & Jason M Crawford
Synthesis and biological evaluation of lipophilic teicoplanin pseudoaglycon derivatives containing a substituted triazole function
The Journal of Antibiotics advance online publication, June 29 2016. doi:10.1038/ja.2016.80
Authors: Zsolt Szűcs, Magdolna Csávás, Erzsébet Rőth, Anikó Borbás, Gyula Batta, Florent Perret, Eszter Ostorházi, Réka Szatmári, Evelien Vanderlinden, Lieve Naesens & Pál Herczegh
Xantholipin B produced by the stnR inactivation mutant Streptomyces flocculus CGMCC 4.1223 WJN-1
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.60
Authors: Sifan Wu, Tingting Huang, Dan Xie, Jing Wo, Xiaozheng Wang, Zixin Deng & Shuangjun Lin
Ogipeptins, novel inhibitors of LPS: physicochemical properties and structural elucidation
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.61
Authors: Yuki Hirota-Takahata, Shiho Kozuma, Nahoki Kuraya, Daisuke Fukuda, Mutsuo Nakajima, Toshio Takatsu & Osamu Ando
Biosynthetic potential of sesquiterpene synthases: product profiles of Egyptian Henbane premnaspirodiene synthase and related mutants
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.68
Authors: Hyun Jo Koo, Christopher R Vickery, Yi Xu, Gordon V Louie, Paul E O'Maille, Marianne Bowman, Charisse M Nartey, Michael D Burkart & Joseph P Noel
Paraphaeosphaeride D and berkleasmin F, new circumventors of arbekacin resistance in MRSA, produced by Paraphaeosphaeria sp. TR-022
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.70
Authors: Takuya Suga, Mayu Shiina, Yukihiro Asami, Masato Iwatsuki, Tsuyoshi Yamamoto, Kenichi Nonaka, Rokuro Masuma, Hidehito Matsui, Hideaki Hanaki, Susumu Iwamoto, Hideyuki Onodera, Kazuro Shiomi & Satoshi Ōmura
Haenamindole and fumiquinazoline analogs from a fungicolous isolate of Penicillium lanosum
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.74
Authors: In Hyun Hwang, Yongsheng Che, Dale C Swenson, James B Gloer, Donald T Wicklow, Stephen W Peterson & Patrick F Dowd
Metacycloprodigiosin induced cell death selectively in β-catenin-mutated tumor cells
The Journal of Antibiotics advance online publication, June 22 2016. doi:10.1038/ja.2016.75
Authors: Hiroaki Ikeda, Yuki Shikata, Ramida Watanapokasin, Etsu Tashiro & Masaya Imoto
Surfactin derivatives from Micromonospora sp. CPCC 202787 and their anti-HIV activities
The Journal of Antibiotics advance online publication, June 15 2016. doi:10.1038/ja.2016.63
Authors: Xu Pang, Jianyuan Zhao, Xiaomei Fang, Hongyu Liu, Yuqin Zhang, Shan Cen & Liyan Yu
Methyltransferases excised from trans-AT polyketide synthases operate on N-acetylcysteamine-bound substrates
The Journal of Antibiotics advance online publication, June 15 2016. doi:10.1038/ja.2016.66
Authors: D Cole Stevens, Drew T Wagner, Hannah R Manion, Bradley K Alexander & Adrian T Keatinge-Clay
Recent advances of Diels–Alderases involved in natural product biosynthesis
The Journal of Antibiotics advance online publication, June 15 2016. doi:10.1038/ja.2016.67
Authors: Atsushi Minami & Hideaki Oikawa
The unique chemistry and biology of the piericidins
The Journal of Antibiotics advance online publication, June 15 2016. doi:10.1038/ja.2016.71
Authors: Xuefeng Zhou & William Fenical
Chemical and biological studies of reveromycin A
The Journal of Antibiotics advance online publication, June 8 2016. doi:10.1038/ja.2016.57
Author: Hiroyuki Osada
Impact of Staphylococcus aureus accessory gene regulator (agr) system on linezolid efficacy by profiling pharmacodynamics and RNAIII expression
The Journal of Antibiotics advance online publication, June 8 2016. doi:10.1038/ja.2016.59
Authors: Rachel L Soon, Justin R Lenhard, Irene Reilly, Tanya Brown, Alan Forrest & Brian T Tsuji
RK-144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441
The Journal of Antibiotics advance online publication, June 8 2016. doi:10.1038/ja.2016.65
Authors: Jun-Pil Jang, Shunji Takahashi, Yushi Futamura, Toshihiko Nogawa, Jae-Hyuk Jang, Jong Seog Ahn & Hiroyuki Osada
Nearly all HIV PIs and the integrase inhibitor elvitegravir require a pharmacokinetic enhancer in order to achieve therapeutic plasma concentrations at the desired dose and frequency. Whereas ritonavir has been the only available pharmacokinetic enhancer for more than a decade, cobicistat has recently emerged as an alternative boosting agent. Cobicistat and ritonavir are equally strong inhibitors of cytochrome P450 (CYP) 3A4 and consequently were shown to be equivalent pharmacokinetic enhancers for elvitegravir and for the PIs atazanavir and darunavir. Since cobicistat is a more selective CYP inhibitor than ritonavir and is devoid of enzyme-inducing properties, differences are expected in their interaction profiles with some co-medications. Drugs whose exposure might be altered by ritonavir but unaltered by cobicistat are drugs primarily metabolized by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 or drugs undergoing mainly glucuronidation. Thus, co-medications should be systematically reviewed when switching the pharmacokinetic enhancer to anticipate potential dosage adjustments.
Rifabutin is a spiro-piperidyl-rifamycin structurally closely related to rifampicin that shares many of its properties. We attempted to address the reasons why this drug, which was recently recognized as a WHO Essential Medicine, still had a far narrower range of indications than rifampicin, 24 years after its launch. In this comprehensive review of the classic and more recent rifabutin experimental and clinical studies, the current state of knowledge about rifabutin is depicted, relying on specific pharmacokinetics, pharmacodynamics, antimicrobial properties, resistance data and side effects compared with rifampicin. There are consistent in vitro data and clinical studies showing that rifabutin has at least equivalent activity/efficacy and acceptable tolerance compared with rifampicin in TB and non-tuberculous mycobacterial diseases. Clinical studies have emphasized the clinical benefits of low rifabutin liver induction in patients with AIDS under PIs, in solid organ transplant patients under immunosuppressive drugs or in patients presenting intolerable side effects related to rifampicin. The contribution of rifabutin for rifampicin-resistant, but rifabutin-susceptible, Mycobacterium tuberculosis isolates according to the present breakpoints has been challenged and is now controversial. Compared with rifampicin, rifabutin's lower AUC is balanced by higher intracellular penetration and lower MIC for most pathogens. Clinical studies are lacking in non-mycobacterial infections.
