Antimicrobial activity and interactions of cationic peptides derived from Galleria mellonella cecropin D-like peptide with model membranes
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.134
Authors: José Oñate-Garzón, Marcela Manrique-Moreno, Steven Trier, Chad Leidy, Rodrigo Torres & Edwin Patiño
Identification of new geldanamycin derivatives from unexplored microbial culture extracts using a MS/MS library
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.143
Authors: Jae Kyoung Lee, Jae-Hyuk Jang, Dong-Jin Park, Chang-Jin Kim, Jong Seog Ahn, Bang Yeon Hwang & Young-Soo Hong
Studies at the ionizable position of cephalosporins and penicillins: hydroxamates as substitutes for the traditional carboxylate group
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.149
Authors: Mark W Majewski, Patricia A Miller & Marvin J Miller
In vitro and in vivo activities of the diazabicyclooctane OP0595 against AmpC-derepressed Pseudomonas aeruginosa
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.150
Authors: Akihiro Morinaka, Yuko Tsutsumi, Keiko Yamada, Yoshihiro Takayama, Shiro Sakakibara, Toshihiko Takata, Takao Abe, Takeshi Furuuchi, Seiichi Inamura, Yoshiaki Sakamaki, Nakako Tsujii & Takashi Ida
Angucycline antibiotic waldiomycin recognizes common structural motif conserved in bacterial histidine kinases
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.151
Authors: Yoko Eguchi, Toshihide Okajima, Naoya Tochio, Yoichi Inukai, Riko Shimizu, Shuhei Ueda, Shoko Shinya, Takanori Kigawa, Tamo Fukamizo, Masayuki Igarashi & Ryutaro Utsumi
Isomethoxyneihumicin, a new cytotoxic agent produced by marine Nocardiopsis alba KM6-1
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.152
Authors: Takashi Fukuda, Misaki Takahashi, Kenichiro Nagai, Enjuro Harunari, Chiaki Imada & Hiroshi Tomoda
Precursor-directed in situ synthesis of Saccharothriolides G and H by the Actinomycete Saccharothrix sp. A1506
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.153
Authors: Shan Lu, Shinichi Nishimura, Masashi Ito, Taira Kato & Hideaki Kakeya
Antibacterial effect of antibiotic-loaded SBA-15 on biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis
The Journal of Antibiotics advance online publication, December 21 2016. doi:10.1038/ja.2016.154
Authors: Anna Aguilar-Colomer, Juan Carlos Doadrio, Concepción Pérez-Jorge, Miguel Manzano, Maria Vallet-Regí & Jaime Esteban
The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.
For many patients living with HIV-1, the efficacy of combined ART (cART) has made the infection turn to a chronic disease. Because cART is associated with a risk of long-term toxicity, switching patients with virological success to another therapy remains a major issue. Studies undertaken and published over recent years have shown that switching patients exhibiting virological suppression to less-drug regimens (LDR) is a possible option of maintenance strategy. The use of ritonavir-boosted PIs (PI/r) as the backbone of LDR-based maintenance therapy is consistent with their virological potency and a high genetic barrier of resistance. Atazanavir is the most documented PI/r regarding maintenance in dual therapy, with favourable results in terms of virological suppression, tolerance improvement and absence of emergence of mutations. Furthermore, atazanavir is the only commonly prescribed PI that can be used after withdrawal of ritonavir, with maintenance of virological suppression whatever the backbone of associated NRTIs. Based on clinical studies, and taking into account the characteristics of the patients included, one may consider that for any patient with a virological suppression on cART for at least 12 months, with the nadir CD4 >100 cells/mm3 and an absence of encephalitis, an LDR-based maintenance therapy including atazanavir can be considered. Cumulative genotypes must be available to make sure that the LDR will not jeopardize future therapeutic options. The final decision regarding the most appropriate LDR must be guided by the objectives shared by the physician and his/her patient.
New aminoglycoside-modifying enzymes APH(3′)-VIII and APH(3′)-IX in Acinetobacter rudis and Acinetobacter gerneri
The Journal of Antibiotics advance online publication, December 14 2016. doi:10.1038/ja.2016.144
Authors: Eun-Jeong Yoon, Catherine Grillot-Courvalin & Patrice Courvalin
Synthesis and antibacterial activity of novel lincomycin derivatives. II. Exploring (7S)-7-(5-aryl-1,3,4-thiadiazol-2-yl-thio)-7-deoxylincomycin derivatives
The Journal of Antibiotics advance online publication, December 7 2016. doi:10.1038/ja.2016.139
Authors: Ko Kumura, Yoshinari Wakiyama, Kazutaka Ueda, Eijiro Umemura, Takashi Watanabe, Megumi Kumura, Takuji Yoshida & Keiichi Ajito
Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance
The Journal of Antibiotics advance online publication, December 7 2016. doi:10.1038/ja.2016.141
Authors: Tomoyasu Hirose, Yasuhiro Kojima, Hidehito Matsui, Hideaki Hanaki, Masato Iwatsuki, Kazuro Shiomi, Satoshi Ōmura & Toshiaki Sunazuka
Nature nurtures the design of new semi-synthetic macrolide antibiotics
The Journal of Antibiotics advance online publication, November 30 2016. doi:10.1038/ja.2016.137
Authors: Prabhavathi Fernandes, Evan Martens & David Pereira
Bacterial proteases, untapped antimicrobial drug targets
The Journal of Antibiotics advance online publication, November 30 2016. doi:10.1038/ja.2016.138
Authors: Elizabeth Culp & Gerard D Wright
Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of MSD-819 (6-chloro-2-quinoxalinecarboxylic acid 1,4-dioxide)
The Journal of Antibiotics advance online publication, November 30 2016. doi:10.1038/ja.2016.140
Authors: Nicola Ooi & Alex J O'Neill
Quinoline and naphthalene derivatives from Saccharopolyspora sp. YIM M13568
The Journal of Antibiotics advance online publication, November 30 2016. doi:10.1038/ja.2016.142
Authors: Mingwei Sun, Jinhuan Ou, Wenjun Li & Chunhua Lu
8′-epimer of herbicidin F and its congeners from Streptomyces sp. YIM 66142
The Journal of Antibiotics advance online publication, November 23 2016. doi:10.1038/ja.2016.133
Authors: Ju-Cheng Zhang, Ya-Bin Yang, Guang-Yi Chen, Xiao-Zhan Li, Ming Hu, Bang-Yan Wang, Bao-Hui Ruan, Hao Zhou, Li-Xing Zhao & Zhong-Tao Ding
Anti-fungal activity of Ctn[15–34], the C-terminal peptide fragment of crotalicidin, a rattlesnake venom gland cathelicidin
The Journal of Antibiotics advance online publication, November 23 2016. doi:10.1038/ja.2016.135
Authors: Carolina Sidrim P Cavalcante, Cláudio B Falcão, Raquel OS Fontenelle, David Andreu & Gandhi Rádis-Baptista
In this brief article, we focus on Oxford University Press's role as the publisher of the JAC and how it supports authors and readers. The article defines the role of the publisher, as opposed to the Editorial team, Editorial Office or Society owner. It reviews three key functions at the publisher, namely, editorial, production and marketing.
In the past 40 years, medical mycology has gone from a curiosity in the basements of medical schools to a mainstream branch of clinical microbiology and infectious diseases. Long gone are the days of carefully curated collections of organisms identified purely based on morphology and skill, the lack of therapeutic interventions beyond amphotericin B and the occasional strange case in the ward of a diabetic patient with mucormycosis. We highlight advances in medical mycology as reflected in the past 40 years of JAC.
Since the Journal of Antimicrobial Chemotherapy was first published in 1975, papers addressing therapeutic drug monitoring (TDM) have been a regular feature. Initially they focused on laboratory aspects of drug concentration measurement then they changed more to the application of TDM in a clinical setting. Over its history, the Journal has provided its readership with the latest technological and scientific advances in TDM and has helped to drive changes in TDM that have directly impacted on patient care. These have varied from improvement in the quality of antimicrobial measurements through better identification of dosage regimens and TDM targets that help predict outcome and adverse events. Despite these advances in our understanding of the science and practice of TDM, there remain many areas of uncertainty. As we move into the next 40 years, it is clear that the Journal will continue to provide the readership with the latest science and opinion in this important area.
First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria.
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been a focus of international attention since its identification in 2012. Epidemiologically it is characterized by sporadic community cases, which are amplified by hospital-based outbreaks. Healthcare facilities in 27 countries from most continents have experienced imported cases, with the most significant outbreak involving 186 cases in Korea. The mortality internationally is 36% and guidance for clinical management has yet to be developed. Most facilities and healthcare providers outside of the Middle East receiving patients have no or little experience in the clinical management of MERS. When a case does occur there is likely little time for a critical appraisal of the literature and putative pharmacological options. We identified published literature on the management of both MERS-CoV and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) through searches of PubMed and WHO and the US CDC websites up to 30 April 2016. A total of 101 publications were retrieved for critical appraisal. Most published literature on therapeutics for MERS are in vitro experiments, animal studies and case reports. Current treatment options for MERS can be categorized as: immunotherapy with virus-specific antibodies in convalescent plasma; polyclonal and monoclonal antibodies produced in vitro or in genetically modified animals; and antiviral agents. The use of any therapeutics in MERS-CoV remains investigational. The therapeutic agents with potential benefits and warranting further investigation include convalescent plasma, interferon-β/ribavirin combination therapy and lopinavir. Corticosteroids, ribavirin monotherapy and mycophenolic acid likely have toxicities that exceed potential benefits.
Bio-based production of fuels and industrial chemicals by repurposing antibiotic-producing type I modular polyketide synthases: opportunities and challenges
The Journal of Antibiotics advance online publication, November 16 2016. doi:10.1038/ja.2016.136
Authors: Satoshi Yuzawa, Jay D Keasling & Leonard Katz
Screening of NCI-DTP library to identify new drug candidates for Borrelia burgdorferi
The Journal of Antibiotics advance online publication, November 9 2016. doi:10.1038/ja.2016.131
Authors: Venkata Raveendra Pothineni, Dhananjay Wagh, Mustafeez Mujtaba Babar, Mohammed Inayathullah, R Edward Watts, Kwang-Min Kim, Mansi B Parekh, Abhijit Achyut Gurjarpadhye, David Solow-Cordero, Lobat Tayebi & Jayakumar Rajadas
A new cytotoxic and anti-fungal C-glycosylated benz[α]anthraquinone from the broth of endophytic Streptomyces blastomycetica strain F4-20
The Journal of Antibiotics advance online publication, November 2 2016. doi:10.1038/ja.2016.126
Authors: He Yan, Yang Li, Xing Y Zhang, Wan Y Zhou & Tao J Feng
Re-identification of the ascofuranone-producing fungus Ascochyta viciae as Acremonium sclerotigenum
The Journal of Antibiotics advance online publication, November 2 2016. doi:10.1038/ja.2016.132
Authors: Yasuaki Hijikawa, Motomichi Matsuzaki, Shigeo Suzuki, Daniel Ken Inaoka, Ryoko Tatsumi, Yasutoshi Kido & Kiyoshi Kita
Isolation and identification of new macrocyclic lactones from a genetically engineered strain Streptomyces bingchenggensis BCJ60
The Journal of Antibiotics advance online publication, October 26 2016. doi:10.1038/ja.2016.130
Authors: Jiansong Li, Shaoyong Zhang, Hui Zhang, Haiyan Wang, Ji Zhang, Anliang Chen, Jidong Wang & Wensheng Xiang
Antimicrobial stewardship programmes are increasingly being used to improve the quality of antimicrobial prescribing, with the dual aim of optimizing clinical outcomes and minimizing the emergence and spread of antimicrobial resistance. The Journal of Antimicrobial Chemotherapy (JAC) is celebrating its 40th anniversary and, as part of activities to commemorate this event, this article highlights the contribution of JAC to antimicrobial stewardship. Papers published in JAC have contributed to the evidence base for stewardship, have highlighted educational and behavioural change initiatives aimed at improving antibiotic prescribing practice, and have actively sought to foster the practice of antimicrobial stewardship amongst its readers.
The treatment of invasive fungal diseases constitutes a significant unmet medical need. There are relatively few antifungal agents in clinical development and a paucity of novel targets. Morbidity and mortality remain high and clinical outcomes are compromised by submaximal efficacy, emergence of drug resistance and drug-related toxicity. Thus, new antifungal agents are urgently required. A deep understanding of exposure–response relationships underpins the development of safe and effective clinical regimens of any therapeutic agent. Pharmacokinetics (PK) and pharmacodynamics (PD) is increasingly recognized as a vital tool in the development of new antimicrobial agents and maximizes the probability that the right dose will be studied the first time. There is currently no information or agreement as to what constitutes an adequate PK/PD package for the development of a new antifungal agent. This review provides a summary of the achievements of antifungal PK/PD for the treatment of invasive candidiasis, invasive aspergillosis and cryptococcal meningoencephalitis, and outlines the necessary components of a PK/PD package for a new antifungal agent. Such information is critical for the accelerated and efficient development of new agents and enables improved clinical outcomes to be secured.
Validation of the mutant selection window hypothesis with fosfomycin against Escherichia coli and Pseudomonas aeruginosa: an in vitro and in vivo comparative study
The Journal of Antibiotics advance online publication, October 19 2016. doi:10.1038/ja.2016.124
Authors: Ai-jun Pan, Qing Mei, Ying Ye, Hong-ru Li, Bao Liu & Jia-bin Li
Microbacterium lacusdiani sp. nov., a phosphate-solubilizing novel actinobacterium isolated from mucilaginous sheath of Microcystis
The Journal of Antibiotics advance online publication, October 19 2016. doi:10.1038/ja.2016.125
Authors: Bing-Huo Zhang, Nimaichand Salam, Juan Cheng, Han-Quan Li, Jian-Yuan Yang, Dai-Ming Zha, Qi-Gen Guo & Wen-Jun Li
Antibiotics in microbial coculture
The Journal of Antibiotics advance online publication, October 19 2016. doi:10.1038/ja.2016.127
Authors: Kenji Ueda & Teruhiko Beppu
Antiviral effect of theaflavins against caliciviruses
The Journal of Antibiotics advance online publication, October 19 2016. doi:10.1038/ja.2016.128
Authors: Mai Ohba, Tomoichiro Oka, Takayuki Ando, Saori Arahata, Asaka Ikegaya, Hirotaka Takagi, Naohisa Ogo, Chelsea Zhu, Kazuhiro Owada, Fumihiko Kawamori, Qiuhong Wang, Linda J Saif & Akira Asai
Amide compound synthesis by adenylation domain of bacillibactin synthetase
The Journal of Antibiotics advance online publication, October 12 2016. doi:10.1038/ja.2016.117
Authors: Tomoko Abe, Yoshiteru Hashimoto, Sayaka Sugimoto, Kenta Kobayashi, Takuto Kumano & Michihiko Kobayashi
Julian Davies and the discovery of kanamycin resistance transposon Tn5
The Journal of Antibiotics advance online publication, October 12 2016. doi:10.1038/ja.2016.120
Author: Douglas E Berg
Production of valuable compounds by molds and yeasts
The Journal of Antibiotics advance online publication, October 12 2016. doi:10.1038/ja.2016.121
Authors: Arnold L Demain & Evan Martens
New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883
The Journal of Antibiotics advance online publication, October 12 2016. doi:10.1038/ja.2016.122
Authors: Zhikai Guo, Guohui Pan, Zhengren Xu, Dong Yang, Hindra , Xiangcheng Zhu, Yong Huang, Li-Xing Zhao, Yi Jiang, Yanwen Duan & Ben Shen
Characterization of the biosynthetic gene cluster (ata) for the A201A aminonucleoside antibiotic from Saccharothrix mutabilis subsp. capreolus
The Journal of Antibiotics advance online publication, October 12 2016. doi:10.1038/ja.2016.123
Authors: Irene Saugar, Brian Molloy, Eloisa Sanz, María Blanca Sánchez, María Fernández-Lobato & Antonio Jiménez
Synthesis and structure–activity relationships of novel lincomycin derivatives part 3: discovery of the 4-(pyrimidin-5-yl)phenyl group in synthesis of 7(S)-thiolincomycin analogs
The Journal of Antibiotics advance online publication, October 5 2016. doi:10.1038/ja.2016.114
Authors: Yoshinari Wakiyama, Ko Kumura, Eijiro Umemura, Satomi Masaki, Kazutaka Ueda, Yasuo Sato, Takashi Watanabe, Yoko Hirai & Keiichi Ajito
Three structurally-related impurities in norvancomycin drug substance
The Journal of Antibiotics advance online publication, October 5 2016. doi:10.1038/ja.2016.115
Authors: Zhibo Jiang, Xuan Lei, Minghua Chen, Bingya Jiang, Linzhuan Wu, Xuexia Zhang, Zhihui Zheng, Xinxin Hu, Xuefu You, Shuyi Si, Lifei Wang & Bin Hong
This review, for the occasion of the 40th anniversary of the Journal of Antimicrobial Chemotherapy (JAC), gives an overview of the manuscripts related to veterinary bacteriology published in the journal in the past 40 years with a focus on ‘One Health’ aspects. From 1975 to 2000 the number of manuscripts related to veterinary medicine was limited, but thereafter, the number steadily increased. Most manuscripts published were related to food-producing animals, but companion animals and minor species were also covered. Subjects included antimicrobial usage in animals and the consequences for human medicine, new resistance genes and mechanisms, the prevalence and epidemiology of antimicrobial resistance, and the emergence of resistant bacteria in animals with zoonotic potential such as livestock-associated MRSA (LA-MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP) and ESBL-producing Enterobacteriaceae. These manuscripts have added to our knowledge on the risks of transmission of resistant bacteria from animals to humans and the importance of the prudent use of antimicrobial agents in veterinary medicine.
The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by MBC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by mutant prevention concentration and 4 were on pharmacokinetics of levofloxacin, and 7 others were included. Likewise, out of five studies on children, two dealt with levofloxacin pharmacokinetic parameters, one reviewed CSF concentrations and two dealt with background information. In adult MDR-TB patients, standard dosing of once-daily 1000 mg levofloxacin in TB treatment did not consistently attain the target concentration (i.e. fAUC/MIC >100 and fAUC/MBC >100) in 80% of the patients with MIC and MBC of 1 mg/L, leaving them at risk of developing drug resistance. However, with an MIC of 0.5 mg/L, 100% of the patients achieved the target concentration. Similarly, paediatric patients failed consistently in achieving given pharmacokinetic/pharmacodynamic targets due to age-related differences, demanding a shift towards once daily dosing of 15–20 mg/kg. Therefore, we recommend therapeutic drug monitoring for patients with strains having MICs of ≥0.5 mg/L and suggest revising the cut-off value from 2 to 1 mg/L.
The monobactam aztreonam is currently being re-examined as a therapeutic agent in light of the global spread of carbapenem resistance in aerobic Gram-negative bacilli and aztreonam's stability to Ambler class B metallo-β-lactamases. Of particular interest are the pharmacokinetic and pharmacodynamic properties of aztreonam alone and in combination with β-lactamase inhibitors. The choice of inhibitor may vary depending on the spectrum of β-lactamases produced by Enterobacteriaceae. The monobactam ring is also being used to produce new developmental monobactams. Thus, a greater understanding of aztreonam pharmacokinetics and dynamics is of great relevance in drug development. This review summarizes the pharmacokinetic profile of aztreonam in man and its pharmacodynamics in human and pre-clinical studies when studied alone and with β-lactamase inhibitors.
During the last decade infections caused by MDR Gram-negative bacteria (GNB) have become increasingly prevalent. Because of their high morbidity and mortality rates, these infections constitute a serious threat to public health worldwide. Ceftazidime/avibactam is a new approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against various β-lactamases produced by MDR GNB. Avibactam has a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC and Klebsiella pneumoniae carbapenemase (KPC) enzymes. Thus, combination with this inhibitor expands ceftazidime's spectrum of activity to MDR Enterobacteriaceae and Pseudomonas aeruginosa strains. In Phase II clinical trials of patients with complicated intra-abdominal infections and complicated urinary tract infections ceftazidime/avibactam exhibited clinical efficacy comparable to those of meropenem and imipenem/cilastatin, respectively. A Phase III clinical trial confirmed the efficacy of ceftazidime/avibactam in patients with MDR Enterobacteriaceae and P. aeruginosa infections. Microbiological surveillance studies, in vivo animal models of infection and pharmacokinetic/pharmacodynamic target attainment analyses are also discussed, to assess the potential role of this new drug in the treatment of infections caused by MDR GNB.
Urinary tract infection (UTI) is one of the most common reasons for prescription of antimicrobials in primary care. Laboratory resistance data produced because of specimen analysis to support individual patient diagnosis and management are generalized to guide empirical therapy across a wider population, but are limited by bias toward certain patient groups and almost certainly overestimate the incidence of resistance. Other methods of surveillance are required to provide unbiased estimates of antimicrobial resistance, but need to be sustainable. Sentinel surveillance, perineal flora sampling and development of clinical algorithms to support more stratified and personalized antimicrobial prescribing need to be further investigated. Linkages to prescription and clinical outcome data are essential if the burden of antimicrobial resistance in UTI is to be understood. Pilot and feasibility studies need to be performed to establish the best approach to enhancing the quality, relevance and sustainability of antimicrobial resistance surveillance in community-acquired UTI.
Novel arginine-containing peptides MBJ-0173 and MBJ-0174 from Mortierella alpina f28740
The Journal of Antibiotics advance online publication, September 14 2016. doi:10.1038/ja.2016.116
Authors: Teppei Kawahara, Masashi Itoh, Miho Izumikawa, Noriaki Sakata, Toshio Tsuchida & Kazuo Shin-ya
ASP2397: a novel antifungal agent produced by Acremonium persicinum MF-347833
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.107
Authors: Ikuko Nakamura, Seiji Yoshimura, Teruhisa Masaki, Shigehiro Takase, Keisuke Ohsumi, Michizane Hashimoto, Shigetada Furukawa & Akihiko Fujie
Isolation of a new antibacterial peptide achromosin from Streptomyces achromogenes subsp. achromogenes based on genome mining
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.108
Authors: Issara Kaweewan, Mayumi Ohnishi-Kameyama & Shinya Kodani
Diapolic acid A–B from an endophytic fungus, Diaporthe terebinthifolii depicting antimicrobial and cytotoxic activity
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.109
Authors: Nalli Yedukondalu, Palak Arora, Bhumika Wadhwa, Fayaz Ahmad Malik, Ram A Vishwakarma, Vivek K Gupta, Syed Riyaz-Ul-Hassan & Asif Ali
Substrate specificity of radical S-adenosyl-l-methionine dehydratase AprD4 and its partner reductase AprD3 in the C3′-deoxygenation of aminoglycoside antibiotics
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.110
Authors: Fumitaka Kudo, Takahiro Tokumitsu & Tadashi Eguchi
A new polysubstituted cyclopentene derivative from Streptomyces sp. HS-NF-1046
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.111
Authors: Mei-yue Gao, Huan Qi, Jian-song Li, Hui Zhang, Ji Zhang, Ji-dong Wang & Wen-sheng Xiang
A new cyano-substituted anthracycline metabolite from Streptomyces sp. HS-NF-1006
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.112
Authors: Xu Wan, Hui-jun Ren, Min-na Du, Huan Qi, Hui Zhang, An-liang Chen & Ji-dong Wang
Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355
The Journal of Antibiotics advance online publication, September 7 2016. doi:10.1038/ja.2016.113
Authors: Toshihiko Nogawa, Akiko Okano, Chung Liang Lim, Yushi Futamura, Takeshi Shimizu, Shunji Takahashi, Darah Ibrahim & Hiroyuki Osada
Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection
The Journal of Antibiotics advance online publication, August 31 2016. doi:10.1038/ja.2016.106
Authors: Ikuko Nakamura, Ryuichi Kanasaki, Koji Yoshikawa, Shigetada Furukawa, Akihiko Fujie, Hiroshi Hamamoto & Kazuhisa Sekimizu
In silico identification of lysocin biosynthetic gene cluster from Lysobacter sp. RH2180-5
The Journal of Antibiotics advance online publication, August 24 2016. doi:10.1038/ja.2016.102
Authors: Suresh Panthee, Hiroshi Hamamoto, Yutaka Suzuki & Kazuhisa Sekimizu
Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews.
Antimicrobial chemotherapy now spans 80 years and four generations. The healthcare epidemiologist has an important role to play in this field. Efforts focus in three areas: (i) minimizing the transmission of antimicrobial-resistant bacteria in healthcare settings (infection control); (ii) optimizing use of currently available antibacterial drugs (antibiotic stewardship); and (iii) recognizing and responding to opportunities for new drug development. For each area, the epidemiologist provides data that address four practical questions—‘What is the problem?’, ‘What should be done?’, ‘Is it being done?’ and ‘Is it working?’. A team approach is crucial to acting on the epidemiological data. Examples are presented to illustrate different roles of the epidemiologist, and tools and measures that have been developed to address some problems of current importance. Monitoring of quality, integrity and security of data remains a major focus. The epidemiologist will continue to have a key role in antimicrobial chemotherapy.
Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%–60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors.
The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2–3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults (A-II) and children (A-I) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen (B-II). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.
The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.
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