Editorial: Celebrating 40 years of the Journal

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Antimicrobial susceptibility testing breakpoints and methods from BSAC to EUCAST

The BSAC Standing Committee on Antimicrobial Susceptibility Testing is one of several European national breakpoint committees that agreed in 2002 to harmonize clinical MIC breakpoints. The process of harmonization has since been completed for commonly used agents, and breakpoints for new agents have been set by EUCAST in accordance with a procedure defined by the EMA. EUCAST breakpoints have now been adopted by a large majority of laboratories in Europe. BSAC implemented the EUCAST breakpoints in its own disc diffusion susceptibility testing method as harmonized breakpoints were agreed to over the years. Since the development of the EUCAST disc diffusion method, several countries with their own disc diffusion methods have switched to the EUCAST method, and BSAC will replace support of its own disc diffusion method with support for the EUCAST method from January 2016. The EUCAST breakpoints are also available in automated systems. The harmonized breakpoints and methods will help to avoid different reports of susceptibility for the same isolate in different countries and enable more reliable comparison of resistance rates in surveillance studies in different countries.

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Database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and DNA polymerase genes of herpes simplex virus types 1 and 2

The use of genotypic resistance testing of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. However, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes, of which the DNA polymerase (Pol) enzyme is targeted by the highly effective antiviral drugs in clinical use. Thus, this review presents a database of all non-synonymous mutations of TK and DNA pol genes of HSV-1 and HSV-2 whose association with resistance or natural gene polymorphism has been clarified by phenotypic and/or functional assays. In addition, the laboratory methods for verifying natural polymorphisms or resistance mutations are summarized. This database can help considerably to facilitate the interpretation of genotypic resistance findings in clinical HSV-1 and HSV-2 strains.

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Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy

The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy.

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A systematic review of the public's knowledge and beliefs about antibiotic resistance

Potential of Staphylococcus aureus isolates carrying different PBP2a alleles to develop resistance to ceftaroline

Missense mutations of PBP2a are associated with reduced susceptibility to ceftaroline and ceftobiprole in African MRSA

Molecular epidemiology of MRSA in 13 ICUs from eight European countries

Detection of MRSA ST3061-t843-mecC and ST398-t011-mecA in white stork nestlings exposed to human residues

Transmission of MRSA between humans and animals on duck and turkey farms

High prevalence of Salmonella and IMP-4-producing Enterobacteriaceae in the silver gull on Five Islands, Australia

Characterization of Acinetobacter johnsonii isolate XBB1 carrying nine plasmids and encoding NDM-1, OXA-58 and PER-1 by genome sequencing

A new mechanism to render clinical isolates of Escherichia coli non-susceptible to imipenem: substitutions in the PBP2 penicillin-binding domain

Identification of Haemophilus haemolyticus in clinical samples and characterization of their mechanisms of antimicrobial resistance

NDM-producing Enterobacteriaceae in Poland, 2012-14: inter-regional outbreak of Klebsiella pneumoniae ST11 and sporadic cases

First nationwide study regarding ceftriaxone resistance and molecular epidemiology of Neisseria gonorrhoeae in China

Indirect resistance to several classes of antibiotics in cocultures with resistant bacteria expressing antibiotic-modifying or -degrading enzymes

Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants

Antibiofilm agents against MDR bacterial strains: is bioactive glass BAG-S53P4 also effective?

Anti-Pseudomonas aeruginosa activity of 1,10-phenanthroline-based drugs against both planktonic- and biofilm-growing cells

Prospective evaluation of an algorithm for the phenotypic screening of carbapenemase-producing Enterobacteriaceae

Relative contribution of biological variation and technical variables to zone diameter variations of disc diffusion susceptibility testing

Evaluation of tedizolid against Staphylococcus aureus and enterococci with reduced susceptibility to vancomycin, daptomycin or linezolid

In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae

In vitro activity of ceftaroline against bacterial pathogens isolated from skin and soft tissue infections in Europe, Russia and Turkey in 2012: results from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance programme

NLF20: an antimicrobial peptide with therapeutic potential against invasive Pseudomonas aeruginosa infection

Rhesus {theta}-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against cystic fibrosis strains of Pseudomonas aeruginosa

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis

Synthesis and structure–activity relationships of novel lincomycin derivatives. Part 1. Newly generated antibacterial activities against Gram-positive bacteria with erm gene by C-7 modification

Synthesis and structure–activity relationships of novel lincomycin derivatives. Part 1. Newly generated antibacterial activities against Gram-positive bacteria with erm gene by C-7 modification

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.119

Authors: Yoshinari Wakiyama, Ko Kumura, Eijiro Umemura, Kazutaka Ueda, Satomi Masaki, Megumi Kumura, Hideki Fushimi & Keiichi Ajito

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Synthesis and structure–activity relationships of novel lincomycin derivatives. Part 2. Synthesis of 7(S)-7-deoxy-7-(4-morpholinocarbonylphenylthio)lincomycin and its 3-dimensional analysis with rRNA

Synthesis and structure–activity relationships of novel lincomycin derivatives. Part 2. Synthesis of 7(S)-7-deoxy-7-(4-morpholinocarbonylphenylthio)lincomycin and its 3-dimensional analysis with rRNA

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.125

Authors: Yoshinari Wakiyama, Ko Kumura, Eijiro Umemura, Satomi Masaki, Kazutaka Ueda, Takashi Watanabe, Mikio Yamamoto, Yoko Hirai & Keiichi Ajito

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Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii

Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.127

Authors: Thien B Tran, Soon-Ee Cheah, Heidi H Yu, Phillip J Bergen, Roger L Nation, Darren J Creek, Anthony Purcell, Alan Forrest, Yohei Doi, Jiangning Song, Tony Velkov & Jian Li

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Amethysione and amethysamide, new metabolites from Streptosporangium amethystogenes BCC 27081

Amethysione and amethysamide, new metabolites from Streptosporangium amethystogenes BCC 27081

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.128

Authors: Chollaratt Boonlarppradab, Chanwit Suriyachadkun, Sumalee Supothina & Pattiyaa Laksanacharoen

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New phenazine analogues from Streptomyces sp. IFM 11694 with TRAIL resistance-overcoming activities

New phenazine analogues from Streptomyces sp. IFM 11694 with TRAIL resistance-overcoming activities

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.129

Authors: Mohamed S Abdelfattah, Naoki Ishikawa, Utpal K Karmakar, Kazuki Yamaku & Masami Ishibashi

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Cell wall-affecting antibiotics modulate natural transformation in SigH-expressing Staphylococcus aureus

Cell wall-affecting antibiotics modulate natural transformation in SigH-expressing Staphylococcus aureus

The Journal of Antibiotics advance online publication, December 16 2015. doi:10.1038/ja.2015.132

Authors: Le Thuy Nguyen Thi, Veronica Medrano Romero & Kazuya Morikawa

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Application of bacterial cytological profiling to crude natural product extracts reveals the antibacterial arsenal of Bacillus subtilis

Application of bacterial cytological profiling to crude natural product extracts reveals the antibacterial arsenal of Bacillus subtilis

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.116

Authors: Poochit Nonejuie, Rachelle M Trial, Gerald L Newton, Anne Lamsa, Varahenage Ranmali Perera, Julieta Aguilar, Wei-Ting Liu, Pieter C Dorrestein, Joe Pogliano & Kit Pogliano

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PM100117 and PM100118, new antitumor macrolides produced by a marine Streptomyces caniferus GUA-06-05-006A

PM100117 and PM100118, new antitumor macrolides produced by a marine Streptomyces caniferus GUA-06-05-006A

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.121

Authors: Marta Pérez, Carmen Schleissner, Rogelio Fernández, Pilar Rodríguez, Fernando Reyes, Paz Zuñiga, Fernando de la Calle & Carmen Cuevas

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Improvement of the productivity of ecumicin, a novel anti-tuberculosis agent, from new Nonomuraea sp. MJM5123

Improvement of the productivity of ecumicin, a novel anti-tuberculosis agent, from new Nonomuraea sp. MJM5123

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.122

Authors: Ying-Yu Jin, Jin-Yong Kim, Seung Hwan Yang, Hanki Lee & Joo-Won Suh

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Improved antibiotic production and silent gene activation in Streptomyces diastatochromogenes by ribosome engineering

Improved antibiotic production and silent gene activation in Streptomyces diastatochromogenes by ribosome engineering

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.123

Authors: Xuping Shentu, Nannan Liu, Gu Tang, Yukinori Tanaka, Kozo Ochi, Jianfeng Xu & Xiaoping Yu

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Unantimycin A, a new neoantimycin analog isolated from a microbial metabolite fraction library

Unantimycin A, a new neoantimycin analog isolated from a microbial metabolite fraction library

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.124

Authors: Chung Liang Lim, Toshihiko Nogawa, Akiko Okano, Yushi Futamura, Makoto Kawatani, Shunji Takahashi, Darah Ibrahim & Hiroyuki Osada

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Maniwamycins: new quorum-sensing inhibitors against Chromobacterium violaceum CV026 were isolated from Streptomyces sp. TOHO-M025

Maniwamycins: new quorum-sensing inhibitors against Chromobacterium violaceum CV026 were isolated from Streptomyces sp. TOHO-M025

The Journal of Antibiotics advance online publication, December 9 2015. doi:10.1038/ja.2015.126

Authors: Atsushi Fukumoto, Chikana Murakami, Yojiro Anzai & Fumio Kato

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Biosynthetic origin of anthracimycin: a tricyclic macrolide from Streptomyces sp.

Biosynthetic origin of anthracimycin: a tricyclic macrolide from Streptomyces sp.

The Journal of Antibiotics advance online publication, December 2 2015. doi:10.1038/ja.2015.118

Authors: Enjuro Harunari, Hisayuki Komaki & Yasuhiro Igarashi

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In vitro activity of dalbavancin and five comparator agents against common and uncommon Gram-positive organisms isolated from cancer patients

In vitro activity of dalbavancin and five comparator agents against common and uncommon Gram-positive organisms isolated from cancer patients

The Journal of Antibiotics advance online publication, December 2 2015. doi:10.1038/ja.2015.120

Authors: Kenneth V I Rolston, Weiqun Wang, Lior Nesher, Samuel A Shelburne & Randall A Prince

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Curromycin A as a GRP78 downregulator and a new cyclic dipeptide from Streptomyces sp.

Curromycin A as a GRP78 downregulator and a new cyclic dipeptide from Streptomyces sp.

The Journal of Antibiotics advance online publication, November 25 2015. doi:10.1038/ja.2015.115

Authors: Yoichi Hayakawa, Minami Akimoto, Akari Ishikawa, Masumi Izawa & Kazuo Shin-ya

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New p-terphenyls from the fruiting bodies of Pseudomerulius curtisii and their antioxidant activity

New p-terphenyls from the fruiting bodies of Pseudomerulius curtisii and their antioxidant activity

The Journal of Antibiotics advance online publication, November 25 2015. doi:10.1038/ja.2015.117

Authors: Byung Soon Hwang, In-Kyoung Lee & Bong-Sik Yun

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Natural product-derived quaternary ammonium compounds with potent antimicrobial activity

Natural product-derived quaternary ammonium compounds with potent antimicrobial activity

The Journal of Antibiotics advance online publication, November 18 2015. doi:10.1038/ja.2015.107

Authors: Maureen D Joyce, Megan C Jennings, Celina N Santiago, Madison H Fletcher, William M Wuest & Kevin PC Minbiole

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Educating healthcare professionals in antimicrobial stewardship: can online-learning solutions help?

Education is widely recognized as one of the cornerstones of successful antimicrobial stewardship programmes. There is evidence of important knowledge flaws around antimicrobial prescribing among both medical students and clinicians. Educational interventions improve antimicrobial prescribing, but traditional tools may be insufficient to deliver training to meet the complex demands of global healthcare professionals working across a diverse range of healthcare and resource settings. The educational solutions increasingly need to be timely, efficient, pragmatic, high quality, aligned to the needs of the professional in a specific context, sustainable and cost-effective. Online learning has been playing a growing role in education about antimicrobial stewardship and the recent phenomenon of massive open online courses (MOOCs) offers novel and additional opportunities to deliver relevant information to a wide range of people. Additional research on MOOCs as an educational approach is needed in order to define their effectiveness, sustainability and the best ways to achieve the intended results. Although the precise value of new online strategies such as MOOCs is ill defined, they certainly will have an important place in increasing awareness and improving antimicrobial prescribing.

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Therapeutic drug monitoring of the {beta}-lactam antibiotics: what is the evidence and which patients should we be using it for?

Traditional antibiotic dosing was not designed for today's escalating antibiotic resistance, lack of novel antibiotics and growing complexity in patient populations. Dosing that ensures optimal antibiotic exposures should be considered essential to increase the likelihood of effective patient treatment. Given the variability in these exposures across different patients, a ‘one-dose-fits-all’ approach is increasingly problematic. Therapeutic drug monitoring (TDM) of the β-lactams, the most widely used antibiotic class, is underutilized in certain populations. Clinical experience with β-lactam TDM remains relatively scarce. Patients most likely to benefit from such an intervention include the critically ill, the obese, the elderly and those with cystic fibrosis. Most centres actively performing β-lactam TDM target a minimum 100% of the time during the dosing interval that the free (unbound) concentration of antibiotic exceeds the MIC of the pathogen (100% fT_>MIC), which is higher than a traditional target supported by in vitro data. Ideally, isolated pathogens should undergo MIC testing along with TDM on a regular basis, allowing clinicians to address the triad of bug, drug and patient (‘mug’) in equal measure.

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Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi

Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of MRSA isolates in south-east London

Frequent occurrence of oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) strains in two African countries

Host specificity in the diversity and transfer of lsa resistance genes in group B Streptococcus

Mutation profiling for detection of isoniazid resistance in Mycobacterium tuberculosis clinical isolates

Reduced susceptibility to biocides in Acinetobacter baumannii: association with resistance to antimicrobials, epidemiological behaviour, biological cost and effect on the expression of genes encoding porins and efflux pumps

Phylogenetic lineages, clones and {beta}-lactamases in an international collection of Klebsiella oxytoca isolates non-susceptible to expanded-spectrum cephalosporins

Genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae from England and Wales

Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S rRNA mutations associated with azithromycin resistance

Genetic environment of metallo-{beta}-lactamase genes in Pseudomonas aeruginosa isolates from the UK

Susceptibility testing challenges with ceftaroline, MRSA and a 1 mg/L breakpoint

Gradual increase in antibiotic concentration affects persistence of Klebsiella pneumoniae

Quantifying the impact of drug combination regimens on TB treatment efficacy and multidrug resistance probability

Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis

New pharmacokinetic/pharmacodynamic studies of systemically administered colistin against Pseudomonas aeruginosa and Acinetobacter baumannii in mouse thigh and lung infection models: smaller response in lung infection

Population pharmacokinetics of rifampicin and 25-deacetyl-rifampicin in healthy Asian adults

Influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1

HIV-1 RNA and HIV-1 DNA persistence during suppressive ART with PI-based or nevirapine-based regimens

Prevalence and type of drug-drug interactions involving ART in patients attending a specialist HIV outpatient clinic in Kampala, Uganda

Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study

Clinical progression of severely immunosuppressed HIV-infected patients depends on virological and immunological improvement irrespective of baseline status

Virological factors associated with outcome of dual maraviroc/raltegravir therapy (ANRS-157 trial)

Bactericidal effects of triclosan in soap both in vitro and in vivo

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre

Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of combination therapy with colistin plus {beta}-lactams

Impact of mupirocin resistance on the transmission and control of healthcare-associated MRSA

Omitted doses as an unintended consequence of a hospital restricted antibacterial system: a retrospective observational study

Growth in nurse prescribing of antibiotics: the Scottish experience 2007-13

Total synthesis of ent-(+)-cinanthrenol A

Total synthesis of ent-(+)-cinanthrenol A

The Journal of Antibiotics advance online publication, November 11 2015. doi:10.1038/ja.2015.114

Authors: Liangyu Zhu & Rongbiao Tong

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Streptomyces hyaluromycini sp. nov., isolated from a tunicate (Molgula manhattensis)

Streptomyces hyaluromycini sp. nov., isolated from a tunicate (Molgula manhattensis)

The Journal of Antibiotics advance online publication, November 4 2015. doi:10.1038/ja.2015.110

Authors: Enjuro Harunari, Moriyuki Hamada, Chiyo Shibata, Tomohiko Tamura, Hisayuki Komaki, Chiaki Imada & Yasuhiro Igarashi

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Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization—a comparison with nitrofurantoin

Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization—a comparison with nitrofurantoin

The Journal of Antibiotics advance online publication, November 4 2015. doi:10.1038/ja.2015.112

Authors: Ravi Vumma, Charlotte Sahlberg Bang, Robert Kruse, Kjell Johansson & Katarina Persson

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Pyrrocidine A, a metabolite of endophytic fungi, has a potent apoptosis-inducing activity against HL60 cells through caspase activation via the Michael addition

Pyrrocidine A, a metabolite of endophytic fungi, has a potent apoptosis-inducing activity against HL60 cells through caspase activation via the Michael addition

The Journal of Antibiotics advance online publication, October 28 2015. doi:10.1038/ja.2015.103

Authors: Shota Uesugi, Nozomi Fujisawa, Jun Yoshida, Mitsuru Watanabe, Shingo Dan, Takao Yamori, Yoshihito Shiono & Ken-ichi Kimura

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Synthesis of Thienamycin methyl ester from 2-deoxy-d-ribose via Kinugasa reaction

Synthesis of Thienamycin methyl ester from 2-deoxy-d-ribose via Kinugasa reaction

The Journal of Antibiotics advance online publication, October 28 2015. doi:10.1038/ja.2015.108

Authors: Magdalena Soluch, Barbara Grzeszczyk, Olga Staszewska-Krajewska, Marek Chmielewski & Bartłomiej Furman

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Micromonospora lycii sp. nov., a novel endophytic actinomycete isolated from wolfberry root (Lycium chinense Mill)

Micromonospora lycii sp. nov., a novel endophytic actinomycete isolated from wolfberry root (Lycium chinense Mill)

The Journal of Antibiotics advance online publication, October 28 2015. doi:10.1038/ja.2015.109

Authors: Junwei Zhao, Lifeng Guo, Chongxi Liu, Yuejing Zhang, Xuejiao Guan, Jiansong Li, Shilin Xu, Wensheng Xiang & Xiangjing Wang

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Prevalence of mutations conferring resistance among multi- and extensively drug-resistant Mycobacterium tuberculosis isolates in China

Prevalence of mutations conferring resistance among multi- and extensively drug-resistant Mycobacterium tuberculosis isolates in China

The Journal of Antibiotics advance online publication, October 21 2015. doi:10.1038/ja.2015.106

Authors: Yan Chen, Bing Zhao, Hai-can Liu, Qing Sun, Xiu-qin Zhao, Zhi-guang Liu, Kang-lin Wan & Li-li Zhao

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Celebrating the 2015 Nobel Prize in Physiology or Medicine of Dr Satoshi Ōmura

Celebrating the 2015 Nobel Prize in Physiology or Medicine of Dr Satoshi Ōmura

The Journal of Antibiotics advance online publication, October 21 2015. doi:10.1038/ja.2015.113

Author: Kuniaki Tatsuta

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Antimycobacterial activity of five efflux pump inhibitors against Mycobacterium tuberculosis clinical isolates

Antimycobacterial activity of five efflux pump inhibitors against Mycobacterium tuberculosis clinical isolates

The Journal of Antibiotics advance online publication, October 14 2015. doi:10.1038/ja.2015.101

Authors: Guilian Li, Jingrui Zhang, Chao Li, Qian Guo, Yi Jiang, Jianhao Wei, Yan Qiu, Xiuqin Zhao, Li-li Zhao, Jianxin Lu & Kanglin Wan

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Coccoquinones A and B, new anthraquinone derivatives produced by Staphylotrichum coccosporum PF1460

Coccoquinones A and B, new anthraquinone derivatives produced by Staphylotrichum coccosporum PF1460

The Journal of Antibiotics advance online publication, October 14 2015. doi:10.1038/ja.2015.102

Authors: Daisuke Tatsuda, Masahide Amemiya, Ryuichi Sawa, Kengo Sumiyoshi, Takumi Watanabe, Isao Momose, Manabu Kawada, Akio Nomoto & Masakatsu Shibasaki

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Increasing antibiotic production yields by favoring the biosynthesis of precursor metabolites glucose-1-phosphate and/or malonyl-CoA in Streptomyces producer strains

Increasing antibiotic production yields by favoring the biosynthesis of precursor metabolites glucose-1-phosphate and/or malonyl-CoA in Streptomyces producer strains

The Journal of Antibiotics advance online publication, October 14 2015. doi:10.1038/ja.2015.104

Authors: Daniel Zabala, Alfredo F Braña, José A Salas & Carmen Méndez

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Aspergillus mulundensis sp. nov., a new species for the fungus producing the antifungal echinocandin lipopeptides, mulundocandins

Aspergillus mulundensis sp. nov., a new species for the fungus producing the antifungal echinocandin lipopeptides, mulundocandins

The Journal of Antibiotics advance online publication, October 14 2015. doi:10.1038/ja.2015.105

Authors: Gerald F Bills, Qun Yue, Li Chen, Yan Li, Zhiqiang An & Jens C Frisvad

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A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics

A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics

The Journal of Antibiotics advance online publication, October 14 2015. doi:10.1038/ja.2015.98

Authors: Matthew J Renwick, David M Brogan & Elias Mossialos

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Antimicrobial resistance: moving from professional engagement to public action

Antimicrobial-resistant infections claim ≥700 000 lives each year globally. It is therefore important that both healthcare professionals and the public know the threat antimicrobial resistance poses and the individual actions they can take to combat antimicrobial resistance. Antibiotic awareness campaigns in England using posters or leaflets have had little or no impact on knowledge, behaviour or prescription rates. Centrally coordinated, multimodal campaigns in two European countries (ongoing for several years and including print and mass media, web site and guidelines, as well as academic detailing and individual feedback to prescribers) have led to reductions in antibiotic use. To change behaviour and reduce antibiotic use in England, a coordinated and comprehensive interdisciplinary and multifaceted (multimodal) approach using behavioural science and targeted at specific groups (both professional and public) is required. Such campaigns should have an integrated evaluation plan using a combination of formative, process and summative measures from the outset to completion of a campaign.

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The 2015 Garrod Lecture: Why is improvement difficult?

The pressing need to measure and improve antibiotic use was recognized >40 years ago, so why have we failed to achieve sustained improvement at scale? In his 2014 Reith Lectures about the future of medicine, the US surgeon Atul Gawande said that failure in medicine is largely due to ineptitude (failure to use existing knowledge) rather than ignorance (lack of knowledge). Consequently, it is notable that most interventions to improve antimicrobial prescribing are either designed to educate individual practitioners or patients about policies or to restrict prescribing to make practitioners follow policies. Interventions that enable practitioners to apply existing knowledge through decision support, feedback and action planning are relatively uncommon. There is an urgent need to improve the design and reporting of interventions to change behaviour. However, achieving sustained improvement at scale will also require a more profound understanding of the role of context. What makes contexts receptive to change and which elements of context, under what circumstances, are important for human performance? Answering these questions will require interdisciplinary work with social scientists to integrate complementary approaches from human factors and ergonomics, improvement science and educational research. We need to rethink professional education to embrace complexity and enable teams to learn in practice. Workplace-based learning of improvement science will enable students and early-career professionals to become change agents and transform training from a burden on clinical teams into a driver for improvement. This will make better use of existing resources, which is the key to sustainability at scale.

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Pulmonary drug delivery: a review on nanocarriers for antibacterial chemotherapy

As the WHO stated, lower respiratory infections are the third leading cause of death. In addition, it is remarkable that antimicrobial resistance represents a huge threat. Thus, new therapeutic weapons are required. Among the possible alternatives, antibiotic encapsulation in nanoparticles has gained much attention in terms of improved tolerability, activity and ability to combat the resistance mechanisms of bacteria. In this regard, this review article focuses on the latest nanocarrier approaches for inhalatory therapy of antibiotics. First, the technology related to lung disposition will be reviewed. Then, nanocarrier systems will be introduced and the challenges required to perform adequate pulmonary deposition analysed. In the following part, drug delivery systems (DDSs) on the market or in clinical trials are described and, finally, new approaches of nanoparticles that have reached pre-clinical stage are enumerated. Altogether, this review aims at gathering together the novel nanosystems for anti-infectious therapy, underlining the potential of DDSs to improve and optimize currently available antibiotic therapies in the context of lung infections.

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Whole-genome analysis of an oxacillin-susceptible CC80 mecA-positive Staphylococcus aureus clinical isolate: insights into the mechanisms of cryptic methicillin resistance

Multiple pathways of cross-resistance to glycopeptides and daptomycin in persistent MRSA bacteraemia

Induced tigecycline resistance in Streptococcus pneumoniae mutants reveals mutations in ribosomal proteins and rRNA

Loss of LPS is involved in the virulence and resistance to colistin of colistin-resistant Acinetobacter nosocomialis mutants selected in vitro

Coexistence of a novel KPC-2-encoding MDR plasmid and an NDM-1-encoding pNDM-HN380-like plasmid in a clinical isolate of Citrobacter freundii

Surveillance for antimicrobial resistance in Australian isolates of Clostridium difficile, 2013-14

Sequencing of plasmids pAMBL1 and pAMBL2 from Pseudomonas aeruginosa reveals a blaVIM-1 amplification causing high-level carbapenem resistance

In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit: mechanisms of resistance and antimicrobial exposure

Evaluation of the RAPIDEC(R) CARBA NP, the Rapid CARB Screen(R) and the Carba NP test for biochemical detection of carbapenemase-producing Enterobacteriaceae

Lack of correlation between the promastigote back-transformation assay and miltefosine treatment outcome

Adaptation to vancomycin pressure of multiresistant Staphylococcus capitis NRCS-A involved in neonatal sepsis

Activity of OP0595/{beta}-lactam combinations against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing {beta}-lactamases

In vitro pharmacodynamics of fosfomycin against clinical isolates of Pseudomonas aeruginosa

A mechanism-based pharmacokinetic/pharmacodynamic model allows prediction of antibiotic killing from MIC values for WT and mutants

Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection

Cell division inhibitors with efficacy equivalent to isoniazid in the acute murine Mycobacterium tuberculosis infection model

Class-specific relative genetic contribution for key antiretroviral drugs

Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades

Virological failure to raltegravir in Spain: incidence, prevalence and clinical consequences

Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study)

Switching to anidulafungin from caspofungin in cancer patients in the setting of liver dysfunction is associated with improvement of liver function tests

Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment

Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis

Budget impact analysis of CYP2C19-guided voriconazole prophylaxis in AML

Outcomes of pulmonary MDR-TB: impacts of fluoroquinolone resistance and linezolid treatment

Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women

Outcome of second- and third-line Helicobacter pylori eradication therapies based on antimicrobial susceptibility testing

Increased resistance rate to ceftazidime among blood culture isolates of ESBL-producing Escherichia coli in a university-affiliated hospital of China

Increased resistance rate to ceftazidime among blood culture isolates of ESBL-producing Escherichia coli in a university-affiliated hospital of China

The Journal of Antibiotics advance online publication, September 30 2015. doi:10.1038/ja.2015.100

Authors: Xiao-Yan Yuan, Dong-Ying Yu, Xue-Hong Qu, Xin-Qiang Xiao, Bo Bi, Sheng-Bo Sun, Ai-Ying Chang & Qi-bo Zhang

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Non-antibiotic 12-membered macrolides: design, synthesis and biological evaluation in a cigarette-smoking model

Non-antibiotic 12-membered macrolides: design, synthesis and biological evaluation in a cigarette-smoking model

The Journal of Antibiotics advance online publication, September 30 2015. doi:10.1038/ja.2015.91

Authors: Akihiro Sugawara, Hideaki Shima, Akito Sueki, Tomoyasu Hirose, Hidehito Matsui, Hayato Nakano, Hideaki Hanaki, Kiyoko S Akagawa, Satoshi Ōmura & Toshiaki Sunazuka

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Streptanoate, a new anticancer butanoate from Streptomyces sp. DC3

Streptanoate, a new anticancer butanoate from Streptomyces sp. DC3

The Journal of Antibiotics advance online publication, September 16 2015. doi:10.1038/ja.2015.95

Authors: Saisattha Noomnual, Nopporn Thasana, Pareenart Sungkeeree, Skorn Mongkolsuk & Suvit Loprasert

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New cytotoxic spectinabilin derivative from ant-associated Streptomyces sp. 1H-GS5

New cytotoxic spectinabilin derivative from ant-associated Streptomyces sp. 1H-GS5

The Journal of Antibiotics advance online publication, September 16 2015. doi:10.1038/ja.2015.99

Authors: Shuang-he Liu, Mei-dong Xu, Hui Zhang, Huan Qi, Ji Zhang, Chong-xi Liu, Ji-dong Wang, Wen-sheng Xiang & Xiang-jing Wang

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Teixobactin, the first of a new class of antibiotics discovered by iChip technology?

Teixobactin is a recently described antibiotic of a new class produced by a hitherto undescribed soil microorganism (provisionally named Eleftheria terrae). It was isolated with a new tool, the iChip, that allowed the environmental bacterium to grow and for the antibiotic it produced to be isolated and subsequently identified. Teixobactin has activity against Gram-positive (but not Gram-negative) organisms and mycobacteria and a novel mode of action inhibiting peptidoglycan biosynthesis. In vitro no teixobactin-resistant Staphylococcus aureus or Mycobacterium tuberculosis were selected. In experimental infections of MRSA and Streptococcus pneumoniae in mice, teixobactin was effective at reducing the bacterial load. Although teixobactin is at an early stage of development and there are no guarantees it will make it to market, the use of the iChip will hopefully result in the discovery of further potential new antibiotics.

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Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA

Mupirocin 2% ointment is used either alone or with skin antiseptics as part of a comprehensive MRSA decolonization strategy. Increased mupirocin use predisposes to mupirocin resistance, which is significantly associated with persistent MRSA carriage. Mupirocin resistance as high as 81% has been reported. There is a strong association between previous mupirocin exposure and both low-level and high-level mupirocin resistance. High-level mupirocin resistance (mupA carriage) is also linked to MDR. Among MRSA isolates, the presence of the qacA and/or qacB gene, encoding resistance to chlorhexidine, ranges from 65% to 91%, which, along with mupirocin resistance, is associated with failed decolonization. This is of significant concern for patient care and infection prevention and control strategies as both these agents are used concurrently for decolonization. Increasing bacterial resistance necessitates the discovery or development of new antimicrobial therapies. These include, for example, polyhexanide, lysostaphin, ethanol, omiganan pentahydrochloride, tea tree oil, probiotics, bacteriophages and honey. However, few of these have been evaluated fully or extensively tested in clinical trials and this is required to in part address the implications of mupirocin resistance.

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Efavirenz and the CNS: what we already know and questions that need to be answered

The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of concentration, to more severe symptoms including depression, suicidal ideation or even psychosis. In addition, efavirenz has recently been associated with mild/moderate neurocognitive impairment, which is of specific relevance given that half of the patients receiving ART eventually suffer some form of HIV-associated neurocognitive disorder. The mechanisms responsible for efavirenz-induced neurotoxicity are unclear, although growing evidence points to disturbances in brain mitochondrial function and bioenergetics. This review offers a comprehensive overview of the current evidence on the interaction that efavirenz displays with the CNS, including the penetration and concentration of the drug in the brain. We discuss the prevalence, types and specificities of its side effects and recently uncovered cellular mechanisms that may be involved in their development.

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Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake

Epidemiology and molecular typing of VRE bloodstream isolates in an Irish tertiary care hospital

High isolation rate of MDR group B streptococci with reduced penicillin susceptibility in Japan

Declining macrolide resistance in Streptococcus pyogenes in Portugal (2007-13) was accompanied by continuous clonal changes

Effective transfer of a 47 kb NDM-1-positive plasmid among Acinetobacter species

A single nucleotide change in mutY increases the emergence of antibiotic-resistant Campylobacter jejuni mutants

OXA-372, a novel carbapenem-hydrolysing class D {beta}-lactamase from a Citrobacter freundii isolated from a hospital wastewater plant

Antibiotic-resistant ST38, ST131 and ST405 strains are the leading uropathogenic Escherichia coli clones in Riyadh, Saudi Arabia

WGS accurately predicts antimicrobial resistance in Escherichia coli

Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism

Early insights into the potential of the Oxford Nanopore MinION for the detection of antimicrobial resistance genes

OP0595, a new diazabicyclooctane: mode of action as a serine {beta}-lactamase inhibitor, antibiotic and {beta}-lactam 'enhancer'

Fitness of artemisinin-resistant Plasmodium falciparum in vitro

6SLN-lipo PGA specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential

Dolutegravir maintains a durable effect against HIV replication in tissue culture even after drug washout

Validation and clinical application of a method to quantify nevirapine in dried blood spots and dried breast-milk spots

Phenotypic resistance in mycobacteria: is it because I am old or fat that I resist you?

Colistin as a potentiator of anti-TB drug activity against Mycobacterium tuberculosis

Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease

Pathogens of skin and skin-structure infections in the UK and their susceptibility to antibiotics, including ceftaroline

Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis

Phase 1 study assessing the steady-state concentration of ceftazidime and avibactam in plasma and epithelial lining fluid following two dosing regimens

Combination of two pathways involved in raltegravir resistance confers dolutegravir resistance

Drug resistance mutations 18 months after discontinuation of nevirapine-based ART for prevention of mother-to-child transmission of HIV in Malawi

Primary resistance to integrase strand-transfer inhibitors in Europe

A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers

High prevalence of azole resistance in Aspergillus fumigatus isolates from high-risk patients

Total synthesis of avermectin B1a revisited

Total synthesis of avermectin B1a revisited

The Journal of Antibiotics advance online publication, September 9 2015. doi:10.1038/ja.2015.47

Authors: Shuji Yamashita, Daisuke Hayashi, Aoi Nakano, Yujiro Hayashi & Masahiro Hirama

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RQN-18690A (18-deoxyherboxidiene) targets SF3b, a spliceosome component, and inhibits angiogenesis

RQN-18690A (18-deoxyherboxidiene) targets SF3b, a spliceosome component, and inhibits angiogenesis

The Journal of Antibiotics advance online publication, September 9 2015. doi:10.1038/ja.2015.94

Authors: Hideaki Kakeya, Daisuke Kaida, Hiromi Sekiya, Koji Nagai, Minoru Yoshida & Hiroyuki Osada

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Conserved biosynthetic pathways for phosalacine, bialaphos and newly discovered phosphonic acid natural products

Conserved biosynthetic pathways for phosalacine, bialaphos and newly discovered phosphonic acid natural products

The Journal of Antibiotics advance online publication, September 2 2015. doi:10.1038/ja.2015.77

Authors: Joshua AV Blodgett, Jun Kai Zhang, Xiaomin Yu & William W Metcalf

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Two rare quinone-type metabolites from the fungus Septofusidium berolinense and their biological activities

Two rare quinone-type metabolites from the fungus Septofusidium berolinense and their biological activities

The Journal of Antibiotics advance online publication, September 2 2015. doi:10.1038/ja.2015.84

Authors: Güner Ekiz, Elif Esin Hameş, Ayşe Nalbantsoy & Erdal Bedir

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Three new milbemycins from a genetically engineered strain S. avermitilis MHJ1011

Three new milbemycins from a genetically engineered strain S. avermitilis MHJ1011

The Journal of Antibiotics advance online publication, September 2 2015. doi:10.1038/ja.2015.90

Authors: Jun-jie Pan, Xu Wan, Hui Zhang, Zhen Chen, Jun Huang, Bo Yang, An-liang Chen & Ji-dong Wang

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Isolation and structure elucidation of new phthalide and phthalane derivatives, isolated as antimicrobial agents from Emericella sp. IFM57991

Isolation and structure elucidation of new phthalide and phthalane derivatives, isolated as antimicrobial agents from Emericella sp. IFM57991

The Journal of Antibiotics advance online publication, August 26 2015. doi:10.1038/ja.2015.85

Authors: Tetsuya Saito, Takeshi Itabashi, Daigo Wakana, Hisashi Takeda, Takashi Yaguchi, Ken-ichi Kawai & Tomoo Hosoe

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Verrulactones D and E with unprecedented skeletons, new inhibitors of Staphylococcus aureus enoyl-ACP reductase, from Penicillium verruculosum F375

Verrulactones D and E with unprecedented skeletons, new inhibitors of Staphylococcus aureus enoyl-ACP reductase, from Penicillium verruculosum F375

The Journal of Antibiotics advance online publication, August 26 2015. doi:10.1038/ja.2015.86

Authors: Nyung Kim, Mi-Jin Sohn, Hiroyuki Koshino & Won-Gon Kim

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Zincmethylphyrins and coproporphyrins, novel growth factors released by Sphingopyxis sp., enable laboratory cultivation of previously uncultured Leucobacter sp. through interspecies mutualism

Zincmethylphyrins and coproporphyrins, novel growth factors released by Sphingopyxis sp., enable laboratory cultivation of previously uncultured Leucobacter sp. through interspecies mutualism

The Journal of Antibiotics advance online publication, August 26 2015. doi:10.1038/ja.2015.87

Authors: Mohammad Nazrul Islam Bhuiyan, Ryogo Takai, Shinya Mitsuhashi, Kengo Shigetomi, Yasuhiro Tanaka, Yoichi Kamagata & Makoto Ubukata

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Structure and activity relationships of the anti-Mycobacterium antibiotics resorcinomycin and pheganomycin

Structure and activity relationships of the anti-Mycobacterium antibiotics resorcinomycin and pheganomycin

The Journal of Antibiotics advance online publication, August 26 2015. doi:10.1038/ja.2015.88

Authors: Yasushi Ogasawara, Koichi Ooya, Michiko Fujimori, Motoyoshi Noike & Tohru Dairi

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Absolute configuration of NFAT-133, an aromatic polyketide with immunosuppressive and antidiabetic activity from actinomycetes

Absolute configuration of NFAT-133, an aromatic polyketide with immunosuppressive and antidiabetic activity from actinomycetes

The Journal of Antibiotics advance online publication, August 19 2015. doi:10.1038/ja.2015.80

Authors: Yanan Yang, Linkai Yu, Hisayuki Komaki, Naoya Oku & Yasuhiro Igarashi

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The 2014 Garrod Lecture: EUCAST - are we heading towards international agreement?

Antimicrobial susceptibility testing with phenotypic methods is based on the measurement of the MIC (mg/L) and breakpoints to categorize bacteria and fungi as susceptible, intermediate or resistant. Phenotypic antimicrobial susceptibility testing requires an agreement on breakpoints and a rigorous standardization of methods and materials. Requirements for defining breakpoints include a definition of doses and dose intervals, information on MIC distributions for the target organisms, definitions of the highest MIC for organisms devoid of phenotypically expressed resistance (the epidemiological cut-off) and information on resistance mechanisms, pharmacokinetics, pharmacodynamics and clinical outcome in trials. In 2001, the breakpoint committees of France, Germany, Norway, Sweden, the Netherlands and the UK were tasked with developing European breakpoints under the umbrella of EUCAST, organized by ESCMID and later also by ECDC. Breakpoints for previously established antibacterial and antifungal agents in Europe have now been harmonized. With the EMA, EUCAST has since 2006 determined breakpoints for new agents. All breakpoints are freely available on the EUCAST web site; these are used in semi-automated antimicrobial susceptibility testing devices and have been employed since 2010 in a EUCAST disc diffusion method. They have been or are now being implemented in most countries inside Europe and many countries outside it. Everything needed to perform and interpret antimicrobial susceptibility testing is freely available from the EUCAST web site, as are aggregated MIC distributions based on more than 26 000 distributions.

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Antibiotic treatment of verocytotoxin-producing Escherichia coli (VTEC) infection: a systematic review and a proposal

Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection

Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials

Not in my backyard: a systematic review of clinicians' knowledge and beliefs about antibiotic resistance

Multiple hospital outbreaks of vanA Enterococcus faecium in Denmark, 2012-13, investigated by WGS, MLST and PFGE

Clonal diversity, virulence patterns and antimicrobial and biocide susceptibility among human, animal and environmental MRSA in Portugal

Molecular characterization of MRSA isolates bracketing the current EUCAST ceftaroline-susceptible breakpoint for Staphylococcus aureus: the role of PBP2a in the activity of ceftaroline

Insights into the evolutionary trajectories of fluoroquinolone resistance in Streptococcus pneumoniae

Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis

Genome sequencing reveals novel deletions associated with secondary resistance to pyrazinamide in MDR Mycobacterium tuberculosis

High levels of macrolide resistance-associated mutations in Mycoplasma genitalium warrant antibiotic susceptibility-guided treatment

Genomic resistance island AGI1 carrying a complex class 1 integron in a multiply antibiotic-resistant ST25 Acinetobacter baumannii isolate

Effect of the efflux pump QepA2 combined with chromosomally mediated mechanisms on quinolone resistance and bacterial fitness in Escherichia coli

Mutagenesis of the CTX-M-type ESBL--is MIC-guided treatment according to the new EUCAST recommendations a safe approach?

Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea

Survey of multidrug resistance integrative mobilizable elements SGI1 and PGI1 in Proteus mirabilis in humans and dogs in France, 2010-13

Full characterization of the integrative and conjugative element carrying the metallo-{beta}-lactamase blaSPM-1 and bicyclomycin bcr1 resistance genes found in the pandemic Pseudomonas aeruginosa clone SP/ST277

Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations

Next-generation sequencing offers new insights into the resistance of Candida spp. to echinocandins and azoles

Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaounde, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles

A UPLC-MS-MS method for the simultaneous quantification of first-line antituberculars in plasma and in PBMCs

Mode of action of closthioamide: the first member of the polythioamide class of bacterial DNA gyrase inhibitors

Synergistic killing of NDM-producing MDR Klebsiella pneumoniae by two 'old' antibiotics--polymyxin B and chloramphenicol

Efficacy of alternative fidaxomicin dosing regimens for treatment of simulated Clostridium difficile infection in an in vitro human gut model

Auranofin efficacy against MDR Streptococcus pneumoniae and Staphylococcus aureus infections

Pharmacokinetics/pharmacodynamics of a {beta}-lactam and {beta}-lactamase inhibitor combination: a novel approach for aztreonam/avibactam

Residual HIV-1 replication may impact immune recovery in patients on first-line lopinavir/ritonavir monotherapy

Analysis of early resistance development at the first failure timepoint in elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate-treated patients

Determinants of virological failure and antiretroviral drug resistance in Mozambique

Actinoplanes bogoriensis sp. nov., a novel actinomycete isolated from leaf litter

Actinoplanes bogoriensis sp. nov., a novel actinomycete isolated from leaf litter

The Journal of Antibiotics advance online publication, August 5 2015. doi:10.1038/ja.2015.81

Authors: Arif Nurkanto, Puspita Lisdiyanti, Moriyuki Hamada, Shanti Ratnakomala, Chiyo Shibata & Tomohiko Tamura

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Penicyrones A and B, an epimeric pair of α-pyrone-type polyketides produced by the marine-derived Penicillium sp.

Penicyrones A and B, an epimeric pair of α-pyrone-type polyketides produced by the marine-derived Penicillium sp.

The Journal of Antibiotics advance online publication, August 5 2015. doi:10.1038/ja.2015.82

Authors: Ying-Yue Bu, Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Kazuyo Ukai & Michio Namikoshi

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Phenolic compounds from the fungus Inonotus obliquus and their antioxidant properties

Phenolic compounds from the fungus Inonotus obliquus and their antioxidant properties

The Journal of Antibiotics advance online publication, July 29 2015. doi:10.1038/ja.2015.83

Authors: Byung Soon Hwang, In-Kyoung Lee & Bong-Sik Yun

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Biological evaluation and determination of the absolute configuration of chloromonilicin, a strong antimicrobial metabolite isolated from Alternaria sonchi

Biological evaluation and determination of the absolute configuration of chloromonilicin, a strong antimicrobial metabolite isolated from Alternaria sonchi

The Journal of Antibiotics advance online publication, July 15 2015. doi:10.1038/ja.2015.74

Authors: Alessio Cimmino, Gennaro Pescitelli, Alexander Berestetskiy, Anna Dalinova, Denis Krivorotov, Angela Tuzi & Antonio Evidente

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Three novel polyene macrolides isolated from cultures of Streptomyces lavenduligriseus

Three novel polyene macrolides isolated from cultures of Streptomyces lavenduligriseus

The Journal of Antibiotics advance online publication, July 15 2015. doi:10.1038/ja.2015.76

Authors: Jiayue Yang, Zhijun Yang, Yu Yin, Min Rao, Yongheng Liang & Mei Ge

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Reviving old antibiotics

In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to ‘re-develop’ these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections.

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A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin

Within-host diversity of MRSA antimicrobial resistances

Characterization of MDR and XDR Streptococcus pneumoniae in Canada, 2007-13

Prevalence of pilus genes in pneumococci isolated from healthy preschool children in Iceland: association with vaccine serotypes and antibiotic resistance

Retention of virulence following adaptation to colistin in Acinetobacter baumannii reflects the mechanism of resistance

Identification of dfrA14 in two distinct plasmids conferring trimethoprim resistance in Actinobacillus pleuropneumoniae

Emergence and spread of O16-ST131 and O25b-ST131 clones among faecal CTX-M-producing Escherichia coli in healthy individuals in Hunan Province, China

A novel alanine to serine substitution mutation in SoxS induces overexpression of efflux pumps and contributes to multidrug resistance in clinical Escherichia coli isolates

Acquired macrolide resistance genes in Haemophilus influenzae?

Description of an original integron encompassing blaVIM-2, qnrVC1 and genes encoding bacterial group II intron proteins in Pseudomonas aeruginosa

Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure

Efavirenz alters mitochondrial respiratory function in cultured neuron and glial cell lines

Antimicrobial activity and skin permeation of iodine present in an iodine-impregnated surgical incise drape

Unravelling of a mechanism of resistance to colistin in Klebsiella pneumoniae using atomic force microscopy

Enhanced efficacy of putative efflux pump inhibitor/antibiotic combination treatments versus MDR strains of Pseudomonas aeruginosa in a Galleria mellonella in vivo infection model

Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV {beta}-lactamases with single amino acid substitutions in the ohm-loop

Identification of an anti-TB compound targeting the tyrosyl-tRNA synthetase

The indirect microscopic observation drug susceptibility assay demonstrated high concordance with the indirect MGIT method for pyrazinamide susceptibility testing

Bedaquiline susceptibility testing of Mycobacterium tuberculosis in an automated liquid culture system

Performance of EUCAST and CLSI approaches for co-amoxiclav susceptibility testing conditions for clinical categorization of a collection of Escherichia coli isolates with characterized resistance phenotypes

In vitro activity of surotomycin against contemporary clinical isolates of toxigenic Clostridium difficile strains obtained in Spain

Recurrence of dual-strain Clostridium difficile infection in an in vitro human gut model

Serum and cellular ribavirin pharmacokinetic and concentration-effect analysis in HCV patients receiving sofosbuvir plus ribavirin

Mitochondrial and apoptotic in vitro modelling of differential HIV-1 progression and antiretroviral toxicity

Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999-2011

Low-level HIV-1 viraemia in patients on HAART: risk factors and management in clinical practice

Candida biomarkers in patients with candidaemia and bacteraemia

The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality

Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial

A fluorescence-based bioassay for antibacterials and its application in screening natural product extracts

A fluorescence-based bioassay for antibacterials and its application in screening natural product extracts

The Journal of Antibiotics advance online publication, July 8 2015. doi:10.1038/ja.2015.71

Authors: Katharina Michels, Ramona Heinke, Pia Schöne, Oscar P Kuipers, Norbert Arnold & Ludger A Wessjohann

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