40 years of veterinary papers in JAC - what have we learnt?

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.

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Pharmacokinetic/pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB

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.

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A review of the pharmacokinetics and pharmacodynamics of aztreonam

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.

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Spotlight on ceftazidime/avibactam: a new option for MDR Gram-negative infections

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.

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Antimicrobial resistance surveillance in urinary tract infections in primary care

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.

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Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis

Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment

Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review

Rilpivirine resistance mutation E138K in HIV-1 reverse transcriptase predisposed by prevalent polymorphic mutations

Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium

P-glycoprotein (ABCB1) activity decreases raltegravir disposition in primary CD4+P-gphigh cells and correlates with HIV-1 viral load

Sequential steps of daptomycin resistance in Enterococcus faecium and reversion to hypersusceptibility through IS-mediated inactivation of the liaFSR operon

Transmission of MDR MRSA between primates, their environment and personnel at a United States primate centre

Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa

New insights into the regulatory pathways associated with the activation of the stringent response in bacterial resistance to the PBP2-targeted antibiotics, mecillinam and OP0595/RG6080

Clonality of erythromycin resistance in Francisella tularensis

Characterization of KPC-encoding plasmids from two endemic settings, Greece and Italy

In vitro biological evaluation of novel broad-spectrum isothiazolone inhibitors of bacterial type II topoisomerases

Activation of type II NADH dehydrogenase by quinolinequinones mediates antitubercular cell death

Structural and sequence analysis of class A {beta}-lactamases with respect to avibactam inhibition: impact of {Omega}-loop variations

Evaluation of different pretreatment protocols to detect accurately clinical carbapenemase-producing Enterobacteriaceae by MALDI-TOF

Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates

High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors

Pharmacodynamics and differential activity of nitrofurantoin against ESBL-positive pathogens involved in urinary tract infections

Comparative efficacy of telavancin and daptomycin in experimental endocarditis due to multi-clonotype MRSA strains

Efficacy of anidulafungin in the treatment of experimental Candida parapsilosis catheter infection using an antifungal-lock technique

Integrated pharmacokinetic-pharmacodynamic modelling to evaluate antimicrobial prophylaxis in abdominal surgery

Non-linear absorption pharmacokinetics of amoxicillin: consequences for dosing regimens and clinical breakpoints

Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa

An update to the HIV-TRePS system: the development and evaluation of new global and local computational models to predict HIV treatment outcomes, with or without a genotype

Novel arginine-containing peptides MBJ-0173 and MBJ-0174 from Mortierella alpina f28740

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

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ASP2397: a novel antifungal agent produced by Acremonium persicinum MF-347833

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

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Isolation of a new antibacterial peptide achromosin from Streptomyces achromogenes subsp. achromogenes based on genome mining

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

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Diapolic acid A–B from an endophytic fungus, Diaporthe terebinthifolii depicting antimicrobial and cytotoxic activity

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

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Substrate specificity of radical S-adenosyl-l-methionine dehydratase AprD4 and its partner reductase AprD3 in the C3′-deoxygenation of aminoglycoside antibiotics

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

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A new polysubstituted cyclopentene derivative from Streptomyces sp. HS-NF-1046

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

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A new cyano-substituted anthracycline metabolite from Streptomyces sp. HS-NF-1006

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

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Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355

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

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