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Antibiotics, Volume 8, Issue 1 (March 2019)

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Cover Story (view full-size image) Pathogenic bacteria that are resistant to antibiotics is one of the most important health [...] Read more.
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Open AccessArticle Characterizing Antimicrobial Use in the Livestock Sector in Three South East Asian Countries (Indonesia, Thailand, and Vietnam)
Antibiotics 2019, 8(1), 33; https://doi.org/10.3390/antibiotics8010033
Received: 31 January 2019 / Revised: 5 March 2019 / Accepted: 15 March 2019 / Published: 25 March 2019
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Abstract
A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was [...] Read more.
A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was high in all sectors studied, and that routine preventative use was of particular importance to broiler production systems. Misleading feed labeling was identified as a hurdle to the collection of accurate antimicrobial use data, with farmers being unaware of the antimicrobials contained in some commercial feed. Economic analysis found that the cost of antimicrobials was low relative to other farm inputs, and that farm profitability was precariously balanced. High disease and poor prices were identified as potential drivers toward economic loss. The research indicates that antimicrobial use in small-scale poultry production systems improves feed conversion ratios and overall productivity. However, data were limited to quantify adequately these potential gains and their impacts on the food supply. During the study, all countries embraced and implemented policies on better management of antimicrobial use in livestock and surveillance of antimicrobial resistance. Future policies need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region. Full article
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Open AccessArticle Activity of Cefepime-Zidebactam against Multidrug-Resistant (MDR) Gram-Negative Pathogens
Antibiotics 2019, 8(1), 32; https://doi.org/10.3390/antibiotics8010032
Received: 18 February 2019 / Revised: 18 March 2019 / Accepted: 19 March 2019 / Published: 23 March 2019
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Abstract
This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum [...] Read more.
This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum of activity, and was highly active against many MDR isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessReview A Review of the Clinical Pharmacokinetics of Polymyxin B
Antibiotics 2019, 8(1), 31; https://doi.org/10.3390/antibiotics8010031
Received: 20 February 2019 / Revised: 12 March 2019 / Accepted: 15 March 2019 / Published: 22 March 2019
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Abstract
Polymyxin B remains an antibiotic of last resort because of its toxicities. Although newer therapies are becoming available, it is anticipated that resistance to these agents will continue to emerge, and understanding the safest and most efficacious manner to deliver polymyxin B will [...] Read more.
Polymyxin B remains an antibiotic of last resort because of its toxicities. Although newer therapies are becoming available, it is anticipated that resistance to these agents will continue to emerge, and understanding the safest and most efficacious manner to deliver polymyxin B will remain highly important. Recent data have demonstrated that polymyxin B may be less nephrotoxic than colistin. Pharmacokinetically, polymyxin B is primarily eliminated via non-renal pathways, and most do not recommend adjusting the dose for renal impairment. However, some recent studies suggest a weak relationship between polymyxin B clearance and patient creatinine clearance. This review article will describe the clinical pharmacokinetics of polymyxin B and address relevant issues in chemistry and assays available. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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Open AccessReview A Mini-Review on Ceftaroline in Bacteremia Patients with Methicillin-Resistant Staphylococcus aureus (MRSA) Infections
Antibiotics 2019, 8(1), 30; https://doi.org/10.3390/antibiotics8010030
Received: 12 February 2019 / Revised: 9 March 2019 / Accepted: 16 March 2019 / Published: 20 March 2019
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Abstract
Objective: The objective of this review is to describe the outcomes of patients treated with ceftaroline in the non-Food and Drug Administration (FDA) approved indication of methicillin-resistant Staphylococcus aureus (MRSA) infections in both pediatric and adult populations. Data sources: A systematic overview was [...] Read more.
Objective: The objective of this review is to describe the outcomes of patients treated with ceftaroline in the non-Food and Drug Administration (FDA) approved indication of methicillin-resistant Staphylococcus aureus (MRSA) infections in both pediatric and adult populations. Data sources: A systematic overview was conducted by searching PubMed, Medline, and The Cochrane Library up to January 2019. Study selection and data extraction: All English-language clinical trials and case reports related to the efficacy of ceftaroline in new, not-yet-approved FDA indications in MRSA infections in pediatric or adult populations. Data synthesis: In the case of MRSA bacteremia (MRSAB) infections, three different randomized studies in pediatric patients showed effectiveness of ceftaroline. When used in the case of adult populations with MRSA bacteremia, a small trial of 16 patients showed 50% clinical success in patients with acute bacterial skin and skin structure infections versus 63% clinical success in patients with community-acquired bacterial pneumonia. Another case series of six refractory case reports showed 50% clinical success of ceftaroline in patients with MRSA. Conclusions: Although there are few case reports and limited data to date, ceftaroline fosamil should continue to be studied as an alternative therapy in MRSA infections in both pediatric and adult populations. Clinical success rates of ceftaroline were, in most cases, considered high when treating patients with MRSA infection. More clinical trials need to be studied. In the specific case of MRSA bacteremia, the treatment options remain few and ceftaroline should be extensively studied for the salvage treatment of MRSAB. Full article
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Open AccessReview Antibiotic Resistance in Pacific Island Countries and Territories: A Systematic Scoping Review
Antibiotics 2019, 8(1), 29; https://doi.org/10.3390/antibiotics8010029
Received: 26 February 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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Abstract
Several studies have investigated antimicrobial resistance in low- and middle-income countries, but to date little attention has been paid to the Pacific Islands Countries and Territories (PICTs). This study aims to review the literature on antibiotic resistance (ABR) in healthcare settings in PICTs [...] Read more.
Several studies have investigated antimicrobial resistance in low- and middle-income countries, but to date little attention has been paid to the Pacific Islands Countries and Territories (PICTs). This study aims to review the literature on antibiotic resistance (ABR) in healthcare settings in PICTs to inform further research and future policy development for the region. Following the PRISMA-ScR checklist health databases and grey literature sources were searched. Three reviewers independently screened the literature for inclusion, data was extracted using a charting tool and the results were described and synthesised. Sixty-five studies about ABR in PICTs were identified and these are primarily about New Caledonia, Fiji and Papua New Guinea. Ten PICTs contributed the remaining 21 studies and nine PICTs were not represented. The predominant gram-positive pathogen reported was community-acquired methicillin resistant S. aureus and the rates of resistance ranged widely (>50% to <20%). Resistance reported in gram-negative pathogens was mainly associated with healthcare-associated infections (HCAIs). Extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolates were reported in New Caledonia (3.4%) and Fiji (22%) and carbapenem resistant A. baumannii (CR-ab) isolates in the French Territories (24.8%). ABR is a problem in the PICTs, but the epidemiology requires further characterisation. Action on strengthening surveillance in PICTs needs to be prioritised so strategies to contain ABR can be fully realised. Full article
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Open AccessArticle Antibiotic Activity Potentiation and Physicochemical Characterization of the Fixed Orbignya speciosa Almond Oil against MDR Staphylococcus aureus and Other Bacteria
Antibiotics 2019, 8(1), 28; https://doi.org/10.3390/antibiotics8010028
Received: 8 February 2019 / Revised: 7 March 2019 / Accepted: 15 March 2019 / Published: 17 March 2019
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Abstract
Orbignya speciosa (babassu) is an important palm tree in Brazil whose fixed almond oil is used in popular medicine and especially in food, in addition to being a research target for the manufacture of biofuels. The aim of this study was to evaluate [...] Read more.
Orbignya speciosa (babassu) is an important palm tree in Brazil whose fixed almond oil is used in popular medicine and especially in food, in addition to being a research target for the manufacture of biofuels. The aim of this study was to evaluate the fixed almond oil physicochemical characterization and its antibacterial activity in isolation and in association with aminoglycosides against standard and multidrug-resistant bacteria. Analyses such as water content, pH, acidity, peroxide index, relative density, and refractive index indicate the stability and chemical quality of the oil. In the oil’s GC/MS chemical composition analysis, a high saturated fatty acid (76.90%) content was observed. Lauric acid (56.28%) and oleic acid (23.10%) were the major oil components. In the antibacterial test, a more significant oil activity was observed against K. pneumoniae KP-ATCC 10031 (minimal inhibitory concentration (MIC) = 406.37 μg/mL) and Staphylococcus aureus ATCC 6538 (MIC = 812.75 μg/mL), but for the other strains—including standard and multi-resistant strains—the oil presented an MIC ≥ 1024 μg/mL. Furthermore, a synergistic effect was observed when the oil was associated with amikacin and gentamicin against S. aureus (SA-10) and an antagonistic effect was observed with amikacin against Escherichia coli. Data indicate the O. speciosa oil as a valuable nutritional source of lauric, oleic, and myristic fatty acids with an ability to modulate aminoglycoside activity. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Open AccessReview A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia
Antibiotics 2019, 8(1), 27; https://doi.org/10.3390/antibiotics8010027
Received: 25 February 2019 / Revised: 8 March 2019 / Accepted: 12 March 2019 / Published: 16 March 2019
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Abstract
Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the [...] Read more.
Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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Open AccessArticle Genetic Profiling and Comparison of Human and Animal Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Serbia
Antibiotics 2019, 8(1), 26; https://doi.org/10.3390/antibiotics8010026
Received: 10 February 2019 / Revised: 9 March 2019 / Accepted: 13 March 2019 / Published: 16 March 2019
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Abstract
The aim of this study was to characterize a collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates of human and animal origin from Serbia. In total, 36 MRSA isolates—30 obtained from humans and six from companion animals—were investigated by PCR for the presence of [...] Read more.
The aim of this study was to characterize a collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates of human and animal origin from Serbia. In total, 36 MRSA isolates—30 obtained from humans and six from companion animals—were investigated by PCR for the presence of antibiotic and biocide resistance determinants and virulence genes (PVL—Panton–Valentine leukocidin, ETs—exfoliative toxins, TSST—toxic shock syndrome toxin, SEs—staphylococcal enterotoxins, and MSCRAMMs—microbial surface components recognizing adhesive matrix molecules and biofilm). Isolates were analyzed by staphylococcal cassette chromosome mec (SCCmec), spa, and dru typing, as well as by multiple locus variable number of tandem repeat analyses (MLVA), multilocus sequence typing (MLST), and subsequently, eBURST. The majority of human MRSA isolates were resistant to gentamicin, erythromycin, clindamycin, and ciprofloxacin. Different antibiotic resistance genes were detected: aac-aphD, ant(6′)-Ia, erm(A), erm(B), erm(C), tet(K), tet(M), fexA, and catpC221. All isolates were susceptible to teicoplanin and linezolid. SCCmec type III was prevalent in human isolates, while SCCmec elements in animals were mostly nontypeable. t037 was the predominant spa type in human and t242 in animal MRSA isolates. The prevalent dru type was dt11c in human and dt10a in animal MRSA isolates. MRSA isolates exhibited 27 different MLVA types. ST239 was predominant in human, while ST5 was prevalent in canine MRSA isolates. PVL was found in two, while tsst-1 was detected in three human isolates. Human-associated clones belonging to ST5, ST45, and ST239 MRSA clones were discovered in companion animals, which suggests anthropozoonotic transmission. Full article
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Open AccessArticle A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters
Antibiotics 2019, 8(1), 25; https://doi.org/10.3390/antibiotics8010025
Received: 5 February 2019 / Revised: 27 February 2019 / Accepted: 12 March 2019 / Published: 15 March 2019
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Abstract
Multidrug efflux systems play a prominent role in medicine, as they are important contributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major facilitator superfamily that expels numerous drug compounds across the inner membrane of Staphylococcus aureus (S. [...] Read more.
Multidrug efflux systems play a prominent role in medicine, as they are important contributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major facilitator superfamily that expels numerous drug compounds across the inner membrane of Staphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new opportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular modeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over 673 compounds from the PubChem database with a high (>80%) level of similarity to the chemical structure of capsaicin was used to study the binding affinity of small molecule compounds for the NorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in particular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of major facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy described in this study, and the structural information of the potential novel inhibitors thus identified, will stimulate others to pursue the development of better drugs to tackle multidrug resistance in S. aureus. Full article
(This article belongs to the Special Issue Chemical Tools for Antibiotics Research)
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Open AccessReview Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity
Antibiotics 2019, 8(1), 24; https://doi.org/10.3390/antibiotics8010024
Received: 31 January 2019 / Revised: 7 March 2019 / Accepted: 11 March 2019 / Published: 14 March 2019
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Abstract
Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and [...] Read more.
Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies. Full article
(This article belongs to the Special Issue Proceedings from the 3rd International Conference on Polymyxins)
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Open AccessArticle Prevalence of Antibiotic Resistance Genes in Multidrug-Resistant Enterobacteriaceae on Portuguese Livestock Manure
Antibiotics 2019, 8(1), 23; https://doi.org/10.3390/antibiotics8010023
Received: 8 January 2019 / Revised: 22 February 2019 / Accepted: 23 February 2019 / Published: 13 March 2019
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Abstract
The exposure of both crop fields and humans to antibiotic-resistant bacteria in animal excreta is an emergent concern of the One Health initiative. This study assessed the contamination of livestock manure from poultry, pig, dairy farms and slaughterhouses in Portugal with resistance determinants. [...] Read more.
The exposure of both crop fields and humans to antibiotic-resistant bacteria in animal excreta is an emergent concern of the One Health initiative. This study assessed the contamination of livestock manure from poultry, pig, dairy farms and slaughterhouses in Portugal with resistance determinants. The resistance profiles of 331 Enterobacteriaceae isolates to eight β-lactam (amoxicillin, cefoxitin, cefotaxime, cefpirome, aztreonam, ceftazidime, imipenem and meropenem) and to five non-β-lactam antibiotics (tetracycline (TET), trimethoprim/sulfamethoxazole (SXT), ciprofloxacin (CIP), chloramphenicol (CHL) and gentamicin) was investigated. Forty-nine integron and non-β-lactam resistance genes were also screened for. Rates of resistance to the 13 antibiotics ranged from 80.8% to 0.6%. Multidrug resistance (MDR) rates were highest in pig farm samples (79%). Thirty different integron and resistance genes were identified. These were mainly associated with resistance to CHL (catI and catII), CIP (mainly, qnrS, qnrB and oqx), TET (mainly tet(A) and tet(M)) and SXT (mostly dfrIa group and sul3). In MDR isolates, integron presence and non-β-lactam resistance to TET, SXT and CHL were positively correlated. Overall, a high prevalence of MDR Enterobacteriaceae was found in livestock manure. The high gene diversity for antibiotic resistance identified in this study highlights the risk of MDR spread within the environment through manure use. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
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Open AccessArticle Chemical Profile, Antibacterial Activity and Antibiotic-Modulating Effect of the Hexanic Zea Mays L. Silk Extract (Poaceae)
Antibiotics 2019, 8(1), 22; https://doi.org/10.3390/antibiotics8010022
Received: 3 February 2019 / Revised: 5 March 2019 / Accepted: 9 March 2019 / Published: 12 March 2019
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Abstract
The present study aimed to determine the chemical profile and to evaluate the antibacterial activity and antibiotic-modulating action of the hexanic Zea mays silk extract in association with aminoglycosides. Standard Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 [...] Read more.
The present study aimed to determine the chemical profile and to evaluate the antibacterial activity and antibiotic-modulating action of the hexanic Zea mays silk extract in association with aminoglycosides. Standard Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 strains, as well as multi-resistant Escherichia coli 27, Staphylococcus aureus 35, and Pseudomonas aeruginosa 31 strains, were used in this study. Phytochemical prospection revealed the presence of the following secondary metabolites: tannins, flavones, flavonoids, and xanthones, with the main chemical constituents being identified in plant extracts obtained with apolar organic solvents such as hexane. The extract presented a minimum inhibitory concentration (MIC) ≥1024 μg/mL against all the tested strains. The association of the extract with aminoglycoside antibiotics showed significant synergistic effects against Staphylococcus aureus and Pseudomonas aeruginosa, except for amikacin, which was antagonized by the extract against E. coli. These results indicate the Zea mays silk presents bioactive compounds with antibiotic-modulating properties. However, further research is required to characterize the effects of isolated compounds and determine their potential for drug development. Full article
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Open AccessArticle Demographic, Knowledge and Impact Analysis of 57,627 Antibiotic Guardians Who Have Pledged to Contribute to Tackling Antimicrobial Resistance
Antibiotics 2019, 8(1), 21; https://doi.org/10.3390/antibiotics8010021
Received: 11 December 2018 / Revised: 24 February 2019 / Accepted: 28 February 2019 / Published: 9 March 2019
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Abstract
In 2014, Public Health England (PHE) developed the behavioural change Antibiotic Guardian (AG) campaign to tackle antimicrobial resistance (AMR). This included an online pledge system aimed at healthcare professionals (HCP) and the public. Demographics of AGs were collected when pledging online and analysed [...] Read more.
In 2014, Public Health England (PHE) developed the behavioural change Antibiotic Guardian (AG) campaign to tackle antimicrobial resistance (AMR). This included an online pledge system aimed at healthcare professionals (HCP) and the public. Demographics of AGs were collected when pledging online and analysed by pledge group, type, geography, and source of hearing of the campaign between 24/07/2014–31/12/2017. Website visitors and acquisition routes were described using Google analytics data. From November 2016, five questions assessed AMR knowledge which was compared to published Eurobarometer AMR survey results for UK. Behaviour change of AGs was also assessed through an impact questionnaire, evaluating the effect of the campaign on self-reported behaviour around AMR. Overall there were 231,460 unique website visitors from 202 countries resulting in 57,627 English and 652 foreign language pledges. Website visitors increased each year with peaks during European Antibiotic Awareness Day and (EAAD) World Antibiotic Awareness Week (WAAW). Self-direction was the largest acquisition route (55%) with pledges more likely via this route than social media (OR 2.6, 95% CI 2.5–2.6). AGs (including the public) were more likely to answer questions correctly than the Eurobarometer UK group (OR 8.5, 95% CI 7.4–9.9). AG campaign engagement has increased over the four years with particular increases in the student group. AGs had greater knowledge compared to the Eurobarometer UK population. The latest impact evaluation of the online pledge scheme highlights that it continues to be an effective and inexpensive way to engage people with the problem of AMR especially among those with prior awareness of the topic. Full article
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Open AccessArticle Characterization and Antimicrobial Activity of Amphiphilic Peptide AP3 and Derivative Sequences
Antibiotics 2019, 8(1), 20; https://doi.org/10.3390/antibiotics8010020
Received: 19 February 2019 / Revised: 27 February 2019 / Accepted: 28 February 2019 / Published: 6 March 2019
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Abstract
The continued emergence of new antibiotic resistant bacterial strains has resulted in great interest in the development of new antimicrobial treatments. Antimicrobial peptides (AMPs) are one of many potential classes of molecules to help meet this emerging need. AMPs are naturally derived sequences, [...] Read more.
The continued emergence of new antibiotic resistant bacterial strains has resulted in great interest in the development of new antimicrobial treatments. Antimicrobial peptides (AMPs) are one of many potential classes of molecules to help meet this emerging need. AMPs are naturally derived sequences, which act as part of the innate immune system of organisms ranging from insects through humans. We investigated the antimicrobial peptide AP3, which is originally isolated from the winter flounder Pleuronectes americanus. This peptide is of specific interest because it does not exhibit the canonical facially amphiphilic orientation of side chains when in a helical orientation. Different analogs of AP3 were synthesized in which length, charge identity, and Trp position were varied to investigate the sequence-structure and activity relationship. We performed biophysical and microbiological characterization using fluorescence spectroscopy, CD spectroscopy, vesicle leakage assays, bacterial membrane permeabilization assays, and minimal inhibitory concentration (MIC) assays. Fluorescence spectroscopy showed that the peptides bind to lipid bilayers to similar extents, while CD spectra show the peptides adopt helical conformations. All five peptides tested in this study exhibited binding to model lipid membranes, while the truncated peptides showed no measurable antimicrobial activity. The most active peptide proved to be the parent peptide AP3 with the highest degree of leakage and bacterial membrane permeabilization. Moreover, it was found that the ability to permeabilize model and bacterial membranes correlated most closely with the ability to predict antimicrobial activity. Full article
(This article belongs to the Special Issue Antimicrobial Peptides, Polymers and Surfaces)
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Open AccessArticle Profluorescent Fluoroquinolone-Nitroxides for Investigating Antibiotic–Bacterial Interactions
Antibiotics 2019, 8(1), 19; https://doi.org/10.3390/antibiotics8010019
Received: 14 February 2019 / Revised: 27 February 2019 / Accepted: 27 February 2019 / Published: 4 March 2019
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Abstract
Fluorescent probes are widely used for imaging and measuring dynamic processes in living cells. Fluorescent antibiotics are valuable tools for examining antibiotic–bacterial interactions, antimicrobial resistance and elucidating antibiotic modes of action. Profluorescent nitroxides are ‘switch on’ fluorescent probes used to visualize and monitor [...] Read more.
Fluorescent probes are widely used for imaging and measuring dynamic processes in living cells. Fluorescent antibiotics are valuable tools for examining antibiotic–bacterial interactions, antimicrobial resistance and elucidating antibiotic modes of action. Profluorescent nitroxides are ‘switch on’ fluorescent probes used to visualize and monitor intracellular free radical and redox processes in biological systems. Here, we have combined the inherent fluorescent and antimicrobial properties of the fluoroquinolone core structure with the fluorescence suppression capabilities of a nitroxide to produce the first example of a profluorescent fluoroquinolone-nitroxide probe. Fluoroquinolone-nitroxide (FN) 14 exhibited significant suppression of fluorescence (>36-fold), which could be restored via radical trapping (fluoroquinolone-methoxyamine 17) or reduction to the corresponding hydroxylamine 20. Importantly, FN 14 was able to enter both Gram-positive and Gram-negative bacterial cells, emitted a measurable fluorescence signal upon cell entry (switch on), and retained antibacterial activity. In conclusion, profluorescent nitroxide antibiotics offer a new powerful tool for visualizing antibiotic–bacterial interactions and researching intracellular chemical processes. Full article
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Open AccessReview CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool
Antibiotics 2019, 8(1), 18; https://doi.org/10.3390/antibiotics8010018
Received: 29 January 2019 / Revised: 14 February 2019 / Accepted: 27 February 2019 / Published: 28 February 2019
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Abstract
Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a [...] Read more.
Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being used in plenty of in vitro and in vivo experiments in recent years. This review illustrates the mechanisms behind CRISPR-Cas systems as a means of bacterial immunity against phage invasion and how these systems were engineered to originate new genetic manipulation tools. Newfound CRISPR-Cas technologies and the up-and-coming applications of these systems on healthcare and other fields of science are also discussed. Full article
(This article belongs to the Special Issue Chemical Tools for Antibiotics Research)
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Open AccessArticle A RADAR-Based Assay to Isolate Covalent DNA Complexes in Bacteria
Antibiotics 2019, 8(1), 17; https://doi.org/10.3390/antibiotics8010017
Received: 1 February 2019 / Revised: 14 February 2019 / Accepted: 21 February 2019 / Published: 27 February 2019
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Abstract
Quinolone antibacterials target the type II topoisomerases gyrase and topoisomerase IV and kill bacterial cells by converting these essential enzymes into cellular poisons. Although much is known regarding the interactions between these drugs and enzymes in purified systems, much less is known regarding [...] Read more.
Quinolone antibacterials target the type II topoisomerases gyrase and topoisomerase IV and kill bacterial cells by converting these essential enzymes into cellular poisons. Although much is known regarding the interactions between these drugs and enzymes in purified systems, much less is known regarding their interactions in the cellular context due to the lack of a widely accessible assay that does not require expensive, specialized equipment. Thus, we developed an assay, based on the “rapid approach to DNA adduct recovery,” or RADAR, assay that is used with cultured human cells, to measure cleavage complex levels induced by treating bacterial cultures with the quinolone ciprofloxacin. Many chemical and mechanical lysis conditions and DNA precipitation conditions were tested, and the method involving sonication in denaturing conditions followed by precipitation of DNA via addition of a half volume of ethanol provided the most consistent results. This assay can be used to complement results obtained with purified enzymes to expand our understanding of quinolone mechanism of action and to test the activity of newly developed topoisomerase-targeted compounds. In addition, the bacterial RADAR assay can be used in other contexts, as any proteins covalently complexed to DNA should be trapped on and isolated with the DNA, allowing them to then be quantified. Full article
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Open AccessArticle Mapping and Analysing Potential Sources and Transmission Routes of Antimicrobial Resistant Organisms in the Environment using Geographic Information Systems—An Exploratory Study
Antibiotics 2019, 8(1), 16; https://doi.org/10.3390/antibiotics8010016
Received: 21 December 2018 / Revised: 21 January 2019 / Accepted: 25 February 2019 / Published: 27 February 2019
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Abstract
Antimicrobial resistance (AMR) is one of the leading threats to human health worldwide. The identification of potential sources of antimicrobial resistant organisms (AROs) and their transmission routes in the environment is important for improving our understanding of AMR and to inform and improve [...] Read more.
Antimicrobial resistance (AMR) is one of the leading threats to human health worldwide. The identification of potential sources of antimicrobial resistant organisms (AROs) and their transmission routes in the environment is important for improving our understanding of AMR and to inform and improve policy and monitoring systems, as well as the identification of suitable sampling locations and potential intervention points. This exploratory study uses geographic information systems (GIS) to analyse the spatial distribution of likely ARO sources and transmission routes in four local authority areas (LAAs) in Ireland. A review of relevant spatial data in each LAA, grouped into themes, and categorised into sources and transmission routes, was undertaken. A range of GIS techniques was used to extract, organise, and collate the spatial data into final products in the form of thematic maps for visual and spatial analysis. The results highlight the location of ‘clusters’ at increased risk of harbouring AMR in each LAA. They also demonstrate the relevance of aquatic transmission routes for ARO mobility and risk of human exposure. The integration of a GIS approach with expert knowledge of AMR is shown to be a useful tool to gain insights into the spatial dimension of AMR and to guide sampling campaigns and intervention points. Full article
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Open AccessArticle Utility of Combination Antimicrobial Therapy in Adults with Bloodstream Infections due to Enterobacteriaceae and Non-Fermenting Gram-Negative Bacilli Based on In Vitro Analysis at Two Community Hospitals
Antibiotics 2019, 8(1), 15; https://doi.org/10.3390/antibiotics8010015
Received: 20 December 2018 / Revised: 5 February 2019 / Accepted: 6 February 2019 / Published: 8 February 2019
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Abstract
This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to [...] Read more.
This study examined the utility of combination therapy for bloodstream isolates of Enterobacteriaceae and non-fermenting Gram-negative bacilli (NFGN) from adults at two community hospitals from January 2010 through to June 2015. Changes to in vitro antimicrobial susceptibilities by adding ciprofloxacin or gentamicin to third-generation cephalosporins (3GC) were examined overall and in patients with risk factors for 3GC resistance. Overall ceftriaxone susceptibility among Enterobacteriaceae was 996/1063 (94%) and 247/295 (84%) in patients with 3GC resistance risk factors. Susceptibilities increased marginally by adding ciprofloxacin or gentamicin (mean difference 2.4% (95% CI 1.5, 3.4) and 3.0% (95% CI 2.0, 4.0), respectively, overall and 5.4% (95% CI 2.8, 8.0) and 7.1% (95% CI 4.2, 10.1), respectively, in patients with risk factors). Eighty-three of 105 (79%) NFGN were susceptible to ceftazidime overall and 20/29 (69%) in patients with prior beta-lactam use. Overall mean increase in susceptibilities was 15.2% (95% CI: 8.3, 22.2) and 17.1% (95% CI: 9.8, 24.5) for ciprofloxacin and gentamicin combinations, respectively; and 27.6% (95% CI: 10.3, 44.9) for either one with recent beta-lactam use. In this setting, empirical combination therapy had limited utility for Enterobacteriaceae bloodstream isolates but provided significant additional antimicrobial coverage to ceftazidime for NFGN, particularly in patients with prior beta-lactam use. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessCommentary Nasal Decolonisation of MRSA
Antibiotics 2019, 8(1), 14; https://doi.org/10.3390/antibiotics8010014
Received: 14 January 2019 / Revised: 28 January 2019 / Accepted: 2 February 2019 / Published: 4 February 2019
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Abstract
The recent demonstration for the first time of urinary monic acid A as a clinical urinary biomarker of exposure to intra-nasal mupirocin during medication for methicillin-resistant Staphylococcus aureus (MRSA) offers a way of verifying adherence to the regimen. However, absence of the biomarker [...] Read more.
The recent demonstration for the first time of urinary monic acid A as a clinical urinary biomarker of exposure to intra-nasal mupirocin during medication for methicillin-resistant Staphylococcus aureus (MRSA) offers a way of verifying adherence to the regimen. However, absence of the biomarker in some patients needs explanation, to ensure that efficient decolonisation has not been compromised by confounding circumstances, and that additional resistance to mupirocin has not unwittingly been encouraged. Full article
Open AccessReview Antibiotic Resistance Can Be Enhanced in Gram-Positive Species by Some Biocidal Agents Used for Disinfection
Antibiotics 2019, 8(1), 13; https://doi.org/10.3390/antibiotics8010013
Received: 18 January 2019 / Revised: 29 January 2019 / Accepted: 1 February 2019 / Published: 1 February 2019
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Abstract
Some biocidal agents used for disinfection have been described to enhance antibiotic resistance in Gram-negative species. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-positive species. A MEDLINE search [...] Read more.
Some biocidal agents used for disinfection have been described to enhance antibiotic resistance in Gram-negative species. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-positive species. A MEDLINE search was performed for each biocidal agent on antibiotic tolerance, antibiotic resistance, horizontal gene transfer, and efflux pump. Most data were reported with food-associated bacterial species. In cells adapted to benzalkonium chloride, a new resistance was most frequently found to ampicillin (seven species), cefotaxime and sulfamethoxazole (six species each), and ceftazidime (five species), some of them with relevance for healthcare-associated infections such as Enterococcus faecium and Enterococcus faecalis. With chlorhexidine, a new resistance was often found to imipenem (ten species) as well as cefotaxime, ceftazidime, and tetracycline (seven species each). Cross-resistance was also found with triclosan and ceftazidime (eight species), whereas it was very uncommon for didecyldimethylammonium chloride or hydrogen peroxide. No cross-resistance to antibiotics has been described after low level exposure to glutaraldehyde, ethanol, propanol, peracetic acid, octenidine, povidone iodine, sodium hypochlorite, and polyhexanide. Preference should be given to disinfectant formulations based on biocidal agents with a low or no selection pressure potential. Full article
Open AccessReview The Use of Tethered Bilayer Lipid Membranes to Identify the Mechanisms of Antimicrobial Peptide Interactions with Lipid Bilayers
Antibiotics 2019, 8(1), 12; https://doi.org/10.3390/antibiotics8010012
Received: 8 January 2019 / Revised: 28 January 2019 / Accepted: 29 January 2019 / Published: 30 January 2019
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Abstract
This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, [...] Read more.
This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents. Full article
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Open AccessArticle The State of Education and Training for Antimicrobial Stewardship Programs in Indian Hospitals―A Qualitative and Quantitative Assessment
Antibiotics 2019, 8(1), 11; https://doi.org/10.3390/antibiotics8010011
Received: 14 December 2018 / Revised: 20 January 2019 / Accepted: 23 January 2019 / Published: 30 January 2019
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Abstract
Background: To understand the role of infrastructure, manpower, and education and training (E&T) in relation to Antimicrobial Stewardship (AMS) in Indian healthcare organizations. Methods: Mixed method approach using quantitative survey and qualitative interviews was applied. Through key informants, healthcare professionals from [...] Read more.
Background: To understand the role of infrastructure, manpower, and education and training (E&T) in relation to Antimicrobial Stewardship (AMS) in Indian healthcare organizations. Methods: Mixed method approach using quantitative survey and qualitative interviews was applied. Through key informants, healthcare professionals from 69 hospitals (public & private) were invited to participate in online survey and follow up qualitative interviews. Thematic analysis was applied to identify the key emerging themes from the interviews. The survey data were analyzed using descriptive statistics. Results: 60 healthcare professionals from 51 hospitals responded to the survey. Eight doctors participated in semi-structured telephone interviews. 69% (27/39) of the respondents received E&T on AMS during undergraduate or postgraduate training. 88% (15/17) had not received any E&T at induction or during employment. In the qualitative interviews three key areas of concern were identified: (1) need for government level endorsement of AMS activities; (2) lack of AMS programs in hospitals; and, (3) lack of postgraduate E&T in AMS for staff. Conclusion: No structured provision of E&T for AMS currently exists in India. Stakeholder engagement is essential to the sustainable design and implementation of bespoke E&T for hospital AMS in India. Full article
Open AccessArticle The Effects of Mentha × piperita Essential Oil on C. albicans Growth, Transition, Biofilm Formation, and the Expression of Secreted Aspartyl Proteinases Genes
Antibiotics 2019, 8(1), 10; https://doi.org/10.3390/antibiotics8010010
Received: 21 December 2018 / Revised: 18 January 2019 / Accepted: 26 January 2019 / Published: 30 January 2019
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Abstract
The rise in resistance and changes in the spectrum of Candida infections have generated enormous interest in developing new antifungal drugs using natural molecules such as plant essential oils (EOs). Antimicrobial activity against foodborne pathogenic and spoilage microorganisms has been reported for EOs. [...] Read more.
The rise in resistance and changes in the spectrum of Candida infections have generated enormous interest in developing new antifungal drugs using natural molecules such as plant essential oils (EOs). Antimicrobial activity against foodborne pathogenic and spoilage microorganisms has been reported for EOs. The goal of this study was to assess the effect of Mentha × piperita essential oil (EO) on C. albicans growth, transition (change from blastospore to hyphae forms), and biofilm formation as well as on the expression of certain virulent genes. We show that whole EO and its vapor attenuated the yeast’s growth, compared to that in the control. The effect of the EO was comparable to that of amphotericin-B (AmB). The EO and its vapor significantly decreased the morphological changes of C. albicans, reduced biofilm formation, and disrupted mature C. albicans biofilms. The effect produced by whole EO on biofilm formation/disruption was notably comparable to that observed with AmB. Exposure of C. albicans to EO and its vapor downregulated the expression of various genes, such as secreted aspartyl proteinases (SAP 1, 2, 3, 9, 10) and hyphal wall protein 1 (HWP1). Altogether, these results provide new insight into the efficacy of Mentha × piperita EO against C. albicans and suggest the potential of Mentha × piperita EO for use as an antifungal therapy in multiple applications. Full article
(This article belongs to the Special Issue Chemical Tools for Antibiotics Research)
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Open AccessArticle New Chloramphenicol Derivatives from the Viewpoint of Anticancer and Antimicrobial Activity
Received: 19 December 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 29 January 2019
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Abstract
Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate 3, with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed [...] Read more.
Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate 3, with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed the best antibacterial and anticancer properties. Using 3 as a prototype, we here explored the influence of the antibacterial and anticancer activity of additional benzyl groups on N1 amino moiety together with modifications of the alkyl length of the aminobutyl fragment of SPD. Our data demonstrate that the novel modifications did not further improve the antibacterial activity of the prototype. However, one of the novel conjugates (4) showed anticancer activity without affecting bacterial growth, thus emerging as a promising anticancer agent, with no adverse effects on bacterial microflora when taken orally. Full article
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Open AccessReview The Quest for Novel Antimicrobial Compounds: Emerging Trends in Research, Development, and Technologies
Received: 8 January 2019 / Revised: 17 January 2019 / Accepted: 20 January 2019 / Published: 24 January 2019
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Abstract
Pathogenic antibiotic resistant bacteria pose one of the most important health challenges of the 21st century. The overuse and abuse of antibiotics coupled with the natural evolutionary processes of bacteria has led to this crisis. Only incremental advances in antibiotic development have occurred [...] Read more.
Pathogenic antibiotic resistant bacteria pose one of the most important health challenges of the 21st century. The overuse and abuse of antibiotics coupled with the natural evolutionary processes of bacteria has led to this crisis. Only incremental advances in antibiotic development have occurred over the last 30 years. Novel classes of molecules, such as engineered antibodies, antibiotic enhancers, siderophore conjugates, engineered phages, photo-switchable antibiotics, and genome editing facilitated by the CRISPR/Cas system, are providing new avenues to facilitate the development of antimicrobial therapies. The informatics revolution is transforming research and development efforts to discover novel antibiotics. The explosion of nanotechnology and micro-engineering is driving the invention of antimicrobial materials, enabling the cultivation of “uncultivable” microbes and creating specific and rapid diagnostic technologies. Finally, a revival in the ecological aspects of microbial disease management, the growth of prebiotics, and integrated management based on the “One Health” model, provide additional avenues to manage this health crisis. These, and future scientific and technological developments, must be coupled and aligned with sound policy and public awareness to address the risks posed by rising antibiotic resistance. Full article
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Open AccessReview Antibiotic Stewardship—Twenty Years in the Making
Received: 5 December 2018 / Revised: 9 January 2019 / Accepted: 21 January 2019 / Published: 24 January 2019
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Abstract
In the last 20 years, efforts were made to optimize antibiotic use in hospitals across the world as a means of addressing the increasing threat of antibiotic resistance. Despite robust evidence supporting optimal practice, antibiotic decision-making remains sub-optimal in many settings, including in [...] Read more.
In the last 20 years, efforts were made to optimize antibiotic use in hospitals across the world as a means of addressing the increasing threat of antibiotic resistance. Despite robust evidence supporting optimal practice, antibiotic decision-making remains sub-optimal in many settings, including in hospitals. Globally, resources remain a limiting factor in the implementation of antibiotic stewardship programs. In addition, antibiotic decision-making is a social process dependent on cultural and contextual factors. Cultural boundaries in healthcare and across specialties still limit the involvement of allied healthcare professionals in stewardship interventions. There is variation in the social norms and antibiotic-prescribing behaviors between specialties in hospitals. The cultural differences between specialties and healthcare professionals (1) shape the shared knowledge within and across specialties in the patient pathway, and (2) result in variation in care, thus impacting patient outcomes. Bespoke stewardship interventions that account for contextual variation in practice are necessary. Full article
Open AccessArticle Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Received: 6 December 2018 / Revised: 13 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
Clavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process are compromised by a degradation phenomenon, [...] Read more.
Clavulanic acid (CA) is a β-lactam antibiotic inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. CA is produced in submerged cultures by the filamentous Gram-positive bacterium Streptomyces clavuligerus; yield and downstream process are compromised by a degradation phenomenon, which is not yet completely elucidated. In this contribution, a study of degradation kinetics of CA at low temperatures (−80, −20, 4, and 25 °C) and pH 6.8 in chemically-defined fermentation broths is presented. Samples of CA in the fermentation broths showed a fast decline of concentration during the first 5 h followed by a slower, but stable, reaction rate in the subsequent hours. A reversible-irreversible kinetic model was applied to explain the degradation rate of CA, its dependence on temperature and concentration. Kinetic parameters for the equilibrium and irreversible reactions were calculated and the proposed kinetic model was validated with experimental data of CA degradation ranging 16.3 mg/L to 127.0 mg/L. Degradation of the chromophore CA-imidazole, which is commonly used for quantifications by High Performance Liquid Chromatography, was also studied at 4 °C and 25 °C, showing a rapid rate of degradation according to irreversible first-order kinetics. A hydrolysis reaction mechanism is proposed as the cause of CA-imidazole loss in aqueous solutions. Full article
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Open AccessEditorial Acknowledgement to Reviewers of Antibiotics in 2018
Published: 10 January 2019
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Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Open AccessArticle Characterization of Two New Multidrug-Resistant Strains of Mycobacterium smegmatis: Tools for Routine In Vitro Screening of Novel Anti-Mycobacterial Agents
Received: 13 November 2018 / Revised: 7 December 2018 / Accepted: 7 December 2018 / Published: 2 January 2019
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Abstract
Mycobacterium tuberculosis is a pathogen of global public health concern. This threat is exacerbated by the emergence of multidrug-resistant and extremely-drug-resistant strains of the pathogen. We have obtained two distinct clones of multidrug-resistant Mycobacterium smegmatis after gradual exposure of Mycobacterium smegmatis mc2 [...] Read more.
Mycobacterium tuberculosis is a pathogen of global public health concern. This threat is exacerbated by the emergence of multidrug-resistant and extremely-drug-resistant strains of the pathogen. We have obtained two distinct clones of multidrug-resistant Mycobacterium smegmatis after gradual exposure of Mycobacterium smegmatis mc2 155 to increasing concentrations of erythromycin. The resulting resistant strains of Mycobacterium smegmatis exhibited robust viability in the presence of high concentrations of erythromycin and were found to be resistant to a wide range of other antimicrobials. They also displayed a unique growth phenotype in comparison to the parental drug-susceptible Mycobacterium smegmatis mc2 155, and a distinct colony morphology in the presence of cholesterol. We propose that these two multidrug-resistant clones of Mycobacterium smegmatis could be used as model organisms at the inceptive phase of routine in vitro screening of novel antimicrobial agents targeted against multidrug-resistant Mycobacterial tuberculosis. Full article
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