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Antibiotics, Volume 8, Issue 1 (March 2019)

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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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Open AccessReview Something Borrowed, Something New: A Governance and Social Construction Framework to Investigate Power Relations and Responses of Diverse Stakeholders to Policies Addressing Antimicrobial Resistance
Received: 6 December 2018 / Revised: 14 December 2018 / Accepted: 19 December 2018 / Published: 24 December 2018
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Abstract
While antimicrobial resistance (AMR) has rapidly ascended the political agenda in numerous high-income countries, developing effective and sustainable policy responses in low- and middle-income countries (LMIC) is far from straightforward, as AMR could be described as a classic ‘wicked problem’. Effective policy responses [...] Read more.
While antimicrobial resistance (AMR) has rapidly ascended the political agenda in numerous high-income countries, developing effective and sustainable policy responses in low- and middle-income countries (LMIC) is far from straightforward, as AMR could be described as a classic ‘wicked problem’. Effective policy responses to combat AMR in LMIC will require a deeper knowledge of the policy process and its actors at all levels—global, regional and national—and their motivations for supporting or opposing policies to combat AMR. The influence of personal interests and connections between for-profit organisations—such as pharmaceutical companies and food producers—and policy actors in these settings is complex and very rarely addressed. In this paper, the authors describe the role of policy analysis focusing on social constructions, governance and power relations in soliciting a better understanding of support and opposition by key stakeholders for alternative AMR mitigation policies. Owing to the lack of conceptual frameworks on the policy process addressing AMR, we propose an approach to researching policy processes relating to AMR currently tested through our empirical programme of research in Cambodia, Pakistan, Indonesia and Tanzania. This new conceptualisation is based on theories of governance and a social construction framework and describes how the framework is being operationalised in several settings. Full article
Open AccessReview Interventions to Reduce Antibiotic Prescribing in LMICs: A Scoping Review of Evidence from Human and Animal Health Systems
Received: 1 November 2018 / Revised: 17 December 2018 / Accepted: 18 December 2018 / Published: 22 December 2018
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Abstract
This review identifies evidence on supply-side interventions to change the practices of antibiotic prescribers and gatekeepers in low- and middle-income countries (LMICs). A total of 102 studies met the inclusion criteria, of which 70 studies evaluated interventions and 32 provided insight into prescribing [...] Read more.
This review identifies evidence on supply-side interventions to change the practices of antibiotic prescribers and gatekeepers in low- and middle-income countries (LMICs). A total of 102 studies met the inclusion criteria, of which 70 studies evaluated interventions and 32 provided insight into prescribing contexts. All intervention studies were from human healthcare settings, none were from animal health. Only one context study examined antibiotic use in animal health. The evidence base is uneven, with the strongest evidence on knowledge and stewardship interventions. The review found that multiplex interventions that combine different strategies to influence behaviour tend to have a higher success rate than interventions based on single strategies. Evidence on prescribing contexts highlights interacting influences including health system quality, education, perceptions of patient demand, bureaucratic processes, profit, competition, and cultures of care. Most interventions took place within one health setting. Very few studies targeted interventions across different kinds of providers and settings. Interventions in hospitals were the most commonly evaluated. There is much less evidence on private and informal private providers who play a major role in drug distribution in LMICs. There were no interventions involving drug detailers or the pharmaceutical companies despite their prominent role in the contextual studies. Full article
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Open AccessBrief Report A Case of Ertapenem Neurotoxicity Resulting in Vocal Tremor and Altered Mentation in a Dialysis Dependent Liver Transplant Patient
Received: 27 November 2018 / Revised: 14 December 2018 / Accepted: 18 December 2018 / Published: 22 December 2018
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Abstract
Carbapenem agents are advanced derivatives of cephalosporins that are active against bacteria that produce extended spectrum beta lactamases (ESBL). These antibiotics are resistant to enzymatic cleavage, and have good central nervous system penetration. Given this fact, it is not surprising that these drugs [...] Read more.
Carbapenem agents are advanced derivatives of cephalosporins that are active against bacteria that produce extended spectrum beta lactamases (ESBL). These antibiotics are resistant to enzymatic cleavage, and have good central nervous system penetration. Given this fact, it is not surprising that these drugs have been reported to cause neurological side effects like seizures and encephalopathy. We report a case of a patient on hemodialytic support who had a notable change in mentation and vocal tremor. This was at first attributed to calcineurin toxicity, but after the finding of a normal tacrolimus level, ertapenem neurotoxicity was suspected. After discontinuation of the offending agent, the patient’s vocal tremor, cognition, and neurological function returned to baseline levels. Full article
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