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Antibiotics, Volume 8, Issue 4 (December 2019) – 115 articles

Cover Story (view full-size image): The spread of resistance and the outer membrane of Gram-negative bacteria, which functions as a barrier, both preclude the clinical use of many antibiotics for treating infections. Recent work has greatly strengthened our understanding of the molecular machines required for outer-membrane assembly. Now, considerable advances have been made in the discovery efforts for novel compounds targeting outer-membrane assembly. Clever strategies, both genetic and biochemical, have identified many promising compounds acting on the outer membrane. Potent new chemicals targeting evolutionarily conserved pathways are now being developed further for future clinical use. Hope for a novel class of outer-membrane-acting antibiotics is now the highest it has been in over forty years. View this paper
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Open AccessCommunication
The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors
Antibiotics 2019, 8(4), 270; https://doi.org/10.3390/antibiotics8040270 - 17 Dec 2019
Cited by 6 | Viewed by 1747
Abstract
Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of [...] Read more.
Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents, encompassing a wide variety of different chemical structures and mechanisms of action, were tested during our experiments. The antibacterial activity of the compounds was tested using the broth microdilution method. Screening and semi-quantitative assessment of QS-inhibition by the compounds was performed using QS-signal molecule-producing and indicator strains. Results: Fourteen pharmaceutical agents showed antibacterial activity in the tested concentration range, while eight drugs (namely 5-fluorouracil, metamizole-sodium, cisplatin, methotrexate, bleomycin, promethazine, chlorpromazine, and thioridazine) showed dose-dependent QS-inhibitory activity in the in vitro model systems applied during the experiments. Conclusions: Virulence inhibitors represent an attractive alternative strategy to combat bacterial pathogens more efficiently. Some of the tested compounds could be considered potential QS-inhibitory agents, warranting further experiments involving additional model systems to establish the extent of their efficacy. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs)
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Open AccessConcept Paper
Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group
Antibiotics 2019, 8(4), 269; https://doi.org/10.3390/antibiotics8040269 - 16 Dec 2019
Cited by 5 | Viewed by 8550
Abstract
Objective: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. Definition: ILADS defines chronic Lyme [...] Read more.
Objective: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. Definition: ILADS defines chronic Lyme disease (CLD) as a multisystem illness with a wide range of symptoms and/or signs that are either continuously or intermittently present for a minimum of six months. The illness is the result of an active and ongoing infection by any of several pathogenic members of the Borrelia burgdorferi sensu lato complex (Bbsl). The infection has variable latency periods and signs and symptoms may wax, wane and migrate. CLD has two subcategories, CLD, untreated (CLD-U) and CLD, previously treated (CLD-PT). The latter requires that CLD manifestations persist or recur following treatment and are present continuously or in a relapsing/remitting pattern for a duration of six months or more. Methods: Systematic review of over 250 peer reviewed papers in the international literature to characterize the clinical spectrum of CLD-U and CLD-PT. Conclusion: This evidence-based definition of chronic Lyme disease clarifies the term’s meaning and the literature review validates that chronic and ongoing Bbsl infections can result in chronic disease. Use of this CLD definition will promote a better understanding of the infection and facilitate future research of this infection. Full article
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
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Open AccessArticle
Development, Validation, and Stability Assessment Application of RP-HPLC-DAD Method for Quantification of Ampicillin in Total Parenteral Nutrition Admixtures
Antibiotics 2019, 8(4), 268; https://doi.org/10.3390/antibiotics8040268 - 15 Dec 2019
Viewed by 1360
Abstract
Background: The administration of total parenteral nutrition (TPN) is a common procedure in intensive care units, where the concomitant use of other intravenous medication is frequently needed. One of the particularly dangerous complications for neurosurgical patients is meningitis, for which high doses of [...] Read more.
Background: The administration of total parenteral nutrition (TPN) is a common procedure in intensive care units, where the concomitant use of other intravenous medication is frequently needed. One of the particularly dangerous complications for neurosurgical patients is meningitis, for which high doses of ampicillin (AMP) are used. In such cases, the addition of AMP to TPN admixtures would be a desirable procedure. Thus, the AMP determination method in TPN admixture was developed and validated. Methods: An isocratic HPLC analysis was performed on a LiChrospher C18 end-capped column (250 mm, 4.6 mm, 5 µm) with a C18 pre-column (LiChrospher 100, 4 mm, 5 µm). The flow rate was 1.0 mL min−1 and the detection wavelength was 230 nm. System suitability parameters, such as capacity factor, numbers of the theoretical plate, asymmetry factor, as well as validation parameters, including method precision, accuracy, linearity, selectivity, and robustness, were set up. Results: The method was shown to be linear, precise, accurate, specific, and robust, and it can be used for the quantitative analysis of AMP in TPN admixtures. Conclusions: The degradation of AMP in the TPN admixtures occurred according to first order kinetics. The degradation rate was high and dependent on the composition of the mixture and the storage conditions (t0.5 varied from 142.44 h to 300.45 h). Full article
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Open AccessCommunication
Exclusive Production of Gentamicin C1a from Micromonospora purpurea by Metabolic Engineering
Antibiotics 2019, 8(4), 267; https://doi.org/10.3390/antibiotics8040267 - 14 Dec 2019
Viewed by 1622
Abstract
Gentamicin C1a is an important precursor to the synthesis of etimicin, a potent antibiotic. Wild type Micromonospora purpurea Gb1008 produces gentamicin C1a, besides four other gentamicin C components: C1, C2, C2a, and C2b. While the previously reported engineered strain M. purpurea GK1101 can [...] Read more.
Gentamicin C1a is an important precursor to the synthesis of etimicin, a potent antibiotic. Wild type Micromonospora purpurea Gb1008 produces gentamicin C1a, besides four other gentamicin C components: C1, C2, C2a, and C2b. While the previously reported engineered strain M. purpurea GK1101 can produce relatively high titers of C1a by blocking the genK pathway, a small amount of undesirable C2b is still being synthesized in cells. Gene genL (orf6255) is reported to be responsible for converting C1a to C2b and C2 to C1 in Micromonospora echinospora ATCC15835. In this work, we identify the genL that is also responsible for the same methylation in Micromonospora purpurea. Based on M. purpurea GK1101, we construct a new strain with genL inactivated and show that no C2b is produced in this strain. Therefore, we successfully engineer a strain of M. purpurea that solely produces gentamicin C1a. This strain can potentially be used in the industrial production of C1a for the synthesis of etimicin. Full article
(This article belongs to the Section Antibiotic Biosynthesis)
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Open AccessArticle
The Inc FII Plasmid and its Contribution in the Transmission of blaNDM-1 and blaKPC-2 in Klebsiella pneumoniae in Egypt
Antibiotics 2019, 8(4), 266; https://doi.org/10.3390/antibiotics8040266 - 13 Dec 2019
Cited by 2 | Viewed by 1557
Abstract
The emergence of blaKPC-2 and blaNDM-1 producing Klebsiella pneumoniae represents a great problem in many Egyptian hospitals. One hundred and twenty-six K. pneumoniae isolates from patients admitted to Assiut University Hospital were identified by an API20E kit. Carbapenemase-producing K. [...] Read more.
The emergence of blaKPC-2 and blaNDM-1 producing Klebsiella pneumoniae represents a great problem in many Egyptian hospitals. One hundred and twenty-six K. pneumoniae isolates from patients admitted to Assiut University Hospital were identified by an API20E kit. Carbapenemase-producing K. pneumoniae (CPKP) was detected by the modified carbapenem inactivation method (mCIM), the EDTA-modified carbapenem inactivation method (eCIM), and an E-test. Based on the polymerase chain reaction, all isolates were negative for bla-VIM-1 and bla-IMP-1, fifteen of these isolates were positive for both blaKPC-2 and blaNDM-1, two isolates were positive for blaKPC-2 only, and twenty-eight isolates were positive for bla-NDM-1 only. Although one isolate was positive for the string test, all CPKP isolates were negative for capsular genes. Only 71.1% of CPKP transferred their plasmids to their corresponding transconjugants (E. coli J53). The resistance patterns of the clinical isolates and their transconjugates were similar, except for 12 isolates, which showed differences with their transconjugates in the resistance profile of four antibiotics. Molecular typing of the plasmids based on replicon typing showed that Inc FIIK and FII plasmids predominated in isolates and their transconjugants carrying blaKPC-2 and/or blaNDM-1. Conjugative Inc FII plasmids play an important role in the spread of CPKP, and their recognition is essential to limit their spread. Full article
(This article belongs to the Special Issue Antibiotics and Environment)
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Open AccessArticle
Short Chain Fatty Acids Commonly Produced by Gut Microbiota Influence Salmonella enterica Motility, Biofilm Formation, and Gene Expression
Antibiotics 2019, 8(4), 265; https://doi.org/10.3390/antibiotics8040265 - 13 Dec 2019
Cited by 4 | Viewed by 1702
Abstract
Short chain fatty acids (SCFAs) are commonly produced by healthy gut microbiota and they have a protective role against enteric pathogens. SCFAs also have direct antimicrobial activity against bacterial pathogens by diffusion across the bacterial membrane and reduction of intracellular pH. Due to [...] Read more.
Short chain fatty acids (SCFAs) are commonly produced by healthy gut microbiota and they have a protective role against enteric pathogens. SCFAs also have direct antimicrobial activity against bacterial pathogens by diffusion across the bacterial membrane and reduction of intracellular pH. Due to this antimicrobial activity, SCFAs have promising applications in human health and food safety. In this study, the minimum inhibitory concentrations (MICs) of four SCFAs (acetic acid, butyric acid, propionic acid, and valeric acid) in Salmonella strains isolated from poultry were determined. The effect of subinhibitory concentrations of SCFAs in Salmonella biofilm formation, motility, and gene expression was also evaluated. Butyric acid, propionic acid, and valeric acid showed a MIC of 3750 µg/mL in all strains tested, while the MIC of acetic acid was between 1875 and 3750 µg/mL. Subinhibitory concentrations of SCFAs significantly (p < 0.05) reduced the motility of all Salmonella strains, especially in the presence of acetic acid. Biofilm formation was also significantly (p < 0.05) lower in the presence of SCFAs in some of the Salmonella strains. Salmonella strain. Salmonella Typhimurium T7 showed significant (p < 0.05) upregulation of important virulence genes, such as invA and hilA, especially in the presence of butyric acid. Therefore, SCFAs are promising substances for the inhibition of the growth of foodborne pathogens. However, it is important to avoid the use of subinhibitory concentrations that could increase the virulence of foodborne pathogen Salmonella. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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Open AccessArticle
Factors Influencing the Onset of Intra- and Post- Operative Complications Following Tooth Exodontia: Retrospective Survey on 1701 Patients
Antibiotics 2019, 8(4), 264; https://doi.org/10.3390/antibiotics8040264 - 13 Dec 2019
Cited by 2 | Viewed by 1636
Abstract
Complications after tooth extraction may occur because of several factors correlated to the patient’s medical history, surgical site or type of intervention. The aim of this retrospective cohort study was to evaluate type and frequency of complications after exodontic surgery, its correlation with [...] Read more.
Complications after tooth extraction may occur because of several factors correlated to the patient’s medical history, surgical site or type of intervention. The aim of this retrospective cohort study was to evaluate type and frequency of complications after exodontic surgery, its correlation with antibiotic administration and between patient’s related systemic factors. From June 2015 until February 2016 1701 exodontic interventions, for a total of 2322 extracted teeth, were carried out at the Unit of Oral Surgery in Trieste. Descriptive statistic, and backward multiple logistic regressions were performed to identify the variables associated with the presence of post-operative alveolitis or any other post-operative complication. The presence of coagulopathy and smoking habit were related to high risk of post-operative alveolitis (OR = 5.51, p = 0.035 and OR = 2.5, p = 0.029, respectively). Tooth fracture was found to be correlated with higher probability of post-operative alveolitis (p = 0.001) and concomitant chemotherapy put at a higher risk post-operative complications, including alveolitis (OR = 29.5, p = 0.018). According to the present results, antibiotic consumption did not seem to reduce the incidence of post-operative infective complications (alveolitis). A careful analysis of medical history, the adequate surgical technique, and the correct instructions in post-surgical behavior, prevent the insurgence of intra and post-operative complications. Full article
(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)
Open AccessReview
Knowledge, Perceptions and Practices of Community Pharmacists Towards Antimicrobial Stewardship: A Systematic Scoping Review
Antibiotics 2019, 8(4), 263; https://doi.org/10.3390/antibiotics8040263 - 12 Dec 2019
Cited by 2 | Viewed by 1952
Abstract
The scope of antimicrobial stewardship (AMS) surveys on community pharmacists (CPs) is uncertain. This study examines the breadth and quality of AMS survey tools measuring the stewardship knowledge, perceptions and practices (KPP) of CPs and analyse survey outcomes. Following PRISMA-ScR checklist and Arksey [...] Read more.
The scope of antimicrobial stewardship (AMS) surveys on community pharmacists (CPs) is uncertain. This study examines the breadth and quality of AMS survey tools measuring the stewardship knowledge, perceptions and practices (KPP) of CPs and analyse survey outcomes. Following PRISMA-ScR checklist and Arksey and O’Malley’s methodological framework seven medical databases were searched. Two reviewers independently screened the literatures, assessed quality of surveys and KPP outcomes were analysed and described. Ten surveys were identified that assessed CPs’ AMS perceptions (n = 7) and practices (n = 8) but none that assessed AMS knowledge. Three survey tools had been formally validated. Most CPs perceived that AMS improved patient care (median 86.0%, IQR, 83.3–93.5%, n = 6), and reduced inappropriate antibiotic use (84.0%, IQR, 83–85%, n = 2). CPs collaborated with prescribers for infection control (54.7%, IQR 34.8–63.2%, n = 4) and for uncertain antibiotic treatment (77.0%, IQR 55.2–77.8%, n = 5). CPs educated patients (53.0%, IQR, 43.2–67.4%, n = 5) and screened guideline-compliance of antimicrobial prescriptions (47.5%, IQR, 25.2–58.3%, n = 3). Guidelines, training, interactions with prescribers, and reimbursement models were major barriers to CP-led AMS implementation. A limited number of validated survey tools are available to assess AMS perceptions and practices of CPs. AMS survey tools require further development to assess stewardship knowledge, stewardship targets, and implementation by CPs. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Tracing Penicillin Movement in Citrus Plants Using Fluorescence-Labeled Penicillin
Antibiotics 2019, 8(4), 262; https://doi.org/10.3390/antibiotics8040262 - 12 Dec 2019
Cited by 1 | Viewed by 1576
Abstract
Huánglóngbìng (HLB), citrus greening, is one of the most destructive diseases of citrus plants worldwide. In North America, HLB is caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus and is transmitted by the Asian citrus psyllid, Diaphorina citri. No cure exists at [...] Read more.
Huánglóngbìng (HLB), citrus greening, is one of the most destructive diseases of citrus plants worldwide. In North America, HLB is caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus and is transmitted by the Asian citrus psyllid, Diaphorina citri. No cure exists at present, and the use of antibiotics for the control of HLB has gained interest due to the significant losses to the citrus industry. Because of unsatisfactory results when using foliar applications of antibiotics, concerns were raised regarding the uptake and translocation of these materials within trees. We, therefore, investigated a method that allows us to study the movement of antibiotic materials in citrus plants. Herein, we utilized a fluorescence-labeled penicillin, BOCILLIN™ FL-Penicillin (FL-penicillin), to study the uptake and translocation of penicillin in citrus plants. FL-penicillin was applied by puncture to the stem of young citrus seedlings and was traced by using fluorescence microscopy. After application, we detected FL-penicillin in the leaves and in the stem xylem and phloem tissues above and below the application site in both intact and partially bark-girdled citrus seedlings, indicating that it is easily taken up and transported through the plant vascular system. In addition, we detected FL-penicillin in the gut of D. citri, which were allowed to feed on the treated plants, suggesting translocation of this molecule into the vascular tissue. We propose that the use of fluorescent-labeled molecules could be an effective tool for understanding the uptake and translocation of antibiotics and other macromolecules in plants and insects. Full article
(This article belongs to the Section Plant-Derived Antibiotics)
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Open AccessReview
Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline
Antibiotics 2019, 8(4), 261; https://doi.org/10.3390/antibiotics8040261 - 11 Dec 2019
Cited by 3 | Viewed by 1909
Abstract
Bedaquiline (BDQ) inhibits ATP generation in Mycobacterium tuberculosis by interfering with the F-ATP synthase activity. Two mechanisms of action of BDQ are broadly accepted. A direct mechanism involves BDQ binding to the enzyme’s c-ring to block its rotation, thus inhibiting ATP synthesis [...] Read more.
Bedaquiline (BDQ) inhibits ATP generation in Mycobacterium tuberculosis by interfering with the F-ATP synthase activity. Two mechanisms of action of BDQ are broadly accepted. A direct mechanism involves BDQ binding to the enzyme’s c-ring to block its rotation, thus inhibiting ATP synthesis in the enzyme’s catalytic α3β3-headpiece. An indirect mechanism involves BDQ uncoupling electron transport in the electron transport chain from ATP synthesis at the F-ATP synthase. In a recently uncovered second direct mechanism, BDQ binds to the enzyme’s ε-subunit to disrupt its ability to link c-ring rotation to ATP synthesis at the α3β3-headpiece. However, this mechanism is controversial as the drug’s binding affinity for the isolated ε-subunit protein is moderate and spontaneous resistance mutants in the ε-subunit cannot be isolated. Recently, the new, structurally distinct BDQ analogue TBAJ-876 was utilized as a chemical probe to revisit BDQ’s mechanisms of action. In this review, we first summarize discoveries on BDQ’s mechanisms of action and then describe the new insights derived from the studies of TBAJ-876. The TBAJ-876 investigations confirm the c-ring as a target, while also supporting a functional role for targeting the ε-subunit. Surprisingly, the new findings suggest that the uncoupler mechanism does not play a key role in BDQ’s anti-mycobacterial activity. Full article
(This article belongs to the Special Issue Antibiotics against Tuberculosis)
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Open AccessReview
The Use of Nanomedicine for Targeted Therapy against Bacterial Infections
Antibiotics 2019, 8(4), 260; https://doi.org/10.3390/antibiotics8040260 - 11 Dec 2019
Cited by 4 | Viewed by 1572
Abstract
The emergence of drug resistance combined with limited success in the discovery of newer and effective antimicrobial chemotherapeutics poses a significant challenge to human and animal health. Nanoparticles may be an approach for effective drug development and delivery against infections caused by multi-drug [...] Read more.
The emergence of drug resistance combined with limited success in the discovery of newer and effective antimicrobial chemotherapeutics poses a significant challenge to human and animal health. Nanoparticles may be an approach for effective drug development and delivery against infections caused by multi-drug resistant bacteria. Here we discuss nanoparticles therapeutics and nano-drug delivery against bacterial infections. The therapeutic efficacy of numerous kinds of nanoparticles including nanoantibiotics conjugates, small molecules capped nanoparticles, polymers stabilized nanoparticles, and biomolecules functionalized nanoparticles has been discussed. Moreover, nanoparticles-based drug delivery systems against bacterial infections have been described. Furthermore, the fundamental limitation of biocompatibility and biosafety of nanoparticles is also conferred. Finally, we propose potential future strategies of nanomaterials as antibacterials. Full article
(This article belongs to the Special Issue Novel Strategies against Pathogenic Bacteria)
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Open AccessArticle
Phylogenetic Diversity, Antimicrobial Susceptibility and Virulence Characteristics of Escherichia coli Isolates from Pigeon Meat
Antibiotics 2019, 8(4), 259; https://doi.org/10.3390/antibiotics8040259 - 10 Dec 2019
Cited by 1 | Viewed by 1528
Abstract
Monitoring resistance to antibiotics in wild animals may assist in evaluating tendencies in the evolution of this major public health problem. The aims of this research work were to determine the patterns of antibiotic resistance in Escherichia coli isolates from the meat of [...] Read more.
Monitoring resistance to antibiotics in wild animals may assist in evaluating tendencies in the evolution of this major public health problem. The aims of this research work were to determine the patterns of antibiotic resistance in Escherichia coli isolates from the meat of wild or domestically reared pigeons from Spain, to detect the presence of virulence and antibiotic resistance genes, and to carry out a phylogenetic classification of the isolates. Of the 37 E. coli strains tested, 32.43% of them belonged to the B2 phylogenetic group, which is often implicated in extra-intestinal infections. None of the strains showed extended-spectrum beta-lactamase activity. All the isolates presented resistance or reduced susceptibility to two or more antibiotics, with high levels of resistance to β-lactams, aminoglycosides and tetracycline. Ten resistance genes were detected, the most frequent of which were ampC, conferring resistance to ampicillin and aadA, conferring resistance to streptomycin. In total, 97.30% of the strains carried virulence factors (between one and five). The strains from pigeons reared in captivity harboured higher average numbers of resistance and virulence genes than isolates from wild pigeons. Pigeon meat is an important reservoir of E. coli with genes for antibiotic resistance and virulence having the potential to cause disease in humans. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Open AccessArticle
Prevention of Pseudomonas aeruginosa Biofilm Formation on Soft Contact Lenses by Allium sativum Fermented Extract (BGE) and Cannabinol Oil Extract (CBD)
Antibiotics 2019, 8(4), 258; https://doi.org/10.3390/antibiotics8040258 - 10 Dec 2019
Cited by 3 | Viewed by 1664
Abstract
Two natural mixtures, Allium sativum fermented extract (BGE) and cannabinol oil extract (CBD), were assessed for their ability to inhibit and remove Pseudomonas aeruginosa biofilms on soft contact lenses in comparison to a multipurpose Soft Contact Lens-care solution present on the Italian market. [...] Read more.
Two natural mixtures, Allium sativum fermented extract (BGE) and cannabinol oil extract (CBD), were assessed for their ability to inhibit and remove Pseudomonas aeruginosa biofilms on soft contact lenses in comparison to a multipurpose Soft Contact Lens-care solution present on the Italian market. Pseudomonas aeruginosa (ATCC 9027 strain) and Pseudomonas aeruginosa clinical strains isolated from ocular swabs were tested. Quantification of the biofilm was done using the microtiter plate assay and the fractional inhibitory concentration index was calculated. Both forms of Pseudomonas aeruginosa generated biofilms. BGE at minimal inhibitory concentration (MIC) showed inhibition percentages higher than 55% for both strains, and CBD inhibited biofilm formation by about 70%. The care solution at MIC inhibited biofilm formation by about 50% for both strains tested. The effect of BGE on the eradication of the microbial biofilm on soft contact lenses at MIC was 45% eradication for P. aeruginosa ATCC 9027 and 36% for P. aeruginosa clinical strain. For CBD, we observed 24% biofilm eradication for both strains. For the care solution, the eradication MICs were 43% eradication for P. aeruginosa ATCC 9027 and 41% for P. aeruginosa clinical strain. It was observed that both the test soft contact lenses solution/BGE (fractional inhibitory concentration index: 0.450) and the test soft contact lenses solution/CBD (fractional inhibitory concentration index: 0.153) combinations exhibited synergistic antibiofilm activity against most of the studied bacteria. The study showed that BGE and CBD have good effect on inhibition of biofilm formation and removal of preformed biofilms, which makes them promising agents that could be exploited to develop more effective care solutions. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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Open AccessReview
Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens
Antibiotics 2019, 8(4), 257; https://doi.org/10.3390/antibiotics8040257 - 09 Dec 2019
Cited by 10 | Viewed by 1960
Abstract
Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneficial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established [...] Read more.
Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneficial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established to be potent antimicrobial agents against a wide range of pathogenic organisms. Various research studies have demonstrated the antimicrobial activity of traditional plants scientifically or experimentally measured with reports on pathogenic microorganisms resistant to antimicrobials. The antimicrobial activity of medicinal plants or their bioactive compounds arising from several functional activities may be capable of inhibiting virulence factors as well as targeting microbial cells. Some bioactive compounds derived from traditional plants manifest the ability to reverse antibiotic resistance and improve synergetic action with current antibiotic agents. Therefore, the advancement of bioactive-based pharmacological agents can be an auspicious method for treating antibiotic-resistant infections. This review considers the functional and molecular roles of medicinal plants and their bioactive compounds, focusing typically on their antimicrobial activities against clinically important pathogens. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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Open AccessArticle
Effect of a Herbal Therapy on Clinical Symptoms of Acute Lower Uncomplicated Urinary Tract Infections in Women: Secondary Analysis from a Randomized Controlled Trial
Antibiotics 2019, 8(4), 256; https://doi.org/10.3390/antibiotics8040256 - 07 Dec 2019
Cited by 1 | Viewed by 1675
Abstract
Background: Antibiotics are commonly used as first-line treatment for acute lower uncomplicated urinary tract infections (uUTIs). However, antimicrobial resistance is a growing global problem and efficacious nonantibiotic treatment options are urgently needed. Methods: A secondary analysis was conducted with data from a [...] Read more.
Background: Antibiotics are commonly used as first-line treatment for acute lower uncomplicated urinary tract infections (uUTIs). However, antimicrobial resistance is a growing global problem and efficacious nonantibiotic treatment options are urgently needed. Methods: A secondary analysis was conducted with data from a randomized, controlled, double-blind trial comparing a fixed combination of extracts of restharrow root, Java tea, and goldenrod herb (Aqualibra®) to placebo in 200 women with acute lower uUTI. Symptom scores reported in the original trial were reanalyzed and adjusted to the definitions of the Acute Cystitis Symptom Score (ACSS). Results: Based on a subgroup of patients with evaluable microbiologic data (n = 122), the decrease of the mean sum-score of three typical ACSS-adjusted symptoms showed significant superiority of the herbal preparation over placebo already after one day of treatment (p = 0.0086); on Day 7, the average difference was −1.9 score points (p < 0.0001). The superior efficacy of the herbal preparation on Day 1 was mainly driven by a difference in response rates of the symptom ‘dysuria’ (group difference: −29.4%, p = 0.0042). Furthermore, significantly fewer patients in the verum group required antibiotic therapy (15.3% vs. 49.2%, p = 0.0001). These results were confirmed in the intention-to-treat (ITT) population (n = 200). Conclusions: A fixed combination of extracts of restharrow root, Java tea, and goldenrod herb was superior to placebo regarding symptom relief and prevention of antibiotic use in women with lower uUTI. Trial registration: ClinicalTrials.gov: NCT04032574. Full article
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Open AccessBrief Report
Ceftazidime–Avibactam versus Meropenem for the Treatment of Complicated Intra-Abdominal Infections
Antibiotics 2019, 8(4), 255; https://doi.org/10.3390/antibiotics8040255 - 06 Dec 2019
Cited by 3 | Viewed by 1376
Abstract
This study reports an integrated analysis of three randomized controlled trials to compare the clinical efficacies and safety of the ceftazidime–avibactam (CAZ–AVI) combination and meropenem in the treatment of adult patients with complicated intra-abdominal infections (cIAIs). Overall, a total of 1677 patients (CAZ–AVI: [...] Read more.
This study reports an integrated analysis of three randomized controlled trials to compare the clinical efficacies and safety of the ceftazidime–avibactam (CAZ–AVI) combination and meropenem in the treatment of adult patients with complicated intra-abdominal infections (cIAIs). Overall, a total of 1677 patients (CAZ–AVI: 835 patients; meropenem: 842 patients) were included in this analysis. CAZ–AVI had a clinical cure rate at test of cure in the clinically evaluable (CE) population similar to that of meropenem (OR, 0.88; 95% CI, 0.58–1.32; I2 = 0%). Similar trends were also observed in the modified intent-to-treat (MITT) population (OR, 0.80; 95% CI, 0.59–1.09; I2 = 0%) and microbiological evaluable (ME) population (OR, 0.73; 95% CI, 0.32–1.68; I2 = 0%). In terms of clinical cure rate at the end of treatment, the efficacy of CAZ–AVI was comparable to that of meropenem in the CE population (OR, 0.77; 95% CI, 0.47–1.25; I2 = 0%), MITT population (OR, 0.70; 95% CI, 0.47–1.06; I2 = 5%), and ME population (OR, 1.26; 95% CI, 0.39–4.08; I2 = 0%). CAZ–AVI had a similar risk of (i) treatment emergent adverse events (TEAEs) (OR, 1.03; 95% CI, 0.79–1.36; I2 = 38%), (ii) any serious adverse events (OR, 0.97; 95% CI, 0.67–1.40; I2 = 0%), (iii) discontinuation of study drug due to TEAE (OR, 2.14; 95% CI, 1.00–4.57), and iv) all-cause mortality (OR, 1.66; 95% CI, 0.78–3.53; I2 = 0%) when compared with meropenem. In conclusion, CAZ–AVI had comparable efficacy and safety profile to those of meropenem in the treatment of cIAI. Full article
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Open AccessEditorial
The Urgent Need for Novel Antimicrobial Agents and Strategies to Fight Antibiotic Resistance
Antibiotics 2019, 8(4), 254; https://doi.org/10.3390/antibiotics8040254 - 06 Dec 2019
Cited by 2 | Viewed by 1548
Abstract
Antibiotic resistance in bacterial pathogens has currently reached very high and alarming levels [...] Full article
Open AccessBrief Report
Antibiotic Susceptibility Patterns of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis Strains from Different Decades
Antibiotics 2019, 8(4), 253; https://doi.org/10.3390/antibiotics8040253 - 06 Dec 2019
Cited by 2 | Viewed by 1682
Abstract
The aim of this study was to determine the antibiotic susceptibility patterns of 57 Aggregatibacter actinomycetemcomitans and 56 Porphyromonas gingivalis strains isolated from subgingival biofilm samples of periodontitis patients in Switzerland from 1980 to 2017. The minimal inhibitory concentrations (MIC) of the most [...] Read more.
The aim of this study was to determine the antibiotic susceptibility patterns of 57 Aggregatibacter actinomycetemcomitans and 56 Porphyromonas gingivalis strains isolated from subgingival biofilm samples of periodontitis patients in Switzerland from 1980 to 2017. The minimal inhibitory concentrations (MIC) of the most commonly used antibiotics in periodontal therapy (amoxicillin, metronidazole, azithromycin, and doxycycline) or in severe body infections (amoxicillin/clavulanic acid, clindamycin, ertapenem, and moxifloxacin) were determined. Furthermore, all the strains were screened for beta-lactamase activity and the presence of selected resistance genes (cfxA, ermF, and tetQ). Overall, there was no significant increase in MIC values over the 37‑year period. Two of the most recent P. gingivalis isolates yielded the highest MIC values. The first isolate was ermF-positive with MIC values >8 µg/mL, 2 µg/mL, and 0.25 µg/mL for clindamycin, azithromycin, and moxifloxacin, respectively. The second isolate showed a high MIC value of 4 µg/mL for moxifloxacin, which was associated with a confirmed single-point mutation in the quinolone resistance-determining region (QRDR) of the gyrA gene. Although there was no significant increase in the antibiotic resistance among the oral bacterial isolates tested, the detection of resistant P. gingivalis isolates underlines the need to optimize the antibiotic therapeutic protocols in dentistry. Full article
(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)
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Open AccessArticle
Antimicrobial Stewardship Programs in Community Health Systems Perceived by Physicians and Pharmacists: A Qualitative Study with Gap Analysis
Antibiotics 2019, 8(4), 252; https://doi.org/10.3390/antibiotics8040252 - 05 Dec 2019
Cited by 1 | Viewed by 1535
Abstract
Antimicrobial stewardship program (ASP) is one of the most important strategies for managing infectious disease treatment and preventing antimicrobial resistance. The successful implementation of ASP in the community health system (CHS) has been challenging. We evaluated perceptions of current ASP, potential setbacks of [...] Read more.
Antimicrobial stewardship program (ASP) is one of the most important strategies for managing infectious disease treatment and preventing antimicrobial resistance. The successful implementation of ASP in the community health system (CHS) has been challenging. We evaluated perceptions of current ASP, potential setbacks of ASP implementation, and future demands on ASP services among physicians and pharmacists in the CHS. The qualitative research was conducted through in-depth individual interviews and focus group discussions with 11 physicians and 11 pharmacists. In addition, a quantitative gap analysis was conducted to assess the different awareness and demands on services of ASP and preferred antimicrobial-related problems (ARP). In overall, perceptions of ASP varied by profession. The identified setbacks were unorganized institutional leadership, the undefined roles of healthcare professionals, a lack of reimbursement, the hierarchical structure of the health system, and the labor-intensive working environment of pharmacy services. Although demands for ASP improvement were similar among professionals, they had different preferences in prioritizing each service item of ASP/ARP development and the profession responsible for each service. Continuous administrative and financial investments, understanding ASP contents, ASP-specific information technology, and interdisciplinary collaboration with good communication among healthcare professions are needed to continue the progression of ASP. Full article
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Open AccessReview
Dissecting the Antimicrobial Composition of Honey
Antibiotics 2019, 8(4), 251; https://doi.org/10.3390/antibiotics8040251 - 05 Dec 2019
Cited by 11 | Viewed by 2753
Abstract
Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but the most noteworthy include the treatment of surface wounds, burns and inflammation. A variety of substances in honey [...] Read more.
Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but the most noteworthy include the treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and secretions from the bee. The use of medical grade honey in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, if medical grade honeys were to be included in clinical treatment, it would reduce the demand for antibiotic usage. In this review, we outline the constituents of honey and how they affect antibiotic potential in a clinical setting. By identifying the key components, we facilitate the development of an optimally antimicrobial honey by either synthetic or semisynthetic production methods. Full article
(This article belongs to the Special Issue Novel Strategies against Pathogenic Bacteria)
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Open AccessArticle
Evaluation of the Antifungal Activity of the Licania Rigida Leaf Ethanolic Extract against Biofilms Formed by Candida Sp. Isolates in Acrylic Resin Discs
Antibiotics 2019, 8(4), 250; https://doi.org/10.3390/antibiotics8040250 - 04 Dec 2019
Cited by 1 | Viewed by 1335
Abstract
Candida sp. treatment has become a challenge due to the formation of biofilms which favor resistance to conventional antifungals, making the search for new compounds necessary. The objective of this study was to identify the composition of the Licania rigida Benth. leaf ethanolic [...] Read more.
Candida sp. treatment has become a challenge due to the formation of biofilms which favor resistance to conventional antifungals, making the search for new compounds necessary. The objective of this study was to identify the composition of the Licania rigida Benth. leaf ethanolic extract and to verify its antifungal activity against Candida sp. and its biofilms. The composition identification was performed using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technique. The antifungal activity of extract and fluconazole against planktonic cells and biofilms was verified through the minimum inhibitory concentration (MIC) following biofilm induction and quantification in acrylic resin discs by reducing tetrazolic salt, with all isolates forming biofilms within 48 h. Six constituents were identified in the extract, and the compounds identified are derivatives from phenolic compounds such as flavonoids (epi) gallocatechin Dimer, epigallocatechin and gallocatechin, Myricetin-O-hexoside, Myricitrin, and Quercetin-O-rhamnoside. The extract reduced biofilm formation in some of the strains analyzed, namely C. tropicalis URM5732, C. krusei INCQS40042, and C. krusei URM6352. This reduction was also observed in the treatment with fluconazole with some of the analyzed strains. The extract showed significant antifungal and anti-biofilm activities with some of the strains tested. Full article
(This article belongs to the Special Issue Biofilm Infections — Time Bomb in Antibiotic Therapy)
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Open AccessCommunication
Synthesis and Identification of Pentathiepin-Based Inhibitors of Sporothrix brasiliensis
Antibiotics 2019, 8(4), 249; https://doi.org/10.3390/antibiotics8040249 - 03 Dec 2019
Cited by 1 | Viewed by 1448
Abstract
Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades [...] Read more.
Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades with a recent hot spot of sporotrichosis infection emerging in the state of Rio de Janeiro. The source of these infections is now at epidemic proportions with more than 4000 cases reported in Rio de Janeiro, Brazil, alone since 1998. We developed a focused library of a rare pentathiepin ring system and identified a potent substitution pattern that yielded compounds 21 and 22. These compounds were more potent than itraconazole which is the current standard of care for sporotrichosis. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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Open AccessArticle
Proteomic and Metabolomic Analyses of a Tea-Tree Oil-Selected Staphylococcus aureus Small Colony Variant
Antibiotics 2019, 8(4), 248; https://doi.org/10.3390/antibiotics8040248 - 03 Dec 2019
Viewed by 1389
Abstract
Tea tree oil (TTO) is hypothesized to kill bacteria by indiscriminately denaturing membrane and protein structures. A Staphylococcus aureus small colony variant (SCV) selected with TTO (SH1000-TTORS-1) demonstrated slowed growth, reduced susceptibility to TTO, a diminutive cell size, and a thinned cell wall. [...] Read more.
Tea tree oil (TTO) is hypothesized to kill bacteria by indiscriminately denaturing membrane and protein structures. A Staphylococcus aureus small colony variant (SCV) selected with TTO (SH1000-TTORS-1) demonstrated slowed growth, reduced susceptibility to TTO, a diminutive cell size, and a thinned cell wall. Utilizing a proteomics and metabolomics approach, we have now revealed that the TTO-selected SCV mutant demonstrated defective fatty acid synthesis, an alteration in the expression of genes and metabolites associated with central metabolism, the induction of a general stress response, and a reduction of proteins critical for active growth and translation. SH1000-TTORS-1 also demonstrated an increase in amino acid accumulation and a decrease in sugar content. The reduction in glycolytic pathway proteins and sugar levels indicated that carbon flow through glycolysis and gluconeogenesis is reduced in SH1000-TTORS-1. The increase in amino acid accumulation coincides with the reduced production of translation-specific proteins and the induction of proteins associated with the stringent response. The decrease in sugar content likely deactivates catabolite repression and the increased amino acid pool observed in SH1000-TTORS-1 represents a potential energy and carbon source which could maintain carbon flow though the tricarboxylic acid (TCA) cycle. It is noteworthy that processes that contribute to the production of the TTO targets (proteins and membrane) are reduced in SH1000-TTORS-1. This is one of a few studies describing a mechanism that bacteria utilize to withstand the action of an antiseptic which is thought to inactivate multiple cellular targets. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Open AccessArticle
Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification
Antibiotics 2019, 8(4), 247; https://doi.org/10.3390/antibiotics8040247 - 03 Dec 2019
Cited by 12 | Viewed by 1439
Abstract
Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB). Many compounds exhibited significant inhibitory activity against MTB H37Rv strains. Indolizines 2d, 2e, and 4 were [...] Read more.
Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB). Many compounds exhibited significant inhibitory activity against MTB H37Rv strains. Indolizines 2d, 2e, and 4 were also found to be active against MTB clinical isolates with multi-resistance to rifampicin and isoniazid. Indolizine 4 was identified as the most promising anti-mycobacterial agent, displaying minimum inhibitory concentration (MIC) values of 4 and 32 μg/mL against H37Rv and MDR strains, respectively. Furthermore, an in silico study was carried out for prospective molecular target identification and revealed favorable interactions with the target enzymes CYP 121, malate synthase, and DNA GyrB ATPase. None of the potent molecules presented toxicity against peripheral blood mononuclear (PBM) cell lines, demonstrating their potentiality to be used for drug-sensitive and drug-resistant tuberculosis therapy. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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Open AccessArticle
Essential Oils with High Activity against Stationary Phase Bartonella henselae
Antibiotics 2019, 8(4), 246; https://doi.org/10.3390/antibiotics8040246 - 30 Nov 2019
Cited by 4 | Viewed by 2875
Abstract
Bartonella henselae is a fastidious Gram-negative intracellular bacterium that can cause cat scratch disease, endocarditis in humans and animals, as well as other complications, leading to acute or chronic infections. The current treatment for Bartonella infections is not very effective presumably due to [...] Read more.
Bartonella henselae is a fastidious Gram-negative intracellular bacterium that can cause cat scratch disease, endocarditis in humans and animals, as well as other complications, leading to acute or chronic infections. The current treatment for Bartonella infections is not very effective presumably due to bacterial persistence. To develop better therapies for persistent and chronic Bartonella infections, in this study, with the help of SYBR Green I/PI viability assay, we performed a high-throughput screening of an essential oil library against the stationary phase B. henselae. We successfully identified 32 essential oils that had high activity, including four essential oils extracted from Citrus plants, three from Origanum, three from Cinnamomum, two from Pelargonium, and two from Melaleuca, as well as frankincense, ylang-ylang, fir needle, mountain savory (winter), citronella, spearmint, elemi, vetiver, clove bud, allspice, and cedarwood essential oils. The minimal inhibitory concentration (MIC) determination of these 32 top hits indicated they were not only active against stationary phase non-growing B. henselae but also had good activity against log-phase growing B. henselae. The time-kill assay showed 13 active hits, including essential oils of oregano, cinnamon bark, mountain savory (winter), cinnamon leaf, geranium, clove bud, allspice, geranium bourbon, ylang-ylang, citronella, elemi, and vetiver, could eradicate all stationary phase B. henselae cells within seven days at the concentration of 0.032% (v/v). Two active ingredients, carvacrol and cinnamaldehyde, of oregano and cinnamon bark essential oils, respectively, were shown to be very active against the stationary phase B. henselae such that they were able to eradicate all the bacterial cells even at the concentration ≤ 0.01% (v/v). More studies are needed to identify the active components of some potent essential oils, decode their antimicrobial mechanisms, and evaluate their activity against Bartonella infections in animal models. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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Open AccessArticle
Optimizing the Dosing Regimens of Daptomycin Based on the Susceptible Dose-Dependent Breakpoint against Vancomycin-Resistant Enterococci Infection
Antibiotics 2019, 8(4), 245; https://doi.org/10.3390/antibiotics8040245 - 29 Nov 2019
Cited by 3 | Viewed by 1574
Abstract
Daptomycin, a lipopeptide antibiotic, is one of the therapeutic options used for the treatment of vancomycin-resistant enterococci (VRE). Recently, the Clinical and Laboratory Standards Institute (CLSI) M100 30th edition has removed the susceptibility (S) breakpoint for Enterococcus faecium and replaced it with a [...] Read more.
Daptomycin, a lipopeptide antibiotic, is one of the therapeutic options used for the treatment of vancomycin-resistant enterococci (VRE). Recently, the Clinical and Laboratory Standards Institute (CLSI) M100 30th edition has removed the susceptibility (S) breakpoint for Enterococcus faecium and replaced it with a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL, with a suggested dosage of 8–12 mg/kg/day. Herein, we aimed to determine the minimum inhibitory concentration (MIC) values of daptomycin against clinical VRE isolates and to study the appropriate daptomycin dosing regimens among critically ill patients based on the new susceptibility CLSI breakpoint. The MIC determination of daptomycin was performed using E-test strips among clinical VRE strains isolated from patients at the Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the ratio of the free area under the curve to MIC (fAUC0–24/MIC) > 27.4 and fAUC0–24/MIC > 20 for survival and microbiological response, respectively, at the first day and steady state. Further, we determined that the simulated daptomycin dosing regimen met the minimum concentration (Cmin) requirements for safety of being below 24.3 mg/L. All of the 48 VRE isolates were E. faecium strains, and the percentiles at the 50th and 90th MIC of daptomycin were 1 and 1.5 μg/mL, respectively. At MIC ≤ 2 μg/mL, a daptomycin dosage of 12 mg/kg/day achieved the PTA target of survival and microbiological response at the first 24 h time point and steady state. For a MIC of 4 μg/mL, none of the dosage regimens achieved the PTA target. For CFR, a dosage of 8–12 mg/kg/day could achieve the 90% CFR target at the first day and steady state. All dosing regimens had a low probability of Cmin being greater than 24.3 mg/L. In conclusion, the MIC of VRE against daptomycin is quite low, and loading and maintenance doses with 8 mg/kg/day were determined to be optimal and safe. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)
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Open AccessArticle
In-Vitro Inhibition of Staphylococcal Pathogenesis by Witch-Hazel and Green Tea Extracts
Antibiotics 2019, 8(4), 244; https://doi.org/10.3390/antibiotics8040244 - 29 Nov 2019
Cited by 5 | Viewed by 1534
Abstract
whISOBAX (WH), an extract of the witch-hazel plant that is native to the Northeast coast of the United States, contains significant amounts of a phenolic compound, Hamamelitannin (HAMA). Green tea (GT) is a widely consumed plant that contains various catechins. Both plants have [...] Read more.
whISOBAX (WH), an extract of the witch-hazel plant that is native to the Northeast coast of the United States, contains significant amounts of a phenolic compound, Hamamelitannin (HAMA). Green tea (GT) is a widely consumed plant that contains various catechins. Both plants have been associated with antimicrobial effects. In this study we test the effects of these two plant extracts on the pathogenesis of staphylococci, and evaluate their effects on bacterial growth, biofilm formation, and toxin production. Our observations show that both extracts have antimicrobial effects against both strains of S. aureus and S. epidermidis tested, and that this inhibitory effect is synergistic. Also, we confirmed that this inhibitory effect does not depend on HAMA, but rather on other phenolic compounds present in WH and GT. In terms of biofilm inhibition, only WH exhibited an effect and the observed anti-biofilm effect was HAMA-depended. Finally, among the tested extracts, only WH exhibited an effect against Staphylococcal Enterotoxin A (SEA) production and this effect correlated to the HAMA present in WH. Our results suggest that GT and WH in combination can enhance the antimicrobial effects against staphylococci. However, only WH can control biofilm development and SEA production, due to the presence of HAMA. This study provides the initial rationale for the development of natural antimicrobials, to protect from staphylococcal colonization, infection, or contamination. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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Open AccessArticle
Knowledge of Antimicrobial Resistance among Veterinary Students and Their Personal Antibiotic Use Practices: A National Cross-Sectional Survey
Antibiotics 2019, 8(4), 243; https://doi.org/10.3390/antibiotics8040243 - 29 Nov 2019
Cited by 5 | Viewed by 1662
Abstract
The challenge of antimicrobial resistance (AMR) is grave in developing countries. Antimicrobials are misused yet stakeholders’ contribution to antimicrobial stewardship is low. Veterinary students are future prescribers and their knowledge could influence progress in combating AMR; hence, there is a need to assess [...] Read more.
The challenge of antimicrobial resistance (AMR) is grave in developing countries. Antimicrobials are misused yet stakeholders’ contribution to antimicrobial stewardship is low. Veterinary students are future prescribers and their knowledge could influence progress in combating AMR; hence, there is a need to assess their knowledge, attitude, and awareness of AMR. A multi-institutional questionnaire was administered to undergraduates in Nigerian veterinary schools. It comprised demographics, own personal antibiotic usage, and knowledge, attitude, and awareness of AMR in humans and animals. Descriptive statistics and logistic regression were used for analyses. Of the 426 respondents, 39.2% reported personal antimicrobial use in the previous six months. Over 60% received knowledge scores lower than average and >87% requested more education on clinical use and prescriptions pre-graduation, monitored dispensing of antimicrobials, conducting AMR research, and confirmed link among human, animal, and environmental health. Less than 25% of respondents were aware of antimicrobial stewardship and global efforts/organizations for AMR. Final year students have 9-fold and 14-fold more satisfactory knowledge on antimicrobials in humans and animals compared with other students, respectively (p = 0.001). Final year students also have more knowledge (13×) and awareness of contributory factors (3×) on AMR (p = 0.001) than other students. Unsatisfactory knowledge on AMR issues exists among veterinary students yet willingness to improve was observed. Identified knowledge, attitude, and gaps in AMR awareness should be targeted by veterinary schools in Nigeria. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Photoinduced Antibacterial Activity of the Essential Oils from Eugenia brasiliensis Lam and Piper mosenii C. DC. by Blue Led Light
Antibiotics 2019, 8(4), 242; https://doi.org/10.3390/antibiotics8040242 - 28 Nov 2019
Cited by 3 | Viewed by 1333
Abstract
The objective of this work was to evaluate the phytochemical composition and the antibacterial and antibiotic-modulating activities of the essential oils of Eugenia brasiliensis Lam (OEEb) and Piper mosenii C. DC (OEPm) singly or in association with blue LED (Light-emitting diode) light. The [...] Read more.
The objective of this work was to evaluate the phytochemical composition and the antibacterial and antibiotic-modulating activities of the essential oils of Eugenia brasiliensis Lam (OEEb) and Piper mosenii C. DC (OEPm) singly or in association with blue LED (Light-emitting diode) light. The antibacterial and antibiotic-modulatory activities of the essential oils on the activity of aminoglycosides were evaluated to determine the minimum inhibitory concentration (MIC, μg/mL) in the presence or absence of exposure to blue LED light. The chemical analysis showed α-pinene and bicyclogermacrene as major constituents of OEPm, whereas α-muurolol was the main compound of OEEb. Both OEEb and OEPm showed MIC ≥ 512 μg/mL against the strains under study. However, the association of these oils with the blue LED light enhanced the action of the aminoglycosides amikacin and gentamicin. In conclusion, the association of aminoglycosides with the blue LED light and essential oils was effective against resistant bacteria. Full article
(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)
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Open AccessReview
Host-Targeted Therapeutics against Multidrug Resistant Intracellular Staphylococcus aureus
Antibiotics 2019, 8(4), 241; https://doi.org/10.3390/antibiotics8040241 - 28 Nov 2019
Cited by 2 | Viewed by 1623
Abstract
Staphylococcus aureus is a facultative intracellular pathogen that invades and replicates within many types of human cells. S. aureus has shown to rapidly overcome traditional antibiotherapy by developing multidrug resistance. Furthermore, intracellular S. aureus is protected from the last-resort antibiotics—vancomycin, daptomycin, and linezolid—as [...] Read more.
Staphylococcus aureus is a facultative intracellular pathogen that invades and replicates within many types of human cells. S. aureus has shown to rapidly overcome traditional antibiotherapy by developing multidrug resistance. Furthermore, intracellular S. aureus is protected from the last-resort antibiotics—vancomycin, daptomycin, and linezolid—as they are unable to achieve plasma concentrations sufficient for intracellular killing. Therefore, there is an urgent need to develop novel anti-infective therapies against S. aureus infections. Here, we review the current state of the field and highlight the exploitation of host-directed approaches as a promising strategy going forward. Full article
(This article belongs to the Special Issue Novel Strategies against Pathogenic Bacteria)
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