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Antibiotics, Volume 7, Issue 4 (December 2018)

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Open AccessEditorial Is Silver the Ultimate Antimicrobial Bullet?
Antibiotics 2018, 7(4), 112; https://doi.org/10.3390/antibiotics7040112
Received: 10 December 2018 / Accepted: 17 December 2018 / Published: 19 December 2018
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Abstract
The use of metal compounds as antimicrobial agents has been around since antiquity, only to be replaced by the introduction of organic antibiotics and antiseptics in the mid-20th century. [...] Full article
(This article belongs to the Special Issue Silver-Based Antimicrobials)
Open AccessConcept Paper Combatting Antibiotic Resistance Together: How Can We Enlist the Help of Industry?
Antibiotics 2018, 7(4), 111; https://doi.org/10.3390/antibiotics7040111
Received: 15 November 2018 / Revised: 11 December 2018 / Accepted: 13 December 2018 / Published: 18 December 2018
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Abstract
The development of antibiotics needs to be supported through new financial stimuli, including help from the public sector. In exchange for public support, industry should be asked to do what is in their power to help curb the inappropriate use of antibiotics. This
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The development of antibiotics needs to be supported through new financial stimuli, including help from the public sector. In exchange for public support, industry should be asked to do what is in their power to help curb the inappropriate use of antibiotics. This work discusses key areas through which industry has an important influence on antibiotic consumption and where agreements can be made alongside financial incentives, even those intended to stimulate very early research. As long as the traditional unit sale-based business model for antibiotics remains in place, profit-making incentives will likely undermine efforts to sell and utilize antibiotics in a sustainable manner. In the short-term, while we try to come to a consensus on how best to fix the market, we need measures to prevent major over-selling and inappropriate promotion—especially for new, badly needed antibiotics that reach the market. This paper explores ways in which the pharmaceutical industry could help buttress sustainable antibiotic use while we search for more long-term, constructive, mutually-beneficial ways to organize the market. Full article
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Open AccessReview Biocidal Agents Used for Disinfection Can Enhance Antibiotic Resistance in Gram-Negative Species
Antibiotics 2018, 7(4), 110; https://doi.org/10.3390/antibiotics7040110
Received: 20 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Biocidal agents used for disinfection are usually not suspected to enhance cross-resistance to antibiotics. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-negative species. A medline search was performed
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Biocidal agents used for disinfection are usually not suspected to enhance cross-resistance to antibiotics. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-negative species. A medline search was performed for each biocidal agent on antibiotic tolerance, antibiotic resistance, horizontal gene transfer, and efflux pump. In cells adapted to benzalkonium chloride a new resistance was most frequently found to ampicillin (eight species), cefotaxime (six species), and sulfamethoxazole (three species), some of them with relevance for healthcare-associated infections such as Enterobacter cloacae or Escherichia coli. With chlorhexidine a new resistance was often found to ceftazidime, sulfamethoxazole and imipenem (eight species each) as well as cefotaxime and tetracycline (seven species each). Cross-resistance to antibiotics was also found with triclosan, octenidine, sodium hypochlorite, and didecyldimethylammonium chloride. No cross-resistance to antibiotics has been described after low level exposure to ethanol, propanol, peracetic acid, polyhexanide, povidone iodine, glutaraldehyde, and hydrogen peroxide. Taking into account that some biocidal agents used in disinfectants have no health benefit (e.g., in alcohol-based hand rubs) but may cause antibiotic resistance it is obvious to prefer products without them. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessCase Report Emerging Chryseobacterium indologenes Infection in Indian Neonatal Intensive Care Units: A Case Report
Antibiotics 2018, 7(4), 109; https://doi.org/10.3390/antibiotics7040109
Received: 8 November 2018 / Revised: 5 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C.
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Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C. indologenes has been widely reported to cause life-threatening infections. Patients on chronic immunosuppressant drugs, harboring invasive devices and indwelling catheters become the nidus for C. indologenes. Typically, C. indologenes causes major health care-associated infections such as pneumonia, empyema, pyelonephritis, cystitis, peritonitis, meningitis, and bacteremia in patients harboring central venous catheters. Management of C. indologenes infection in neonates is not adequately documented owing to underreporting, particularly in India. Because of its multidrug resistance and the scant availability of data from the literature, the effective empirical treatment of C. indologenes is challenging. We present an uncommon case of bacteremia caused by C. indologenes in a preterm newborn baby with moderate respiratory distress syndrome who was successfully treated. We also provide a review of infections in the neonatal age group. Henceforth, in neonates receiving treatments involving invasive equipment use and long-term antibiotic therapy, multidrug resistant C. indologenes should be considered an HCAP. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessCase Report A Case of Hypokalemia Possibly Induced by Nafcillin
Antibiotics 2018, 7(4), 108; https://doi.org/10.3390/antibiotics7040108
Received: 8 November 2018 / Revised: 5 December 2018 / Accepted: 10 December 2018 / Published: 12 December 2018
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Abstract
(1) Background: The use of intravenous antibiotics for severe infections is a common practice, either as inpatient or outpatient treatment. In the case of methicillin-susceptible Staphylococcus aureus (MSSA), nafcillin is a commonly prescribed intravenous antibiotic, given its known efficacy to treat infections related
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(1) Background: The use of intravenous antibiotics for severe infections is a common practice, either as inpatient or outpatient treatment. In the case of methicillin-susceptible Staphylococcus aureus (MSSA), nafcillin is a commonly prescribed intravenous antibiotic, given its known efficacy to treat infections related to this organism effectively. However, it is not without side effects. (2) Methods: We present an interesting case of persistent hypokalemia in a patient after he was started on nafcillin infusion for an MSSA infection, which eventually resolved with the completion of the treatment. (3) Results: Hypokalemia is a known side effect of nafcillin infusion, and it is believed to be mainly due to its antibiotic effect as a non-absorbable ion in the distal tubule and/or intracellular redistribution due to volume depletion. (4) Conclusions: A review of the available literature revealed that hypokalemia is a known side effect of nafcillin infusion; however, if present, it is usually mild, and only a few cases of severe hypokalemia have been reported. Usually, hypokalemia resolves when the nafcillin infusion is stopped; however, in certain cases, when this is not possible, oral potassium replacement can be used while the patient is receiving nafcillin. Clinicians should be aware of this rare, but possible, complication when using nafcillin. Full article
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Open AccessArticle Optimization and Validation of a Chromatographic Method for the Quantification of Isoniazid in Urine of Tuberculosis Patients According to the European Medicines Agency Guideline
Antibiotics 2018, 7(4), 107; https://doi.org/10.3390/antibiotics7040107
Received: 27 November 2018 / Revised: 8 December 2018 / Accepted: 9 December 2018 / Published: 11 December 2018
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Abstract
Isoniazid is a drug that is widely used against tuberculosis. However, it shows high interpatient variability in metabolism kinetics and clinical effect, which complicates the prescription of the medication and jeopardizes the success of the therapy. Therefore, in a specific patient, the pharmacokinetics
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Isoniazid is a drug that is widely used against tuberculosis. However, it shows high interpatient variability in metabolism kinetics and clinical effect, which complicates the prescription of the medication and jeopardizes the success of the therapy. Therefore, in a specific patient, the pharmacokinetics of the drug must be elucidated to decide the proper dosage and intake frequency to make the drug suitable for therapeutic drug monitoring. This can be performed by the quantification of the drug in urine as this process is non-invasive and allows the effects of long-time exposure to be inferred. The paper describes the development of a micellar liquid chromatographic method to quantify isoniazid in urine samples. Extraction steps were avoided, making the procedure easy to handle and reducing the waste of toxic organic solvents. Isoniazid was eluted in less than 5 min without interference from other compounds of the urine using a mobile phase containing 0.15 SDS–12.5% 1-propanol (v/v)–Na2HPO4 0.01 M buffered at pH 7, running at 1 mL/min under isocratic mode through a C18 column with the detection wavelength at 265 nm. The method was validated by following the requirements of the Guidelines on Bioanalytical Method Validation issued by the European Medicines Agency (EMA) in terms of selectivity, calibration curve (r2 = 0.9998 in the calibration range (0.03–10.0 μg/mL), limit of detection and quantification (10 and 30 ng/mL respectively), precision (<16.0%), accuracy (−0.9 to +8.5%), carry-over, matrix effect, and robustness. The developed method was applied to quantify isoniazid in urine samples of patients of an Indian hospital with good results. The method was found to be useful for routine analysis to check the amount of isoniazid in these patients and could be used in its therapeutic monitoring. Full article
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Open AccessArticle Cost-Effectiveness Analysis of the Use of Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing in Primary Care
Antibiotics 2018, 7(4), 106; https://doi.org/10.3390/antibiotics7040106
Received: 19 October 2018 / Revised: 20 November 2018 / Accepted: 3 December 2018 / Published: 7 December 2018
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Abstract
More appropriate and measured use of antibiotics may be achieved using point-of-care (POC) C-reactive protein (CRP) testing, but there is limited evidence of cost-effectiveness in routine practice. A decision analytic model was developed to estimate the cost-effectiveness of testing, compared with standard care,
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More appropriate and measured use of antibiotics may be achieved using point-of-care (POC) C-reactive protein (CRP) testing, but there is limited evidence of cost-effectiveness in routine practice. A decision analytic model was developed to estimate the cost-effectiveness of testing, compared with standard care, in adults presenting in primary care with symptoms of acute respiratory tract infection (ARTI). Analyses considered (1) pragmatic use of testing, reflective of routine clinical practice, and (2) testing according to clinical guidelines. Threshold and scenario analysis were performed to identify cost-effective scenarios. In patients with symptoms of ARTI and based on routine practice, the incremental cost-effectiveness ratios of CRP testing were £19,705 per quality-adjusted-life-year (QALY) gained and £16.07 per antibiotic prescription avoided. Following clinical guideline, CRP testing in patients with lower respiratory tract infections (LRTIs) cost £4390 per QALY gained and £9.31 per antibiotic prescription avoided. At a threshold of £20,000 per QALY, the probabilities of POC CRP testing being cost-effective were 0.49 (ARTI) and 0.84 (LRTI). POC CRP testing as implemented in routine practice is appreciably less cost-effective than when adhering to clinical guidelines. The implications for antibiotic resistance and Clostridium difficile infection warrant further investigation. Full article
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Open AccessArticle Bystander Phage Therapy: Inducing Host-Associated Bacteria to Produce Antimicrobial Toxins against the Pathogen Using Phages
Antibiotics 2018, 7(4), 105; https://doi.org/10.3390/antibiotics7040105
Received: 8 November 2018 / Revised: 30 November 2018 / Accepted: 3 December 2018 / Published: 4 December 2018
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Abstract
Brevibacillus laterosporus is often present in beehives, including presence in hives infected with the causative agent of American Foulbrood (AFB), Paenibacillus larvae. In this work, 12 B. laterosporus bacteriophages induced bactericidal products in their host. Results demonstrate that P. larvae is susceptible
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Brevibacillus laterosporus is often present in beehives, including presence in hives infected with the causative agent of American Foulbrood (AFB), Paenibacillus larvae. In this work, 12 B. laterosporus bacteriophages induced bactericidal products in their host. Results demonstrate that P. larvae is susceptible to antimicrobials induced from field isolates of the bystander, B. laterosporus. Bystander antimicrobial activity was specific against the pathogen and not other bacterial species, indicating that the production was likely due to natural competition between the two bacteria. Three B. laterosporus phages were combined in a cocktail to treat AFB. Healthy hives treated with B. laterosporus phages experienced no difference in brood generation compared to control hives over 8 weeks. Phage presence in bee larvae after treatment rose to 60.8 ± 3.6% and dropped to 0 ± 0.8% after 72 h. In infected hives the recovery rate was 75% when treated, however AFB spores were not susceptible to the antimicrobials as evidenced by recurrence of AFB. We posit that the effectiveness of this treatment is due to the production of the bactericidal products of B. laterosporus when infected with phages resulting in bystander-killing of P. larvae. Bystander phage therapy may provide a new avenue for antibacterial production and treatment of disease. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessCase Report Bloodstream Infection due to Piperacillin/Tazobactam Non-Susceptible, Cephalosporin-Susceptible Escherichia coli: A Missed Opportunity for De-Escalation of Therapy
Antibiotics 2018, 7(4), 104; https://doi.org/10.3390/antibiotics7040104
Received: 31 October 2018 / Revised: 21 November 2018 / Accepted: 29 November 2018 / Published: 1 December 2018
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Abstract
An increasing number of reports describing Escherichia coli isolates with piperacillin/tazobactam resistance, despite retained cephalosporin susceptibility, suggest further emergence of this phenotypic resistance pattern. In this report, a patient with metastatic breast cancer presented to medical care after two days of chills, nausea,
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An increasing number of reports describing Escherichia coli isolates with piperacillin/tazobactam resistance, despite retained cephalosporin susceptibility, suggest further emergence of this phenotypic resistance pattern. In this report, a patient with metastatic breast cancer presented to medical care after two days of chills, nausea, vomiting, reduced oral intake, and generalized weakness. Blood and urine cultures grew E. coli as identified by rapid diagnostics multiplex PCR and MALDI-TOF, respectively. The patient continued to manifest signs of sepsis with hypotension and tachypnea during the first three days of hospitalization despite empirical antimicrobial therapy with intravenous piperacillin/tazobactam. After in vitro antimicrobial susceptibility testing demonstrated a piperacillin/tazobactam minimal inhibitory concentration (MIC) of 64 and a ceftriaxone MIC of ≤1 mcg/mL, antimicrobial therapy was switched from intravenous piperacillin/tazobactam to ceftriaxone. All symptoms and signs of infection resolved within 48 h of starting ceftriaxone therapy. This report describes the clinical failure of piperacillin/tazobactam in the treatment of a bloodstream infection due to E. coli harboring a phenotypic resistance pattern of isolated piperacillin/tazobactam non-susceptibility. The case demonstrates the role of cephalosporins as potential treatment options and highlights the value of early de-escalation of antimicrobial therapy based on rapid diagnostic testing for microbial identification. Full article
Open AccessArticle Induction of Biofilm Formation in Klebsiella pneumoniae ATCC 13884 by Several Drugs: The Possible Role of Quorum Sensing Modulation
Antibiotics 2018, 7(4), 103; https://doi.org/10.3390/antibiotics7040103
Received: 28 October 2018 / Revised: 14 November 2018 / Accepted: 20 November 2018 / Published: 28 November 2018
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Abstract
Bacterial resistance is caused by several biochemical factors, the formation of biofilm being one of the main causes. This process is triggered by Quorum Sensing (QS), through the production of endogenous molecules, although other substances such as natural products can also
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Bacterial resistance is caused by several biochemical factors, the formation of biofilm being one of the main causes. This process is triggered by Quorum Sensing (QS), through the production of endogenous molecules, although other substances such as natural products can also do this. In this work, we aimed to determine whether some drugs are involved in the induction of biofilm formation in Klebsiella pneumoniae ATCC 13884, and thus, increase bacterial resistance. For this, the effect of 22 drugs on K. pneumoniae ATCC 13884 growth was determined at sub-plasmatic concentrations; the production of autoinducer lactones was established by HPLC and with a biosensor. The induction of biofilm formation was determined through crystal violet assay at 585 nm in a microplate reader and using urethral catheters. According to the in vitro assays, some drugs were found to induce biofilm formation in K. pneumoniae ATCC 13884. The effect of acetaminophen, hydrochlorothiazide, and progesterone stood out. The first drug caused several changes in the biochemistry of K. pneumoniae ATCC 13884 related to QS: high synthesis of N-hexanoyl-homoserine lactone, increasing bacterial populations by 27% and biofilm formation by 49%, and a more gentamicin resistant biofilm. Furthermore, it increased the colonization area of urethral catheters. Hydrochlorothiazide showed the biggest increase in the induction of biofilm formation of 51%, and progesterone displayed the greatest ability to provoke bacterial mass adherence but had no effects on K. pneumoniae ATCC 13884 bacterial population growth. Full article
(This article belongs to the Special Issue Chemical Tools for Antibiotics Research)
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Open AccessArticle Bibliometric Analysis of Global Research on Clavulanic Acid
Antibiotics 2018, 7(4), 102; https://doi.org/10.3390/antibiotics7040102
Received: 8 September 2018 / Revised: 18 October 2018 / Accepted: 18 October 2018 / Published: 26 November 2018
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Abstract
Clavulanic acid (CA), a potent inhibitor of the β-lactam, ase enzyme, is frequently co-formulated with a broad spectrum of antibiotics to treat infections caused by β-lactamase-producing pathogens. In order to evaluate the impact and the progress of CA studies in the last four
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Clavulanic acid (CA), a potent inhibitor of the β-lactam, ase enzyme, is frequently co-formulated with a broad spectrum of antibiotics to treat infections caused by β-lactamase-producing pathogens. In order to evaluate the impact and the progress of CA studies in the last four decades, a bibliometric analysis of the global scientific production of CA was carried out. A total of 39,758 records in the field of CA were indexed in the Scopus database for a 43-year period of study (1975–2017). The results indicated that CA studies have grown, showing three phases (1975–1999, 2000–2003 and 2004–2017) based on records of publications; the results showed a sigmoidal profile. Medicine was the main subject area for CA studies, whereas biochemistry, genetics and molecular biology were areas of research for CA production by Streptomyces clavuligerus (S. clavuligerus). Nevertheless, chemical engineering (as a subject area) had the highest increase in the percentage of publications related to CA production by S. clavuligerus. The United States, France, the United Kingdom, Spain and Brazil were the leading countries in the scientific production of studies on both CA and CA related to S. clavuligerus. This analysis allowed the identification of the area of knowledge with the highest impact on CA studies, the top researchers and their geographic distribution, and also helped to highlight the existence of antibiotic-resistant bacteria as an emergent area in CA research. Full article
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Open AccessArticle Fighting Fire with Fire: Phage Potential for the Treatment of E. coli O157 Infection
Antibiotics 2018, 7(4), 101; https://doi.org/10.3390/antibiotics7040101
Received: 23 October 2018 / Revised: 9 November 2018 / Accepted: 14 November 2018 / Published: 16 November 2018
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Abstract
Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of
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Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessArticle Silver Nanoparticle Conjugation-Enhanced Antibacterial Efficacy of Clinically Approved Drugs Cephradine and Vildagliptin
Antibiotics 2018, 7(4), 100; https://doi.org/10.3390/antibiotics7040100
Received: 17 August 2018 / Revised: 9 October 2018 / Accepted: 19 October 2018 / Published: 15 November 2018
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Abstract
This paper sets out to determine whether silver nanoparticles conjugation enhance the antibacterial efficacy of clinically approved drugs. Silver conjugated Cephradine and Vildagliptin were synthesized and thoroughly characterized by ultraviolet visible spectrophotometry (UV-vis), Fourier transform infrared (FT-IR) spectroscopic methods, atomic force microscopy (AFM),
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This paper sets out to determine whether silver nanoparticles conjugation enhance the antibacterial efficacy of clinically approved drugs. Silver conjugated Cephradine and Vildagliptin were synthesized and thoroughly characterized by ultraviolet visible spectrophotometry (UV-vis), Fourier transform infrared (FT-IR) spectroscopic methods, atomic force microscopy (AFM), and dynamic light scattering (DLS) analysis. Using antibacterial assays, the effects of drugs alone and drugs-conjugated with silver nanoparticles were tested against a variety of Gram-negative and Gram-positive bacteria including neuropathogenic Escherichia coli K1, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus and Streptococcus pyogenes. Cytopathogenicity assays were performed to determine whether pretreatment of bacteria with drugs inhibit bacterial-mediated host cell cytotoxicity. The UV-vis spectra of both silver-drug nanoconjugates showed a characteristic surface plasmon resonance band in the range of 400–450 nm. AFM further confirmed the morphology of nanoparticles and revealed the formation of spherical nanoparticles with size distribution of 30–80 nm. FT-IR analysis demonstrated the involvement of Hydroxyl groups in both drugs in the stabilization of silver nanoparticles. Antibacterial assays showed that silver nanoparticle conjugation enhanced antibacterial potential of both Cephradine and Vildagliptin compared to the drugs alone. Pretreatment of bacteria with drugs inhibited E. coli K1-mediated host cell cytotoxicity. In summary, conjugation with silver nanoparticle enhanced antibacterial effects of clinically approved Cephradine. These findings suggest that modifying and/or repurposing clinically approved drugs using nanotechnology is a feasible approach in our search for effective antibacterial molecules. Full article
(This article belongs to the Special Issue Silver-Based Antimicrobials)
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Open AccessArticle Development of Immunochromatographic Assay for Determination of Tetracycline in Human Serum
Antibiotics 2018, 7(4), 99; https://doi.org/10.3390/antibiotics7040099
Received: 26 October 2018 / Revised: 12 November 2018 / Accepted: 12 November 2018 / Published: 13 November 2018
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Abstract
Determining antibiotic concentration in human blood provides useful pharmacokinetic information. Commonly used methods such as ELISA require a long time to obtain results and thus cannot be applied when information is needed immediately. In this study, a novel antibody-based lateral flow technique was
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Determining antibiotic concentration in human blood provides useful pharmacokinetic information. Commonly used methods such as ELISA require a long time to obtain results and thus cannot be applied when information is needed immediately. In this study, a novel antibody-based lateral flow technique was developed for tetracycline detection in human serum. Contrary to tests developed to analyze food samples, the features of work with serum as analyzed probe were studied for the first time here. The application of labeled and unlabeled specific antibodies was compared. For this purpose, specific and anti-species antibodies were labeled with gold nanoparticles and used for antigen–antibody interaction on the membrane surface with observed staining in the test zone. For both schemes, optimal conditions were established to provide the best sensitivity. The developed assay has a limit of visual detection as low as 35 and 11 ng/mL for the direct and indirect labeled antibodies, respectively. The limit of instrumental detection is from 0.4 to 3.5 ng/mL for diluted and undiluted sera. The use of indirect antibody labeling showed a small increase in sensitivity compared to traditional direct antibody labeling. The developed method showed no cross-reactivity with antibiotics of other classes. The method was used to test samples of serum. The results showed high correlation with the data obtained by ELISA (R2 = 0.98968). The assay provides a quick assessment of the amount of antibiotics in the blood and keeps them under control throughout the duration of therapy. Full article
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Open AccessArticle Alkaloid-Rich Crude Extracts, Fractions and Piperamide Alkaloids of Piper guineense Possess Promising Antibacterial Effects
Antibiotics 2018, 7(4), 98; https://doi.org/10.3390/antibiotics7040098
Received: 6 October 2018 / Revised: 1 November 2018 / Accepted: 6 November 2018 / Published: 9 November 2018
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Abstract
Piper guineense is a food and medicinal plant commonly used to treat infectious diseases in West-African traditional medicine. In a bid to identify new antibacterial compounds due to bacterial resistance to antibiotics, twelve extracts of P. guineense fruits and leaves, obtained by sequential
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Piper guineense is a food and medicinal plant commonly used to treat infectious diseases in West-African traditional medicine. In a bid to identify new antibacterial compounds due to bacterial resistance to antibiotics, twelve extracts of P. guineense fruits and leaves, obtained by sequential extraction, as well as the piperine and piperlongumine commercial compounds were evaluated for antibacterial activity against human pathogenic bacteria. HPLC-DAD and UHPLC/Q-TOF MS analysis were conducted to characterize and identify the compounds present in the extracts with promising antibacterial activity. The extracts, with the exception of the hot water decoctions and macerations, contained piperamide alkaloids as their main constituents. Piperine, dihydropiperine, piperylin, dihydropiperylin or piperlonguminine, dihydropiperlonguminine, wisanine, dihydrowisanine and derivatives of piperine and piperidine were identified in a hexane extract of the leaf. In addition, some new piperamide alkaloids were identified, such as a piperine and a piperidine alkaloid derivative and two unknown piperamide alkaloids. To the best of our knowledge, there are no piperamides reported in the literature with similar UVλ absorption maxima and masses. A piperamide alkaloid-rich hexane leaf extract recorded the lowest MIC of 19 µg/mL against Sarcina sp. and gave promising growth inhibitory effects against S. aureus and E. aerogenes as well, inhibiting the growth of both bacteria with a MIC of 78 µg/mL. Moreover, this is the first report of the antibacterial activity of P. guineense extracts against Sarcina sp. and E. aerogenes. Marked growth inhibition was also obtained for chloroform extracts of the leaves and fruits against P. aeruginosa with a MIC value of 78 µg/mL. Piperine and piperlongumine were active against E. aerogenes, S. aureus, E. coli, S. enterica, P. mirabilis and B. cereus with MIC values ranging from 39–1250 µg/mL. Notably, the water extracts, which were almost devoid of piperamide alkaloids, were not active against the bacterial strains. Our results demonstrate that P. guineense contains antibacterial alkaloids that could be relevant for the discovery of new natural antibiotics. Full article
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Open AccessArticle Antimicrobial Stewardship Programmes in Community Healthcare Organisations in England: A Cross-Sectional Survey to Assess Implementation of Programmes and National Toolkits
Antibiotics 2018, 7(4), 97; https://doi.org/10.3390/antibiotics7040097
Received: 11 October 2018 / Revised: 29 October 2018 / Accepted: 31 October 2018 / Published: 7 November 2018
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Abstract
Objective: The aim of this study was to assess antimicrobial stewardship activities in Community Healthcare Organisations (CHOs) with focus on the implementation of the two national antimicrobial stewardship toolkits, TARGET (Treat Antibiotics Responsibly, Guidance, Education, Tools) and SSTF (Start Smart, then Focus). The
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Objective: The aim of this study was to assess antimicrobial stewardship activities in Community Healthcare Organisations (CHOs) with focus on the implementation of the two national antimicrobial stewardship toolkits, TARGET (Treat Antibiotics Responsibly, Guidance, Education, Tools) and SSTF (Start Smart, then Focus). The study utilised a web-based survey comprising 34 questions concerning antimicrobial policies and awareness and implementation of antimicrobial stewardship toolkits. This was distributed to pharmacy teams in all 26 CHOs in England. Twenty CHOs (77%) responded. An antimicrobial stewardship (AMS) committee was active in 50% of CHOs; 25% employed a substantive pharmacist post and 70% had a local antibiotic policy. Fourteen of the responding CHOs were aware of both AMS toolkits, five organisations were aware of either SSTF or TARGET, and one organisation was not aware of either toolkit. Of the organisations aware of SSTF and TARGET, eight had formally reviewed both toolkits, though three had not reviewed either. Less than half of the respondents had developed local action plans for either toolkit. National guidance in England has focused attention on initiatives to improve AMS implementation in primary and secondary care; more work is required to embed AMS activities and the implementation of national AMS toolkit recommendations within CHOs. Full article
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Open AccessCase Report First Description of Colistin and Tigecycline-Resistant Acinetobacter baumannii Producing KPC-3 Carbapenemase in Portugal
Antibiotics 2018, 7(4), 96; https://doi.org/10.3390/antibiotics7040096
Received: 7 September 2018 / Revised: 29 October 2018 / Accepted: 2 November 2018 / Published: 6 November 2018
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Abstract
Herein, we describe a case report of carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates that were identified from the same patient at a Tertiary University Hospital Centre in Portugal. Antimicrobial susceptibility and the molecular characterization of resistance and virulence determinants were performed. PCR
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Herein, we describe a case report of carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates that were identified from the same patient at a Tertiary University Hospital Centre in Portugal. Antimicrobial susceptibility and the molecular characterization of resistance and virulence determinants were performed. PCR screening identified the presence of the resistance genes blaKPC-3, blaTEM-1 and blaSHV-1 in both isolates. The KPC-3 K. pneumoniae isolate belonged to the ST-14 high risk clone and accumulated an uncommon resistance and virulence profile additional to a horizontal dissemination capacity. In conclusion, the molecular screening led to the first identification of the A. baumannii KPC-3 producer in Portugal with a full antimicrobial resistance profile including tigecycline and colistin. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessArticle The Consequences of AMR Education and Awareness Raising: Outputs, Outcomes, and Behavioural Impacts of an Antibiotic-Related Educational Activity in Lao PDR
Antibiotics 2018, 7(4), 95; https://doi.org/10.3390/antibiotics7040095
Received: 2 September 2018 / Revised: 19 October 2018 / Accepted: 30 October 2018 / Published: 1 November 2018
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Abstract
Education and awareness raising are the primary tools of global health policy to change public behaviour and tackle antimicrobial resistance. Considering the limitations of an awareness agenda, and the lack of social research to inform alternative approaches, our objective was to generate new
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Education and awareness raising are the primary tools of global health policy to change public behaviour and tackle antimicrobial resistance. Considering the limitations of an awareness agenda, and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages and also to learn about people’s conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity’s outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the educational activity influenced the awareness and understanding of “drug resistance”, whereas the effects on attitudes were minor. The evidence on the behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance. Full article
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Open AccessArticle Antibiotic Activity of Actinobacteria from the Digestive Tract of Millipede Nedyopus dawydoffiae (Diplopoda)
Antibiotics 2018, 7(4), 94; https://doi.org/10.3390/antibiotics7040094
Received: 10 September 2018 / Revised: 17 October 2018 / Accepted: 24 October 2018 / Published: 29 October 2018
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Abstract
Because of the spread of drug resistance, it is necessary to look for new antibiotics that are effective against pathogenic microorganisms. The purpose of this study was to analyse the species composition of actinobacteria isolated from the digestive tract of the millipedes Nedyopus
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Because of the spread of drug resistance, it is necessary to look for new antibiotics that are effective against pathogenic microorganisms. The purpose of this study was to analyse the species composition of actinobacteria isolated from the digestive tract of the millipedes Nedyopus dawydoffiae and to determine their antimicrobial properties. Species identification was carried out on the basis of the morphological and culture properties and the sequence of the 16S rRNA gene. Actinobacteria were grown in different liquid media. Antibiotic properties were determined against some Gram-positive and Gram-negative bacteria as well as fungi. Of the 15 isolated strains, 13 have antibiotic activity against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus—MRSA) and fungi, but there was no antibiotic activity against Gram-negative test strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. It was established that antibiotic-producing actinobacteria belong to eight species of the genus Streptomyces. Depending on the nutrient medium, actinobacteria demonstrate different antimicrobial activities. As an example, S. hydrogenans shows that even strains selected in one population differ by the range of antimicrobial activity and the level of biosynthesis. Since the antibiotic production is considered as a feature for species competition in the microbiota community, the variability of antibiotic production among different strains of the same species is an adaptive characteristic for the competition in millipedes’ digestive tract community. Full article
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Open AccessReview Antimicrobial Silver in Medicinal and Consumer Applications: A Patent Review of the Past Decade (2007–2017)
Antibiotics 2018, 7(4), 93; https://doi.org/10.3390/antibiotics7040093
Received: 20 August 2018 / Revised: 8 October 2018 / Accepted: 16 October 2018 / Published: 26 October 2018
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Abstract
The use of silver to control infections was common in ancient civilizations. In recent years, this material has resurfaced as a therapeutic option due to the increasing prevalence of bacterial resistance to antimicrobials. This renewed interest has prompted researchers to investigate how the
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The use of silver to control infections was common in ancient civilizations. In recent years, this material has resurfaced as a therapeutic option due to the increasing prevalence of bacterial resistance to antimicrobials. This renewed interest has prompted researchers to investigate how the antimicrobial properties of silver might be enhanced, thus broadening the possibilities for antimicrobial applications. This review presents a compilation of patented products utilizing any forms of silver for its bactericidal actions in the decade 2007–2017. It analyses the trends in patent applications related to different forms of silver and their use for antimicrobial purposes. Based on the retrospective view of registered patents, statements of prognosis are also presented with a view to heightening awareness of potential industrial and health care applications. Full article
(This article belongs to the Special Issue Silver-Based Antimicrobials)
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Open AccessArticle Explorative Study on Isolation and Characterization of a Microviridae G4 Bacteriophage, EMCL318, against Multi-Drug-resistant Escherichia coli 15-318
Antibiotics 2018, 7(4), 92; https://doi.org/10.3390/antibiotics7040092
Received: 29 September 2018 / Revised: 21 October 2018 / Accepted: 24 October 2018 / Published: 26 October 2018
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Abstract
Bacteriophages screened and isolated from sewage water samples exhibited antibacterial activities against multi-drug-resistant Escherichia coli strains. Five different water samples from Canadian habitats such as Kamloops Wastewater Treatment Center, Domtar, the Pacific Ocean, Bisaro Anima Cave, and alkali ponds, were used in this
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Bacteriophages screened and isolated from sewage water samples exhibited antibacterial activities against multi-drug-resistant Escherichia coli strains. Five different water samples from Canadian habitats such as Kamloops Wastewater Treatment Center, Domtar, the Pacific Ocean, Bisaro Anima Cave, and alkali ponds, were used in this study. Four Enterobacteriaceae strains including one non-resistant and three clinical multi-drug Escherichia coli strains (E. coli 15-102, E. coli 15-124, and E. coli 15-318) were selected as target bacteria to screen for the bacteriophages from these collected water samples. Seeded agar assay technique was implemented for the screening. It was found that only sewage water sample exhibited a significant number of plaques count with the E. coli 15-318 (1.82 × 102 plaques/plate) cells in comparison to E. coli non-resistant strain K12 (8 plaques/plate). The phage did not produce plaques in the E. coli 15-124 and E. coli 15-102 strains. The bacteriophage, designated EMCL318, was isolated, purified, characterized, and identified to belong to the G4 species of the Family Microviridae, GenBank accession number MG563770. This is an explorative study conducted in order to reveal the viruses as alternative potentials to fight against emerging and existing multi-drug-resistant infectious diseases. Full article
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Open AccessArticle Microbiome Analysis of Biofilms of Silver Nanoparticle-Dispersed Silane-Based Coated Carbon Steel Using a Next-Generation Sequencing Technique
Antibiotics 2018, 7(4), 91; https://doi.org/10.3390/antibiotics7040091
Received: 16 August 2018 / Revised: 25 September 2018 / Accepted: 16 October 2018 / Published: 22 October 2018
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Abstract
Previously, we demonstrated that silver nanoparticle-dispersed silane-based coating could inhibit biofilm formation in conditions where seawater was used as a bacterial source and circulated in a closed laboratory biofilm reactor. However, it is still unclear whether the microbiome of a biofilm of silver
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Previously, we demonstrated that silver nanoparticle-dispersed silane-based coating could inhibit biofilm formation in conditions where seawater was used as a bacterial source and circulated in a closed laboratory biofilm reactor. However, it is still unclear whether the microbiome of a biofilm of silver nanoparticle-dispersed silane-based coating samples (Ag) differs from that of a biofilm of non-dispersed silane-based coating samples (Non-Ag). This study aimed to perform a microbiome analysis of the biofilms grown on the aforementioned coatings using a next-generation sequencing (NGS) technique. For this, a biofilm formation test was conducted by allowing seawater to flow through a closed laboratory biofilm reactor; subsequently, DNAs extracted from the biofilms of Ag and Non-Ag were used to prepare 16S rRNA amplicon libraries to analyze the microbiomes by NGS. Results of the operational taxonomy unit indicated that the biofilms of Non-Ag and Ag comprised one and no phyla of archaea, respectively, whereas Proteobacteria was the dominant phylum for both biofilms. Additionally, in both biofilms, Non-Ag and Ag, Marinomonas was the primary bacterial group involved in early stage biofilm formation, whereas Anaerospora was primarily involved in late-stage biofilm formation. These results indicate that silver nanoparticles will be unrelated to the bacterial composition of biofilms on the surface of silane-based coatings, while they control biofilm formation there. Full article
(This article belongs to the Special Issue Silver-Based Antimicrobials)
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Open AccessReview Advances in Antarctic Research for Antimicrobial Discovery: A Comprehensive Narrative Review of Bacteria from Antarctic Environments as Potential Sources of Novel Antibiotic Compounds Against Human Pathogens and Microorganisms of Industrial Importance
Antibiotics 2018, 7(4), 90; https://doi.org/10.3390/antibiotics7040090
Received: 13 July 2018 / Revised: 5 September 2018 / Accepted: 4 October 2018 / Published: 19 October 2018
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Abstract
The recent emergence of antibiotic-resistant bacteria has become a critical public health problem. It is also a concern for industries, since multidrug-resistant microorganisms affect the production of many agricultural and food products of economic importance. Therefore, discovering new antibiotics is crucial for controlling
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The recent emergence of antibiotic-resistant bacteria has become a critical public health problem. It is also a concern for industries, since multidrug-resistant microorganisms affect the production of many agricultural and food products of economic importance. Therefore, discovering new antibiotics is crucial for controlling pathogens in both clinical and industrial spheres. Most antibiotics have resulted from bioprospecting in natural environments. Today, however, the chances of making novel discoveries of bioactive molecules from various well-known sources have dramatically diminished. Consequently, unexplored and unique environments have become more likely avenues for discovering novel antimicrobial metabolites from bacteria. Due to their extreme polar environment, Antarctic bacteria in particular have been reported as a potential source for new antimicrobial compounds. We conducted a narrative review of the literature about findings relating to the production of antimicrobial compounds by Antarctic bacteria, showing how bacterial adaptation to extreme Antarctic conditions confers the ability to produce these compounds. We highlighted the diversity of antibiotic-producing Antarctic microorganisms, including the phyla Proteobacteria, Actinobacteria, Cyanobacteria, Firmicutes, and Bacteroidetes, which has led to the identification of new antibiotic molecules and supports the belief that research on Antarctic bacterial strains has important potential for biotechnology applications, while providing a better understanding of polar ecosystems. Full article
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Open AccessArticle Identification of Essential Oils with Strong Activity against Stationary Phase Borrelia burgdorferi
Antibiotics 2018, 7(4), 89; https://doi.org/10.3390/antibiotics7040089
Received: 28 August 2018 / Revised: 10 October 2018 / Accepted: 10 October 2018 / Published: 16 October 2018
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Abstract
Lyme disease is the most common vector borne-disease in the United States (US). While the majority of the Lyme disease patients can be cured with 2–4 weeks antibiotic treatment, about 10–20% of patients continue to suffer from persisting symptoms. While the cause of
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Lyme disease is the most common vector borne-disease in the United States (US). While the majority of the Lyme disease patients can be cured with 2–4 weeks antibiotic treatment, about 10–20% of patients continue to suffer from persisting symptoms. While the cause of this condition is unclear, persistent infection was proposed as one possibility. It has recently been shown that B. burgdorferi develops dormant persisters in stationary phase cultures that are not killed by the current Lyme antibiotics, and there is interest in identifying novel drug candidates that more effectively kill such forms. We previously identified some highly active essential oils with excellent activity against biofilm and stationary phase B. burgdorferi. Here, we screened another 35 essential oils and found 10 essential oils (Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cuminum cyminum L. seeds, Cymbopogon martini var. motia Bruno grass, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, Amyris balsamifera L. wood, Thymus vulgaris L. leaves, Litsea cubeba (Lour.) Pers. fruits, Eucalyptus citriodora Hook. leaves) and the active component of cinnamon bark cinnamaldehyde (CA) at a low concentration of 0.1% have strong activity against stationary phase B. burgdorferi. At a lower concentration of 0.05%, essential oils of Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Cymbopogon martini var. motia Bruno grass and CA still exhibited strong activity against the stationary phase B. burgdorferi. CA also showed strong activity against replicating B. burgdorferi, with a MIC of 0.02% (or 0.2 μg/mL). In subculture studies, the top five essential oil hits Allium sativum L. bulbs, Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers, and Litsea cubeba (Lour.) Pers. fruits completely eradicated all B. burgdorferi stationary phase cells at 0.1%, while Cymbopogon martini var. motia Bruno grass, Eucalyptus citriodora Hook. leaves, Amyris balsamifera L. wood, Cuminum cyminum L. seeds, and Thymus vulgaris L. leaves failed to do so as shown by visible spirochetal growth after 21-day subculture. At concentration of 0.05%, only Allium sativum L. bulbs essential oil and CA sterilized the B. burgdorferi stationary phase culture, as shown by no regrowth during subculture, while Pimenta officinalis Lindl. berries, Commiphora myrrha (T. Nees) Engl. resin, Hedychium spicatum Buch.-Ham. ex Sm. flowers and Litsea cubeba (Lour.) Pers. fruits essential oils all had visible growth during subculture. Future studies are needed to determine if these highly active essential oils could eradicate persistent B. burgdorferi infection in vivo. Full article
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Open AccessArticle Study of Disinfectant Resistance Genes in Ocular Isolates of Pseudomonas aeruginosa
Antibiotics 2018, 7(4), 88; https://doi.org/10.3390/antibiotics7040088
Received: 25 September 2018 / Revised: 11 October 2018 / Accepted: 11 October 2018 / Published: 15 October 2018
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Abstract
Background: The prevalence of disinfectant resistance in Pseudomonas aeruginosa is on the rise. P. aeruginosa is the most common bacteria isolated from cases of microbial keratitis. Many multi-purpose contact lens disinfectant solutions are available to decontaminate contact lenses before use and to help
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Background: The prevalence of disinfectant resistance in Pseudomonas aeruginosa is on the rise. P. aeruginosa is the most common bacteria isolated from cases of microbial keratitis. Many multi-purpose contact lens disinfectant solutions are available to decontaminate contact lenses before use and to help reduce the incidence of infections. However, with increasing disinfectant resistance, the effect of multi-purpose disinfectant solutions may diminish. The goal of this study was to examine genes associated with disinfectant resistance in ocular isolates of P. aeruginosa and understand the strain’s susceptibility to different multipurpose disinfectant solutions. Methods: Seven potential disinfectant resistance genes were used in BLASTn searches against the whole genomes of 13 eye isolates of P. aeruginosa. A microdilution broth method was used to examine susceptibility to four different multipurpose disinfectant solutions. Results: All strains possessed the sugE2, sugE3 and emrE (qacE) genes. The sugE1 and qacEdelta1 genes were present in 6/13 isolates. No strains contained the qacF or qacG genes. All tested disinfectant solutions had the ability to kill all test strains at 100% concentration, with some strains being susceptible at 1:8 dilutions of the disinfecting solutions. However, the presence of disinfectant resistance genes was not associated with susceptibility to multi-purpose disinfectants. Conclusion: All four tested contact lens disinfectant preparations are effective against P. aeruginosa isolates regardless of the presence of disinfectant resistance genes. Full article
Open AccessCase Report Resolving Digital Staphylococcal Osteomyelitis Using Bacteriophage—A Case Report
Antibiotics 2018, 7(4), 87; https://doi.org/10.3390/antibiotics7040087
Received: 28 August 2018 / Revised: 18 September 2018 / Accepted: 19 September 2018 / Published: 2 October 2018
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Abstract
Infections involving diabetic foot ulcers (DFU) are a major public health problem and have a substantial negative impact on patient outcomes. Osteomyelitis in an ulcerated foot substantially increases the difficulty of successful treatment. While literature suggests that osteomyelitis in selected patients can sometimes
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Infections involving diabetic foot ulcers (DFU) are a major public health problem and have a substantial negative impact on patient outcomes. Osteomyelitis in an ulcerated foot substantially increases the difficulty of successful treatment. While literature suggests that osteomyelitis in selected patients can sometimes be treated conservatively, with no, or minimal removal of bone, we do not yet have clear treatment guidelines and the standard treatment failure fallback remains amputation. The authors report on the successful treatment, with a long term follow up, of a 63 YO diabetic female with distal phalangeal osteomyelitis using bacteriophage, a form of treatment offering the potential for improved outcomes in this era of escalating antibiotic resistance and the increasingly recognized harms associated with antibiotic therapy. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessCommunication Comparative Genomics among Closely Related Streptomyces Strains Revealed Specialized Metabolite Biosynthetic Gene Cluster Diversity
Antibiotics 2018, 7(4), 86; https://doi.org/10.3390/antibiotics7040086
Received: 12 September 2018 / Revised: 27 September 2018 / Accepted: 28 September 2018 / Published: 2 October 2018
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Abstract
Specialized metabolites are of great interest due to their possible industrial and clinical applications. The increasing number of antimicrobial resistant infectious agents is a major health threat and therefore, the discovery of chemical diversity and new antimicrobials is crucial. Extensive genomic data from
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Specialized metabolites are of great interest due to their possible industrial and clinical applications. The increasing number of antimicrobial resistant infectious agents is a major health threat and therefore, the discovery of chemical diversity and new antimicrobials is crucial. Extensive genomic data from Streptomyces spp. confirm their production potential and great importance. Genome sequencing of the same species strains indicates that specialized metabolite biosynthetic gene cluster (SMBGC) diversity is not exhausted, and instead, a pool of novel specialized metabolites still exists. Here, we analyze the genome sequence data from six phylogenetically close Streptomyces strains. The results reveal that the closer strains are phylogenetically, the number of shared gene clusters is higher. Eight specialized metabolites comprise the core metabolome, although some strains have only six core gene clusters. The number of conserved gene clusters common between the isolated strains and their closest phylogenetic counterparts varies from nine to 23 SMBGCs. However, the analysis of these phylogenetic relationships is not affected by the acquisition of gene clusters, probably by horizontal gene transfer events, as each strain also harbors strain-specific SMBGCs. Between one and 15 strain-specific gene clusters were identified, of which up to six gene clusters in a single strain are unknown and have no identifiable orthologs in other species, attesting to the existing SMBGC novelty at the strain level. Full article
(This article belongs to the Special Issue Actinomycetes: The Antibiotics Producers)
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Open AccessReview Mining Actinomycetes for Novel Antibiotics in the Omics Era: Are We Ready to Exploit This New Paradigm?
Antibiotics 2018, 7(4), 85; https://doi.org/10.3390/antibiotics7040085
Received: 6 August 2018 / Revised: 20 September 2018 / Accepted: 21 September 2018 / Published: 25 September 2018
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Abstract
The current spread of multi-drug resistance in a number of key pathogens and the lack of therapeutic solutions in development to address most of the emerging infections in the clinic that are difficult to treat have become major concerns. Microbial natural products represent
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The current spread of multi-drug resistance in a number of key pathogens and the lack of therapeutic solutions in development to address most of the emerging infections in the clinic that are difficult to treat have become major concerns. Microbial natural products represent one of the most important sources for the discovery of potential new antibiotics and actinomycetes have been one of the most relevant groups that are prolific producers of these bioactive compounds. Advances in genome sequencing and bioinformatic tools have collected a wealth of knowledge on the biosynthesis of these molecules. This has revealed the broad untapped biosynthetic diversity of actinomycetes, with large genomes and the capacity to produce more molecules than previously estimated, opening new opportunities to identify the novel classes of compounds that are awaiting to be discovered. Comparative genomics, metabolomics and proteomics and the development of new analysis and genetic engineering tools provide access to the integration of new knowledge and better understanding of the physiology of actinomycetes and their tight regulation of the production of natural products antibiotics. This new paradigm is fostering the development of new genomic-driven and culture-based strategies, which aims to deliver new chemical classes of antibiotics to be developed to the clinic and replenish the exhausted pipeline of drugs for fighting the progression of infection diseases in the near future. Full article
(This article belongs to the Special Issue Actinomycetes: The Antibiotics Producers)
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