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Antibiotics, Volume 9, Issue 10 (October 2020) – 89 articles

Cover Story (view full-size image): Tailed bacteriophages, the most common type of phages used in antibacterial therapy, are much more diverse than originally thought based on their morphology. In this paper, we use a combination of genomic, proteomic and phylogenetic approaches to delineate a new family of phages related to Escherichia phage N4, a short-tailed phage with a characteristic large virion-associated RNA polymerase. The new family is tentatively named “Schitoviridae” after the discoverer of phage N4, comprises 115 analysed genomes and is proposed to be divided into eight subfamilies and numerous new genera. The cover image shows a gene-sharing network of schitoviruses and other bacteriophages on the left and a virus proteomic tree of selected podoviruses on the right, on a background of N4 TEM copies (TEM donated to A Kropinski by HW Ackermann). View this paper.
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Article
Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy
Antibiotics 2020, 9(10), 723; https://doi.org/10.3390/antibiotics9100723 - 21 Oct 2020
Cited by 3 | Viewed by 789
Abstract
Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin [...] Read more.
Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017–2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Article
Antibiotic Adsorption by Metal-Organic Framework (UiO-66): A Comprehensive Kinetic, Thermodynamic, and Mechanistic Study
Antibiotics 2020, 9(10), 722; https://doi.org/10.3390/antibiotics9100722 - 21 Oct 2020
Cited by 2 | Viewed by 1091
Abstract
Bacterial antibiotic resistance has been deemed one of the largest modern threats to human health. One of the root causes of antibiotic resistance is the inability of traditional wastewater management techniques, such as filtration and disinfection, to completely eliminate residual antibiotics from domestic [...] Read more.
Bacterial antibiotic resistance has been deemed one of the largest modern threats to human health. One of the root causes of antibiotic resistance is the inability of traditional wastewater management techniques, such as filtration and disinfection, to completely eliminate residual antibiotics from domestic and industrial effluents. In this study, we examine the ability of UiO-66; a metal-organic framework (MOF); in removing the antibiotic Doxycycline from aqueous environments. This study’s findings suggest that UiO-66 was able to remove nearly 90% of the initial Doxycycline concentration. To correlate the isothermal data, Langmuir and Freundlich models were used. It was determined that the Langmuir model was best suited. Pseudo-first and -second order models were examined for kinetic data, where the pseudo-second order model was best suited—consistent with the maximum theoretical adsorption capacity found by the Langumir model. Thermodynamic analysis was also examined by studying UiO-66 adsorption under different temperatures. Mechanisms of adsorption were also analyzed through measuring adsorption at varying pH levels, thermogravimetric analysis (TGA), Infrared spectroscopy (IR) and Brunauer–Emmet–Teller (BET). This study also explores the possibility of recycling MOFs through exposure to gamma radiation, heat, and heating under low pressure, in order for UiO-66 to be used in multiple, consecutive cycles of Doxycycline removal. Full article
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Editorial
Editorial for the Special Issue: “Phage Therapy: A Biological Approach to Treatment of Bacterial Infections”
Antibiotics 2020, 9(10), 721; https://doi.org/10.3390/antibiotics9100721 - 21 Oct 2020
Viewed by 687
Abstract
The emergence of antibiotic-resistant bacteria presents a major challenge in terms of increased morbidity, mortality, and healthcare costs [...] Full article
Article
Effect of Fosfomycin on Cyclosporine Nephrotoxicity
Antibiotics 2020, 9(10), 720; https://doi.org/10.3390/antibiotics9100720 - 21 Oct 2020
Viewed by 893
Abstract
Fosfomycin (Fos) has emerged as a potential treatment against multidrug-resistant organisms, however, there has been little work done on its influence on calcineurin inhibitor nephrotoxicity (CIN). This study was designed to evaluate the effect of Fos in combination with cyclosporine (CsA) on CIN. [...] Read more.
Fosfomycin (Fos) has emerged as a potential treatment against multidrug-resistant organisms, however, there has been little work done on its influence on calcineurin inhibitor nephrotoxicity (CIN). This study was designed to evaluate the effect of Fos in combination with cyclosporine (CsA) on CIN. Two sets of experiments were undertaken. In the first, Wistar rats received different doses of Fos: 0, 62.5, 125, 250, and 500 mg/kg. In the second, rats were divided into four groups: control, CsA 15 mg/kg s.c., CsA + fosfomycin 62.5 mg/kg (CsA + LF), and CsA + Fos 500 mg/kg (CsA + HF). CsA was administrated daily for 14 days, whereas Fos administration started on the ninth day followed by two more doses, delivered 48 h apart. The administration of different Fos doses did not alter renal function. In contrast, CsA induced arteriolopathy, hypoperfusion, a reduction in the glomerular filtration rate, and downregulation of eNOS, angiotensinogen, and AT1R mRNA levels. Lower doses of Fos did not modify CIN. Instead, the CsA + HF group exhibited greater hypoperfusion, arteriolopathy, and oxidative stress, and increased mRNA levels of pro-inflammatory cytokines. This study shows that Fos administered by itself at different doses did not cause renal injury, but when it was given repeatedly at high dosages (500 mg/kg) in combination with CsA, it increased CIN through the promotion of greater oxidative stress and renal inflammation. Full article
(This article belongs to the Section The Global Need for Effective Antibiotics)
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Review
Relationship between Virulence and Resistance among Gram-Negative Bacteria
Antibiotics 2020, 9(10), 719; https://doi.org/10.3390/antibiotics9100719 - 20 Oct 2020
Cited by 11 | Viewed by 1249
Abstract
Bacteria present in the human body are innocuous, providing beneficial functions, some of which are necessary for correct body function. However, other bacteria are able to colonize, invade, and cause damage to different tissues, and these are categorised as pathogens. These pathogenic bacteria [...] Read more.
Bacteria present in the human body are innocuous, providing beneficial functions, some of which are necessary for correct body function. However, other bacteria are able to colonize, invade, and cause damage to different tissues, and these are categorised as pathogens. These pathogenic bacteria possess several factors that enable them to be more virulent and cause infection. Bacteria have a great capacity to adapt to different niches and environmental conditions (presence of antibiotics, iron depletion, etc.). Antibiotic pressure has favoured the emergence and spread of antibiotic-resistant bacteria worldwide. Several studies have reported the presence of a relationship (both positive and negative, and both direct and indirect) between antimicrobial resistance and virulence among bacterial pathogens. This review studies the relationship among the most important Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) taking into account two points of view: (i) the effect the acquisition of resistance has on virulence, and (ii) co-selection of resistance and virulence. The relationship between resistance and virulence among bacteria depends on the bacterial species, the specific mechanisms of resistance and virulence, the ecological niche, and the host. Full article
Article
Peptidomic Analysis of Skin Secretions of the Caribbean Frogs Leptodactylus insularum and Leptodactylus nesiotus (Leptodactylidae) Identifies an Ocellatin with Broad Spectrum Antimicrobial Activity
Antibiotics 2020, 9(10), 718; https://doi.org/10.3390/antibiotics9100718 - 20 Oct 2020
Cited by 3 | Viewed by 1308
Abstract
Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the [...] Read more.
Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1–16) fragment, ocellatin-2I and its (1–16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25–62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens. Full article
(This article belongs to the Special Issue Development of Antimicrobial Peptides from Amphibian)
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Article
Antibacterial and Cytotoxic Activities of Ten Commercially Available Essential Oils
Antibiotics 2020, 9(10), 717; https://doi.org/10.3390/antibiotics9100717 - 20 Oct 2020
Cited by 5 | Viewed by 1581
Abstract
There is a huge concern in the medical field concerning the emergence of bacterial resistance to antibiotics. Essential oils are a source of antibacterial compounds that can overcome this problem. Ten essential oils that are commercially available were investigated in the present study: [...] Read more.
There is a huge concern in the medical field concerning the emergence of bacterial resistance to antibiotics. Essential oils are a source of antibacterial compounds that can overcome this problem. Ten essential oils that are commercially available were investigated in the present study: ajowan, basil, German chamomile, Chinese cinnamon, coriander, clove, lemongrass, Spanish lavender, oregano and palmarosa. Their direct, synergistic and indirect antibacterial activities were evaluated against different human pathogenic Gram-positive and Gram-negative strains. To evaluate their possible use in clinics, the cytotoxicity of these essential oils was also tested on keratinocyte and epithelial cell lines. Except for the Chinese cinnamon, coriander and lemongrass, all other essential oils presented no cytotoxicity at 32 and 16 μg/mL. The highest indirect antibacterial activities were observed with the palmarosa and Spanish lavender in association with penicillin V. These two associations presented a 64-fold decrease against a resistant strain of Staphylococcus aureus, however, at a cytotoxic concentration. It can also be highlighted that when tested at a non-cytotoxic concentration, the activity of oregano in association with penicillin V presented an eight-fold decrease. These results show the interest to use essential oils in combination with antibiotics to reduce their concentrations inside drugs. Full article
(This article belongs to the Special Issue Antibacterial Activity of Plant Extracts and Essential Oils)
Review
Antibacterial Property and Biocompatibility of Silver, Copper, and Zinc in Titanium Dioxide Layers Incorporated by One-Step Micro-Arc Oxidation: A Review
Antibiotics 2020, 9(10), 716; https://doi.org/10.3390/antibiotics9100716 - 20 Oct 2020
Cited by 10 | Viewed by 1524
Abstract
Titanium (Ti) and its alloys are commonly used in medical devices. However, biomaterial-associated infections such as peri-implantitis and prosthetic joint infections are devastating and threatening complications for patients, dentists, and orthopedists and are easily developed on titanium surfaces. Therefore, this review focuses on [...] Read more.
Titanium (Ti) and its alloys are commonly used in medical devices. However, biomaterial-associated infections such as peri-implantitis and prosthetic joint infections are devastating and threatening complications for patients, dentists, and orthopedists and are easily developed on titanium surfaces. Therefore, this review focuses on the formation of biofilms on implant surfaces, which is the main cause of infections, and one-step micro-arc oxidation (MAO) as a coating technology that can be expected to prevent infections due to the implant. Many researchers have provided sufficient data to prove the efficacy of MAO for preventing the initial stages of biofilm formation on implant surfaces. Silver (Ag), copper (Cu), and zinc (Zn) are well used and are incorporated into the Ti surface by MAO. In this review, the antibacterial properties, cytotoxicity, and durability of these elements on the Ti surface incorporated by one-step MAO will be summarized. This review is aimed at enhancing the importance of the quantitative control of Ag, Cu, and Zn for their use in implant surfaces and the significance of the biodegradation behavior of these elements for the development of antibacterial properties. Full article
(This article belongs to the Special Issue Specialized Coatings Interacting with Human Pathogens)
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Article
Aureolic Acid Group of Agents as Potential Antituberculosis Drugs
Antibiotics 2020, 9(10), 715; https://doi.org/10.3390/antibiotics9100715 - 19 Oct 2020
Viewed by 1140
Abstract
Mycobacterium tuberculosis is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, [...] Read more.
Mycobacterium tuberculosis is one of the most dangerous pathogens. Bacterial resistance to antituberculosis drugs grows each year, but searching for new drugs is a long process. Testing for available drugs to find active against mycobacteria may be a good alternative. In this work, antibiotics of the aureolic acid group were tested on a model organism Mycobacterium smegmatis. We presumed that antibiotics of this group may be potential G4 ligands. However, this was not confirmed in our analyses. We determined the antimicrobial activity of these drugs and revealed morphological changes in the cell structure upon treatment. Transcriptomic analysis documented increased expression of MSMEG_3743/soj and MSMEG_4228/ftsW, involved in cell division. Therefore, drugs may affect cell division, possibly disrupting the function of the Z-ring and the formation of a septum. Additionally, a decrease in the transcription level of several indispensable genes, such as nitrate reductase subunits (MSMEG_5137/narI and MSMEG_5139/narX) and MSMEG_3205/hisD was shown. We concluded that the mechanism of action of aureolic acid and its related compounds may be similar to that bedaquiline and disturb the NAD+/NADH balance in the cell. All of this allowed us to conclude that aureolic acid derivatives can be considered as potential antituberculosis drugs. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Letter
Aminoglycoside Antibiotics Inhibit Mycobacteriophage Infection
Antibiotics 2020, 9(10), 714; https://doi.org/10.3390/antibiotics9100714 - 19 Oct 2020
Cited by 1 | Viewed by 1074
Abstract
Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are [...] Read more.
Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 cannot infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but the phage infection was not affected in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, it could be speculated that the amino sugar group of aminoglycoside might selectively inhibit mycobacteriophage DNA replication. Our discovery that broad-spectrum antibiotics inhibit phage infection is of great value. This study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis. Full article
(This article belongs to the Section Bacteriophages)
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Article
Preoperative Antibiotic Prophylaxis in Elective Minor Surgical Procedures among Adults in Southern Italy
Antibiotics 2020, 9(10), 713; https://doi.org/10.3390/antibiotics9100713 - 18 Oct 2020
Cited by 3 | Viewed by 867
Abstract
Little is known regarding the factors associated with surgical antibiotic prophylaxis (SAP) compliance in elective minor surgery. The purposes of this cross-sectional study were to identify the frequency of inappropriate SAP administration and to understand the characteristics associated with such inappropriateness in a [...] Read more.
Little is known regarding the factors associated with surgical antibiotic prophylaxis (SAP) compliance in elective minor surgery. The purposes of this cross-sectional study were to identify the frequency of inappropriate SAP administration and to understand the characteristics associated with such inappropriateness in a sample of elective minor surgical procedures. The study was performed between May and July 2019 among a random sample of patients aged 18 years and older in seven public hospitals randomly selected in the Campania and Calabria Regions of Italy. Globally, only 45% of SAP approaches were deemed completely in accordance with the evidence-based guidelines. Patients with an ordinary admission, those who underwent local anesthesia, those receiving plastic and reconstructive and ophthalmology surgery, and those who had not received a prosthetic implant were more likely to receive an appropriate SAP approach; those receiving obstetrics, gynecological, and urological surgical procedures were less likely than those who underwent abdominal, vascular, and breast surgery. The course of antibiotic prophylaxis was not consistent with the guidelines in 48.5% procedures with one or more reasons for inappropriateness. Appropriate time of the SAP administration was more frequently observed in patients who were older, those with a Charlson comorbidity index of 0, those who did not receive a prosthetic implant, and those receiving plastic and reconstructive surgery; it was less likely in patients receiving obstetrics, gynecological, and urological surgeries compared with those who underwent abdominal, vascular, and breast surgery. Aspects of SAP that need to be improved are molecule choice, time of administration, and specific surgical procedures. Hospital managers should involve surgeons and anesthesiologists in initiatives tailored to optimize SAP prescribing. Full article
(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Resistance in Hospital)
Review
Antibacterial Use of Macroalgae Compounds against Foodborne Pathogens
Antibiotics 2020, 9(10), 712; https://doi.org/10.3390/antibiotics9100712 - 17 Oct 2020
Cited by 6 | Viewed by 3391
Abstract
The search for food resources is a constant in human history. Nowadays, the search for natural and safe food supplies is of foremost importance. Accordingly, there is a renewed interest in eco-friendly and natural products for substitution of synthetic additives. In addition, microbial [...] Read more.
The search for food resources is a constant in human history. Nowadays, the search for natural and safe food supplies is of foremost importance. Accordingly, there is a renewed interest in eco-friendly and natural products for substitution of synthetic additives. In addition, microbial contamination of food products during their obtaining and distribution processes is still a sanitary issue, and an important target for the food industry is to avoid food contamination and its related foodborne illnesses. These diseases are fundamentally caused by certain microorganisms listed in this review and classified according to their Gram negative or positive character. Algae have proven to possess high nutritional value and a wide variety of biological properties due to their content in active compounds. Among these capabilities, macroalgae are recognized for having antimicrobial properties. Thus, the present paper revises the actual knowledge of microbial contaminants in the food industry and proposes antimicrobial algal compounds against those pathogenic bacteria responsible for food contamination as valuable molecules for its growth inhibition. The capacity of algae extracts to inhibit some major food pathogen growth was assessed. Moreover, the main applications of these compounds in the food industry were discussed while considering their favorable effects in terms of food safety and quality control. Full article
(This article belongs to the Special Issue Challenges in Antibiotics Analysis)
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Article
Single Cell Analysis of Drug Susceptibility of Mycobacterium abscessus during Macrophage Infection
Antibiotics 2020, 9(10), 711; https://doi.org/10.3390/antibiotics9100711 - 17 Oct 2020
Viewed by 1195
Abstract
Mycobacterium abscessus is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As M. abscessus possesses multiple mechanisms of drug resistance, treatments of M. abscessus are of poor efficacy. Therefore, there is an urgent need for new therapeutic [...] Read more.
Mycobacterium abscessus is an emerging health risk to immunocompromised individuals and to people with pre-existing pulmonary conditions. As M. abscessus possesses multiple mechanisms of drug resistance, treatments of M. abscessus are of poor efficacy. Therefore, there is an urgent need for new therapeutic strategies targeting M. abscessus. We describe an experimental system for screening of compounds for their antimicrobial activity against intracellular M. abscessus using flow cytometry and imaging flow cytometry. The assay allows simultaneous analysis of multiple parameters, such as proportion of infected host cells, bacterial load per host cell from the infected population, and host cell viability. We verified the suitability of this method using two antibiotics with known activity against M. abscessus: clarithromycin and amikacin. Our analysis revealed a high degree of infection heterogeneity, which correlated with host cell size. A higher proportion of the larger host cells is infected with M. abscessus as compared to smaller host cells, and infected larger cells have higher intracellular bacterial burden than infected smaller cells. Clarithromycin treatment has a more pronounced effect on smaller host cells than on bigger host cells, suggesting that heterogeneity within the host cell population has an effect on antibiotic susceptibility of intracellular bacteria. Full article
(This article belongs to the Special Issue Mycobacterial Infections and Therapy)
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Article
Prevalence of Antibiotic-Resistant Pulmonary Tuberculosis in Bangladesh: A Systematic Review and Meta-Analysis
Antibiotics 2020, 9(10), 710; https://doi.org/10.3390/antibiotics9100710 - 17 Oct 2020
Cited by 3 | Viewed by 1796
Abstract
Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, [...] Read more.
Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5–57.1], 14.3% [95% CI: 11.4–17.2], 22.2% [95% CI: 18.8–25.7], 7.7% [95% CI: 5.6–9.7], and 0.3% [95% CI: 0.0–1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended. Full article
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Article
Antibiotic Resistance of Human Periodontal Pathogen Parvimonas micra Over 10 Years
Antibiotics 2020, 9(10), 709; https://doi.org/10.3390/antibiotics9100709 - 17 Oct 2020
Cited by 1 | Viewed by 927
Abstract
Changes were evaluated over 10 years in the in vitro resistance of human periodontopathic strains of Parvimonas micra to four antibiotics. Subgingival biofilms culture positive for P. micra from 300 United States adults with severe periodontitis in 2006, and from a similar group [...] Read more.
Changes were evaluated over 10 years in the in vitro resistance of human periodontopathic strains of Parvimonas micra to four antibiotics. Subgingival biofilms culture positive for P. micra from 300 United States adults with severe periodontitis in 2006, and from a similar group of 300 patients in 2016, were plated onto anaerobically incubated enriched Brucella blood agar alone, or supplemented with either doxycycline (4 mg/L), clindamycin (4 mg/L), amoxicillin (8 mg/L), or metronidazole (16 mg/L). P. micra growth on antibiotic-supplemented media indicated in vitro resistance to the evaluated antibiotic concentration. P. micra resistance was significantly more frequent among patients in 2016, as compared to 2006, for doxycycline (11.3% vs. 0.3% patients; 37.7-fold increase), and clindamycin (47.3% vs. 2.0% patients; 23.7-fold increase) (both p < 0.001), whereas resistance to amoxicillin (2.3% vs. 1.0% patients) and metronidazole (0% vs. 0.3% patients) remained low and statistically unchanged between the two patient groups (p-values > 0.05). No P. micra isolates in 2006 or 2016 were jointly resistant in vitro to both amoxicillin and metronidazole. The alarming increases in subgingival P. micra resistance to doxycycline and clindamycin raise serious questions about the empiric use of these antibiotics, either locally or systemically, in the treatment of United States periodontitis patients harboring subgingival P. micra. Full article
(This article belongs to the Special Issue Antibiotic Treatment of Oral Infections)
Article
Prevalence and Epidemiology of Multidrug-Resistant Pathogens in the Food Chain and the Urban Environment in Northwestern Germany
Antibiotics 2020, 9(10), 708; https://doi.org/10.3390/antibiotics9100708 - 16 Oct 2020
Cited by 2 | Viewed by 978
Abstract
The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales [...] Read more.
The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales (Col-E), as well as vancomycin-resistant enterococci (VRE). In total, 505 samples from four stages of meat production, i.e., slaughterhouses, meat-processing plants, fresh food products and the urban environment, were collected in northwestern Germany in 2018/2019 and screened for the presence of MDRB using both culture-based and PCR-based techniques. We detected genes encoding for carbapenemases in 9–56% (blaOXA-48, blaKPC, blaNDM, blaVIM) and colistin resistance-encoding mcr genes in 9–26% of the samples from all stages. Culture-based analysis found CPE and VRE only in environmental samples (11% and 7%, respectively), but Col-E and ESBL-producers in 1–7% and 12–46% of samples from all stages, respectively. Overall, our results showed that ESBL-producers and mcr-carrying Col-E were common in food-producing animals at slaughterhouses, in meat-processing plants and in food items at retail, while CPE and VRE were only found in the environment. The discrepancy between detected carbapenemase genes and isolated CPE emphasizes the need for more sensitive detection methods for CPE monitoring. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Is Antimicrobial Dosing Adjustment Associated with Better Outcomes in Patients with Severe Obesity and Bloodstream Infections? An Exploratory Study
Antibiotics 2020, 9(10), 707; https://doi.org/10.3390/antibiotics9100707 - 16 Oct 2020
Cited by 1 | Viewed by 933
Abstract
The impact of adjusted treatment on clinical outcomes in patients with severe obesity is unclear. This study included adults with severe obesity admitted for bloodstream infections between 2005 and 2015. The patients were grouped according to the percentage of the appropriateness of the [...] Read more.
The impact of adjusted treatment on clinical outcomes in patients with severe obesity is unclear. This study included adults with severe obesity admitted for bloodstream infections between 2005 and 2015. The patients were grouped according to the percentage of the appropriateness of the dosage of their antimicrobial treatment: 80–100% = good, 20–79% = moderate, and 0–19% = poor. The association between antimicrobial adjustment and a composite of unfavourable outcomes [intensive care unit stay ≥72 h, duration of sepsis >3 days, length of stay ≥7 days or all-cause 30-day mortality] was assessed using logistic regression. Of 110 included episodes, the adjustment was rated good in 47 (43%) episodes, moderate in 31 (28%), and poor in 32 (29%). Older age, Pitt bacteremia score ≥2, sepsis on day 1, and infection site were independent risk factors for unfavourable outcomes. The level of appropriateness was not associated with unfavourable outcomes. The number of antimicrobials, consultation with an infectious disease specialist, blood urea nitrogen 7–10.9 mmol/L, and hemodialysis were significantly associated with adjusted antimicrobial dosing. While the severity of the infection had a substantial impact on the measured outcomes, we did not find an association between dosing optimization and better outcomes. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 1st Volume)
Review
Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors
Antibiotics 2020, 9(10), 706; https://doi.org/10.3390/antibiotics9100706 - 16 Oct 2020
Cited by 7 | Viewed by 1223
Abstract
The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in [...] Read more.
The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)
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Article
Investigation of Outbreaks of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae in Three Neonatal Intensive Care Units Using Whole Genome Sequencing
Antibiotics 2020, 9(10), 705; https://doi.org/10.3390/antibiotics9100705 - 16 Oct 2020
Cited by 3 | Viewed by 791
Abstract
Infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are on a constant rise and are a noted cause of outbreaks in neonatal intensive care units (NICUs). We used whole genome sequencing (WGS) to investigate the epidemiology of consecutive and overlapping outbreaks caused by [...] Read more.
Infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are on a constant rise and are a noted cause of outbreaks in neonatal intensive care units (NICUs). We used whole genome sequencing (WGS) to investigate the epidemiology of consecutive and overlapping outbreaks caused by ESBL-KP in NICUs in three hospitals in close proximity. Clonality of 43 ESBL-KP isolates from 40 patients was determined by BOX-PCR. Short-read sequencing was performed on representative isolates from each clone. The dominant clones from each NICU were sequenced using long-read sequencing. Bioinformatics methods were used to define multilocus sequence type (MLST), analyze plasmid content, resistomes, and virulence factors. In each NICU, we found a unique dominant clone (ST985, ST37, and ST35), each belonging to a distinct sequence type (ST), as well as satellite clones. A satellite strain in NICU-2 (ST35) was the dominant strain in NICU-3, where it was isolated four weeks later, suggesting transmission. NICU-1- and NICU-2-dominant strains had blaCTX-M-15 carried on a similar transposable element (Tn3-ISEcp1) but at different locations: on a plasmid and on the chromosome, respectively. We concluded that the overlapping ESBL-KP outbreaks were a combination of clonal transmission within NICUs, possible transposable element transmission between NICUs, and repeated importation of ESBL-KP from the community. Full article
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Article
A Qualitative Study of Pregnant Women’s Perspectives on Antibiotic Use for Mom and Child: Implications for Developing Tailored Health Education Interventions
Antibiotics 2020, 9(10), 704; https://doi.org/10.3390/antibiotics9100704 - 15 Oct 2020
Cited by 3 | Viewed by 1505
Abstract
The overutilization of antibiotics during pregnancy and early life are associated with adverse health outcomes for mothers and infants. In this study, we explored pregnant women’s opinions and concerns of antibiotics and how perceptions may affect their health-related decision-making. We conducted 18 in-depth, [...] Read more.
The overutilization of antibiotics during pregnancy and early life are associated with adverse health outcomes for mothers and infants. In this study, we explored pregnant women’s opinions and concerns of antibiotics and how perceptions may affect their health-related decision-making. We conducted 18 in-depth, semi-structured interviews with pregnant women and used the Health Belief Model (HBM) as a framework to analyze the data. We found that mothers generally understood the benefits of antibiotics and were aware that antibiotics are clinically effective for treating bacterial infections. Importantly, perceived barriers related to antibiotic use included concerns regarding the impact of antibiotics on breastfeeding efficacy, microbial health, and societal factors such as antimicrobial resistance. The prescription of antibiotics by a healthcare provider was a cue to action for women, as they trusted providers to recommend medications that were safe for them and their infants. Overall, mothers shared that receiving education on the effects of antibiotics would improve their self-efficacy and decision-making surrounding the use of antibiotics for treating illness. Implications for tailored perinatal health education interventions to enhance antibiotic use, knowledge, and decision-making are discussed. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Article
The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status
Antibiotics 2020, 9(10), 703; https://doi.org/10.3390/antibiotics9100703 - 15 Oct 2020
Cited by 1 | Viewed by 983
Abstract
The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox [...] Read more.
The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensisahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors. Full article
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Review
Alternative Anti-Infective Treatments to Traditional Antibiotherapy against Staphylococcal Veterinary Pathogens
Antibiotics 2020, 9(10), 702; https://doi.org/10.3390/antibiotics9100702 - 15 Oct 2020
Cited by 2 | Viewed by 1050
Abstract
The genus Staphylococcus encompasses many species that may be pathogenic to both humans and farm animals. These bacteria have the potential to acquire multiple resistant traits to the antimicrobials currently used in the veterinary or medical settings. These pathogens may commonly cause zoonoses, [...] Read more.
The genus Staphylococcus encompasses many species that may be pathogenic to both humans and farm animals. These bacteria have the potential to acquire multiple resistant traits to the antimicrobials currently used in the veterinary or medical settings. These pathogens may commonly cause zoonoses, and the infections they cause are becoming difficult to treat due to antimicrobial resistance. Therefore, the development of novel alternative treatments to traditional antibiotherapy has gained interest in recent years. Here, we reviewed the most promising therapeutic strategies developed to control staphylococcal infections in the veterinary field to overcome antibiotic resistance. Full article
Article
Antibiogram Profiles and Risk Factors for Multidrug Resistance of Salmonella enterica Recovered from Village Chickens (Gallus gallus domesticus Linnaeus) and Other Environmental Sources in the Central and Southern Peninsular Malaysia
Antibiotics 2020, 9(10), 701; https://doi.org/10.3390/antibiotics9100701 - 15 Oct 2020
Cited by 4 | Viewed by 1227
Abstract
The emergence of multidrug resistance (MDR), including colistin resistance, among Enterobacteriaceae recovered from food animals poses a serious public health threat because of the potential transmission of these resistant variants to humans along the food chain. Village chickens or Ayam Kampung are free-range [...] Read more.
The emergence of multidrug resistance (MDR), including colistin resistance, among Enterobacteriaceae recovered from food animals poses a serious public health threat because of the potential transmission of these resistant variants to humans along the food chain. Village chickens or Ayam Kampung are free-range birds and are preferred by a growing number of consumers who consider these chickens to be organic and more wholesome. The current study investigates the antibiogram profiles of Salmonella isolates recovered from village chicken flocks in South-central Peninsular Malaysia. A total of 34 isolates belonging to eight serotypes isolated from village chickens were screened for resistance towards antimicrobials including colistin according to the WHO and OIE recommendations of critical antibiotics. S. Weltevreden accounted for 20.6% of total isolates, followed by serovars Typhimurium and Agona (17.6%). The majority of isolates (73.5%) demonstrated resistance to one or more antimicrobials. Eight isolates (23.5%) were resistant to ≥3 antimicrobial classes. Colistin resistance (minimum inhibitory concentrations: 4–16 mg/L) was detected among five isolates (14.7%), including S. Weltevreden, S. Albany, S. Typhimurium, and Salmonella spp. Univariable analysis of risk factors likely to influence the occurrence of MDR Salmonella revealed that the flock size, poultry production system, and use of antibiotics in the farm were not significantly (p > 0.05) associated with MDR Salmonella. The current study highlights that MDR Salmonella occur at a lower level in village chickens compared to that found in live commercial chickens. However, MDR remains a problem even among free-range chickens with minimal exposure to antibiotics. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Article
Dalbavancin in the Treatment of Bacteremia and Endocarditis in People with Barriers to Standard Care
Antibiotics 2020, 9(10), 700; https://doi.org/10.3390/antibiotics9100700 - 15 Oct 2020
Cited by 7 | Viewed by 1255
Abstract
Introduction: Dalbavancin is an antibiotic administered by intravenous infusion weekly or bi-weekly and is currently FDA-approved only for treatment of skin and soft-tissue infections. It has shown promise, but is not considered the standard of care, for bacteremia and infective endocarditis (IE), which [...] Read more.
Introduction: Dalbavancin is an antibiotic administered by intravenous infusion weekly or bi-weekly and is currently FDA-approved only for treatment of skin and soft-tissue infections. It has shown promise, but is not considered the standard of care, for bacteremia and infective endocarditis (IE), which typically require outpatient parenteral antibiotic therapy (OPAT) for prolonged durations. People who inject drugs (PWID) with bacteremia or IE are often perceived as having barriers to OPAT and standard daily-administered antibiotics, prompting off-label use of dalbavancin in this population. Methods: A retrospective review of adult patients receiving at least one dose of dalbavancin for bacteremia or IE was conducted between 1 November 2017 and 31 October 2019. Outcomes and reasons for use of dalbavancin were recorded, including specific barriers to standard therapy. Results: Stated reasons for dalbavancin use in the 18 patients identified included active injection drug use (50%), inability to arrange standard OPAT due to patient adherence or inability to place in skilled nursing facility (SNF) (22%), risk for additional infections or other morbidity with OPAT (22%), and patient preference (6%). In 11 patients (61%) SNF placement was not attempted due to behavioral issues or patient declination. There were five patients who did not complete their intended course of treatment (28%). At 90 days, eight patients (44%) achieved a clinical or biologic cure, six (33%) failed treatment, and four (22%) were lost to follow-up. Conclusion: Dalbavancin may have a role as salvage therapy in the treatment of IE and bacteremia in PWID who have significant barriers to standard treatment. Full article
Review
The Hydric Environment: A Hub for Clinically Relevant Carbapenemase Encoding Genes
Antibiotics 2020, 9(10), 699; https://doi.org/10.3390/antibiotics9100699 - 15 Oct 2020
Cited by 1 | Viewed by 882
Abstract
Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing Enterobacterales (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is [...] Read more.
Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing Enterobacterales (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is attributed in part to its location onto mobile genetic elements. During the last decade, carbapenemase producing bacteria have been isolated from non-human sources including the aquatic environment. Aquatic ecosystems are particularly impacted by anthropic activities, which conduce to a bidirectional exchange between aquatic environments and human beings and therefore the aquatic environment may constitute a hub for CPE and CEG. More recently, the isolation of autochtonous aquatic bacteria carrying acquired CEG have been reported and suggest that CEG exchange by horizontal gene transfer occurred between allochtonous and autochtonous bacteria. Hence, aquatic environment plays a central role in persistence, dissemination and emergence of CEG both within environmental ecosystem and human beings, and deserves to be studied with particular attention. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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Article
Comparative Evaluation of qnrA, qnrB, and qnrS Genes in Enterobacteriaceae Ciprofloxacin-Resistant Cases, in Swine Units and a Hospital from Western Romania
Antibiotics 2020, 9(10), 698; https://doi.org/10.3390/antibiotics9100698 - 14 Oct 2020
Cited by 4 | Viewed by 996
Abstract
Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans [...] Read more.
Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA (E. coli) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids’ migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs (p > 0.05). The presence of plasmids qnrA, qnrB, and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer. Full article
Article
Antiviral Effects of Lindera obtusiloba Leaf Extract on Murine Norovirus-1 (MNV-1), a Human Norovirus Surrogate, and Potential Application to Model Foods
Antibiotics 2020, 9(10), 697; https://doi.org/10.3390/antibiotics9100697 - 14 Oct 2020
Cited by 1 | Viewed by 995
Abstract
Noroviruses are the leading cause of acute gastroenteritis and food poisoning worldwide. In this study, we investigated the anti-noroviral activity of Lindera obtusiloba leaf extract (LOLE) using murine norovirus (MNV-1), a surrogate of human norovirus. Preincubation of MNV-1 with LOLE at 4, 8, [...] Read more.
Noroviruses are the leading cause of acute gastroenteritis and food poisoning worldwide. In this study, we investigated the anti-noroviral activity of Lindera obtusiloba leaf extract (LOLE) using murine norovirus (MNV-1), a surrogate of human norovirus. Preincubation of MNV-1 with LOLE at 4, 8, or 12 mg/mL for 1 h at 25 °C significantly reduced viral infectivity, by 51.8%, 64.1%, and 71.2%, respectively. Among LOLE single compounds, β-pinene (49.7%), α-phellandrene (26.2%), and (+)-limonene (17.0%) demonstrated significant inhibitory effects on viral infectivity after pretreatment with MNV-1, suggesting that the anti-noroviral effects of LOLE may be due to the synergetic activity of several compounds, with β-pinene as a key molecule. The inhibitory effect of LOLE was tested on the edible surfaces of lettuce, cabbage, and oysters, as well as on stainless steel. After one hour of incubation at 25°C, LOLE (12 mg/mL) pretreatment significantly reduced MNV-1 plaque formation on lettuce (76.4%), cabbage (60.0%), oyster (38.2%), and stainless-steel (62.8%). These results suggest that LOLE effectively inhibits norovirus on food and metal surfaces. In summary, LOLE, including β-pinene, may inactivate norovirus and could be used as a natural agent promoting food safety and hygiene. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Essential Oils)
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Article
Dalbavancin, Vancomycin and Daptomycin Alone and in Combination with Cefazolin against Resistant Phenotypes of Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model
Antibiotics 2020, 9(10), 696; https://doi.org/10.3390/antibiotics9100696 - 14 Oct 2020
Cited by 4 | Viewed by 1516
Abstract
The most efficacious antimicrobial therapy to aid in the successful elimination of resistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of S. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in combination with cefazolin (CFZ). [...] Read more.
The most efficacious antimicrobial therapy to aid in the successful elimination of resistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of S. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in combination with cefazolin (CFZ). The objective of this study was to observe whether there was a therapeutic improvement in adding a beta-lactam to a glycopeptide, lipopeptide, or a lipoglycopeptide. We completed a series of in vitro tests including minimum inhibitory concentration testing (MIC) of the antimicrobials in combination, time-kill analysis (TKA), and a 168 h (7-day) one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model on two daptomycin non-susceptible (DNS), vancomycin intermediate S. aureus strains (VISA), D712 and 6913. Results from our MIC testing demonstrated a minimum 2-fold and a maximum 32-fold reduction in MIC values for DAL, VAN, and DAP in combination with CFZ, in contrast to either agent used alone. The TKAs completed on four strains paralleled the enhanced activity demonstrated via the combination MICs. In the one-compartment PK/PD models, the combination of DAP plus CFZ or VAN plus CFZ resulted in a significant (p < 0.001) improvement in bactericidal activity and overall reduction in CFU/ml over the 7-day period. While the addition of CFZ to DAL improved time to bactericidal activity, DAL alone demonstrated equal and more sustained overall activity compared to all other treatments. The use of DAL alone, with or without CFZ and the combinations of VAN or DAP with CFZ appear to result in increased bactericidal activity against various recalcitrant S. aureus phenotypes. Full article
(This article belongs to the Special Issue Methicillin-Resistant Staphylococci)
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Article
Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors
Antibiotics 2020, 9(10), 695; https://doi.org/10.3390/antibiotics9100695 - 14 Oct 2020
Cited by 5 | Viewed by 981
Abstract
The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,b [...] Read more.
The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,ba,b) were synthesized by a series of various reactions, starting with 3-aminothieno[2,3-b]pyridine-2-carboxamides (1a,b). Condensation of compounds 1a,b with cyclohexanone gave 1’H-spiro[cyclohexane-1,2’-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin]-4’(3’H)-ones (2a,b), which in turn were utilized to afford the target 4-substituted derivatives (3a,b8a,b). In vitro antibacterial activity evaluations of all the new compounds (2a,b8a,b) were performed against six strains of Gram-negative and Gram-positive bacteria. The target compounds showed significant antibacterial activity, especially against Gram-negative strains. Moreover, the compounds (2a,b; 3a,b; 4a,b; and 5a,b) that exhibited potent activity against Escherichia coli were selected to screen their inhibitory activity against Escherichia coli topoisomerase II (DNA gyrase and topoisomerase IV) enzymes. Compounds 4a and 4b showed potent dual inhibition of the two enzymes with IC50 values of 3.44 µΜ and 5.77 µΜ against DNA gyrase and 14.46 µΜ and 14.89 µΜ against topoisomerase IV, respectively. In addition, docking studies were carried out to give insight into the binding mode of the tested compounds within the E. coli DNA gyrase B active site compared with novobiocin. Full article
(This article belongs to the Special Issue Design and Synthesis of Antibacterial Heterocycle-Based Compounds)
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Review
Impetigo Animal Models: A Review of Their Feasibility and Clinical Utility for Therapeutic Appraisal of Investigational Drug Candidates
Antibiotics 2020, 9(10), 694; https://doi.org/10.3390/antibiotics9100694 - 14 Oct 2020
Cited by 1 | Viewed by 1210
Abstract
Impetigo (school sores), a superficial skin infection commonly seen in children, is caused by the gram-positive bacteria Staphylococcus aureus and/or Streptococcus pyogenes. Antibiotic treatments, often topical, are used as the first-line therapy for impetigo. The efficacy of potential new antimicrobial compounds is [...] Read more.
Impetigo (school sores), a superficial skin infection commonly seen in children, is caused by the gram-positive bacteria Staphylococcus aureus and/or Streptococcus pyogenes. Antibiotic treatments, often topical, are used as the first-line therapy for impetigo. The efficacy of potential new antimicrobial compounds is first tested in in vitro studies and, if effective, followed by in vivo studies using animal models and/or humans. Animal models are critical means for investigating potential therapeutics and characterizing their safety profile prior to human trials. Although several reviews of animal models for skin infections have been published, there is a lack of a comprehensive review of animal models simulating impetigo for the selection of therapeutic drug candidates. This review critically examines the existing animal models for impetigo and their feasibility for testing the in vivo efficacy of topical treatments for impetigo and other superficial bacterial skin infections. Full article
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