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Antibiotics
Volume 12
Issue 1
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Antibiotics, Volume 12, Issue 1 (January 2023) – 184 articles

Cover Story (view full-size image): The synthesis and antiribosomal and antibacterial activity of both anomers of a novel apralog, 5-O-(5-amino-3-C-dimethylaminopropyl-D-ribofuranosyl)apramycin, are reported. Both anomers show excellent activity for the inhibition of bacterial ribosomes and that of MRSA and various wild-type Gram-negative pathogens. The new compounds retain activity in the presence of the aminoglycoside phosphoryltransferase aminoglycoside modifying enzymes that act on the primary hydroxy group of typical 4,5-(2-deoxystreptamine)-type aminoglycoside and related apramycin derivatives. Unexpectedly, the two anomers have comparable activity for the inhibition of both bacterial ribosomes and the various bacterial strains tested. View this paper
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17 pages, 895 KiB  
Review
Antimicrobial Peptides against Bacterial Pathogens: Innovative Delivery Nanosystems for Pharmaceutical Applications
by Esther Imperlini, Federica Massaro and Francesco Buonocore
Antibiotics 2023, 12(1), 184; https://doi.org/10.3390/antibiotics12010184 - 16 Jan 2023
Cited by 13 | Viewed by 4592
Abstract
The introduction of antibiotics has revolutionized the treatment and prevention of microbial infections. However, the global spread of pathogens resistant to available antibiotics is a major concern. Recently, the WHO has updated the priority list of multidrug-resistant (MDR) species for which the discovery [...] Read more.
The introduction of antibiotics has revolutionized the treatment and prevention of microbial infections. However, the global spread of pathogens resistant to available antibiotics is a major concern. Recently, the WHO has updated the priority list of multidrug-resistant (MDR) species for which the discovery of new therapeutics is urgently needed. In this scenario, antimicrobial peptides (AMPs) are a new potential alternative to conventional antibiotics, as they show a low risk of developing antimicrobial resistance, thus preventing MDR bacterial infections. However, there are limitations and challenges related to the clinical impact of AMPs, as well as great scientific efforts to find solutions aimed at improving their biological activity, in vivo stability, and bioavailability by reducing the eventual toxicity. To overcome some of these issues, different types of nanoparticles (NPs) have been developed for AMP delivery over the last decades. In this review, we provide an update on recent nanosystems applied to AMPs, with special attention on their potential pharmaceutical applications for the treatment of bacterial infections. Among lipid nanomaterials, solid lipid NPs and lipid nanocapsules have been employed to enhance AMP solubility and protect peptides from proteolytic degradation. In addition, polymeric NPs, particularly nanogels, are able to help in reducing AMP toxicity and also increasing AMP loading. To boost AMP activity instead, mesoporous silica or gold NPs can be selected due to their easy surface functionalization. They have been also used as nanocarriers for different AMP combinations, thus synergistically potentiating their action against pathogens. Full article
(This article belongs to the Special Issue Reviews on Antimicrobial Peptides)
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9 pages, 680 KiB  
Article
Fluoroquinolones Are Useful as Directed Treatment for Complicated UTI in a Setting with a High Prevalence of Quinolone-Resistant Microorganisms
by Arturo Artero, Ian López-Cruz, Laura Piles, Juan Alberola, José María Eiros, Sofia Salavert and Manuel Madrazo
Antibiotics 2023, 12(1), 183; https://doi.org/10.3390/antibiotics12010183 - 16 Jan 2023
Cited by 1 | Viewed by 4120
Abstract
Fluoroquinolones (FQs) have been widely used for treating urinary tract infections (UTIs); however, the increasing emergence of resistant strains has compromised their use. We aimed to know the usefulness of FQs for the treatment of community-acquired UTI in a setting with a high [...] Read more.
Fluoroquinolones (FQs) have been widely used for treating urinary tract infections (UTIs); however, the increasing emergence of resistant strains has compromised their use. We aimed to know the usefulness of FQs for the treatment of community-acquired UTI in a setting with a high prevalence of fluoroquinolone-resistant microorganisms. A prospective observational study of patients diagnosed with community-acquired UTI was conducted, in which their outcomes according to whether they had FQs or not in their empirical and directed treatments were compared. A multivariate analysis was performed to identify risk factors for UTIs due to ciprofloxacin-resistant microorganisms. A total of 419 patients were included; 162 (38.7%) patients were treated with FQs, as empirical treatment in 27 (6.4%), and as directed treatment in 135 (32.2%). In-hospital mortality (2.2% vs. 6.6%, p 0.044) and 30-day mortality (4.4 vs. 11%, p 0.028) were both lower in the group of patients directly treated with FQ, while there were no differences when FQs were used as empirical treatment. A total of 37.2% of the cases were resistant to ciprofloxacin, which was associated with healthcare-associated UTI (OR 2.7, 95% CI 2–3.7) and prior exposure to FQs (OR 2.7, 95 % CI 1.9–3.7). In conclusion, our findings show that in a setting with a high prevalence of community-acquired UTI caused by quinolone-resistant microorganisms, FQs as directed treatment for community-acquired UTI were associated with better outcomes than other antibiotics, but their use as empirical treatment is not indicated, even in those cases without risk factors for quinolones resistance. Full article
(This article belongs to the Special Issue The Interplay between Urinary Tract Infections and Antimicrobial Resistance)
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14 pages, 1041 KiB  
Article
Antibacterial Activity of Selected Essential Oils against Foodborne Pathogens and Their Application in Fresh Turkey Sausages
by Branislav Šojić, Predrag Ikonić, Sunčica Kocić-Tanackov, Tatjana Peulić, Nemanja Teslić, Miloš Županjac, Ivana Lončarević, Zoran Zeković, Milica Popović, Stefan Vidaković and Branimir Pavlić
Antibiotics 2023, 12(1), 182; https://doi.org/10.3390/antibiotics12010182 - 16 Jan 2023
Cited by 11 | Viewed by 2756
Abstract
Essential oils (EOs) isolated from different plant materials, namely Origanum majorana L., Satureja hortensis L., and Satureja montana L. (OMEO, SHEO, and SMEO, respectively), were used in fresh turkey sausage processing. The chemical composition and in vitro antimicrobial potential of selected EOs and [...] Read more.
Essential oils (EOs) isolated from different plant materials, namely Origanum majorana L., Satureja hortensis L., and Satureja montana L. (OMEO, SHEO, and SMEO, respectively), were used in fresh turkey sausage processing. The chemical composition and in vitro antimicrobial potential of selected EOs and their mixture were determined. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against foodborne pathogens (Escherichia coli, Salmonella Enteritidis, and Listeria monocytogenes) ranged in the interval of 0.44–7.1 µL/mL. Fresh turkey sausages were produced with EOs addition and marked as follows: TOMEO—0.150 µL/g OMEO; TSHEO—0.150 µL/g SHEO; TSMEO—0.150 µL/g SMEO; TEOM—0.050 µL/g OMEO, 0.050 µL/g SHEO and 0.050 µL/g SMEO, and control (C) (without EOs). Microbiological profile and biogenic amines content in fresh turkey sausages were recorded during storage. The selected EOs and their mixture efficiently reduced bacterial growth and biogenic amines formation and accumulation. The lowest Enterobacteriaceae count and total biogenic amine (BA) concentration were determined through treatment TSHEO. The results of this study show that selected EOs could be useful in fresh turkey sausage processing in order to improve safety and shelf-life. Full article
(This article belongs to the Special Issue Advances in the Discovery of Novel Antimicrobial Agents in Nature and Their Applications)
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25 pages, 3462 KiB  
Article
Preparation of Bioactive De-Chlorophyll Rhein-Rich Senna alata Extract
by Wah Wah Aung, Kanokpon Panich, Suchawalee Watthanophas, Sutada Naridsirikul, Juthaporn Ponphaiboon, Wantanwa Krongrawa, Pattranit Kulpicheswanich, Sontaya Limmatvapirat and Chutima Limmatvapirat
Antibiotics 2023, 12(1), 181; https://doi.org/10.3390/antibiotics12010181 - 16 Jan 2023
Cited by 6 | Viewed by 3296
Abstract
Senna alata leaves display various biological activities as a result of their rhein and phenolic composition. The objective of this study was to develop bioactive de-chlorophyll rhein-rich S. alata extracts. The rhein content was quantified using a validated high-performance liquid chromatography–diode array detection [...] Read more.
Senna alata leaves display various biological activities as a result of their rhein and phenolic composition. The objective of this study was to develop bioactive de-chlorophyll rhein-rich S. alata extracts. The rhein content was quantified using a validated high-performance liquid chromatography–diode array detection (HPLC–DAD) method. The best process parameters for maximizing rhein were established using ultrasound-assisted extraction (UAE). The optimal conditions for the parameters were determined using the Box–Behnken design (BBD); 95% v/v ethanol was used as the extraction solvent at 59.52 °C for 18.4 min with a solvent-to-solid ratio of 25.48:1 (mL/g) to obtain the predicted value of rhein at 10.44 mg/g extract. However, the color of the rhein-rich extract remained dark brown. For the removal of chlorophyll, liquid–liquid extraction with vegetable oils and adsorption with bleaching agents were employed. The bleaching agents were significantly more effective at removing chlorophyll and had less of an effect on the reduction in rhein content than vegetable oils. The presence of rhein and phenolics in the de-chlorophyll extracts might be responsible for their antioxidant, anti-inflammatory, and antibacterial activities. These findings indicate that rhein-rich extract and its de-chlorophyll extracts possess sufficient biological activities for the further development of cosmeceuticals and pharmaceuticals. Full article
(This article belongs to the Special Issue Antioxidant and Antibacterial Activity of Plant Extracts)
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33 pages, 17163 KiB  
Review
Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria
by Nina Compagne, Anais Vieira Da Cruz, Reinke T. Müller, Ruben C. Hartkoorn, Marion Flipo and Klaas M. Pos
Antibiotics 2023, 12(1), 180; https://doi.org/10.3390/antibiotics12010180 - 15 Jan 2023
Cited by 40 | Viewed by 6972
Abstract
Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely [...] Read more.
Antimicrobial resistance (AMR) has become a major problem in public health leading to an estimated 4.95 million deaths in 2019. The selective pressure caused by the massive and repeated use of antibiotics has led to bacterial strains that are partially or even entirely resistant to known antibiotics. AMR is caused by several mechanisms, among which the (over)expression of multidrug efflux pumps plays a central role. Multidrug efflux pumps are transmembrane transporters, naturally expressed by Gram-negative bacteria, able to extrude and confer resistance to several classes of antibiotics. Targeting them would be an effective way to revive various options for treatment. Many efflux pump inhibitors (EPIs) have been described in the literature; however, none of them have entered clinical trials to date. This review presents eight families of EPIs active against Escherichia coli or Pseudomonas aeruginosa. Structure–activity relationships, chemical synthesis, in vitro and in vivo activities, and pharmacological properties are reported. Their binding sites and their mechanisms of action are also analyzed comparatively. Full article
(This article belongs to the Special Issue Efflux Pumps in Bacteria: What They Do and How We Can Stop Them)
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21 pages, 4060 KiB  
Article
Chemical Profile, Anti-Microbial and Anti-Inflammaging Activities of Santolina rosmarinifolia L. Essential Oil from Portugal
by Jorge M. Alves-Silva, Maria José Gonçalves, Ana Silva, Carlos Cavaleiro, Maria Teresa Cruz and Lígia Salgueiro
Antibiotics 2023, 12(1), 179; https://doi.org/10.3390/antibiotics12010179 - 15 Jan 2023
Cited by 6 | Viewed by 2975
Abstract
Fungal infections and the accompanying inflammatory responses are associated with great morbidity and mortality due to the frequent relapses triggered by an increased resistance to antifungal agents. Furthermore, this inflammatory state can be exacerbated during inflammaging and cellular senescence. Essential oils (EO) are [...] Read more.
Fungal infections and the accompanying inflammatory responses are associated with great morbidity and mortality due to the frequent relapses triggered by an increased resistance to antifungal agents. Furthermore, this inflammatory state can be exacerbated during inflammaging and cellular senescence. Essential oils (EO) are receiving increasing interest in the field of drug discovery due to their lipophilic nature and complex composition, making them suitable candidates in the development of new antifungal drugs and modulators of numerous molecular targets. This work chemically characterized the EO from Santolina rosmarinifolia L., collected in Setúbal (Portugal), and assessed its antifungal potential by determining its minimum inhibitory (MIC) and minimum lethal (MLC) concentration in accordance with the Clinical Laboratory Standard Guidelines (CLSI) guidelines, as well as its effect on several Candida albicans virulence factors. The anti-inflammatory effect was unveiled using lipopolysaccharide (LPS)-stimulated macrophages by assessing several pro-inflammatory mediators. The wound healing and anti-senescence potential of the EO was also disclosed. The EO was mainly characterized by β-pinene (29.6%), borneol (16.9%), myrcene (15.4%) and limonene (5.7%). It showed a strong antifungal effect against yeasts and filamentous fungi (MIC = 0.07–0.29 mg/mL). Furthermore, it inhibited dimorphic transition (MIC/16), decreased biofilm formation with a preeminent effect after 24 h (MIC/2) and disrupted preformed biofilms in C. albicans. Additionally, the EO decreased nitric oxide (NO) release (IC50 = 0.52 mg/mL) and pro-IL-1β and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated macrophages, promoted wound healing (91% vs. 81% closed wound) and reduced cellular senescence (53% vs. 73% β-galactosidase-positive cells). Overall, this study highlights the relevant pharmacological properties of S. rosmarinifolia, opening new avenues for its industrial exploitation. Full article
(This article belongs to the Special Issue Antimicrobial Activities of Plant Extracts)
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16 pages, 2581 KiB  
Article
Antibacterial Activity of Biodegradable Films Incorporated with Biologically-Synthesized Silver Nanoparticles and the Evaluation of Their Migration to Chicken Meat
by Meiriele da S. das Neves, Sara Scandorieiro, Giovana N. Pereira, Jhonatan M. Ribeiro, Amedea B. Seabra, Adriana P. Dias, Fabio Yamashita, Claudia B. dos R. Martinez, Renata K. T. Kobayashi and Gerson Nakazato
Antibiotics 2023, 12(1), 178; https://doi.org/10.3390/antibiotics12010178 - 15 Jan 2023
Cited by 8 | Viewed by 2809
Abstract
The food industry has been exploring the association of polymers with nanoparticles in packaging production, and active products are essential to increase the shelf life of food and avoid contamination. Our study developed starch-poly (adipate co-terephthalate butyl) films with silver nanoparticles produced with [...] Read more.
The food industry has been exploring the association of polymers with nanoparticles in packaging production, and active products are essential to increase the shelf life of food and avoid contamination. Our study developed starch-poly (adipate co-terephthalate butyl) films with silver nanoparticles produced with Fusarium oxysporum components (bio-AgNPs), intending to control foodborne pathogens. The bio-AgNPs showed activity against different Salmonella serotypes, including multidrug-resistant Salmonella Saint Paul and Salmonella Enteritidis, with minimum bactericidal concentrations ranging from 4.24 to 16.98 µg/mL. Biodegradable films with bio-AgNPs inhibited the growth of up to 106Salmonella isolates. Silver migration from the films to chicken was analyzed using electrothermal atomic absorption spectrophotometry, and the results showed migration values (12.94 mg/kg and 3.79 mg/kg) above the limits allowed by the European Food Safety Authority (EFSA) (0.05 mg/kg). Thus, it is necessary to improve the technique to avoid the migration of silver to chicken meat, since these concentrations can be harmful. Full article
(This article belongs to the Special Issue Nanotechnology for Antimicrobials in Medicine and Agriculture)
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24 pages, 2078 KiB  
Article
A Comparative Study on Chemical Compositions and Biological Activities of Four Amazonian Ecuador Essential Oils: Curcuma longa L. (Zingiberaceae), Cymbopogon citratus (DC.) Stapf, (Poaceae), Ocimum campechianum Mill. (Lamiaceae), and Zingiber officinale Roscoe (Zingiberaceae)
by Alessandra Guerrini, Massimo Tacchini, Ilaria Chiocchio, Alessandro Grandini, Matteo Radice, Immacolata Maresca, Guglielmo Paganetto and Gianni Sacchetti
Antibiotics 2023, 12(1), 177; https://doi.org/10.3390/antibiotics12010177 - 15 Jan 2023
Cited by 9 | Viewed by 3512
Abstract
Essential oils (EOs) and their vapour phase of Curcuma longa (Zingiberaceae), Cymbopogon citratus (Poaceae), Ocimum campechianum (Lamiaceae), and Zingiber officinale (Zingiberaceae) of cultivated plants grown in an Amazonian Ecuador area were chemically characterised by Gas Chromatography-Flame Ionization Detector (GC-FID), Gas Chromatography–Mass Spectrometry (GC-MS), [...] Read more.
Essential oils (EOs) and their vapour phase of Curcuma longa (Zingiberaceae), Cymbopogon citratus (Poaceae), Ocimum campechianum (Lamiaceae), and Zingiber officinale (Zingiberaceae) of cultivated plants grown in an Amazonian Ecuador area were chemically characterised by Gas Chromatography-Flame Ionization Detector (GC-FID), Gas Chromatography–Mass Spectrometry (GC-MS), and Head Space–Gas Chromatograph-Flame Ionization Detector–Mass Spectrometry (HS-GC-FID-MS).figure The EOs analyses led to the identification of 25 compounds for C. longa (99.46% of the total; ar-turmerone: 23.35%), 18 compounds for C. citratus (99.59% of the total; geraniol: 39.43%), 19 compounds for O. campechianum (96.24% of the total; eugenol: 50.97%), and 28 for Z. officinale (98.04% of the total; α-Zingiberene: 15.45%). The Head Space fractions (HS) revealed C. longa mainly characterised by limonene and 1,8-cineole (37.35%) and α-phellandrene (32.33%); Z. officinale and C. citratus showed camphene (50.39%) and cis-Isocitral (15.27%) as the most abundant compounds, respectively. O. campechianum EO revealed a higher amount of sesquiterpenes (10.08%), mainly characterised by E-caryophyllene (4.95%), but monoterpene fraction remained the most abundant (89.94%). The EOs were tested for antioxidant, antimicrobial, and mutagen-protective properties and compared to the Thymus vulgaris EO as a positive reference. O. campechianum EO was the most effective in all the bioactivities checked. Similar results emerged from assaying the bioactivity of the vapour phase of O. campechianum EO. The antioxidant and antimicrobial activity evaluation of O. campechianum EO were repeated through HP-TLC bioautography assay, pointing out eugenol as the lead compound for bioactivity. The mutagen-protective evaluation checked through Ames’s test properly modified evidenced a better capacity of O. campechianum EO compared with the other EOs, reducing the induced mutagenicity at 0.1 mg/plate. However, even with differences in efficacy, the overall results suggest important perspectives for the functional use of the four studied EOs. Full article
(This article belongs to the Special Issue Plant Essential Oils: Chemistry, Antibacterial Activity and Perspectives of Biotechnological Applications)
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11 pages, 1385 KiB  
Article
Infection-Related Ventilator-Associated Complications in Critically Ill Patients with Trauma: A Retrospective Analysis
by Emanuele Russo, Marta Velia Antonini, Andrea Sica, Cristian Dell’Amore, Costanza Martino, Emiliano Gamberini, Luca Bissoni, Alessandro Circelli, Giuliano Bolondi, Domenico Pietro Santonastaso, Francesco Cristini, Luigi Raumer, Fausto Catena and Vanni Agnoletti
Antibiotics 2023, 12(1), 176; https://doi.org/10.3390/antibiotics12010176 - 15 Jan 2023
Cited by 5 | Viewed by 2716
Abstract
Background: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). Methods: [...] Read more.
Background: Trauma is a leading cause of death and disability. Patients with trauma undergoing invasive mechanical ventilation (IMV) are at risk for ventilator-associated events (VAEs) potentially associated with a longer duration of IMV and increased stay in the intensive care unit (ICU). Methods: We conducted a retrospective cohort study aimed to evaluate the incidence of infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneumonia (PVAP), and their characteristics among patients experiencing severe trauma that required ICU admission and IMV for at least four days. We also determined pathogens implicated in PVAP episodes and characterized the use of antimicrobial therapy. Results: In total, 88 adult patients were included in the main analysis. In this study, we observed that 29.5% of patients developed a respiratory infection during ICU stay. Among them, five patients (19.2%) suffered from respiratory infections due to multi-drug resistant bacteria. Patients who developed IVAC/PVAP presented lower total GCS (median value, 7; (IQR, 9) vs. 12.5, (IQR, 8); p = 0.068) than those who did not develop IVAC/PVAP. Conclusions: We observed that less than one-third of trauma patients fulfilling criteria for ventilator associated events developed a respiratory infection during the ICU stay. Full article
(This article belongs to the Special Issue Antibiotic Treatment on Surgical Infections)
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11 pages, 1019 KiB  
Article
Impact of the Duration of Postoperative Antibiotics on the Prognosis of Patients with Infective Endocarditis
by Jinnam Kim, Jung Ho Kim, Hi Jae Lee, Se Ju Lee, Changhyup Kim, Jung Ah Lee, Ki Hyun Lee, Won Kyung Pyo, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Seung Hyun Lee, Jun Yong Choi and Joon-Sup Yeom
Antibiotics 2023, 12(1), 173; https://doi.org/10.3390/antibiotics12010173 - 15 Jan 2023
Cited by 1 | Viewed by 2663
Abstract
Appropriate postoperative antibiotic treatment in patients with infective endocarditis (IE) reduces the risks of recurrence and mortality. However, concerns about adverse drug reactions arise due to prolonged antibiotic usage. Therefore, we compared the recurrence and mortality rates according to the duration of postoperative [...] Read more.
Appropriate postoperative antibiotic treatment in patients with infective endocarditis (IE) reduces the risks of recurrence and mortality. However, concerns about adverse drug reactions arise due to prolonged antibiotic usage. Therefore, we compared the recurrence and mortality rates according to the duration of postoperative antibiotic therapy in patients with IE. From 2005 to 2017, we retrospectively reviewed 416 patients with IE treated at a tertiary hospital in South Korea; among these, 216 patients who underwent heart valve surgery and received appropriate antibiotics were enrolled. The patients were divided into two groups based on the duration of usage of postoperative antibiotic therapy; the duration of postoperative antibiotic therapy was more than two weeks in 156 patients (72.2%) and two weeks or less in 60 patients (27.8%). The primary endpoint was IE relapse. The secondary endpoints were 1-year IE recurrence, 1-year mortality, and postoperative complication rates. The median age was 53 (interquartile range: 38–62) years. The relapse rate of IE was 0.9% (2/216). There was no statistical difference in relapse (0.0% vs. 1.3%, p = 0.379), 1-year recurrence (1.7% vs. 1.3%, p = 0.829), or 1-year mortality (10.0% vs. 5.8%, p = 0.274) between patients with postoperative antibiotic administration of two weeks or less versus more than two weeks. The duration of postoperative antibiotic therapy did not affect the 1-year mortality rate (log-rank test, p = 0.393). In conclusion, there was no statistically significant difference in recurrence, mortality, or postoperative complications according to the duration of postoperative antibiotic therapy. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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12 pages, 723 KiB  
Article
Studying the Association between Antibiotic Resistance Genes and Insertion Sequences in Metagenomes: Challenges and Pitfalls
by Lucie Galiot, Xavier C. Monger and Antony T. Vincent
Antibiotics 2023, 12(1), 175; https://doi.org/10.3390/antibiotics12010175 - 14 Jan 2023
Cited by 7 | Viewed by 2411
Abstract
Antibiotic resistance is an issue in many areas of human activity. The mobilization of antibiotic resistance genes within the bacterial community makes it difficult to study and control the phenomenon. It is known that certain insertion sequences, which are mobile genetic elements, can [...] Read more.
Antibiotic resistance is an issue in many areas of human activity. The mobilization of antibiotic resistance genes within the bacterial community makes it difficult to study and control the phenomenon. It is known that certain insertion sequences, which are mobile genetic elements, can participate in the mobilization of antibiotic resistance genes and in the expression of these genes. However, the magnitude of the contribution of insertion sequences to the mobility of antibiotic resistance genes remains understudied. In this study, the relationships between insertion sequences and antibiotic resistance genes present in the microbiome were investigated using two public datasets. The first made it possible to analyze the effects of different antibiotics in a controlled mouse model. The second dataset came from a study of the differences between conventional and organic-raised cattle. Although it was possible to find statistically significant correlations between the insertion sequences and antibiotic resistance genes in both datasets, several challenges remain to better understand the contribution of insertion sequences to the motility of antibiotic resistance genes. Obtaining more complete and less fragmented metagenomes with long-read sequencing technologies could make it possible to understand the mechanisms favoring horizontal transfers within the microbiome with greater precision. Full article
(This article belongs to the Special Issue When Communities Matter: Interplay between Mobile Genetic Elements and Antibiotic Resistance)
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16 pages, 2206 KiB  
Article
Chemical Composition, Antioxidants, Antibacterial, and Insecticidal Activities of Origanum elongatum (Bonnet) Emberger & Maire Aerial Part Essential Oil from Morocco
by Imane Tagnaout, Hannou Zerkani, Noureddine Bencheikh, Smail Amalich, Mohamed Bouhrim, Ramzi A. Mothana, Mohammed R. Alhuzani, Rachid Bouharroud, Christophe Hano and Touriya Zair
Antibiotics 2023, 12(1), 174; https://doi.org/10.3390/antibiotics12010174 - 14 Jan 2023
Cited by 10 | Viewed by 2974
Abstract
The aim of this research is to profile the chemical composition of the essential oil (EO) extracted from the aerial parts of Origanum elongatum (O. elongatum) and to evaluate its antioxidant, antibacterial and insecticidal activities on Ceratitis capitata adults. Gas chromatography [...] Read more.
The aim of this research is to profile the chemical composition of the essential oil (EO) extracted from the aerial parts of Origanum elongatum (O. elongatum) and to evaluate its antioxidant, antibacterial and insecticidal activities on Ceratitis capitata adults. Gas chromatography coupled with mass spectrometry (GC/MS) revealed a total of 27 constituents in EO of O. elongatum, which accounted for 99.08% of its constituents. Carvacrol (57.32%) was a main component, followed by p-cymene (14.70%) and γ-terpinene (9.84%). The antioxidant activity of O. elongatum EO was investigated using DPPH (1,1-diphenyl-2-picrylhydrazyl), FRAP (Ferric reducing antioxidant power), and TCA (the total antioxidant capacity) methods. This EO exhibited a remarkable antiradical and reducing power against DPPH (IC50 = 2.855 ± 0.018μL/mL), FRAP (EC0.5 = 0.124 ± 0.013µL/mL) and TCA (IC50 = 14.099 ± 0.389 mg AAE/g of the EO). The antibacterial tests in vitro, using the disc and dilution methods, were carried out on nine pathogenic bacteria isolated from the hospital patients, such as Enterococcus faecalis, Serratia fonticola, Staphylococcus aureus, Acinétobacter baumannii, Klebsiella oxytoca, Klebsiella pneumoniae sensible, E.coli sensible, E.coli resistante, and Enterobacter aerogenes. The EO demonstrated a considerable antibacterial activity with minimum inhibitory concentrations (MIC) from 2 to 8 µL/mL against all strains except Staphylococcus aureus (MIC = 32 µL/mL). Regarding the insecticidal activity, the fumigation test indicated a high efficacy (100% mortality), and a lethal dose of LD50  =  17 ± 0.53 μL/L air was found after 24 h of exposureTherefore, O. elongatum EO could be utilized as a natural antioxidant, antibiotic and biopesticides. Full article
(This article belongs to the Special Issue Antioxidant and Antibacterial Activity of Plant Extracts)
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13 pages, 1475 KiB  
Article
Burden of Hospitalizations Related to Pneumococcal Infection in Spain (2016–2020)
by Ruth Gil-Prieto, Nizar Allouch, Isabel Jimeno, Valentín Hernández-Barrera, Raquel Arguedas-Sanz and Ángel Gil-de-Miguel
Antibiotics 2023, 12(1), 172; https://doi.org/10.3390/antibiotics12010172 - 14 Jan 2023
Cited by 3 | Viewed by 2498
Abstract
Pneumococcal infection strongly contributes to morbidity and mortality in Spain. A total of 253,899 hospitalizations related to pneumococcal infection occurred from 2016 to 2020. Fifty-eight percent were men, the mean age was 67 years old, and the average length of hospitalization was 12.72 [...] Read more.
Pneumococcal infection strongly contributes to morbidity and mortality in Spain. A total of 253,899 hospitalizations related to pneumococcal infection occurred from 2016 to 2020. Fifty-eight percent were men, the mean age was 67 years old, and the average length of hospitalization was 12.72 days. The annual hospitalization rate was 10.84 hospitalizations per 10,000 population, increasing significantly with age, reaching 65.75 per 10,000 population in those aged >85 years. The hospitalization rates for pneumococcal pneumonia, sepsis, and meningitis were 2.91, 0.12, and 0.08 hospitalizations per 10,000, respectively, and reached the highest value in those aged >85 for pneumococcal pneumonia and sepsis, with 22.29 and 0.71 hospitalizations per 10,000, respectively, and in children up to 1 year old for pneumococcal meningitis, with 0.33 hospitalizations per 10,000. The total number of deaths during the study period was 35,716, with a case-fatality rate of 14.07%. For pneumococcal pneumonia, sepsis, and meningitis, the case-fatality rates were 8.47%, 23.71%, and 9.99%, respectively. The case-fatality rate increased with age and did not vary by sex. The annual cost of these hospitalizations was more than EUR 359 million. There is therefore a high burden of disease and mortality caused by pneumococcal infection in our country, especially in elderly individuals. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Streptococcus pneumoniae as a Paradigm of Respiratory Pathogen: What Is Next?)
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13 pages, 1726 KiB  
Article
Evaluation of Everolimus Activity against Mycobacterium tuberculosis Using In Vitro Models of Infection
by Delia Mercedes Bianco, Flavio De Maio, Giulia Santarelli, Ivana Palucci, Alessandro Salustri, Giada Bianchetti, Giuseppe Maulucci, Franco Citterio, Maurizio Sanguinetti, Enrica Tamburrini, Michela Sali and Giovanni Delogu
Antibiotics 2023, 12(1), 171; https://doi.org/10.3390/antibiotics12010171 - 13 Jan 2023
Cited by 5 | Viewed by 2552
Abstract
Even though Everolimus has been investigated in a phase II randomized trial as a host-directed therapy (HDT) to treat tuberculosis (TB), an oncological patient treated with Everolimus for a neuroendocrine pancreatic neoplasia developed active TB twice and a non-tuberculous mycobacterial (NTM) infection in [...] Read more.
Even though Everolimus has been investigated in a phase II randomized trial as a host-directed therapy (HDT) to treat tuberculosis (TB), an oncological patient treated with Everolimus for a neuroendocrine pancreatic neoplasia developed active TB twice and a non-tuberculous mycobacterial (NTM) infection in a year and a half time span. To investigate this interesting case, we isolated and genotypically characterized the Mycobacterium tuberculosis (Mtb) clinical strain from the patient and tested the effect of Everolimus on its viability in an axenic culture and in a peripheral blood mononuclear cell (PBMCs) infection model. To exclude strain-specific resistance, we tested the activity of Everolimus against Mtb strains of ancient and modern lineages. Furthermore, we investigated the Everolimus effect on ROS production and autophagy modulation during Mtb infection. Everolimus did not have a direct effect on mycobacteria viability and a negligible effect during Mtb infection in host cells, although it stimulated autophagy and ROS production. Despite being a biologically plausible HDT against TB, Everolimus does not exert a direct or indirect activity on Mtb. This case underlines the need for a careful approach to drug repurposing and implementation and the importance of pre-clinical experimental studies. Full article
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15 pages, 3911 KiB  
Article
Azithromycin Susceptibility Testing and Molecular Investigation of Neisseria gonorrhoeae Isolates Collected in Russia, 2020–2021
by Ilya Kandinov, Boris Shaskolskiy, Dmitry Kravtsov, Alexandra Vinokurova, Sofya Gorshkova, Alexey Kubanov, Victoria Solomka, Julia Shagabieva, Dmitry Deryabin, Ekaterina Dementieva and Dmitry Gryadunov
Antibiotics 2023, 12(1), 170; https://doi.org/10.3390/antibiotics12010170 - 13 Jan 2023
Cited by 5 | Viewed by 2678
Abstract
The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected [...] Read more.
The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected in 2020–2021, 22 isolates (13.6%) were phenotypically resistant to azithromycin. Mutations in 23S rRNA genes were found only in two isolates; erm and mefA genes were absent. Azithromycin resistance was shown to be predominantly associated with mutations in the mtrR and mtrD genes of the MtrCDE efflux pump and their mosaic alleles which may have formed due to a horizontal transfer from N. meningitidis. A total of 30 types of mtrR alleles and 10 types of mtrD alleles were identified including mosaic variants. Matching between the mtrR and mtrD alleles was revealed to indicate the cooperative molecular evolution of these genes. A link between the mtrR and mtrD alleles and NG-MAST types was found only for NG-MAST 228 and 807, typical of N. gonorrhoeae in Russia. The high level of resistance to azithromycin in Russia may be related to the spread of multiple transferable resistance to antimicrobials regardless of their use in the treatment of gonococcal infection. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Sexually Transmitted Pathogens)
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22 pages, 1918 KiB  
Article
Multidrug-Resistant ESBL-Producing E. coli in Clinical Samples from the UK
by Delveen R. Ibrahim, Christine E. R. Dodd, Dov J. Stekel, Remilekun T. Meshioye, Mathew Diggle, Michelle Lister and Jon L. Hobman
Antibiotics 2023, 12(1), 169; https://doi.org/10.3390/antibiotics12010169 - 13 Jan 2023
Cited by 22 | Viewed by 4972
Abstract
Globally, cephalosporin therapy failure is a serious problem for infection control. One causative agent of cephalosporin-resistant infections is multidrug-resistant (MDR) E. coli producing extended-spectrum β-lactamases (ESBLs) and/or plasmid-encoded AmpC (pAmpC) β-lactamases. We evaluated the occurrence of ESBL/pAmpC genetic determinants in phenotypically MDR E. [...] Read more.
Globally, cephalosporin therapy failure is a serious problem for infection control. One causative agent of cephalosporin-resistant infections is multidrug-resistant (MDR) E. coli producing extended-spectrum β-lactamases (ESBLs) and/or plasmid-encoded AmpC (pAmpC) β-lactamases. We evaluated the occurrence of ESBL/pAmpC genetic determinants in phenotypically MDR E. coli isolated from clinical samples of blood, faeces, ear effusion, urine and sputum from a UK hospital. Phenotypic resistance profiling for 18 antibiotics (from seven classes) showed that 32/35 isolates were MDR, with resistance to 4–16 of the tested antibiotics. Of the isolates, 97.1% showed resistance to ampicillin, 71.4% showed resistance to co-amoxiclav, cefotaxime, ceftazidime and ceftiofur, and 68.5% showed resistance to cefquinome. blaCTX-M, blaTEM and blaOXA-1 genes were detected in 23, 13 and 12 strains, respectively, and Intl1 was detected in 17 isolates. The most common subtypes among the definite sequence types were CTX-M-15 (40%) and TEM-1 (75%). No E. coli isolates carried pAmpC genes. Significant correlations were seen between CTX-M carriage and cefotaxime, ceftiofur, aztreonam, ceftazidime and cefquinome resistance; between blaCTX-M, blaTEM and blaOXA-1 carriage and ciprofloxacin resistance; and between Intl1 carriage and trimethoprim/sulfamethoxazole resistance. Thus, MDR phenotypes may be conferred by a relatively small number of genes. The level and pattern of antibiotic resistance highlight the need for better antibiotic therapy guidelines, including reduced use and improved surveillance. Full article
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11 pages, 897 KiB  
Article
Hospital Antibiotic Use during COVID-19 Pandemic in Italy
by Alessandro Perrella, Filomena Fortinguerra, Andrea Pierantozzi, Nicolina Capoluongo, Novella Carannante, Andrea Lo Vecchio, Francesca Futura Bernardi, Francesco Trotta and Agnese Cangini
Antibiotics 2023, 12(1), 168; https://doi.org/10.3390/antibiotics12010168 - 13 Jan 2023
Cited by 16 | Viewed by 3347
Abstract
Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020–2021 with those related to 2019 in order to evaluate the [...] Read more.
Antimicrobial resistance (AMR) represents a major issue in healthcare being correlated to global inappropriate use of antibiotics. The aim of this study was to compare the data on hospital antibiotic consumption in 2020–2021 with those related to 2019 in order to evaluate the impact of the COVID-19 pandemic on antibiotic prescriptions and appropriate use at national level and in the different geographical areas. To estimate the consumption of antibiotics, two indicators were calculated: “number of DDD per 1000 inhabitants per day” and “number of DDD per 100 hospitalisation days”. Consumption data on antibiotics dispensed in public health facilities were based on the Italian “traceability of medicines” information flow. Data on hospitalisation days were extracted from the Italian “hospital discharge form” flow. Pearson correlation analysis was performed between the number of patients hospitalised for COVID-19 and the consumption of antibiotics in public healthcare facilities. During 2020, about 1.7 DDD/1000 inhabitants per day (12.3% of the overall consumption of reimbursed antibiotics) were dispensed exclusively in Italian hospitals (+0.8% compared to 2019). Considering the number of DDD per 100 hospitalisation days, consumption increased by 19.3% in 2020 compared to 2019. Comparing the first semester of 2020 and 2019, a decrease of DDD/1000 inhabitants per day was observed (−1.6%) at national level, with opposite trends in the different geographical areas; an increase in the use of azithromycin and carbapenems was also observed, with a stable consumption of third-generation cephalosporins. The use of antibiotics in the second semester of 2020 compared to the same period of 2019 showed a clear reduction at national level (−8.5%), appreciable to a similar extent in all geographic areas. In the first semester of 2021 compared to the same period of 2020, there was a huge reduction (−31.4%) in consumption at national level. However, the variations were heterogeneous between different geographical areas. To our knowledge, this study represents the most comprehensive analysis performed on antibiotic consumption data in hospital settings in Italy during the COVID-19 pandemic to date. Despite international and national guideline recommendations, a substantial overall increase in antibiotic prescriptions was observed during the COVID-19 pandemic, with variability in terms of geographical distribution and prescription strategies. These findings may be related to the dichotomy between perceived and real significance of guidelines, expert panels, or consensus. Therefore, new approaches or strategies to antimicrobial stewardship should be proposed. Full article
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8 pages, 235 KiB  
Perspective
Enlisting Probiotics to Combat Recurrent Urinary Tract Infections in Women—A Military Strategy for Meeting the Challenge
by Richard A. Watson
Antibiotics 2023, 12(1), 167; https://doi.org/10.3390/antibiotics12010167 - 13 Jan 2023
Cited by 2 | Viewed by 6373
Abstract
For decades, the potential role of probiotics in the prevention and treatment of recurrent urinary tract infections has been extensively studied. However, achieving an effective problem-solving strategy has thus far proven elusive. Perhaps adopting a military paradigm might expedite our assault on chronic, [...] Read more.
For decades, the potential role of probiotics in the prevention and treatment of recurrent urinary tract infections has been extensively studied. However, achieving an effective problem-solving strategy has thus far proven elusive. Perhaps adopting a military paradigm might expedite our assault on chronic, recurring bacteriuria in women. What is needed is a targeted strategy with specific attention to (1) the enemy: the case-specific uropathogen; (2) the battlefield: the extraordinarily complex interplay of factors within the bladder, unique to a given patient, which interface with profoundly important influences from the gut biome, as well as the vaginal biota; (3) the weapon: an antimicrobial probiotic with demonstrated activity against that specific uropathogen; (4) a new strategy: taking these complexities into account, we posit a key role for the instillation of case-specific lactobacilli directly into the bladder of the designated patient. This newly proposed, targeted intervention might be termed “Probiotic Intravesical Organic Therapy—PIVOT”; and (5) the long campaign: reaching clinically proven success may entail a long campaign. However, already, on many fronts, the elements necessary for victory recently seem to be falling into place. Full article
(This article belongs to the Special Issue Urinary Tract Infections: Epidemiology, Mechanisms of Infection and Treatment Options)
13 pages, 879 KiB  
Article
First and Second-Line Anti-Tuberculosis Drug-Resistance Patterns in Pulmonary Tuberculosis Patients in Zambia
by Ngula Monde, Musso Munyeme, Gershom Chongwe, Jonas Johansson Wensman, Mildred Zulu, Seter Siziya, Rabecca Tembo, Kabengele K. Siame, Obi Shambaba and Sydney Malama
Antibiotics 2023, 12(1), 166; https://doi.org/10.3390/antibiotics12010166 - 12 Jan 2023
Cited by 11 | Viewed by 4431
Abstract
Background: Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, [...] Read more.
Background: Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study. Methods: A total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants’ social–demographic characteristics were obtained using a pre-test checklist. Results: Overall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5–31.6%). A total of 9.8% (13/132, 95% CI: 5.3–16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3–16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1–146.5%) to have drug-resistant TB than those who had no history of being treated for TB. Conclusion: This study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring. Full article
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16 pages, 4953 KiB  
Article
Antimicrobial Susceptibility and Molecular Features of Colonizing Isolates of Pseudomonas aeruginosa and the Report of a Novel Sequence Type (ST) 3910 from Thailand
by Arnon Chukamnerd, Rattanaruji Pomwised, Sarunyou Chusri, Kamonnut Singkhamanan, Sanicha Chumtong, Kongpop Jeenkeawpiam, Chanida Sakunrang, Kuwanhusna Saroeng, Phanvasri Saengsuwan, Monwadee Wonglapsuwan and Komwit Surachat
Antibiotics 2023, 12(1), 165; https://doi.org/10.3390/antibiotics12010165 - 12 Jan 2023
Cited by 5 | Viewed by 3220
Abstract
Pseudomonas aeruginosa is an important pathogen as it can cause hospital-acquired infections. Additionally, it can also colonize in patients and in other various environments. Hence, this study aimed to investigate the antimicrobial susceptibility, and to study the molecular features, of colonizing isolates of [...] Read more.
Pseudomonas aeruginosa is an important pathogen as it can cause hospital-acquired infections. Additionally, it can also colonize in patients and in other various environments. Hence, this study aimed to investigate the antimicrobial susceptibility, and to study the molecular features, of colonizing isolates of P. aeruginosa from Songklanagarind Hospital, Thailand. Genomic DNA extraction, whole-genome sequencing (WGS), and bioinformatics analysis were performed in all studied isolates. The findings demonstrated that the majority of isolates were non-susceptible to colistin and carbapenem. For in silico study, multilocus sequence typing (MLST) revealed one novel sequence type (ST) 3910 and multiple defined STs. The isolates carried several antimicrobial resistance genes (blaOXA-50, aph(3′)-IIb, etc.) and virulence-associated genes (fleN, waaA, etc.). CRISPR-Cas sequences with different spacers and integrated bacteriophage sequences were also identified in these isolates. Very high SNPs were found in the alignments of the novel ST-3910 isolate with other isolates. A comparative genomic analysis exhibited phylogenetic clustering of our colonizing isolates with clinical isolates from many countries. Interestingly, ST-3981, ST-3982, ST-3983, ST-3984, ST-3985, ST-3986, ST-3986, ST-3986, ST-3987, and ST-3988, the new STs from published genomes, were assigned in this study. In conclusion, this WGS data might be useful for tracking the spread of P. aeruginosa colonizing isolates. Full article
(This article belongs to the Special Issue Mechanism of Carbapenem Resistance in Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa)
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12 pages, 1877 KiB  
Article
Prevalence and Antibiogram Pattern of Klebsiella pneumoniae in a Tertiary Care Hospital in Makkah, Saudi Arabia: An 11-Year Experience
by Naif A. Jalal, Abdulrahman M. Al-Ghamdi, Aiman M. Momenah, Sami S. Ashgar, Farkad Bantun, Fayez Saeed Bahwerth, Sumyya H. Hariri, Ayman K. Johargy, Abeer A. Barhameen, Hamdi M. Al-Said and Hani Faidah
Antibiotics 2023, 12(1), 164; https://doi.org/10.3390/antibiotics12010164 - 12 Jan 2023
Cited by 12 | Viewed by 3805
Abstract
Infectious disease is one of the greatest causes of morbidity and mortality worldwide, and with the emergence of antimicrobial resistance, the situation is worsening. In order to prevent this crisis, antimicrobial resistance needs to be monitored carefully to control the spread of multidrug-resistant [...] Read more.
Infectious disease is one of the greatest causes of morbidity and mortality worldwide, and with the emergence of antimicrobial resistance, the situation is worsening. In order to prevent this crisis, antimicrobial resistance needs to be monitored carefully to control the spread of multidrug-resistant bacteria. Therefore, in this study, we aimed to determine the prevalence of infection caused by Klebsiella pneumoniae and investigate the antimicrobial profile pattern of K. pneumoniae in the last eleven years. This retrospective study was conducted in a tertiary hospital in Makkah, Saudi Arabia. Data were collected from January 2011 to December 2021. From 2011 to 2021, a total of 61,027 bacterial isolates were collected from clinical samples, among which 14.7% (n = 9014) were K. pneumoniae. The antibiotic susceptibility pattern of K. pneumoniae revealed a significant increase in the resistance rate in most tested antibiotics during the study period. A marked jump in the resistance rate was seen in amoxicillin/clavulanate and piperacillin/tazobactam, from 33.6% and 13.6% in 2011 to 71.4% and 84.9% in 2021, respectively. Ceftazidime, cefotaxime, and cefepime resistance rates increased from 29.9%, 26.2%, and 53.9%, respectively, in 2011 to become 84.9%, 85.1%, and 85.8% in 2021. Moreover, a significant increase in the resistance rate was seen in both imipenem and amikacin, with an average resistance rate rise from 6.6% for imipenem and 11.9% for amikacin in 2011 to 59.9% and 62.2% in 2021, respectively. The present study showed that the prevalence and drug resistance of K. pneumoniae increased over the study period. Thus, preventing hospital-acquired infection and the reasonable use of antibiotics must be implemented to control and reduce antimicrobial resistance. Full article
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16 pages, 1688 KiB  
Article
Antibacterial Effect of 16 Essential Oils and Modulation of mex Efflux Pumps Gene Expression on Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates: Is Cinnamon a Good Fighter?
by Răzvan Lucian Coșeriu, Camelia Vintilă, Mirela Pribac, Anca Delia Mare, Cristina Nicoleta Ciurea, Radu Ovidiu Togănel, Anca Cighir, Anastasia Simion and Adrian Man
Antibiotics 2023, 12(1), 163; https://doi.org/10.3390/antibiotics12010163 - 12 Jan 2023
Cited by 11 | Viewed by 5086
Abstract
The purpose of the study was to describe the antimicrobial activity of 16 common essential oils (EOs) on multidrug-resistant (MDR) Pseudomonas aeruginosa clinical isolates, including the determination of the effects on mex efflux pumps gene expression. Seventy-two clinical isolates of P. aeruginosa collected [...] Read more.
The purpose of the study was to describe the antimicrobial activity of 16 common essential oils (EOs) on multidrug-resistant (MDR) Pseudomonas aeruginosa clinical isolates, including the determination of the effects on mex efflux pumps gene expression. Seventy-two clinical isolates of P. aeruginosa collected between 2020–2022 were screened for susceptibility to EOs using Kirby–Bauer disk diffusion to identify potential candidates for future alternative therapies. The minimal inhibitory concentration (MIC) was further determined for the EO that proved antibacterial activity following the disk diffusion screening. Positive and negative controls were also used for method validation. Since cinnamon EO exhibited the best antimicrobial activity, it was further used to evaluate its influence on mex A, B, C, E, and X efflux pumps gene expression using real-time RT-PCR. Cinnamon EO inhibited all P. aeruginosa strains, followed by thyme EO (37.5%, n = 27) and lavender EO (12.5%, n = 9). The other EOs were less efficient. The MIC detection showed that cinnamon at a concentration of 0.05% v/v inhibited all MDR P. aeruginosa isolates. Thyme, turmeric, peppermint, basil, clove, and lavender EOs presented various results, most of them having activity at concentrations higher than 12.5% v/v. By studying the activity of cinnamon EO on mex efflux pumps, it was found that mexA and mexB (66.5%) were generally under-expressed. The remarkable results produced using the very low concentrations of cinnamon EO, with 100% antimicrobial activity against multi-, extended-, and pan- drug-resistant (MDR, XDR, PDR) P. aeruginosa clinical isolates, completed with the severe alteration of the RNA messaging system, supports its potential to be used as adjuvant treatment, with impact on therapeutic results. Full article
(This article belongs to the Special Issue Antioxidant and Antibacterial Activity of Plant Extracts)
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19 pages, 975 KiB  
Article
Prevalence, Antimicrobial Resistance and Toxin-Encoding Genes of Clostridioides difficile from Environmental Sources Contaminated by Feces
by Khald Blau and Claudia Gallert
Antibiotics 2023, 12(1), 162; https://doi.org/10.3390/antibiotics12010162 - 12 Jan 2023
Cited by 7 | Viewed by 2189
Abstract
Clostridioides difficile (C. difficile) is the most common pathogen causing antibiotic-associated intestinal diseases in humans and some animal species, but it can also be present in various environments outside hospitals. Thus, the objective of this study was to investigate the presence [...] Read more.
Clostridioides difficile (C. difficile) is the most common pathogen causing antibiotic-associated intestinal diseases in humans and some animal species, but it can also be present in various environments outside hospitals. Thus, the objective of this study was to investigate the presence and the characteristics of toxin-encoding genes and antimicrobial resistance of C. difficile isolates from different environmental sources. C. difficile was found in 32 out of 81 samples (39.50%) after selective enrichment of spore-forming bacteria and in 45 samples (55.56%) using a TaqMan-based qPCR assay. A total of 169 C. difficile isolates were recovered from those 32 C. difficile-positive environmental samples. The majority of environmental C. difficile isolates were toxigenic, with many (88.75%) positive for tcdA and tcdB. Seventy-four isolates (43.78%) were positive for binary toxins, cdtA and cdtB, and 19 isolates were non-toxigenic. All the environmental C. difficile isolates were susceptible to vancomycin and metronidazole, and most isolates were resistant to ciprofloxacin (66.86%) and clindamycin (46.15%), followed by moxifloxacin (13.02%) and tetracycline (4.73%). Seventy-five isolates (44.38%) showed resistance to at least two of the tested antimicrobials. C. difficile strains are commonly present in various environmental sources contaminated by feces and could be a potential source of community-associated C. difficile infections. Full article
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14 pages, 737 KiB  
Review
The Role of Biomarkers in Influenza and COVID-19 Community-Acquired Pneumonia in Adults
by Raquel Carbonell, Gerard Moreno, Ignacio Martín-Loeches, María Bodí and Alejandro Rodríguez
Antibiotics 2023, 12(1), 161; https://doi.org/10.3390/antibiotics12010161 - 12 Jan 2023
Cited by 8 | Viewed by 3347
Abstract
Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza [...] Read more.
Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza virus and SARS-CoV-2 pneumonia. Moreover, mixed viral and bacterial pneumonia is common and a risk factor for severity of disease. It is critical for clinicians the early identification of the pathogen causing infection to avoid inappropriate antibiotics, as well as to predict clinical outcomes. It has been extensively reported that biomarkers could be useful for these purposes. This review describe current evidence and provide recommendations about the use of biomarkers in influenza and SARS-CoV-2 pneumonia, focusing mainly on procalcitonin (PCT) and C-reactive protein (CRP). Evidence was based on a qualitative analysis of the available scientific literature (meta-analyses, randomized controlled trials, observational studies and clinical guidelines). Both PCT and CRP levels provide valuable information about the prognosis of influenza and SARS-CoV-2 pneumonia. Additionally, PCT levels, considered along with other clinical, radiological and laboratory data, are useful for early diagnosis of mixed viral and bacterial CAP, allowing the proper management of the disease and adequate antibiotics prescription. The authors propose a practical PCT algorithm for clinical decision-making to guide antibiotic initiation in cases of influenza and SARS-CoV-2 pneumonia. Further well-design studies are needed to validate PCT algorithm among these patients and to confirm whether other biomarkers are indeed useful as diagnostic or prognostic tools in viral pneumonia. Full article
(This article belongs to the Special Issue The Optimization of Antimicrobial Prescribing and Stewardship)
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29 pages, 2472 KiB  
Review
Coumarin Triazoles as Potential Antimicrobial Agents
by Siddappa A. Patil, Aravind R. Nesaragi, Raúl R. Rodríguez-Berrios, Sydney M. Hampton, Alejandro Bugarin and Shivaputra A. Patil
Antibiotics 2023, 12(1), 160; https://doi.org/10.3390/antibiotics12010160 - 12 Jan 2023
Cited by 12 | Viewed by 3531
Abstract
Currently, in hospitals and community health centers, microbial infections are highly common diseases and are a leading cause of death worldwide. Antibiotics are generally used to fight microbial infections; however, because of the abuse of antibiotics, microbes have become increasingly more resistant to [...] Read more.
Currently, in hospitals and community health centers, microbial infections are highly common diseases and are a leading cause of death worldwide. Antibiotics are generally used to fight microbial infections; however, because of the abuse of antibiotics, microbes have become increasingly more resistant to most of them. Therefore, medicinal chemists are constantly searching for new or improved alternatives to combat microbial infections. Coumarin triazole derivatives displayed a variety of therapeutic applications, such as antimicrobial, antioxidant, and anticancer activities. This review summarizes the advances of coumarin triazole derivatives as potential antimicrobial agents covering articles published from 2006 to 2022. Full article
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23 pages, 2185 KiB  
Review
Interconnected Set of Enzymes Provide Lysine Biosynthetic Intermediates and Ornithine Derivatives as Key Precursors for the Biosynthesis of Bioactive Secondary Metabolites
by Paloma Liras and Juan Francisco Martín
Antibiotics 2023, 12(1), 159; https://doi.org/10.3390/antibiotics12010159 - 12 Jan 2023
Cited by 1 | Viewed by 3979
Abstract
Bacteria, filamentous fungi, and plants synthesize thousands of secondary metabolites with important biological and pharmacological activities. The biosynthesis of these metabolites is performed by networks of complex enzymes such as non-ribosomal peptide synthetases, polyketide synthases, and terpenoid biosynthetic enzymes. The efficient production of [...] Read more.
Bacteria, filamentous fungi, and plants synthesize thousands of secondary metabolites with important biological and pharmacological activities. The biosynthesis of these metabolites is performed by networks of complex enzymes such as non-ribosomal peptide synthetases, polyketide synthases, and terpenoid biosynthetic enzymes. The efficient production of these metabolites is dependent upon the supply of precursors that arise from primary metabolism. In the last decades, an impressive array of biosynthetic enzymes that provide specific precursors and intermediates leading to secondary metabolites biosynthesis has been reported. Suitable knowledge of the elaborated pathways that synthesize these precursors or intermediates is essential for advancing chemical biology and the production of natural or semisynthetic biological products. Two of the more prolific routes that provide key precursors in the biosynthesis of antitumor, immunosuppressant, antifungal, or antibacterial compounds are the lysine and ornithine pathways, which are involved in the biosynthesis of β-lactams and other non-ribosomal peptides, and bacterial and fungal siderophores. Detailed analysis of the molecular genetics and biochemistry of the enzyme system shows that they are formed by closely related components. Particularly the focus of this study is on molecular genetics and the enzymatic steps that lead to the formation of intermediates of the lysine pathway, such as α-aminoadipic acid, saccharopine, pipecolic acid, and related compounds, and of ornithine-derived molecules, such as N5-Acetyl-N5-Hydroxyornithine and N5-anhydromevalonyl-N5-hydroxyornithine, which are precursors of siderophores. We provide evidence that shows interesting functional relationships between the genes encoding the enzymes that synthesize these products. This information will contribute to a better understanding of the possibilities of advancing the industrial applications of synthetic biology. Full article
(This article belongs to the Special Issue Feature Review Papers in Antibiotic Biosynthesis)
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12 pages, 1714 KiB  
Article
Relationship between Penicillin-Binding Proteins Alterations and β-Lactams Non-Susceptibility of Diseased Pig-Isolated Streptococcus suis
by Kamonwan Lunha, Wiyada Chumpol, Surasak Jiemsup, Sukuma Samngamnim, Pornchalit Assavacheep and Suganya Yongkiettrakul
Antibiotics 2023, 12(1), 158; https://doi.org/10.3390/antibiotics12010158 - 12 Jan 2023
Cited by 7 | Viewed by 2468
Abstract
Streptococcus suis is a zoonotic pathogen causing disease in both animals and humans, and the emergence of increasingly resistant bacteria to antimicrobial agents has become a significant challenge globally. The objective of this study was to investigate the genetic basis for declining susceptibility [...] Read more.
Streptococcus suis is a zoonotic pathogen causing disease in both animals and humans, and the emergence of increasingly resistant bacteria to antimicrobial agents has become a significant challenge globally. The objective of this study was to investigate the genetic basis for declining susceptibility to penicillin and other β-lactams among S. suis. Antimicrobial susceptibility testing and penicillin-binding proteins (PBP1a, PBP2a, PBP2b, and PBP2x) sequence analysis were performed on 225 S. suis isolated from diseased pigs. This study found that a growing trend of isolates displayed reduced susceptibility to β-lactams including penicillin, ampicillin, amoxicillin/clavulanic acid, and cephalosporins. A total of 342 substitutions within the transpeptidase domain of four PBPs were identified, of which 18 substitutions were most statistically associated with reduced β-lactams susceptibility. Almost all the S. suis isolates which exhibited penicillin-non-susceptible phenotype (71.9%) had single nucleotide polymorphisms, leading to alterations of PBP1a (P409T) and PBP2a (T584A and H588Y). The isolates may manifest a higher level of penicillin resistance by additional mutation of M341I in the 339STMK active site motif of PBP2x. The ampicillin-non-susceptible isolates shared the mutations in PBP1a (P409T) and PBP2a (T584A and H588Y) with additional alterations of PBP2b (T625R) and PBP2x (T467S). The substitutions, including PBP1a (M587S/T), PBP2a (M433T), PBP2b (I428L), and PBP2x (Q405E/K/L), appeared to play significant roles in mediating the reduction in amoxicillin/clavulanic acid susceptibility. Among the cephalosporins, specific mutations strongly associated with the decrease in cephalosporins susceptibility were observed for ceftiofur: PBP1a (S477D/G), PBP2a (E549Q and A568S), PBP2b (T625R), and PBP2x (Q453H). It is concluded that there was genetically widespread presence of PBPs substitutions associated with reduced susceptibility to β-lactam antibiotics. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Animal and Zoonotic Pathogens)
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10 pages, 968 KiB  
Article
Molecular Characterization of Community- and Hospital- Acquired Methicillin-Resistant Staphylococcus aureus Isolates during COVID-19 Pandemic
by Muhammad Sohail, Moazza Muzzammil, Moaz Ahmad, Sabahat Rehman, Mohammed Garout, Taghreed M. Khojah, Kholoud M. Al-Eisa, Samar A. Breagesh, Rola M. Al Hamdan, Halimah I. Alibrahim, Zainab A. Alsoliabi, Ali A. Rabaan and Naveed Ahmed
Antibiotics 2023, 12(1), 157; https://doi.org/10.3390/antibiotics12010157 - 12 Jan 2023
Cited by 7 | Viewed by 3515
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant superbug that causes various types of community- and hospital-acquired infectious diseases. The current study was aimed to see the genetic characteristics and gene expression of MRSA isolates of nosocomial origin. A total of 221 MRSA isolates [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant superbug that causes various types of community- and hospital-acquired infectious diseases. The current study was aimed to see the genetic characteristics and gene expression of MRSA isolates of nosocomial origin. A total of 221 MRSA isolates were identified from 2965 clinical samples. To identify the bacterial isolates, the clinical samples were inoculated on blood agar media plates first and incubated at 37 °C for 18–24 h. For further identification, the Gram staining and various biochemical tests were performed once the colonies appeared on the inoculated agar plates. The phenotypic identification of antibiotic susceptibility patterns was carried out using Kirby–Bauer disk diffusion method by following the Clinical and Laboratory Standards Institute (CLSI) 2019 guidelines. The biofilm-producing potentials of MRSA were checked quantitatively using a spectrophotometric assay. All strains were characterized genotypically by SCCmec and agr typing using the specific gene primers. Furthermore, a total of twelve adhesion genes were amplified in all MRSA isolates. MRSA was a frequently isolated pathogen (44% community acquired (CA)-MRSA and 56% hospital acquired (HA)-MRSA), respectively. Most of the MRSA isolates were weak biofilm producers (78%), followed by moderate (25%) and strong (7%) biofilm producers, respectively. Prominent adhesion genes were clfB (100%), icaAD (91%), fib (91%), sdrC (91%) followed by eno (89%), fnbA (77%), sdrE (67%), icaBC (65%), clfA (65%), fnbB (57%), sdrD (57%), and cna (48%), respectively. The results of the current study will help to understand and manage the spectrum of biofilm-producing MRSA-associated hospital-acquired infections and to provide potential molecular candidates for the identification of biofilm-producing MRSA. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Hospital- and Community-Associated Infections)
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18 pages, 638 KiB  
Review
Is There Any Benefit to the Use of Antibiotics with Indwelling Catheters after Urologic Surgery in Adults
by Fenizia Maffucci, Chrystal Chang, Jay Simhan and Joshua A. Cohn
Antibiotics 2023, 12(1), 156; https://doi.org/10.3390/antibiotics12010156 - 12 Jan 2023
Cited by 5 | Viewed by 3455
Abstract
Antibiotic stewardship in urologic reconstruction is critically important, as many patients will require indwelling catheters for days to weeks following surgery and thus are at risk of both developing catheter-associated urinary tract infections (CAUTI) as well as multi-drug resistant (MDR) uropathogens. Accordingly, limiting [...] Read more.
Antibiotic stewardship in urologic reconstruction is critically important, as many patients will require indwelling catheters for days to weeks following surgery and thus are at risk of both developing catheter-associated urinary tract infections (CAUTI) as well as multi-drug resistant (MDR) uropathogens. Accordingly, limiting antibiotic use, when safe, should help reduce antibiotic resistance and the prevalence of MDR organisms. However, there is significant heterogeneity in how antibiotics are prescribed to patients who need indwelling urethral catheters post-operatively. We performed a literature review to determine if there are benefits in the use of antibiotics for various clinical scenarios that require post-operative indwelling catheters for greater than 24 h. In general, for patients undergoing prostatectomy, transurethral resection of the prostate, and/or urethroplasty, antibiotic administration may be limited without increased risk of CAUTI. However, more work is needed to identify optimal antibiotic regimens for these and alternative urologic procedures, whether certain sub-populations benefit from longer courses of antibiotics, and effective non-antibiotic or non-systemic therapies. Full article
(This article belongs to the Special Issue Urinary Tract Infections: Epidemiology, Mechanisms of Infection and Treatment Options)
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11 pages, 2118 KiB  
Article
Biofilm Formation Ability of ESBL/pAmpC-Producing Escherichia coli Isolated from the Broiler Production Pyramid
by Andrea Laconi, Roberta Tolosi, Ilias Apostolakos and Alessandra Piccirillo
Antibiotics 2023, 12(1), 155; https://doi.org/10.3390/antibiotics12010155 - 11 Jan 2023
Cited by 4 | Viewed by 2212
Abstract
Escherichia coli able to produce extended spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (pAmpCs) represents a serious threat to public health, since these genes confer resistance to critically important antimicrobials (i.e., third generation cephalosporins) and can be transferred to non-resistant bacteria via plasmids. [...] Read more.
Escherichia coli able to produce extended spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (pAmpCs) represents a serious threat to public health, since these genes confer resistance to critically important antimicrobials (i.e., third generation cephalosporins) and can be transferred to non-resistant bacteria via plasmids. E. coli are known to be able to form a biofilm, which represents a favorable environment for the exchange of resistance determinants. Here, we assessed the ability of 102 ESBL/pAmpC-producing E. coli isolated from the broiler production pyramid to form a biofilm and to identify genetic factors involved in biofilm formation. All but one of the ESBL/pAmpC-producing E. coli were able to form a biofilm, and this represents a great concern to public health. E. coli belonging to phylogroups D, E, and F, as well as strains harboring the blaCTX-M-type gene, seem to be associated with an increased biofilm capability (p < 0.05). Furthermore, virulence genes involved in adherence and invasion (i.e., csgBAC, csgDEFG, matABCDEF, and sfaX) seem to enhance biofilm formation in E. coli. Efforts should be made to reduce the presence of ESBL/pAmpC- and biofilm-producing E. coli in the broiler production pyramid and, therefore, the risk of dissemination of resistant bacteria and genes. Full article
(This article belongs to the Special Issue Antimicrobial and Antifungal Resistance in Domestic Animals, Synanthropic Species and Wildlife)
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