Antibiotics

10 pages, 1398 KiB

Open AccessArticle

Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations

by Ines Mack, Mike Sharland, Janneke M. Brussee, Sophia Rehm, Katharina Rentsch and Julia Bielicki

Antibiotics 2021, 10(2), 225; https://doi.org/10.3390/antibiotics10020225 - 23 Feb 2021

Cited by 4 | Viewed by 3790

Abstract

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be [...] Read more.

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI −55.7%, +29.9%) at 8°C and 72.3% (95% CI −82.8%, −61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI −51.9%, +21.2%) at 23 °C and 21.7% (−28.2%, −15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children. Full article

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14 pages, 2069 KiB

Open AccessArticle

Development of Europium-Sensitized Fluorescence-Based Method for Sensitive Detection of Oxytetracycline in Citrus Tissues

by Faraj Hijaz, Yasser Nehela, Pedro Gonzalez-Blanco and Nabil Killiny

Antibiotics 2021, 10(2), 224; https://doi.org/10.3390/antibiotics10020224 - 23 Feb 2021

Cited by 6 | Viewed by 2381

Abstract

Antimicrobial compounds have been successfully used to control many plant and animal diseases. Recently, oxytetracycline (OTC) and streptomycin have been approved for the treatment of Huanglongbing in citrus. Since the application of OTC is under strict regulations, several methods have been developed to [...] Read more.

Antimicrobial compounds have been successfully used to control many plant and animal diseases. Recently, oxytetracycline (OTC) and streptomycin have been approved for the treatment of Huanglongbing in citrus. Since the application of OTC is under strict regulations, several methods have been developed to determine and monitor its levels in the environment including high-performance liquid chromatography, ELISA, colorimetric, and fluorometric assays. In this study, we developed a fluorometric method for the determination of OTC in plant tissues based on its complexation with europium. Our preliminary trials showed that phenols and flavonoids interfere with the europium assay by reacting with the sensitizing reagent, cetyltrimethylammonium chloride. Consequently, we used the 60 mg hydrophilic–lipophilic balanced (HLB) cartridges to purify the OTC from the plant matrix. The recovery of OTC from spiked leaf samples was 75 ± 7.6%. Using the 500 mg HLB, we were able to detect 0.3 ppm OTC in the final sample extract, which corresponds to 3 µg g⁻¹ fresh weight (FWT). The developed method was successfully used to measure the level of OTC in leaves obtained from trunk-injected trees. The results obtained by the europium method were similar to those obtained using the ELISA assay. We also tested the cross-reactivity of OTC metabolites with the europium method. The 4-epi-OTC showed a high cross-reactivity (50.0 ± 3.6%) with europium assay, whereas α-apo-OTC and β-apo-OTC showed small cross-reactivity. We showed that the europium-sensitized fluorescence-based method can be successfully used to assess OTC in citrus plant tissues after a cleanup step. Our results showed that this method was sensitive, reproducible, and can be used to analyze many samples simultaneously. Full article

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19 pages, 1843 KiB

Open AccessArticle

Pharmacological Potential and Chemical Characterization of Bridelia ferruginea Benth.—A Native Tropical African Medicinal Plant

by Mohamad Fawzi Mahomoodally, Sharmeen Jugreet, Kouadio Ibrahime Sinan, Gokhan Zengin, Gunes Ak, Ramazan Ceylan, József Jekő, Zoltán Cziáky, Paola Angelini, Giancarlo Angeles Flores, Roberto Venanzoni, Simonetta Cristina Di Simone, Luigi Menghini, Giustino Orlando, Claudio Ferrante, Ouattara Katinan Etienne and Massimo Tacchini

Antibiotics 2021, 10(2), 223; https://doi.org/10.3390/antibiotics10020223 - 23 Feb 2021

Cited by 19 | Viewed by 3285

Abstract

To avail the possible pharmacological actions of Brideliaferruginea Benth., the present investigation was designed to quantitatively analyze the total flavonoid and phenolic contents and assess the various antioxidant and enzyme inhibition properties of leaf and stem bark extracts (ethyl acetate, water and [...] Read more.

To avail the possible pharmacological actions of Brideliaferruginea Benth., the present investigation was designed to quantitatively analyze the total flavonoid and phenolic contents and assess the various antioxidant and enzyme inhibition properties of leaf and stem bark extracts (ethyl acetate, water and methanolic) of B. ferruginea. Anti-proliferative effect was also investigated against human colon cancer cells (HCT116) as well as the antimicrobial potential against multiple bacterial and fungal (yeasts and dermatophytes) strains. The methanolic and water extracts of the stem bark demonstrated the highest phenolic content (193.58 ± 0.98 and 187.84 ± 1.88 mg/g, respectively), while the leaf extracts showed comparatively higher flavonoid contents (24.37–42.31 mg/g). Overall, the methanolic extracts were found to possess the most significant antioxidant potency. Compared to the other extracts, methanolic extracts of the B. ferruginea were revealed to be most potent inhibitors of acetyl- and butyryl-cholinesterases, tyrosinase α-amylase, except α-glucosidase. Only the ethyl acetate extracts were found to inhibit glucosidase. Additionally, the stem bark methanolic extract also showed potent inhibitory activity against E. coli and gram-positive bacteria (MIC (minimum inhibitory concentration): 2.48–62.99 µg/mL), as well as all the tested fungi (MIC: 4.96–62.99 µg/mL). In conclusion, B. ferruginea can be regarded as a promising source of bioactive compounds displaying multifunctional pharmacological activities and thus is a potential candidate for further investigations in the endeavor to develop botanical formulations for pharmaceutical and cosmeceutical industries. Full article

(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products)

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14 pages, 1263 KiB

Open AccessArticle

Modeling the Growth and Death of Staphylococcus aureus against Melaleuca armillaris Essential Oil at Different pH Conditions

by Daniel Buldain, Lihuel Gortari Castillo, María Laura Marchetti, Karen Julca Lozano, Arnaldo Bandoni and Nora Mestorino

Antibiotics 2021, 10(2), 222; https://doi.org/10.3390/antibiotics10020222 - 23 Feb 2021

Cited by 8 | Viewed by 2897

Abstract

Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful in describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the antimicrobial activity of Melaleuca armillaris EO obtained from plants placed in [...] Read more.

Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful in describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the antimicrobial activity of Melaleuca armillaris EO obtained from plants placed in the province of Buenos Aires (Argentina) against Staphylococcus aureus. The minimum inhibitory and bactericidal concentrations were close and decreased, slightly acidifying the medium from pH 7.4 to 6.5 and 5.0. This result was also evidenced by applying a sigmoid model, where the time and EO concentration necessaries to achieve 50% of the maximum effect decreased when the medium was acidified. Moreover, at pH 7.4, applying the Gompertz model, we found that subinhibitory concentrations of EO decreased the growth rate and the maximum population density and increased the latency period concerning the control. Additionally, we established physicochemical parameters for quality control and standardization of M. armillaris EO. Mathematical modeling allowed us to estimate key parameters in the behavior of S. aureus and Melaleuca armillaris EO at different pH. This is interesting in situations where the pH changes are relevant, such as the control of intracellular infections in public health or the development of preservatives for the food industry. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Essential Oils)

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15 pages, 989 KiB

Open AccessArticle

Tracking Reservoirs of Antimicrobial Resistance Genes in a Complex Microbial Community Using Metagenomic Hi-C: The Case of Bovine Digital Dermatitis

by Ashenafi F. Beyi, Alan Hassall, Gregory J. Phillips and Paul J. Plummer

Antibiotics 2021, 10(2), 221; https://doi.org/10.3390/antibiotics10020221 - 23 Feb 2021

Cited by 5 | Viewed by 3061

Abstract

Bovine digital dermatitis (DD) is a contagious infectious cause of lameness in cattle with unknown definitive etiologies. Many of the bacterial species detected in metagenomic analyses of DD lesions are difficult to culture, and their antimicrobial resistance status is largely unknown. Recently, a [...] Read more.

Bovine digital dermatitis (DD) is a contagious infectious cause of lameness in cattle with unknown definitive etiologies. Many of the bacterial species detected in metagenomic analyses of DD lesions are difficult to culture, and their antimicrobial resistance status is largely unknown. Recently, a novel proximity ligation-guided metagenomic approach (Hi-C ProxiMeta) has been used to identify bacterial reservoirs of antimicrobial resistance genes (ARGs) directly from microbial communities, without the need to culture individual bacteria. The objective of this study was to track tetracycline resistance determinants in bacteria involved in DD pathogenesis using Hi-C. A pooled sample of macerated tissues from clinical DD lesions was used for this purpose. Metagenome deconvolution using ProxiMeta resulted in the creation of 40 metagenome-assembled genomes with ≥80% complete genomes, classified into five phyla. Further, 1959 tetracycline resistance genes and ARGs conferring resistance to aminoglycoside, beta-lactams, sulfonamide, phenicol, lincosamide, and erythromycin were identified along with their bacterial hosts. In conclusion, the widespread distribution of genes conferring resistance against tetracycline and other antimicrobials in bacteria of DD lesions is reported for the first time. Use of proximity ligation to identify microorganisms hosting specific ARGs holds promise for tracking ARGs transmission in complex microbial communities. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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10 pages, 1252 KiB

Open AccessArticle

Mapping the Implementation of a Clinical Pharmacist-Driven Antimicrobial Stewardship Programme at a Tertiary Care Centre in South India

by Vrinda Nampoothiri, Akkulath Sangita Sudhir, Mariam Varsha Joseph, Zubair Mohamed, Vidya Menon, Esmita Charani and Sanjeev Singh

Antibiotics 2021, 10(2), 220; https://doi.org/10.3390/antibiotics10020220 - 23 Feb 2021

Cited by 18 | Viewed by 3212

Abstract

In many parts of the world, including in India, pharmacist roles in antimicrobial stewardship (AMS) programmes remain unexplored. We describe the evolution and effect of the role of adding clinical pharmacists to a multidisciplinary AMS at a tertiary care teaching hospital in Kerala, [...] Read more.

In many parts of the world, including in India, pharmacist roles in antimicrobial stewardship (AMS) programmes remain unexplored. We describe the evolution and effect of the role of adding clinical pharmacists to a multidisciplinary AMS at a tertiary care teaching hospital in Kerala, India. Through effective leadership, multidisciplinary AMS (February 2016) and antitubercular therapy (ATT) stewardship programmes (June 2017) were established. Clinical pharmacists were introduced as core members of the programmes, responsible for the operational delivery of key stewardship interventions. Pharmacy-led audit and feedback monitored the appropriateness of antimicrobial prescriptions and compliance to AMS/ATT recommendations. Between February 2016 and January 2017, 56% (742/1326) of antimicrobial prescriptions were appropriate, and 54% (318/584) of recommendations showed compliance. By the third year of the AMS, appropriateness increased to 80% (1752/2190), and compliance to the AMS recommendations to 70% (227/325). The appropriateness of ATT prescriptions increased from a baseline of 61% (95/157) in the first year, to 72% (62/86, June 2018–February 2019). The compliance to ATT recommendations increased from 42% (25/60) to 58% (14/24). Such a model can be effective in implementing sustainable change in low- and middle-income countries (LMICs) such as India, where the shortage of infectious disease physicians is a major impediment to the implementation and sustainability of AMS programmes. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Secondary Care across Different Resource Settings)

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8 pages, 272 KiB

Open AccessArticle

Spread of Linezolid-Resistant Enterococcus spp. in Human Clinical Isolates in the Czech Republic

by Lucia Mališová, Vladislav Jakubů, Katarína Pomorská, Martin Musílek and Helena Žemličková

Antibiotics 2021, 10(2), 219; https://doi.org/10.3390/antibiotics10020219 - 22 Feb 2021

Cited by 14 | Viewed by 2562

Abstract

The aim of this study was to map and investigate linezolid resistance mechanisms in linezolid-resistant enterococci in the Czech Republic from 2009 to 2019. Altogether, 1442 isolates of Enterococcus faecium and Enterococcus faecalis were examined in the National Reference Laboratory for Antibiotics. Among [...] Read more.

The aim of this study was to map and investigate linezolid resistance mechanisms in linezolid-resistant enterococci in the Czech Republic from 2009 to 2019. Altogether, 1442 isolates of Enterococcus faecium and Enterococcus faecalis were examined in the National Reference Laboratory for Antibiotics. Among them, 8% of isolates (n = 115) were resistant to linezolid (E. faecium/n = 106, E. faecalis/n = 9). Only three strains of E. faecium were resistant to tigecycline, 72.6% of isolates were resistant to vancomycin. One isolate of E. faecium harbored the cfr gene. The majority (87%, n = 11) of E. faecium strains were resistant to linezolid because of the mutation G2576T in the domain V of the 23S rRNA. This mutation was detected also in two strains of E. faecalis. The presence of the optrA gene was the dominant mechanism of linezolid resistance in E. faecalis isolates. None of enterococci contained cfrB, poxtA genes, or any amino acid mutation in genes encoding ribosomal proteins. No mechanism of resistance was identified in 4 out of 106 E. faecium linezolid resistant isolates in this study. Seventeen sequence types (STs) including four novel STs were identified in this work. Clonal complex CC17 was found in all E. faecium isolates. Full article

(This article belongs to the Special Issue Hospital Acquired Infections, Multidrug Resistant (MDR) Bacteria, Alternative Approaches to Antibiotic Therapy)

11 pages, 280 KiB

Open AccessArticle

Impact of Treating Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Prospective Cohort Study

by Sara Fontserè, Carmen Infante-Domínguez, Alejandro Suárez-Benjumea, Marta Suñer-Poblet, Carmen González-Corvillo, Guillermo Martín-Gutiérrez, Gabriel Bernal, Jerónimo Pachón, María Eugenia Pachón-Ibáñez and Elisa Cordero

Antibiotics 2021, 10(2), 218; https://doi.org/10.3390/antibiotics10020218 - 22 Feb 2021

Cited by 4 | Viewed by 2024

Abstract

This study aims to define the epidemiologic, clinical, and microbiological features of asymptomatic bacteriuria (AB) and cystitis in kidney transplantation recipients (KTRs), and to determine the impact of antimicrobial therapy of AB and the risk factors of cystitis. We conducted a prospective observational [...] Read more.

This study aims to define the epidemiologic, clinical, and microbiological features of asymptomatic bacteriuria (AB) and cystitis in kidney transplantation recipients (KTRs), and to determine the impact of antimicrobial therapy of AB and the risk factors of cystitis. We conducted a prospective observational study of AB and cystitis in KTRs from January to June 2017. One-hundred ninety seven KTRs were included: 175 (88.8%) with AB and 22 (11.2%) with cystitis. The most frequent etiologies were Escherichia coli, Klebsiellapneumoniae, Enterococcusfaecalis, and Pseudomonas aeruginosa. No differences were observed regarding the etiologies, antimicrobial susceptibility patterns, and microbiologic outcomes in AB vs. cystitis. The treatment of AB diminished the microbiological cure and increased the rates of microbiologic relapses and reinfections; in addition, treated AB patients showed a trend of developing symptomatic urinary tract infection in the following six months. The analysis of the data identified the following independent risk factors for cystitis during the six months of follow-up: AB treatment, thymoglobulin induction, previous acute pyelonephritis, and time since transplantation < 1 year. In summary, considering the lack of clinical benefits of treating AB and its impact on cystitis development in the follow-up, we support the recommendation of not screening for or treating AB. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Infection Control)

11 pages, 576 KiB

Open AccessArticle

Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures

by Aleksandra Gostyńska, Ludwika Piwowarczyk, Malwina Nadolna, Anna Jelińska, Katarzyna Dettlaff, Magdalena Ogrodowczyk, Maria Popielarz-Brzezińska and Maciej Stawny

Antibiotics 2021, 10(2), 217; https://doi.org/10.3390/antibiotics10020217 - 22 Feb 2021

Cited by 9 | Viewed by 3059

Abstract

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In [...] Read more.

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM–PN admixture samples. Physicochemical properties of MPM–PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM–PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM–Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM–Kabiven, MPM–Nutriflex Lipid Special, and MPM–Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM–Olimel), significant differences in zeta potential (MPM–Olimel, MPM–Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM–Kabiven, MPM–Olimel, and MPM–Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios. Full article

(This article belongs to the Special Issue Interactions Between Antibiotics and Other Drugs - Common Clinical Problem)

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16 pages, 5623 KiB

Open AccessArticle

Knowledge, Attitude, and Practices (KAP) Survey among Veterinarians, and Risk Factors Relating to Antimicrobial Use and Treatment Failure in Dairy Herds of India

by Deepthi Vijay, Jasbir Singh Bedi, Pankaj Dhaka, Randhir Singh, Jaswinder Singh, Anil Kumar Arora and Jatinder Paul Singh Gill

Antibiotics 2021, 10(2), 216; https://doi.org/10.3390/antibiotics10020216 - 22 Feb 2021

Cited by 21 | Viewed by 5283

Abstract

The indiscriminate usage of antimicrobials in the animal health sector contributes immensely to antimicrobial resistance (AMR). The present study aims to assess the antimicrobial usage pattern and risk factors for AMR in animal husbandry sector of India. A cross-sectional survey about Knowledge, Attitude, [...] Read more.

The indiscriminate usage of antimicrobials in the animal health sector contributes immensely to antimicrobial resistance (AMR). The present study aims to assess the antimicrobial usage pattern and risk factors for AMR in animal husbandry sector of India. A cross-sectional survey about Knowledge, Attitude, and Practices (KAP) among veterinarians was carried out using a questionnaire comprising of 52 parameters associated with antibiotic use and the emergence of AMR in dairy herds. Respondents’ KAP scores were estimated to rank their level of knowledge, attitude, and practice. Furthermore, risk factors associated with treatment failure were analyzed by univariable and multivariable analyses. Out of a total of 466 respondents, the majority had average knowledge (69.5%), neutral attitude (93.2%), and moderate practice (51.3%) scores toward judicious antibiotic usage. Veterinarians reported mastitis (88.0%), reproductive disorders (76.6%), and hemoprotozoan infections (49.6%) as the top three disease conditions that require antibiotic usage. Most of the veterinarians (90.6%) resorted to their “own experience” as the main criteria for antibiotic choice. The use of the highest priority critically important antimicrobials (HPCIA) listed by the World Health Organization (WHO) in animals, particularly quinolones (76.8%) and third-generation cephalosporins (47.8%), has been reported. On multivariable regression analysis of the risk factors, the lack of cooperation of the dairy farmers in the completion of a prescribed antibiotic course by the veterinarian and the demand for antibiotic use even in conditions not requiring antibiotic use were found to be significantly associated with the outcome variable “treatment failure” having respective odds of 1.8 (95%CI: 1.1–3.0) and 3.6 (95%CI: 2.3–5.8) (p < 0.05). The average KAP score of veterinarians, poor farm management practices, lack of awareness among farmers on prudent antibiotic use, and lack of antibiotic stewardship are the significant factors that need attention to combat the rising AMR in veterinary sector in India. Full article

(This article belongs to the Special Issue Monitoring and Surveillance of Veterinary Antimicrobial Use and Antibiotic Resistance in Animals)

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13 pages, 4091 KiB

Open AccessArticle

Baicalein Inhibits Streptococcus mutans Biofilms and Dental Caries-Related Virulence Phenotypes

by Aparna Vijayakumar, Hema Bhagavathi Sarveswari, Sahana Vasudevan, Karthi Shanmugam, Adline Princy Solomon and Prasanna Neelakantan

Antibiotics 2021, 10(2), 215; https://doi.org/10.3390/antibiotics10020215 - 21 Feb 2021

Cited by 21 | Viewed by 3501

Abstract

Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need [...] Read more.

Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need to identify compounds that curb the virulence of pathobionts without microbial killing. Through this study, we have demonstrated for the first time that 5,6,7-trihydroxyflavone (Baicalein) significantly downregulates crucial caries-related virulence phenotypes in Streptococcus mutans. Baicalein significantly inhibited biofilm formation by Streptococcus mutans UA159 (MBIC₅₀ = 200 μM), without significant growth inhibition. Notably, these concentrations of baicalein did not affect the commensal S. gordonii. Strikingly, baicalein significantly reduced cell surface hydrophobicity, autoaggregation and acid production by S. mutans. Mechanistic studies (qRT-PCR) showed downregulation of various genes regulating biofilm formation, surface attachment, quorum sensing, acid production and competence. Finally, we demonstrate the potential translational value of baicalein by reporting synergistic interaction with fluoride against S. mutans biofilms. Full article

(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products)

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11 pages, 1446 KiB

Open AccessArticle

Role of Antimicrobial Susceptibility Testing before First-Line Treatment Containing Clarithromycin for Helicobacter pylori Eradication in the Clinical Setting

by Seokin Kang, Yuri Kim, Ji Yong Ahn, Hwoon-Yong Jung, Nayoung Kim, Hee Kyong Na, Jeong Hoon Lee, Kee Wook Jung, Do Hoon Kim, Kee Don Choi, Ho June Song and Gin Hyug Lee

Antibiotics 2021, 10(2), 214; https://doi.org/10.3390/antibiotics10020214 - 21 Feb 2021

Cited by 8 | Viewed by 3142

Abstract

Background: Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST). Methods: 257 [...] Read more.

Background: Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST). Methods: 257 patients with H. pylori infection, with AST, performed before the eradication of clarithromycin-containing regimens were enrolled and divided into two groups: the SGT and ET groups. Results: Eradication rates in the SGT and ET groups were 85.4% and 58.4% (P < 0.01), respectively. In triple therapy (TT), eradication rates of the SGT and ET groups were 85.1% and 56.6% (P < 0.01), respectively. In sequential therapy (SET), eradication rates of the SGT and ET groups were 86.2% and 65.6% (P = 0.06), respectively. According to AST, TT had an eradication rate of 84.6% with strains susceptible to clarithromycin and amoxicillin and 11.1% with strains resistant to both. SET had an eradication rate of 89.5% with strains susceptible to clarithromycin, amoxicillin, and metronidazole, whereas it was 0% with strains resistant to clarithromycin and metronidazole. Conclusions: SGT as first-line treatment improved eradication rates of TT and SET by 28.5 (P < 0.01) and 20.6 (P = 0.06) percent points, respectively, compared with ET. Full article

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10 pages, 1779 KiB

Open AccessArticle

Isolation and Characterization of Antibacterial Carotane Sesquiterpenes from Artemisia argyi Associated Endophytic Trichoderma virens QA-8

by Xiao-Shan Shi, Yin-Ping Song, Ling-Hong Meng, Sui-Qun Yang, Dun-Jia Wang, Xing-Wang Zhou, Nai-Yun Ji, Bin-Gui Wang and Xiao-Ming Li

Antibiotics 2021, 10(2), 213; https://doi.org/10.3390/antibiotics10020213 - 20 Feb 2021

Cited by 13 | Viewed by 2248

Abstract

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in [...] Read more.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I–M (1–5), which have diverse substitution patterns, and seven known related analogues (6–12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1–3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7β-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents. Full article

(This article belongs to the Special Issue Novel Fungal Metabolites with Antimicrobial Activities)

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12 pages, 1212 KiB

Open AccessReview

Attacins: A Promising Class of Insect Antimicrobial Peptides

by Francesco Buonocore, Anna Maria Fausto, Giulia Della Pelle, Tomislav Roncevic, Marco Gerdol and Simona Picchietti

Antibiotics 2021, 10(2), 212; https://doi.org/10.3390/antibiotics10020212 - 20 Feb 2021

Cited by 43 | Viewed by 5030

Abstract

Insects produce a large repertoire of antimicrobial peptides (AMPs) as the first line of defense against bacteria, viruses, fungi or parasites. These peptides are produced from a large precursor that contains a signal domain, which is cleaved in vivo to produce the mature [...] Read more.

Insects produce a large repertoire of antimicrobial peptides (AMPs) as the first line of defense against bacteria, viruses, fungi or parasites. These peptides are produced from a large precursor that contains a signal domain, which is cleaved in vivo to produce the mature protein with antimicrobial activity. At present, AMPs from insects include several families which can be classified as cecropins, ponericins, defensins, lebocins, drosocin, Metchnikowin, gloverins, diptericins and attacins according to their structure and/or function. This short review is focused on attacins, a class of glycine-rich peptides/proteins that have been first discovered in the cecropia moth (Hyalophora cecropia). They are a rather heterogeneous group of immunity-related proteins that exhibit an antimicrobial effect mainly against Gram-negative bacteria. Here, we discuss different attacin and attacin-like AMPs that have been discovered so far and analyze their structure and phylogeny. Special focus is given to the physiological importance and mechanism of action of attacins against microbial pathogens together with their potential pharmacological applications, emphasizing their roles as antimicrobials. Full article

(This article belongs to the Special Issue Therapeutic Use of Antimicrobial Peptides: Joys and Sorrows)

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20 pages, 723 KiB

Open AccessReview

The Antimicrobial Effect of Cold Atmospheric Plasma against Dental Pathogens—A Systematic Review of In-Vitro Studies

by Gert Jungbauer, Dominick Moser, Steffen Müller, Wolfgang Pfister, Anton Sculean and Sigrun Eick

Antibiotics 2021, 10(2), 211; https://doi.org/10.3390/antibiotics10020211 - 20 Feb 2021

Cited by 29 | Viewed by 4115

Abstract

Interest in the application of cold atmospheric plasma (CAP) in the medical field has been increasing. Indications in dentistry are surface modifications and antimicrobial interventions. The antimicrobial effect of CAP is mainly attributed to the generation of reactive oxygen and reactive nitrogen species. [...] Read more.

Interest in the application of cold atmospheric plasma (CAP) in the medical field has been increasing. Indications in dentistry are surface modifications and antimicrobial interventions. The antimicrobial effect of CAP is mainly attributed to the generation of reactive oxygen and reactive nitrogen species. The aim of this article is to systematically review the available evidence from in-vitro studies on the antimicrobial effect of CAP on dental pathogens. A database search was performed (PubMed, Embase, Scopus). Data concerning the device parameters, experimental set-ups and microbial cultivation were extracted. The quality of the studies was evaluated using a newly designed assessment tool. 55 studies were included (quality score 31–92%). The reduction factors varied strongly among the publications although clusters could be identified between groups of set pathogen, working gases, and treatment time intervals. A time-dependent increase of the antimicrobial effect was observed throughout the studies. CAP may be a promising alternative for antimicrobial treatment in a clinically feasible application time. The introduced standardized protocol is able to compare the outcome and quality of in-vitro studies. Further studies, including multi-species biofilm models, are needed to specify the application parameters of CAP before CAP should be tested in randomized clinical trials. Full article

(This article belongs to the Special Issue Alternatives to Antibiotics in Dentistry)

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14 pages, 2529 KiB

Open AccessArticle

Activity of Imipenem, Meropenem, Cefepime, and Sulbactam in Combination with the β-Lactamase Inhibitor LN-1-255 against Acinetobacter spp.

by Cristina Lasarte-Monterrubio, Juan C. Vázquez-Ucha, Maria Maneiro, Jorge Arca-Suárez, Isaac Alonso, Paula Guijarro-Sánchez, John D. Buynak, Germán Bou, Concepción González-Bello and Alejandro Beceiro

Antibiotics 2021, 10(2), 210; https://doi.org/10.3390/antibiotics10020210 - 20 Feb 2021

Cited by 4 | Viewed by 3429

Abstract

Treatment of infections caused by Acinetobacter spp., particularly A. baumannii, is a major clinical problem due to its high rates of antibiotic resistance. New strategies must be developed; therefore, restoration of β-lactam efficacy through the use of β-lactamase inhibitors is paramount. Activities [...] Read more.

Treatment of infections caused by Acinetobacter spp., particularly A. baumannii, is a major clinical problem due to its high rates of antibiotic resistance. New strategies must be developed; therefore, restoration of β-lactam efficacy through the use of β-lactamase inhibitors is paramount. Activities of the antibiotics imipenem, meropenem, cefepime, and sulbactam in combination with the penicillin-sulfone inhibitor LN-1-255 were tested by microdilution against 148 isolates of Acinetobacter spp. collected in 14 hospitals in Spain in 2020. Relevantly, the MIC₉₀ (i.e., minimum concentration at which 90% of isolates were inhibited) of antibiotics in combination with LN-1-255 decreased 4- to 8-fold for all of the Acinetobacter isolates. Considering only the carbapenem-resistant A. baumannii isolates, which produce carbapenem-hydrolyzing class D β-lactamases, the addition of LN-1-255 decreased the resistance rates from 95.1% to 0% for imipenem, from 100% to 9.8% for meropenem, from 70.7% to 7.3% for cefepime, and sulbactam resistance rates from 9.8% to 0% and intermediate susceptibility rates from 53.7% to 2.4%. The inhibitor also decreased the minimum inhibitory concentrations (MICs) when tested against non-carbapenem-resistant Acinetobacter spp. isolates. In conclusion, combining LN-1-255 with imipenem, meropenem, cefepime, and sulbactam to target A. baumannii, and especially carbapenem-resistant isolates, represents an attractive option that should be developed for the treatment of infections caused by this pathogen. Full article

(This article belongs to the Special Issue Non-antimicrobial Agents as Adjuvants against Bacterial Infections)

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30 pages, 1054 KiB

Open AccessEditor’s ChoiceReview

Rapid Methods for Antimicrobial Resistance Diagnostics

by Georgia D. Kaprou, Ieva Bergšpica, Elena A. Alexa, Avelino Alvarez-Ordóñez and Miguel Prieto

Antibiotics 2021, 10(2), 209; https://doi.org/10.3390/antibiotics10020209 - 20 Feb 2021

Cited by 54 | Viewed by 15275

Abstract

Antimicrobial resistance (AMR) is one of the most challenging threats in public health; thus, there is a growing demand for methods and technologies that enable rapid antimicrobial susceptibility testing (AST). The conventional methods and technologies addressing AMR diagnostics and AST employed in clinical [...] Read more.

Antimicrobial resistance (AMR) is one of the most challenging threats in public health; thus, there is a growing demand for methods and technologies that enable rapid antimicrobial susceptibility testing (AST). The conventional methods and technologies addressing AMR diagnostics and AST employed in clinical microbiology are tedious, with high turnaround times (TAT), and are usually expensive. As a result, empirical antimicrobial therapies are prescribed leading to AMR spread, which in turn causes higher mortality rates and increased healthcare costs. This review describes the developments in current cutting-edge methods and technologies, organized by key enabling research domains, towards fighting the looming AMR menace by employing recent advances in AMR diagnostic tools. First, we summarize the conventional methods addressing AMR detection, surveillance, and AST. Thereafter, we examine more recent non-conventional methods and the advancements in each field, including whole genome sequencing (WGS), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) spectrometry, Fourier transform infrared (FTIR) spectroscopy, and microfluidics technology. Following, we provide examples of commercially available diagnostic platforms for AST. Finally, perspectives on the implementation of emerging concepts towards developing paradigm-changing technologies and methodologies for AMR diagnostics are discussed. Full article

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13 pages, 1769 KiB

Open AccessArticle

A Novel Ivermectin-Derived Compound D4 and Its Antimicrobial/Biofilm Properties against MRSA

by Xinyi Tan, Haoji Xie, Bin Zhang, Jiale Zhou, Zhende Dou, Xiao Wang and Ning Wang

Antibiotics 2021, 10(2), 208; https://doi.org/10.3390/antibiotics10020208 - 20 Feb 2021

Cited by 10 | Viewed by 3878

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms infection is still a serious threat to global health. It is urgent to develop efficient drugs by repositioning or designing drugs to solve this problem. In this study, the antibacterial/biofilm activity and mechanisms of ivermectin (D) [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms infection is still a serious threat to global health. It is urgent to develop efficient drugs by repositioning or designing drugs to solve this problem. In this study, the antibacterial/biofilm activity and mechanisms of ivermectin (D) and its 4″-position amino substitution derivative (D4) against MRSA were investigated. The minimum inhibitory concentration (MIC) of D was 20 μg/mL, which is four times higher than D4 (MIC = 5 μg/mL). The mechanism research demonstrated that D4 was more potent than D at destroying bacterial cell wall, permeating cell membrane (6.25–36.0% vs 1.92–6.04%) and binding to MRSA genomic DNA. Moreover, after incubation with 10–40 μg/mL D4 for 24 h, the percentages of biofilm decreased by 21.2–92.9%, which was more effective than D (no significant change at 40 μg/mL). The antibiofilm effect is achieved by regulating the expression of related genes (RSH, relQ, rsbU, sigB, spA, and icaD). Additionally, though the higher hemolysis makes D4 a safety risk for intravenous injection, other administration options could be considered as well. Therefore, all the results have indicated that D4 may be a potential candidate compound for the treatment of MRSA and its biofilm infections. Full article

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5 pages, 207 KiB

Open AccessEditorial

Toward a New Future for Essential Oils

by Edoardo Napoli and Maura Di Vito

Antibiotics 2021, 10(2), 207; https://doi.org/10.3390/antibiotics10020207 - 19 Feb 2021

Cited by 13 | Viewed by 2471

Abstract

Essential oils (EOs) are peculiar phytocomplexes in the already widely varied world of natural bioactive substances [...] Full article

(This article belongs to the Special Issue Chemical Composition and Biological Activities of Essential Oils)

12 pages, 1336 KiB

Open AccessArticle

Antimicrobial Resistance and Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Isolated from Slaughtered Pigs and Pork in the Central Region of Thailand

by Wimonrat Tanomsridachchai, Kanjana Changkaew, Ruchirada Changkwanyeun, Watsawan Prapasawat, Apiradee Intarapuk, Yukari Fukushima, Nattapong Yamasamit, Thoko Flav Kapalamula, Chie Nakajima, Orasa Suthienkul and Yasuhiko Suzuki

Antibiotics 2021, 10(2), 206; https://doi.org/10.3390/antibiotics10020206 - 19 Feb 2021

Cited by 18 | Viewed by 3156

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) have been a major public health concern in humans. Among MRSA, livestock-associated (LA)-MRSA strains have always been associated with exposure to livestock or their products and have emerged in different countries globally. Although studies have identified LA-MRSA from healthy [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) have been a major public health concern in humans. Among MRSA, livestock-associated (LA)-MRSA strains have always been associated with exposure to livestock or their products and have emerged in different countries globally. Although studies have identified LA-MRSA from healthy pigs and pork in Thailand, prevalence in slaughtered pigs is still unknown. In addition, there are few reports on the epidemiology and molecular characteristics of LA-MRSA in Thailand. Hence, this is the first report investigating the epidemiology and molecular characteristics of MRSA in individual slaughtered pigs and pork in Thailand. A total of 204 nasal swab and 116 retailed pork samples were collected from three slaughterhouses and four fresh markets, respectively. Individual samples were used for screening for MRSA and obtained isolates were examined for drug- resistance profiling for 12 antimicrobial agents of 10 drug classes. In addition, SCCmec typing and multi-locus sequence typing were conducted to obtain genotype profiles. MRSA were isolated from 11 and 52 nasal swab and pork samples, respectively. The prevalence was significantly higher in the pork than in the nasal swab samples (p-value < 0.05). A high prevalence of ST9-SCCmecIX and ST398-SCCmecV with high-level antimicrobial resistance from markets and slaughterhouses indicated the spreading of MRSA with these genotypes in the Thai swine processing chains and suggested the need for further investigation to determine a control. Full article

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16 pages, 1212 KiB

Open AccessArticle

Natural Agents against Bovine Mastitis Pathogens

by Zorana Kovačević, Miodrag Radinović, Ivana Čabarkapa, Nebojša Kladar and Biljana Božin

Antibiotics 2021, 10(2), 205; https://doi.org/10.3390/antibiotics10020205 - 19 Feb 2021

Cited by 35 | Viewed by 4528

Abstract

Bovine mastitis is the most widespread and economically important disease worldwide. The present study aimed to determine bioactive compounds in two essential oils (EOs) from wild (Thymus serpyllum) and common thyme (Thymus vulgaris) and to assess the antioxidant potential as well as antibacterial [...] Read more.

Bovine mastitis is the most widespread and economically important disease worldwide. The present study aimed to determine bioactive compounds in two essential oils (EOs) from wild (Thymus serpyllum) and common thyme (Thymus vulgaris) and to assess the antioxidant potential as well as antibacterial efficacy of the EOs against mastitis-associated bacteria. The study also included antibiotic susceptibility tests. The strains were previously isolated from lactating animals with clinical and subclinical mastitis. The antioxidant potential of the commercial EOs of wild and common thyme was evaluated by five in vitro assays. The antibacterial activity was performed using the microdilution technique, while antibiotic susceptibility testing was performed by the Kirby–Bauer disc diffusion method. The dominant compound in wild thyme was thymol (45.22%), followed by p-cymene (23.83%) and γ-terpinene (3.12%), while in common thyme, it was thymol (54.17%), followed by γ-terpinene (22.18%) and p-cymene (16.66%). Among the fourteen mastitis-associated bacteria, strain IX Streptococcus spp. (β-hemolytic) was the most sensitive to the tested EOs (minimum inhibitory concentration (MIC)/minimal bactericidal concentration (MBC) were 0.78/1.56 and 0.39/0.78 mg/mL for T. serpyllum (TS) and T. vulgaris (TV), respectively). Regarding Streptococcus spp. β heamoliticus, MICs for TS ranged from 0.78 to 1.56 mg/mL, while for the same oil, MBCs ranged from 1.56 to 12.5 mg/mL. In the case of T. vulgaris, MICs ranged from 0.39 to 3.125 mg/ mL, while MBCs ranged from 3.125 to 6.25 mg/mL. TV is more active against E. coli, E. sakazakii, and Streptococcus spp., while it is less effective against Staphylococcus spp. than TS. The study revealed that the tested EOs possess remarkable antioxidative and antibacterial activities and could be used in the development of pharmaceutical formulation as an alternative to conventional mastitis therapy. Full article

(This article belongs to the Special Issue Optimization of Veterinary Antimicrobial Treatment in Companion and Food Animals)

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13 pages, 921 KiB

Open AccessArticle

Searching for Small Molecules as Antibacterials: Non-Cytotoxic Diarylureas Analogues of Triclocarban

by Alessia Catalano, Domenico Iacopetta, Antonio Rosato, Lara Salvagno, Jessica Ceramella, Francesca Longo, Maria Stefania Sinicropi and Carlo Franchini

Antibiotics 2021, 10(2), 204; https://doi.org/10.3390/antibiotics10020204 - 19 Feb 2021

Cited by 12 | Viewed by 2529

Abstract

Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as [...] Read more.

Triclocarban (TCC), a broad-spectrum lipophilic antimicrobial agent, is a diarylurea derivative that has been used for more than 60 years as a major ingredient of toys, clothing, food packaging materials, food industry floors, medical supplies and especially of personal care products, such as soaps, toothpaste and shampoo. In September 2016, the U.S. FDA banned nineteen antimicrobial ingredients, including TCC, in over-the-counter consumer antiseptic wash products, due to their toxicity. Withdrawal of TCC has prompted efforts to search for new antimicrobial compounds. In this paper, we present the synthesis and biological evaluation, as antibiotic and non-cytotoxic agents, of a series of diarylureas, analogues of TCC. These compounds are characterized by an intriguingly simple chemistry and can be easily synthesized. Among the synthesized compounds, 1ab and 1bc emerge as the most interesting compounds as they show the same activity of TCC (MIC = 16 µg/mL) against Staphylococcus aureus, and a higher activity than TCC against Enterococcus faecalis (MIC = 32 µg/mL versus MIC = 64 µg/mL). Moreover, 1ab and 1bc show no cytotoxicity towards the human mammary epithelial cells MCF-10A and embryonic kidney epithelial cells Hek-293, in opposition to TCC, which exhibits a marked cytotoxicity on the same cell lines and shows a good antitumor activity on a panel of cell lines tested. Full article

(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities?)

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27 pages, 8065 KiB

Open AccessArticle

Vapor Phosphorylation of Cellulose by Phosphorus Trichlo-Ride: Selective Phosphorylation of 6-Hydroxyl Function—The Synthesis of New Antimicrobial Cellulose 6-Phosphate(III)-Copper Complexes

by Marcin H. Kudzin, Zdzisława Mrozińska and Paweł Urbaniak

Antibiotics 2021, 10(2), 203; https://doi.org/10.3390/antibiotics10020203 - 19 Feb 2021

Cited by 7 | Viewed by 2859

Abstract

This research is focused on a synthesis of copper-cellulose phosphates antimicrobial complexes. Vapor-phase phosphorylations of cellulose were achieved by exposing microcrystalline cellulose to phosphorus trichloride (PCl₃) vapors. The cellulose-O-dichlorophosphines (Cell-O-PCl₂) formed were hydrolyzed to cellulose- [...] Read more.

This research is focused on a synthesis of copper-cellulose phosphates antimicrobial complexes. Vapor-phase phosphorylations of cellulose were achieved by exposing microcrystalline cellulose to phosphorus trichloride (PCl₃) vapors. The cellulose-O-dichlorophosphines (Cell-O-PCl₂) formed were hydrolyzed to cellulose-O-hydrogenphosphate (P(III)) (Cell-O-P(O)(H)(OH)), which, in turn, were converted into corresponding copper(II) complexes (Cell-O-P(O)(H)(OH)∙Cu²⁺). The analysis of the complexes Cell-O-P(O)(H)(OH)∙Cu²⁺ covered: scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), atomic absorption spectrometry with flame excitation (FAAS), and bioactivity tests against representative Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The antimicrobial tests of synthesized Cell-O-P(O)(H)(OH)∙Cu²⁺ revealed their potential applications as an antibacterial material. Full article

(This article belongs to the Special Issue Antimicrobial Materials and Surface)

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14 pages, 1776 KiB

Open AccessReview

Genetic and Chemical Engineering of Phages for Controlling Multidrug-Resistant Bacteria

by Dingming Guo, Jingchao Chen, Xueyang Zhao, Yanan Luo, Menglu Jin, Fenxia Fan, Chaiwoo Park, Xiaoman Yang, Chuqing Sun, Jin Yan, Weihua Chen and Zhi Liu

Antibiotics 2021, 10(2), 202; https://doi.org/10.3390/antibiotics10020202 - 19 Feb 2021

Cited by 17 | Viewed by 4677

Abstract

Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. [...] Read more.

Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. Phage therapy is regarded as one of the most promising alternative strategies to fight pathogens in the post-antibiotic era. Recently, genetic and chemical engineering methods have been applied in phage modification. Among them, genetic engineering includes the expression of toxin proteins, modification of host recognition receptors, and interference of bacterial phage-resistant pathways. Chemical engineering, meanwhile, involves crosslinking phage coats with antibiotics, antimicrobial peptides, heavy metal ions, and photothermic matters. Those advances greatly expand the host range of phages and increase their bactericidal efficiency, which sheds light on the application of phage therapy in the control of multidrug-resistant pathogens. This review reports on engineered phages through genetic and chemical approaches. Further, we present the obstacles that this novel antimicrobial has incurred. Full article

(This article belongs to the Special Issue Bacteriophages: An Inspiration for the Development of New Antimicrobial and Antibiofilm Agents)

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10 pages, 1366 KiB

Open AccessArticle

Pharmacodynamics of Ceftibuten: An Assessment of an Oral Cephalosporin against Enterobacterales in a Neutropenic Murine Thigh Model

by Maxwell J. Lasko, Tomefa E. Asempa and David P. Nicolau

Antibiotics 2021, 10(2), 201; https://doi.org/10.3390/antibiotics10020201 - 19 Feb 2021

Cited by 5 | Viewed by 3014

Abstract

Efforts to develop and pair novel oral β-lactamase inhibitors with existing β-lactam agents to treat extended spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales are gaining ground. Ceftibuten is an oral third-generation cephalosporin capable of achieving high urine concentrations; however, there are no robust data [...] Read more.

Efforts to develop and pair novel oral β-lactamase inhibitors with existing β-lactam agents to treat extended spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales are gaining ground. Ceftibuten is an oral third-generation cephalosporin capable of achieving high urine concentrations; however, there are no robust data describing its pharmacodynamic profile. This study characterizes ceftibuten pharmacokinetics and pharmacodynamics in a neutropenic murine thigh infection model. Enterobacterales isolates expressing no known clinically-relevant enzymatic resistance (n = 7) or harboring an ESBL (n = 2) were evaluated. The ceftibuten minimum inhibitory concentrations (MICs) were 0.03–4 mg/L. Nine ceftibuten regimens, including a human-simulated regimen (HSR) equivalent to clinical ceftibuten doses of 300 mg taken orally every 8 h, were utilized to achieve various fT > MICs. A sigmoidal E_max model was fitted to fT > MIC vs. change in log₁₀ CFU/thigh to determine the requirements for net stasis and 1-log₁₀ CFU/thigh bacterial burden reduction. The growth of the 0 h and 24 h control groups was 5.97 ± 0.37 and 8.51 ± 0.84 log₁₀ CFU/thigh, respectively. Ceftibuten HSR resulted in a -0.49 to -1.43 log₁₀ CFU/thigh bacterial burden reduction at 24 h across the isolates. Stasis and 1-log₁₀ CFU/thigh reduction were achieved with a fT > MIC of 39% and 67%, respectively. The fT > MIC targets identified can be used to guide ceftibuten dosage selection to optimize the likelihood of clinical efficacy. Full article

(This article belongs to the Section Mechanisms and Structural Biology of Antibiotic Action)

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13 pages, 513 KiB

Open AccessArticle

Assessment of Appropriateness of Antimicrobial Therapy in Resource-Constrained Settings: Development and Piloting of a Novel Tool—AmRAT

by Ashish Kumar Kakkar, Nusrat Shafiq, Neeru Sahni, Ritin Mohindra, Navjot Kaur, Nanda Gamad, Aditi Panditrao, Dimple Kondal, Samir Malhotra, Praveen Kumar M, Rachna Rohilla, Samiksha Bhattacharjee, Ankit Kumar, Ritika Kondel Bhandari, Avaneesh Kumar Pandey, Imraan Rather, Chakrant Mothsara, Cvn Harish, Devaraj Belavagi and Gopal Vishwas

Antibiotics 2021, 10(2), 200; https://doi.org/10.3390/antibiotics10020200 - 19 Feb 2021

Cited by 4 | Viewed by 2955

Abstract

Inappropriate antimicrobial prescribing is considered to be the leading cause of high burden of antimicrobial resistance (AMR) in resource-constrained lower- and middle-income countries. Under its global action plan, the World Health Organization has envisaged tackling the AMR threat through promotion of rational antibiotic [...] Read more.

Inappropriate antimicrobial prescribing is considered to be the leading cause of high burden of antimicrobial resistance (AMR) in resource-constrained lower- and middle-income countries. Under its global action plan, the World Health Organization has envisaged tackling the AMR threat through promotion of rational antibiotic use among prescribers. Given the lack of consensus definitions and other associated challenges, we sought to devise and validate an Antimicrobial Rationality Assessment Tool—AmRAT—for standardizing the assessment of appropriateness of antimicrobial prescribing. A consensus algorithm was developed by a multidisciplinary team consisting of intensivists, internal medicine practitioners, clinical pharmacologists, and infectious disease experts. The tool was piloted by 10 raters belonging to three groups of antimicrobial stewardship (AMS) personnel: Master of Pharmacology (M.Sc.) (n = 3, group A), Doctor of Medicine (MD) residents (n = 3, group B), and DM residents in clinical pharmacology (n = 4, group C) using retrospective patient data from 30 audit and feedback forms collected as part of an existing AMS program. Percentage agreement and the kappa (κ) coefficients were used to measure inter-rater agreements amongst themselves and with expert opinion. Sensitivity and specificity estimates were analyzed comparing their assessments against the gold standard. For the overall assessment of rationality, the mean percent agreement with experts was 76.7% for group A, 68.9% for group B, and 77.5% for group C. The kappa values indicated moderate agreement for all raters in group A (κ 0.47–0.57), and fair to moderate in group B (κ 0.22–0.46) as well as group C (κ 0.37–0.60). Sensitivity and specificity for the same were 80% and 68.6%, respectively. Though evaluated by raters with diverse educational background and variable AMS experience in this pilot study, our tool demonstrated high percent agreement and good sensitivity and specificity, assuring confidence in its utility for assessing appropriateness of antimicrobial prescriptions in resource-constrained healthcare environments. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Secondary Care across Different Resource Settings)

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11 pages, 1195 KiB

Open AccessArticle

Antimicrobial Prescription Pattern in Ho Teaching Hospital, Ghana: Seasonal Determination Using a Point Prevalence Survey

by Cornelius C. Dodoo, Emmanuel Orman, Thelma Alalbila, Adelaide Mensah, Jonathan Jato, Kwadwo A. Mfoafo, Isaac Folitse, Araba Hutton-Nyameaye, Inemesit Okon Ben, Paapa Mensah-Kane, Emmanuel Sarkodie, Eneyi Kpokiri, Misha Ladva, Benedict Awadzi and Yogini Jani

Antibiotics 2021, 10(2), 199; https://doi.org/10.3390/antibiotics10020199 - 18 Feb 2021

Cited by 15 | Viewed by 3713

Abstract

A standardised Global Point Prevalence Survey (PPS) tool was used to determine the antimicrobial prescription pattern in the Ho Teaching Hospital on two separate occasions in a total of 14 wards in the hospital, including dedicated wards for paediatrics and neonates. Manually collected [...] Read more.

A standardised Global Point Prevalence Survey (PPS) tool was used to determine the antimicrobial prescription pattern in the Ho Teaching Hospital on two separate occasions in a total of 14 wards in the hospital, including dedicated wards for paediatrics and neonates. Manually collected and anonymised data were entered, validated, analysed and reported using a web-based global PPS application. With 147 and 153 patients considered in the July 2019 and January 2020 surveys, respectively, 98 patients (66.7%) and 84 patients (54.9%) had received one or more antimicrobials. The prevalence of antimicrobial use in the adult wards was 64.3% (72/112) and 53.4% (63/118) in the first and second surveys, respectively. The prevalence in the paediatric wards was 60.0% (12/20) and 62.5% (10/16), respectively, in the two surveys, while that in the neonatal wards was 93.3% (14/15) and 57.9% (11/19), respectively. β-lactams were the most used antibiotics in both periods. Malaria was the most common diagnosis requiring the use of antimicrobials in July 2019, accounting for 19.4% of the diagnoses, whereas in January 2020, it was skin and soft-tissue conditions (28.1%). This reflects a seasonal association between malaria and rainfall patterns. Out of the antimicrobials prescribed during each of the survey periods, 95% were used for empirical treatment, and this could be attributed to a number of reasons, including logistical challenges, among others, that require further exploration in the context of local, national and international policy recommendations. Full article

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10 pages, 685 KiB

Open AccessArticle

Multidrug-Resistant Coagulase-Negative Staphylococci Isolated from Bloodstream in the uMgungundlovu District of KwaZulu-Natal Province in South Africa: Emerging Pathogens

by Jonathan Asante, Bakoena A. Hetsa, Daniel G. Amoako, Akebe Luther King Abia, Linda A. Bester and Sabiha Y. Essack

Antibiotics 2021, 10(2), 198; https://doi.org/10.3390/antibiotics10020198 - 18 Feb 2021

Cited by 21 | Viewed by 2677

Abstract

Coagulase-negative staphylococci (CoNS) are increasingly associated with nosocomial infections, especially among the immunocompromised and those with invasive medical devices, posing a significant concern. We report on clinical multidrug-resistant CoNS from the uMgungundlovu District, KwaZulu-Natal Province, South Africa, as emerging pathogens. One hundred and [...] Read more.

Coagulase-negative staphylococci (CoNS) are increasingly associated with nosocomial infections, especially among the immunocompromised and those with invasive medical devices, posing a significant concern. We report on clinical multidrug-resistant CoNS from the uMgungundlovu District, KwaZulu-Natal Province, South Africa, as emerging pathogens. One hundred and thirty presumptive CoNS were obtained from blood cultures. Culture, biochemical tests, and the Staphaurex™ Latex Agglutination Test were used for the initial identification of CoNS isolates; confirmation and speciation were undertaken by the VITEK 2 system. Susceptibilities of isolates against a panel of 20 antibiotics were determined using the Kirby-Bauer disk diffusion method, and the multiple antibiotic resistance (MAR) indices of the isolates were determined. The polymerase chain reaction (PCR) was used to amplify the mecA gene to confirm methicillin resistance. Overall, 89/130 presumptive CoNS isolates were confirmed as CoNS by the VITEK 2 system. Of these, 68 (76.4%) isolates were putatively methicillin-resistant by the phenotypic cefoxitin screen test and 63 (92.6%) were mecA positive. Staphylococcus epidermidis (19.1%), S. hominis ssp. hominis (15.7%), and S. haemolyticus (16.9%) were the most common CoNS species. Isolates showed high percentage resistance against penicillin (100.0%), erythromycin (74.2%), and azithromycin (74.2%) while displaying high susceptibilities to linezolid (95.5%), gentamicin (95.5%), and tigecycline (94.4%). Multidrug resistance (MDR) was observed in 76.4% of isolates. MAR index calculation revealed 71.9% of isolates with MAR index >0.2 and 20.2% >0.5. Isolates with the highest MAR indices (0.7 and 0.8) were recovered from the neonatal intensive care unit. Fifty-one MDR antibiograms were observed. The high prevalence of methicillin resistance and multidrug resistance in several species of CoNS necessitates surveillance of this emerging pathogen, currently considered a contaminant of microbial cultures. Full article

(This article belongs to the Special Issue Healthcare Infections, Healthcare Environment and Antimicrobial Resistance)

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10 pages, 269 KiB

Open AccessArticle

Prevalence and Characterization of Methicillin-Resistant Staphylococcus aureus from Community- and Hospital-Associated Infections: A Tertiary Care Center Study

by Puthiya Purayil Preeja, Sanath H. Kumar and Veena Shetty

Antibiotics 2021, 10(2), 197; https://doi.org/10.3390/antibiotics10020197 - 18 Feb 2021

Cited by 27 | Viewed by 3480

Abstract

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly prevalent in both community and hospital settings. The aim of this study was to determine the prevalence, molecular characteristics and antibiotic resistance profiles of CA-MRSA from community- and hospital-associated infections in a tertiary care [...] Read more.

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly prevalent in both community and hospital settings. The aim of this study was to determine the prevalence, molecular characteristics and antibiotic resistance profiles of CA-MRSA from community- and hospital-associated infections in a tertiary care hospital in Mangalore, India. Of 520 S. aureus isolates, 362 were from inpatients (IP) and 158 were from outpatients (OP). One-hundred and thirty-two MRSA isolates obtained from 94 inpatients and 38 outpatients with complete clinical details were further analyzed. Of these, 81 (61.4%) were CA-MRSA (IP-47.9%, OP-94.7%) and 51 (38.6%) were HA-MRSA (IP-52.1%, OP-5.3%). All (100%) MRSA isolates were mecA gene positive. SCCmec typing identified SCCmec type IV (50.6%) and SCCmec type V (66.7%) in CA-MRSA, while SCCmec type I (41.2%), SCCmec type III (19.6%), SCCmec type IV (31.4%) and SCCmec type V (25.5%) were detected in HA-MRSA isolates. The Panton–Valentine Leukocidin (PVL) gene was found in 70.4% of CA-MRSA, 43.1% of HA-MRSA with SCCmec type IV and SCCmec type V, and in 7.8% of true HA-MRSA. The antibiotic resistance profiles were determined by the disc diffusion method. Resistance to cefoxitin was used to identify MRSA. A significant difference (p < 0.05) was observed between CA-MRSA and HA-MRSA with respect to resistance against cephalexin, cefotaxime, levofloxacin, linezolid and teicoplanin. CA-MRSA was predominantly resistant to ciprofloxacin (86.4%), erythromycin (66.7%), ofloxacin (49.4%), cefotaxime (44.4%), gentamicin (40.7%) and clindamycin (40.7%), while HA-MRSA showed resistance against ciprofloxacin (80.4%), erythromycin (80.1%), cefotaxime (70.6%),ofloxacin (58.8%), clindamycin (47.1%) and levofloxacin (41.2%).This study reports the prevalence of CA-MRSA in community and hospital settings and the possibility of multidrug-resistant CA-MRSA replacing HA-MRSA in hospitals. The observations from our study emphasize the need for urgent measures to manage this emerging crisis in healthcare settings. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

10 pages, 609 KiB

Open AccessEditor’s ChoiceArticle

Impact of the COVID-19 Pandemic on Antibiotic Prescribing for Common Infections in The Netherlands: A Primary Care-Based Observational Cohort Study

by Alma C. van de Pol, Josi A. Boeijen, Roderick P. Venekamp, Tamara Platteel, Roger A. M. J. Damoiseaux, Marlous F. Kortekaas and Alike W. van der Velden

Antibiotics 2021, 10(2), 196; https://doi.org/10.3390/antibiotics10020196 - 18 Feb 2021

Cited by 47 | Viewed by 4467

Abstract

In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic [...] Read more.

In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic prescribing in Dutch primary care. All patients included in the routine health care database of the Julius General Practitioners’ Network were followed from March through May 2019 (n = 389,708) and March through May 2020 (n = 405,688). We extracted data on consultations for respiratory/ear, urinary tract, gastrointestinal and skin infections using the International Classification of Primary Care (ICPC) codes. These consultations were combined in disease episodes and linked to antibiotic prescriptions. The numbers of infectious disease episodes (total and those treated with antibiotics), complications, and antibiotic prescription rates (i.e., proportion of episodes treated with antibiotics) were calculated and compared between the study periods in 2019 and 2020. Fewer episodes were observed during the pandemic months than in the same months in 2019 for both the four infectious disease entities and complications such as pneumonia, mastoiditis and pyelonephritis. The largest decline was seen for gastrointestinal infections (relative risk (RR), 0.54; confidence interval (CI), 0.51 to 0.58) and skin infections (RR, 0.71; CI, 0.67 to 0.75). The number of episodes treated with antibiotics declined as well, with the largest decrease seen for respiratory/ear infections (RR, 0.54; CI, 0.52 to 0.58). The antibiotic prescription rate for respiratory/ear infections declined from 21% to 13% (difference −8.0% (CI, −8.8 to −7.2)), yet the prescription rates for other infectious disease entities remained similar or increased slightly. The decreases in primary care infectious disease episodes and antibiotic use were most pronounced in weeks 15–19, mid-COVID-19 wave, after an initial peak in respiratory/ear infection presentation in week 11, the first week of lock-down. In conclusion, our findings indicate that the COVID-19 pandemic has had profound effects on the presentation of infectious disease episodes and antibiotic use in primary care in the Netherlands. Consequently, the number of infectious disease episodes treated with antibiotics decreased. We found no evidence of an increase in complications. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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Antibiotics, Volume 10, Issue 2 (February 2021) – 130 articles

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