Antibiotics

9 pages, 549 KiB

Open AccessArticle

COSUTI: A Core Outcome Set (COS) for Interventions for the Treatment of Uncomplicated Urinary Tract Infection (UTI) in Adults

by Claire Beecher, Sinead Duane, Akke Vellinga, Andrew W. Murphy, Martin Cormican, Andrew Smyth, Patricia Healy, Michael Moore, Paul Little, Carmel Geoghegan and Declan Devane

Antibiotics 2022, 11(12), 1846; https://doi.org/10.3390/antibiotics11121846 - 19 Dec 2022

Cited by 2 | Viewed by 2084

Abstract

Background: Uncomplicated urinary tract infections (UTIs) are among the most common presentations of bacterial infections in the outpatient setting. The variation of outcomes reported in trials to assess the most effective treatment interventions for uncomplicated UTIs has meant that comparing and synthesising the [...] Read more.

Background: Uncomplicated urinary tract infections (UTIs) are among the most common presentations of bacterial infections in the outpatient setting. The variation of outcomes reported in trials to assess the most effective treatment interventions for uncomplicated UTIs has meant that comparing and synthesising the outcomes across trials is challenging and limits the reliability of evidence which would otherwise inform healthcare decisions. Objective: Develop a Core Outcome Set (COS) for interventions for the treatment of uncomplicated UTIs in otherwise healthy adults. Methods: The COS development consisted of three phases: (1) A systematic review to identify outcomes reported in randomised trials and systematic reviews of randomised trials comparing the effectiveness of any interventions for the treatment of uncomplicated UTI in otherwise healthy adults; (2) Outcomes identified in the systematic review were prioritised in an online 3-round modified Delphi survey with healthcare practitioners (n = 68), researchers (n = 5), and people who have experienced or cared for someone experiencing a UTI (n = 180); (3) An online consensus meeting to determine the final COS with healthcare practitioners and policymakers (n = 9), researchers (n = 4), and people who have experienced or cared for someone experiencing a UTI (n = 7). Results: We identified a large number of outcomes. Through the use of robust consensus methods, those outcomes were reduced to a core set of six outcomes that should, at a minimum, be measured and reported in randomised trials and systematic reviews of interventions treating uncomplicated UTIs in adults. Full article

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

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14 pages, 2405 KiB

Open AccessArticle

Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer

by Anchalee Rawangkan, Pattama Wongsirisin, Grissana Pook-In, Achiraya Siriphap, Atchariya Yosboonruang, Anong Kiddee, Jureeporn Chuerduangphui, Nanthawan Reukngam, Acharaporn Duangjai, Surasak Saokaew and Ratsada Praphasawat

Antibiotics 2022, 11(12), 1845; https://doi.org/10.3390/antibiotics11121845 - 19 Dec 2022

Cited by 4 | Viewed by 2592

Abstract

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new [...] Read more.

Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G₀/G₁ phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs. Full article

(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities? 2nd Volume)

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25 pages, 3625 KiB

Open AccessArticle

Essential Oils of Aromatic Plant Species from the Atlantic Rainforest Exhibit Extensive Chemical Diversity and Antimicrobial Activity

by Crislene V. Perigo, Lenita L. Haber, Roselaine Facanali, Maria A. R. Vieira, Roseli B. Torres, Luís C. Bernacci, Elsie F. Guimarães, João B. Baitello, Marcos E. G. Sobral, Vera Quecini and Marcia Ortiz M. Marques

Antibiotics 2022, 11(12), 1844; https://doi.org/10.3390/antibiotics11121844 - 19 Dec 2022

Cited by 2 | Viewed by 2470

Abstract

Microbial resistance, caused by the overuse or inadequate application of antibiotics, is a worldwide crisis, increasing the risk of treatment failure and healthcare costs. Plant essential oils (EOs) consist of hydrophobic metabolites with antimicrobial activity. The antimicrobial potential of the chemical diversity of [...] Read more.

Microbial resistance, caused by the overuse or inadequate application of antibiotics, is a worldwide crisis, increasing the risk of treatment failure and healthcare costs. Plant essential oils (EOs) consist of hydrophobic metabolites with antimicrobial activity. The antimicrobial potential of the chemical diversity of plants from the Atlantic Rainforest remains scarcely characterized. In the current work, we determined the metabolite profile of the EOs from aromatic plants from nine locations and accessed their antimicrobial and biocidal activity by agar diffusion assays, minimum inhibitory concentration, time-kill and cell-component leakage assays. The pharmacokinetic properties of the EO compounds were investigated by in silico tools. More than a hundred metabolites were identified, mainly consisting of sesqui and monoterpenes. Individual plants and botanical families exhibited extensive chemical variations in their EO composition. Probabilistic models demonstrated that qualitative and quantitative differences contribute to chemical diversity, depending on the botanical family. The EOs exhibited antimicrobial biocidal activity against pathogenic bacteria, fungi and multiple predicted pharmacological targets. Our results demonstrate the antimicrobial potential of EOs from rainforest plants, indicate novel macromolecular targets, and contribute to highlighting the chemical diversity of native species. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms)

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37 pages, 1659 KiB

Open AccessEditor’s ChoiceReview

The Blood–Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults

by Nicholas Haddad, Maddie Carr, Steve Balian, James Lannin, Yuri Kim, Courtney Toth and Jennifer Jarvis

Antibiotics 2022, 11(12), 1843; https://doi.org/10.3390/antibiotics11121843 - 19 Dec 2022

Cited by 17 | Viewed by 25094

Abstract

Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for [...] Read more.

Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for therapy of CNS infections, some with established roles and indications, others with experimental reporting based on case studies or small series. This review delves into the specifics of the commonly utilized antibacterial agents, updating their therapeutic use in CNS infections from the pharmacokinetic and pharmacodynamic perspectives, with a focus on the optimization of dosing and route of administration that have been described to achieve good clinical outcomes. We also provide a concise synopsis regarding the most focused, clinically relevant information as pertains to each class and subclass of antimicrobial therapeutics. CNS infection morbidity and mortality remain high, and aggressive management is critical in ensuring favorable patient outcomes while averting toxicity and upholding patient safety. Full article

(This article belongs to the Special Issue Optimizing Antibiotics’ Pharmacokinetic/Pharmacodynamic (PK/PD) and Tissue Concentrations)

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18 pages, 2120 KiB

Open AccessArticle

In Silico and In Vitro Analysis of Sulforaphane Anti-Candida Activity

by Bruna L. R. Silva, Gisele Simão, Carmem D. L. Campos, Cinara R. A. V. Monteiro, Laryssa R. Bueno, Gabriel B. Ortis, Saulo J. F. Mendes, Israel Viegas Moreira, Daniele Maria-Ferreira, Eduardo M. Sousa, Flávia C. B. Vidal, Cristina de Andrade Monteiro, Valério Monteiro-Neto and Elizabeth S. Fernandes

Antibiotics 2022, 11(12), 1842; https://doi.org/10.3390/antibiotics11121842 - 19 Dec 2022

Cited by 3 | Viewed by 2937

Abstract

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous [...] Read more.

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)

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12 pages, 1261 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Amphotericin B Formulations Based on Organic Salts and Ionic Liquids against Leishmania infantum

by Ricardo Ferraz, Nuno Santarém, Andreia F. M. Santos, Manuel L. Jacinto, Anabela Cordeiro-da-Silva, Cristina Prudêncio, João Paulo Noronha, Luis C. Branco and Željko Petrovski

Antibiotics 2022, 11(12), 1841; https://doi.org/10.3390/antibiotics11121841 - 19 Dec 2022

Cited by 3 | Viewed by 2559

Abstract

Nowadays, organic salts and ionic liquids (OSILs) containing active pharmaceutical ingredients (APIs) are being explored as drug delivery systems in modern therapies (OSILs-API). In that sense, this work is focused on the development of novel OSILs-API based on amphotericin B through an innovative [...] Read more.

Nowadays, organic salts and ionic liquids (OSILs) containing active pharmaceutical ingredients (APIs) are being explored as drug delivery systems in modern therapies (OSILs-API). In that sense, this work is focused on the development of novel OSILs-API based on amphotericin B through an innovative procedure and the evaluation of the respective biological activity against Leishmania infantum. Several ammonium, methylimidazolium, pyridinium and phosphonium organic cations combined with amphotericin B as anion were synthesized in moderate to high yields and high purities by the water-reduced buffer neutralization method. All prepared compounds were characterized to confirm the desired chemical structure and the specific optical rotation ([α]_D²⁵) was also determined. The biological assays performed on L. infantum promastigotes showed increased activity against this parasitic disease when compared with the starting chloride forms and amphotericin B alone, highlighting [P_6,6,6,14][AmB] as the most promising formulation. Possible synergism in the antiprotozoal activity was also evaluated for [P_6,6,6,14][AmB], since it was proven to be the compound with the highest toxicity. This work reported a simple synthetic method, which can be applied to prepare other organic salts based on molecules containing fragile chemical groups, demonstrating the potential of these OSILs-AmB as possible agents against leishmaniasis. Full article

(This article belongs to the Special Issue Novel Antiprotozoal Drug Formulations and Treatments)

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10 pages, 568 KiB

Open AccessArticle

Prescription of Choreito, a Japanese Kampo Medicine, with Antimicrobials for Treatment of Acute Cystitis: A Retrospective Cohort Study

by Toru Sugihara, Jun Kamei, Hideo Yasunaga, Yusuke Sasabuchi and Tetsuya Fujimura

Antibiotics 2022, 11(12), 1840; https://doi.org/10.3390/antibiotics11121840 - 18 Dec 2022

Cited by 1 | Viewed by 2823

Abstract

Choreito, a Japanese Kampo medicine, is used to treat Japanese female patients for the quick relief of inflammatory symptoms associated with acute cystitis. We evaluated whether Choreito is effective in reducing antibiotic use and the number of clinic visits for these patients. Females [...] Read more.

Choreito, a Japanese Kampo medicine, is used to treat Japanese female patients for the quick relief of inflammatory symptoms associated with acute cystitis. We evaluated whether Choreito is effective in reducing antibiotic use and the number of clinic visits for these patients. Females aged 18–49 years who had acute cystitis for the first time, with no history of medical insurance use within 90 days prior to their visit, and no hospitalizations within the 30 days after their first visit were identified from the JMDC Claims Database between April 2018 and March 2021. For the 30 days after their first visit, patients who were given their first antimicrobial prescriptions with or without Choreito were compared regarding (i) the number of clinic visits, (ii) total antimicrobial prescription days, and (iii) the number of antimicrobial prescriptions adjusted for their age, Charlson comorbidity index, and the COVID-19 pandemic period (after April 2020). For the 319 and 8515 patients with or without a Choreito prescription, respectively, multivariable Poisson regression analyses showed that Choreito was significantly associated with a 5% shortening of a patient’s total antimicrobial prescription days (Beta, 0.950; p = 0.038), whereas no significant difference was observed in the number of clinic visits and antimicrobial prescriptions (p = 0.624 and p = 0.732, respectively). The prescription of Choreito in combination with antimicrobials was associated with a slight reduction in total antimicrobial use for acute cystitis among females. Full article

(This article belongs to the Special Issue Antibiotic Treatment in Urinary Tract Infections (UTIs))

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21 pages, 1668 KiB

Open AccessEditor’s ChoiceReview

β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity

by João Gonçalves Pereira, Joana Fernandes, Ana Rita Duarte and Susana Mendes Fernandes

Antibiotics 2022, 11(12), 1839; https://doi.org/10.3390/antibiotics11121839 - 18 Dec 2022

Cited by 11 | Viewed by 5287

Abstract

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in [...] Read more.

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome. Full article

(This article belongs to the Special Issue Antibiotics Treatment Optimization in Vulnerable Populations)

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19 pages, 670 KiB

Open AccessReview

An Assessment of the In Vitro Models and Clinical Trials Related to the Antimicrobial Activities of Phytochemicals

by Jonathan Kopel, Julianna McDonald and Abdul Hamood

Antibiotics 2022, 11(12), 1838; https://doi.org/10.3390/antibiotics11121838 - 17 Dec 2022

Cited by 8 | Viewed by 2626

Abstract

An increased number antibiotic-resistant bacteria have emerged with the rise in antibiotic use worldwide. As such, there has been a growing interest in investigating novel antibiotics against antibiotic-resistant bacteria. Due to the extensive history of using plants for medicinal purposes, scientists and medical [...] Read more.

An increased number antibiotic-resistant bacteria have emerged with the rise in antibiotic use worldwide. As such, there has been a growing interest in investigating novel antibiotics against antibiotic-resistant bacteria. Due to the extensive history of using plants for medicinal purposes, scientists and medical professionals have turned to plants as potential alternatives to common antibiotic treatments. Unlike other antibiotics in use, plant-based antibiotics have the innate ability to eliminate a broad spectrum of microorganisms through phytochemical defenses, including compounds such as alkaloids, organosulfur compounds, phenols, coumarins, and terpenes. In recent years, these antimicrobial compounds have been refined through extraction methods and tested against antibiotic-resistant strains of Gram-negative and Gram-positive bacteria. The results of the experiments demonstrated that plant extracts successfully inhibited bacteria independently or in combination with other antimicrobial products. In this review, we examine the use of plant-based antibiotics for their utilization against antibiotic-resistant bacterial infections. In addition, we examine recent clinical trials utilizing phytochemicals for the treatment of several microbial infections. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)

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16 pages, 3732 KiB

Open AccessArticle

Role of PatAB Transporter in Efflux of Levofloxacin in Streptococcus pneumoniae

by Mónica Amblar, Ángel Zaballos and Adela G de la Campa

Antibiotics 2022, 11(12), 1837; https://doi.org/10.3390/antibiotics11121837 - 17 Dec 2022

Cited by 4 | Viewed by 1867

Abstract

PatAB is an ABC bacterial transporter that facilitates the export of antibiotics and dyes. The overexpression of patAB genes conferring efflux-mediated fluoroquinolone resistance has been observed in several laboratory strains and clinical isolates of Streptococcus pneumoniae. Using transformation and whole-genome sequencing, we [...] Read more.

PatAB is an ABC bacterial transporter that facilitates the export of antibiotics and dyes. The overexpression of patAB genes conferring efflux-mediated fluoroquinolone resistance has been observed in several laboratory strains and clinical isolates of Streptococcus pneumoniae. Using transformation and whole-genome sequencing, we characterized the fluoroquinolone-resistance mechanism of one S. pneumoniae clinical isolate without mutations in the DNA topoisomerase genes. We identified the PatAB fluoroquinolone efflux-pump as the mechanism conferring a low-level resistance to ciprofloxacin (8 µg/mL) and levofloxacin (4 µg/mL). Genetic transformation experiments with different amplimers revealed that the entire patA plus the 5’-terminus of patB are required for levofloxacin–efflux. By contrast, only the upstream region of the patAB operon, plus the region coding the N-terminus of PatA containing the G39D, T43A, V48A and D100N amino acid changes, are sufficient to confer a ciprofloxacin–efflux phenotype, thus suggesting differences between fluoroquinolones in their binding and/or translocation pathways. In addition, we identified a novel single mutation responsible for the constitutive and ciprofloxacin-inducible upregulation of patAB. This mutation is predicted to destabilize the putative rho-independent transcriptional terminator located upstream of patA, increasing transcription of downstream genes. This is the first report demonstrating the role of the PatAB transporter in levofloxacin–efflux in a pneumoccocal clinical isolate. Full article

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

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13 pages, 1946 KiB

Open AccessArticle

Oligopeptide Sortase Inhibitor Modulates Staphylococcus aureus Cell Adhesion and Biofilm Formation

by Svetlana A. Bozhkova, Ekaterina M. Gordina, Dmitry V. Labutin and Konstantin V. Kudryavtsev

Antibiotics 2022, 11(12), 1836; https://doi.org/10.3390/antibiotics11121836 - 17 Dec 2022

Cited by 6 | Viewed by 1787

Abstract

Prevention of bacterial adhesion is one of the most important antivirulence strategies for meeting the global challenge posed by antimicrobial resistance. We aimed to investigate the influence of a peptidic S. aureus sortase A inhibitor on bacterial adhesion to eukaryotic cells and biofilm [...] Read more.

Prevention of bacterial adhesion is one of the most important antivirulence strategies for meeting the global challenge posed by antimicrobial resistance. We aimed to investigate the influence of a peptidic S. aureus sortase A inhibitor on bacterial adhesion to eukaryotic cells and biofilm formation as a potential method for reducing S. aureus virulence. The pentapeptide LPRDA was synthesized and characterized as a pure individual organic compound. Incubation of MSSA and MRSA strains with LPRDA induced a subsequent reduction in staphylococcal adhesion to Vero cells and biofilm formation, as visualized by microscopic and spectrophotometric methods, respectively. LPRDA did not have a cytotoxic effect on eukaryotic or bacterial cells. The pentapeptide LPRDA deserves further investigation using in vitro and in vivo models of Gram-positive bacteriemia as a potential antibacterial agent with an antiadhesive mechanism of action. Full article

(This article belongs to the Special Issue Antimicrobial Activity and Mechanisms of Action of Peptides)

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8 pages, 1469 KiB

Open AccessBrief Report

Genomic Analysis of Klebsiella pneumoniae ST258 Strain Coproducing KPC-2 and CTX-M-14 Isolated from Poultry in the Brazilian Amazon Region

by Tiago Barcelos Valiatti, Rodrigo Cayô, Fernanda Fernandes Santos, Francisco Ozório Bessa-Neto, Ramon Giovani Brandão Silva, Ruanita Veiga, Márcia de Nazaré Miranda Bahia, Lívia Maria Guimarães Dutra Guerra, Antônio Carlos Campos Pignatari, Cintya de Oliveira Souza, Danielle Murici Brasiliense and Ana Cristina Gales

Antibiotics 2022, 11(12), 1835; https://doi.org/10.3390/antibiotics11121835 - 17 Dec 2022

Cited by 1 | Viewed by 2483

Abstract

This study aimed to characterize a Klebsiella pneumoniae strain (KP411) recovered from the stool samples of poultry (Gallus gallus) in the Brazilian Amazon Region. The whole-genome sequencing of KP411 revealed the presence of an important arsenal of antimicrobial resistance genes to [...] Read more.

This study aimed to characterize a Klebsiella pneumoniae strain (KP411) recovered from the stool samples of poultry (Gallus gallus) in the Brazilian Amazon Region. The whole-genome sequencing of KP411 revealed the presence of an important arsenal of antimicrobial resistance genes to β-lactams (bla_CTX-M-14, bla_TEM-1B, bla_KPC-2, bla_SVH-11), aminoglycosides [aph(3″)- Ib, aph(6)-Id, aph(3′)-Ia], sulfonamides (sul1, sul2), quinolones (oqxAB), fosfomycin (fosA^KP), and macrolides [mph(A)]. Furthermore, our analyses revealed that the KP411 strain belongs to the ST258 clonal lineage, which is one of the main epidemic clones responsible for the dissemination of KPC-2 worldwide. Our data suggest that food-producing animals may act as reservoirs of multidrug-resistant K. pneumoniae belonging to the ST258 clone, and, consequently, contribute to their dissemination to humans and the environment. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Profiles of Gram-Negative Bacteria)

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24 pages, 3892 KiB

Open AccessArticle

The Anti-Virulence Effect of Vismia guianensis against Candida albicans and Candida glabrata

by Elizangela Pestana Motta, Josivan Regis Farias, Arthur André Castro da Costa, Anderson França da Silva, Alberto Jorge Oliveira Lopes, Maria do Socorro Sousa Cartágenes, Roberto Nicolete, Afonso Gomes Abreu, Elizabeth Soares Fernandes, Flavia Raquel Fernandes Nascimento, Cláudia Quintino da Rocha, Cristina Andrade Monteiro and Rosane Nassar Meireles Guerra

Antibiotics 2022, 11(12), 1834; https://doi.org/10.3390/antibiotics11121834 - 16 Dec 2022

Cited by 2 | Viewed by 2202

Abstract

In folk medicine, Vismia guianensis is used to treat skin diseases and mycoses in the Amazon region. We evaluated the anti-Candida activity of the hydroalcoholic extract from the leaves of Vismia guianensis (EHVG). HPLC-PDA and FIA-ESI-IT-MSⁿ were used to chemically characterize [...] Read more.

In folk medicine, Vismia guianensis is used to treat skin diseases and mycoses in the Amazon region. We evaluated the anti-Candida activity of the hydroalcoholic extract from the leaves of Vismia guianensis (EHVG). HPLC-PDA and FIA-ESI-IT-MSⁿ were used to chemically characterize EHVG. The anti-Candida activity was determined in vitro by the minimum inhibitory concentrations (MIC) against Candida glabrata (ATCC-2001); Candida albicans (ATCC-90028, ATCC-14053, and ATCC-SC5314), and C. albicans clinical isolates. EHVG effects on adhesion, growth, and biofilm formation were also determined. Molecular docking was used to predict targets for EHVG compounds. The main compounds identified included anthraquinone, vismione D, kaempferol, quercetin, and vitexin. EHVG was fungicidal against all tested strains. C. albicans ATCC 14053 and C. glabrata ATCC 2001 were the most sensitive strains, as the extract inhibited their virulence factors. In silico analysis indicated that vismione D presented the best antifungal activity, since it was the most effective in inhibiting CaCYP51, and may act as anti-inflammatory and antioxidant agent, according to the online PASS prediction. Overall, the data demonstrate that EHVG has an anti-Candida effect by inhibiting virulence factors of the fungi. This activity may be related to its vismione D content, indicating this compound may represent a new perspective for treating diseases caused by Candida sp. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)

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22 pages, 524 KiB

Open AccessArticle

Use of Antimicrobials by Class in Pigs in Germany—A Longitudinal Description Considering Different International Categorisation Systems

by Clarissa Bonzelett, Anne Schnepf, Maria Hartmann, Annemarie Käsbohrer and Lothar Kreienbrock

Antibiotics 2022, 11(12), 1833; https://doi.org/10.3390/antibiotics11121833 - 16 Dec 2022

Cited by 1 | Viewed by 1945

Abstract

Antimicrobial usage in both human and veterinary medicine is considered one of the main drivers of antimicrobial resistance; its reduction poses a serious challenge. To analyse the associations between usage and resistance, data from monitoring systems and classification of all antimicrobial substances are [...] Read more.

Antimicrobial usage in both human and veterinary medicine is considered one of the main drivers of antimicrobial resistance; its reduction poses a serious challenge. To analyse the associations between usage and resistance, data from monitoring systems and classification of all antimicrobial substances are crucial. In this analysis, we investigated longitudinal data collected between 2013 and 2020 within the Veterinary Consumption of Antibiotics project from pig farms in Germany, including all antimicrobial classes, but focusing on critically important antimicrobials: third- and fourth-generation cephalosporins, fluoroquinolones, macrolides, and polymyxins. Analysing the treatment frequency, we found that a reduction in antimicrobial use in all types of pig production has occurred over time, accompanied by a rising percentage of farms without any usage. The lists of the World Health Organisation, World Organisation for Animal Health, and European Medicine Agency classify different antimicrobial substances as critically important. The vast differences between the respective weighted treatment frequencies allocated to the antimicrobials of main interest reflect the huge impact of the three categorisation systems. We concluded that, with the aim of creating national treatment guidelines supporting veterinarians to make treatment decisions, the list of the European Medicine Agency is the most suitable. Full article

(This article belongs to the Section Antibiotics in Animal Health)

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27 pages, 4080 KiB

Open AccessArticle

Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii

by Filomena Sannio, Antonella Brizzi, Rosita Del Prete, Marialuce Avigliano, Tiziana Simone, Carlotta Pagli, Teresa Ferraro, Filomena De Luca, Marco Paolino, Federico Corelli, Claudia Mugnaini and Jean-Denis Docquier

Antibiotics 2022, 11(12), 1832; https://doi.org/10.3390/antibiotics11121832 - 16 Dec 2022

Cited by 3 | Viewed by 1812

Abstract

The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the [...] Read more.

The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the WHO to include carbapenem-resistant A. baumannii as a “critical priority” for the discovery and development of new antibacterial agents. In a previous work, we identified several series of compounds showing either direct-acting or synergistic activity against relevant Gram-negative species, including A. baumannii. Among these, two pyrazole compounds, despite being devoid of any direct-acting activity, showed remarkable synergistic activity in the presence of a subinhibitory concentration of colistin on K. pneumoniae and A. baumannii and served as a starting point for the synthesis of new analogues. In this work, a new series of 47 pyrazole compounds was synthesized. Some compounds showed significant direct-acting antibacterial activity on Gram-positive organisms. Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii, including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens. Full article

(This article belongs to the Special Issue Latest Progress in the Polymyxin Class of Antibiotics)

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12 pages, 1954 KiB

Open AccessArticle

Staphylococcus aureus-Cure-Associated Antigens Elicit Type 3 Immune Memory T Cells

by Kamila R. Santos, Fernando N. Souza, Eduardo M. Ramos-Sanchez, Camila F. Batista, Luiza C. Reis, Wesley L. Fotoran, Marcos B. Heinemann, Adriano F. Cunha, Mussya C. Rocha, Angélica R. Faria, Hélida M. Andrade, Mônica M. O. P. Cerqueira, Magnus Gidlund, Hiro Goto and Alice Maria M. P. Della Libera

Antibiotics 2022, 11(12), 1831; https://doi.org/10.3390/antibiotics11121831 - 16 Dec 2022

Viewed by 1866

Abstract

Background: Staphylococcus aureus is one of the most frequently major mastitis pathogens that cause clinical and subclinical mastitis worldwide. Current antimicrobial treatments are usually ineffective, and the commercially available vaccines lack proven effectiveness. The immunological response elicited by the recombinant S. aureus-cure-associated [...] Read more.

Background: Staphylococcus aureus is one of the most frequently major mastitis pathogens that cause clinical and subclinical mastitis worldwide. Current antimicrobial treatments are usually ineffective, and the commercially available vaccines lack proven effectiveness. The immunological response elicited by the recombinant S. aureus-cure-associated proteins phosphoglycerate kinase (PGK), enolase (ENO), and elongation factor-G (EF-G) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA vaccination was studied in this work. Methods: Here, twenty-three C57BL/6 mice were divided into four groups and vaccinated with: G1: none (control); G2: GM-CSF DNA plasmid DNA vaccine; G3: the combination of EF-G+ENO+PGK; and G4: the combinations of EF-G+ENO+PGK proteins plus GM-CSF plasmid DNA vaccine. After 44 days, spleen cells were collected for immunophenotyping and lymphocyte proliferation evaluation by flow cytometry upon S. aureus stimulus. Results: Immunization with the three S. aureus recombinant proteins alone resulted in a higher percentage of IL-17A⁺ cells among CD8⁺ T central memory cells, as well as the highest intensity of IL-17A production by overall lymphocytes indicating that the contribution of the combined lymphocyte populations is crucial to sustaining a type 3 cell immunity environment. Conclusion: The immunization with three S. aureus-cure-associated recombinant proteins triggered type 3 immunity, which is a highly interesting path to pursue an effective bovine S. aureus mastitis vaccine. Full article

(This article belongs to the Special Issue Mastitis: Causative Agents, Drug Resistance, and Treatment Approaches)

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10 pages, 269 KiB

Open AccessArticle

Pharmacokinetic of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series

by Simone Mornese Pinna, Silvia Corcione, Amedeo De Nicolò, Giorgia Montrucchio, Silvia Scabini, Davide Vita, Ilaria De Benedetto, Tommaso Lupia, Jacopo Mula, Giovanni Di Perri, Antonio D’Avolio and Francesco Giuseppe De Rosa

Antibiotics 2022, 11(12), 1830; https://doi.org/10.3390/antibiotics11121830 - 16 Dec 2022

Cited by 6 | Viewed by 4064

Abstract

Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fC_trough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to [...] Read more.

Background: Cefiderocol is a novel parenteral siderophore cephalosporin, demonstrating enhanced activity against multidrug-resistant (MDR) Gram-negative bacteria and difficult-to-treat Acinetobacter baumannii (DTR-AB). Plasma-free trough concentration (fC_trough) over the minimum inhibitory concentration (MIC) was reported as the best pharmacokinetic parameter to describe the microbiological efficacy of cefiderocol. Materials and methods: We retrospectively described the pharmacokinetic and pharmacodynamic profile of three critically ill patients admitted to the intensive care unit, receiving cefiderocol under compassionate use to treat severe DTR-AB infections while undergoing continuous venovenous haemofiltration. Cefiderocol was administrated at a dosage of 2 g every 8 h infused over 3 h. Therapeutic drug monitoring (TDM) was assessed at the steady state. Cthrough was evaluated by assuming a plasma protein binding of 58.0%. The fCmin/MIC was calculated assuming a cefiderocol MIC equal to the PK-PD breakpoint of susceptibility ≤ 2. The association between the PK/PD parameters and microbiological outcome was assessed. Results: fC_trough/MIC were >12 in 2 patients and 2.9 in the 1 who rapidly recovered from renal failure. Microbiological cure occurred in 3/3 of patients. None of the 3 patients died within 30 days. Conclusions: A cefiderocol dosage of 2 g q8 h in critically ill patients with AKI undergoing CVVH may bring about a very high plasma concentration, corresponding to essentially 100% free time over the MIC for DTR-AB. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics and Dose Optimization of Anti-infectives in Critical Care)

14 pages, 478 KiB

Open AccessArticle

E-Learning versus Face-to-Face Methodology for Learning Antimicrobial Resistance and Prescription Practice in a Tertiary Hospital of a Middle-Income Country

by Paulina Isabel Armas Freire, Gilberto Gambero Gaspar, Jeannete Zurita, Grace Salazar, Jorge Washington Velez and Valdes Roberto Bollela

Antibiotics 2022, 11(12), 1829; https://doi.org/10.3390/antibiotics11121829 - 16 Dec 2022

Cited by 2 | Viewed by 2511

Abstract

Background: Antimicrobial resistance is a growing health problem worldwide. One strategy to face this problem in a reasonable way is training health personnel for the rational use of antimicrobials. There are some difficulties associated with medical staff to receiving training with E-learning education, [...] Read more.

Background: Antimicrobial resistance is a growing health problem worldwide. One strategy to face this problem in a reasonable way is training health personnel for the rational use of antimicrobials. There are some difficulties associated with medical staff to receiving training with E-learning education, but there is a lack of studies and insufficient evidence of the effectiveness of this method compared to face-to-face learning. Methods: An educational intervention on antimicrobial resistance (AMR) and antimicrobial prescription practice (APP) was designed and implemented using two approaches: face-to-face and E-learning among physicians of the intensive care unit (ICU) and internal medicine ward (IMW) at Eugenio Espejo Hospital in Quito. Modalities of interventions were compared to propose a strategy of continuous professional development (CPD) for all hospital staff. An interventional study was proposed using a quasi-experimental approach that included 91 physicians, of which 49 belong to the IMW and 42 to the ICU. All of them received training on AMR—half in a face-to-face mode and the other half in an asynchronous E-learning mode. They then all participated on APP training but with switched groups; those who previously participated in the face-to-face experience participated in an E-learning module and vice-versa. We evaluated self-perception about basic knowledge, attitudes and referred practices towards AMR and APP before and after the intervention. A review of medical records was conducted before and after training by checking antimicrobial prescriptions for all patients in the ICU and IMW with bacteremia, urinary tract infection (UTI), pneumonia, and skin and soft tissue infection. The study received IRB clearance, and we used SPSS for statistical analysis. Results: No statistically significant difference was observed between the E-learning and the face-to-face methodology for AMR and APP. Both methodologies improved knowledge, attitudes and referred practices. In the case of E-learning, there was a self-perception of improved attitudes (p < 0.05) and practices (p < 0.001) for both AMR and APP. In face-to-face, there was a perception of improvement only in attitudes (p < 0.001) for APP. In clinical practice, the use of antimicrobials significantly improved in all domains after training, including empirical and targeted treatment of bacteremia and pneumonia (p < 0.001) and targeted treatment of UTI (p < 0.05). For the empirical treatment of pneumonia, the mean number of antibiotics was reduced from 1.87 before to 1.05 after the intervention (p = 0.003), whereas in the targeted management of bacteremia, the number of antibiotics was reduced from 2.19 to 1.53 (p = 0.010). Conclusions: There was no statistically significant difference between the effect of E-learning and face-to-face strategy in terms of teaching AMR and APP. Adequate self-reported attitudes and practices in E-learning exceed those of the face-to-face approach. The empiric and targeted use of antimicrobials improved in all reviewed cases, and we observed an overall decrease in antibiotic use. Satisfaction with training was high for both methods, and participants valued the flexibility and accessibility of E-learning. Full article

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

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23 pages, 1903 KiB

Open AccessArticle

Quantification of Total and Viable Cells and Determination of Serogroups and Antibiotic Resistance Patterns of Listeria monocytogenes in Chicken Meat from the North-Western Iberian Peninsula

by Cristina Rodríguez-Melcón, Alexandra Esteves, Sarah Panera-Martínez, Rosa Capita and Carlos Alonso-Calleja

Antibiotics 2022, 11(12), 1828; https://doi.org/10.3390/antibiotics11121828 - 16 Dec 2022

Cited by 4 | Viewed by 2685

Abstract

Twenty samples of minced chicken meat procured from butcher’s shops in León (Spain; 10 samples) and Vila Real (Portugal; 10 samples) were analyzed. Microbial concentrations (log₁₀ cfu/g) of 7.53 ± 1.02 (viable aerobic microbiota), 7.13 ± 1.07 (psychrotrophic microorganisms), and 4.23 ± [...] Read more.

Twenty samples of minced chicken meat procured from butcher’s shops in León (Spain; 10 samples) and Vila Real (Portugal; 10 samples) were analyzed. Microbial concentrations (log₁₀ cfu/g) of 7.53 ± 1.02 (viable aerobic microbiota), 7.13 ± 1.07 (psychrotrophic microorganisms), and 4.23 ± 0.88 (enterobacteria) were found. The detection method described in the UNE-EN ISO 11290-1 standard (based on isolation from the chromogenic medium OCLA) with confirmation by the polymerase chain reaction (PCR; lmo1030) (OCLA–PCR), revealed Listeria monocytogenes in 14 samples (70.0% of the total), nine of Spanish origin and five of Portuguese (p > 0.05). The levels of viable and inactivated L. monocytogenes in the samples were determined with a q-PCR using propidium monoazide (PMAxx) as a viability marker. Seven samples tested positive both with the OCLA–PCR and with the q-PCR, with estimated concentrations of viable cells varying between 2.15 log₁₀ cfu/g (detection limit) and 2.94 log₁₀ cfu/g. Three samples tested negative both with the OCLA–PCR and with the q-PCR. Seven samples were positive with the OCLA–PCR, but negative with the q-PCR, and three samples tested negative with the OCLA–PCR and positive with the q-PCR. The percentage of viable cells relative to the total ranged between 2.4% and 86.0%. Seventy isolates of L. monocytogenes (five from each positive sample) were classified in PCR serogroups with a multiplex PCR assay. L. monocytogenes isolates belonged to serogroups IIa (52 isolates; 74.3%), IIc (7; 10.0%), IVa (2; 2.9%), and IVb (9; 12.9%). The susceptibility of the 70 isolates to 15 antibiotics of clinical interest was tested. The strains presented resistance to between three and eight antibiotics. The average number of resistances was greater (p < 0.001) among strains isolated from Spanish samples (6.20 ± 1.08), than in those from Portugal (5.00 ± 1.08). In both groups of strains, a prevalence of resistance higher than 95% was observed for oxacillin, cefoxitin, cefotaxime, and cefepime. The need to handle minced chicken meat correctly, taking care to cook it sufficiently and to avoid cross-contamination, so as to reduce the danger of listeriosis, is emphasized. A combination of culture-dependent and culture-independent methods offers complementary routes for the detection in food of the cells of L. monocytogenes in various different physiological states. Full article

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9 pages, 1413 KiB

Open AccessArticle

Characterization of the Composition Variation of Healthy Human Gut Microbiome in Correlation with Antibiotic Usage and Yogurt Consumption

by Shaofei Yan, Xiaofan Zhang, Xiaofang Jia, Jiguo Zhang, Xiaomin Han, Chang Su, Jianyun Zhao, Wanglong Gou, Jin Xu and Bing Zhang

Antibiotics 2022, 11(12), 1827; https://doi.org/10.3390/antibiotics11121827 - 16 Dec 2022

Cited by 2 | Viewed by 2148

Abstract

Antibiotic usage and yogurt consumption are the major interventions for gut microbiota, yet their shared characteristics and disparities in healthy human gut microbiome remain unclear. This study aimed to decipher the composition changes among healthy humans, comparing antibiotic usage and yogurt consumption. The [...] Read more.

Antibiotic usage and yogurt consumption are the major interventions for gut microbiota, yet their shared characteristics and disparities in healthy human gut microbiome remain unclear. This study aimed to decipher the composition changes among healthy humans, comparing antibiotic usage and yogurt consumption. The relative bacterial abundances of 1113 fecal samples were collected from an ongoing, population-based longitudinal cohort study in China that covered lifestyle, diet, disease status and physical measurements, and biological indicators of participants were obtained by the sequencing of 16S rRNA. The samples were divided into three groups, which were antibiotic users (122), yogurt consumers (497) and controls (494), where data visualization, alpha diversity, beta diversity and LEfSe analysis were conducted. At the family level, the relative abundances of Streptococcaceae, Enterobacteriaceae and Enterococcaceae families in antibiotic users increased almost 50%, 70% and 200%, respectively, while yogurt consumption also increased relative abundances of Streptococcaceae and Enterococcaceae, but not Enterobacteriaceae. Alpha diversity analyses suggested that the microbiome of the antibiotic usage and yogurt consumption groups exhibited an alpha diversity lower than that of the control. LEfSe analysis showed that, at the family level, the number of biomarkers in the yogurt consumption and antibiotic usage group were respectively 5 and 7, lower than that of the control (13). This study demonstrated the importance in considering the potential assistance of yogurt consumption on ARG gene transfer from commensal bacteria to pathogens in the human gut, which may pose a risk for human health. Antibiotic usage and yogurt consumption share more identical changes on healthy human gut flora than disparities. Therefore, in order to understand the potential risks of antibiotic usage and yogurt consumption on antibiotic resistance transmission in human gut microbiota, further research needs to be undertaken. Full article

(This article belongs to the Special Issue Antibiotic Residues, Antimicrobial Resistance and Intervention Strategies of Foodborne Pathogens)

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31 pages, 953 KiB

Open AccessReview

Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine

by Hiba Alaoui Mdarhri, Rachid Benmessaoud, Houda Yacoubi, Lina Seffar, Houda Guennouni Assimi, Mouhsine Hamam, Rihabe Boussettine, Najoie Filali-Ansari, Fatima Azzahra Lahlou, Idrissa Diawara, Moulay Mustapha Ennaji and Mohamed Kettani-Halabi

Antibiotics 2022, 11(12), 1826; https://doi.org/10.3390/antibiotics11121826 - 16 Dec 2022

Cited by 34 | Viewed by 6518

Abstract

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have [...] Read more.

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new β-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance. Full article

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11 pages, 534 KiB

Open AccessArticle

Prevalence and Phenotypic Antimicrobial Resistance among ESKAPE Bacteria and Enterobacterales Strains in Wild Birds

by Tamara Pasqualina Russo, Adriano Minichino, Antonio Gargiulo, Lorena Varriale, Luca Borrelli, Antonino Pace, Antonio Santaniello, Marina Pompameo, Alessandro Fioretti and Ludovico Dipineto

Antibiotics 2022, 11(12), 1825; https://doi.org/10.3390/antibiotics11121825 - 15 Dec 2022

Cited by 13 | Viewed by 3220

Abstract

Antimicrobial resistance (AMR) is a current public health issue globally. To counter this phenomenon and prioritize AMR in the health sector, the World Health Organization (WHO) published a list of bacterial pathogens against which the development of new antimicrobial agents is urgently needed, [...] Read more.

Antimicrobial resistance (AMR) is a current public health issue globally. To counter this phenomenon and prioritize AMR in the health sector, the World Health Organization (WHO) published a list of bacterial pathogens against which the development of new antimicrobial agents is urgently needed, designating the ESKAPE pathogens (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) with a ‘priority status’. Moreover, the One Health High Level Expert Panel (OHHLEP) states that human health is closely linked to animal and environmental health, thus promoting a holistic One Health approach in order to be prepared to address possible emerging health threats from the human–animal–environment interface. Wild birds may host and spread pathogens, integrating the epidemiology of infectious diseases. The aim of this study was to examine the role of wild birds as a source of ESKAPE bacteria and other antibiotic-resistant enterobacterales. A total of fifty strains within the ESKAPE group were detected in 40/163 cloacal samples of examined birds (24.5%). Additionally, different strains of enterobacterales were detected in 88/163 cloacal samples (53.9%). Isolated strains exhibited antimicrobial resistance, including towards critically important antibiotics (e.g., third, fourth, fifth generation cephalosporins, fluoroquinolones) for human medicine. Our results confirm that wild birds are potential reservoirs of several pathogens and antimicrobial-resistant bacteria and that they could be involved in the dissemination of those bacteria across different environments, with resulting public health concerns. Full article

(This article belongs to the Special Issue Antimicrobial and Antifungal Resistance in Domestic Animals, Synanthropic Species and Wildlife)

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37 pages, 956 KiB

Open AccessArticle

Ongoing Efforts to Improve Antimicrobial Utilization in Hospitals among African Countries and Implications for the Future

by Zikria Saleem, Brian Godman, Aislinn Cook, Muhammad Arslan Khan, Stephen M. Campbell, Ronald Andrew Seaton, Linda Siachalinga, Abdul Haseeb, Afreenish Amir, Amanj Kurdi, Julius C. Mwita, Israel Abebrese Sefah, Sylvia A. Opanga, Joseph O. Fadare, Olayinka O. Ogunleye, Johanna C. Meyer, Amos Massele, Dan Kibuule, Aubrey C. Kalungia, Moyad Shahwan, Hellen Nabayiga, Giuseppe Pichierri and Catrin E. Moore Show full author list Hide full author list

Antibiotics 2022, 11(12), 1824; https://doi.org/10.3390/antibiotics11121824 - 15 Dec 2022

Cited by 39 | Viewed by 5838

Abstract

There are serious concerns with rising antimicrobial resistance (AMR) across countries increasing morbidity, mortality and costs. These concerns have resulted in a plethora of initiatives globally and nationally including national action plans (NAPs) to reduce AMR. Africa is no exception, especially with the [...] Read more.

There are serious concerns with rising antimicrobial resistance (AMR) across countries increasing morbidity, mortality and costs. These concerns have resulted in a plethora of initiatives globally and nationally including national action plans (NAPs) to reduce AMR. Africa is no exception, especially with the highest rates of AMR globally. Key activities in NAPs include gaining a greater understanding of current antimicrobial utilization patterns through point prevalence surveys (PPS) and subsequently instigating antimicrobial stewardship programs (ASPs). Consequently, there is a need to comprehensively document current utilization patterns among hospitals across Africa coupled with ASP studies. In total, 33 PPS studies ranging from single up to 18 hospitals were documented from a narrative review with typically over 50% of in-patients prescribed antimicrobials, up to 97.6% in Nigeria. The penicillins, ceftriaxone and metronidazole, were the most prescribed antibiotics. Appreciable extended prescribing of antibiotics up to 6 days or more post-operatively was seen across Africa to prevent surgical site infections. At least 19 ASPs have been instigated across Africa in recent years to improve future prescribing utilizing a range of prescribing indicators. The various findings resulted in a range of suggested activities that key stakeholders, including governments and healthcare professionals, should undertake in the short, medium and long term to improve future antimicrobial prescribing and reduce AMR across Africa. Full article

(This article belongs to the Special Issue Antibiotic Use and Stewardship in Hospital)

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7 pages, 455 KiB

Open AccessBrief Report

T2Bacteria and T2Resistance Assays in Critically Ill Patients with Sepsis or Septic Shock: A Descriptive Experience

by Daniele Roberto Giacobbe, Francesca Crea, Paola Morici, Laura Magnasco, Vincenzo Di Pilato, Federica Briano, Edward Willison, Rachele Pincino, Silvia Dettori, Stefania Tutino, Simone Esposito, Erika Coppo, Chiara Dentone, Federica Portunato, Malgorzata Mikulska, Chiara Robba, Antonio Vena, Denise Battaglini, Iole Brunetti, Lorenzo Ball, Paolo Pelosi, Anna Marchese and Matteo Bassetti Show full author list Hide full author list

Antibiotics 2022, 11(12), 1823; https://doi.org/10.3390/antibiotics11121823 - 15 Dec 2022

Cited by 6 | Viewed by 1660

Abstract

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested [...] Read more.

The use of rapid molecular tests may anticipate the identification of causative agents and resistance determinants in the blood of critically ill patients with sepsis. From April to December 2021, all intensive care unit patients with sepsis or septic shock who were tested with the T2Bacteria and T2Resistance assays were included in a retrospective, single center study. The primary descriptive endpoints were results of rapid molecular tests and concomitant blood cultures. Overall, 38 combinations of T2Bacteria and T2Resistance tests were performed. One or more causative agent(s) were identified by the T2Bacteria assay in 26% of episodes (10/38), whereas negative and invalid results were obtained in 66% (25/38) and 8% (3/38) of episodes, respectively. The same pathogen detected by the T2Bacteria test grew from blood cultures in 30% of cases (3/10). One or more determinant(s) of resistance were identified by the T2Resistance assay in 11% of episodes (4/38). Changes in therapy based on T2Bacteria and/or T2Resistance results occurred in 21% of episodes (8/38). In conclusion, T2Bacteria/T2Resistance results can influence early treatment decisions in critically ill patients with sepsis or septic shock in real-life practice. Large, controlled studies remain necessary to confirm a favorable impact on patients’ outcomes and antimicrobial stewardship interventions. Full article

(This article belongs to the Special Issue Infection Control and Antibiotic Use in Hospital)

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42 pages, 4428 KiB

Open AccessReview

Strategies to Mitigate and Treat Orthopaedic Device-Associated Infections

by Darragh G. Kennedy, Aoife M. O’Mahony, Eamonn P. Culligan, Caitriona M. O’Driscoll and Katie B. Ryan

Antibiotics 2022, 11(12), 1822; https://doi.org/10.3390/antibiotics11121822 - 15 Dec 2022

Cited by 14 | Viewed by 5415

Abstract

Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for [...] Read more.

Orthopaedic device implants play a crucial role in restoring functionality to patients suffering from debilitating musculoskeletal diseases or to those who have experienced traumatic injury. However, the surgical implantation of these devices carries a risk of infection, which represents a significant burden for patients and healthcare providers. This review delineates the pathogenesis of orthopaedic implant infections and the challenges that arise due to biofilm formation and the implications for treatment. It focuses on research advancements in the development of next-generation orthopaedic medical devices to mitigate against implant-related infections. Key considerations impacting the development of devices, which must often perform multiple biological and mechanical roles, are delineated. We review technologies designed to exert spatial and temporal control over antimicrobial presentation and the use of antimicrobial surfaces with intrinsic antibacterial activity. A range of measures to control bio-interfacial interactions including approaches that modify implant surface chemistry or topography to reduce the capacity of bacteria to colonise the surface, form biofilms and cause infections at the device interface and surrounding tissues are also reviewed. Full article

(This article belongs to the Special Issue Novel and Improved Strategies for the Detection, Diagnosis and Treatment of Biofilm-Associated Infections)

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20 pages, 680 KiB

Open AccessReview

Current and Emerging Treatment Options for Multidrug Resistant Escherichia coli Urosepsis: A Review

by Mikaela M. Walker, Jason A. Roberts, Benjamin A. Rogers, Patrick N. A. Harris and Fekade B. Sime

Antibiotics 2022, 11(12), 1821; https://doi.org/10.3390/antibiotics11121821 - 15 Dec 2022

Cited by 17 | Viewed by 5739

Abstract

Escherichia coli is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, E. coli places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through [...] Read more.

Escherichia coli is a versatile commensal and pathogenic member of the human microflora. As the primary causative pathogen in urosepsis, E. coli places an immense burden on healthcare systems worldwide. To further exacerbate the issue, multi drug resistance (MDR) has spread rapidly through E. coli populations, making infections more troublesome and costlier to treat. This paper aimed to review the literature concerning the development of MDR in uropathogenic E. coli (UPEC) and explore the existing evidence of current and emerging treatment strategies. While some MDR strains maybe treated with β-lactam-β-lactamase inhibitor combinations as well as cephalosporins, cephamycin, temocillin and fosfomycin, current treatment strategies for many MDR UPEC strains are reliant on carbapenems. Carbapenem overreliance may contribute to the alarming dissemination of carbapenem-resistance amongst some UPEC communities, which has ushered in a new age of difficult to treat infections. Alternative treatment options for carbapenem resistant UPEC may include novel β-lactam-β-lactamase or carbapenemase inhibitor combinations, cefiderocol, polymyxins, tigecycline, aminoglycosides or fosfomycin. For metallo-β-lactamase producing strains (e.g., NDM, IMP-4), combinations of cefazidime-avibacam with aztreonam have been used. Additionally, the emergence of new antimicrobials brings new hope to the treatment of such infections. However, continued research is required to successfully bring these into the clinic for the treatment of MDR E. coli urosepsis. Full article

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18 pages, 6347 KiB

Open AccessArticle

Fabrication and Evaluation of Basil Essential Oil-Loaded Halloysite Nanotubes in Chitosan Nanocomposite Film and Its Application in Food Packaging

by Narayan Chaudhary, Gourav Mishra, Tushar Yadav, Nishant Srivastava, Vimal K. Maurya and Shailendra K. Saxena

Antibiotics 2022, 11(12), 1820; https://doi.org/10.3390/antibiotics11121820 - 15 Dec 2022

Cited by 7 | Viewed by 2824

Abstract

Increasing health concerns regarding the use of plasticware have led to the development of ecofriendly biodegradable packaging film from natural polymer and food additives. In the present study, basil essential oil (BEO) loaded halloysite nanotubes (HNTs) composite films were synthesized using a solution [...] Read more.

Increasing health concerns regarding the use of plasticware have led to the development of ecofriendly biodegradable packaging film from natural polymer and food additives. In the present study, basil essential oil (BEO) loaded halloysite nanotubes (HNTs) composite films were synthesized using a solution casting method. The effects of BEO and nanotube concentration on the mechanical, physical, structural, barrier, and antioxidant properties of films were evaluated. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) demonstrated well-dispersed HNTs and BEO in tailored composite films. The addition of BEO in Chitosan (Ch) film caused darkening of the film color; furthermore, the incorporation of HNTs in varied concentrations increased opaqueness in Ch/BEO film. The Ch/BEO film, upon adding HNTs 5–30 wt%, exhibited a corresponding increase in the film thickness (0.108–0.135 mm) when compared with the Ch/BEO film alone (0.081 mm). The BEO-loaded HNTs composite films displayed reduced moisture content and characteristic barrier and UV properties. The Ch/BEO film with 15 wt% HNTs was found to have enhanced antioxidant activity. The Ch/BEO/HNTs composite also managed to prevent broccoli florets from losing weight and firmness during storage. The enhanced barrier and antioxidant qualities of the nanocomposite film suggest its potential application in the food processing and packaging sector. This is the first ever report on the fabrication of nanocomposite film using BEO and HNTs for food packaging. The low production cost and ecofriendly approach make the film acceptable for further research and commercialization thereafter. Full article

(This article belongs to the Special Issue New Antibacterial Nanostructured Coatings for Biomedical Applications)

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14 pages, 1748 KiB

Open AccessArticle

In Vitro Antifungal Activity of Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II against Cryptococcus neoformans var. grubii

by Silvia Katherine Carvajal, Yerly Vargas-Casanova, Héctor Manuel Pineda-Castañeda, Javier Eduardo García-Castañeda, Zuly Jenny Rivera-Monroy and Claudia Marcela Parra-Giraldo

Antibiotics 2022, 11(12), 1819; https://doi.org/10.3390/antibiotics11121819 - 15 Dec 2022

Viewed by 1652

Abstract

Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. [...] Read more.

Cryptococcosis is associated with high rates of morbidity and mortality. The limited number of antifungal agents, their toxicity, and the difficulty of these molecules in crossing the blood–brain barrier have made the exploration of new therapeutic candidates against Cryptococcus neoformans a priority task. To optimize the antimicrobial functionality and improve the physicochemical properties of AMPs, chemical strategies include combinations of peptide fragments into one. This study aimed to evaluate the binding of the minimum activity motif of bovine lactoferricin (LfcinB) and buforin II (BFII) against C. neoformans var. grubii. The antifungal activity against these chimeras was evaluated against (i) the reference strain H99, (ii) three Colombian clinical strains, and (iii) eleven mutant strains, with the aim of evaluating the possible antifungal target. We found high activity against these strains, with a MIC between 6.25 and 12.5 µg/mL. Studies were carried out to evaluate the effect of the combination of fluconazole treatments, finding a synergistic effect. Finally, when fibroblast cells were treated with 12.5 µg/mL of the chimeras, a viability of more than 65% was found. The results obtained in this study identify these chimeras as potential antifungal molecules for future therapeutic applications against cryptococcosis. Full article

(This article belongs to the Special Issue Antimicrobial Peptides from Natural Sources to Synthetic Optimization)

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15 pages, 1924 KiB

Open AccessArticle

In Vitro Assessment of Antimicrobial Activity of Phytobiotics Composition towards of Avian Pathogenic Escherichia coli (APEC) and Other E. coli Strains Isolated from Broiler Chickens

by Karolina A. Chodkowska, Hubert Iwiński, Karolina Wódz, Tomasz Nowak and Henryk Różański

Antibiotics 2022, 11(12), 1818; https://doi.org/10.3390/antibiotics11121818 - 15 Dec 2022

Cited by 6 | Viewed by 2698

Abstract

Escherichia coli infections (including APEC) in broiler chickens are not only a health and economic problem of the flock, but also a significant health threat to poultry meat consumers. The prophylactic and therapeutic effects of the phytobiotic composition on E. coli in broiler [...] Read more.

Escherichia coli infections (including APEC) in broiler chickens are not only a health and economic problem of the flock, but also a significant health threat to poultry meat consumers. The prophylactic and therapeutic effects of the phytobiotic composition on E. coli in broiler chickens were previously described. However, most of the data were related to the reference strains (for both in vitro and in vivo models). Based on the previous studies in human and animals, E. coli strains seem to be multidrug resistance. This, in turn, makes it necessary to develop effective alternative methods of treating this type of infection already at the stage of poultry production. In the present study, the antibacterial activity against various strains of E. coli (including APEC) was assessed for two innovative phytobiotics mixtures: H1, containing thymol, menthol, linalool, trans-anethole, methyl salicylate, 1,8-cineol, and p-cymene; H2, in addition to compounds from H1, containing terpinen-4-ol and γ-terpinene. The unique mixtures of phytobiotics used in the experiment were effective against various strains of E. coli, also against APEC, isolated from broiler chickens from traditional industrial breeding, as well as against those showing colistin resistance. The minimum inhibitory concentration (MIC) values for these unique mixtures were: For H1 1:512 for APEC and non-APEC E. coli strains isolated from day old chicks (DOCs), 1:512 for non-APEC, and 1:1024 for non-APEC isolated from broilers sample. For mixture H2, MIC for APEC from both type of samples (DOCs and broilers) was 1:1024 and for non-APEC (DOCs and broilers) was 1:512. The results suggest that phytobiotic compositions used in this study can be successfully used as a natural alternative to antibiotics in the treatment of E. coli infections in broiler chickens. The promising results may be a crucial point for further analyses in broiler flocks exposed to E. coli infections and where it is necessary to reduce the level of antibiotics or completely eliminate them, thus reducing the risk of foodborne infections. Full article

(This article belongs to the Special Issue Medicinal Plants as a Source of Novel Classes of Antimicrobial Agents)

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Open AccessArticle

Molecular Genetic Epidemiology of an Emerging Antimicrobial-Resistant Klebsiella pneumoniae Clone (ST307) Obtained from Clinical Isolates in Central Panama

by Virginia Núñez-Samudio, Gumercindo Pimentel-Peralta, Mellissa Herrera, Maydelin Pecchio, Johana Quintero and Iván Landires

Antibiotics 2022, 11(12), 1817; https://doi.org/10.3390/antibiotics11121817 - 14 Dec 2022

Cited by 3 | Viewed by 2079

Abstract

Klebsiella pneumoniae has been among the main pathogens contributing to the burden of antimicrobial resistance (AMR) in the last decade, and K. pneumoniae AMR strains predominantly cluster in the ST258 clonal complex. However, ST307 is emerging as an important high-risk clone. In Central [...] Read more.

Klebsiella pneumoniae has been among the main pathogens contributing to the burden of antimicrobial resistance (AMR) in the last decade, and K. pneumoniae AMR strains predominantly cluster in the ST258 clonal complex. However, ST307 is emerging as an important high-risk clone. In Central America, there have been few studies on the molecular epidemiology of the K. pneumoniae strains involved in infections. Materials and Methods: We conducted an epidemiological study in three reference hospitals in the central region of Panama, using isolates of K. pneumoniae involved in infections, and identifying their AMR profile, associated clinical risk factors, and molecular typing using a multilocus sequence typing (ST) scheme. Results: Six STs were detected: 307 (55%), 152, 18, 29, 405, and 207. CTX-M-15- and TEM-type beta-lactamases were identified in 100% of ESBL-producing strains; substitutions in gyrA Ser83Ile and parC Ser80Ile were identified in all ST307s; and in ST152 gyrA Ser83Phe, Asp87Ala, and parC Ser80Ile, the qnrB gene was detected in all strains resistant to ciprofloxacin. Conclusions: We present the first report on ST307 in three reference hospitals in the central region of Panama, which is a high-risk emerging clone and represents a public health alert for potential difficulties in managing K. pneumoniae infections in Panama, and which may extend to other Central American countries. Full article

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Antibiotics, Volume 11, Issue 12 (December 2022) – 171 articles

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