Antibiotics

35 pages, 3348 KiB

Open AccessReview

Unraveling the Role of Metals and Organic Acids in Bacterial Antimicrobial Resistance in the Food Chain

by Andreia Rebelo, Agostinho Almeida, Luísa Peixe, Patrícia Antunes and Carla Novais

Antibiotics 2023, 12(9), 1474; https://doi.org/10.3390/antibiotics12091474 - 21 Sep 2023

Cited by 7 | Viewed by 3080

Antimicrobial resistance (AMR) has a significant impact on human, animal, and environmental health, being spread in diverse settings. Antibiotic misuse and overuse in the food chain are widely recognized as primary drivers of antibiotic-resistant bacteria. However, other antimicrobials, such as metals and organic [...] Read more.

Antimicrobial resistance (AMR) has a significant impact on human, animal, and environmental health, being spread in diverse settings. Antibiotic misuse and overuse in the food chain are widely recognized as primary drivers of antibiotic-resistant bacteria. However, other antimicrobials, such as metals and organic acids, commonly present in agri-food environments (e.g., in feed, biocides, or as long-term pollutants), may also contribute to this global public health problem, although this remains a debatable topic owing to limited data. This review aims to provide insights into the current role of metals (i.e., copper, arsenic, and mercury) and organic acids in the emergence and spread of AMR in the food chain. Based on a thorough literature review, this study adopts a unique integrative approach, analyzing in detail the known antimicrobial mechanisms of metals and organic acids, as well as the molecular adaptive tolerance strategies developed by diverse bacteria to overcome their action. Additionally, the interplay between the tolerance to metals or organic acids and AMR is explored, with particular focus on co-selection events. Through a comprehensive analysis, this review highlights potential silent drivers of AMR within the food chain and the need for further research at molecular and epidemiological levels across different food contexts worldwide. Full article

(This article belongs to the Special Issue Environmental Hotspots and Drivers of Antimicrobial Resistance)

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27 pages, 1844 KiB

Open AccessReview

Insight on Incorporation of Essential Oils as Antimicrobial Substances in Biopolymer-Based Active Packaging

by Ana Tomić, Olja Šovljanski and Tamara Erceg

Antibiotics 2023, 12(9), 1473; https://doi.org/10.3390/antibiotics12091473 - 21 Sep 2023

Cited by 9 | Viewed by 2374

Abstract

The increasing interest in microbiological food safety requires the development of sensitive and reliable analyses and technologies for preserving food products’ freshness and quality. Different types of packaging systems are one of the solutions for controlling microbiological activity in foods. During the last [...] Read more.

The increasing interest in microbiological food safety requires the development of sensitive and reliable analyses and technologies for preserving food products’ freshness and quality. Different types of packaging systems are one of the solutions for controlling microbiological activity in foods. During the last decades, the development of biopolymer-based active packaging with essential oil incorporation systems has resulted in technologies with exceptional application potential, primarily in the food industry. There is no doubt that this principle can facilitate food status monitoring, reduce food waste, extend the shelf life, improve the overall quality of food, or indicate a larger problem during the storage, production, and distribution of foodstuffs. On the other hand, most antimicrobial packaging systems are in the development phase, while the sensitivity, selectivity, complexity, and, above all, safety of these materials are just some of the essential questions that need to be answered before they can be widely used. The incorporation of essential oils as antimicrobial substances in biopolymer-based active packaging holds significant promise for enhancing food safety, extending shelf life, and offering more sustainable packaging solutions. While challenges exist, ongoing research and innovation in this field are likely to lead to the development of effective and environmentally friendly packaging systems with enhanced antimicrobial properties. Full article

(This article belongs to the Special Issue Advances in the Discovery of Novel Antimicrobial Agents in Nature and Their Applications)

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11 pages, 2260 KiB

Open AccessArticle

Mechanism of Action of Streptococcus downii, a New Bacterial Species with Probiotic Potential

by Lucía Martínez-Lamas, Eliane García-Mato, Anniris Rincón-Quintero, Berta Rivas-Mundiña, Pedro Diz-Dios and Maximiliano Álvarez-Fernández

Antibiotics 2023, 12(9), 1472; https://doi.org/10.3390/antibiotics12091472 - 21 Sep 2023

Cited by 1 | Viewed by 1628

Abstract

Streptococcus downii is a recently reported bacterial species of oral origin, with inhibitory capacity against Streptococcus mutans, Actinomyces naeslundii, Veillonella parvula and Aggregatibacter actinomycetemcomitans, which confers upon it the potential of being an oral probiotic. The aim of the present [...] Read more.

Streptococcus downii is a recently reported bacterial species of oral origin, with inhibitory capacity against Streptococcus mutans, Actinomyces naeslundii, Veillonella parvula and Aggregatibacter actinomycetemcomitans, which confers upon it the potential of being an oral probiotic. The aim of the present study was to identify the potential mechanisms by which S. downii exerts its inhibitory effect on S. mutans. To this end, the study assessed the consumption of glucose and proteins available in the culture medium, the modification of the pH, the production of short-chain fatty acids, the changes in the protein panel of the inhibition halo, the production of hydrogen peroxide and the effect of proteinase K. There were no differences in the glucose values or in the protein content of the medium, but there was a reduction in pH (with no effect on the growth of S. mutans). Significant increases were detected in the levels of lactic and formic acid (with no effect on the growth of S. mutans), as well as changes in the peptide panel (with no effect on the growth of S. mutans). The inhibitory effect was maintained in the presence of peroxidase but disappeared after adding proteinase K. Based on these results, it is suggested that the main mechanism of inhibition of S. downii against S. mutans is the production of bacteriocins. Full article

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18 pages, 346 KiB

Open AccessReview

Overview of Direct and Indirect Effects of Antibiotics on Terrestrial Organisms

by Alessandra Narciso, Anna Barra Caracciolo and Chiara De Carolis

Antibiotics 2023, 12(9), 1471; https://doi.org/10.3390/antibiotics12091471 - 21 Sep 2023

Cited by 2 | Viewed by 1653

Abstract

Antibiotics (ABs) have made it possible to treat bacterial infections, which were in the past untreatable and consequently fatal. Regrettably, their use and abuse among humans and livestock led to antibiotic resistance, which has made them ineffective in many cases. The spread of [...] Read more.

Antibiotics (ABs) have made it possible to treat bacterial infections, which were in the past untreatable and consequently fatal. Regrettably, their use and abuse among humans and livestock led to antibiotic resistance, which has made them ineffective in many cases. The spread of antibiotic resistance genes (ARGs) and bacteria is not limited to nosocomial environments, but also involves water and soil ecosystems. The environmental presence of ABs and ARGs is a hot topic, and their direct and indirect effects, are still not well known or clarified. A particular concern is the presence of antibiotics in agroecosystems due to the application of agro-zootechnical waste (e.g., manure and biosolids), which can introduce antibiotic residues and ARGs to soils. This review provides an insight of recent findings of AB direct and indirect effects on terrestrial organisms, focusing on plant and invertebrates. Possible changing in viability and organism growth, AB bioaccumulation, and shifts in associated microbiome composition are reported. Oxidative stress responses of plants (such as reactive oxygen species production) to antibiotics are also described. Full article

(This article belongs to the Special Issue Environmental Fate and Effects of Antibiotics and Antibiotic Resistance Genes)

7 pages, 961 KiB

Open AccessCase Report

The First Lethal Infection by Oligella ureolytica: A Case Report and Review of the Literature

by Pierre Serandour, Chloé Plouzeau, Anthony Michaud, Lauranne Broutin, Julie Cremniter, Christophe Burucoa and Maxime Pichon

Antibiotics 2023, 12(9), 1470; https://doi.org/10.3390/antibiotics12091470 - 21 Sep 2023

Cited by 2 | Viewed by 1925

Abstract

Oligella ureolytica is a Gram-negative bacillus, a member of the Alcaligenaceae family, that had never previously been reported as lethal. Herein, a case of fatal infection caused by Oligella ureolytica in an elderly woman with suspected bladder cancer is reported. The species identification [...] Read more.

Oligella ureolytica is a Gram-negative bacillus, a member of the Alcaligenaceae family, that had never previously been reported as lethal. Herein, a case of fatal infection caused by Oligella ureolytica in an elderly woman with suspected bladder cancer is reported. The species identification was confirmed through Sanger sequencing of the bacterial 16S rRNA sequence and compared to published sequences for phylogenetic analysis. Initial antibiotic therapy with ceftriaxone and oxacillin was initiated but had to be switched due to resistance. Cefepime in combination with metronidazole was administered, unfortunately failing to prevent the patient’s death. Further studies are needed to explore additional factors influencing clinical outcomes in Oligella ureolytica infections. Full article

(This article belongs to the Special Issue Pathophysiology, Diagnosis and Therapy of Sepsis)

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13 pages, 1313 KiB

Open AccessArticle

The Direction of the Antibacterial Effect of Rutin Hydrate and Amikacin

by Maria Miklasińska-Majdanik, Małgorzata Kępa, Tomasz J. Wąsik, Karolina Zapletal-Pudełko, Magdalena Klim and Robert D. Wojtyczka

Antibiotics 2023, 12(9), 1469; https://doi.org/10.3390/antibiotics12091469 - 21 Sep 2023

Cited by 9 | Viewed by 1686

Abstract

The aim of the presented study was to examine the in vitro antimicrobial activity of rutin hydrate (RH) alone and in combination with amikacin against 12 reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity assay was evaluated in the concentration range [...] Read more.

The aim of the presented study was to examine the in vitro antimicrobial activity of rutin hydrate (RH) alone and in combination with amikacin against 12 reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity assay was evaluated in the concentration range of 2–2048 µg/mL. A serial microdilution method was used to determine the minimal inhibitory concentration (MIC) of the examined compound against reference strains. RH showed varying potential against the tested strains with MICs ranging from 128 to 1024 µg/mL. In order to examine the combinatory profile of RH and amikacin, the fractional inhibitory concentrations (FICs) were determined. The RH–amikacin combination was more active against Gram-negative bacteria where four synergism and two additive interactions were noted. For four out of six Gram-positive isolates, an indifferent effect of RH and amikacin was demonstrated, and for two strains, the tested combination had an additive effect. The results of this study showed that RH possesses antimicrobial potential in vitro towards the tested reference isolates. Moreover, it shows a promising combined effect with amikacin against Gram-negative bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Natural Products and Plants Extracts)

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30 pages, 1877 KiB

Open AccessReview

Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance

by Zsuzsanna Schelz, Hiba F. Muddather and István Zupkó

Antibiotics 2023, 12(9), 1468; https://doi.org/10.3390/antibiotics12091468 - 20 Sep 2023

Cited by 5 | Viewed by 2124

Abstract

Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, [...] Read more.

Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases. Full article

(This article belongs to the Special Issue The Role of Efflux Pump Inhibitor in Bacterial Multidrug Resistance, 2nd Edition)

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18 pages, 2926 KiB

Open AccessArticle

Streptomyces rugosispiralis sp. nov., a Novel Actinobacterium Isolated from Peat Swamp Forest Soil That Produces Ansamycin Derivatives and Nocardamines

by Trinset Weeraphan, Khomsan Supong, Paranee Sripreechasak, Rumpa Jutakanoke, Supalerk Kowinthanaphat, Somboon Tanasupawat, Pattama Pittayakhajonwut and Wongsakorn Phongsopitanun

Antibiotics 2023, 12(9), 1467; https://doi.org/10.3390/antibiotics12091467 - 20 Sep 2023

Cited by 1 | Viewed by 2005

Abstract

Actinomycetes, especially the genus Streptomyces, are one of the most promising sources of bioactive natural products. In this study, a novel Streptomyces strain, RCU-064^T, was isolated from a soil sample collected from a peat swamp forest in Thailand. Strain RCU-064 [...] Read more.

Actinomycetes, especially the genus Streptomyces, are one of the most promising sources of bioactive natural products. In this study, a novel Streptomyces strain, RCU-064^T, was isolated from a soil sample collected from a peat swamp forest in Thailand. Strain RCU-064^T showed the highest 16S rRNA gene sequence similarity (99.06%) with Streptomyces malaysiensis NBRC 16446^T. Based on a polyphasic approach, strain RCU-064^T represents a novel species of the genus Streptomyces, for which the name Streptomyces rugosispiralis sp. nov. is proposed. The chemical isolation of the crude ethyl acetate extracts of the strain led to the isolation of six compounds: (1) geldanamycin, (2) 17-O-demethylgeldanamycin, (3) reblastatin, (4) 17-demethoxyreblastatin, (5) nocardamine, and (6) dehydroxynocardamine. These compounds were evaluated for their biological activities. All compounds showed no antimicrobial activity against tested microorganisms used in this study. Compounds (1)–(4) displayed cytotoxic activity against the NCI-H187 cell line, with IC₅₀ values ranging from 0.045–4.250 µg/mL. Cytotoxicity against the MCF-7 cell line was found in compounds (1) and (3) with IC₅₀ values of 3.51 and 1.27 µg/mL, respectively. Compounds (5) and (6) exhibited cytotoxicity only against Vero cells (IC₅₀ of 16.57 µg/mL) and NCI-H187 cells (IC₅₀ of 13.96 µg/mL), respectively. These results indicate that peat swamp forest soil remains a promising reservoir of novel actinomycetes capable of producing bioactive natural products. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Natural Products and Plants Extracts)

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21 pages, 3748 KiB

Open AccessArticle

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications

by Rajaguru Arivuselvam, Ayed A. Dera, Syed Parween Ali, Yasser Alraey, Ahmed Saif, Umme Hani, Sivaa Arumugam Ramakrishnan, Mohamed Sheik Tharik Abdul Azeeze, Raman Rajeshkumar, Aishwarya Susil, Haritha Harindranath and B. R. Prashantha Kumar

Antibiotics 2023, 12(9), 1466; https://doi.org/10.3390/antibiotics12091466 - 20 Sep 2023

Cited by 4 | Viewed by 3858

Abstract

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including [...] Read more.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets. Full article

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10 pages, 931 KiB

Open AccessArticle

Poor Sensitivity of the MALDI Biotyper^® MBT Subtyping Module for Detection of Klebsiella pneumoniae Carbapenemase (KPC) in Klebsiella Species

by Luz Cuello, Judith Alvarez Otero, Kerryl E. Greenwood-Quaintance, Liang Chen, Blake Hanson, Jinnethe Reyes, Lauren Komarow, Lizhao Ge, Zane D. Lancaster, Garrett G. Gordy, Audrey N. Schuetz and Robin Patel

Antibiotics 2023, 12(9), 1465; https://doi.org/10.3390/antibiotics12091465 - 20 Sep 2023

Cited by 1 | Viewed by 1813

Abstract

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper^® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect [...] Read more.

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper^® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for bla_KPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of bla_KPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the bla_KPC-positive Klebsiella isolates. Full article

(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)

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19 pages, 825 KiB

Open AccessFeature PaperReview

ICU-Acquired Colonization and Infection Related to Multidrug-Resistant Bacteria in COVID-19 Patients: A Narrative Review

by Alexandre Gaudet, Louis Kreitmann and Saad Nseir

Antibiotics 2023, 12(9), 1464; https://doi.org/10.3390/antibiotics12091464 - 20 Sep 2023

Cited by 5 | Viewed by 2036

Abstract

A large proportion of ICU-acquired infections are related to multidrug-resistant bacteria (MDR). Infections caused by these bacteria are associated with increased mortality, and prolonged duration of mechanical ventilation and ICU stay. The aim of this narrative review is to report on the association [...] Read more.

A large proportion of ICU-acquired infections are related to multidrug-resistant bacteria (MDR). Infections caused by these bacteria are associated with increased mortality, and prolonged duration of mechanical ventilation and ICU stay. The aim of this narrative review is to report on the association between COVID-19 and ICU-acquired colonization or infection related to MDR bacteria. Although a huge amount of literature is available on COVID-19 and MDR bacteria, only a few clinical trials have properly evaluated the association between them using a non-COVID-19 control group and accurate design and statistical methods. The results of these studies suggest that COVID-19 patients are at a similar risk of ICU-acquired MDR colonization compared to non-COVID-19 controls. However, a higher risk of ICU-acquired infection related to MDR bacteria has been reported in several studies, mainly ventilator-associated pneumonia and bloodstream infection. Several potential explanations could be provided for the high incidence of ICU-acquired infections related to MDR. Immunomodulatory treatments, such as corticosteroids, JAK2 inhibitors, and IL-6 receptor antagonist, might play a role in the pathogenesis of these infections. Additionally, a longer stay in the ICU was reported in COVID-19 patients, resulting in higher exposure to well-known risk factors for ICU-acquired MDR infections, such as invasive procedures and antimicrobial treatment. Another possible explanation is the surge during successive COVID-19 waves, with excessive workload and low compliance with preventive measures. Further studies should evaluate the evolution of the incidence of ICU-acquired infections related to MDR bacteria, given the change in COVID-19 patient profiles. A better understanding of the immune status of critically ill COVID-19 patients is required to move to personalized treatment and reduce the risk of ICU-acquired infections. The role of specific preventive measures, such as targeted immunomodulation, should be investigated. Full article

(This article belongs to the Special Issue Antibiotic Resistant Pathogens in Hospital)

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11 pages, 1260 KiB

Open AccessArticle

Resistome and Genome Analysis of an Extensively Drug-Resistant Klebsiella michiganensis KMIB106: Characterization of a Novel KPC Plasmid pB106-1 and a Novel Cointegrate Plasmid pB106-IMP Harboring bla_IMP-4 and bla_SHV-12

by Linjing Wang, Haijun Chen, Wanting Liu, Ling Yang, Zhenbo Xu and Dingqiang Chen

Antibiotics 2023, 12(9), 1463; https://doi.org/10.3390/antibiotics12091463 - 20 Sep 2023

Cited by 1 | Viewed by 1546

Abstract

Klebsiella michiganensis is a recently emerging human pathogen causing nosocomial infections. This study aimed to characterize the complete genome sequence of a clinical Klebsiella michiganensis strain KMIB106 which exhibited extensive drug-resistance. The whole genome of the strain was sequenced using PacBio RS III [...] Read more.

Klebsiella michiganensis is a recently emerging human pathogen causing nosocomial infections. This study aimed to characterize the complete genome sequence of a clinical Klebsiella michiganensis strain KMIB106 which exhibited extensive drug-resistance. The whole genome of the strain was sequenced using PacBio RS III systems and Illumina Nextseq 500. Annotation, transposable elements and resistance gene identification were analyzed by RAST, prokka and Plasmid Finder, respectively. According to the results, KMIB106 was resistant to multiple antimicrobials, including carbapenems, but it remained susceptible to aztreonam. The genome of KMIB106 consisted of a single chromosome and three predicted plasmids. Importantly, a novel KPC plasmid pB106-1 was found to carry the array of resistance genes in a highly different order in its variable regions, including mphA, msrE, mphE, ARR-3, addA16, sul1, dfrA27, tetD and fosA3. Plasmid pB106-2 is a typical IncFII plasmid with no resistant gene. Plasmid pB106-IMP consists of the IncN and IncX3 backbones, and two resistance genes, bla_IMP-4 and bla_SHV-12, were identified. Our study for the first time reported an extensively drug-resistant Klebsiella michiganensis strain recovered from a child with a respiratory infection in Southern China, which carries three mega plasmids, with pB106-1 firstly identified to carry an array of resistance genes in a distinctive order, and pB106-IMP identified as a novel IncN-IncX3 cointegrate plasmid harboring two resistance genes bla_IMP-4 and bla_SHV-12. Full article

(This article belongs to the Section Antibiofilm Strategies)

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25 pages, 1200 KiB

Open AccessArticle

Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of Xenorhabdus budapestensis and X. szentirmaii Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including Histomonas meleagridis and Leishmania donovani Species

by András Fodor, Claudia Hess, Petra Ganas, Zsófia Boros, János Kiss, László Makrai, Károly Dublecz, László Pál, László Fodor, Anna Sebestyén, Michael G. Klein, Eustachio Tarasco, Manjusha M. Kulkarni, Bradford S. McGwire, Tibor Vellai and Michael Hess

Antibiotics 2023, 12(9), 1462; https://doi.org/10.3390/antibiotics12091462 - 19 Sep 2023

Cited by 1 | Viewed by 1858

Abstract

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of [...] Read more.

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic–nematode species, release a series of non-ribosomal templated anti-microbial peptides. Some may be potential drug candidates. The ability of an entomopathogenic–nematode/entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product. This explains that those gene complexes that are responsible for the biosynthesis of different non-ribosomal templated anti-microbial protective peptides (including those that are potently capable of inactivating the protist mammalian pathogen Leishmania donovanii and the gallinaceous bird pathogen Histomonas meleagridis) are co-regulated. Our approach is based on comparative anti-microbial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated anti-microbial peptides that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourage us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing entomopathogenic-bacterium (EPB) strains producing and releasing single, harmless, non-ribosomal templated anti-microbial peptides with considerable drug, (probiotic)-candidate potential. Full article

(This article belongs to the Special Issue Potential of Antimicrobial Peptides for an Exciting Future)

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12 pages, 1716 KiB

Open AccessArticle

Microbial Community and Abundance of Selected Antimicrobial Resistance Genes in Poultry Litter from Conventional and Antibiotic-Free Farms

by Camilla Smoglica, Muhammad Farooq, Fausto Ruffini, Fulvio Marsilio and Cristina Esmeralda Di Francesco

Antibiotics 2023, 12(9), 1461; https://doi.org/10.3390/antibiotics12091461 - 19 Sep 2023

Cited by 1 | Viewed by 1399

Abstract

In this study, a culture-independent approach was applied to compare the microbiome composition and the abundance of the antimicrobial resistance genes (ARGs) aadA2 for aminoglycosides, tet(A), tet(B), tet(K), and tet(M) for tetracyclines, and mcr-1 for colistin in [...] Read more.

In this study, a culture-independent approach was applied to compare the microbiome composition and the abundance of the antimicrobial resistance genes (ARGs) aadA2 for aminoglycosides, tet(A), tet(B), tet(K), and tet(M) for tetracyclines, and mcr-1 for colistin in broiler litter samples collected from conventional and antibiotic-free flocks located in Central Italy. A total of 13 flocks and 26 litter samples, collected at the beginning and at the end of each rearing cycle, were submitted to 16s rRNA sequence analysis and quantitative PCR for targeted ARGs. Firmicutes resulted in the dominant phylum in both groups of flocks, and within it, the Clostridia and Bacilli classes showed a similar distribution. Conversely, in antibiotic-free flocks, a higher frequency of Actinobacteria class and Clostridiaceae, Lactobacillaceae, Corynebacteriaceae families were reported, while in the conventional group, routinely treated with antibiotics for therapeutic purposes, the Bacteroidia class and the Enterobacteriaceae and Bacillaceae families were predominant. All investigated samples were found to be positive for at least one ARG, with the mean values of aadA2 and tet(A) the highest in conventional flocks by a significant margin. The results suggest that antibiotic use can influence the frequency of resistance determinants and the microbial community in poultry flocks, even though other environmental factors should also be investigated more deeply in order to identify additional drivers of antimicrobial resistance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in One Health Perspective: New Insights in Human, Animal, and Environment Interlace)

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12 pages, 900 KiB

Open AccessArticle

Sequential or Combination Treatments as Rescue Therapies in Immunocompromised Patients with Persistent SARS-CoV-2 Infection in the Omicron Era: A Case Series

by Bianca Maria Longo, Francesco Venuti, Alberto Gaviraghi, Tommaso Lupia, Fabio Antonino Ranzani, Andrea Pepe, Laura Ponzetta, Davide Vita, Tiziano Allice, Vanesa Gregorc, Pio Manlio Mirko Frascione, Francesco Giuseppe De Rosa, Andrea Calcagno and Stefano Bonora

Antibiotics 2023, 12(9), 1460; https://doi.org/10.3390/antibiotics12091460 - 19 Sep 2023

Cited by 5 | Viewed by 2028

Abstract

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed [...] Read more.

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients. Full article

(This article belongs to the Special Issue Healthcare-Associated Infections (HAIs): Prevention, Control and Surveillance)

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17 pages, 2679 KiB

Open AccessArticle

Antibacterial and Antibiofilm Activity of Endophytic Alternaria sp. Isolated from Eremophila longifolia

by Daniel J. Caruso, Enzo A. Palombo, Simon E. Moulton, Peter J. Duggan and Bita Zaferanloo

Antibiotics 2023, 12(9), 1459; https://doi.org/10.3390/antibiotics12091459 - 19 Sep 2023

Cited by 2 | Viewed by 2021

Abstract

The threat to public health resulting from the emergence of antimicrobial resistance (AMR) is ever rising. One of the major bacterial pathogens at the forefront of this problem is methicillin-resistant Staphylococcus aureus, or MRSA, for which there is a great need to [...] Read more.

The threat to public health resulting from the emergence of antimicrobial resistance (AMR) is ever rising. One of the major bacterial pathogens at the forefront of this problem is methicillin-resistant Staphylococcus aureus, or MRSA, for which there is a great need to find alternative treatments. One of the most promising alternatives is endophytic fungi, which were shown to produce a vast array of bioactive compounds, including many novel antibacterial compounds. In this study, two endophytic Alternaria sp., EL 24 and EL 35, were identified from the leaves of Eremophila longifolia. Ethyl acetate (EtOAc) extracts of their culture filtrates were found to inhibit both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. The activity of each extract was shown to be greatly affected by the growth medium, with considerable reductions in minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) observed when tested in tryptic soy broth with glucose (TSBG) compared with Mueller–Hinton broth (MHB). Both extracts displayed significant (p ≤ 0.05) antibiofilm activity against all three S. aureus strains, the greatest of which was that of EL 35, which reduced biofilm formation by M180920 by 72%, while that of EL 24 resulted in a 57% reduction against ATCC 25923. Both extracts also disrupted established biofilms, of which the most effective was EL 35, which reduced the M180920 biofilm by 64%, while EL 24 also performed best against M180920, reducing biofilm by 54%. Gas chromatography–mass spectrometry (GC-MS) analysis of the EL 24 EtOAc extract revealed five known compounds. This study highlights the promise of endophytic fungi from Australian plants as a potential source of substances effective against important bacterial pathogens. Further understanding of the responsible compounds and their mechanisms could lead to the development of treatments effective against MRSA, as well as novel biofilm-resistant biomedical materials, contributing towards reducing the burden of AMR. Full article

(This article belongs to the Special Issue Microbial Biofilms, Antimicrobials, and Virulence Determinants)

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12 pages, 2749 KiB

Open AccessArticle

Prevalence and Phylogenetic Analysis of Lipoprotein-Gene ragB-1 of Porphyromonas gingivalis—A Pilot Study

by Sarah Böcher, Hendrik L. Meyer, Evdokia Dafni and Georg Conrads

Antibiotics 2023, 12(9), 1458; https://doi.org/10.3390/antibiotics12091458 - 19 Sep 2023

Viewed by 1160

Abstract

Porphyromonas gingivalis (P.g.) is a key pathogen involved in periodontal diseases. The aim of this study was to investigate the prevalence and phylogenetic origin of the lipoprotein-gene ragB in its most virulent variant, ragB-1 (co-transcribed with ragA-1 as locus rag-1), [...] Read more.

Porphyromonas gingivalis (P.g.) is a key pathogen involved in periodontal diseases. The aim of this study was to investigate the prevalence and phylogenetic origin of the lipoprotein-gene ragB in its most virulent variant, ragB-1 (co-transcribed with ragA-1 as locus rag-1), in different P.g. strains collected worldwide. A total of 138 P.g. strains were analyzed for the presence of ragB-1 by pooled analysis and subsequently individual PCRs. Sequencing a core fragment of ragB-1 of the individual strains made it possible to carry out a phylogenetic classification using sequence alignment. In total, 22 of the 138 P.g. strains tested positive for ragB-1, corresponding to a prevalence of 16%. The fragment investigated was highly conserved, with variations in the base sequence detected in only three strains (OMI 1072, OMI 1081, and OMI 1074). In two strains, namely OMI 1072 (original name: I-433) and OMI 1081 (original name: I-372), which originate from monkeys, two amino-acid alterations were apparent. Since ragB-1 has also been found in animal strains, it may be concluded that rag-1 was transferred from animals to humans and that this originally virulent variant was weakened by mutations over time so that new, less virulent, adapted commensal versions of rag (rag-2, -3, and -4), with P.g. as the host, evolved. Full article

(This article belongs to the Special Issue Antibacterial Treatment in Periodontal and Endodontic Therapy, 2nd Edition)

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11 pages, 719 KiB

Open AccessArticle

Surveillance of Multidrug-Resistant Pathogens in Neonatal Intensive Care Units of Palermo, Italy, during SARS-CoV-2 Pandemic

by Giorgio Graziano, Veronica Notarbartolo, Walter Priano, Carmelo Massimo Maida, Vincenzo Insinga, Grazia Rinaudo, Arianna Russo, Roberta Palermo, Francesco Vitale and Mario Giuffrè

Antibiotics 2023, 12(9), 1457; https://doi.org/10.3390/antibiotics12091457 - 19 Sep 2023

Cited by 1 | Viewed by 1926

Abstract

Background: Antimicrobial resistance (AMR) is a topic of concern, especially in high-level care departments like neonatal intensive care units (NICUs). The systematic use of an “active” epidemiological surveillance system allows us to observe and analyze any changes in microbial distribution, limiting the risk [...] Read more.

Background: Antimicrobial resistance (AMR) is a topic of concern, especially in high-level care departments like neonatal intensive care units (NICUs). The systematic use of an “active” epidemiological surveillance system allows us to observe and analyze any changes in microbial distribution, limiting the risk of healthcare-associated infection (HAI) development. Methods: We have conducted a longitudinal observational study in the five NICUs of Palermo, comparing the “pre-pandemic period” (March 2014–February 2020) with the “pandemic” one (March 2020–February 2022). The primary aim of the study was to evaluate the cumulative prevalence of carriage from multi-drug resistant (MDR) bacteria in the cumulative NICUs (NICU C). Results: During the “pre-pandemic period”, 9407 swabs were collected (4707 rectal, 4700 nasal); on the contrary, during the “pandemic period”, a total of 2687 swabs were collected (1345 rectal, 1342 nasal). A statistically significant decrease in MDR-Gram-negative bacteria (GNB) carriage prevalence was detected during the pandemic. At the same time, there was a general worsening of the carriage of carbapenemase-forming MDR-GNB (CARBA-R+) and methicillin-resistant Staphylococcus aureus (MRSA) during the pandemic period. A significant reduction in methicillin-susceptible Staphylococcus aureus (MSSA) carriage was detected too. Conclusions: The surveillance of MDRO carriage in NICUs is fundamental for limiting the social and economic burden of HAIs. Full article

(This article belongs to the Special Issue The One Health Strategy in Antimicrobial Resistance and Antimicrobial Use Surveillance Programs)

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10 pages, 1928 KiB

Open AccessArticle

Knowledge, Attitudes, and Practices Regarding Antibiotic Sales in Pharmacies in Medellín, Colombia 2023

by Daniel Ricardo Montes Colonia, Daniela Ramírez Patiño and Luis Felipe Higuita-Gutiérrez

Antibiotics 2023, 12(9), 1456; https://doi.org/10.3390/antibiotics12091456 - 19 Sep 2023

Cited by 2 | Viewed by 1559

Abstract

Objective: Describe the knowledge, attitudes, and practices regarding the sale of antibiotics in pharmacies in Medellín, Colombia. Method: A cross-sectional descriptive study was conducted in 277 selected pharmacies using a stratified sampling method with proportional allocation to represent all areas of the city. [...] Read more.

Objective: Describe the knowledge, attitudes, and practices regarding the sale of antibiotics in pharmacies in Medellín, Colombia. Method: A cross-sectional descriptive study was conducted in 277 selected pharmacies using a stratified sampling method with proportional allocation to represent all areas of the city. Knowledge, attitudes, and practices (KAPs) were assessed using a scale, analyzed with absolute and relative frequencies for each item, and represented in a global score ranging from 0 to 100, with a higher score indicating better KAPs. Data were analyzed using relative frequencies with 95% confidence intervals, the Mann-Whitney U test, the Kruskal-Wallis test, and linear regression. Results: Of the included pharmacies, 52.6% were chain pharmacies, 48.4% were attended by pharmacy assistants, and 59% of pharmacists had more than 5 years of experience. The median knowledge score was 70.8 (IQR 58.3–87.5), with 35.3% of pharmacists believing that antibiotics are effective in treating the common cold, 35.2% for treating COVID-19, and 29.4% considering them available for sale without a medical prescription. The attitude score was 53.3 (40.0–66.7), with 60.9% agreeing that prohibiting the sale of antibiotics without a prescription would decrease their sales. The practice score was 62.5 (40.0–79.2), with 65.4% of pharmacists stating that they sometimes sell antibiotics without a prescription due to patients struggling to obtain a medical consultation, 61.3% admitting to selling antibiotics without a prescription for urinary tract infections, and 41.3% for upper respiratory tract infections. Practices were predominantly influenced by pharmacy type (chain or independent) and, to a lesser extent, by knowledge and attitudes. Conclusion: Pharmacists in Medellín exhibit inadequate knowledge, attitudes, and practices regarding the use and sale of antibiotics without a medical prescription. These findings align with international evidence highlighting the need for educational and regulatory strategies promoting rational antibiotic use in pharmacies. Full article

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

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11 pages, 1201 KiB

Open AccessArticle

A Prospective, Randomized, Comparative Study of Topical Minocycline Gel 4% with Topical Clindamycin Phosphate Gel 1% in Indian Patients with Acne Vulgaris

by Bela Shah, Deval Mistry, Nelry Gonsalves, Presha Vasani, Dhiraj Dhoot and Hanmant Barkate

Antibiotics 2023, 12(9), 1455; https://doi.org/10.3390/antibiotics12091455 - 19 Sep 2023

Cited by 2 | Viewed by 2795

Abstract

Acne vulgaris is characterized by inflammatory and non-inflammatory skin lesions with a high prevalence among adolescents in India. Not enough studies are reported on the use of topical antibiotics for the management of acne in the Indian population. The proposed study aims to [...] Read more.

Acne vulgaris is characterized by inflammatory and non-inflammatory skin lesions with a high prevalence among adolescents in India. Not enough studies are reported on the use of topical antibiotics for the management of acne in the Indian population. The proposed study aims to compare the efficacy and safety of topical minocycline gel 4% with topical clindamycin gel 1% in the Indian population. A randomized, open-label, double-arm study was planned at two centers in India. One hundred patients were enrolled and randomized equally to two treatment arms. The drugs were applied once daily, preferably at the same time each day. The number of inflammatory and non-inflammatory lesions, as well as the investigator’s global assessment (IGA), were obtained at the baseline and on weeks 3, 6, 9, and 12. The change in these parameters from baseline to week 12 was compared between the two treatment arms. A tolerability assessment was also performed on selected parameters. The age of patients ranged between 14 and 31 years, with female preponderance in each arm. On week 12, the percent change in inflammatory and non-inflammatory lesions in the minocycline 4% arm was significantly higher than in the clindamycin 1% arm (p < 0.0001). The IGA treatment success was significantly higher in the minocycline arm compared to the clindamycin arm on weeks 9 and 12, with p-values of 0.001 and 0.015, respectively. Tolerability assessment revealed significantly improved parameter performance in the minocycline arm compared to the clindamycin arm. On subgroup analysis, in adolescents, minocycline was found to be more efficacious than clindamycin. The comparative assessment resulted in a significantly improved performance of minocycline gel 4% compared to clindamycin gel 1% in the Indian population, thus making it a preferred choice for the treatment of moderate-to-severe acne in India. Full article

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13 pages, 1780 KiB

Open AccessArticle

Urinary Tract Infection and Antimicrobial Resistance Patterns: 5-Year Experience in a Tertiary Pediatric Nephrology Center in the Southwestern Region of Poland

by Anna Kawalec, Justyna Józefiak and Katarzyna Kiliś-Pstrusińska

Antibiotics 2023, 12(9), 1454; https://doi.org/10.3390/antibiotics12091454 - 19 Sep 2023

Cited by 6 | Viewed by 2587

Abstract

(1) Background: Urinary tract infections (UTIs) are among the most common infections in the pediatric population. This study aimed to analyze the urine culture results and antimicrobial patterns over the last 5 years in children diagnosed with UTI. (2) Methods: Retrospective analysis of [...] Read more.

(1) Background: Urinary tract infections (UTIs) are among the most common infections in the pediatric population. This study aimed to analyze the urine culture results and antimicrobial patterns over the last 5 years in children diagnosed with UTI. (2) Methods: Retrospective analysis of medical records of 242 patients hospitalized in the Pediatric Nephrology Department diagnosed with a UTI in the years 2018–2022. (3) Results: The most common causative agent was E. coli, responsible for 64% of UTIs, followed by Klebsiella spp. (16%), Pseudomonas spp. (6%), Enterobacter spp. (4%), Proteus spp. (4%), and Enterococcus spp. (3%). Non-E. coli UTIs were significantly more frequently observed in patients with congenital anomalies of the kidney and urinary tract or neurogenic bladder and patients receiving antibiotic prophylaxis. For the whole study period, 32% of E. coli were resistant to amoxicillin/clavulanic acid, 23.3% to trimethoprim/sulfamethoxazole, 12.2% to ciprofloxacin, and 4.4% to nitrofurantoin. During 2018–2022, the prevalence of E. coli resistant to amoxicillin/clavulanic acid varied from 16.7% to 41.2%, and resistance to cefuroxime increased four times (from 4% in 2018 to 16.7% in 2022). Starting in 2021, all isolated E. coli strains were classified as susceptible-increased exposure or resistant to cefuroxime. (4) Conclusion: Managing pediatric UTIs remains challenging in clinical practice. The choice of optimal empiric treatment should be considered following local recommendations and individual risk factors assessment and require careful dosage adjustment. Observed changes in antimicrobial resistance indicated the need for frequent updating of local recommendations for the management of pediatric patients with UTIs. Full article

(This article belongs to the Special Issue Urinary Tract Infections and Antibiotic Intervention)

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11 pages, 770 KiB

Open AccessArticle

Bloodstream Infection Due to Coagulase-Negative Staphylococci: Impact of Species on Prevalence of Infective Endocarditis

by Sara F. Haddad, Brian D. Lahr, Sebastian Santos Patarroyo, Supavit Chesdachai, Kami D. Kies, John C. O’Horo, Daniel C. DeSimone, Parham Sendi and Larry M. Baddour

Antibiotics 2023, 12(9), 1453; https://doi.org/10.3390/antibiotics12091453 - 18 Sep 2023

Cited by 2 | Viewed by 3080

Abstract

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective [...] Read more.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant. Full article

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11 pages, 835 KiB

Open AccessSystematic Review

Predicting Extended-Spectrum Beta-Lactamase and Carbapenem Resistance in Enterobacteriaceae Bacteremia: A Diagnostic Model Systematic Review and Meta-Analysis

by Tristan T. Timbrook and McKenna J. Fowler

Antibiotics 2023, 12(9), 1452; https://doi.org/10.3390/antibiotics12091452 - 17 Sep 2023

Cited by 3 | Viewed by 2598

Abstract

Enterobacteriaceae bacteremia, particularly when associated with antimicrobial resistance, can result in increased mortality, emphasizing the need for timely effective therapy. Clinical risk prediction models are promising tools, stratifying patients based on their risk of resistance due to ESBL and carbapenemase-producing Enterobacteriaceae in bloodstream [...] Read more.

Enterobacteriaceae bacteremia, particularly when associated with antimicrobial resistance, can result in increased mortality, emphasizing the need for timely effective therapy. Clinical risk prediction models are promising tools, stratifying patients based on their risk of resistance due to ESBL and carbapenemase-producing Enterobacteriaceae in bloodstream infections (BSIs) and, thereby, improving therapeutic decisions. This systematic review and meta-analysis synthesized the literature on the performance of these models. Searches of PubMed and EMBASE led to the identification of 10 relevant studies with 6106 unique patient encounters. Nine studies concerned ESBL prediction, and one focused on the prediction of carbapenemases. For the two ESBL model derivation studies, the discrimination performance showed sensitivities of 53–85% and specificities of 93–95%. Among the four ESBL model derivation and validation studies, the sensitivities were 43–88%, and the specificities were 77–99%. The sensitivity and specificity for the subsequent external validation studies were 7–37% and 88–96%, respectively. For the three external validation studies, only two models were evaluated across multiple studies, with a pooled AUROC of 65–71%, with one study omitting the sensitivity/specificity. Only two studies measured clinical utility through hypothetical therapy assessments. Given the limited evidence on their interventional application, it would be beneficial to further assess these or future models, to better understand their clinical utility and ensure their safe and impactful implementation. Full article

(This article belongs to the Special Issue Strategies for Combatting Multidrug-Resistant and Extensively Drug-Resistant Bacteria: Current Challenges and Future Prospects)

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18 pages, 1179 KiB

Open AccessArticle

Chemical Characterization and Antifungal Activity of Blue Tansy (Tanacetum annuum) Essential Oil and Crude Extracts against Fusarium oxysporum f. sp. albedinis, an Agent Causing Bayoud Disease of Date Palm

by Hajar Ettakifi, Kaoutar Abbassi, Safae Maouni, El Hadi Erbiai, Abderrahmane Rahmouni, Mounir Legssyer, Rabah Saidi, Zouhaire Lamrani, Joaquim C. G. Esteves da Silva, Eugénia Pinto and Abdelfettah Maouni

Antibiotics 2023, 12(9), 1451; https://doi.org/10.3390/antibiotics12091451 - 16 Sep 2023

Cited by 2 | Viewed by 2086

Abstract

Tanacetum annuum L. is a Mediterranean plant, commonly known as Blue Tansy due to its blue colour as an essential oil, which is widely used for medicinal purposes. However, there are no studies on the bioactive compounds (especially, phenolic compounds) and the biological [...] Read more.

Tanacetum annuum L. is a Mediterranean plant, commonly known as Blue Tansy due to its blue colour as an essential oil, which is widely used for medicinal purposes. However, there are no studies on the bioactive compounds (especially, phenolic compounds) and the biological properties of their organic extracts. Herein, the purpose of the present work was to investigate the chemical composition of the essential oil and crude extracts of the T. annuum aerial parts collected from northern Morocco and to evaluate their antioxidant and antifungal activity against Fusarium oxysporum f. sp. albedinis, an agent causing Bayoud disease of the date palm, an important food source and commercial perennial crop in the Sahara and North Africa. Chemically, Folin–Ciocalteu and aluminium chloride colourimetric methods were used to determine the total phenolic (TPC) and total flavonoid (TFC) contents, respectively; polyphenols were characterized using HPLC-MS, while GC-MS was used to analyse the essential oil composition. Moreover, the evaluation of antioxidant and antifungal activities was carried out using the DPPH test and microdilution method, respectively. The results showed that the three T. annuum parts (stems, leaves and flowers) extracts contained important TPC and TFC with values varied between 51.32 and 116.32 mg/g of dry crude extract (DCE). HPLC-MS analysis revealed the identification and quantification of 19 phenolic acids and flavonoids with an emphasis on apigenin 7-glucoside (4540 µg/g of dry weight (DW)), luteolin 7-glucoside (2804 µg/g DW) and salicylic acid (1878 µg/g DW). Additionally, 39 biomolecules were identified in the essential oil using GC-MS, which were predominated by camphor (16.69%), α-pinene (12.37%), bornyl acetate (11.97%) and limonene (11.10%). The methanolic and hydro-methanolic extracts of T. annuum parts demonstrated a strong antioxidant property with IC₅₀ values ranging between 0.22 and 0.65 mg/mL. Concerning antifungal activity, the essential oil and crude extracts of the Moroccan Blue Tansy exhibited a potent capacity against F. oxysporum f. sp. albedinis at low concentrations, with MIC and MFC values of 3.33 and 4.58 µL/mL for the essential oil and values of 3.33 and 9.17 mg/mL for crude extracts, respectively. Overall, these results demonstrated T. annuum as an important source of bioactive compounds and contribute significantly to the potential of using essential oils and extracts for controlling the Bayoud disease of date palms. Moreover, the finding suggests that T. annuum can be highly useful for phytosanitary and pharmaceutical industries. Full article

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

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16 pages, 1882 KiB

Open AccessArticle

Effect of Hydrogen Peroxide on Cyanobacterial Biofilms

by Maria João Romeu, João Morais, Vítor Vasconcelos and Filipe Mergulhão

Antibiotics 2023, 12(9), 1450; https://doi.org/10.3390/antibiotics12091450 - 16 Sep 2023

Cited by 1 | Viewed by 2025

Abstract

Although a range of disinfecting formulations is commercially available, hydrogen peroxide is one of the safest chemical agents used for disinfection in aquatic environments. However, its effect on cyanobacterial biofilms is poorly investigated. In this work, biofilm formation by two filamentous cyanobacterial strains [...] Read more.

Although a range of disinfecting formulations is commercially available, hydrogen peroxide is one of the safest chemical agents used for disinfection in aquatic environments. However, its effect on cyanobacterial biofilms is poorly investigated. In this work, biofilm formation by two filamentous cyanobacterial strains was evaluated over seven weeks on two surfaces commonly used in marine environments: glass and silicone-based paint (Sil-Ref) under controlled hydrodynamic conditions. After seven weeks, the biofilms were treated with a solution of hydrogen peroxide (H₂O₂) to assess if disinfection could affect long-term biofilm development. The cyanobacterial biofilms appeared to be tolerant to H₂O₂ treatment, and two weeks after treatment, the biofilms that developed on glass by one of the strains presented higher biomass amounts than the untreated biofilms. This result emphasizes the need to correctly evaluate the efficiency of disinfection in cyanobacterial biofilms, including assessing the possible consequences of inefficient disinfection on the regrowth of these biofilms. Full article

(This article belongs to the Special Issue Antibiotic Residues and Antimicrobial-Resistant Bacteria in the Environment)

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19 pages, 1128 KiB

Open AccessArticle

Analyses of Extended-Spectrum-β-Lactamase, Metallo-β-Lactamase, and AmpC-β-Lactamase Producing Enterobacteriaceae from the Dairy Value Chain in India

by Tushar Kumar Dey, Johanna Frida Lindahl, Åke Lundkvist, Delia Grace, Ram Pratim Deka, Rajeswari Shome, Samiran Bandyopadhyay, Naresh Kumar Goyal, Garima Sharma and Bibek Ranjan Shome

Antibiotics 2023, 12(9), 1449; https://doi.org/10.3390/antibiotics12091449 - 14 Sep 2023

Cited by 2 | Viewed by 2343

Abstract

The consumption of milk contaminated with antibiotic-resistant bacteria poses a significant health threat to humans. This study aimed to investigate the prevalence of Enterobacteriaceae producing β-lactamases (ESBL, MBL, and AmpC) in cow and buffalo milk samples from two Indian states, Haryana and Assam. [...] Read more.

The consumption of milk contaminated with antibiotic-resistant bacteria poses a significant health threat to humans. This study aimed to investigate the prevalence of Enterobacteriaceae producing β-lactamases (ESBL, MBL, and AmpC) in cow and buffalo milk samples from two Indian states, Haryana and Assam. A total of 401 milk samples were collected from dairy farmers and vendors in the specified districts. Microbiological assays, antibiotic susceptibility testing, and PCR-based genotyping were employed to analyze 421 Gram-negative bacterial isolates. The overall prevalence of β-lactamase genes was 10% (confidence interval (CI) (7–13)), with higher rates in Haryana (13%, CI (9–19)) compared to Assam (7%, CI (4–11)). The identified β-lactamase genes in isolates were bla_CMY, bla_MOX, bla_FOX, bla_EBC, and bla_DHA, associated with AmpC production. Additionally, bla_CTX-M1, bla_SHV, and bla_TEM were detected as ESBL producers, while bla_VIM, bla_IMP, bla_SPM, bla_SIM, and bla_GIM were identified as MBL producers. Notably, Shigella spp. were the dominant β-lactamase producers among identified Enterobacteriaceae. This study highlights the presence of various prevalent β-lactamase genes in milk isolates, indicating the potential risk of antimicrobial-resistant bacteria in dairy products. The presence of β-lactam resistance raises concern as this could restrict antibiotic options for treatment. The discordance between genotypic and phenotypic methods emphasizes the necessity for comprehensive approaches that integrate both techniques to accurately assess antibiotic resistance. Urgent collaborative action incorporating rational and regulated use of antibiotics across the dairy value chain is required to address the global challenge of β-lactam resistance. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)

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11 pages, 600 KiB

Open AccessArticle

Bloodstream Infections in Intensive Care Unit during Four Consecutive SARS-CoV-2 Pandemic Waves

by Giacomo Pozza, Giacomo Casalini, Cosmin Lucian Ciubotariu, Andrea Giacomelli, Miriam Galimberti, Martina Zacheo, Andrea Rabbione, Margherita Pieruzzi, Letizia Oreni, Laura Galimberti, Riccardo Colombo, Giuliano Rizzardini, Cristina Pagani, Sara Giordana Rimoldi, Cecilia Bonazzetti, Anna Lisa Ridolfo and Spinello Antinori

Antibiotics 2023, 12(9), 1448; https://doi.org/10.3390/antibiotics12091448 - 14 Sep 2023

Cited by 2 | Viewed by 1304

Abstract

Critically ill COVID-19 patients are at an increased risk of bloodstream infections (BSIs). We performed a retrospective observational single-center study on COVID-19 patients admitted to intensive care unit (ICU) to assess the incidence of BSIs in four consecutive periods: 21 February–31 July 2020 [...] Read more.

Critically ill COVID-19 patients are at an increased risk of bloodstream infections (BSIs). We performed a retrospective observational single-center study on COVID-19 patients admitted to intensive care unit (ICU) to assess the incidence of BSIs in four consecutive periods: 21 February–31 July 2020 (W1), 1 August 2020–31 January 2021 (W2), 1 February–30 September 2021 (W3) and 1 October 2021 and 30 April 2022 (W4). BSIs that occurred 48 h after ICU admission were included. The crude incidence of BSIs was estimated by means of Poisson distribution normalized to 1000 patient-days. A total of 404 critically ill COVID-19 patients were admitted to ICU, of whom 284 (61%) developed at least one episode of BSI with an overall crude incidence of 87 events every 1000 patient-days (95% CI 77–98) without a significant difference in consecutive epidemic periods (p = 0.357). Gram-positive bacteria were the most frequent etiological agents of BSIs, contributing to 74.6% episodes. A progressive decrease in BSIs due to Enterococcus spp. was observed (W1 57.4%, W2 43.7%, W3 35.7% and W4 32.7%; p = 0.004). The incidence of BSIs remained stable during different epidemic periods. Enterococcus spp. prevalence was significantly reduced, although still accounted for one third of BSIs in more recent epidemic periods. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance)

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15 pages, 4476 KiB

Open AccessArticle

Pseudouridine Synthase RsuA Confers a Survival Advantage to Bacteria under Streptomycin Stress

by Sudeshi M. Abedeera, Kumudie S. Jayalath, Jiale Xie, Rushdhi M. Rauff and Sanjaya C. Abeysirigunawardena

Antibiotics 2023, 12(9), 1447; https://doi.org/10.3390/antibiotics12091447 - 14 Sep 2023

Cited by 1 | Viewed by 1370

Abstract

Bacterial ribosome small subunit rRNA (16S rRNA) contains 11 nucleotide modifications scattered throughout all its domains. The 16S rRNA pseudouridylation enzyme, RsuA, which modifies U516, is a survival protein essential for bacterial survival under stress conditions. A comparison of the growth curves of [...] Read more.

Bacterial ribosome small subunit rRNA (16S rRNA) contains 11 nucleotide modifications scattered throughout all its domains. The 16S rRNA pseudouridylation enzyme, RsuA, which modifies U516, is a survival protein essential for bacterial survival under stress conditions. A comparison of the growth curves of wildtype and RsuA knock-out E. coli strains illustrates that RsuA renders a survival advantage to bacteria under streptomycin stress. The RsuA-dependent growth advantage for bacteria was found to be dependent on its pseudouridylation activity. In addition, the role of RsuA as a trans-acting factor during ribosome biogenesis may also play a role in bacterial growth under streptomycin stress. Furthermore, circular dichroism spectroscopy measurements and RNase footprinting studies have demonstrated that pseudouridine at position 516 influences helix 18 structure, folding, and streptomycin binding. This study exemplifies the importance of bacterial rRNA modification enzymes during environmental stress. Full article

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

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13 pages, 1307 KiB

Open AccessReview

Detection, Identification and Diagnostic Characterization of the Staphylococcal Small Colony-Variant (SCV) Phenotype

by Karsten Becker

Antibiotics 2023, 12(9), 1446; https://doi.org/10.3390/antibiotics12091446 - 14 Sep 2023

Cited by 5 | Viewed by 3510

Abstract

While modern molecular methods have decisively accelerated and improved microbiological diagnostics, phenotypic variants still pose a challenge for their detection, identification and characterization. This particularly applies if they are unstable and hard to detect, which is the case for the small-colony-variant (SCV) phenotype [...] Read more.

While modern molecular methods have decisively accelerated and improved microbiological diagnostics, phenotypic variants still pose a challenge for their detection, identification and characterization. This particularly applies if they are unstable and hard to detect, which is the case for the small-colony-variant (SCV) phenotype formed by staphylococci. On solid agar media, staphylococcal SCVs are characterized by tiny colonies with deviant colony morphology. Their reduced growth rate and fundamental metabolic changes are the result of their adaptation to an intracellular lifestyle, regularly leading to specific auxotrophies, such as for menadione, hemin or thymidine. These alterations make SCVs difficult to recognize and render physiological, biochemical and other growth-based methods such as antimicrobial susceptibility testing unreliable or unusable. Therefore, diagnostic procedures require prolonged incubation times and, if possible, confirmation by molecular methods. A special approach is needed for auxotrophy testing. However, standardized protocols for SCV diagnostics are missing. If available, SCVs and their putative parental isolates should be genotyped to determine clonality. Since their detection has significant implications for the treatment of the infection, which is usually chronic and relapsing, SCV findings should be specifically reported, commented on, and managed in close collaboration with the microbiological laboratory and the involved clinicians. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Richard Proctor—Outstanding Contributions in the Fields of Persistent Staphylococcus aureus Infections)

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10 pages, 1659 KiB

Open AccessArticle

In Vitro Efficacy of Dalbavancin as a Long-Acting Anti-Biofilm Agent Loaded in Bone Cement

by Mar Sánchez-Somolinos, Marta Díaz-Navarro, Antonio Benjumea, José Matas, Javier Vaquero, Patricia Muñoz, Pablo Sanz-Ruíz and María Guembe

Antibiotics 2023, 12(9), 1445; https://doi.org/10.3390/antibiotics12091445 - 13 Sep 2023

Viewed by 1422

Abstract

Based on previous studies by our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin [...] Read more.

Based on previous studies by our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin over a 3-month period. We designed an in vitro model in which we calculated the percentage reduction in log cfu/mL counts of sonicated steel discs contaminated with staphylococci and further exposed to bone cement discs loaded with 2.5% or 5% vancomycin and dalbavancin at various timepoints (24 h, 48 h, 1 week, 2 weeks, 6 weeks, and 3 months). In addition, we tested the anti-biofilm activity of eluted vancomycin and dalbavancin at each timepoint based on a 96-well plate model in which we assessed the percentage reduction in metabolic activity. We observed a significant decrease in the dalbavancin concentration from 2 weeks of incubation, with sustained anti-biofilm activity up to 3 months. In the case of vancomycin, we observed a significant decrease at 1 week. The concentration gradually increased, leading to significantly lower anti-biofilm activity. The percentage reduction in cfu/mL counts was higher for dalbavancin than for vancomycin at both the 2.5% and the 5% concentrations. The reduction in log cfu/mL counts was higher for S. epidermidis than for S. aureus and was particularly more notable for 5% dalbavancin at 3 months. In addition, the percentage reduction in metabolic activity also decreased at 3 months in 5% dalbavancin and 5% vancomycin, with more notable values recorded for the latter. Full article

(This article belongs to the Special Issue Prevention and Antibiotic Treatment of Periprosthetic Joint Infection)

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Antibiotics, Volume 12, Issue 9 (September 2023) – 129 articles

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