Journal Description
Antibiotics
Antibiotics
is an international, peer-reviewed, open access journal on all aspects of antibiotics, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q1 (General Pharmacology, Toxicology and Pharmaceutics )
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.7 days after submission; acceptance to publication is undertaken in 2.5 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.8 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Accordance of Registered Drug Packages with Guideline-Recommended Treatment Durations for Community-Acquired Pneumonia—A New Antibiotic Stewardship Target?
Antibiotics 2024, 13(6), 546; https://doi.org/10.3390/antibiotics13060546 (registering DOI) - 12 Jun 2024
Abstract
In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers’ choice of treatment duration. The aim of this study was to investigate the
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In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers’ choice of treatment duration. The aim of this study was to investigate the accordance of approved antibiotic packages with national guidelines for the treatment of community-acquired pneumonia (CAP). For the purpose of this study, criteria were developed to determine the accordance of approved antibiotic packages for treating CAP (criteria), which are based on recommendations from national guidelines for treating CAP. Subsequently, the accordance of approved antibiotic packages with the number of antibiotic doses resulting from the specified criteria was determined. Of 39 identified therapeutic option-package size combinations, 11 were found to be matched (28.2%), meaning there were no leftover medication units after completing therapy, and 28 were mismatched combinations (71.8%), indicating that there were excess doses of antibiotics remaining at the end of therapy. The results of this research showed a significant non-accordance of the approved antibiotic packages with the national guidelines for the treatment of CAP and, consequently, the creation of a large amount of residues of unit doses of antibiotics in the community.
Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Antimicrobial Use in Healthcare Settings)
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Open AccessSystematic Review
The Evolving Challenge of Appropriate Antibiotics Use in Hospitalized COVID-19 Patients: A Systematic Literature Review
by
Guido Granata and Stefania Cicalini
Antibiotics 2024, 13(6), 545; https://doi.org/10.3390/antibiotics13060545 (registering DOI) - 12 Jun 2024
Abstract
The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31
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The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 March 2024 to assess the current burden of bacterial infection and the evidence for antibiotic use in hospitalized COVID-19 patients. Published articles providing data on antibiotic use in COVID-19 patients were identified through computerized literature searches with the search terms [(antibiotic) AND (COVID-19)] or [(antibiotic treatment) AND (COVID-19)]. PubMed and SCOPUS databases were searched from 1 January 2022 to 31 March 2024. No attempt was made to obtain information about unpublished studies. English language restriction was applied. The quality of the included studies was evaluated by the tool recommended by the Joanna Briggs Institute. Both quantitative and qualitative information were summarized by means of textual descriptions. Five hundred fifty-one studies were identified, and twenty-nine studies were included in this systematic review. Of the 29 included studies, 18 studies were on the prevalence of bacterial infection and antibiotic use in hospitalized COVID-19 patients; 4 studies reported on the efficacy of early antibiotic use in COVID-19; 4 studies were on the use of sepsis biomarkers to improve antibiotic use; 3 studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19-hospitalized patients. The quality of included studies was high in 35% and medium in 62%. High rates of hospital-acquired infections were reported among COVID-19 patients, ranging between 7.5 and 37.7%. A high antibiotic resistance rate was reported among COVID-19 patients developing hospital-acquired infections, with a high in-hospital mortality rate. The studies evaluating multi-faceted antimicrobial stewardship interventions reported efficacy in decreasing antibiotic consumption and lower in-hospital mortality.
Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Anti-Infective Activity of Momordica charantia Extract with Molecular Docking of Its Triterpenoid Glycosides
by
Mohammed Aldholmi, Rizwan Ahmad, Mohammad Habeeb Shaikh, Ayad Mohammed Salem, Maher Alqurashi and Mansour Alturki
Antibiotics 2024, 13(6), 544; https://doi.org/10.3390/antibiotics13060544 - 11 Jun 2024
Abstract
Momordica charantia, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial, antifungal, and antiviral activity of different bitter melon fruit parts originating from India and
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Momordica charantia, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial, antifungal, and antiviral activity of different bitter melon fruit parts originating from India and Saudi Arabia. The in vitro experiments are supported by the molecular docking of karavilosides to verify their role in the bioactivity. The antimicrobial assays revealed activity against Candida albicans, Escherichia coli, and Staphylococcus aureus. The extracts exhibited the potent inhibition of HIV-I reverse transcriptase, with an IC50 of 0.125 mg/mL observed for the pith extract originating from Saudi Arabia and the standard drug doxorubicin. The molecular docking of karavilosides exhibited a significant affinity to reverse transcriptase comparable to Rilpivirine and higher than that of doxorubicin. These outcomes encourage the precious bioactive components of the seed and pith of the Saudi bitter melon fruits to be further studied for isolation and structure elucidation.
Full article
(This article belongs to the Special Issue Plants, Lichens, Fungi, and Algae Extracts and Derivatives with Antimicrobial Properties for Nutrition and Health)
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Open AccessArticle
Whole-Genome Sequencing of Human and Porcine Escherichia coli Isolates on a Commercial Pig Farm in South Africa
by
Wilhelmina Strasheim, Michelle Lowe, Anthony M. Smith, Eric M. C. Etter and Olga Perovic
Antibiotics 2024, 13(6), 543; https://doi.org/10.3390/antibiotics13060543 - 11 Jun 2024
Abstract
Escherichia coli is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole-genome
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Escherichia coli is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole-genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harbored a richer diversity of antibiotic resistance genes as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%, 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169), were detected at low frequencies. Sequence type complex (STc) 10 was the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human–livestock interface according to multilocus sequence typing (MLST). Core-genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2–HC200 was observed. In conclusion, even though the isolates shared a spatiotemporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles and cgMLST and HC according to the source of isolation.
Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Animals and Animal Products and Its Environmental Transmission Aspects)
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Open AccessArticle
Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching
by
Jae Myung Cha, Jin Young Yoon, Min Seob Kwak, Moonhyung Lee and Young-Seok Cho
Antibiotics 2024, 13(6), 542; https://doi.org/10.3390/antibiotics13060542 - 10 Jun 2024
Abstract
Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of
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Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.
Full article
(This article belongs to the Special Issue Clostridioides difficile Infection, 3rd Edition)
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Open AccessReview
Current and Future Perspectives on the Management of Helicobacter pylori: A Narrative Review
by
Charlene Deane, Orlaith Kelly and Colm O’Morain
Antibiotics 2024, 13(6), 541; https://doi.org/10.3390/antibiotics13060541 - 10 Jun 2024
Abstract
The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination.
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The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination. This review article provides an overview of the shift in the management of H. pylori from a reactive approach towards a proactive ‘screen and treat’ approach; the article reflects the current pharmacological landscape for H. pylori treatment by exploring similarities such as the first-line prescription of quadruple therapy in most countries and provides a summary table of the best practice guidance from Europe, Asia, and North America. It explores significant ongoing challenges in management, such as rising antimicrobial resistance rates, and explores a potential ‘work smart’ approach to antimicrobial susceptibility testing. We explore the role of registry databases in providing data on treatment efficacy and safety and how they can support a strategic approach to H. pylori treatment. We question if such a database’s availability, update, and regular audit should serve as a key quality indicator in a population screening programme. Despite a call for vaccination against H. pylori and decades of research, not many have made it to a phase-three clinical trial. We explore the challenges that have complicated the development of such a vaccine, such as the genetic diversity of H. pylori, immunotolerance, and limitations of mouse models in research; we reflect on how these challenges are contributing to a low likelihood of having a vaccine in the short–medium term. Lastly, it explores the heterogeneity in research on probiotics and their role as an adjunct in the management of H. pylori.
Full article
(This article belongs to the Special Issue Helicobacter pylori Infection - New Data and Approaches on Diagnosis, Pathogenesis, Antibiotic Resistance and Advances in Therapy)
Open AccessArticle
Enhanced Anti-Bacterial Activity of Arachidonic Acid against the Cariogenic Bacterium Streptococcus mutans in Combination with Triclosan and Fluoride
by
Avraham Melkam, Ronit Vogt Sionov, Miriam Shalish and Doron Steinberg
Antibiotics 2024, 13(6), 540; https://doi.org/10.3390/antibiotics13060540 - 10 Jun 2024
Abstract
Dental caries is a global health problem that requires better prevention measures. One of the goals is to reduce the prevalence of the cariogenic Gram-positive bacterium Streptococcus mutans. We have recently shown that naturally occurring arachidonic acid (AA) has both anti-bacterial and
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Dental caries is a global health problem that requires better prevention measures. One of the goals is to reduce the prevalence of the cariogenic Gram-positive bacterium Streptococcus mutans. We have recently shown that naturally occurring arachidonic acid (AA) has both anti-bacterial and anti-biofilm activities against this bacterium. An important question is how these activities are affected by other anti-bacterial compounds commonly used in mouthwashes. Here, we studied the combined treatment of AA with chlorhexidine (CHX), cetylpyridinium chloride (CPC), triclosan, and fluoride. Checkerboard microtiter assays were performed to determine the effects on bacterial growth and viability. Biofilms were quantified using the MTT metabolic assay, crystal violet (CV) staining, and live/dead staining with SYTO 9/propidium iodide (PI) visualized by spinning disk confocal microscopy (SDCM). The bacterial morphology and the topography of the biofilms were visualized by high-resolution scanning electron microscopy (HR-SEM). The effect of selected drug combinations on cell viability and membrane potential was investigated by flow cytometry using SYTO 9/PI staining and the potentiometric dye DiOC2(3), respectively. We found that CHX and CPC had an antagonistic effect on AA at certain concentrations, while an additive effect was observed with triclosan and fluoride. This prompted us to investigate the triple treatment of AA, triclosan, and fluoride, which was more effective than either compound alone or the double treatment. We observed an increase in the percentage of PI-positive bacteria, indicating increased bacterial cell death. Only AA caused significant membrane hyperpolarization, which was not significantly enhanced by either triclosan or fluoride. In conclusion, our data suggest that AA can be used together with triclosan and fluoride to improve the efficacy of oral health care.
Full article
Open AccessArticle
Environmentally Relevant Antibiotic Concentrations Exert Stronger Selection Pressure on River Biofilm Resistomes than AMR-Reservoir Effluents
by
Gabriela Flores-Vargas, Jordyn Bergsveinson and Darren R. Korber
Antibiotics 2024, 13(6), 539; https://doi.org/10.3390/antibiotics13060539 - 10 Jun 2024
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Freshwater environments are primary receiving systems of wastewater and effluents, which carry low concentrations of antibiotics and antimicrobial-resistant (AMR) bacteria and genes. Aquatic microbial communities are thus exposed to environmentally relevant concentrations of antibiotics (ERCA) that presumably influence the acquisition and spread of
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Freshwater environments are primary receiving systems of wastewater and effluents, which carry low concentrations of antibiotics and antimicrobial-resistant (AMR) bacteria and genes. Aquatic microbial communities are thus exposed to environmentally relevant concentrations of antibiotics (ERCA) that presumably influence the acquisition and spread of environmental AMR. Here, we analyzed ERCA exposure with and without the additional presence of municipal wastewater treatment plant effluent (W) and swine manure run-off (M) on aquatic biofilm resistomes. Microscopic analyses revealed decreased taxonomic diversity and biofilm structural integrity, while metagenomic analysis revealed an increased abundance of resistance, virulence, and mobile element-related genes at the highest ERCA exposure levels, with less notable impacts observed when solely exposed to W or M effluents. Microbial function predictions indicated increased gene abundance associated with energy and cell membrane metabolism and heavy metal resistance under ERCA conditions. In silico predictions of increased resistance mechanisms did not correlate with observed phenotypic resistance patterns when whole communities were exposed to antimicrobial susceptibility testing. This reveals important insight into the complexity of whole-community coordination of physical and genetic responses to selective pressures. Lastly, the environmental AMR risk assessment of metagenomic data revealed a higher risk score for biofilms grown at sub-MIC antibiotic conditions.
Full article
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Open AccessArticle
Do High Doses of Multiple Antibiotics Loaded into Bone Cement Spacers Improve the Success Rate in Staphylococcal Periprosthetic Joint Infection When Rifampicin Cannot Be Employed?
by
Lourdes Prats-Peinado, Tanya Fernández-Fernández, Miguel Márquez-Gómez, José Antonio Matas-Diaz, Mar Sánchez-Somolinos, Sofía de la Villa-Martínez, Javier Vaquero-Martín and Pablo Sanz-Ruiz
Antibiotics 2024, 13(6), 538; https://doi.org/10.3390/antibiotics13060538 - 10 Jun 2024
Abstract
Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims
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Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10–147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.
Full article
(This article belongs to the Special Issue Local Antibiotics: Antibiotic Loaded Bone Cement and Drug Containing Medical Devices in Orthopaedic Surgery)
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Open AccessArticle
Incidence of Antibiotic Exposure for Suspected and Proven Neonatal Early-Onset Sepsis between 2019 and 2021: A Retrospective, Multicentre Study
by
Liesanne E. J. van Veen, Bo M. van der Weijden, Niek B. Achten, Lotte van der Lee, Jeroen Hol, Maaike C. van Rossem, Maarten Rijpert, Anna O. J. Oorthuys, Ron H. T. van Beek, Gerdien H. Dubbink-Verheij, René F. Kornelisse, Laura H. van der Meer-Kapelle, Karen Van Mechelen, Suzanne Broekhuizen, A. Carin M. Dassel, J. W. F. M. Corrie Jacobs, Paul W. T. van Rijssel, Gerdien A. Tramper-Stranders, Annemarie M. C. van Rossum and Frans B. Plötz
Antibiotics 2024, 13(6), 537; https://doi.org/10.3390/antibiotics13060537 - 10 Jun 2024
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Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for
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Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5–4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2–2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09–0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS.
Full article
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Open AccessArticle
Antibacterial Activities of Phenolic Compounds in Miang Extract: Growth Inhibition and Change in Protein Expression of Extensively Drug-Resistant Klebsiella pneumoniae
by
Pannita Anek, Sutita Kumpangcum, Sittiruk Roytrakul, Chartchai Khanongnuch, Chalermpong Saenjum and Kulwadee Phannachet
Antibiotics 2024, 13(6), 536; https://doi.org/10.3390/antibiotics13060536 - 9 Jun 2024
Abstract
The rising incidence of extensively drug-resistant (XDR) Klebsiella pneumoniae, including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. Miang, known as chewing tea, is produced from Camellia sinensis var. assamica or Assam tea leaves fermentation. Previous studies
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The rising incidence of extensively drug-resistant (XDR) Klebsiella pneumoniae, including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. Miang, known as chewing tea, is produced from Camellia sinensis var. assamica or Assam tea leaves fermentation. Previous studies revealed that the extract of Miang contains various phenolic and flavonoid compounds with numerous biological activities including antibacterial activity. However, the antibacterial activity of Miang against XDR bacteria especially colistin-resistant strains had not been investigated. In this study, the compositions of phenolic and flavonoid compounds in fresh, steamed, and fermented Assam tea leaves were examined by HPLC, and their antibacterial activities were evaluated by the determination of the MIC and MBC. Pyrogallol was detected only in the extract from Miang and showed the highest activities with an MIC of 0.25 mg/mL and an MBC of 0.25–0.5 mg/mL against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli ATCC 25922, colistin-resistant E. coli, and colistin-resistant K. pneumoniae. The effects on morphology and proteomic changes in K. pneumoniae NH54 treated with Miang extract were characterized by SEM and label-free quantitative shotgun proteomics analysis. The results revealed that Miang extract caused the decrease in bacterial cell wall integrity and cell lysis. The up- and downregulated expression with approximately a 2 to >5-fold change in proteins involved in peptidoglycan synthesis and outer membrane, carbohydrate, and amino acid metabolism were identified. These findings suggested that Miang containing pyrogallol and other secondary metabolites from fermentation has potential as an alternative candidate with an antibacterial agent or natural active pharmaceutical ingredient against XDR bacteria including colistin-resistant bacteria.
Full article
(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)
Open AccessArticle
Comparative Genomics of an Emerging Multidrug-Resistant blaNDM-Carrying ST182 Lineage in Enterobacter cloacae Complex
by
Angeliki Mavroidi, Elisavet Froukala and Athanasios Tsakris
Antibiotics 2024, 13(6), 535; https://doi.org/10.3390/antibiotics13060535 - 8 Jun 2024
Abstract
Background: Enterobacter cloacae, E. hormaechei and related subspecies remain the most clinically relevant among the Enterobacter cloacae complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93,
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Background: Enterobacter cloacae, E. hormaechei and related subspecies remain the most clinically relevant among the Enterobacter cloacae complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93, ST90 and ST78. Instead, ST182 has been sporadically reported among E. hormaechei strains, and recently, outbreaks of blaNDM-producing ST182 clonal strains have emerged. Herein, we aimed to investigate the presence of ST182 and explore its evolution and modes of blaNDM acquisition. Methods: A phylogenetic analysis of 646 MLST STs identified among 4685 E. hormaechei whole-genome sequencing (WGS) assemblies deposited in public repositories was performed, as well as an in silico comparative and phylogenomic analyses for 55 WGS assemblies of ST182. blaNDM-harboring contigs were also compared to published plasmid sequences. Results: ST182 E. hormaechei strains were recovered from patients on five continents during 2011–2021. They were divided into three major genomic clusters, comprising a separate clonal complex with six other STs. In 30 out of 55 ST182 WGS assemblies, blaNDM-harboring structures were identified that were similar to the plasmids predominant in Gram-negative bacteria, harboring resistance genes to multiple antibiotic classes and virulence genes. No associations between the genomic clusters and the country/continent of isolation or the presence and the plasmid types of the blaNDM-harboring contigs were observed. Conclusions: Our findings show that ST182 E. hormaechei strains have been identified in the past decade worldwide; 54.5% of them carried diverse blaNDM genetic structures, suggesting recent acquisition of the blaNDM alleles. Thus, blaNDM-harboring ST182 is an emerging multidrug-resistant and virulent lineage in ECC strains that requires close monitoring.
Full article
(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)
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Open AccessArticle
Mobile Colistin-Resistant Genes mcr-1, mcr-2, and mcr-3 Identified in Diarrheal Pathogens among Infants, Children, and Adults in Bangladesh: Implications for the Future
by
Shafiuzzaman Sarker, Reeashat Muhit Neeloy, Marnusa Binte Habib, Umme Laila Urmi, Mamun Al Asad, Abu Syed Md. Mosaddek, Mohammad Rabiul Karim Khan, Shamsun Nahar, Brian Godman and Salequl Islam
Antibiotics 2024, 13(6), 534; https://doi.org/10.3390/antibiotics13060534 - 7 Jun 2024
Abstract
Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phenotypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern.
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Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phenotypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reactions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilution and E-test by minimal inhibitory concentration (MIC) measurements. Over 31.6% (71/225) of isolates showed colistin resistance according to agar dilution assessment (MIC > 2 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, and mcr-3, with co-occurrence occurring in two isolates). Clinical breakout MIC values (≥4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens included twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudomonas parafulva. The mcr-genes appeared to be significantly associated with phenotypic colistin resistance phenomena (p = 0.000), with 100% colistin-resistant isolates showing MDR phenomena. The age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacteria have emerged in Bangladesh, which warrants further research to determine their spread and instigate activities to reduce resistance.
Full article
(This article belongs to the Special Issue Antimicrobial Strategies to Limit Infection and Inflammation of Mucosal Surfaces)
Open AccessArticle
Companion Animal Owners’ Knowledge, Attitudes and Perceptions Regarding Antibiotic Use in Portugal
by
Margarida Correia Dias, Russell Alpizar-Jara, Catarina Lavrador, Cátia Marques, Els M. Broens and Elsa L. Duarte
Antibiotics 2024, 13(6), 533; https://doi.org/10.3390/antibiotics13060533 - 7 Jun 2024
Abstract
While multiple studies have focused on the motivations surrounding antibiotic prescription among veterinarians, little is known about companion animal owners’ knowledge, attitude and perception (KAP) regarding the topic. A nationwide survey directed toward Portuguese dog and cat owners was conducted online and at
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While multiple studies have focused on the motivations surrounding antibiotic prescription among veterinarians, little is known about companion animal owners’ knowledge, attitude and perception (KAP) regarding the topic. A nationwide survey directed toward Portuguese dog and cat owners was conducted online and at veterinary practices to characterize their KAP regarding antibiotics. After database curation, a total of 423 valid submissions were considered. Although 97.9% of respondents stated that they knew what an antibiotic was, 23.5% and 19.2% answered that they were used to treat viral and fungal infections, respectively. Antimicrobial effectiveness was favored over cost when 87.7% of owners agreed they would prefer to spend more money to identify the appropriate antibiotic. Around 87% of respondents recognized antibiotic resistance as a significant health problem and 74.6% strongly agreed/somewhat agreed that antibiotic use in pets may contribute to resistance development. However, only 25.3% recognized that this could promote resistance dissemination, showing little awareness of the interconnection between human and animal health. Moreover, 55.6% of respondents were neutral when asked whether antibiotics used in veterinary medicine were also important for humans. These findings suggest that communication between veterinarians and pet owners can still be improved to further clarify the impact that antibiotic use has in pets from a One-Health perspective, also enabling antimicrobial stewardship interventions.
Full article
(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Companion Animals II)
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Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review
by
Marko Nemet and Marija Vukoja
Antibiotics 2024, 13(6), 532; https://doi.org/10.3390/antibiotics13060532 - 6 Jun 2024
Abstract
Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden
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Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden of comorbidities. In this narrative review, we evaluated the current evidence on the association between OSA and the incidence and outcomes of acute LRTIs in adults, specifically community-acquired pneumonia and viral pneumonia caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have demonstrated that OSA patients are more likely to develop bacterial pneumonia and exhibit a higher risk of invasive pneumococcal disease. The risk intensifies with the severity of OSA, influencing hospitalization rates and the need for intensive care. OSA is also associated with an increased risk of contracting influenza and suffering more severe disease, potentially necessitating hospitalization. Similarly, OSA contributes to increased COVID-19 disease severity, reflected by higher rates of hospitalization, longer hospital stays, and a higher incidence of acute respiratory failure. The effect of OSA on mortality rates from these infections is, however, somewhat ambiguous. Finally, we explored antibiotic therapy for OSA patients with LRTIs, addressing care settings, empirical regimens, risks, and pharmacokinetic considerations. Given the substantial burden of OSA and its significant interplay with acute LRTIs, enhanced screening, targeted vaccinations, and optimized management strategies for OSA patients should be prioritized.
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(This article belongs to the Special Issue Pulmonary Infections: Pathogenesis and Antimicrobial Treatment)
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Open AccessArticle
Genomic Characterization of Multidrug-Resistant Enterobacteriaceae Clinical Isolates from Southern Thailand Hospitals: Unraveling Antimicrobial Resistance and Virulence Mechanisms
by
Thunchanok Yaikhan, Sirikan Suwannasin, Kamonnut Singkhamanan, Sarunyou Chusri, Rattanaruji Pomwised, Monwadee Wonglapsuwan and Komwit Surachat
Antibiotics 2024, 13(6), 531; https://doi.org/10.3390/antibiotics13060531 - 6 Jun 2024
Abstract
The emergence and spread of antimicrobial resistance (AMR) among Enterobacteriaceae pose significant threats to global public health. In this study, we conducted a short-term surveillance effort in Southern Thailand hospitals to characterize the genomic diversity, AMR profiles, and virulence factors of Enterobacteriaceae strains.
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The emergence and spread of antimicrobial resistance (AMR) among Enterobacteriaceae pose significant threats to global public health. In this study, we conducted a short-term surveillance effort in Southern Thailand hospitals to characterize the genomic diversity, AMR profiles, and virulence factors of Enterobacteriaceae strains. We identified 241 carbapenem-resistant Enterobacteriaceae, of which 12 were selected for whole-genome sequencing (WGS) and genome analysis. The strains included Proteus mirabilis, Serratia nevei, Klebsiella variicola, Klebsiella aerogenes, Klebsiella indica, Klebsiella grimontii, Phytobacter ursingii, Phytobacter palmae, Kosakonia spp., and Citrobacter freundii. The strains exhibited high levels of multidrug resistance, including resistance to carbapenem antibiotics. Whole-genome sequencing revealed a diverse array of antimicrobial resistance genes (ARGs), with strains carrying genes for ß-lactamase, efflux pumps, and resistance to other antibiotic classes. Additionally, stress response, metal tolerance, and virulence-associated genes were identified, highlighting the adaptability and pathogenic potential of these strains. A plasmid analysis identified several plasmid replicons, including IncA/C2, IncFIB(K), and Col440I, as well as several plasmids identical to those found globally, indicating the potential for the horizontal gene transfer of ARGs. Importantly, this study also identified a novel species of Kosakonia spp. PSU27, adding to the understanding of the genetic diversity and resistance mechanisms of Enterobacteriaceae in Southern Thailand. The results reported in this study highlight the critical importance of implementing effective antimicrobial management programs and developing innovative treatment approaches to urgently tackle AMR.
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(This article belongs to the Special Issue Genomic Characterization of Antimicrobial Resistance and Evolution Mechanism of Bacteria)
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Open AccessArticle
Comparison of the Impact of VRP-034 and Polymyxin B upon Markers of Kidney Injury in Human Proximal Tubule Monolayers In Vitro
by
Keith Pye, Elena Tasinato, Siannah Shuttleworth, Claire Devlin and Colin Brown
Antibiotics 2024, 13(6), 530; https://doi.org/10.3390/antibiotics13060530 - 6 Jun 2024
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In this study, we assessed the impact of commercially available polymyxin B against VRP-034 (novel formulation of polymyxin B) using a validated in vitro human renal model, aProximateTM. Freshly isolated primary proximal tubule cells (PTCs) were cultured in Transwell plates and
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In this study, we assessed the impact of commercially available polymyxin B against VRP-034 (novel formulation of polymyxin B) using a validated in vitro human renal model, aProximateTM. Freshly isolated primary proximal tubule cells (PTCs) were cultured in Transwell plates and treated with various concentrations of the formulations for up to 48 h. The functional expression of megalin–cubilin receptors in PTC monolayers was validated using FITC-conjugated albumin uptake assays. Polymyxin B and VRP-034 were evaluated at six concentrations (0.3, 1, 3, 10, 30, and 60 µM), and nephrotoxicity was assessed through measurements of transepithelial electrical resistance (TEER), intracellular adenosine triphosphate (ATP) levels, lactate dehydrogenase (LDH) release, and novel injury biomarkers [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and clusterin]. Additionally, histological analysis using annexin V apoptosis staining was performed. Our results indicated a significant decrease in TEER with polymyxin B at concentrations ≥10 μM compared to VRP-034. Toxic effects were observed from ATP and LDH release only at concentrations ≥30 μM for both formulations. Furthermore, injury biomarker release was higher with polymyxin B compared to VRP-034, particularly at concentrations ≥10 µM. Histologically, polymyxin B-treated PTCs showed increased apoptosis compared to VRP-034-treated cells. Overall, VRP-034 demonstrated improved tolerance in the aProximateTM model compared to polymyxin B, suggesting its potential as a safer alternative for renal protection.
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Open AccessArticle
Antimicrobial and Antibiofilm Effects of Bithionol against Mycobacterium abscessus
by
Dan Cao, Xin Yuan, Xiuzhi Jiang, Tiantian Wu, Yanghui Xiang, Zhongkang Ji, Jiaying Liu, Xu Dong, Kefan Bi, Tone Tønjum, Kaijin Xu and Ying Zhang
Antibiotics 2024, 13(6), 529; https://doi.org/10.3390/antibiotics13060529 - 5 Jun 2024
Abstract
Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug
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Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 μM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 μM to 2.5 μM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time–kill curve study and also electron microscopy study. Interestingly, it was found that at 128 μg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 μg/mL, 99% at 32 μg/mL, and 90% at 16 μg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities.
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(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)
Open AccessArticle
Deciphering the Antibacterial Mechanisms of 5-Fluorouracil in Escherichia coli through Biochemical and Transcriptomic Analyses
by
Muchen Zhang, Huangwei Song, Siyuan Yang, Yan Zhang, Yunrui Tian, Yang Wang and Dejun Liu
Antibiotics 2024, 13(6), 528; https://doi.org/10.3390/antibiotics13060528 - 5 Jun 2024
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The emergence of carbapenem-resistant Gram-negative pathogens presents a clinical challenge in infection treatment, prompting the repurposing of existing drugs as an essential strategy to address this crisis. Although the anticancer drug 5-fluorouracil (5-FU) has been recognized for its antibacterial properties, its mechanisms are
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The emergence of carbapenem-resistant Gram-negative pathogens presents a clinical challenge in infection treatment, prompting the repurposing of existing drugs as an essential strategy to address this crisis. Although the anticancer drug 5-fluorouracil (5-FU) has been recognized for its antibacterial properties, its mechanisms are not fully understood. Here, we found that the minimal inhibitory concentration (MIC) of 5-FU against Escherichia coli was 32–64 µg/mL, including strains carrying blaNDM-5, which confers resistance to carbapenems. We further elucidated the antibacterial mechanism of 5-FU against E. coli by using genetic and biochemical analyses. We revealed that the mutation of uracil phosphoribosyltransferase-encoding gene upp increased the MIC of 5-FU against E. coli by 32-fold, indicating the role of the upp gene in 5-FU resistance. Additionally, transcriptomic analysis of E. coli treated with 5-FU at 8 µg/mL and 32 µg/mL identified 602 and 1082 differentially expressed genes involved in carbon and nucleic acid metabolism, DNA replication, and repair pathways. The biochemical assays showed that 5-FU induced bacterial DNA damage, significantly increased intracellular ATP levels and the NAD+/NADH ratio, and promoted reactive oxygen species (ROS) production. These findings suggested that 5-FU may exert antibacterial effects on E. coli through multiple pathways, laying the groundwork for its further development as a therapeutic candidate against carbapenem-resistant bacterial infections.
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Open AccessArticle
Emergence of Plasmid-Mediated Quinolone Resistance (PMQR) Genes in Campylobacter coli in Tunisia and Detection of New Sequence Type ST13450
by
Manel Gharbi, Rihab Tiss, Melek Chaouch, Safa Hamrouni and Abderrazak Maaroufi
Antibiotics 2024, 13(6), 527; https://doi.org/10.3390/antibiotics13060527 - 5 Jun 2024
Abstract
The aim of this study is to investigate the occurrence of plasmid mediated quinolone resistance (PMQR) determinants in Campylobacter coli isolates collected from broilers, laying hens and poultry farm environments. One hundred and thirty-nine C. coli isolates were isolated from broilers (n = 41), laying
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The aim of this study is to investigate the occurrence of plasmid mediated quinolone resistance (PMQR) determinants in Campylobacter coli isolates collected from broilers, laying hens and poultry farm environments. One hundred and thirty-nine C. coli isolates were isolated from broilers (n = 41), laying hens (n = 53), eggs (n = 4) and the environment (n = 41) of 23 poultry farms located in northeastern of Tunisia. Antimicrobial susceptibility testing was performed on all isolates according to the recommendation of the European Committee on Antimicrobial Susceptibility Testing guidelines. The detection of PMQR genes: qnrA, qnrB, qnrC, qnrD, qnrS, qepA, and aac(6)-Ib gene was performed using polymerase chain reaction (PCR) and specific primers. aac(6′)-Ib amplicons were further analyzed by digestion with BtsCI to identify the aac(6′)-Ib-cr variant. Mutations in GyrA and the occurrence of RE-CmeABC efflux pump were determined by mismatch amplification mutation assay (MAMA) PCR and PCR, respectively. In addition, eleven isolates were selected to determine their clonal lineage by MLST. The 139 C. coli isolates were resistant to ciprofloxacin, and 86 (61.8%) were resistant to nalidixic acid. High rates of resistance were also observed toward erythromycin (100%), azithromycin (96.4%), tetracycline (100%), chloramphenicol (98.56%), ampicillin (66.1%), amoxicillin-clavulanic acid (55.39%), and kanamycin (57.55%). However, moderate resistance rates were observed for gentamicin (9.35%) and streptomycin (22.3%). All quinolone-resistant isolates harbored the Thr-86-Ile amino acid substitution in GyrA, and the RE-CmeABC efflux pump was detected in 40.28% of isolates. Interestingly, the qnrB, qnrS, qepA, and aac(6′)-Ib-cr were detected in 57.7%, 61.15%, 21.58%, and 10% of isolates, respectively. The eleven isolates studied by MLST belonged to a new sequence type ST13450. This study described for the first time the occurrence of PMQR genes in C. coli isolates in Tunisia and globally.
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(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)
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