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Antibiotics, Volume 12, Issue 4 (April 2023) – 164 articles

Cover Story (view full-size image): Acinetobacter baumannii is a Gram-negative organism listed as an urgent threat pathogen by the World Health Organization (WHO). Co-expression of multiple classes of β-lactamases, enzymes able to hydrolyse β-lactams, is present in Carbapenem-resistant A. baumannii. Herein, we describe the activity of CR167, a previously identified β-lactamase inhibitor, against β-lactamases in A. baumannii, ADC-33 and OXA-24/40. These investigations demonstrate CR167 as a valuable cross-class (C and D) inhibitor and describe our attempts to further improve its activity. Five chiral analogues of CR167 were rationally designed, synthesized, and tested in enzymatic and microbiological assays. The structure activity relationships (SAR) are highlighted, offering insights into the main determinants for cross-class C/D inhibitors and impetus for novel drug design. View this paper
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Article
The National Implementation of a Community Pharmacy Antimicrobial Stewardship Intervention (PAMSI) through the English Pharmacy Quality Scheme 2020 to 2022
Antibiotics 2023, 12(4), 793; https://doi.org/10.3390/antibiotics12040793 - 21 Apr 2023
Cited by 1 | Viewed by 1084
Abstract
Since 2020, England’s Pharmacy Quality Scheme (PQS) has incentivised increased antimicrobial stewardship (AMS) activities in community pharmacy. In 2020/21, this included the requirement for staff to complete an AMS e-Learning module, pledge to be an Antibiotic Guardian and develop an AMS Action plan. [...] Read more.
Since 2020, England’s Pharmacy Quality Scheme (PQS) has incentivised increased antimicrobial stewardship (AMS) activities in community pharmacy. In 2020/21, this included the requirement for staff to complete an AMS e-Learning module, pledge to be an Antibiotic Guardian and develop an AMS Action plan. To build and embed these initiatives, in 2021/22, the PQS required the use of the TARGET Antibiotic Checklist (an AMS tool for use when patients present with a prescription for antibiotics to support conducting and recording of a series of safety and appropriateness checks against each prescribed antibiotic). This paper describes the implementation of the national PQS criteria from 2020 to 2022, and details community pharmacies’ AMS activities and barriers to implementation of the 2021/22 criteria. A total of 8374 community pharmacies submitted data collected using the TARGET Antibiotic Checklist for 213,105 prescriptions; 44% surpassed the required number for the PQS. Pharmacy teams reported checking the following: duration, dose, and appropriateness of antibiotics; patient allergies and medicine interactions (94–95%); antibiotic prescribing guideline adherence (89%); and the patient’s previous use of antibiotics (81%). The prescriber was contacted for 1.3% of TARGET Antibiotic Checklists (2741), and the most common reasons for such contacts were related to dose, duration, and possible patient allergy. A total of 105 pharmacy staff responded to a follow-up questionnaire, which suggested that some AMS principles had been embedded into daily practice; however, the necessary time commitment was a barrier. The PQS was able to incentivise mass AMS activities at pace over consecutive years for England’s community pharmacies simultaneously. Future research should monitor the continuation of activities and the wider impacts on primary care. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: Primary Care Perspectives and Practices)
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Article
Equine Gram-Negative Oral Microbiota: An Antimicrobial Resistances Watcher?
Antibiotics 2023, 12(4), 792; https://doi.org/10.3390/antibiotics12040792 - 21 Apr 2023
Viewed by 704
Abstract
Horses are considered as reservoirs of multidrug resistant bacteria that can be spread through the environment and possibly to humans. The aim of this study was to characterize the oral Gram-negative microbiota of healthy horses and evaluate their antimicrobial susceptibility profile in a [...] Read more.
Horses are considered as reservoirs of multidrug resistant bacteria that can be spread through the environment and possibly to humans. The aim of this study was to characterize the oral Gram-negative microbiota of healthy horses and evaluate their antimicrobial susceptibility profile in a One Health approach. For this purpose, samples were collected from the gingival margin of healthy horses, free of antimicrobial therapy, cultured in selective mediums, identified, and tested for antimicrobial susceptibility. Fifty-five Gram-negative isolates were identified, with 89.5% being zoonotic and 62% affecting humans, which were also found commonly in the environment. Forty-eight isolates (96%) were MDR. The phenotypic resistance presented as higher to macrolides (81.8%), β-lactams (55.4%), and quinolones (50%), and lower to sulfonamides (27.3%), tetracyclines, and amphenicols (both with 30.9%). In total, 51.5% of the isolates presented resistance to carbapenems. In addition to being the first report on the commensal oral microbiota of horses and respective susceptibility profile, this study highlights the horse as a valuable sentinel that can control the evolution and transmission of multidrug-resistant bacteria between the “One Health triad” since it is in contact with humans, other animals, and the environment, in different geographic locations. Full article
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Article
Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study
Antibiotics 2023, 12(4), 791; https://doi.org/10.3390/antibiotics12040791 - 21 Apr 2023
Viewed by 502
Abstract
Microdialysis is a catheter-based method suitable for dynamic sampling of unbound antibiotic concentrations. Intravenous antibiotic concentration sampling by microdialysis has several advantages and may be a superior alternative to standard plasma sampling. We aimed to compare concentrations obtained by continuous intravenous microdialysis sampling [...] Read more.
Microdialysis is a catheter-based method suitable for dynamic sampling of unbound antibiotic concentrations. Intravenous antibiotic concentration sampling by microdialysis has several advantages and may be a superior alternative to standard plasma sampling. We aimed to compare concentrations obtained by continuous intravenous microdialysis sampling and by standard plasma sampling of both vancomycin and meropenem in a porcine model. Eight female pigs received 1 g of both vancomycin and meropenem, simultaneously over 100 and 10 min, respectively. Prior to drug infusion, an intravenous microdialysis catheter was placed in the subclavian vein. Microdialysates were collected for 8 h. From a central venous catheter, plasma samples were collected in the middle of every dialysate sampling interval. A higher area under the concentration/time curve and peak drug concentration were found in standard plasma samples compared to intravenous microdialysis samples, for both vancomycin and meropenem. Both vancomycin and meropenem concentrations obtained with intravenous microdialysis were generally lower than from standard plasma sampling. The differences in key pharmacokinetic parameters between the two sampling techniques underline the importance of further investigations to find the most suitable and reliable method for continuous intravenous antibiotic concentration sampling. Full article
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Article
Using an Antibiogram Profile to Improve Infection Control and Rational Antimicrobial Therapy in an Urban Hospital in The Gambia, Strategies and Lessons for Low- and Middle-Income Countries
Antibiotics 2023, 12(4), 790; https://doi.org/10.3390/antibiotics12040790 - 21 Apr 2023
Viewed by 969
Abstract
Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility [...] Read more.
Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia. Full article
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Article
Exposure to Non-Antimicrobial Drugs and Risk of Infection with Antibiotic-Resistant Enterobacteriaceae
Antibiotics 2023, 12(4), 789; https://doi.org/10.3390/antibiotics12040789 - 20 Apr 2023
Viewed by 655
Abstract
Antimicrobial resistance (AMR) has consistently been linked to antibiotic use. However, the roles of commonly prescribed non-antimicrobial drugs as drivers of AMR may be under-appreciated. Here, we studied a cohort of patients with community-acquired pyelonephritis and assessed the association of exposure to non-antimicrobial [...] Read more.
Antimicrobial resistance (AMR) has consistently been linked to antibiotic use. However, the roles of commonly prescribed non-antimicrobial drugs as drivers of AMR may be under-appreciated. Here, we studied a cohort of patients with community-acquired pyelonephritis and assessed the association of exposure to non-antimicrobial drugs at the time of hospital admission with infection with drug-resistant organisms (DRO). Associations identified on bivariate analyses were tested using a treatment effects estimator that models both outcome and treatment probability. Exposure to proton-pump inhibitors, beta-blockers, and antimetabolites was significantly associated with multiple resistance phenotypes. Clopidogrel, selective serotonin reuptake inhibitors, and anti-Xa agents were associated with single-drug resistance phenotypes. Antibiotic exposure and indwelling urinary catheters were covariates associated with AMR. Exposure to non-antimicrobial drugs significantly increased the probability of AMR in patients with no other risk factors for resistance. Non-antimicrobial drugs may affect the risk of infection with DRO through multiple mechanisms. If corroborated using additional datasets, these findings offer novel directions for predicting and mitigating AMR. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Article
Antibiotic Consumption in a Cohort of Hospitalized Adults with Viral Respiratory Tract Infection
Antibiotics 2023, 12(4), 788; https://doi.org/10.3390/antibiotics12040788 - 20 Apr 2023
Viewed by 639
Abstract
Development of antibiotic resistance, a threat to global health, is driven by inappropriate antibiotic usage. Respiratory tract infections (RTIs) are frequently treated empirically with antibiotics, despite the fact that a majority of the infections are caused by viruses. The purpose of this study [...] Read more.
Development of antibiotic resistance, a threat to global health, is driven by inappropriate antibiotic usage. Respiratory tract infections (RTIs) are frequently treated empirically with antibiotics, despite the fact that a majority of the infections are caused by viruses. The purpose of this study was to determine the prevalence of antibiotic treatment in hospitalized adults with viral RTIs, and to investigate factors influencing the antibiotic decision-making. We conducted a retrospective observational study of patients ≥ 18 years, hospitalized in 2015–2018 with viral RTIs. Microbiological data were taken from the laboratory information system and information on antibiotic treatment drawn from the hospital records. To investigate decisions for prescribing antibiotic treatment, we evaluated relevant factors such as laboratory and radiological results, in addition to clinical signs. In 951 cases without secondary bacterial RTIs (median age 73 years, 53% female), 720 (76%) were prescribed antibiotic treatment, most frequently beta-lactamase-sensitive penicillins, but cephalosporins were prescribed as first-line in 16% of the cases. The median length of treatment (LOT) in the patients treated with antibiotics was seven days. Patients treated with antibiotics had an average of two days longer hospital stay compared to patients with no such treatment, but no difference in mortality was found. Our study revealed that there is still a role for antimicrobial stewardship to further improve antibiotic use in patients admitted for viral RTIs in a country with relatively low antibiotic consumption. Full article
(This article belongs to the Special Issue Optimization of Antimicrobial Stewardship in Public Health)
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Article
A Cysteine-Reloading Process Initiating the Biosynthesis of the Bicyclic Scaffold of Dithiolopyrrolones
Antibiotics 2023, 12(4), 787; https://doi.org/10.3390/antibiotics12040787 - 20 Apr 2023
Viewed by 572
Abstract
Dithiolopyrrolone antibiotics are well known for their outstanding biological activities, and their biosynthesis has been studied vigorously. However, the biosynthesis mechanism of the characteristic bicyclic scaffold is still unknown after years of research. To uncover this mechanism, a multi-domain non-ribosomal peptide synthase DtpB [...] Read more.
Dithiolopyrrolone antibiotics are well known for their outstanding biological activities, and their biosynthesis has been studied vigorously. However, the biosynthesis mechanism of the characteristic bicyclic scaffold is still unknown after years of research. To uncover this mechanism, a multi-domain non-ribosomal peptide synthase DtpB from the biosynthetic gene cluster of thiolutin was selected as an object to study. We discovered that its adenylation domain not only recognized and adenylated cysteine, but also played an essential role in the formation of the peptide bond. Notably, an eight-membered ring compound was also discovered as an intermediate during the formation of the bicyclic structure. Based on these findings, we propose a new mechanism for the biosynthesis of the bicyclic scaffold of dithiolopyrrolones, and unveil additional functions of the adenylation domain. Full article
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Article
Molecular Modification of Kex2 P1’ Site Enhances Expression and Druggability of Fungal Defensin
Antibiotics 2023, 12(4), 786; https://doi.org/10.3390/antibiotics12040786 - 20 Apr 2023
Viewed by 594
Abstract
Pichia pastoris is the widely used expression system for producing recombinant secretory proteins. It is known that Kex2 protease plays a vital role in the process of protein secretion, in which the P1’ site affects its cleavage efficiency. To enhance the expression level [...] Read more.
Pichia pastoris is the widely used expression system for producing recombinant secretory proteins. It is known that Kex2 protease plays a vital role in the process of protein secretion, in which the P1’ site affects its cleavage efficiency. To enhance the expression level of fungal defensin-derived peptide NZ2114, this work attempts to optimize the P1’ site of Kex2 by replacing it with 20 amino acids in turn. The results showed that when the amino acid of the P1’ site was changed to Phe (F), the yield of target peptide significantly increased from 2.39 g/L to 4.81 g/L. Additionally, the novel peptide F-NZ2114 (short for FNZ) showed strong antimicrobial activity against Gram-positive (G+) bacteria, especially for Staphylococcus aureus and Streptococcus agalactiae (MIC: 4–8 μg/mL). The FNZ was very stable and retained high activity in various conditions; in addition, a low cytotoxicity and no hemolysis were observed even at a high concentration of 128 μg/mL, and a longer postantibiotic effect was reached. The above results indicate that this engineering strategy provided a feasible optimization scheme for enhancing the expression level and druggability of this antimicrobial peptide from fungal defensin and other similar targets by this updated recombinant yeast. Full article
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Article
In Vitro Activity of Cefiderocol on Multiresistant Bacterial Strains and Genomic Analysis of Two Cefiderocol Resistant Strains
Antibiotics 2023, 12(4), 785; https://doi.org/10.3390/antibiotics12040785 - 20 Apr 2023
Viewed by 676
Abstract
Cefiderocol is a new siderophore cephalosporin that is effective against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to evaluate the activity of this new antimicrobial agent against a collection of pathogens using broth microdilution assays and to analyze [...] Read more.
Cefiderocol is a new siderophore cephalosporin that is effective against multidrug-resistant Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to evaluate the activity of this new antimicrobial agent against a collection of pathogens using broth microdilution assays and to analyze the possible mechanism of cefiderocol resistance in two resistant Klebsiella pneumoniae isolates. One hundred and ten isolates were tested, comprising 67 Enterobacterales, two Acinetobacter baumannii, one Achromobacter xylosoxidans, 33 Pseudomonas aeruginosa and seven Stenotrophomonas maltophilia. Cefiderocol showed good in vitro activity, with an MIC < 2 μg/mL, and was able to inhibit 94% of the tested isolates. We observed a resistance rate of 6%. The resistant isolates consisted of six Klebsiella pneumoniae and one Escherichia coli, leading to a resistance rate of 10.4% among the Enterobacterales. Whole-genome sequencing analysis was performed on two cefiderocol-resistant Klebsiella pneumoniae isolates to investigate the possible mutations responsible for the observed resistance. Both strains belonged to ST383 and harbored different resistant and virulence genes. The analysis of genes involved in iron uptake and transport showed the presence of different mutations located in fhuA, fepA, iutA, cirA, sitC, apbC, fepG, fepC, fetB, yicI, yicJ, and yicL. Furthermore, for the first time, to the best of our knowledge, we described two Klebsiella pneumoniae isolates that synthesize a truncated fecA protein due to the transition from G to A, leading to a premature stop codon in the amino acid position 569, and a TonB protein carrying a 4-amino acid insertion (PKPK) after Lysine 103. In conclusion, our data show that cefiderocol is an effective drug against multidrug-resistant Gram-negative bacteria. However, the higher resistance rate observed in Enterobacterales underlines the need for active surveillance to limit the spread of these pathogens and to avoid the risks associated with the emergence of resistance to new drugs. Full article
(This article belongs to the Special Issue Epidemiology of ESBL-Producing Enterobacteriaceae)
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Article
On the Potential of Relational Databases for the Detection of Clusters of Infection and Antibiotic Resistance Patterns
Antibiotics 2023, 12(4), 784; https://doi.org/10.3390/antibiotics12040784 - 19 Apr 2023
Viewed by 429
Abstract
In recent years, several bacterial strains have acquired significant antibiotic resistance and can, therefore, become difficult to contain. To counteract such trends, relational databases can be a powerful tool for supporting the decision-making process. The case of Klebsiella pneumoniae diffusion in a central [...] Read more.
In recent years, several bacterial strains have acquired significant antibiotic resistance and can, therefore, become difficult to contain. To counteract such trends, relational databases can be a powerful tool for supporting the decision-making process. The case of Klebsiella pneumoniae diffusion in a central region of Italy was analyzed as a case study. A specific relational database is shown to provide very detailed and timely information about the spatial–temporal diffusion of the contagion, together with a clear assessment of the multidrug resistance of the strains. The analysis is particularized for both internal and external patients. Tools such as the one proposed can, therefore, be considered important elements in the identification of infection hotspots, a key ingredient of any strategy to reduce the diffusion of an infectious disease at the community level and in hospitals. These types of tools are also very valuable in the decision-making process related to antibiotic prescription and to the management of stockpiles. The application of this processing technology to viral diseases such as COVID-19 is under investigation. Full article
(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)
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Article
New Antimicrobial Resistance Strategies: An Adaptive Resistance Network Conferring Reduced Glycopeptide Susceptibility in VISA
Antibiotics 2023, 12(4), 783; https://doi.org/10.3390/antibiotics12040783 - 19 Apr 2023
Viewed by 783
Abstract
Background: Vancomycin-intermediate Staphylococcus aureus (VISA) emerges typically in the healthcare-associated methicillin-resistant S. aureus and more rarely in community-acquired S. aureus (CA-MRSA). VISA is a serious concern for public health due to its association with persistent infections, the failure of vancomycin treatment, and [...] Read more.
Background: Vancomycin-intermediate Staphylococcus aureus (VISA) emerges typically in the healthcare-associated methicillin-resistant S. aureus and more rarely in community-acquired S. aureus (CA-MRSA). VISA is a serious concern for public health due to its association with persistent infections, the failure of vancomycin treatment, and poor clinical outcomes. Currently, the burden of VISA is somewhat high, even though vancomycin is the mainstay treatment for severe MRSA infections. The molecular mechanisms of reduced glycopeptide susceptibility in S. aureus are constantly under investigation but have still not yet been fully characterized. Methods: Our goal was to investigate the reduced glycopeptide susceptibility mechanisms emerging in a VISA CA-MRSA versus its vancomycin-susceptible (VSSA) CA-MRSA parents in a hospitalized patient undergoing glycopeptide treatment. Comparative integrated omics, Illumina MiSeq whole-genome sequencing (WGS), RNA-Seq, and bioinformatics were performed. Results: Through a comparison of VISA CA-MRSA vs. its VSSA CA-MRSA parent, mutational and transcriptomic adaptations were found in a pool of genes involved, directly or indirectly, in the biosynthesis of the glycopeptide target conferring or supporting the VISA phenotype, and its cross-resistance with daptomycin. This pool included key genes responsible for the biosynthesis of the peptidoglycan precursors, i.e., D-Ala, the D-Ala-D-Ala dipeptide termini of the pentapeptide, and its incorporation in the nascent pentapeptide, as key targets of the glycopeptide resistance. Furthermore, accessory glycopeptide-target genes involved in the pathways corroborated the key adaptations, and thus, supported the acquisition of the VISA phenotype i.e., transporters, nucleotide metabolism genes, and transcriptional regulators. Finally, transcriptional changes were also found in computationally predicted cis-acting small antisense RNA triggering genes related both to the key or accessory adaptive pathways. Conclusion: Our investigation describes an adaptive resistance pathway acquired under antimicrobial therapy conferring reduced glycopeptide susceptibility in a VISA CA-MRSA due to a comprehensive network of mutational and transcriptional adaptations in genes involved in pathways responsible for the biosynthesis of glycopeptide’s target or supporters of the key resistance path. Full article
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Article
Assessment of Prevalence and Diversity of Antimicrobial Resistant Escherichia coli from Retail Meats in Southern California
Antibiotics 2023, 12(4), 782; https://doi.org/10.3390/antibiotics12040782 - 19 Apr 2023
Viewed by 806
Abstract
Retail meat products may serve as reservoirs and conduits for antimicrobial resistance, which is frequently monitored using Escherichia coli as indicator bacteria. In this study, E. coli isolation was conducted on 221 retail meat samples (56 chicken, 54 ground turkey, 55 ground beef, [...] Read more.
Retail meat products may serve as reservoirs and conduits for antimicrobial resistance, which is frequently monitored using Escherichia coli as indicator bacteria. In this study, E. coli isolation was conducted on 221 retail meat samples (56 chicken, 54 ground turkey, 55 ground beef, and 56 pork chops) collected over a one-year period from grocery stores in southern California. The overall prevalence of E. coli in retail meat samples was 47.51% (105/221), with E. coli contamination found to be significantly associated with meat type and season of sampling. From antimicrobial susceptibility testing, 51 isolates (48.57%) were susceptible to all antimicrobials tested, 54 (51.34%) were resistant to at least 1 drug, 39 (37.14%) to 2 or more drugs, and 21 (20.00%) to 3 or more drugs. Resistance to ampicillin, gentamicin, streptomycin, and tetracycline were significantly associated with meat type, with poultry counterparts (chicken or ground turkey) exhibiting higher odds for resistance to these drugs compared to non-poultry meats (beef and pork). From the 52 E. coli isolates selected to undergo whole-genome sequencing (WGS), 27 antimicrobial resistance genes (ARGs) were identified and predicted phenotypic AMR profiles with an overall sensitivity and specificity of 93.33% and 99.84%, respectively. Clustering assessment and co-occurrence networks revealed that the genomic AMR determinants of E. coli from retail meat were highly heterogeneous, with a sparsity of shared gene networks. Full article
(This article belongs to the Special Issue Research of Antimicrobial Resistance in the Food Chain)
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Review
Clinical Diagnostics of Bacterial Infections and Their Resistance to Antibiotics—Current State and Whole Genome Sequencing Implementation Perspectives
Antibiotics 2023, 12(4), 781; https://doi.org/10.3390/antibiotics12040781 - 19 Apr 2023
Viewed by 1009
Abstract
Antimicrobial resistance (AMR), defined as the ability of microorganisms to withstand antimicrobial treatment, is responsible for millions of deaths annually. The rapid spread of AMR across continents warrants systematic changes in healthcare routines and protocols. One of the fundamental issues with AMR spread [...] Read more.
Antimicrobial resistance (AMR), defined as the ability of microorganisms to withstand antimicrobial treatment, is responsible for millions of deaths annually. The rapid spread of AMR across continents warrants systematic changes in healthcare routines and protocols. One of the fundamental issues with AMR spread is the lack of rapid diagnostic tools for pathogen identification and AMR detection. Resistance profile identification often depends on pathogen culturing and thus may last up to several days. This contributes to the misuse of antibiotics for viral infection, the use of inappropriate antibiotics, the overuse of broad-spectrum antibiotics, or delayed infection treatment. Current DNA sequencing technologies offer the potential to develop rapid infection and AMR diagnostic tools that can provide information in a few hours rather than days. However, these techniques commonly require advanced bioinformatics knowledge and, at present, are not suited for routine lab use. In this review, we give an overview of the AMR burden on healthcare, describe current pathogen identification and AMR screening methods, and provide perspectives on how DNA sequencing may be used for rapid diagnostics. Additionally, we discuss the common steps used for DNA data analysis, currently available pipelines, and tools for analysis. Direct, culture-independent sequencing has the potential to complement current culture-based methods in routine clinical settings. However, there is a need for a minimum set of standards in terms of evaluating the results generated. Additionally, we discuss the use of machine learning algorithms regarding pathogen phenotype detection (resistance/susceptibility to an antibiotic). Full article
(This article belongs to the Special Issue Diagnostics, Treatment and Prevention of Bacterial Infections)
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Article
Evaluation of a Pediatric Community-Acquired Pneumonia Antimicrobial Stewardship Intervention at an Academic Medical Center
Antibiotics 2023, 12(4), 780; https://doi.org/10.3390/antibiotics12040780 - 19 Apr 2023
Viewed by 437
Abstract
(1) Background: Pneumonia is the leading diagnosis associated with antibiotic use in hospitalized children. The Infectious Diseases Society of America published pediatric community-acquired pneumonia (CAP) guidelines in 2011, but adherence to recommendations varies across institutions. The purpose of this study was to evaluate [...] Read more.
(1) Background: Pneumonia is the leading diagnosis associated with antibiotic use in hospitalized children. The Infectious Diseases Society of America published pediatric community-acquired pneumonia (CAP) guidelines in 2011, but adherence to recommendations varies across institutions. The purpose of this study was to evaluate the impact of an antimicrobial stewardship intervention on antibiotic prescribing in pediatric patients admitted to an academic medical center. (2) Methods: This single-center pre/post-intervention evaluation included children admitted for CAP during three time periods (pre-intervention and post-intervention groups 1 and 2). The primary outcomes were changes in inpatient antibiotic selection and duration following the interventions. Secondary outcomes included discharge antibiotic regimens, length of stay, and 30-day readmission rates. (3) Results: A total of 540 patients were included in this study. Most patients were under five years of age (69%). Antibiotic selection significantly improved, with prescriptions for ceftriaxone decreasing (p < 0.001) and ampicillin increasing (p < 0.001) following the interventions. Antibiotic duration decreased from a median of ten days in the pre-intervention group and post-intervention group 1 to eight days in post-intervention group 2. (4) Conclusions: Our antibiotic stewardship intervention directed at pediatric CAP treatment resulted in improved antibiotic prescriptions and provides data that can be used to further educate providers at our institution. Full article
(This article belongs to the Special Issue Antimicrobial Treatment of Lower Respiratory Tract Infections)
Article
Antimicrobial Activity of Apis mellifera Bee Venom Collected in Northern Peru
Antibiotics 2023, 12(4), 779; https://doi.org/10.3390/antibiotics12040779 - 19 Apr 2023
Viewed by 776
Abstract
Due to the emergence of microorganisms resistant to antibiotics and the failure of antibiotic therapies, there is an urgent need to search for new therapeutic options, as well as new molecules with antimicrobial potential. The objective of the present study was to evaluate [...] Read more.
Due to the emergence of microorganisms resistant to antibiotics and the failure of antibiotic therapies, there is an urgent need to search for new therapeutic options, as well as new molecules with antimicrobial potential. The objective of the present study was to evaluate the in vitro antibacterial activity of Apis mellifera venom collected in the beekeeping areas of the city of Lambayeque in northern Peru against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Bee venom extraction was performed by electrical impulses and separated using the Amicon ultra centrifugal filter. Subsequently, the fractions were quantified by spectrometric 280 nm and evaluated under denaturant conditions in SDS-PAGE. The fractions were pitted against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Pseudomonas aeruginosa ATCC 27853. A purified fraction (PF) of the venom of A. mellifera and three low molecular weight bands of 7 KDa, 6 KDa, and 5 KDa were identified that showed activity against E. coli with a MIC of 6.88 µg/mL, while for P. aeruginosa and S. aureus, it did not present a MIC. No hemolytic activity at a concentration lower than 15.6 µg/mL and no antioxidant activity. The venom of A. mellifera contains a potential presence of peptides and a predilection of antibacterial activity against E. coli. Full article
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)
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Review
Enterococcal Urinary Tract Infections: A Review of the Pathogenicity, Epidemiology, and Treatment
Antibiotics 2023, 12(4), 778; https://doi.org/10.3390/antibiotics12040778 - 19 Apr 2023
Viewed by 995
Abstract
Urinary tract infections (UTIs) are among the most common causes of infections worldwide and can be caused by numerous uropathogens. Enterococci are Gram-positive, facultative anaerobic commensal organisms of the gastrointestinal tract that are known uropathogens. Enterococcus spp. has become a leading cause of [...] Read more.
Urinary tract infections (UTIs) are among the most common causes of infections worldwide and can be caused by numerous uropathogens. Enterococci are Gram-positive, facultative anaerobic commensal organisms of the gastrointestinal tract that are known uropathogens. Enterococcus spp. has become a leading cause of healthcare associated infections, ranging from endocarditis to UTIs. In recent years, there has been an increase in multidrug resistance due to antibiotic misuse, especially in enterococci. Additionally, infections due to enterococci pose a unique challenge due to their ability to survive in extreme environments, intrinsic antimicrobial resistance, and genomic malleability. Overall, this review aims to highlight the pathogenicity, epidemiology, and treatment recommendations (according to the most recent guidelines) of enterococci. Full article
Article
Socioeconomic and Governance Factors Disentangle the Relationship between Temperature and Antimicrobial Resistance: A 10-Year Ecological Analysis of European Countries
Antibiotics 2023, 12(4), 777; https://doi.org/10.3390/antibiotics12040777 - 19 Apr 2023
Viewed by 393
Abstract
Although previous studies showed that warmer temperatures may be associated with increased antimicrobial resistance (AMR) rates, unmeasured factors may explain the observed relationship. We conducted a ten-year ecological analysis to evaluate whether temperature change was associated with AMR across 30 European countries, considering [...] Read more.
Although previous studies showed that warmer temperatures may be associated with increased antimicrobial resistance (AMR) rates, unmeasured factors may explain the observed relationship. We conducted a ten-year ecological analysis to evaluate whether temperature change was associated with AMR across 30 European countries, considering predictors that can determine a geographical gradient. Using four data sources, we created a dataset of: annual temperature change (FAOSTAT database); AMR proportions for ten pathogen–antibiotic combinations (ECDC atlas); consumption of antibiotics for systemic use in the community (ESAC-Net database); population density, gross domestic product (GDP) per capita, and governance indicators (World Bank DataBank). Data were obtained for each country and year (2010–2019) and analyzed through multivariable models. We found evidence of a positive linear association between temperature change and AMR proportion across all countries, years, pathogens, and antibiotics (β = 0.140; 95%CI = 0.039; 0.241; p = 0.007), adjusting for the effect of covariates. However, when GDP per capita and the governance index were included in the multivariable model, temperature change was no longer associated with AMR. Instead, the main predictors were antibiotic consumption (β = 0.506; 95%CI = 0.366; 0.646; p < 0.001), population density (β = 0.143; 95%CI = 0.116; 0.170; p < 0.001), and the governance index (β = −1.043; 95%CI = −1.207; −0.879; p < 0.001). Ensuring the appropriate use of antibiotics and improving governance efficiency are the most effective ways of counteracting AMR. It is necessary to conduct further experimental studies and obtain more detailed data to investigate whether climate change affects AMR. Full article
(This article belongs to the Special Issue Hospital Infections and Antimicrobial Resistance)
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Article
Analysis of Cellular Damage Resulting from Exposure of Bacteria to Graphene Oxide and Hybrids Using Fourier Transform Infrared Spectroscopy
Antibiotics 2023, 12(4), 776; https://doi.org/10.3390/antibiotics12040776 - 18 Apr 2023
Viewed by 601
Abstract
With the increase in antimicrobial resistance, there is an urgent need to find new antimicrobials. Four particulate antimicrobial compounds, graphite (G), graphene oxide (GO), silver–graphene oxide (Ag-GO) and zinc oxide–graphene oxide (ZnO-GO) were tested against Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae [...] Read more.
With the increase in antimicrobial resistance, there is an urgent need to find new antimicrobials. Four particulate antimicrobial compounds, graphite (G), graphene oxide (GO), silver–graphene oxide (Ag-GO) and zinc oxide–graphene oxide (ZnO-GO) were tested against Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The antimicrobial effects on the cellular ultrastructure were determined using Fourier transform infrared spectroscopy (FTIR), and selected FTIR spectral metrics correlated with cell damage and death arising from exposure to the GO hybrids. Ag-GO caused the most severe damage to the cellular ultrastructure, whilst GO caused intermediate damage. Graphite exposure caused unexpectedly high levels of damage to E. coli, whereas ZnO-GO exposure led to relatively low levels of damage. The Gram-negative bacteria demonstrated a stronger correlation between FTIR metrics, indicated by the perturbation index and the minimal bactericidal concentration (MBC). The blue shift of the combined ester carbonyl and amide I band was stronger for the Gram-negative varieties. FTIR metrics tended to provide a better assessment of cell damage based on correlation with cellular imaging and indicated that damage to the lipopolysaccharide, peptidoglycan and phospholipid bilayers had occurred. Further investigations into the cell damage caused by the GO-based materials will allow the development of this type of carbon-based multimode antimicrobials. Full article
(This article belongs to the Special Issue Biofilm Formation and Control)
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Article
Antimicrobial Resistance Patterns of Enterobacter cloacae and Klebsiella aerogenes Strains Isolated from Clinical Specimens: A Twenty-Year Surveillance Study
Antibiotics 2023, 12(4), 775; https://doi.org/10.3390/antibiotics12040775 - 18 Apr 2023
Viewed by 732
Abstract
We retrospectively analyzed the antimicrobial data of Enterobacter spp. strains isolated from hospitalized subjects and outpatients over 20 years (2000–2019). A total of 2277 non-duplicate Enterobacter spp. isolates, 1037 from outpatients (45%) and 1240 from hospitalized subjects (55%), were retrieved. Most of samples [...] Read more.
We retrospectively analyzed the antimicrobial data of Enterobacter spp. strains isolated from hospitalized subjects and outpatients over 20 years (2000–2019). A total of 2277 non-duplicate Enterobacter spp. isolates, 1037 from outpatients (45%) and 1240 from hospitalized subjects (55%), were retrieved. Most of samples are infections of the urinary tract. Considering Enterobacter aerogenes, now classified as Klebsiella aerogenes, and Enterobacter cloacae, representing more than 90% of all isolates, except for aminoglycosides and fluroquinolones, which showed significant antibiotic decreasing trends (p < 0.01), none of the other antimicrobial agents tested showed significant changes in both groups (p > 0.05). Conversely, there was a significant increasing resistance trend for fosfomycin (p < 0.01), among both community and hospital-related subjects, most probably owing to uncontrolled and improper usage. Surveillance studies on antibiotic resistance at the local and regional level are required to detect new resistance mechanisms, reduce inappropriate antimicrobial consumption, and increase the focus on antimicrobial stewardship. Full article
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Review
The Epidemiology of Antibiotic-Related Adverse Events in the Treatment of Diabetic Foot Infections: A Narrative Review of the Literature
Antibiotics 2023, 12(4), 774; https://doi.org/10.3390/antibiotics12040774 - 18 Apr 2023
Viewed by 677
Abstract
The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative [...] Read more.
The use of antibiotics for the treatment of diabetic foot infections (DFIs) over an extended period of time has been shown to be associated with adverse events (AEs), whereas interactions with concomitant patient medications must also be considered. The objective of this narrative review was to summarize the most frequent and most severe AEs reported in prospective trials and observational studies at the global level in DFI. Gastrointestinal intolerances were the most frequent AEs, from 5% to 22% among all therapies; this was more common when prolonged antibiotic administration was combined with oral beta-lactam or clindamycin or a higher dose of tetracyclines. The proportion of symptomatic colitis due to Clostridium difficile was variable depending on the antibiotic used (0.5% to 8%). Noteworthy serious AEs included hepatotoxicity due to beta-lactams (5% to 17%) or quinolones (3%); cytopenia’s related to linezolid (5%) and beta-lactams (6%); nausea under rifampicin, and renal failure under cotrimoxazole. Skin rash was found to rarely occur and was commonly associated with the use of penicillins or cotrimoxazole. AEs from prolonged antibiotic use in patients with DFI are costly in terms of longer hospitalization or additional monitoring care and can trigger additional investigations. The best way to prevent AEs is to keep the duration of antibiotic treatment short and with the lowest dose clinically necessary. Full article
(This article belongs to the Special Issue Feature Papers in Therapy of Diabetic Foot Infections)
Article
Peptide-Resorcinarene Conjugates Obtained via Click Chemistry: Synthesis and Antimicrobial Activity
Antibiotics 2023, 12(4), 773; https://doi.org/10.3390/antibiotics12040773 - 18 Apr 2023
Viewed by 521
Abstract
Antimicrobial resistance (AMR) is one of the top ten threats to public health, as reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases [...] Read more.
Antimicrobial resistance (AMR) is one of the top ten threats to public health, as reported by the World Health Organization (WHO). One of the causes of the growing AMR problem is the lack of new therapies and/or treatment agents; consequently, many infectious diseases could become uncontrollable. The need to discover new antimicrobial agents that are alternatives to the existing ones and that allow mitigating this problem has increased, due to the rapid and global expansion of AMR. Within this context, both antimicrobial peptides (AMPs) and cyclic macromolecules, such as resorcinarenes, have been proposed as alternatives to combat AMR. Resorcinarenes present multiple copies of antibacterial compounds in their structure. These conjugate molecules have exhibited antifungal and antibacterial properties and have also been used in anti-inflammatory, antineoplastic, and cardiovascular therapies, as well as being useful in drug and gene delivery systems. In this study, it was proposed to obtain conjugates that contain four copies of AMP sequences over a resorcinarene core. Specifically, obtaining (peptide)4-resorcinarene conjugates derived from LfcinB (20–25): RRWQWR and BF (32–34): RLLR was explored. First, the synthesis routes that allowed obtaining: (a) alkynyl-resorcinarenes and (b) peptides functionalized with the azide group were established. These precursors were used to generate (c) (peptide)4-resorcinarene conjugates by azide-alkyne cycloaddition CuAAC, a kind of click chemistry. Finally, the conjugates’ biological activity was evaluated: antimicrobial activity against reference strains and clinical isolates of bacteria and fungi, and the cytotoxic activity over erythrocytes, fibroblast, MCF-7, and HeLa cell lines. Our results allowed establishing a new synthetic route, based on click chemistry, for obtaining macromolecules derived from resorcinarenes functionalized with peptides. Moreover, it was possible to identify promising antimicrobial chimeric molecules that may lead to advances in the development of new therapeutic agents. Full article
(This article belongs to the Section Antimicrobial Peptides)
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Article
Co-Selection of Bacterial Metal and Antibiotic Resistance in Soil Laboratory Microcosms
Antibiotics 2023, 12(4), 772; https://doi.org/10.3390/antibiotics12040772 - 18 Apr 2023
Viewed by 545
Abstract
Accumulation of heavy metals (HMs) in agricultural soil following the application of superphosphate fertilisers seems to induce resistance of soil bacteria to HMs and appears to co-select for resistance to antibiotics (Ab). This study aimed to investigate the selection of co-resistance of soil [...] Read more.
Accumulation of heavy metals (HMs) in agricultural soil following the application of superphosphate fertilisers seems to induce resistance of soil bacteria to HMs and appears to co-select for resistance to antibiotics (Ab). This study aimed to investigate the selection of co-resistance of soil bacteria to HMs and Ab in uncontaminated soil incubated for 6 weeks at 25 °C in laboratory microcosms spiked with ranges of concentrations of cadmium (Cd), zinc (Zn) and mercury (Hg). Co-selection of HM and Ab resistance was assessed using plate culture on media with a range of HM and Ab concentrations, and pollution-induced community tolerance (PICT) assays. Bacterial diversity was profiled via terminal restriction fragment length polymorphism (TRFLP) assay and 16S rDNA sequencing of genomic DNA isolated from selected microcosms. Based on sequence data, the microbial communities exposed to HMs were found to differ significantly compared to control microcosms with no added HM across a range of taxonomic levels. Full article
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Article
Replacement of the Double Meropenem Disc Test with a Lateral Flow Assay for the Detection of Carbapenemase-Producing Enterobacterales and Pseudomonas aeruginosa in Clinical Laboratory Practice
Antibiotics 2023, 12(4), 771; https://doi.org/10.3390/antibiotics12040771 - 17 Apr 2023
Viewed by 682
Abstract
The prompt detection of carbapenemases among Gram-negative bacteria isolated from patients’ clinical infection samples and surveillance cultures is important for the implementation of infection control measures. In this context, we evaluated the effectiveness of replacing phenotypic tests for the detection of carbapenemase producers [...] Read more.
The prompt detection of carbapenemases among Gram-negative bacteria isolated from patients’ clinical infection samples and surveillance cultures is important for the implementation of infection control measures. In this context, we evaluated the effectiveness of replacing phenotypic tests for the detection of carbapenemase producers with the immunochromatographic Carbapenem-Resistant K.N.I.V.O. Detection K-Set lateral flow assay (LFA). In total, 178 carbapenem-resistant Enterobacterales and 32 carbapenem-resistant Pseudomonas aeruginosa isolated in our hospital were tested with both our established phenotypic and molecular testing procedures and the LFA. The Kappa coefficient of agreement for Enterobacterales was 0.85 (p < 0.001) and 0.6 (p < 0.001) for P. aeruginosa. No major disagreements were observed and notably, in many cases, the LFA detected more carbapenemases than the double meropenem disc test, especially regarding OXA-48 in Enterobacterales and VIM in P. aeruginosa. Overall, the Carbapenem-Resistant K.N.I.V.O. Detection K-Set was very effective and at least equivalent to the standard procedures used in our lab. However, it was much faster as it provided results in 15 min compared to a minimum of 18–24 h for the phenotypic tests. Full article
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Article
Evaluation of Implementation and Effectiveness of China’s Antibiotic Stewardship in the First Affiliated Hospital of Sun Yat-sen University
Antibiotics 2023, 12(4), 770; https://doi.org/10.3390/antibiotics12040770 - 17 Apr 2023
Viewed by 501
Abstract
Antibiotic stewardship has been prioritized by governments and health care organizations in recent years as antibiotic resistance is markedly increasing. A tertiary hospital in Guangzhou, China was chosen as a study example to undertake an implementation and effectiveness evaluation of China’s antibiotic stewardship [...] Read more.
Antibiotic stewardship has been prioritized by governments and health care organizations in recent years as antibiotic resistance is markedly increasing. A tertiary hospital in Guangzhou, China was chosen as a study example to undertake an implementation and effectiveness evaluation of China’s antibiotic stewardship to improve and promote antimicrobial stewardship nationwide. The general surgery department of the study hospital was utilized to examine surgical site infection, and samples from across the hospital were used to identify bloodstream infection. Data was analyzed using descriptive analysis, the Mann–Kendall trend test, logit model and panel data model, and t-tests. In terms of prophylactic and therapeutic antibiotic rational use, respectively, we evaluated implementation conditions, the correlation between implementation and corresponding disease progress, and the cost-effectiveness of China’s antibiotic stewardship. For perioperative prophylactic antibiotic use, antibiotic stewardship was found to have been well-implemented, cost-effective, and reduced the incidence of surgical site infection. However, concerning therapeutic use and antibiotic-resistant bacterial infection prophylaxis, the complexity of influencing factors and the contradiction between stewardship implementation and clinical demand needs to be further evaluated. Full article
(This article belongs to the Special Issue Antibiotics Use and Stewardship in China)
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Article
Phenotypic and Genotypic Characteristics of Antimicrobial Resistance in Citrobacter freundii Isolated from Domestic Ducks (Anas platyrhynchos domesticus) in Bangladesh
Antibiotics 2023, 12(4), 769; https://doi.org/10.3390/antibiotics12040769 - 17 Apr 2023
Viewed by 1028
Abstract
Antimicrobial resistance (AMR) in Citrobacter freundii poses a serious challenge as this species is one of the sources of nosocomial infection and causes diarrheal infections in humans. Ducks could be the potential source of multidrug-resistant (MDR) C. freundii; however, AMR profiles in [...] Read more.
Antimicrobial resistance (AMR) in Citrobacter freundii poses a serious challenge as this species is one of the sources of nosocomial infection and causes diarrheal infections in humans. Ducks could be the potential source of multidrug-resistant (MDR) C. freundii; however, AMR profiles in C. freundii from non-human sources in Bangladesh have remained elusive. This study aimed to detect C. freundii in domestic ducks (Anas platyrhynchos domesticus) in Bangladesh and to determine their phenotypic and genotypic antibiotic susceptibility patterns. A total of 150 cloacal swabs of diseased domestic ducks were screened using culturing, staining, biochemical, polymerase chain reaction (PCR), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) to detect C. freundii. Phenotypic and genotypic antibiotic susceptibility patterns were done by the disk diffusion method and PCR, respectively. In total, 16.67% (25/150) of the samples were positive for C. freundii. C. freundii isolates showed a range of 20% to 96% resistance to cefotaxime, gentamicin, levofloxacin, ciprofloxacin, cotrimoxazole, tetracycline, ampicillin, and cephalexin. More than 60% of the isolates were phenotypically MDR, and the index of multiple antibiotic resistance ranged from 0.07 to 0.79. Genes encoding resistance to beta-lactams [blaTEM-1-88% (22/25), blaCMY-2-56% (14/25), blaCMY-9-8% (2/25), and blaCTX-M-14-20% (5/25)], sulfonamides [sul1-52% (13/25), sul2-24% (6/25)], tetracyclines [tetA-32% (8/25) and tetB-4% (1/25)], aminoglycosides [aacC4-16% (4/25)], and fluoroquinolones [qnrA-4% (1/25), qnrB-12% (3/25), and qnrS-4% (1/25)] were detected in the isolated C. freundii. To the best of our knowledge, this is the first study in Bangladesh to detect MDR C. freundii with their associated resistance genes from duck samples. We suggest addressing the burden of diseases in ducks and humans and associated AMR issues using the One Health approach. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Veterinary Science)
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Article
Provision of Microbiology, Infection Services and Antimicrobial Stewardship in Intensive Care: A Survey across the Critical Care Networks in England and Wales
Antibiotics 2023, 12(4), 768; https://doi.org/10.3390/antibiotics12040768 - 17 Apr 2023
Viewed by 795
Abstract
Infection rounds in Intensive Care Units (ICU) can impact antimicrobial stewardship (AMS). The aim of this survey was to assess the availability of microbiology, infection, AMS services, and antimicrobial prescribing practices in the UK ICUs. An online questionnaire was sent to clinical leads [...] Read more.
Infection rounds in Intensive Care Units (ICU) can impact antimicrobial stewardship (AMS). The aim of this survey was to assess the availability of microbiology, infection, AMS services, and antimicrobial prescribing practices in the UK ICUs. An online questionnaire was sent to clinical leads for ICUs in each region listed in the Critical Care Network for the UK. Out of 217 ICUs, 87 deduplicated responses from England and Wales were analyzed. Three-quarters of those who responded had a dedicated microbiologist, and 50% had a dedicated infection control prevention nurse. Infection rounds varied in their frequency, with 10% providing phone advice only. Antibiotic guidance was available in 99% of the units; only 8% of those were ICU-specific. There were variations in the availability of biomarkers & the duration of antibiotics prescribed for pneumonia (community, hospital, or ventilator), urinary, intra-abdominal, and line infections/sepsis. Antibiotic consumption data were not routinely discussed in a multi-disciplinary meeting. The electronic prescription was available in ~60% and local antibiotic surveillance data in only 47% of ICUs. The survey highlights variations in practice and AMS services and may offer the opportunity to further collaborations and share learnings to support the safe use of antimicrobials in the ICU. Full article
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Article
Bacterial Aetiology of Neonatal Sepsis and Antimicrobial Resistance Pattern at the Regional Referral Hospital, Dar es Salam, Tanzania; A Call to Strengthening Antibiotic Stewardship Program
Antibiotics 2023, 12(4), 767; https://doi.org/10.3390/antibiotics12040767 - 16 Apr 2023
Viewed by 545
Abstract
The diagnosis of neonatal sepsis in lower-income countries is mainly based on clinical presentation. The practice necessitates empirical treatment with limited aetiology and antibiotic susceptibility profile knowledge, prompting the emergence and spread of antimicrobial resistance. We conducted a cross-sectional study to determine the [...] Read more.
The diagnosis of neonatal sepsis in lower-income countries is mainly based on clinical presentation. The practice necessitates empirical treatment with limited aetiology and antibiotic susceptibility profile knowledge, prompting the emergence and spread of antimicrobial resistance. We conducted a cross-sectional study to determine the aetiology of neonatal sepsis and antimicrobial resistance patterns. We recruited 658 neonates admitted to the neonatal ward with signs and symptoms of sepsis and performed 639 automated blood cultures and antimicrobial susceptibility testing. Around 72% of the samples were culture positive; Gram-positive bacteria were predominantly isolated, contributing to 81%. Coagulase-negative Staphylococci were the most isolates, followed by Streptococcus agalactiae. Overall, antibiotic resistance among Gram-positive pathogens ranged from 23% (Chloramphenicol) to 93% (Penicillin) and from 24.7% (amikacin) to 91% (ampicillin) for Gram-negative bacteria. Moreover, about 69% of Gram-positive and 75% of Gram-negative bacteria were multidrug-resistant (MDR). We observed about 70% overall proportion of MDR strains, non-significantly more in Gram-negative than Gram-positive pathogens (p = 0.334). In conclusion, the pathogen causing neonatal sepsis in our setting exhibited a high resistance rate to commonly used antibiotics. The high rate of MDR pathogens calls for strengthening antibiotic stewardship programs. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Article
Fomitopsis officinalis: Spatial (Pileus and Hymenophore) Metabolomic Variations Affect Functional Components and Biological Activities
Antibiotics 2023, 12(4), 766; https://doi.org/10.3390/antibiotics12040766 - 16 Apr 2023
Viewed by 712
Abstract
Fomitopsis officinalis is a holartic polyporous mushroom that forms large fruiting bodies on old standing trees, fallen logs, or stumps. F. officinalis is a medicinal mushroom species that is most commonly used in traditional European medicine. In this study, we explore the spatial [...] Read more.
Fomitopsis officinalis is a holartic polyporous mushroom that forms large fruiting bodies on old standing trees, fallen logs, or stumps. F. officinalis is a medicinal mushroom species that is most commonly used in traditional European medicine. In this study, we explore the spatial metabolic differences in F. officinalis’ mushroom parts, i.e., the cap (median and apical parts) and the hymenium. Additionally, chromatographic analysis was conducted in order to unravel the composition of specialized metabolites in the hydroalcoholic mushroom extracts. The potential antifungal and bacterial effects of extracts were tested against pathogen strains of Gram+ and Gram– bacteria, and yeast, dermatophytic, and fungal-pool species. Extracts from the apical part were the richest in terms of phenolic compounds; consistent with this finding, the extracts were also the most effective antiradical and antimicrobial agents with MIC values < 100 µg/mL for most of the tested bacterial and dermatophytic species. According to these findings, F. officinalis extracts are valuable sources of primary and secondary metabolites, thus suggesting potential applications in the formulation of food supplements with biological properties in terms of antioxidant and antimicrobial activities. Full article
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Review
The Influence of Helicobacter pylori on Human Gastric and Gut Microbiota
Antibiotics 2023, 12(4), 765; https://doi.org/10.3390/antibiotics12040765 - 16 Apr 2023
Viewed by 939
Abstract
Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected [...] Read more.
Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected by H. pylori colonization, with consequent effects on the gastrointestinal microbiota, exerted via the regulation of various factors, including gastric acidity, host immune responses, antimicrobial peptides, and virulence factors. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Notably, therapy regimens integrated with probiotics have been shown to reduce the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient’s compliance. In light of the deep impact of gut microbiota alterations on human health, the present article aims to provide an overview of the complex interaction between H. pylori and the gastrointestinal microbiota, focusing also on the consequences of eradication therapies and the effects of probiotic supplementation. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Therapy for Helicobacter pylori Infection)
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Article
Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
Antibiotics 2023, 12(4), 764; https://doi.org/10.3390/antibiotics12040764 - 16 Apr 2023
Viewed by 634
Abstract
(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 [...] Read more.
(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [Cmin] value of 3 mg/L normalized to the maintenance dose of 8 mg/kg/day) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated; (3) Results: Overall, 50 patients were included. The median average voriconazole Cmin was 2.47 (1.75–3.33) mg/L. The median (IQR) voriconazole concentration/dose ratio (C/D) was 0.29 (0.14–0.46). A CRP value > 11.46 mg/dL was associated with the achievement of voriconazole Cmin > 3 mg/L, with an AUC of 0.667 (95% CI 0.593–0.735; p < 0.001). A PCT value > 0.3 ng/mL was associated with the attainment of voriconazole Cmin > 3 mg/L (AUC 0.651; 95% CI 0.572–0.725; p = 0.0015). (4) Conclusions: Our findings suggest that in critically ill patients with CAPA, CRP and PCT values above the identified thresholds may cause the downregulation of voriconazole metabolism and favor voriconazole overexposure, leading to potentially toxic concentrations. Full article
(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)
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