Antibiotics

11 pages, 11891 KiB

Open AccessArticle

Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses

by Sudhanshu Shekhar, Navdeep Kaur Brar, Anders P. Håkansson and Fernanda Cristina Petersen

Antibiotics 2023, 12(2), 423; https://doi.org/10.3390/antibiotics12020423 - 20 Feb 2023

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Abstract

Emerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor cells) [...] Read more.

Emerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor cells) on T cell responses to Streptococcus pneumoniae. Lung cells and splenocytes were isolated from the infant mice subjected to intranasal administration of amoxicillin, HAMLET, or a combination of HAMLET and amoxicillin, and cultured with S. pneumoniae to measure T cell responses. After in-vitro stimulation with S. pneumoniae, lung cells from amoxicillin- or amoxicillin plus HAMLET-treated mice produced lower levels of Th17 (IL-17A), but not Th1 (IFN-γ), cytokine than mice receiving HAMLET or PBS. IL-17A/IFN-γ cytokine levels produced by the stimulated splenocytes, on the other hand, revealed no significant difference among treatment groups. Further analysis of T cell cytokine profiles by flow cytometry showed that lung CD4+, but not CD8+, T cells from amoxicillin- or HAMLET plus amoxicillin-treated mice expressed decreased levels of IL-17A compared to those from HAMLET-exposed or control mice. Collectively, these results indicate that exposure of infant mice to amoxicillin, but not HAMLET, may suppress lung Th17 responses to S. pneumoniae. Full article

(This article belongs to the Special Issue Resistance to Antibacterials in Human Pathogens)

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10 pages, 2550 KiB

Open AccessArticle

The Activity of Calcium Glycerophosphate and Fluoride against Cariogenic Biofilms of Streptococcus mutans and Candida albicans Formed In Vitro

by Thamires Priscila Cavazana, Thayse Yumi Hosida, Caio Sampaio, Leonardo Antônio de Morais, Douglas Roberto Monteiro, Juliano Pelim Pessan and Alberto Carlos Botazzo Delbem

Antibiotics 2023, 12(2), 422; https://doi.org/10.3390/antibiotics12020422 - 20 Feb 2023

Cited by 2 | Viewed by 1296

Abstract

This study evaluated the effects of calcium glycerophosphate (CaGP), with or without fluoride (F), on dual-species biofilms of Streptococcus mutans and Candida albicans. The biofilms were treated three times with 0.125, 0.25, and 0.5% CaGP solutions, with or without 500 ppm F [...] Read more.

This study evaluated the effects of calcium glycerophosphate (CaGP), with or without fluoride (F), on dual-species biofilms of Streptococcus mutans and Candida albicans. The biofilms were treated three times with 0.125, 0.25, and 0.5% CaGP solutions, with or without 500 ppm F (NaF). Additionally, 500 and 1100 ppm F-solutions and artificial saliva served as controls. After the final treatment, the microbial viability and biofilm structure, metabolic activity, total biomass production, and the composition of the extracellular matrix composition were analyzed. Regardless of the presence of F, 0.25 and 0.5% CaGP promoted a higher biomass production and metabolic activity increase than the controls (p < 0.05). F-free CaGP solutions reduced bacterial cell population significantly more than the 500 ppm F group or the negative control (p < 0.05). All the groups reduced the proteins, and 0.5% CaGP combined with F led to the highest reduction in the carbohydrate and nucleic acids content of the extracellular matrix (p < 0.05). It can be concluded that CaGP alone affected the number of bacterial cells and, when combined with F, reduced its production of biomass, metabolic activity, and the expression of the extracellular matrix components. Full article

(This article belongs to the Special Issue Synthesis and Biological Activity of Antimicrobial Agents, 2nd Volume)

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15 pages, 2268 KiB

Open AccessArticle

Plant Secondary Metabolites on Efflux-Mediated Antibiotic Resistant Stenotrophomonas Maltophilia: Potential of Herbal-Derived Efflux Pump Inhibitors

by Thi Huyen Thu Nguyen, Ngoc Anh Thơ Nguyen, Hai Dang Nguyen, Thi Thu Hien Nguyen, Mai Huong Le, Minh Quan Pham, Huu Nghi Do, Kim Chi Hoang, Serge Michalet, Marie-Geneviève Dijoux-Franca and Hoang Nam Pham

Antibiotics 2023, 12(2), 421; https://doi.org/10.3390/antibiotics12020421 - 20 Feb 2023

Cited by 3 | Viewed by 1954

Abstract

During the process of adapting to metal contamination, plants produce secondary metabolites that have the potential to modulate multidrug-resistant (MDR) phenotypes; this is achieved by inhibiting the activity of efflux pumps to reduce the minimum inhibitory concentrations (MICs) of antimicrobial substrates. Our study [...] Read more.

During the process of adapting to metal contamination, plants produce secondary metabolites that have the potential to modulate multidrug-resistant (MDR) phenotypes; this is achieved by inhibiting the activity of efflux pumps to reduce the minimum inhibitory concentrations (MICs) of antimicrobial substrates. Our study evaluated the effect of secondary metabolites of belowground parts of Pteris vittata L. and Fallopia japonica, two metal-tolerant plants from northern Vietnam, on six antibiotic-resistant Stenotrophomonas maltophilia strains possessing efflux pump resistance mechanisms that were isolated from soil and clinical samples. The chemical composition of aqueous and dichloromethane (DCM) fractions extracted from P. vittata and F. japonica was determined using UHPLC-DAD-ESI/QTOF analysis. The antibacterial and efflux pump inhibitory activities of the four fractions were evaluated for the six strains (K279a, 0366, BurA1, BurE1, PierC1, and 502) using a microdilution assay at fraction concentrations of 62.5, 125, and 250 μg/mL. The DCM fraction of F. japonica exhibited remarkable antibacterial activity against strain 0366, with a MIC of 31.25 μg/mL. Furthermore, this fraction also significantly decreased gentamicin MIC: four-fold and eight-fold reductions for BurA1 and BurE1 strains, respectively (when tested at 250 μg/mL), and two-fold and eight-fold reductions for K279a and BurE1 strains, respectively (when tested at 125 μg/mL). Pure emodin, the main component identified in the DCM fraction of F. japonica, and sennidine A&B only reduced by half the MIC of gentamicin (when tested at 30 μg/mL). Our results suggest that the DCM fraction components of F. japonica underground parts may be potential candidates for new bacterial efflux pump inhibitors (EPIs). Full article

(This article belongs to the Special Issue Efflux Pumps in Bacteria: What They Do and How We Can Stop Them)

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19 pages, 2612 KiB

Open AccessArticle

Antimicrobial Susceptibility Profile of Pathogenic and Commensal Bacteria Recovered from Cattle and Goat Farms

by Winnie Mukuna, Tobenna Aniume, Bharat Pokharel, Collins Khwatenge, Ashesh Basnet and Agnes Kilonzo-Nthenge

Antibiotics 2023, 12(2), 420; https://doi.org/10.3390/antibiotics12020420 - 20 Feb 2023

Cited by 3 | Viewed by 2084

Abstract

The use of antibiotics in food animals results to antimicrobial resistant bacteria that complicates the ability to treat infections. The purpose of this study was to investigate the prevalence of pathogenic and commensal bacteria in soil, water, manure, and milk from cattle and [...] Read more.

The use of antibiotics in food animals results to antimicrobial resistant bacteria that complicates the ability to treat infections. The purpose of this study was to investigate the prevalence of pathogenic and commensal bacteria in soil, water, manure, and milk from cattle and goat farms. A total of 285 environmental and 81 milk samples were analyzed for Enterobacteriaceae by using biochemical and PCR techniques. Susceptibility to antibiotics was determined by the Kirby–Bauer disk diffusion technique. A total of 15 different Enterobacteriaceae species were identified from goat and cattle farms. Manure had significantly higher (p < 0.05) Enterobacteriaceae (52.0%) than soil (37.2%), trough water (5.4%), and runoff water (5.4%). There was a significant difference (p < 0.05) in Enterobacteriaceae in goat milk (53.9%) and cow milk (46.2%). Enterobacteriaceae from environment showed 100% resistance to novobiocin, erythromycin, and vancomycin E. coli O157:H7, Salmonella spp., Enterococcus spp., and Listeria monocytogenes displayed three, five, six, and ten. AMR patterns, respectively. NOV-TET-ERY-VAN was the most common phenotype observed in all isolates. Our study suggest that cattle and goat farms are reservoirs of multidrug-resistant bacteria. Food animal producers should be informed on the prudent use of antimicrobials, good agricultural practices, and biosecurity measures. Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine, 2nd Volume)

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13 pages, 808 KiB

Open AccessArticle

The RND Efflux Pump Gene Expression in the Biofilm Formation of Acinetobacter baumannii

by Ola A. Abd El-Rahman, Fatma Rasslan, Safaa S. Hassan, Hossam M. Ashour and Reham Wasfi

Antibiotics 2023, 12(2), 419; https://doi.org/10.3390/antibiotics12020419 - 20 Feb 2023

Cited by 6 | Viewed by 2401

Abstract

Multidrug resistant (MDR) Acinetobacter baumannii is a critical opportunistic pathogen in healthcare-associated infections (HAI). This is attributed to several factors, including its ability to develop biofilms that can enhance antimicrobial resistance (AMR) in addition to creating an environment for horizontal transfer of antibiotic [...] Read more.

Multidrug resistant (MDR) Acinetobacter baumannii is a critical opportunistic pathogen in healthcare-associated infections (HAI). This is attributed to several factors, including its ability to develop biofilms that can enhance antimicrobial resistance (AMR) in addition to creating an environment for horizontal transfer of antibiotic resistance genes. The role of the efflux pump in biofilm formation is important for studies on alternative treatments for biofilms. One of the significant efflux pump families is the RND efflux pump family, which is common in Gram negative bacteria. The aim is to study the role of the RND efflux pump in biofilm formation by A. baumannii. The biofilm formation potential of thirty-four MDR A. baumannii isolates was evaluated by crystal violet assays. The effect of efflux pump inhibition and activation was studied using the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and the RND efflux pump substrate levofloxacin (at sub-MIC), respectively. The isolates were genotypically grouped by enterobacterial repetitive intergenic consensus (ERIC) typing and the expression of adeABC, adeFGH, and adeIJK efflux pump genes was measured by qPCR. Overall, 88.2% (30/34) of isolates were biofilm producers (the phenotype was variable including strong and weak producers). Efflux pump inhibition by CCCP reduced the biofilm formation significantly (p < 0.05) in 17.6% (6/34) of some isolates, whereas sub-MICs of the substrate levofloxacin increased biofilm formation in 20.5% (7/34) of other isolates. Overexpression of the three RND efflux pump genes was detected in five out of eleven selected isolates for qPCR with remarkable overexpression in the adeJ gene. No correlation was detected between the biofilm phenotype pattern and the RND efflux pump gene expression in biofilm cells relative to planktonic cells. In conclusion, the role of the RND efflux pumps AdeABC, AdeFGH, and AdeIJK in biofilm formation does not appear to be pivotal and the expression differs according to the genetic background of each strain. Thus, these pumps may not be a promising target for biofilm inhibition. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)

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12 pages, 964 KiB

Open AccessArticle

Molecular Detection of Tetracycline-Resistant Genes in Multi-Drug-Resistant Escherichia coli Isolated from Broiler Meat in Bangladesh

by Gazi Sofiul Alam, Mohammad Mahmudul Hassan, Md. Ahaduzzaman, Chandan Nath, Pronesh Dutta, Hamida Khanom, Shahneaz Ali Khan, Md Ridoan Pasha, Ariful Islam, Ricardo Soares Magalhaes and Rowland Cobbold

Antibiotics 2023, 12(2), 418; https://doi.org/10.3390/antibiotics12020418 - 20 Feb 2023

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Abstract

This study aimed to estimate the antimicrobial resistance (AMR) patterns and tetracycline-resistant gene profiles of Escherichia coli (E. coli) from broiler meat and livers sourced from live bird markets (LBMs) and supermarkets (SMs) in Chattogram, Bangladesh. In total, 405 samples were [...] Read more.

This study aimed to estimate the antimicrobial resistance (AMR) patterns and tetracycline-resistant gene profiles of Escherichia coli (E. coli) from broiler meat and livers sourced from live bird markets (LBMs) and supermarkets (SMs) in Chattogram, Bangladesh. In total, 405 samples were collected from SMs and LBMs, comprising muscle (n = 215) and liver (n = 190) samples. Disc diffusion tests were used to determine antimicrobial susceptibility profiles. PCR was used to identify E. coli and tetracycline-resistant genes. Over half (57%) of the chicken product samples were positive for E. coli. The AMR profiling of these isolates showed that the highest prevalence of resistance was against sulphamethoxazole–trimethoprim (89%), followed by tetracycline (87%), ampicillin (83%), and ciprofloxacin (61%). Among the antimicrobials listed by the World Health Organization as critically important, E. coli isolates were found to be resistant to cephalexin (37%), gentamicin (32%), and colistin sulfate (21%). A large proportion of E. coli demonstrated multi-drug resistance (MDR). Most (84%) of the tetracycline-resistant isolates encoded tetA. Of the remaining isolates, 0.5% encoded tetC, 6.0% encoded two genes, and 3.6% of isolates were tetD, which was newly identified by this study in Bangladesh. Broiler products in Bangladesh are frequently contaminated with multi-drug-resistant E. coli, with differential carriage of tetracycline genes. The prevalence of tetracycline resistance among E. coli indicates a concern for poultry health and welfare regarding the management of colibacillosis. It also indicates growing public health risks of AMR among broiler-associated pathogens, which can be transferred to humans via the food chain. Appropriate control measures should be developed and implemented, focused on the rational use of antimicrobials in poultry farming systems, to mitigate risk from this drug-resistant zoonotic pathogen from foods of animal origin and to protect public health. Full article

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

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20 pages, 1202 KiB

Open AccessReview

Bacteriophage Therapy as an Application for Bacterial Infection in China

by Shuang Liang, Yanling Qi, Huabo Yu, Wuwen Sun, Sayed Haidar Abbas Raza, Nada Alkhorayef, Samia S. Alkhalil, Essam Eldin Abdelhady Salama and Lei Zhang

Antibiotics 2023, 12(2), 417; https://doi.org/10.3390/antibiotics12020417 - 20 Feb 2023

Cited by 6 | Viewed by 3976

Abstract

Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics [...] Read more.

Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics of phage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment. The data showed that phage had a good therapeutic effect on drug-resistant bacteria in veterinary fields, as well as in the clinical treatment of humans. However, we need to take more consideration of the narrow lysis spectrum, the immune response, the issues of storage, and the pharmacokinetics of phages. Due to the particularity of bacteriophage as a bacterial virus, there is no unified standard or regulation for the use of bacteriophage in the world at present, which hinders the application of bacteriophage as a substitute for antibiotic biological products. We aimed to highlight the rapidly advancing field of phage therapy as well as the challenges that China faces in reducing its reliance on antibiotics. Full article

(This article belongs to the Special Issue Insights into Antibiotics in Human, Animal, and Agriculture: Resistance, Determinant, and Treatment)

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11 pages, 1404 KiB

Open AccessArticle

Quinolone Resistance Genes and Their Contribution to Resistance in Vibrio cholerae Serogroup O139

by Yan-Yan Zhou, Li-Yan Ma, Li Yu, Xin Lu, Wei-Li Liang, Biao Kan and Jian-Rong Su

Antibiotics 2023, 12(2), 416; https://doi.org/10.3390/antibiotics12020416 - 20 Feb 2023

Cited by 2 | Viewed by 1530

Abstract

Background. Quinolones are commonly used for reducing the duration of diarrhea, infection severity, and limiting further transmission of disease related to Vibrio cholerae, but V. cholerae susceptibility to quinolone decreases over time. In addition to mutations in the quinolone-resistance determining regions (QRDRs), [...] Read more.

Background. Quinolones are commonly used for reducing the duration of diarrhea, infection severity, and limiting further transmission of disease related to Vibrio cholerae, but V. cholerae susceptibility to quinolone decreases over time. In addition to mutations in the quinolone-resistance determining regions (QRDRs), the presence of qnr and other acquired genes also contributes to quinolone resistance. Results. We determined the prevalence of quinolone resistance related genes among V. cholerae O139 strains isolated in China. We determined that eight strains carried qnrVC, which encodes a pentapeptide repeat protein of the Qnr subfamily, the members of which protect topoisomerases from quinolone action. Four qnrVC alleles were detected: qnrVC1, qnrVC5, qnrVC12, and qnrVC9. However, the strains carrying qnrVC1, qnrVC5, and qnrVC12 were ciprofloxacin (CIP)-sensitive. Contrastingly, the strain carrying qnrVC9 demonstrated high CIP resistance. qnrVC9 was carried by a small plasmid, which was conjugative and contributed to the high CIP resistance to the receptor V. cholerae strain. The same plasmid was also detected in V. vulnificus. The qnrVC1, qnrVC5, and qnrVC12 were cloned into expression plasmids and conferred CIP resistance on the host V. cholerae O139 strain. Conclusions. Our results revealed the contribution of quinolone resistance mediated by the qnrVC9 carried on the small plasmid and its active horizontal transfer among Vibrio species. The results also suggested the different effects of qnrVC alleles in different V. cholerae strains, which is possibly due to differences in sequences of qnrVC alleles and even the genetic characteristics of the host strains. Full article

(This article belongs to the Special Issue Frontier of Antibiotics in China)

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14 pages, 8772 KiB

Open AccessArticle

Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells

by Mengyao Li, Mohammad A. K. Azad, Philip E. Thompson, Kade D. Roberts, Tony Velkov, Yan Zhu and Jian Li

Antibiotics 2023, 12(2), 415; https://doi.org/10.3390/antibiotics12020415 - 20 Feb 2023

Viewed by 1565

Abstract

Polymyxins are last-line antibiotics for the treatment of Gram-negative ‘superbugs’. However, nephrotoxicity can occur in up to 60% of patients administered intravenous polymyxins. The mechanisms underpinning nephrotoxicity remain unclear. To understand polymyxin-induced nephrotoxicity, human renal proximal tubule cells were treated for 24 h [...] Read more.

Polymyxins are last-line antibiotics for the treatment of Gram-negative ‘superbugs’. However, nephrotoxicity can occur in up to 60% of patients administered intravenous polymyxins. The mechanisms underpinning nephrotoxicity remain unclear. To understand polymyxin-induced nephrotoxicity, human renal proximal tubule cells were treated for 24 h with 0.1 mM polymyxin B or two new analogues, FADDI-251 or FADDI-287. Transcriptomic analysis was performed, and differentially expressed genes (DEGs) were identified using ANOVA (FDR < 0.2). Cell viability following treatment with polymyxin B, FADDI-251 or FADDI-287 was 66.0 ± 5.33%, 89.3 ± 3.96% and 90.4 ± 1.18%, respectively. Transcriptomics identified 430, 193 and 150 DEGs with polymyxin B, FADDI-251 and FADDI-287, respectively. Genes involved with metallothioneins and Toll-like receptor pathways were significantly perturbed by all polymyxins. Only polymyxin B induced perturbations in signal transduction, including FGFR2 and MAPK signaling. SIGNOR network analysis showed all treatments affected essential regulators in the immune system, autophagy, cell cycle, oxidative stress and apoptosis. All polymyxins caused significant perturbations of metal homeostasis and TLR signaling, while polymyxin B caused the most dramatic perturbations of the transcriptome. This study reveals the impact of polymyxin structure modifications on transcriptomic responses in human renal tubular cells and provides important information for designing safer new-generation polymyxins. Full article

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18 pages, 2303 KiB

Open AccessArticle

Evaluation of Commercial Anti-Listerial Products for Improvement of Food Safety in Ready-to-Eat Meat and Dairy Products

by Pilar Colás-Medà, Inmaculada Viñas and Isabel Alegre

Antibiotics 2023, 12(2), 414; https://doi.org/10.3390/antibiotics12020414 - 20 Feb 2023

Cited by 1 | Viewed by 1708

Abstract

In ready-to-eat products, such as cooked ham, fresh cheese, and fuet in which Listeria monocytogenes is a concern, the use of biopreservation techniques represents an additional hurdle to inhibit pathogen growth during storage. The objective of this study was to apply several biopreservation [...] Read more.

In ready-to-eat products, such as cooked ham, fresh cheese, and fuet in which Listeria monocytogenes is a concern, the use of biopreservation techniques represents an additional hurdle to inhibit pathogen growth during storage. The objective of this study was to apply several biopreservation techniques in three different food matrices to reduce the growth of Listeria innocua, used as a surrogate of L. monocytogenes. Several lactic acid bacteria, the bacteriocin nisin, the bacteriophage PhageGuard Listex^TM P100, and the enzyme lysozyme were evaluated. Cooked ham treated with the bacteriophage PhageGuard Listex^TM at 0.5% or with the lactic acid bacteria SafePro^® B-SF-43 (25 g/100 kg) reduced L. innocua population to below the detection limit after 7 days of storage (4 °C plus modified atmosphere packaging). In fresh cheese, the application of PhageGuard Listex^TM at 0.2 and 0.5% reduced L. innocua counts by more than 3.4 logarithmic units after 6 days at 4 °C. In fuet, the 1.0% of PhageGuard Listex^TM reduced L. innocua population by 0.7 ± 0.2 logarithmic units in front of control with no significant differences to other evaluated biopreservative agents. The present results confirm that the application of biopreservation techniques was able to inhibit L. innocua in fuet, cooked ham, and fresh cheese, and suggest that the type of food matrix and its physicochemical characteristics influence the biopreservative efficacy. Full article

(This article belongs to the Special Issue Detection and Control of Pathogens in Food Production)

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12 pages, 662 KiB

Open AccessReview

Ventilator-Associated Pneumonia in Immunosuppressed Patients

by Louis Kreitmann, Alexandre Gaudet and Saad Nseir

Antibiotics 2023, 12(2), 413; https://doi.org/10.3390/antibiotics12020413 - 20 Feb 2023

Cited by 3 | Viewed by 3121

Abstract

Immunocompromised patients—including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases—account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and [...] Read more.

Immunocompromised patients—including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases—account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT). Recent studies have shed light on some of the specific features of VAP and VAT in immunocompromised patients, which is the subject of this narrative review. Contrary to previous belief, the incidence of VAP and VAT might actually be lower in immunocompromised than non-immunocompromised patients. Further, the relationship between immunosuppression and the incidence of VAP and VAT related to multidrug-resistant (MDR) bacteria has also been challenged recently. Etiological diagnosis is essential to select the most appropriate treatment, and the role of invasive sampling, specifically bronchoscopy with bronchoalveolar lavage, as well as new molecular syndromic diagnostic tools will be discussed. While bacteria—especially gram negative bacteria—are the most commonly isolated pathogens in VAP and VAT, several opportunistic pathogens are a special concern among immunocompromised patients, and must be included in the diagnostic workup. Finally, the impact of immunosuppression on VAP and VAT outcomes will be examined in view of recent papers using improved statistical methodologies and treatment options—more specifically empirical antibiotic regimens—will be discussed in light of recent findings on the epidemiology of MDR bacteria in this population. Full article

(This article belongs to the Special Issue Antibiotic Based Strategies for Prevention or Therapy of MDR Pneumonia)

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21 pages, 3286 KiB

Open AccessArticle

A Novel Strategy for the Design of Aurein 1.2 Analogs with Enhanced Bioactivities by Conjunction of Cell-Penetrating Regions

by Fengting Liao, Yuping Chen, Anmei Shu, Xiaoling Chen, Tao Wang, Yangyang Jiang, Chengbang Ma, Mei Zhou, Tianbao Chen, Chris Shaw and Lei Wang

Antibiotics 2023, 12(2), 412; https://doi.org/10.3390/antibiotics12020412 - 19 Feb 2023

Cited by 1 | Viewed by 1642

Abstract

The rational design modification of membrane-active peptide structures by introducing additional membrane-penetrating regions has become a good strategy for the improvement of action and potency. Aurein 1.2 (GLFDIIKKIAESF-NH₂) is a multifunctional antimicrobial peptide isolated from the green and golden bell frog, [...] Read more.

The rational design modification of membrane-active peptide structures by introducing additional membrane-penetrating regions has become a good strategy for the improvement of action and potency. Aurein 1.2 (GLFDIIKKIAESF-NH₂) is a multifunctional antimicrobial peptide isolated from the green and golden bell frog, Litoria aurea, and the southern bell frog Litoria raniformis skin secretions. Its bio-functionality has been widely investigated. However, its lack of a potent action failed to provide aurein 1.2 with a competitive edge for further development as a therapeutic agent for clinical use. Herein, aurein 1.2 was chosen as a template for rational modification to achieve a more potent bio-functionality. KLA-2 (GLFDIIKKLAKLAESF-NH₂), which a double KLA region inserted into the sequence, presented a 2–16-fold enhancement of antimicrobial activity, a 2–8-fold greater anti-biofilm activity (including biofilm prevention and eradication), and a 7-fold more potent anti-proliferation activity and hence was regarded as the most broad-spectrum active peptide. Additionally, with respect to antimicrobial activity, the IIKK-modified analog, IK-3 (GLFDIIKKIIKKIIKKI-NH₂), also demonstrated a potent enhancement of activity against various pathogens, exhibiting a 2–8-fold enhanced activity compared to the parent peptide. Moreover, the selectivities of KLA-1 and KLA-2 were enhanced significantly. In conclusion, peptide modification, through the introduction of additional membrane penetrating regions, can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development. Full article

(This article belongs to the Special Issue Design, Synthesis, and Application of Antimicrobial Peptides)

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9 pages, 550 KiB

Open AccessArticle

Antimicrobial Consumption in the Livestock Sector in Bhutan: Volumes, Values, Rates, and Trends for the Period 2017–2021

by Ratna B. Gurung, Karma P. Zangmo, James R. Gilkerson, Glenn F. Browning, Angeline S. Ferdinand and Mauricio J. C. Coppo

Antibiotics 2023, 12(2), 411; https://doi.org/10.3390/antibiotics12020411 - 18 Feb 2023

Cited by 1 | Viewed by 1387

Abstract

Data on the use of antimicrobials in humans and livestock may provide evidence to guide policy changes to mitigate the risk of antimicrobial resistance (AMR). However, there is limited information available about antimicrobial use in livestock in low- and middle-income countries, even though [...] Read more.

Data on the use of antimicrobials in humans and livestock may provide evidence to guide policy changes to mitigate the risk of antimicrobial resistance (AMR). However, there is limited information available about antimicrobial use in livestock in low- and middle-income countries, even though these nations are most vulnerable to the impact of AMR. This study aimed to assess the consumption of veterinary antimicrobials in Bhutan and identify areas for improvement to reduce the use of antimicrobials in livestock. National data on livestock numbers and annual procurement of veterinary antimicrobials over five years (2017–2021) were used to calculate rates of antimicrobial consumption and annual national expenditure on veterinary antimicrobials in Bhutan. The rate of antimicrobial consumption in Bhutan was 3.83 mg per population correction unit, which is lower than most countries in Europe, comparable with the rates of consumption in Iceland and Norway, and approximately 120-fold lower than published rates of antimicrobial consumption in South Asian countries, including Nepal and Pakistan. The low rates of antimicrobial consumption by the animal health sector in Bhutan could be attributable to stronger governance of antimicrobial use in Bhutan, higher levels of compliance with regulation, and better adherence to standard guidelines for antimicrobial treatment of livestock. Full article

(This article belongs to the Special Issue Antibiotics Use in Farms)

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18 pages, 2358 KiB

Open AccessArticle

Genotypic Diversity, Antibiotic Resistance, and Virulence Phenotypes of Stenotrophomonas maltophilia Clinical Isolates from a Thai University Hospital Setting

by Orathai Yinsai, Manu Deeudom and Kwanjit Duangsonk

Antibiotics 2023, 12(2), 410; https://doi.org/10.3390/antibiotics12020410 - 18 Feb 2023

Cited by 4 | Viewed by 1673

Abstract

Stenotrophomonas maltophilia is a multidrug-resistant organism that is emerging as an important opportunistic pathogen. Despite this, information on the epidemiology and characteristics of this bacterium, especially in Thailand, is rarely found. This study aimed to determine the demographic, genotypic, and phenotypic characteristics of [...] Read more.

Stenotrophomonas maltophilia is a multidrug-resistant organism that is emerging as an important opportunistic pathogen. Despite this, information on the epidemiology and characteristics of this bacterium, especially in Thailand, is rarely found. This study aimed to determine the demographic, genotypic, and phenotypic characteristics of S. maltophilia isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand. A total of 200 S. maltophilia isolates were collected from four types of clinical specimens from 2015 to 2016 and most of the isolates were from sputum. In terms of clinical characteristics, male and aged patients were more susceptible to an S. maltophilia infection. The majority of included patients had underlying diseases and were hospitalized with associated invasive procedures. The antimicrobial resistance profiles of S. maltophilia isolates showed the highest frequency of resistance to ceftazidime and the lower frequency of resistance to chloramphenicol, levofloxacin, trimethoprim/sulfamethoxazole (TMP/SMX), and no resistance to minocycline. The predominant antibiotic resistance genes among the 200 isolates were the smeF gene (91.5%), followed by bla_L1 and bla_L2 genes (43% and 10%), respectively. Other antibiotic resistance genes detected were floR (8.5%), intI1 (7%), sul1 (6%), mfsA (4%) and sul2 (2%). Most S. maltophilia isolates could produce biofilm and could swim in a semisolid medium, however, none of the isolates could swarm. All isolates were positive for hemolysin production, whereas 91.5% and 22.5% of isolates could release protease and lipase enzymes, respectively. In MLST analysis, a high degree of genetic diversity was observed among the 200 S. maltophilia isolates. One hundred and forty-one sequence types (STs), including 130 novel STs, were identified and categorized into six different clonal complex groups. The differences in drug resistance patterns and genetic profiles exhibited various phenotypes of biofilm formation, motility, toxin, and enzymes production which support this bacterium in its virulence and pathogenicity. This study reviewed the characteristics of genotypes and phenotypes of S. maltophilia from Thailand which is necessary for the control and prevention of S. maltophilia local spreading. Full article

(This article belongs to the Special Issue Insights into Antibiotics in Human, Animal, and Agriculture: Resistance, Determinant, and Treatment)

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11 pages, 430 KiB

Open AccessSystematic Review

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review

by Qin Xiang Ng, Natasha Yixuan Ong, Dawn Yi Xin Lee, Chun En Yau, Yu Liang Lim, Andrea Lay Hoon Kwa and Ban Hock Tan

Antibiotics 2023, 12(2), 409; https://doi.org/10.3390/antibiotics12020409 - 18 Feb 2023

Cited by 15 | Viewed by 3113

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed [...] Read more.

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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13 pages, 1499 KiB

Open AccessArticle

Genomic Evidence for Direct Transmission of mecC-MRSA between a Horse and Its Veterinarian

by Ervin Albert, Judit Sahin-Tóth, Andrea Horváth, Márton Papp, Imre Biksi and Orsolya Dobay

Antibiotics 2023, 12(2), 408; https://doi.org/10.3390/antibiotics12020408 - 17 Feb 2023

Cited by 5 | Viewed by 1796

Abstract

Methicillin-resistant Staphylococcus aureus bearing the mecC gene (mecC-MRSA) has been reported from animals and humans in recent years. This study describes the first mecC-MRSA isolates of human and equine origin in Hungary (two isolates from horses and one from a [...] Read more.

Methicillin-resistant Staphylococcus aureus bearing the mecC gene (mecC-MRSA) has been reported from animals and humans in recent years. This study describes the first mecC-MRSA isolates of human and equine origin in Hungary (two isolates from horses and one from a veterinarian, who treated one of the infected horses, but was asymptomatic). MRSA isolates were identified by cultivation and PCR detection of the species-specific spa gene and mecA/mecC methicillin resistance genes. The isolates were characterized by antibiotic susceptibility testing, MLST, spa, SCCmec typing, PFGE and whole genome sequencing (WGS). All three isolates belonged to the ST130-t843-SCCmec XI genotype, and carried the mecC and blaZ genes. Apart from beta-lactam drugs, they were sensitive to all tested antibiotics. The isolates of the infected horse and its veterinarian had the same PFGE pulsotype and showed only slight differences with WGS. Hence, this is the first description of direct transmission of a mecC-carrying MRSA between a horse and its veterinarian. The emergence of mecC in the country highlights the importance of the appropriate diagnostics in MRSA identification. Full article

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

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15 pages, 1645 KiB

Open AccessArticle

Antimicrobial Properties of Bacillus Probiotics as Animal Growth Promoters

by Charlie Tran, Darwin Horyanto, Dragana Stanley, Ian E. Cock, Xiaojing Chen and Yunjiang Feng

Antibiotics 2023, 12(2), 407; https://doi.org/10.3390/antibiotics12020407 - 17 Feb 2023

Cited by 11 | Viewed by 2082 | Correction

Abstract

Antibiotic growth promoters (AGPs) suppress the growth of infectious pathogens. These pathogens negatively impact agricultural production worldwide and often cause health problems if left untreated. Here, we evaluate six Bacillus strains (BPR-11, BPR-12, BPR-13, BPR-14, BPR-16 and BPR-17), which are known for their [...] Read more.

Antibiotic growth promoters (AGPs) suppress the growth of infectious pathogens. These pathogens negatively impact agricultural production worldwide and often cause health problems if left untreated. Here, we evaluate six Bacillus strains (BPR-11, BPR-12, BPR-13, BPR-14, BPR-16 and BPR-17), which are known for their ability to survive harsh environmental conditions, as AGP replacements in animal feed. Four of these Bacillus strains (BPR-11, BPR-14, BPR-16 and BPR-17) showed antimicrobial activity against the pathogenic strains Clostridium perfringens, Escherichia coli and Staphylococcus aureus at 25 μg/mL, with BPR-16 and BPR-17 also able to inhibit Pseudomonas aeruginosa and Salmonella enterica at 100 μg/mL. Further chemical investigation of BPR-17 led to the identification of eight metabolites, namely C16, C15, C14 and C13 surfactin C (1–4), maculosin (5), maculosine 2 (6), genistein (7) and daidzein (8). Purified compounds (1–4) were able to inhibit all the tested pathogens with MIC values ranging from 6.25 to 50 μg/mL. Maculosin (5) and maculosine 2 (6) inhibited C. perfringens, E. coli and S. aureus with an MIC of 25 μg/mL while genistein (7) and daidzein (8) showed no activity. An animal trial involving feeding BPR-11, BPR-16 and BPR-17 to a laboratory poultry model led to an increase in animal growth, and a decrease in feed conversion ratio and mortality. The presence of surfactin C analogues (3–4) in the gut following feeding with probiotics was confirmed using an LC–MS analysis. The investigation of these Bacillus probiotics, their metabolites, their impacts on animal performance indicators and their presence in the gastrointestinal system illustrates that these probiotics are effective alternatives to AGPs. Full article

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

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14 pages, 1802 KiB

Open AccessReview

Subpopulations in Strains of Staphylococcus aureus Provide Antibiotic Tolerance

by Matipaishe Mashayamombe, Miguel Carda-Diéguez, Alex Mira, Robert Fitridge, Peter S. Zilm and Stephen P. Kidd

Antibiotics 2023, 12(2), 406; https://doi.org/10.3390/antibiotics12020406 - 17 Feb 2023

Cited by 2 | Viewed by 1831

Abstract

The ability of Staphylococcus aureus to colonise different niches across the human body is linked to an adaptable metabolic capability, as well as its ability to persist within specific tissues despite adverse conditions. In many cases, as S. aureus proliferates within an anatomical [...] Read more.

The ability of Staphylococcus aureus to colonise different niches across the human body is linked to an adaptable metabolic capability, as well as its ability to persist within specific tissues despite adverse conditions. In many cases, as S. aureus proliferates within an anatomical niche, there is an associated pathology. The immune response, together with medical interventions such as antibiotics, often removes the S. aureus cells that are causing this disease. However, a common issue in S. aureus infections is a relapse of disease. Within infected tissue, S. aureus exists as a population of cells, and it adopts a diversity of cell types. In evolutionary biology, the concept of “bet-hedging” has established that even in positive conditions, there are members that arise within a population that would be present as non-beneficial, but if those conditions change, these traits could allow survival. For S. aureus, some of these cells within an infection have a reduced fitness, are not rapidly proliferating or are the cause of an active host response and disease, but these do remain even after the disease seems to have been cleared. This is true for persistence against immune responses but also as a continual presence in spite of antibiotic treatment. We propose that the constant arousal of suboptimal populations at any timepoint is a key strategy for S. aureus long-term infection and survival. Thus, understanding the molecular basis for this feature could be instrumental to combat persistent infections. Full article

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

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11 pages, 659 KiB

Open AccessArticle

Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome

by Youssef Madney, Shaimaa Aboubakr, Reham Khedr, Hanafy Hafez, Naglaa Ahmed, Khaled Elsheshtawy, Mervat Elanany, Abdelhamid Salahelden, Lobna Shalaby and Ola Galal Behairy

Antibiotics 2023, 12(2), 405; https://doi.org/10.3390/antibiotics12020405 - 17 Feb 2023

Cited by 4 | Viewed by 2158

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children’s cancer hospital in Egypt (2013–2017). Two hundred and fifty-four pediatric [...] Read more.

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children’s cancer hospital in Egypt (2013–2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4–8 μg/mL in 100 (45%) and >8 μg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 μg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups. Full article

(This article belongs to the Special Issue Carbapenem-Resistant Organisms (CRO) as Leading Cause of Hospital Associated Infections)

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18 pages, 1712 KiB

Open AccessEditor’s ChoiceArticle

Investigation of α,ω-Disubstituted Polyamine-Cholic Acid Conjugates Identifies Hyodeoxycholic and Chenodeoxycholic Scaffolds as Non-Toxic, Potent Antimicrobials

by Kenneth Sue, Melissa M. Cadelis, Thomas Troia, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel and Brent R. Copp

Antibiotics 2023, 12(2), 404; https://doi.org/10.3390/antibiotics12020404 - 17 Feb 2023

Cited by 1 | Viewed by 1259

Abstract

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic [...] Read more.

With the increased incidence of antibiotic resistance, the discovery and development of new antibacterials is of increasing importance and urgency. The report of the natural product antibiotic squalamine in 1993 has stimulated a lot of interest in the study of structurally simplified cholic acid-polyamine derivatives. We report the synthesis of a focused set of deoxycholic acid-polyamine conjugates and the identification of hyodeoxycholic acid derivatives as being potently active towards S. aureus MRSA and some fungal strains, but with no attendant cytotoxicity or hemolytic properties. Analogue 7e exhibited bactericidal activity towards a range of Gram-positive bacteria, while preliminary investigation of its mechanism of action ruled out the bacterial membrane as being a primary cellular target as determined using an ATP-release bioluminescence assay. Full article

(This article belongs to the Special Issue Discovery and Development of the Novel Antimicrobial Agent)

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22 pages, 4586 KiB

Open AccessArticle

ABC Transporters and CYP3A4 Mediate Drug Interactions between Enrofloxacin and Salinomycin Leading to Increased Risk of Drug Residues and Resistance

by Min Chen, Yujuan Yang, Yupeng Ying, Jiamin Huang, Mengyuan Sun, Mian Hong, Haizhen Wang, Shuyu Xie and Dongmei Chen

Antibiotics 2023, 12(2), 403; https://doi.org/10.3390/antibiotics12020403 - 17 Feb 2023

Cited by 1 | Viewed by 1646

Abstract

Enrofloxacin (ENR) is one of the most common drugs used in poultry production to treat bacterial diseases, and there is a high risk of drug interactions (DDIs) between polyether anticoccidial drugs added to poultry feed over time. This may affect the efficacy of [...] Read more.

Enrofloxacin (ENR) is one of the most common drugs used in poultry production to treat bacterial diseases, and there is a high risk of drug interactions (DDIs) between polyether anticoccidial drugs added to poultry feed over time. This may affect the efficacy of antibiotics or lead to toxicity, posing a potential risk to the environment and food safety. This study aimed to investigate the DDI of ENR and salinomycin (SAL) in broilers and the mechanism of their DDI. We found that SAL increased the area under the curve and elimination half-life of ENR and ciprofloxacin (CIP) by 1.3 and 2.4 times, 1.2 and 2.5 times, respectively. Cytochrome 3A4 (CYP3A4), p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were important factors for the DDI between ENR and SAL in broilers. ENR and SAL are substrates of CYP3A4, P-gp and BCRP in broilers; ENR and SAL inhibited the expression of CYP3A4 activity in a time- and concentration-dependent. Meanwhile, ENR downregulated the expression of P-gp and BCRP in a time- and concentration-dependent manner. A single oral administration of SAL inhibited CYP3A4, P-gp, and BCRP, but long-term mixed feeding upregulated the expression of CYP3A4, P-gp, and BCRP. Molecular docking revealed that ENR and SAL compete with each other for CYP3A4 to affect hepatic metabolism, and compete with ATP for P-gp and BCRP binding sites to inhibit efflux. ENR and SAL in broilers can lead to severe DDI. Drug residues and resistance following co-administration of ENR and SAL and other SAL-based drug-feed interactions warrant further study. Full article

(This article belongs to the Special Issue Pharmacokinetics/Pharmacodynamics Analysis of Veterinary Antimicrobial Agents)

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19 pages, 1097 KiB

Open AccessFeature PaperReview

Overview of Virulence and Antibiotic Resistance in Campylobacter spp. Livestock Isolates

by Iulia Adelina Bunduruș, Igori Balta, Lavinia Ștef, Mirela Ahmadi, Ioan Peț, David McCleery and Nicolae Corcionivoschi

Antibiotics 2023, 12(2), 402; https://doi.org/10.3390/antibiotics12020402 - 17 Feb 2023

Cited by 13 | Viewed by 3258

Abstract

Campylobacter remains the most prevalent foodborne pathogen bacterium responsible for causing gastroenteritis worldwide. Specifically, this pathogen colonises a ubiquitous range of environments, from poultry, companion pets and livestock animals to humans. The bacterium is uniquely adaptable to various niches, leading to complicated gastroenteritis [...] Read more.

Campylobacter remains the most prevalent foodborne pathogen bacterium responsible for causing gastroenteritis worldwide. Specifically, this pathogen colonises a ubiquitous range of environments, from poultry, companion pets and livestock animals to humans. The bacterium is uniquely adaptable to various niches, leading to complicated gastroenteritis and, in some cases, difficult to treat due to elevated resistance to certain antibiotics. This increased resistance is currently detected via genomic, clinical or epidemiological studies, with the results highlighting worrying multi-drug resistant (MDR) profiles in many food and clinical isolates. The Campylobacter genome encodes a rich inventory of virulence factors offering the bacterium the ability to influence host immune defences, survive antimicrobials, form biofilms and ultimately boost its infection-inducing potential. The virulence traits responsible for inducing clinical signs are not sufficiently defined because several populations have ample virulence genes with physiological functions that reflect their pathogenicity differences as well as a complement of antimicrobial resistance (AMR) systems. Therefore, exhaustive knowledge of the virulence factors associated with Campylobacter is crucial for collecting molecular insights into the infectivity processes, which could pave the way for new therapeutical targets to combat and control the infection and mitigate the spread of MDR bacteria. This review provides an overview of the spread and prevalence of genetic determinants associated with virulence and antibiotic resistance from studies performed on livestock animals. In addition, we have investigated the relevant coincidental associations between the prevalence of the genes responsible for pathogenic virulence, horizontal gene transfer (HGT) and transmissibility of highly pathogenic Campylobacter strains. Full article

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11 pages, 2111 KiB

Open AccessArticle

Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action

by Carmen-Ecaterina Leferman, Laura Stoica, Bogdan Alexandru Stoica, Alin Dumitru Ciubotaru, Aida Corina Badescu, Camelia-Margareta Bogdanici, Tiberiu Paul Neagu and Cristina-Mihaela Ghiciuc

Antibiotics 2023, 12(2), 401; https://doi.org/10.3390/antibiotics12020401 - 16 Feb 2023

Cited by 6 | Viewed by 1708

Abstract

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The [...] Read more.

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative. Full article

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19 pages, 2587 KiB

Open AccessArticle

Surveillance on ESBL-Escherichia coli and Indicator ARG in Wastewater and Reclaimed Water of Four Regions of Spain: Impact of Different Disinfection Treatments

by Márcia Oliveira, Pilar Truchado, Rebeca Cordero-García, María I. Gil, Manuel Abellán Soler, Amador Rancaño, Francisca García, Avelino Álvarez-Ordóñez and Ana Allende

Antibiotics 2023, 12(2), 400; https://doi.org/10.3390/antibiotics12020400 - 16 Feb 2023

Cited by 2 | Viewed by 1992

Abstract

In the present study, the occurrence of indicator antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) both in the influent and the effluent of four Spanish wastewater treatment plants (WWTPs) was monitored for 12 months, and the susceptibility profiles of 89 recovered extended [...] Read more.

In the present study, the occurrence of indicator antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) both in the influent and the effluent of four Spanish wastewater treatment plants (WWTPs) was monitored for 12 months, and the susceptibility profiles of 89 recovered extended spectrum β-lactamase (ESBL)-producing Escherichia coli isolates were obtained against a wide range of antimicrobials. The aim of the study was to better understand whether the current wastewater treatment practices allow us to obtain safe reclaimed water mitigating the spread of ARB and ARGs to the environment. Results showed high concentrations of ESBL-producing E. coli as well as a high prevalence of a range of ARGs in the influent samples. The reclamation treatments implemented in the WWTPs were effective in reducing both the occurrence of ESBL E. coli and ARGs, although significant differences were observed among WWTPs. Despite these reductions in occurrence observed upon wastewater treatment, our findings suggest that WWTP effluents may represent an important source of ARGs, which could be transferred among environmental bacteria and disseminate antimicrobial resistance through the food chain. Remarkably, no major differences were observed in the susceptibility profiles of the ESBL E. coli isolated from influent and effluent waters, indicating that water treatments do not give rise to the emergence of new resistance phenotypes. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Food-borne Pathogens)

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19 pages, 1252 KiB

Open AccessReview

Evidence-Based Treatment of Pseudomonas aeruginosa Infections: A Critical Reappraisal

by Arta Karruli, Christian Catalini, Chiara D’Amore, Francesco Foglia, Fabio Mari, Arjan Harxhi, Massimiliano Galdiero and Emanuele Durante-Mangoni

Antibiotics 2023, 12(2), 399; https://doi.org/10.3390/antibiotics12020399 - 16 Feb 2023

Cited by 13 | Viewed by 13545

Abstract

Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due [...] Read more.

Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due to MDR/XDR P. aeruginosa. P. aeruginosa has inherent resistance to many drug classes, the capacity to form biofilms, and most importantly, the ability to quickly acquire resistance to ongoing treatments. Based on the presence of risk factors for MDR/XDR infections and local epidemiology, where large proportions of strains are resistant to classic beta-lactams, the recommended empirical treatment for suspected P. aeruginosa infections is based on ceftolozane-tazobactam or ceftazidime-avibactam. Where local epidemiology indicates low rates of MDR/XDR and there are no risk factors, a third or fourth generation cephalosporin can be used in the context of a “carbapenem-sparing” strategy. Whenever feasible, antibiotic de-escalation is recommended after antimicrobial susceptibility tests suggest that it is appropriate, and de-escalation is based on different resistance mechanisms. Cefiderocol and imipenem-cilastatin-relebactam withstand most resistance mechanisms and may remain active in cases with resistance to other new antibiotics. Confronting the growing threat of MDR/XDR P. aeruginosa, treatment choices should be wise, sparing newer antibiotics when dealing with a suspected/confirmed susceptible P. aeruginosa strain and choosing the right option for MDR/XDR P. aeruginosa based on specific types and resistance mechanisms. Full article

(This article belongs to the Special Issue Emerging Treatment Options for Multidrug-Resistant Bacterial and Fungal Infections)

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23 pages, 5491 KiB

Open AccessReview

Photo-Antibacterial Activity of Two-Dimensional (2D)-Based Hybrid Materials: Effective Treatment Strategy for Controlling Bacterial Infection

by Neetu Talreja, Divya Chauhan and Mohammad Ashfaq

Antibiotics 2023, 12(2), 398; https://doi.org/10.3390/antibiotics12020398 - 16 Feb 2023

Cited by 3 | Viewed by 1887

Abstract

Bacterial contamination in water bodies is a severe scourge that affects human health and causes mortality and morbidity. Researchers continue to develop next-generation materials for controlling bacterial infections from water. Photo-antibacterial activity continues to gain the interest of researchers due to its adequate, [...] Read more.

Bacterial contamination in water bodies is a severe scourge that affects human health and causes mortality and morbidity. Researchers continue to develop next-generation materials for controlling bacterial infections from water. Photo-antibacterial activity continues to gain the interest of researchers due to its adequate, rapid, and antibiotic-free process. Photo-antibacterial materials do not have any side effects and have a minimal chance of developing bacterial resistance due to their rapid efficacy. Photocatalytic two-dimensional nanomaterials (2D-NMs) have great potential for the control of bacterial infection due to their exceptional properties, such as high surface area, tunable band gap, specific structure, and tunable surface functional groups. Moreover, the optical and electric properties of 2D-NMs might be tuned by creating heterojunctions or by the doping of metals/carbon/polymers, subsequently enhancing their photo-antibacterial ability. This review article focuses on the synthesis of 2D-NM-based hybrid materials, the effect of dopants in 2D-NMs, and their photo-antibacterial application. We also discuss how we could improve photo-antibacterials by using different strategies and the role of artificial intelligence (AI) in the photocatalyst and in the degradation of pollutants. Finally, we discuss was of improving the photo-antibacterial activity of 2D-NMs, the toxicity mechanism, and their challenges. Full article

(This article belongs to the Special Issue Synthesis and Biological Activity of Antimicrobial Agents, 2nd Volume)

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15 pages, 2493 KiB

Open AccessSystematic Review

The Role of Antibiotic Prophylaxis in Anastomotic Leak Prevention during Elective Colorectal Surgery: Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Lidia Castagneto-Gissey, Maria Francesca Russo, James Casella-Mariolo, Angelo Serao, Rosa Marcellinaro, Vito D’Andrea, Massimo Carlini and Giovanni Casella

Antibiotics 2023, 12(2), 397; https://doi.org/10.3390/antibiotics12020397 - 16 Feb 2023

Cited by 4 | Viewed by 1866

Abstract

Introduction: Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and [...] Read more.

Introduction: Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and alterations in its composition may be largely to blame for anastomotic insufficiency. The use of specific antibiotics for preoperative large bowel decontamination could significantly influence the rate of ALs. The aim of this study was to systematically assess the various antibiotic prophylactic regimen strategies for primary prevention of ALs during colorectal surgery, in view of the available evidence. Methods: A systematic review of the literature was conducted, and randomized clinical trials (RCTs) analyzing prophylactic antibiotic bowel preparation in colorectal surgery were included. PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from inception through to 30 November 2022. The methodological quality of the included trials was evaluated. The primary outcome was AL rate; secondary outcomes were superficial/deep surgical site infections (SSIs). The PRISMA guidelines were used to carry out the present systematic review. Results: Thirteen RCTs published between 1977 and 2022, with a total of 4334 patients were included in the meta-analysis. Antibiotic prophylaxis was administered orally in 11/13 studies and intravenously in 2 studies. Patients randomly assigned to antibiotic prophylaxis, regardless of the regimen, had a reduced risk of ALs (p = 0.003) compared to mechanical bowel preparation (MBP) alone. The use of antibiotic prophylaxis was also more effective in significantly reducing SSIs (p < 0.001). Conclusions: The evidence points to an advantage of oral antibiotic prophylaxis in terms of AL rate, a significant contributor to perioperative morbidity, mortality, and rising healthcare expenditures. In light of such results, the use of antibiotic prophylaxis should be strongly encouraged prior to colorectal surgery. Full article

(This article belongs to the Special Issue Optimization of Antimicrobial Stewardship in Public Health)

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13 pages, 1982 KiB

Open AccessArticle

Emergence and Evolution of OXA-23-Producing ST46_Pas-ST462_Oxf-KL28-OCL1 Carbapenem-Resistant Acinetobacter baumannii Mediated by a Novel ISAba1-Based Tn7534 Transposon

by Haiyang Liu, Xiaochen Liu, Jintao He, Linghong Zhang, Feng Zhao, Zhihui Zhou, Xiaoting Hua and Yunsong Yu

Antibiotics 2023, 12(2), 396; https://doi.org/10.3390/antibiotics12020396 - 16 Feb 2023

Viewed by 1531

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates of global clone 1 (GC1) and global clone 2 (GC2) have been widely reported. Nevertheless, non-GC1 and non-GC2 CRAB strains have been studied less. In particular, no reports concerning sequence type 46 (ST46_Pas) CRAB strains have [...] Read more.

Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates of global clone 1 (GC1) and global clone 2 (GC2) have been widely reported. Nevertheless, non-GC1 and non-GC2 CRAB strains have been studied less. In particular, no reports concerning sequence type 46 (ST46_Pas) CRAB strains have been described thus far. In this work, the genomic features and possible evolution mechanism of ST46_Pas OXA-23-producing CRAB isolates from clinical specimens are reported for the first time. Antimicrobial susceptibility testing of three ST46_Pas strains revealed identical resistance profiles (resistance to imipenem, meropenem, ciprofloxacin and the combination of cefoperazone/sulbactam at a 2:1 ratio). They were found to belong to ST46_Pas and ST462_Oxf with capsular polysaccharide 28 (KL28) and lipooligosaccharide 1 (OCL1), respectively. Whole-genome sequencing (WGS) revealed that all contained one copy of chromosomal bla_OXA-23, which was located in a novel ISAba1-based Tn7534 composite transposon. In particular, another copy of the Tn7534 composite transposon was identified in an Hgz_103-type plasmid with 9 bp target site duplications (TSDs, ACAACATGC) in the A. baumannii ZHOU strain. As the strains originated from two neighboring intensive care units (ICUs), ST46_Pas OXA-23-producing CRAB strains may have evolved via transposition events or a pdif module. Based on the GenBank database, ST46_Pas strains were collected from various sources; however, most were collected in Hangzhou (China) from 2014 to 2021. Pan-genome analysis revealed 3276 core genes, 0 soft-core genes, 768 shell genes and 443 cloud genes shared among all ST46_Pas strains. In conclusion, the emergence of ST46_Pas CRAB strains might present a new threat to healthcare settings; therefore, effective surveillance is required to prevent further dissemination. Full article

(This article belongs to the Special Issue Pathogenic Bacteria: Genomics, Virulence Factors, and Antibiotic Resistance)

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14 pages, 1202 KiB

Open AccessArticle

Antibiotic Drug Resistance Pattern of Uropathogens in Pediatric Patients in Pakistani Population

by Zakia Iqbal, Ahsan Sattar Sheikh, Anwaar Basheer, Hadiqa tul Hafsa, Mehboob Ahmed, Anjum Nasim Sabri and Samiah Shahid

Antibiotics 2023, 12(2), 395; https://doi.org/10.3390/antibiotics12020395 - 15 Feb 2023

Cited by 1 | Viewed by 1655

Abstract

The common prevalent diseases in the age of 0 to 6 are related to urinary tract infections. If not properly diagnosed, they will lead to urological and nephrological complications. Uropathogens are developing resistance against most drugs and are harder to treat. A study [...] Read more.

The common prevalent diseases in the age of 0 to 6 are related to urinary tract infections. If not properly diagnosed, they will lead to urological and nephrological complications. Uropathogens are developing resistance against most drugs and are harder to treat. A study was done on the inpatients and outpatients of the two hospitals located in Lahore. A total of 39,750 samples that were both male and female were collected. Escherichia and Klebsiella were found in 234 samples based on biochemical characterization, growth on CLED agar, and white blood cell/pus cell (WBC) microscopy. In comparison to males, female samples had a higher number of uropathogens (1:1.29). From the samples of Shaikh Zayed Hospital (SZH), the ratio of Klebsiella to Escherichia (1:1.93) was reported, while this ratio was 1.84:1 from the Children Hospital (CH). The incidence of UTI was higher in the month of September. Randomly selected Escherichia and Klebsiella were verified via a 16S rRNA sequence. Antibiotic resistance profiling of isolated bacterial strains was done against 23 antibiotics. The most efficient antibiotics against Klebsiella and Escherichia were colistin sulphate (100% sensitivity against bacteria from CH; 99.3% against strains from SZH) and polymyxin B (100% sensitivity against strains from SZH; 98.8% against strains from CH). Sensitivity of the total tested strains against meropenem (74%, SZH; 70% CH), Fosfomycin (68%, SZH; 73% CH strains), amikacin (74% SZH; 55% CH), and nitrofurantoin (71% SZH;67% CH) was found, Amoxicillin, ampicillin, and cefuroxime showed 100 to ≥90% resistance and are the least effective. Full article

(This article belongs to the Special Issue Antibiotic Use and Antimicrobial Stewardship for Children in the Emergency Department)

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12 pages, 1314 KiB

Open AccessArticle

Case Study: Using a Shared International Database to Document Veterinary Consumption of Antibiotics in Pakistan

by Mashkoor Mohsin, Umar Farooq, Maria Hartmann, Sandra Brogden, Lothar Kreienbrock and Julia Stoffregen

Antibiotics 2023, 12(2), 394; https://doi.org/10.3390/antibiotics12020394 - 15 Feb 2023

Viewed by 1336

Abstract

In this paper, we present a case study of Pakistan documenting the use of antimicrobial drugs in poultry flocks in the VetCAb-ID database. Unlike other databases, this system allows international users to upload their data directly. Based on expert interviews and a review [...] Read more.

In this paper, we present a case study of Pakistan documenting the use of antimicrobial drugs in poultry flocks in the VetCAb-ID database. Unlike other databases, this system allows international users to upload their data directly. Based on expert interviews and a review of the latest publications on the topic, we provide an alternative approach to harmonizing data collection among countries. This paper will provide impetus to formulate joint requirement documentation for an AMU database on a global level that international users can adapt for their own purposes and projects. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)

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Antibiotics, Volume 12, Issue 2 (February 2023) – 239 articles

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