Antibiotics

13 pages, 1583 KiB

Open AccessArticle

Resilience of Loin Meat Microbiota and of Resistance Genes to a Chlortetracycline Treatment in Weaned Piglets

by Xavier C. Monger, Linda Saucier, Alex-An Gilbert, Sophie Gosselin, Éric Pouliot, Sylvain Fournaise and Antony T. Vincent

Antibiotics 2024, 13(10), 997; https://doi.org/10.3390/antibiotics13100997 - 21 Oct 2024

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Abstract

Objectives: This project studied the impact of a chlortetracycline treatment in weaning piglets on the taxonomy and antibiotic resistance gene (ARG) content of the microbiomes on carcasses and loins. Methods: Two groups of piglets from two farrowing barns with either an average or [...] Read more.

Objectives: This project studied the impact of a chlortetracycline treatment in weaning piglets on the taxonomy and antibiotic resistance gene (ARG) content of the microbiomes on carcasses and loins. Methods: Two groups of piglets from two farrowing barns with either an average or a lower sanitary health status were used. Each group was divided in half: a control group and a treatment group receiving feed supplemented with 660 g of chlortetracycline per tonne for 21 days. The piglets then went through fattening and were sent to the abattoir when they reached the targeted slaughter weight. Results: The microbiomes of the pig carcasses and loins were sampled, and DNA was extracted and sequenced with a whole-genome approach. The microbiomes of the carcasses differed depending on the farrowing barn source in both taxonomical composition and ARG content; however, the microbiomes on the loins were similar, regardless of the farrowing barn source and the treatment group. Conclusions: While there were differences in the carcass microbiomes between treatments after processing by the abattoir, the loin microbiomes were consistent and unaffected by treatment with chlortetracycline or the sanitary status of the farrowing barn. Full article

(This article belongs to the Special Issue Antibiotics Use in Farms, 2nd Edition)

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23 pages, 926 KiB

Open AccessReview

The Synergy of Machine Learning and Epidemiology in Addressing Carbapenem Resistance: A Comprehensive Review

by Aikaterini Sakagianni, Christina Koufopoulou, Petros Koufopoulos, Georgios Feretzakis, Dimitris Kalles, Evgenia Paxinou, Pavlos Myrianthefs and Vassilios S. Verykios

Antibiotics 2024, 13(10), 996; https://doi.org/10.3390/antibiotics13100996 - 21 Oct 2024

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Abstract

Background/Objectives: Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one of the last lines of antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability to combat resistant pathogens. This review aims [...] Read more.

Background/Objectives: Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one of the last lines of antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability to combat resistant pathogens. This review aims to explore the integration of machine learning (ML) and epidemiological approaches to understand, predict, and combat carbapenem-resistant pathogens. It examines how leveraging large datasets and advanced computational techniques can identify patterns, predict outbreaks, and inform targeted intervention strategies. Methods: The review synthesizes current knowledge on the mechanisms of carbapenem resistance, highlights the strengths and limitations of traditional epidemiological methods, and evaluates the transformative potential of ML. Real-world applications and case studies are used to demonstrate the practical benefits of combining ML and epidemiology. Technical and ethical challenges, such as data quality, model interpretability, and biases, are also addressed, with recommendations provided for overcoming these obstacles. Results: By integrating ML with epidemiological analysis, significant improvements can be made in predictive accuracy, identifying novel patterns in disease transmission, and designing effective public health interventions. Case studies illustrate the benefits of interdisciplinary collaboration in tackling carbapenem resistance, though challenges such as model interpretability and data biases must be managed. Conclusions: The combination of ML and epidemiology holds great promise for enhancing our capacity to predict and prevent carbapenem-resistant infections. Future research should focus on overcoming technical and ethical challenges to fully realize the potential of these approaches. Interdisciplinary collaboration is key to developing sustainable strategies to combat antimicrobial resistance (AMR), ultimately improving patient outcomes and safeguarding public health. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens)

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14 pages, 680 KiB

Open AccessReview

Gut Microbiota and New Microbiome-Targeted Drugs for Clostridioides difficile Infections

by Ahran Lee, Jung Sik Yoo and Eun-Jeong Yoon

Antibiotics 2024, 13(10), 995; https://doi.org/10.3390/antibiotics13100995 - 20 Oct 2024

Cited by 1 | Viewed by 2168

Abstract

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, [...] Read more.

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice. Full article

(This article belongs to the Special Issue Antibiotic-Associated Dysbiosis and Management)

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25 pages, 1091 KiB

Open AccessEditor’s ChoiceArticle

Combinations of Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry

by Gagan Tiwana, Ian Edwin Cock and Matthew James Cheesman

Antibiotics 2024, 13(10), 994; https://doi.org/10.3390/antibiotics13100994 - 19 Oct 2024

Cited by 1 | Viewed by 1376

Abstract

Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates [...] Read more.

Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against Escherichia coli and an extended spectrum β-lactamase (ESBL) E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited Klebsiella pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study. Full article

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

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14 pages, 2115 KiB

Open AccessArticle

Pharmacokinetics of Vancomycin in Healthy Korean Volunteers and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients with Normal Renal Function

by Yong Kyun Kim, Doy Kim, Gaeun Kang, Dae Young Zang and Dong-Hwan Lee

Antibiotics 2024, 13(10), 993; https://doi.org/10.3390/antibiotics13100993 - 19 Oct 2024

Viewed by 1102

Abstract

Background/Objectives: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the [...] Read more.

Background/Objectives: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration–time curve (AUC) in adult patients with normal renal function. Methods: We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling. The population PK parameters derived were employed in Monte Carlo simulations to evaluate the adequacy of the current dosing regimen and to formulate dosing recommendations. Results: The PK profiles were optimally described by a two-compartment model, with body weight and age as significant covariates affecting total clearance. The simulations indicated that to achieve a therapeutic target—defined as an AUC at steady-state over 24 h of 400–600 mg·h/L—daily doses ranging from 60 to 70 mg/kg are necessary in adults with normal renal function. Conclusions: This study underscores the need to actively adjust dosage and administration based on a vancomycin PK model that adequately reflects the demographic characteristics of patients to meet both safety and efficacy standards. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Optimizing Antibiotic Dose in Critically Ill Patients)

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17 pages, 8873 KiB

Open AccessArticle

Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against Staphylococcus aureus

by Rita Morigi, Daniele Esposito, Matteo Calvaresi, Tainah Dorina Marforio, Giovanna Angela Gentilomi, Francesca Bonvicini and Alessandra Locatelli

Antibiotics 2024, 13(10), 992; https://doi.org/10.3390/antibiotics13100992 - 19 Oct 2024

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Abstract

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against Staphylococcus aureus was demonstrated [...] Read more.

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against Staphylococcus aureus was demonstrated for a subset of compounds (range: 13.8–90.1 µM) in the absence of toxicity towards epithelial cells and human red blood cells. The best performing derivative was further investigated to measure its anti-biofilm potential and its effectiveness against methicillin-resistant Staphylococcus aureus strains. A structure–activity relationship study of the synthesized molecules led to the recognition of some important structural requirements for the observed antibacterial activity. Molecular docking followed by molecular dynamics (MD) simulations identified the binding site of the active compound FtsZ, a key protein in bacterial cell division, and the mechanism of action, i.e., the inhibition of its polymerization. The overall results may pave the way for a further rational development of isatin hybrids as FtsZ inhibitors, with a broader spectrum of activity against human pathogens and higher potency. Full article

(This article belongs to the Special Issue Discovery and Design of New Antimicrobial Agents)

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12 pages, 249 KiB

Open AccessReview

Antibiotic Prophylaxis and Treatment for Cardiac Device Infections

by Claudio Pandozi, Andrea Matteucci, Carlo Pignalberi, Luca Sgarra, Michela Bonanni, Marco Valerio Mariani, Vincenzo Mirco La Fazia, Lorenzo Nesti, Stefania Angela Di Fusco, Federico Nardi and Furio Colivicchi

Antibiotics 2024, 13(10), 991; https://doi.org/10.3390/antibiotics13100991 - 18 Oct 2024

Viewed by 1905

Abstract

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing [...] Read more.

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship for Surgical Antibiotic Prophylaxis and Surgical Site Infections)

11 pages, 2366 KiB

Open AccessArticle

Ceftazidime–Avibactam Versus Polymyxin-Based Combination Therapies: A Study on 30-Day Mortality in Carbapenem-Resistant Enterobacterales Bloodstream Infections in an OXA-48-Endemic Region

by Rıdvan Dumlu, Meyha Şahin, Okan Derin, Özlem Gül, Sedef Başgönül, Rehile Zengin, Çiğdem Arabacı, Funda Şimşek, Serap Gençer, Ayşe Sesin Kocagöz and Ali Mert

Antibiotics 2024, 13(10), 990; https://doi.org/10.3390/antibiotics13100990 - 18 Oct 2024

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Abstract

Background: Ceftazidime–avibactam (CAZ-AVI) is recommended as first-line treatment for Oxacillinase-48 (OXA-48) β-Lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, while polymyxin-based combination therapies (PBCTs) are used as a last resort when CAZ-AVI is unavailable. Research comparing the effectiveness of CAZ-AVI and PBCT in CRE blood [...] Read more.

Background: Ceftazidime–avibactam (CAZ-AVI) is recommended as first-line treatment for Oxacillinase-48 (OXA-48) β-Lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, while polymyxin-based combination therapies (PBCTs) are used as a last resort when CAZ-AVI is unavailable. Research comparing the effectiveness of CAZ-AVI and PBCT in CRE blood stream infections (CRE-BSIs) is limited, mostly focusing on Klebsiella pneumoniae carbapenemase (KPC)-producing isolates. In Turkey, OXA-48 is endemic and OXA-48-Like is common. Therefore, our study aimed to compare the impact of these treatments on 30-day mortality in patients with CRE-BSIs in endemic regions. Methods: Retrospective data from January 2019 to May 2023 were collected from four tertiary healthcare centers in Istanbul. Demographic, clinical, and outcome data of ICU patients treated with CAZ-AVI monotherapy or PBCT for CRE-BSIs were analyzed. The effect on 30-day survival was evaluated using Cox regression analysis post propensity score matching (PSM). Results: Out of 151 patients, 44.4% (n: 67) received CAZ-AVI and 55.6% (n: 84) received PBCT. All-cause mortality rates were 20% (n: 13) with CAZ-AVI and 36.9% (n: 31) with PBCT. Cox regression analysis post PSM indicated CAZ-AVI monotherapy significantly reduced the mortality risk compared to PBCT (HR: 0.16, 95%CI: 0.07–0.37, p < 0.001), while age increased the risk (HR: 1.02 per year, 95% CI 1.0–1.04, p: 0.01). Conclusions: In OXA-48-predominant areas, CAZ-AVI demonstrated significantly lower mortality in patients with CRE-BSIs compared to PBCT. The results were attributed to the pharmacokinetic and pharmacodynamic disadvantages of polymyxins compared to CAZ-AVI, and the impact of age-related physical conditions. Therefore, CAZ-AVI should be the preferred treatment for CRE-BSIs in OXA-48-endemic regions. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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13 pages, 2230 KiB

Open AccessArticle

Goondapyrones A–J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived Streptomyces sp.

by Shengbin Jin, David F. Bruhn, Cynthia T. Childs, Erica Burkman, Yovany Moreno, Angela A. Salim, Zeinab G. Khalil and Robert J. Capon

Antibiotics 2024, 13(10), 989; https://doi.org/10.3390/antibiotics13100989 - 18 Oct 2024

Cited by 1 | Viewed by 1089

Abstract

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm Dirofilaria immitis microfilaria and/or the gastrointestinal parasite [...] Read more.

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm Dirofilaria immitis microfilaria and/or the gastrointestinal parasite Haemonchus contortus L1–L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of Streptomyces sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A–J (1–10), together with the known actinopyrones A (11) and C (12). Structures for 1–12 were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against D. immitis mf motility (e.g., EC₅₀ 0.05 μM for 1; EC₅₀ 2.7 μM for 5) and H. contortus L1–L3 larvae development (e.g., EC₅₀ 0.58 μM for 1; EC₅₀ 8.2 μM for 5), respectively. Full article

(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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8 pages, 787 KiB

Open AccessArticle

Can a Shorter Dwell Time Reduce Infective Complications Associated with the Use of Umbilical Catheters?

by Martina Buttera, Lucia Corso, Leonardo Casadei, Cinzia Valenza, Francesca Sforza, Francesco Candia, Francesca Miselli, Cecilia Baraldi, Licia Lugli, Alberto Berardi and Lorenzo Iughetti

Antibiotics 2024, 13(10), 988; https://doi.org/10.3390/antibiotics13100988 - 18 Oct 2024

Viewed by 914

Abstract

Background: Umbilical venous catheters (UVCs) are the standard of care in neonatal intensive care units (NICUs) to administer fluids, parenteral nutrition and medications, although complications may occur, including central line-associated blood stream infections (CLABSIs). However, the dwell time to reduce CLABSI risk remains [...] Read more.

Background: Umbilical venous catheters (UVCs) are the standard of care in neonatal intensive care units (NICUs) to administer fluids, parenteral nutrition and medications, although complications may occur, including central line-associated blood stream infections (CLABSIs). However, the dwell time to reduce CLABSI risk remains an open issue. Methods: We performed a single-center retrospective study of newborns hospitalized in the Modena NICU with at least one UVC inserted over a 6-year period (period 1: January 2011–December 2013; period 2: January 2019–December 2021). We selected a non-consecutive 6-year period to emphasize the differences in UVC management practices that have occurred over time in our NICU. The UVC dwell time and catheter-related complications during the first 4 weeks of life were examined. Results: The UVC dwell time was shorter in period 2 (median 4 days vs. 5 days, p < 0.00001). Between the two periods, the incidence of CLABSIs remained unchanged (p = 0.5425). However, in period 2, there was an increased need for peripherally inserted central catheters (PICCs) after UVC removal, with a rise in PICC infections after UVC removal (p = 0.0239). Conclusions: In our NICU, shortening UVC dwell time from 5 to 4 days did not decrease the UVC-related complications. Instead, the earlier removal of UVCs led to a higher number of PICCs inserted, possibly increasing the overall infectious risk. Full article

(This article belongs to the Special Issue Sepsis Management and Antibiotic Therapy)

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13 pages, 3984 KiB

Open AccessArticle

Impact of Nutrient Starvation on Biofilm Formation in Pseudomonas aeruginosa: An Analysis of Growth, Adhesion, and Spatial Distribution

by Laura Maria De Plano, Manuela Caratozzolo, Sabrina Conoci, Salvatore P. P. Guglielmino and Domenico Franco

Antibiotics 2024, 13(10), 987; https://doi.org/10.3390/antibiotics13100987 - 18 Oct 2024

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Abstract

Objectives: This study investigates the impact of nutrient availability on the growth, adhesion, and biofilm formation of Pseudomonas aeruginosa ATCC 27853 under static conditions. Methods: Bacterial behaviour was evaluated in nutrient-rich Luria–Bertani (LB) broth and nutrient-limited M9 media, specifically lacking carbon (M9-C), nitrogen [...] Read more.

Objectives: This study investigates the impact of nutrient availability on the growth, adhesion, and biofilm formation of Pseudomonas aeruginosa ATCC 27853 under static conditions. Methods: Bacterial behaviour was evaluated in nutrient-rich Luria–Bertani (LB) broth and nutrient-limited M9 media, specifically lacking carbon (M9-C), nitrogen (M9-N), or phosphorus (M9-P). Bacterial adhesion was analysed microscopically during the transition from reversible to irreversible attachment (up to 120 min) and during biofilm production/maturation stages (up to 72 h). Results: Results demonstrated that LB and M9 media supported bacterial growth, whereas nutrient-starved conditions halted growth, with M9-C and M9-N inducing stationary phases and M9-P leading to cell death. Fractal analysis was employed to characterise the spatial distribution and complexity of bacterial adhesion patterns, revealing that nutrient-limited conditions affected both adhesion density and biofilm architecture, particularly in M9-C. In addition, live/dead staining confirmed a higher proportion of dead cells in M9-P over time (at 48 and 72 h). Conclusions: This study highlights how nutrient starvation influences biofilm formation and bacterial dispersion, offering insights into the survival strategies of P. aeruginosa in resource-limited environments. These findings should contribute to a better understanding of biofilm dynamics, with implications for managing biofilm-related infections and industrial biofouling. Full article

(This article belongs to the Special Issue Molecular Mechanism of Antibiotic Resistance in Microbial Biofilms)

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13 pages, 2160 KiB

Open AccessArticle

Boosting Expression of a Specifically Targeted Antimicrobial Peptide K in Pichia pastoris by Employing a 2A Self-Cleaving Peptide-Based Expression System

by Yunhui Zhu, Yuwen Li, Yuxin Fang, Mingyang Hu, Lu Zhao, Mingrui Sui and Na Dong

Antibiotics 2024, 13(10), 986; https://doi.org/10.3390/antibiotics13100986 - 18 Oct 2024

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Abstract

Background/Objectives: The current epidemic of drug-resistance bacterial strains is one of the most urgent threats to human health. Antimicrobial peptides (AMPs) are known for their good activity against multidrug resistance bacteria. Specifically targeted AMPs (STAMPs) are a fraction of AMPs that target specific [...] Read more.

Background/Objectives: The current epidemic of drug-resistance bacterial strains is one of the most urgent threats to human health. Antimicrobial peptides (AMPs) are known for their good activity against multidrug resistance bacteria. Specifically targeted AMPs (STAMPs) are a fraction of AMPs that target specific bacteria and maintain the balance of the healthy microbiota of a host. We reported a STAMP Peptide K (former name: peptide 13) for E. coli. The aim of this study was to effectively produce peptide K using methylotrophic yeast Pichia pastoris. Methods: Three inserts (sequence of peptide K (K), two copies of peptide K fused with 2A sequence (KTK), and two copies of peptide K fused with 2A and an extra α mating factor (KTAK)) were designed to investigate the effect of the number of repeats and the trafficking of peptide on the yield. Results: The yield from KTK was the highest—more than two-fold higher compared with K—implying the role of the 2A sequence in heterologous peptide expression apart from the co-translation. Then, the fermentation condition for KTK was optimized. The optimized yield of KTK was 6.67 mg/mL, suggesting the efficiency of the expression system. Selectivity, antibacterial activity, biocompatibility, and the stability of the fermentation product were equivalent to the chemically synthesized peptide. The actional mechanism of the fermentation product included membrane permeabilization and ROS induction. Conclusions: Together, our work provided a new perspective to augment the yield of the antimicrobial peptide in the microbial system, building a technological foundation for their large-scale production and expanding the market application of AMPs. Full article

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14 pages, 3842 KiB

Open AccessArticle

Beneficial Effects Induced by a Proprietary Blend of a New Bromelain-Based Polyenzymatic Complex Plus N-Acetylcysteine in Urinary Tract Infections: Results from In Vitro and Ex Vivo Studies

by Lucia Recinella, Morena Pinti, Maria Loreta Libero, Silvia Di Lodovico, Serena Veschi, Anna Piro, Daniele Generali, Alessandra Acquaviva, Nilofar Nilofar, Giustino Orlando, Annalisa Chiavaroli, Claudio Ferrante, Luigi Menghini, Simonetta Cristina Di Simone, Luigi Brunetti, Mara Di Giulio and Sheila Leone

Antibiotics 2024, 13(10), 985; https://doi.org/10.3390/antibiotics13100985 - 18 Oct 2024

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Abstract

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli [...] Read more.

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO^®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Extracts from Plants, 2nd Edition)

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11 pages, 2448 KiB

Open AccessArticle

Validation of Recombinase Polymerase Amplification with In-House Lateral Flow Assay for mcr-1 Gene Detection of Colistin Resistant Escherichia coli Isolates

by Naeem Ullah, Nutchaba Suchanta, Umaporn Pimpitak, Pitak Santanirand, Nutthee Am-In and Nuntaree Chaichanawongsaroj

Antibiotics 2024, 13(10), 984; https://doi.org/10.3390/antibiotics13100984 - 17 Oct 2024

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Abstract

Background/Objectives: The emergence of the mobilized colistin resistance 1 (mcr-1) gene, which causes colistin resistance, is a serious concern in animal husbandry, particularly in pigs. Although antibiotic regulations in many countries have prohibited the use of colistin in livestock, the persistence [...] Read more.

Background/Objectives: The emergence of the mobilized colistin resistance 1 (mcr-1) gene, which causes colistin resistance, is a serious concern in animal husbandry, particularly in pigs. Although antibiotic regulations in many countries have prohibited the use of colistin in livestock, the persistence and dissemination of this plasmid-mediated gene require effective and rapid monitoring. Therefore, a rapid, sensitive, and specific method combining recombinase polymerase amplification (RPA) with an in-house lateral flow assay (LFA) for the mcr-1 gene detection was developed. Methods: The colistin agar test and broth microdilution were employed to screen 152 E. coli isolates from pig fecal samples of five antibiotic-used farms. The established RPA-in-house LFA was validated with PCR for mcr-1 gene detection. Results: The RPA-in-house LFA was completed within 35 min (20 min of amplification and 5–15 min on LFA detection) at 37 °C. The sensitivity, specificity, and accuracy were entirely 100% in concordance with PCR results. No cross-reactivity was detected with seven common pathogenic bacteria or other mcr gene variants. Conclusions: Therefore, the in-house RPA-LFA serves as a point-of-care testing tool that is rapid, simple, and portable, facilitating effective surveillance of colistin resistance in both veterinary and clinical settings, thereby enhancing health outcomes. Full article

(This article belongs to the Special Issue Insights into Antibiotics in Human, Animal, and Agriculture: Resistance, Determinant, and Treatment, 2nd Edition)

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28 pages, 7318 KiB

Open AccessSystematic Review

Molecular Epidemiology of Pseudomonas aeruginosa in Brazil: A Systematic Review and Meta-Analysis

by Yan Corrêa Rodrigues, Marcos Jessé Abrahão Silva, Herald Souza dos Reis, Pabllo Antonny Silva dos Santos, Daniele Melo Sardinha, Maria Isabel Montoril Gouveia, Carolynne Silva dos Santos, Davi Josué Marcon, Caio Augusto Martins Aires, Cintya de Oliveira Souza, Ana Judith Pires Garcia Quaresma, Luana Nepomuceno Gondim Costa Lima, Danielle Murici Brasiliense and Karla Valéria Batista Lima

Antibiotics 2024, 13(10), 983; https://doi.org/10.3390/antibiotics13100983 - 17 Oct 2024

Viewed by 1513

Abstract

Background: Globally, Pseudomonas aeruginosa is a high-priority opportunistic pathogen which displays several intrinsic and acquired antimicrobial resistance (AMR) mechanisms, leading to challenging treatments and mortality of patients. Moreover, its wide virulence arsenal, particularly the type III secretion system (T3SS) exoU⁺ virulotype, plays [...] Read more.

Background: Globally, Pseudomonas aeruginosa is a high-priority opportunistic pathogen which displays several intrinsic and acquired antimicrobial resistance (AMR) mechanisms, leading to challenging treatments and mortality of patients. Moreover, its wide virulence arsenal, particularly the type III secretion system (T3SS) exoU⁺ virulotype, plays a crucial role in pathogenicity and poor outcome of infections. In depth insights into the molecular epidemiology of P. aeruginosa, especially the prevalence of high-risk clones (HRCs), are crucial for the comprehension of virulence and AMR features and their dissemination among distinct strains. This study aims to evaluate the prevalence and distribution of HRCs and non-HRCs among Brazilian isolates of P. aeruginosa. Methods: A systematic review and meta-analysis were conducted on studies published between 2011 and 2023, focusing on the prevalence of P. aeruginosa clones determined by multilocus sequence typing (MLST) in Brazil. Data were extracted from retrospective cross-sectional and case-control studies, encompassing clinical and non-clinical samples. The analysis included calculating the prevalence rates of various sequence types (STs) and assessing the regional variability in the distribution of HRCs and non-HRCs. Results: A total of 872 samples were analyzed within all studies, of which 298 (34.17%) were MLST typed, identifying 78 unique STs. HRCs accounted for 48.90% of the MLST-typed isolates, with ST277 being the most prevalent (100/298—33.55%), followed by ST244 (29/298—9.73%), ST235 (13/298—4.36%), ST111 (2/298—0.67%), and ST357 (2/298—0.67%). Significant regional variability was observed, with the Southeast region showing a high prevalence of ST277, while the North region shows a high prevalence of MLST-typed samples and HRCs. Conclusions: Finally, this systematic review and meta-analysis highlight the role of P. aeruginosa clones in critical issue of AMR in P. aeruginosa in Brazil and the need of integration of comprehensive data from individual studies. Full article

(This article belongs to the Special Issue Mechanism of Carbapenem Resistance in Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa)

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14 pages, 2862 KiB

Open AccessArticle

Investigation into the Effectiveness of an Herbal Combination (Angocin^®Anti-Infekt N) in the Therapy of Acute Bronchitis: A Retrospective Real-World Cohort Study

by Nina Kassner, Meinolf Wonnemann, Yvonne Ziegler, Rainer Stange and Karel Kostev

Antibiotics 2024, 13(10), 982; https://doi.org/10.3390/antibiotics13100982 - 17 Oct 2024

Viewed by 1469

Abstract

Background: The goal of this study was to evaluate whether the medical recommendation of Angocin^®Anti-Infekt N (heretofore referenced as Angocin^®) on the day of diagnosis of acute bronchitis is negatively associated with the recurrence of acute bronchitis diagnosis, antibiotic [...] Read more.

Background: The goal of this study was to evaluate whether the medical recommendation of Angocin^®Anti-Infekt N (heretofore referenced as Angocin^®) on the day of diagnosis of acute bronchitis is negatively associated with the recurrence of acute bronchitis diagnosis, antibiotic prescriptions, incidence of chronic bronchitis, and duration of sick leave. Methods: This study included patients in general practices in Germany with a first documented diagnosis of acute bronchitis between 2005 and 2022 (index date) and a prescription of Angocin^®, thyme products, essential oils, mucolytics or antibiotics on the index date. The association between Angocin^® prescription and the risks of a relapse of acute bronchitis, development of chronic bronchitis, or subsequent antibiotic prescription were evaluated using Cox regression models. Univariable conditional logistic regression models were used to investigate the association between Angocin^® prescription and duration of sick leave. Results: After a 1:5 propensity score matching, 598 Angocin^® patients and 2990 patients in each of the four comparison cohorts were available for analysis. Angocin^® prescription was associated with significantly lower incidence of a renewed confirmed diagnosis of acute bronchitis as compared to essential oils (Hazard ratio (HR): 0.61; 95% Confidence Interval (CI): 0.46–0.80), thyme products (HR: 0.70; 95% CI: 0.53–0.91), mucolytics (HR: 0.65; 95% CI: 0.49–0.85) or antibiotics (HR: 0.64; 95% CI: 0.49–0.84). Also, there were significantly lower incidences of subsequent re-prescriptions of antibiotics when compared to mucolytics (HR: 0.73; 95% CI: 0.53–0.99) or antibiotics (HR: 0.53; 95% CI: 0.39–0.72) and a significantly lower risk of chronic bronchitis as compared to essential oils (HR: 0.60; 95% CI: 0.46–0.78), thyme products (HR: 0.53; 95% CI: 0.41–0.69), mucolytics (HR: 0.49; 95% CI: 0.38–0.63) or antibiotics (HR: 0.59; 95% CI: 0.45–0.76). Conclusions: Considering the limitations of the study, the results shed light on the sustaining effectiveness of Angocin^® prescription in the management of acute bronchitis and the associated outcomes when compared to several other treatments commonly used for this condition. Full article

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16 pages, 1026 KiB

Open AccessArticle

Point-Prevalence Survey of Antimicrobial Use and Healthcare-Associated Infections in Four Acute Care Hospitals in Kazakhstan

by Yuliya Semenova, Aizhan Yessmagambetova, Zaure Akhmetova, Manar Smagul, Akniyet Zharylkassynova, Bibigul Aubakirova, Kateryna Soiak, Zhanar Kosherova, Ainur Aimurziyeva, Larissa Makalkina, Ainur Ikhambayeva and Lisa Lim

Antibiotics 2024, 13(10), 981; https://doi.org/10.3390/antibiotics13100981 - 17 Oct 2024

Cited by 2 | Viewed by 1150

Abstract

Background/Objectives: Few studies have examined the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in acute care hospitals in Kazakhstan. This study aimed to address this gap by conducting a point-prevalence survey (PPS) of HAIs and AMU, as well as evaluating hospital [...] Read more.

Background/Objectives: Few studies have examined the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in acute care hospitals in Kazakhstan. This study aimed to address this gap by conducting a point-prevalence survey (PPS) of HAIs and AMU, as well as evaluating hospital antibiotic consumption via internationally recognized methodologies. Methods: PPS was conducted in four acute care hospitals in Kazakhstan on 11 May 2022, following the methodology of the European Center for Disease Prevention and Control, and included 701 patients. Antibiotic consumption in the same hospitals was assessed via the Global Antimicrobial Resistance and Use Surveillance System methodology. Results: HAIs were observed in 3.8% of patients (27/701), with intensive care unit wards accounting for 48.1% of these cases (13/27). Pseudomonas aeruginosa was the most frequently identified pathogen (5 out of 14 documented cases, 35.7%). Resistance to carbapenems was the most common resistance, followed by resistance to glycopeptides and third-generation cephalosporins. The rate of AMU was 38.2%, with an average of 1.37 antibiotics administered per patient. Surgical prophylaxis lasting more than one day was the most common indication for antimicrobial prescription (44.8%). Ceftriaxone and cefazolin are the most commonly used antibiotics. Conclusions: The results of this study are important for understanding the current situation in Kazakhstan and for informing national antimicrobial stewardship and infection control strategies. Full article

(This article belongs to the Special Issue Preventing Antimicrobial Resistance in Hospitals: Infection Control and Antibiotic Use)

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25 pages, 1319 KiB

Open AccessArticle

Multitarget Phytocomplex: Focus on Antibacterial Profiles of Grape Pomace and Sambucus ebulus L. Lyophilisates Against Extensively Drug-Resistant (XDR) Bacteria and In Vitro Antioxidative Power

by Vladimir S. Kurćubić, Vesna Đurović, Slaviša B. Stajić, Marko Dmitrić, Saša Živković, Luka V. Kurćubić, Pavle Z. Mašković, Jelena Mašković, Milan Mitić, Vladimir Živković and Vladimir Jakovljević

Antibiotics 2024, 13(10), 980; https://doi.org/10.3390/antibiotics13100980 - 17 Oct 2024

Viewed by 1251

Abstract

Objectives: This study was conceived with the aim of translating the experience and knowledge of the research group into the design and creation of multi-active phytocomplex cocktails from lyophilised winery by-products (Grape Pomace—GP) and weeds (Sambucus ebulus L., Dwarf Elder—DE). Methods: Quantification [...] Read more.

Objectives: This study was conceived with the aim of translating the experience and knowledge of the research group into the design and creation of multi-active phytocomplex cocktails from lyophilised winery by-products (Grape Pomace—GP) and weeds (Sambucus ebulus L., Dwarf Elder—DE). Methods: Quantification of bioactive molecules was performed by high-performance liquid chromatography (HPLC) method. Results: In the extract obtained from lyophilised GP, the most dominant component that was quantified was petunidin-3-glucoside. Prominent compounds that were quantified in DE extract were cyanidin derivatives. The total number of microorganisms in lyophilisates is low, but some of them still survive lyophilisation. Antibacterial activity was determined by microdilution, the minimum inhibitory concentration (MIC) of the tested bacteria ranged from 0.78 mg/mL to 25.00 mg/mL. Antibacterial susceptibility testing (AST) revealed that Klebsiella spp. and Acinetobacter baumannii complex are extensively drug-resistant (XDR). Conclusions: The GP + DE cocktail showed very strong AB power against both tested XDR bacteria. The total phenolic content and antioxidative effect (determined spectrophotometrically) indicate their linear correlation. Full article

(This article belongs to the Special Issue Comprehensively Addressing Antimicrobial Resistance, Improving Food Safety and Achieving the One Health Goals: Global Challenges)

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9 pages, 1714 KiB

Open AccessArticle

The Efficacy of Topical Cefiderocol Treatment of Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis Is Dependent upon the State of the Corneal Epithelium

by Eric G. Romanowski, Jonathan B. Mandell, Vishal Jhanji and Robert M.Q. Shanks

Antibiotics 2024, 13(10), 979; https://doi.org/10.3390/antibiotics13100979 - 17 Oct 2024

Viewed by 1242

Abstract

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium [...] Read more.

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log₁₀ greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium. Full article

(This article belongs to the Collection Antibiotics in Ophthalmology Practice)

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17 pages, 2278 KiB

Open AccessSystematic Review

Insights into the Rising Threat of Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa Epidemic Infections in Eastern Europe: A Systematic Literature Review

by Michal Piotrowski, Irina Alekseeva, Urs Arnet and Emre Yücel

Antibiotics 2024, 13(10), 978; https://doi.org/10.3390/antibiotics13100978 - 17 Oct 2024

Cited by 1 | Viewed by 1691

Abstract

Background: Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, [...] Read more.

Background: Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. Methods: Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. Results: This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-β-lactamase-producing CRPA strains. Conclusions: This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed. Full article

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16 pages, 4257 KiB

Open AccessArticle

Investigation of the Impact of Antibiotic Administration on the Preterm Infants’ Gut Microbiome Using Next-Generation Sequencing—Based 16S rRNA Gene Analysis

by Ahmet Aktaş, Berkay Yekta Ekren, Beril Yaşa, Osman Uğur Sezerman and Yaşar Nakipoğlu

Antibiotics 2024, 13(10), 977; https://doi.org/10.3390/antibiotics13100977 - 16 Oct 2024

Viewed by 1188

Abstract

Background: The human gut microbiota is an extensive population of microorganisms, and it shows significant variations between periods of optimal health and periods of illness. Vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae (CRKP) are both pathogenic agents (BPAs) that can colonize in the [...] Read more.

Background: The human gut microbiota is an extensive population of microorganisms, and it shows significant variations between periods of optimal health and periods of illness. Vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae (CRKP) are both pathogenic agents (BPAs) that can colonize in the gut after dysbiosis of microbiotal composition following antibiotic treatment. Methods: This study aimed to investigate the impact of antibiotics on the microbiotal composition of the gut. For this purpose, the first pass meconiums of 20 patients and the first rectal swabs containing BPAs of the same patients after antibiotic treatment were studied using next-generation sequencing-based 16S rRNA gene analysis. The V1–V9 region of 16S rRNA was sequenced with Oxford Nanopore. Results: Twenty-five phyla were detected in the meconiums, and 12 of them were absent after antibiotic treatment. The four most prevalent phyla in meconiums were Bacillota, Pseudomonadota, Bacteroidota, and Actinomycetota. Only the relative abundance of Pseudomonadota was increased, while a significant decrease was observed in the other three phyla (p < 0.05). A significant decrease was observed in alpha-diversity in rectal swabs containing BPAs versus meconiums (p = 0.00408), whereas an increased variance was observed in beta-diversity in all samples (p < 0.05). As a result of a LEfSe analysis, Pseudomonadota was found to have a higher relative abundance in rectal swabs, and Bacillota was significantly higher in the meconiums of the twins. Conclusions: Our study strongly verified the relationship between the administration of antibiotics, dysbiosis, and colonization of BPAs in the infants’ gut microbiota. Further research would be beneficial and needed, comprising the natural development process of the infants’ gut microbiota. Full article

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16 pages, 1294 KiB

Open AccessReview

Molecular Mechanisms of Biofilm Formation in Helicobacter pylori

by Kartika Afrida Fauzia, Wiwin Is Effendi, Ricky Indra Alfaray, Hoda M. Malaty, Yoshio Yamaoka and Muhammad Mifthussurur

Antibiotics 2024, 13(10), 976; https://doi.org/10.3390/antibiotics13100976 - 16 Oct 2024

Cited by 1 | Viewed by 1933

Abstract

Background: Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study [...] Read more.

Background: Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. Methods: We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. Results: The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. Conclusions: This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of H. pylori Infection)

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13 pages, 1815 KiB

Open AccessArticle

Development of a High-Resolution Melting Method for the Detection of Clarithromycin-Resistant Helicobacter pylori in the Gastric Microbiome

by Zupeng Kuang, Huishu Huang, Ling Chen, Yanyan Shang, Shixuan Huang, Jun Liu, Jianhui Chen, Xinqiang Xie, Moutong Chen, Lei Wu, He Gao, Hui Zhao, Ying Li and Qingping Wu

Antibiotics 2024, 13(10), 975; https://doi.org/10.3390/antibiotics13100975 - 16 Oct 2024

Viewed by 1021

Abstract

Background: The issue of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLR) has consistently posed challenges for clinical treatment. Hence, a rapid susceptibility testing (AST) method urgently needs to be developed. Methods: In the present study, 35 isolates of H. pylori [...] Read more.

Background: The issue of Helicobacter pylori (H. pylori) resistance to clarithromycin (CLR) has consistently posed challenges for clinical treatment. Hence, a rapid susceptibility testing (AST) method urgently needs to be developed. Methods: In the present study, 35 isolates of H. pylori were isolated from 203 gastritis patients of the Guangzhou cohort, and the antimicrobial resistance phenotypes were associated with their genomes to analyze the relevant mutations. Based on these mutations, a rapid detection system utilizing high-resolution melting (HRM) curve analysis was designed and verified by the Shenzhen cohort, which consisted of 38 H. pylori strains. Results: Genomic analysis identified the mutation of the 2143 allele from A to G (A2143G) of 23S rRNA as the most relevant mutation with CLR resistance (p < 0.01). In the HRM system, the wild-type H. pylori showed a melting temperature (Tm) of 79.28 ± 0.01 °C, while the mutant type exhibited a Tm of 79.96 ± 0.01 °C. These differences enabled a rapid distinction between two types of H. pylori (p < 0.01). Verification examinations showed that this system could detect target DNA as low as 0.005 ng/μL in samples without being affected by other gastric microorganisms. The method also showed a good performance in the Shenzhen validation cohort, with 81.58% accuracy, and 100% specificity. Conclusions: We have developed an HRM system that can accurately and quickly detect CLR resistance in H. pylori. This method can be directly used for the detection of gastric microbiota samples and provides a new benchmark for the simple detection of H. pylori resistance. Full article

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13 pages, 416 KiB

Open AccessArticle

The Impact of Clinical Pharmacist-Driven Weekend Antimicrobial Stewardship Coverage at a Quaternary Hospital

by Hazem Elrefaei, Wasim S. El Nekidy, Rama Nasef, Manal Motasem, Yara Mkarim, Osama Al Quteimat, Mohamed Hisham, Rami Ismail, Emna Abidi, Claude Afif and Rania El Lababidi

Antibiotics 2024, 13(10), 974; https://doi.org/10.3390/antibiotics13100974 - 16 Oct 2024

Viewed by 1026

Abstract

Background and objective: Extending a consistent pharmacy antimicrobial stewardship weekend service was a newly implemented initiative. We sought to evaluate the impact of incorporating an Infectious Diseases (ID)-trained clinical pharmacist into an antimicrobial stewardship program (AMS) during weekends. Results: The number of documented [...] Read more.

Background and objective: Extending a consistent pharmacy antimicrobial stewardship weekend service was a newly implemented initiative. We sought to evaluate the impact of incorporating an Infectious Diseases (ID)-trained clinical pharmacist into an antimicrobial stewardship program (AMS) during weekends. Results: The number of documented interventions was 451 on 362 patients compared to 115 interventions on 108 patients during the pre-implementation period (p = 0.04), with interventions primarily targeting Watch antibiotics, as classified by the WHO AWaRe classification. A reduction in the LOS was observed, with a median of 16 days (8–34) during the post-implementation period compared to 27.5 days (10–56) during the pre-implementation period (p = 0.001). The median DOT increased during the post-implementation period to 8 (6–11), versus the increase to 7 (4–11) during the pre-implementation period (p ≤ 0.001). Finally, there was no significant difference observed in healthcare-associated CDI and infection-related readmission. Methods: This is a retrospective single-center, pre–post quasi-experimental study. Data including the documented pharmacist interventions were collected from the electronic medical record (EMR), the pre-implementation phase was in 2020, and post-implementation was in 2021. The primary outcome was to identify the number of AMS interventions through prospective audit and feedback review analysis. Secondary outcomes included antibiotic days of therapy (DOT), length of hospital stay (LOS), healthcare-associated Clostridioides difficile infection (CDI), and infection-related readmission. Conclusions: The pharmacist-driven weekend AMS is an opportunity for pharmacists to intervene and optimize patients’ care plans. This initiative demonstrated significant increased AMS-related interventions, promoted judicious antimicrobial use, and contributed to a reduced length of hospital stay. Our findings need to be replicated in a larger prospective study. Full article

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

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21 pages, 6105 KiB

Open AccessArticle

Guanethidine Restores Tetracycline Sensitivity in Multidrug-Resistant Escherichia coli Carrying tetA Gene

by Xiaoou Zhao, Mengna Zhang, Zhendu Zhang, Lei Wang, Yu Wang, Lizai Liu, Duojia Wang, Xin Zhang, Luobing Zhao, Yunhui Zhao, Xiangshu Jin, Xiaoxiao Liu and Hongxia Ma

Antibiotics 2024, 13(10), 973; https://doi.org/10.3390/antibiotics13100973 - 15 Oct 2024

Viewed by 1288

Abstract

The worrying issue of antibiotic resistance in pathogenic bacteria is aggravated by the scarcity of novel therapeutic agents. Antibiotic adjuvants offer a promising solution due to their cost-effectiveness and high efficacy in addressing this issue, such as the β-lactamase inhibitor sulbactam (a β-lactam [...] Read more.

The worrying issue of antibiotic resistance in pathogenic bacteria is aggravated by the scarcity of novel therapeutic agents. Antibiotic adjuvants offer a promising solution due to their cost-effectiveness and high efficacy in addressing this issue, such as the β-lactamase inhibitor sulbactam (a β-lactam adjuvant) and the dihydrofolate reductase inhibitor trimethoprim (a sulfonamide adjuvant). This study aimed to discover potential adjuvants for tetracyclines from a list of previously approved drugs to restore susceptibility to Escherichia coli carrying the tetA gene. We have screened guanethidine, a compound from the Chinese pharmacopoeia, which effectively potentiates the activity of tetracyclines by reversing resistance in tetA-positive Escherichia coli, enhancing its antibacterial potency, and retarding the development of resistance. Guanethidine functions via the inhibition of the TetA efflux pump, thereby increasing the intracellular concentration of tetracyclines. Our findings suggest that guanethidine holds promise as an antibiotic adjuvant. Full article

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23 pages, 4140 KiB

Open AccessReview

The Opportunistic Pathogen Staphylococcus warneri: Virulence and Antibiotic Resistance, Clinical Features, Association with Orthopedic Implants and Other Medical Devices, and a Glance at Industrial Applications

by Stefano Ravaioli, Andrea De Donno, Giulia Bottau, Davide Campoccia, Alessandra Maso, Paolo Dolzani, Paulraj Balaji, Francesco Pegreffi, Maria Daglia and Carla Renata Arciola

Antibiotics 2024, 13(10), 972; https://doi.org/10.3390/antibiotics13100972 - 15 Oct 2024

Cited by 1 | Viewed by 3583

Abstract

In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the [...] Read more.

In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the healthy human and animal microbiota of the skin and mucosae, it can take on the role of an opportunistic pathogen capable of causing a variety of infections, ranging from mild to life-threatening, not only in immunocompromised patients but even, although rarely, in healthy people. Here, in addition to a concise discussion of the identification and distinguishing features of S. warneri compared to other staphylococcal species, a systematic overview of the findings from case reports and clinical studies is provided. The paper highlights the virulence and antibiotic resistance profiles of S. warneri, the different clinical contexts in which it has proven to be a serious pathogen, emphasizing its ability to colonize artificial prosthetic materials and its tropism for musculoskeletal and cardiovascular tissues. Some original data on orthopedic implant infections by S. warneri complement the discussion. Finally, from a different perspective, the paper addresses the possibilities of industrial exploitation of this bacterium. Full article

(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)

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17 pages, 2081 KiB

Open AccessArticle

Identifying Potential Natural Antibiotics from Unani Formulas through Machine Learning Approaches

by Ahmad Kamal Nasution, Muhammad Alqaaf, Rumman Mahfujul Islam, Sony Hartono Wijaya, Naoaki Ono, Shigehiko Kanaya and Md. Altaf-Ul-Amin

Antibiotics 2024, 13(10), 971; https://doi.org/10.3390/antibiotics13100971 - 14 Oct 2024

Viewed by 1419

Abstract

The Unani Tibb is a medical system of Greek descent that has undergone substantial dissemination since the 11th century and is currently prevalent in modern South and Central Asia, particularly in primary health care. The ingredients of Unani herbal medicines are primarily derived [...] Read more.

The Unani Tibb is a medical system of Greek descent that has undergone substantial dissemination since the 11th century and is currently prevalent in modern South and Central Asia, particularly in primary health care. The ingredients of Unani herbal medicines are primarily derived from plants. Our research aimed to address the pressing issues of antibiotic resistance, multi-drug resistance, and the emergence of superbugs by examining the molecular-level effects of Unani ingredients as potential new natural antibiotic candidates. We utilized a machine learning approach to tackle these challenges, employing decision trees, kernels, neural networks, and probability-based methods. We used 12 machine learning algorithms and several techniques for preprocessing data, such as Synthetic Minority Over-sampling Technique (SMOTE), Feature Selection, and Principal Component Analysis (PCA). To ensure that our model was optimal, we conducted grid-search tuning to tune all the hyperparameters of the machine learning models. The application of Multi-Layer Perceptron (MLP) with SMOTE pre-processing techniques resulted in an impressive accuracy precision and recall values. This analysis identified 20 important metabolites as essential components of the formula, which we predicted as natural antibiotics. In the final stage of our investigation, we verified our prediction by conducting a literature search for journal validation or by analyzing the structural similarity with known antibiotics using asymmetric similarity. Full article

(This article belongs to the Special Issue Antibiotic Adjuvants: An Approach to Overcoming Multi-Drug Resistance and Biofilm Infections)

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13 pages, 3663 KiB

Open AccessArticle

Enhancing Stability and Investigating Target Attainment of Benzylpenicillin in Outpatient Parenteral Antimicrobial Therapy: Insights from In Vitro and In Vivo Evaluations

by Katharina M. Rentsch, Nina Khanna, Delia Halbeisen and Michael Osthoff

Antibiotics 2024, 13(10), 970; https://doi.org/10.3390/antibiotics13100970 - 14 Oct 2024

Viewed by 1000

Abstract

Background/Objective: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use [...] Read more.

Background/Objective: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use of benzylpenicillin in OPAT requires special consideration because of its limited stability at elevated temperatures. Methods: We tested the benzylpenicillin stability, pH, and degradation of products in elastomeric pumps at different concentrations in saline and in buffered solution containing sodium citrate during a prolonged storage and at high temperatures (seven days at 2–8 °C followed by 24 h at 37 °C). Additionally, drug concentrations during intermittent bolus infusion and during OPAT were determined in five patients. The concentrations and degradation products of benzylpenicillin were measured using liquid chromatography mass spectrometry (LC-MS/MS). Results: Unbuffered benzylpenicillin solutions that were already degraded during refrigerator storage and analyte concentration were not measurable after 8 days. The stability of the buffered solutions was acceptable at all three of the tested concentrations (97.6 ± 1.3%, 96.3 ± 0.8%, and 94.9 ± 1.1% for 10 Mio IU, 20 Mio IU, and 40 Mio IU of benzylpenicillin). The stability was influenced by benzylpenicillin concentration, and several breakdown products were identified. Benzylpenicillin concentrations were measured in five patients during OPAT and ranged from 7.2 to 60 mg/L. Conclusions: Benzylpenicillin buffered with sodium citrate is a safe and convenient option for use in continuous infusions during OPAT and should be favored over broad-spectrum antibiotics. Therapeutic drug monitoring data indicate sufficient to high plasma levels when patients received benzylpenicillin as continuous infusions. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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10 pages, 577 KiB

Open AccessArticle

Three Days of Oral Azithromycin Versus Five Days of Oral Clarithromycin in the Treatment of Campylobacter Enterocolitis in Children: A Prospective Study

by Hyun Mi Kang, Yoon Kyung Cho, Ye Ji Kim, Dae Chul Jeong and In Hyuk Yoo

Antibiotics 2024, 13(10), 969; https://doi.org/10.3390/antibiotics13100969 - 14 Oct 2024

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Abstract

Objective: This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. Methods: A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day [...] Read more.

Objective: This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. Methods: A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day course of azithromycin or a 5-day course of clarithromycin. Symptoms were monitored daily, and changes in laboratory markers (WBC counts, CRP levels, and stool calprotectin) were compared. Results: A total of 29 pediatric patients were included, with 14 patients in the azithromycin group and 15 patients in the clarithromycin group. The median age of patients in the azithromycin group was 10.0 years (interquartile range [IQR]: 5.0–13.0), and in the clarithromycin group, the median age was 9.0 years (IQR: 7.0–13.0) (p = 0.793). The median time to clinical resolution was 3.0 days (IQR: 2.0–3.0) in the azithromycin group and 2.0 days (IQR: 2.0–3.0) in the clarithromycin group (p = 0.132). There were no significant differences in the duration of individual symptoms, including fever, vomiting, and abdominal pain. The length of hospital stay was also similar, with a median stay of 4 days (IQR: 3.0–5.0) in both groups (p = 0.394). Both antibiotics were well-tolerated, with no significant adverse events or treatment discontinuation reported. Conclusions: Clarithromycin was found to be as effective as azithromycin in treating pediatric Campylobacter enterocolitis, with similar clinical outcomes and improvements in laboratory markers. Full article

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Open AccessArticle

A Machine Learning Approach to Determine Risk Factors for Respiratory Bacterial/Fungal Coinfection in Critically Ill Patients with Influenza and SARS-CoV-2 Infection: A Spanish Perspective

by Alejandro Rodríguez, Josep Gómez, Ignacio Martín-Loeches, Laura Claverias, Emili Díaz, Rafael Zaragoza, Marcio Borges-Sa, Frederic Gómez-Bertomeu, Álvaro Franquet, Sandra Trefler, Carlos González Garzón, Lissett Cortés, Florencia Alés, Susana Sancho, Jordi Solé-Violán, Ángel Estella, Julen Berrueta, Alejandro García-Martínez, Borja Suberviola, Juan J. Guardiola and María Bodí Show full author list Hide full author list

Antibiotics 2024, 13(10), 968; https://doi.org/10.3390/antibiotics13100968 - 14 Oct 2024

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Abstract

Background: Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. Methods: We conducted [...] Read more.

Background: Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. Methods: We conducted a secondary analysis of two prospective multicenter cohort studies with confirmed influenza A (H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). The performance of these models was assessed by the area under the ROC curve (AUC) and out-of-bag (OOB) methods for MLR and RF, respectively. Results: Of the 8902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male, and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall, the predictive models showed modest performances, with an AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA, and shock were factors associated with BFC in most models. Conclusions: Machine learning models do not adequately predict the presence of co-infection in critically ill patients with pandemic virus infection. However, the presence of factors such as advanced age, elevated procalcitonin or CPR, and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU. Full article

(This article belongs to the Special Issue Infection Diagnostics and Antimicrobial Therapy for Critical Patient)

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Antibiotics, Volume 13, Issue 10 (October 2024) – 85 articles

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