Antibiotics

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 (registering DOI) - 15 Oct 2024

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 (registering DOI) - 14 Oct 2024

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 (registering DOI) - 14 Oct 2024

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 (registering DOI) - 14 Oct 2024

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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17 pages, 835 KiB

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 (registering DOI) - 14 Oct 2024

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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20 pages, 902 KiB

Open AccessArticle

Pharmacists’ Knowledge, Perception, and Prescribing Practice of Probiotics in the UAE: A Cross-Sectional Study

by Maram O. Abbas, Hanan Ahmed, Eisha Hamid, Dyshania Padayachee, Menah Talla Abdulbadia, Sohila Khalid, Ahmed Abuelhana and Bazigha K. Abdul Rasool

Antibiotics 2024, 13(10), 967; https://doi.org/10.3390/antibiotics13100967 (registering DOI) - 13 Oct 2024

Abstract

Background: The human body is a complex and interconnected system where trillions of microorganisms, collectively known as the gut microbiota, coexist with these cells. Besides maintaining digestive health, this relationship also impacts well-being, including immune function, metabolism, and mental health. As frontline healthcare [...] Read more.

Background: The human body is a complex and interconnected system where trillions of microorganisms, collectively known as the gut microbiota, coexist with these cells. Besides maintaining digestive health, this relationship also impacts well-being, including immune function, metabolism, and mental health. As frontline healthcare providers, pharmacists are pivotal in promoting the benefits of probiotics for immune support. This study explored pharmacists’ knowledge, perception, and practice behavior in the UAE towards the implication of probiotic application beyond digestive health, such as cardiovascular and mental health impacts and their diverse dosage forms. Method: An online self-administered survey was distributed among pharmacists in the UAE. Data were collected through personal visits to pharmacies, where pharmacists were approached and asked to complete the questionnaire. The sample size included 407 pharmacists, determined using the formula for proportions with a 95% confidence level and a 5% margin of error. Statistical analysis was performed using SPSS version 29. Descriptive statistics were used to summarize demographic characteristics and survey responses. The knowledge levels were categorized into poor, moderate, and good. Chi-square analysis was employed to investigate associations between demographic factors and knowledge levels, with a significance level set at p < 0.05, enhancing the robustness of the study’s findings. Results: This study included 407 completed eligible responses. About 63.56% of participants were female, with 52.1% employed in pharmacy chains. While 91.2% of pharmacists recognized probiotics’ role in immune support, only 30% were aware of their cardiovascular benefits. Moreover, chewing gum was the least known dosage form of probiotics, recognized by only 16.7% of respondents. Additionally, only 57% of the participants recognized liposomes as a dosage form. In practice, most pharmacists recommended storing probiotics at room temperature, accounting for 66.6%. The most prevalent misconception encountered in the pharmacy setting was the belief that probiotics are primarily intended for gastrointestinal tract problems, at 79.1% of the respondents. Regarding perception, the agreement was observed regarding the safety of probiotics for all ages. Perceived barriers included the high cost of probiotics, with the majority (86.5%) indicating this as a significant obstacle, while lack of demand was identified as the minor barrier by 64.6%. Additionally, an association was found at a significance level of p < 0.05 with knowledge, gender, educational level, type and location of pharmacy, and source of information. Conclusions: The study highlights knowledge gaps in pharmacists’ understanding of probiotic applications beyond digestive health, particularly cardiovascular health and depression. Targeted educational interventions are necessary to address these gaps. The findings underscore the importance of ongoing professional development for pharmacists, enhancing their role in patient education and the promotion of probiotics for overall health. Full article

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15 pages, 1330 KiB

Open AccessArticle

Antibiotic Resistance Pattern of Pathogens Isolated from Pediatric Patients during and after the COVID-19 Pandemic

by Andreea-Loredana Golli, Simona Georgiana Popa, Monica Laura Cara, George-Alin Stoica, Dragos Fortofoiu and Maria Stoica

Antibiotics 2024, 13(10), 966; https://doi.org/10.3390/antibiotics13100966 (registering DOI) - 13 Oct 2024

Abstract

Background/Objectives: The present study aims to highlight the possible significant changes due to the COVID-19 pandemic in the resistance of pathogens involved in cases of pediatric infections. Methods: This study included children hospitalized in the Pediatric Intensive Care Unit, Surgery and [...] Read more.

Background/Objectives: The present study aims to highlight the possible significant changes due to the COVID-19 pandemic in the resistance of pathogens involved in cases of pediatric infections. Methods: This study included children hospitalized in the Pediatric Intensive Care Unit, Surgery and Pediatrics from a tertiary teaching hospital, during and after the COVID-19 period (2020–2023). Results: The research included 845 samples collected during 2020–2023, from 685 pediatric patients. A total of 937 bacterial isolates were obtained, of which 509 isolates (54.32%) were Gram-negative bacteria. Around 30% of all the pathogens were multidrug-resistant (MDR), with a statistically significant increase post-pandemic, in the case of the MDR Escherichia coli strains (p < 0.05). A very high percentage of MDR Acinetobacter spp. isolates was found, with an important, but not statistically significant, increase in the post-pandemic period. The highest percentage of the MDR Gram-positive pathogens was registered in the case of S. aureus strains (31.80%). Over 20% of the Coagulase-negative Staphylococci (CoNS) strains isolated between 2020 and 2023 were MDR, with an important increase in the post-COVID-19 period. The proportion of carbapenem-resistant Gram-negative pathogens significantly decreased in the post-COVID-19 period compared with the COVID-19 period (p < 0.05), especially in the case of the Klebsiella spp. strains. Conclusions: Our findings revealed the increase in the post-COVID-19 period of the prevalence of MDR strains of Acinetobacter spp., CoNS, and Escherichia coli isolated in pediatric patient samples and a significant decline in the trend of the carbapenem-resistant Gram-negative pathogens, which may be due to the testing rate and to the specific pathology of the pediatric patients hospitalized in the two periods. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Hospital-Acquired Infections)

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14 pages, 950 KiB

Open AccessSystematic Review

Newer Therapies for Refractory Helicobacter pylori Infection in Adults: A Systematic Review

by Ligang Liu and Milap C. Nahata

Antibiotics 2024, 13(10), 965; https://doi.org/10.3390/antibiotics13100965 (registering DOI) - 12 Oct 2024

Abstract

Background: Helicobacter pylori (H. pylori) infection is a global health concern, affecting approximately two-thirds of the world’s population. Standard first-line treatment regimens often fail, necessitating alternative rescue therapies. Objectives: This review aims to evaluate the efficacy and safety of newer treatment [...] Read more.

Background: Helicobacter pylori (H. pylori) infection is a global health concern, affecting approximately two-thirds of the world’s population. Standard first-line treatment regimens often fail, necessitating alternative rescue therapies. Objectives: This review aims to evaluate the efficacy and safety of newer treatment regimens in patients who have failed initial H. pylori eradication therapy. Methods: A comprehensive literature search was conducted in PubMed, the Cochrane Library, and Embase. Inclusion criteria were randomized controlled trials (RCTs) published after 2010, involving patients with previous H. pylori treatment failure and interventions with vonoprazan-based therapy, high-dose PPI–amoxicillin dual therapy (HDDT), or rifabutin-containing triple therapy. Results: 10 RCTs were included. HDDT demonstrated high eradication rates (81.3% to 89.2%), particularly when combined with metronidazole (92.6%), although at an increased frequency of adverse events. Vonoprazan-based regimens achieved comparable or higher eradication rates (83.3% to 89.5%) compared to PPI-based therapies, with similar adverse events. Rifabutin-containing triple therapy showed high efficacy (80.7% to 100%), particularly in patients with a history of multiple treatment failures, and it was associated with lower adverse events compared to bismuth-containing regimens. Conclusions: HDDT, vonoprazan-based therapy, and rifabutin-based therapy have proven to be effective and safe rescue regimens for treating H. pylori infection. Additional large-scale randomized studies are needed to determine the optimal doses and durations of these regimens to achieve the highest eradication rate with the lowest incidence of adverse events among patients with refractory H. pylori infections globally. Full article

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

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15 pages, 2336 KiB

Open AccessArticle

Characterization of Human Breast Milk-Derived Limosilactobacillus reuteri MBHC 10138 with Respect to Purine Degradation, Anti-Biofilm, and Anti-Lipid Accumulation Activities

by Jinhua Cheng, Joo-Hyung Cho and Joo-Won Suh

Antibiotics 2024, 13(10), 964; https://doi.org/10.3390/antibiotics13100964 (registering DOI) - 12 Oct 2024

Abstract

Background: Human breast milk is a valuable source of potential probiotic candidates. The bacteria isolated from human breast milk play an important role in the development of the infant gut microbiota, exhibiting diverse biological functions. Methods: In this study, Limosilactobacillus reuteri MBHC 10138 [...] Read more.

Background: Human breast milk is a valuable source of potential probiotic candidates. The bacteria isolated from human breast milk play an important role in the development of the infant gut microbiota, exhibiting diverse biological functions. Methods: In this study, Limosilactobacillus reuteri MBHC 10138 isolated from breast milk was characterized in terms of its probiotic safety characteristics and potential efficacy in hyperuricemia, obesity, lipid liver, and dental caries, conditions which Korean consumers seek to manage using probiotics. Results: Strain MBHC 10138 demonstrated a lack of D-lactate and biogenic amine production as well as a lack of bile salt deconjugation and hemolytic activity. It also exhibited susceptibility to common antibiotics, tolerance to simulated oral–gastric–intestinal conditions, and superior biological activity compared to three L. reuteri reference strains, including KACC 11452 and MJ-1, isolated from feces, and a commercial strain isolated from human breast milk. Notably, L. reuteri MBHC 10138 showed high capabilities in assimilating guanosine (69.48%), inosine (81.92%), and adenosine (95.8%), strongly inhibited 92.74% of biofilm formation by Streptococcus mutans, and reduced lipid accumulation by 32% in HepG2 cells. Conclusions: These findings suggest that strain MBHC 10138, isolated from human breast milk, has potential to be developed as a probiotic for managing hyperuricemia, obesity, and dental caries after appropriate in vivo studies. Full article

(This article belongs to the Section Antibiofilm Strategies)

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32 pages, 26302 KiB

Open AccessArticle

Development of Novel Biocomposites with Antimicrobial-Activity-Based Magnesium-Doped Hydroxyapatite with Amoxicillin

by Carmen Cimpeanu, Daniela Predoi, Carmen Steluta Ciobanu, Simona Liliana Iconaru, Krzysztof Rokosz, Mihai Valentin Predoi, Steinar Raaen and Monica Luminita Badea

Antibiotics 2024, 13(10), 963; https://doi.org/10.3390/antibiotics13100963 (registering DOI) - 12 Oct 2024

Abstract

Background/Objectives: A biocomposite based on magnesium-doped hydroxyapatite and enriched with amoxicillin (MgHApOx) was synthesized using the coprecipitation method and is presented here for the first time. Methods: The stability of MgHAp and MgHApOx suspensions was evaluated by ultrasound measurements. The structure [...] Read more.

Background/Objectives: A biocomposite based on magnesium-doped hydroxyapatite and enriched with amoxicillin (MgHApOx) was synthesized using the coprecipitation method and is presented here for the first time. Methods: The stability of MgHAp and MgHApOx suspensions was evaluated by ultrasound measurements. The structure of the synthesized MgHAp and MgHApOx was examined with X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The crystalline structure was determined by X-ray diffraction. The FTIR data were collected in the range of 4000–400 cm⁻¹. The morphology of the nanoparticles was evaluated by scanning electron microscopy (SEM). Furthermore, the biocompatible properties of MgHAp, MgHApOx and amoxicillin (Ox) suspensions were assessed using human fetal osteoblastic cells (hFOB 1.19 cell line). The antimicrobial properties of the MgHAp, MgHApOx and Ox suspension nanoparticles were assessed using the standard reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231. Results: X-ray studies have shown that the biocomposite retains the characteristics of HAp and amoxicillin. The SEM assessment exhibited that the apatite contains particles at nanometric scale with acicular flakes morphology. The XRD and SEM results exhibited crystalline nanoparticles. The average crystallite size calculated from XRD analysis increased from 15.31 nm for MgHAp to 17.79 nm in the case of the MgHApOx sample. The energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) analysis highlighted the presence of the constituent elements of MgHAp and amoxicillin. Moreover, XPS confirmed the substitution of Ca²⁺ ions with Mg²⁺ and the presence of amoxicillin constituents in the MgHAp lattice. The results of the in vitro antimicrobial assay demonstrated that MgHAp, MgHApOx and Ox suspensions exhibited good antimicrobial activity against the tested microbial strains. The results showed that the antimicrobial activity of the samples was influenced by the presence of the antibiotic and also by the incubation time. Conclusions: The findings from the biological assays indicate that MgHAp and MgHApOx are promising candidates for the development of new biocompatible and antimicrobial agents for biomedical applications. Full article

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21 pages, 1022 KiB

Open AccessArticle

Genomic Analyses of Methicillin-Resistant Staphylococcus pseudintermedius from Companion Animals Reveal Changing Clonal Populations, Multidrug Resistance, and Virulence

by Mattias Myrenås, Karl Pedersen and Ulrika Windahl

Antibiotics 2024, 13(10), 962; https://doi.org/10.3390/antibiotics13100962 (registering DOI) - 12 Oct 2024

Abstract

Background/Objectives: Staphylococcus pseudintermedius is part of the normal microbiota in dogs. Since 2006, an increase in multidrug-resistant clones of methicillin-resistant S. pseudintermedius has been reported, as well as zoonotic transmission. Longitudinal investigations into clonal population structures, antibiotic resistance patterns, and the presence of [...] Read more.

Background/Objectives: Staphylococcus pseudintermedius is part of the normal microbiota in dogs. Since 2006, an increase in multidrug-resistant clones of methicillin-resistant S. pseudintermedius has been reported, as well as zoonotic transmission. Longitudinal investigations into clonal population structures, antibiotic resistance patterns, and the presence of resistance and virulence genes are important tools for gaining knowledge of the mechanisms behind the emergence of such clones. Methods: We investigated 87% of all non-repetitive MRSP isolates from dogs and cats in Sweden over a ten-year period (n = 356). All isolates were subjected to staphylococcal chromosomal cassette mec identification, whole-genome sequencing, multi-locus sequence typing, and analyses of genomic relatedness, as well as investigation of phenotypical resistance patterns and the presence of antibiotic resistance genes and virulence genes. Results: A considerable increase over time in the number of clonal lineages present was observed, indicating genomic diversification, and four clones became dominant: ST71, ST258, ST265, and ST551. In total, 96% of the isolates were multidrug-resistant. Statistically significant differences in resistance to several antibiotic classes between the four dominant clones were present. All isolates carried several virulence genes encoding factors associated with attachment, colonization, toxin synthesis, quorum sensing, antibiotic resistance, and immune evasion. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Companion and Food-Producing Animals, 2nd Edition)

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16 pages, 2379 KiB

Open AccessArticle

Linezolid Pharmacokinetics in Critically Ill Patients: Continuous Versus Intermittent Infusion

by Ligia-Ancuța Hui, Constantin Bodolea, Adina Popa, Ana-Maria Vlase, Elisabeta Ioana Hirișcău and Laurian Vlase

Antibiotics 2024, 13(10), 961; https://doi.org/10.3390/antibiotics13100961 (registering DOI) - 11 Oct 2024

Abstract

Background: Linezolid has been found to have considerable interindividual variability, especially in critically ill patients, which can lead to suboptimal plasma concentration. To overcome this shortcoming, several solutions have been proposed. These include using loading dose, higher maintenance doses, and dose stratification according [...] Read more.

Background: Linezolid has been found to have considerable interindividual variability, especially in critically ill patients, which can lead to suboptimal plasma concentration. To overcome this shortcoming, several solutions have been proposed. These include using loading dose, higher maintenance doses, and dose stratification according to the patient’s particularities, therapeutic drug monitoring, and drug administration via continuous infusion (CI) instead of intermittent infusion (II). In the present study, we aim to compare the pharmacokinetic (PK) parameters of linezolid after administration as II versus CI to critically ill patients. Methods: In a prospective study conducted in an intensive care unit, we compared the same two daily doses of linezolid administered via II versus CI. The serum concentration was measured, and pharmacokinetic parameters were calculated. The pharmacokinetic/pharmacodynamic (PK/PD) indices for efficacy chosen were area under the concentration–time curve at steady state divided by the minimum inhibitory concentration over 80 (AUC24–48/MIC > 80). Results: Greater serum concentration variability was observed in the II group than in the CI group. The %T > MIC > 80% was achieved for MICs of 1 and 2 µg/mL 100% of the time, whereas for the II group, this was 93% and 73%, respectively. AUC24–48/MIC > 80 was reached in 100% of cases in the CI group compared with 87% in the II group for a MIC of 1 µg/mL. Conclusions: The two infusion methods may be used comparably, but utilizing CI as an alternative to II may have potential benefits, including avoiding periods of suboptimal concentrations, which may enhance safety profiles and clinical outcomes. Considering the relatively few studies performed on linezolid to date, which are increasing in number, the results of the present study may be of interest. Full article

(This article belongs to the Special Issue Editorial Board Members' Collection Series: Bridging the Gap: Translational and Clinical Approaches on Antibiotic Pharmacokinetics and Pharmacodynamics)

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14 pages, 3510 KiB

Open AccessArticle

Impact of Predation by Ciliate Tetrahymena borealis on Conjugation in Aeromonas salmonicida subsp. salmonicida

by Alicia F. Durocher, Valérie E. Paquet, Rébecca E. St-Laurent, Caroline Duchaine and Steve J. Charette

Antibiotics 2024, 13(10), 960; https://doi.org/10.3390/antibiotics13100960 - 11 Oct 2024

Abstract

Background/Objectives: Antibiotic resistance gene (ARG) spread is driven by horizontal gene transfer (HGT). Ciliated protozoa may contribute to this process, as their predation has been shown to facilitate HGT in certain bacteria. Here, this phenomenon was further investigated using A. salmonicida subsp. salmonicida. [...] Read more.

Background/Objectives: Antibiotic resistance gene (ARG) spread is driven by horizontal gene transfer (HGT). Ciliated protozoa may contribute to this process, as their predation has been shown to facilitate HGT in certain bacteria. Here, this phenomenon was further investigated using A. salmonicida subsp. salmonicida. This fish pathogen bears an extensive and dynamic plasmidome, suggesting a high potential for HGT. Methods: A. salmonicida strains carrying one of three conjugative plasmids bearing ARGs (pSN254b, pRAS1b or pAsa4b) were cocultured with a recipient, either A. salmonicida, E. coli or A. hydrophila. Conjugation rates were assessed in the presence and absence of the ciliate Tetrahymena borealis. PCR genotyping confirmed the acquisition of the conjugative plasmids and was used to verify the mobilization of other plasmids. Results: The basal rate of conjugation observed was high. Under the conditions studied, ciliate predation did not appear to influence the conjugation rate, except at higher proportions of ciliates, which typically hampered conjugation. Microscopy revealed that most bacteria were digested in these conditions. PCR screening demonstrated that small mobilizable plasmids from A. salmonicida (pAsa1, pAsa2, pAsa3, and pAsal1) were acquired by the recipients along with the conjugative plasmids, with a slight effect of the ciliates in some donor/recipient cell combination. Conclusions: These results highlight how A. salmonicida can conjugate efficiently with different species and how complex its relationship with ciliates is. Full article

(This article belongs to the Special Issue Advances in Plasmid Mediated Antimicrobial Resistance)

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14 pages, 2854 KiB

Open AccessArticle

Serotype Distribution and Antimicrobial Resistance of Salmonella Isolates from Poultry Sources in China

by Chu Wang, Xianwen Wang, Juyuan Hao, He Kong, Liyuan Zhao, Mingzhen Li, Ming Zou and Gang Liu

Antibiotics 2024, 13(10), 959; https://doi.org/10.3390/antibiotics13100959 - 11 Oct 2024

Abstract

Background: Salmonella is an important zoonotic pathogen, of which poultry products are important reservoirs. This study analyzed the prevalence, antimicrobial resistance, and characterization of Salmonella from broiler and laying hen sources in China. Methods: A total of 138 (12.27%) strains of Salmonella were [...] Read more.

Background: Salmonella is an important zoonotic pathogen, of which poultry products are important reservoirs. This study analyzed the prevalence, antimicrobial resistance, and characterization of Salmonella from broiler and laying hen sources in China. Methods: A total of 138 (12.27%) strains of Salmonella were isolated from 1125 samples from broiler slaughterhouses (20.66%, 44/213), broiler farms (18.21%, 55/302), and laying hen farms (6.39%, 39/610). Multiplex PCR was used to identify the serotypes. Antibiotic susceptibility testing to a set of 21 antibiotics was performed and all strains were screened by PCR for 24 selected antimicrobial resistance genes (ARGs). In addition, 24 strains of Salmonella were screened out by whole-genome sequencing together with 65 released Salmonella genomes to evaluate phylogenetic characteristics, multilocus sequence typing (MLST), and plasmid carriage percentages. Results: A total of 11 different serotypes were identified, with the dominance of S. Enteritidis (43/138, 31.16%), S. Newport (30/138, 21.74%), and S. Indiana (19/138, 13.77%). The results showed that S. Enteritidis (34.34%, 34/99) and S. Newport (51.28%, 20/39) were the dominant serotypes of isolates from broilers and laying hens, respectively. The 138 isolates showed the highest resistance to sulfisoxazole (SXZ, 100%), nalidixic acid (NAL, 54.35%), tetracycline (TET, 47.83%), streptomycin (STR, 39.86%), ampicillin (AMP, 39.13%), and chloramphenicol (CHL, 30.43%), while all the strains were sensitive to both tigacycline (TIG) and colistin (COL). A total of 45.65% (63/138) of the isolates were multidrug-resistant (MDR) strains, and most of them (61/63, 96.83%) were from broiler sources. The results of PCR assays revealed that 63.77% of the isolates were carrying the quinolone resistance gene qnrD, followed by gyrB (58.70%) and the trimethoprim resistance gene dfrA12 (52.17%). Moreover, a total of thirty-four ARGs, eighty-nine virulence genes, and eight plasmid replicons were detected in the twenty-four screened Salmonella strains, among which S. Indiana was detected to carry the most ARGs and the fewest plasmid replicons and virulence genes compared to the other serotypes. Conclusions: This study revealed a high percentage of multidrug-resistant Salmonella from poultry sources, stressing the importance of continuous monitoring of Salmonella serotypes and antimicrobial resistance in the poultry chain, and emergency strategies should be implemented to address this problem. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Infections in Animals)

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29 pages, 16864 KiB

Open AccessSystematic Review

A Systematic Review and Comprehensive Analysis of mcr Gene Prevalence in Bacterial Isolates in Arab Countries

by Mouayad Zuheir Bakleh, Muhammad Kohailan, Muhammad Marwan and Abdallah Alhaj Sulaiman

Antibiotics 2024, 13(10), 958; https://doi.org/10.3390/antibiotics13100958 - 11 Oct 2024

Abstract

Background: The resurgence of colistin has become critical in combating multidrug-resistant Gram-negative bacteria. However, the emergence of mobilized colistin resistance (mcr) genes presents a crucial global challenge, particularly in the Arab world, which includes regions with unique conditions and ongoing conflicts [...] Read more.

Background: The resurgence of colistin has become critical in combating multidrug-resistant Gram-negative bacteria. However, the emergence of mobilized colistin resistance (mcr) genes presents a crucial global challenge, particularly in the Arab world, which includes regions with unique conditions and ongoing conflicts in some parts. Methods: To address this issue, a systematic review was conducted using multiple databases, including Cochrane, PubMed, Scopus, Web of Science, and Arab World Research Source. Results: A total of 153 studies were included, revealing substantial heterogeneity in the prevalence of mcr genes across 15 Arab countries, with notable findings indicating that Egypt and Lebanon reported the highest number of cases. The analysis indicated that the most prevalent sequence types were ST10, ST101, and ST1011, all of which are Escherichia coli strains linked to significant levels of colistin resistance and multiple antimicrobial resistance profiles. Conclusions: By analyzing the diverse findings from different Arab countries, this review lays a critical foundation for future research and highlights the necessity for enhanced surveillance and targeted interventions to address the looming threat of colistin resistance in the region. Systematic review registration: PROSPERO CRD42024584379. Full article

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20 pages, 1121 KiB

Open AccessArticle

Phenotypic and Genotypic Characterization of Escherichia coli and Salmonella spp. Isolates from Pigs at Slaughterhouse and from Commercial Pork Meat in Portugal

by Carlota Gonçalves, Leonor Silveira, João Rodrigues, Rosália Furtado, Sónia Ramos, Alexandra Nunes and Ângela Pista

Antibiotics 2024, 13(10), 957; https://doi.org/10.3390/antibiotics13100957 - 11 Oct 2024

Abstract

Background: Foodborne diseases are a serious public health concern, and food-producing animals are a major source of contamination. Methods: The present study analysed Escherichia coli and Salmonella spp. isolated from faecal samples of 100 fattening pigs and from 52 samples of pork meat. [...] Read more.

Background: Foodborne diseases are a serious public health concern, and food-producing animals are a major source of contamination. Methods: The present study analysed Escherichia coli and Salmonella spp. isolated from faecal samples of 100 fattening pigs and from 52 samples of pork meat. Results: The results showed that the majority of the analysed meat samples were considered satisfactory in terms of microbiological quality (92.3% for E. coli and 94.2% for Salmonella spp.). Salmonella spp. was identified in 5.8% of the meat samples, whereas E. coli was detected in 89.5% of all samples (69.2% in meat and 100% in faecal samples). Furthermore, 1.9% of the faecal samples contained Shiga-toxin-producing E. coli and 3.9% contained enterotoxigenic E. coli. All sequenced isolates presented virulence genes for extraintestinal pathogenic E. coli. Moreover, 75.0% of E. coli isolates from meat and 71.8% from faeces samples showed antibiotic resistance, with 40.7% and 51.4%, respectively, being multidrug-resistant (MDR). The most prevalent resistances were to tetracycline, ampicillin, and sulfamethoxazole, and one E. coli isolate showed resistance to extended-spectrum β-lactamase. Conclusions: This study highlights the role of pigs as a potential source of human contamination and the importance of a One Health approach to ensure food safety and to promote public health. Full article

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

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10 pages, 255 KiB

Open AccessArticle

Optimization of Screening Media to Improve Antimicrobial Biodiscovery from Soils in Undergraduate/Citizen Science Research-Engaged Initiatives

by Leah McPhillips, John O’Callaghan, Carmel Shortiss, Stephen A. Jackson and Niall D. O’Leary

Antibiotics 2024, 13(10), 956; https://doi.org/10.3390/antibiotics13100956 - 11 Oct 2024

Abstract

Background/Objectives: Research-engaged academic institutions offer the opportunity to couple undergraduate education/citizen science projects with antimicrobial biodiscovery research. Several initiatives reflecting this ethos have been reported internationally (e.g., Small World, Tiny Earth, MicroMundo, Antibiotics Unearthed). These programs target soil habitats due to their high [...] Read more.

Background/Objectives: Research-engaged academic institutions offer the opportunity to couple undergraduate education/citizen science projects with antimicrobial biodiscovery research. Several initiatives reflecting this ethos have been reported internationally (e.g., Small World, Tiny Earth, MicroMundo, Antibiotics Unearthed). These programs target soil habitats due to their high microbial diversity and promote initial screening with non-selective, nutrient media such as tryptic soy agar (TSA). However, evaluation of published outputs to date indicates that isolate recovery on TSA is consistently dominated by the genera Bacillus, Pseudomonas, and Paenibacillus. In this study, we evaluated the potential of soil extract agar to enhance soil isolate diversity and antibiosis induction outcomes in our undergraduate Antibiotics Unearthed research program. Methods: We comparatively screened 229 isolates from woodland and garden soil samples on both tryptic soy agar (TSA) and soil extract agar (SEA) for antimicrobial activity against a panel of clinically relevant microbial pathogens. Results: On one or both media, 15 isolates were found to produce zones of clearing against respective pathogens. 16S rRNA gene sequencing linked the isolates with three genera: Streptomyces (7), Paenibacillus (6), and Pseudomonas (2). Six of the Streptomyces isolates and one Pseudomonas demonstrated antimicrobial activity when screened on SEA, with no activity on TSA. Furthermore, incorporation of the known secondary metabolite inducer N acetyl-glucosamine (20 mM) into SEA media altered the pathogen inhibition profiles of 14 isolates and resulted in broad-spectrum activity of one Streptomyces isolate, not observed on SEA alone. In conclusion, SEA was found to expand the diversity of culturable isolates from soil and specifically enhanced the recovery of members of the genus Streptomyces. SEA was also found to be a superior media for antibiosis induction among Streptomyces isolates when compared to TSA. It was noted that Paenibacillus isolates’ antibiosis induction demonstrated a strain-specific response with respect to the growth media used. Conclusions: The authors propose SEA inclusion of in soil screening protocols as a cost-effective, complementary strategy to greatly enhance outcomes in undergraduate/citizen science-engaged antimicrobial biodiscovery initiatives. Full article

19 pages, 4842 KiB

Open AccessArticle

A Surveillance Study of Culturable and Antimicrobial-Resistant Bacteria in Two Urban WWTPs in Northern Spain

by Mario Sergio Pino-Hurtado, Rosa Fernández-Fernández, Allelen Campaña-Burguet, Carmen González-Azcona, Carmen Lozano, Myriam Zarazaga and Carmen Torres

Antibiotics 2024, 13(10), 955; https://doi.org/10.3390/antibiotics13100955 - 11 Oct 2024

Abstract

Background/Objectives: Wastewater treatment plants (WWTPs) are hotspots for the spread of antimicrobial resistance into the environment. This study aimed to estimate the proportion of clinically relevant antimicrobial-resistant bacteria in two Spanish urban WWTPs, located in the region of La Rioja (Spain); Methods: Ninety-four [...] Read more.

Background/Objectives: Wastewater treatment plants (WWTPs) are hotspots for the spread of antimicrobial resistance into the environment. This study aimed to estimate the proportion of clinically relevant antimicrobial-resistant bacteria in two Spanish urban WWTPs, located in the region of La Rioja (Spain); Methods: Ninety-four samples (48 water/46 sludge) were collected and streaked on ten different selective media, in order to recover the culturable bacterial diversity with relevant resistance phenotypes: Extended-Spectrum β-Lactamase-producing Escherichia coli/Klebsiella pneumoniae (ESBL-Ec/Kp), Carbapenem-resistant Enterobacteriaceae (CR-E), Methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococcus faecium/faecalis (VR-E. faecium/faecalis). Isolates were identified by MALDI-TOF and were tested for antimicrobial susceptibility using the disk diffusion method. The confirmation of ESBL production was performed by the double-disk test; Results: A total of 914 isolates were recovered (31 genera and 90 species). Isolates with clinically relevant resistance phenotypes such as ESBL-Ec/Kp and CR-E were recovered in the effluent (0.4 × 10⁰–4.8 × 10¹ CFU/mL) and organic amendment samples (1.0–10¹–6.0 × 10² CFU/mL), which are discharged to surface waters/agricultural fields. We reported the presence of VR-E. faecium in non-treated sludge and in the digested sludge samples (1.3 × 10¹–1 × 10³ CFU/mL). MRSA was also recovered, but only in low abundance in the effluent (0.2 × 10¹ CFU/mL); Conclusions: This study highlights the need for improved wastewater technologies and stricter regulations on the use of amendment sludge in agriculture. In addition, regular monitoring and surveillance of WWTPs are critical for early detection and the mitigation of risks associated with the spread of antimicrobial resistance. Full article

(This article belongs to the Special Issue Tracking Reservoirs of Antimicrobial Resistance Genes in Environment)

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13 pages, 2866 KiB

Open AccessArticle

Comparative Properties of Helical and Linear Amphipathicity of Peptides Composed of Arginine, Tryptophan, and Valine

by Jessie Klousnitzer, Wenyu Xiang, Vania M. Polynice and Berthony Deslouches

Antibiotics 2024, 13(10), 954; https://doi.org/10.3390/antibiotics13100954 - 11 Oct 2024

Abstract

Background: The persistence of antibiotic resistance has incited a strong interest in the discovery of agents with novel antimicrobial mechanisms. The direct killing of multidrug-resistant bacteria by cationic antimicrobial peptides (AMPs) underscores their importance in the fight against infections associated with antibiotic resistance. [...] Read more.

Background: The persistence of antibiotic resistance has incited a strong interest in the discovery of agents with novel antimicrobial mechanisms. The direct killing of multidrug-resistant bacteria by cationic antimicrobial peptides (AMPs) underscores their importance in the fight against infections associated with antibiotic resistance. Despite a vast body of AMP literature demonstrating a plurality in structural classes, AMP engineering has been largely skewed toward peptides with idealized amphipathic helices (H-amphipathic). In contrast to helical amphipathicity, we designed a series of peptides that display the amphipathic motifs in the primary structure. We previously developed a rational framework for designing AMP libraries of H-amphipathic peptides consisting of Arg, Trp, and Val (H-RWV, with a confirmed helicity up to 88% in the presence of membrane lipids) tested against the most common MDR organisms. Methods: In this study, we re-engineered one of the series of the H-RWV peptides (8, 10, 12, 14, and 16 residues in length) to display the amphipathicity in the primary structure by side-by-side (linear) alignment of the cationic and hydrophobic residues into the 2 separate linear amphipathic (L-amphipathic) motifs. We compared the 2 series of peptides for antibacterial activity, red blood cell (RBC) lysis, killing and membrane-perturbation properties. Results: The L-RWV peptides achieved the highest antibacterial activity at a minimum length of 12 residues (L-RWV12, minimum optimal length or MOL) with the lowest mean MIC of 3–4 µM, whereas the MOL for the H-RWV series was reached at 16 residues (H-RWV16). Overall, H-RWV16 displayed the lowest mean MIC at 2 µM but higher levels of RBC lysis (25–30%), while the L-RWV series displayed minor RBC lytic effects at the test concentrations. Interestingly, when the S. aureus strain SA719 was chosen because of its susceptibility to most of the peptides, none of the L-RWV peptides demonstrated a high level of membrane perturbation determined by propidium iodide incorporation measured by flow cytometry, with <50% PI incorporation for the L-RWV peptides. By contrast, most H-RWV peptides displayed almost up to 100% PI incorporation. The results suggest that membrane perturbation is not the primary killing mechanism of the L-amphipathic RWV peptides, in contrast to the H-RWV peptides. Conclusions: Taken together, the data indicate that both types of amphipathicity may provide different ideal pharmacological properties that deserve further investigation. Full article

(This article belongs to the Special Issue Computational Approaches in Discovery and Design of Antimicrobial Peptides - 2nd Edition)

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