Antibiotics

15 pages, 298 KiB

Open AccessArticle

Combinatory Use of hLF(1-11), a Synthetic Peptide Derived from Human Lactoferrin, and Fluconazole/Amphotericin B against Malassezia furfur Reveals a Synergistic/Additive Antifungal Effect

by Carlo P. J. M. Brouwer, Bart Theelen, Youp van der Linden, Nick Sarink, Mahfuzur Rahman, Saleh Alwasel, Claudia Cafarchia, Mick M. Welling and Teun Boekhout

Antibiotics 2024, 13(8), 790; https://doi.org/10.3390/antibiotics13080790 - 22 Aug 2024

Viewed by 853

Abstract

Objective: The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and [...] Read more.

Objective: The increasing resistance of Malassezia yeasts against commonly used antifungal drugs dictates the need for novel antifungal compounds. Human lactoferrin-based peptides show a broad spectrum of antimicrobial activities. Various assays were performed to find the optimal growth conditions of the yeasts and to assess cell viability, using media with low lipid content to avoid peptide binding to medium components. Methods: In the current study, we tested the antimicrobial susceptibility of 30 strains of M. furfur that cover the known IGS1 genotypic variation. Results: hLF(1-11) inhibited the growth of all species tested, resulting in minimum inhibitory concentrations (MIC) values ranging from 12.5 to 100 μg/mL. In the combinatory tests, the majority of fractional inhibitory concentration indexes (FIC) for the tested strains of M. furfur were up to 1.0, showing that there is a synergistic or additive effect on the efficacy of the antifungal drugs when used in combination with hLF(1-11). Conclusion: Results showed that hLF(1-11) could be combined with fluconazole or amphotericin for the antimicrobial treatment of resistant strains, enhancing the potency of these antifungal drugs, resulting in an improved outcome for the patient. Full article

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

31 pages, 852 KiB

Open AccessReview

Infection Prevention and Control Strategies According to the Type of Multidrug-Resistant Bacteria and Candida auris in Intensive Care Units: A Pragmatic Resume including Pathogens R₀ and a Cost-Effectiveness Analysis

by Chiara Fanelli, Laura Pistidda, Pierpaolo Terragni and Daniela Pasero

Antibiotics 2024, 13(8), 789; https://doi.org/10.3390/antibiotics13080789 - 22 Aug 2024

Viewed by 2496

Abstract

Multidrug-resistant organism (MDRO) outbreaks have been steadily increasing in intensive care units (ICUs). Still, healthcare institutions and workers (HCWs) have not reached unanimity on how and when to implement infection prevention and control (IPC) strategies. We aimed to provide a pragmatic physician practice-oriented [...] Read more.

Multidrug-resistant organism (MDRO) outbreaks have been steadily increasing in intensive care units (ICUs). Still, healthcare institutions and workers (HCWs) have not reached unanimity on how and when to implement infection prevention and control (IPC) strategies. We aimed to provide a pragmatic physician practice-oriented resume of strategies towards different MDRO outbreaks in ICUs. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios; education, isolation, decolonization, screening, and hygiene practices; outbreak reporting; cost-effectiveness; reproduction numbers (R₀); and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician lose sight of the big picture. IPC strategies have proven their cost-effectiveness regardless of typology, country, and pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, the elaboration of a rapid outbreak recognition tool (i.e., an easy-to-use mathematical model) would improve early diagnosis and prevent spreading. Further studies are needed to express views in favor or against MDRO decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategy application has made and still makes ICUs major MDRO reservoirs in the community. In a not-too-distant future, genetic engineering and phage therapies could represent a plot twist in MDRO IPC strategies. Full article

(This article belongs to the Special Issue Antibacterial Resistance and Infection Control in ICU)

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20 pages, 3903 KiB

Open AccessReview

Artificial Intelligence-Driven Analysis of Antimicrobial-Resistant and Biofilm-Forming Pathogens on Biotic and Abiotic Surfaces

by Akanksha Mishra, Nazia Tabassum, Ashish Aggarwal, Young-Mog Kim and Fazlurrahman Khan

Antibiotics 2024, 13(8), 788; https://doi.org/10.3390/antibiotics13080788 - 22 Aug 2024

Cited by 3 | Viewed by 2091

Abstract

The growing threat of antimicrobial-resistant (AMR) pathogens to human health worldwide emphasizes the need for more effective infection control strategies. Bacterial and fungal biofilms pose a major challenge in treating AMR pathogen infections. Biofilms are formed by pathogenic microbes encased in extracellular polymeric [...] Read more.

The growing threat of antimicrobial-resistant (AMR) pathogens to human health worldwide emphasizes the need for more effective infection control strategies. Bacterial and fungal biofilms pose a major challenge in treating AMR pathogen infections. Biofilms are formed by pathogenic microbes encased in extracellular polymeric substances to confer protection from antimicrobials and the host immune system. Biofilms also promote the growth of antibiotic-resistant mutants and latent persister cells and thus complicate therapeutic approaches. Biofilms are ubiquitous and cause serious health risks due to their ability to colonize various surfaces, including human tissues, medical devices, and food-processing equipment. Detection and characterization of biofilms are crucial for prompt intervention and infection control. To this end, traditional approaches are often effective, yet they fail to identify the microbial species inside biofilms. Recent advances in artificial intelligence (AI) have provided new avenues to improve biofilm identification. Machine-learning algorithms and image-processing techniques have shown promise for the accurate and efficient detection of biofilm-forming microorganisms on biotic and abiotic surfaces. These advancements have the potential to transform biofilm research and clinical practice by allowing faster diagnosis and more tailored therapy. This comprehensive review focuses on the application of AI techniques for the identification of biofilm-forming pathogens in various industries, including healthcare, food safety, and agriculture. The review discusses the existing approaches, challenges, and potential applications of AI in biofilm research, with a particular focus on the role of AI in improving diagnostic capacities and guiding preventative actions. The synthesis of the current knowledge and future directions, as described in this review, will guide future research and development efforts in combating biofilm-associated infections. Full article

(This article belongs to the Special Issue Epidemiology of Clinically Relevant Bacteria and Antimicrobial Resistance)

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21 pages, 7367 KiB

Open AccessArticle

In Vitro and In Silico Studies of the Antimicrobial Activity of Prenylated Phenylpropanoids of Green Propolis and Their Derivatives against Oral Bacteria

by Tatiana M. Vieira, Julia G. Barco, Sara L. de Souza, Anna L. O. Santos, Ismail Daoud, Seyfeddine Rahali, Noureddine Amdouni, Jairo K. Bastos, Carlos H. G. Martins, Ridha Ben Said and Antônio E. M. Crotti

Antibiotics 2024, 13(8), 787; https://doi.org/10.3390/antibiotics13080787 - 22 Aug 2024

Viewed by 998

Abstract

Artepillin C, drupanin, and plicatin B are prenylated phenylpropanoids that naturally occur in Brazilian green propolis. In this study, these compounds and eleven of their derivatives were synthesized and evaluated for their in vitro antimicrobial activity against a representative panel of oral bacteria [...] Read more.

Artepillin C, drupanin, and plicatin B are prenylated phenylpropanoids that naturally occur in Brazilian green propolis. In this study, these compounds and eleven of their derivatives were synthesized and evaluated for their in vitro antimicrobial activity against a representative panel of oral bacteria in terms of their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Plicatin B (2) and its hydrogenated derivative 8 (2′,3′,7,8-tetrahydro-plicatin B) were the most active compounds. Plicatin B (2) displayed strong activity against all the bacteria tested, with an MIC of 31.2 μg/mL against Streptococcus mutans, S. sanguinis, and S. mitis. On the other hand, compound 8 displayed strong activity against S. mutans, S. salivarius, S. sobrinus, Lactobacillus paracasei (MIC = 62.5 μg/mL), and S. mitis (MIC = 31.2 μg/mL), as well as moderate activity against Enterococcus faecalis and S. sanguinis (MIC = 125 μg/mL). Compounds 2 and 8 displayed bactericidal effects (MBC: MIC ≤ 4) against all the tested bacteria. In silico studies showed that the complexes formed by compounds 2 and 8 with the S. mitis, S. sanguinis, and S. mutans targets (3LE0, 4N82, and 3AIC, respectively) had energy score values similar to those of the native S. mitis, S. sanguinis, and S. mutans ligands due to the formation of strong hydrogen bonds. Moreover, all the estimated physicochemical parameters satisfied the drug-likeness criteria without violating the Lipinski, Veber, and Egan rules, so these compounds are not expected to cause problems with oral bioavailability and pharmacokinetics. Compounds 2 and 8 also had suitable ADMET parameters, as the online server pkCSM calculates. These results make compounds 2 and 8 good candidates as antibacterial agents against oral bacteria. Full article

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

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26 pages, 513 KiB

Open AccessReview

Rapid Phenotypic and Genotypic Antimicrobial Susceptibility Testing Approaches for Use in the Clinical Laboratory

by Siham Hattab, Adrienne H. Ma, Zoon Tariq, Ilianne Vega Prado, Ian Drobish, Rachel Lee and Rebecca Yee

Antibiotics 2024, 13(8), 786; https://doi.org/10.3390/antibiotics13080786 - 22 Aug 2024

Viewed by 1743

Abstract

The rapid rise in increasingly resistant bacteria has become a major threat to public health. Antimicrobial susceptibility testing (AST) is crucial in guiding appropriate therapeutic decisions and infection prevention practices for patient care. However, conventional culture-based AST methods are time-consuming and labor-intensive. Therefore, [...] Read more.

The rapid rise in increasingly resistant bacteria has become a major threat to public health. Antimicrobial susceptibility testing (AST) is crucial in guiding appropriate therapeutic decisions and infection prevention practices for patient care. However, conventional culture-based AST methods are time-consuming and labor-intensive. Therefore, rapid AST approaches exist to address the delayed gap in time to actionable results. There are two main types of rapid AST technologies— phenotypic and genotypic approaches. In this review, we provide a summary of all commercially available rapid AST platforms for use in clinical microbiology laboratories. We describe the technologies utilized, performance characteristics, acceptable specimen types, types of resistance detected, turnaround times, limitations, and clinical outcomes driven by these rapid tests. We also discuss crucial factors to consider for the implementation of rapid AST technologies in a clinical laboratory and what the future of rapid AST holds. Full article

(This article belongs to the Special Issue Rapid Antibiotic Susceptibility Testing)

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15 pages, 705 KiB

Open AccessArticle

Phytochemical Study of Ethanol Extract of Gnaphalium uliginosum L. and Evaluation of Its Antimicrobial Activity

by Lilia Davydova, Angelina Menshova, Georgiy Shumatbaev, Vasily Babaev and Evgeny Nikitin

Antibiotics 2024, 13(8), 785; https://doi.org/10.3390/antibiotics13080785 - 22 Aug 2024

Viewed by 714

Abstract

This study evaluates the antibacterial and antifungal effects of ethanol extracts from Gnaphalium uliginosum L. derived from freshly harvested plant biomass, including stems, leaves, flowers, and roots. The extract was analyzed using gas chromatography-mass spectrometry (GC-MS) to determine its antimicrobial activity against phytopathogenic [...] Read more.

This study evaluates the antibacterial and antifungal effects of ethanol extracts from Gnaphalium uliginosum L. derived from freshly harvested plant biomass, including stems, leaves, flowers, and roots. The extract was analyzed using gas chromatography-mass spectrometry (GC-MS) to determine its antimicrobial activity against phytopathogenic bacteria and fungi. Two methods were used in the experiments: agar well diffusion and double serial dilution. Extraction was carried out using the maceration method with different temperature regimes (25 °C, 45 °C, and 75 °C) and the ultrasonic method at various powers (63–352 W) for different durations (5 and 10 min). It was found that the 70% ethanol extract obtained through the ultrasonic experiment at 189 W power for 10 min and at 252 W power for 5 min had the highest antimicrobial activity compared to the maceration method. The most sensitive components of the extracts were the Gram-positive phytopathogenic bacteria Clavibacter michiganensis and the Gram-negative phytopathogenic bacteria Erwinia carotovora spp., with MIC values of 156 μg/mL. Among the fungi, the most sensitive were Rhizoctonia solani and Alternaria solani (MIC values in the range of 78–156 µg/mL). The evaluation of the antimicrobial activity of extracts using the diffusion method established the presence of a growth suppression zone in the case of C. michiganensis (15–17 mm for flowers, leaves, and total biomass), which corresponds to the average level of antimicrobial activity. These findings suggest that G. uliginosum has potential as a source of biologically active compounds for agricultural use, particularly for developing novel biopesticides. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms, 2nd Edition)

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15 pages, 580 KiB

Open AccessArticle

Challenges Facing Two Outbreaks of Carbapenem-Resistant Acinetobacter baumannii: From Cefiderocol Susceptibility Testing to the Emergence of Cefiderocol-Resistant Mutants

by Montserrat Rodríguez-Aguirregabiria, Fernando Lázaro-Perona, Juana Begoña Cacho-Calvo, Mª Soledad Arellano-Serrano, Juan Carlos Ramos-Ramos, Eduardo Rubio-Mora, Mariana Díaz-Almirón and Mª José Asensio-Martín

Antibiotics 2024, 13(8), 784; https://doi.org/10.3390/antibiotics13080784 - 21 Aug 2024

Viewed by 1039

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient’s conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics [...] Read more.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient’s conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed. Overall, 28 patients were included. Ten patients (35.71%) had ventilator-associated pneumonia (VAP), ten (35.71%) had a bloodstream infection (BSI), and eight (28.57%) were only colonized. Recurrent infection occurred in 25% (5/20) of infected patients. Two different strains of A. baumannii were isolated from the index patient of the first outbreak. The first strain belonged to the ST85 and carried the bla_NDM-1 carbapenemase gene, while the second belonged to the ST2 and carried bla_OXA-23, and bla_OXA-66 carbapenemase genes. The phylogenetic analysis revealed that the ST2 strain was the cause of the major outbreak, and mutations in the AmpC gene were related to progressive increasing minimum inhibitory concentration (MIC) and finally, cefiderocol-resistance in one strain. The CRAB isolates from the second outbreak were also identified as ST2. Cefiderocol-resistant strains tests identified by the disc diffusion method were involved in 24% (6/25) of nosocomial infections. Using broth microdilution (BMD) ComASP^® only, 33.3% (2/6) of these strains were cefiderocol-resistant. All-cause ICU mortality was 21.4%. Conclusions: Cefiderocol is the first approved siderophore cephalosporin for the treatment of CRAB infections. Cefiderocol-resistant strains were related with bla_NDM-1 carbapenemase and mutations in the AmpC gene. Cefiderocol-resistant strains or that cannot be properly interpreted by disk diffusion, should be retested using BMD for definitive categorization. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Therapy in Intensive Care Unit)

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37 pages, 9611 KiB

Open AccessReview

Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic–Antimicrobial Peptide Conjugates

by Maria Cristina Bellucci, Carola Romani, Monica Sani and Alessandro Volonterio

Antibiotics 2024, 13(8), 783; https://doi.org/10.3390/antibiotics13080783 - 21 Aug 2024

Viewed by 1087

Abstract

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective [...] Read more.

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Structure–Activity Relationship Studies on Antimicrobial Peptides)

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11 pages, 2278 KiB

Open AccessArticle

Poor Outcomes of Girdlestone Resection Arthroplasty in Injection Drug Users: A Retrospective Study

by Henry T. Shu, Diane Ghanem, Oscar Covarrubias, Zaid Elsabbagh, Alice J. Hughes, Rachel B. Sotsky, Janet D. Conway, Jamie Ferguson, Greg M. Osgood and Babar Shafiq

Antibiotics 2024, 13(8), 782; https://doi.org/10.3390/antibiotics13080782 - 21 Aug 2024

Viewed by 658

Abstract

This retrospective cohort study aims to investigate the clinical outcomes of Girdlestone resection arthroplasty (GRA) in injection drug users with septic hip arthritis. Patients who underwent primary GRA for septic hip arthritis secondary to injection drug use at two academic trauma centers from [...] Read more.

This retrospective cohort study aims to investigate the clinical outcomes of Girdlestone resection arthroplasty (GRA) in injection drug users with septic hip arthritis. Patients who underwent primary GRA for septic hip arthritis secondary to injection drug use at two academic trauma centers from 2015 to 2023 were retrospectively reviewed. Patient demographics, surgical details, and follow-up outcomes, including patient-reported outcome measures, were collected and analyzed. The cohort included 15 patients, with a mean age of 44 ± 11 years and a mean follow-up period of 25 ± 20 months. Among the 15 patients, overall mortality was 27%, and only 4 patients underwent total hip arthroplasty (THA) following GRA. Infection resolution rates were significantly higher in patients who received an antibiotic spacer (75% vs. 0%, p = 0.048). GRA in injection drug users is associated with high mortality and low conversion rates to THA. The use of an antibiotic spacer during GRA significantly improves infection resolution rates. Larger studies are required to determine the optimal management strategies for this patient population. Full article

(This article belongs to the Special Issue Diagnosis and Antimicrobial Therapy of Osteoarticular Infection)

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12 pages, 428 KiB

Open AccessArticle

Efficacy and Safety of Oral Neomycin for the Decolonization of Carbapenem-Resistant Enterobacterales: An Open-Label Randomized Controlled Trial

by Lalita Tancharoen, Ananya Srisomnuek, Surapee Tiengrim, Narisara Thamthaweechok, Teerawit Tangkorskul and Visanu Thamlikitkul

Antibiotics 2024, 13(8), 781; https://doi.org/10.3390/antibiotics13080781 - 20 Aug 2024

Viewed by 932

Abstract

Background: Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66–85% of isolates. This study evaluated the efficacy and safety of neomycin [...] Read more.

Background: Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66–85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization. Methods: In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (n = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (n = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2. Results: The two groups’ baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, p = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8–53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group’s rate (73.1% vs. 61.5%, p = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects. Conclusions: Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization. Full article

(This article belongs to the Special Issue Antimicrobial Prescribing, Population Use and Resistance, Impact in Global Health, 2nd Edition)

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25 pages, 2098 KiB

Open AccessArticle

Antibiotic Residues and Resistance in Three Wastewater Treatment Plants in Romania

by Svetlana Iuliana Polianciuc, Alexandra Ciorîță, Maria Loredana Soran, Ildiko Lung, Béla Kiss, Maria Georgia Ștefan, Daniel Corneliu Leucuța, Anca Elena Gurzău, Rahela Carpa, Liora Mihaela Colobațiu and Felicia Loghin

Antibiotics 2024, 13(8), 780; https://doi.org/10.3390/antibiotics13080780 - 19 Aug 2024

Viewed by 1036

Abstract

This study evaluates antibiotic residues and bacterial loads in influent and effluent samples from three wastewater treatment plants (WWTPs) in Romania, across four seasons from 2021 to 2022. Analytical methods included solid-phase extraction and high-performance liquid chromatography (HPLC) to quantify antibiotic concentrations, while [...] Read more.

This study evaluates antibiotic residues and bacterial loads in influent and effluent samples from three wastewater treatment plants (WWTPs) in Romania, across four seasons from 2021 to 2022. Analytical methods included solid-phase extraction and high-performance liquid chromatography (HPLC) to quantify antibiotic concentrations, while microbiological assays estimated bacterial loads and assessed antibiotic resistance patterns. Statistical analyses explored the impact of environmental factors such as temperature and rainfall on antibiotic levels. The results showed significant seasonal variations, with higher antibiotic concentrations in warmer seasons. Antibiotic removal efficiency varied among WWTPs, with some antibiotics being effectively removed and others persisting in the effluent, posing high environmental risks and potential for antibiotic resistance development. Bacterial loads were higher in spring and summer, correlating with increased temperatures. Eight bacterial strains were isolated, with higher resistance during warmer seasons, particularly to amoxicillin and clarithromycin. Full article

(This article belongs to the Special Issue Antibiotics and Environment − Research and Development toward the One Health Approach)

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10 pages, 1359 KiB

Open AccessArticle

EDBD—3,6-Epidioxy-1,10-Bisaboladiene—An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection

by Eric Umehara, Thainá R. Teixeira, Rayssa A. Cajás, Monique C. Amaro, Josué de Moraes and João Henrique G. Lago

Antibiotics 2024, 13(8), 779; https://doi.org/10.3390/antibiotics13080779 - 18 Aug 2024

Viewed by 833

Abstract

Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to [...] Read more.

Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against Schistosoma mansoni Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of Drimys brasiliensis afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against S. mansoni. EDBD exhibited a significant reduction in S. mansoni viability in vitro, with an effective concentration (EC₅₀) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of S. mansoni-infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel’s efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment. Full article

(This article belongs to the Special Issue Antiparasitic Natural Products)

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21 pages, 4502 KiB

Open AccessArticle

Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms

by Li Tan, Rong Ma, Adam J. Katz and Nicole Levi

Antibiotics 2024, 13(8), 778; https://doi.org/10.3390/antibiotics13080778 - 17 Aug 2024

Viewed by 1014

Abstract

The family of ESKAPE pathogens is comprised of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. Together they are the main contributors of nosocomial infections and are well established for their ability to “escape” antibiotics. Farnesol is [...] Read more.

The family of ESKAPE pathogens is comprised of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. Together they are the main contributors of nosocomial infections and are well established for their ability to “escape” antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties. In a proprietary emulsion, farnesol has been shown to be capable of disrupting S. aureus, P. aeruginosa, and A. baumannii biofilms. The current work demonstrates that this farnesol emulsion reduces the number of viable bacteria, while also leading to reductions in biomass, of the other three ESKAPE pathogens: Enterococcus faecium, Klebsiella pneumoniae, and Enterobacter, both in vitro and in an ex vivo human skin model. A concentration of 0.5 mg/mL was effective for impeding biofilm development of all three bacteria, while 1 mg/mL for E. faecium and K. pneumoniae, or 0.2 mg/mL for E. cloacae, was able to kill bacteria in established biofilms. Contrary to antibiotics, no resistance to farnesol was observed for E. faecium or K. pneumoniae. The results indicate that farnesol is effective for direct cell killing and also has the ability to induce biofilm detachment from surfaces, as confirmed using Live/Dead image analysis. Our findings confirm that farnesol emulsion is an effective broad-spectrum agent to impede ESKAPE biofilms. Full article

(This article belongs to the Special Issue Combating Biofilm-Related Infections: Novel Therapeutics and Strategies)

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19 pages, 3823 KiB

Open AccessArticle

Green Synthesis of Silver Nanoparticle from Anadenanthera colubrina Extract and Its Antimicrobial Action against ESKAPEE Group Bacteria

by Anastácia Nikolaos Deonas, Lucas Marcelino dos Santos Souza, Gabriel Jonathan Sousa Andrade, Jennifer Germiniani-Cardozo, Débora Dahmer, Admilton Gonçalves de Oliveira, Gerson Nakazato, José Marcelo Domingues Torezan and Renata Katsuko Takayama Kobayashi

Antibiotics 2024, 13(8), 777; https://doi.org/10.3390/antibiotics13080777 - 16 Aug 2024

Cited by 1 | Viewed by 965

Abstract

Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from Anadenanthera colubrina (Vell.) Brenan var. colubrina. The methodology included obtaining the extract [...] Read more.

Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from Anadenanthera colubrina (Vell.) Brenan var. colubrina. The methodology included obtaining the extract and characterizing the AgNPs, which revealed antimicrobial activity against MDR bacteria. A. colubrina species is valued in indigenous and traditional medicine for its medicinal properties. Herein, it was employed to synthesize AgNPs with effective antibacterial activity (MIC = 19.53–78.12 μM) against clinical isolates from the ESKAPEE group, known for causing high hospitalization costs and mortality rates. Despite its complexity, AgNP synthesis is an affordable method with minimal environmental impacts and risks. Plant-synthesized AgNPs possess unique characteristics that affect their biological activity and cytotoxicity. In this work, A. colubrina bark extract resulted in the synthesis of nanoparticles measuring 75.62 nm in diameter, with a polydispersity index of 0.17 and an average zeta potential of −29 mV, as well as low toxicity for human erythrocytes, with a CC₅₀ value in the range of 961 μM. This synthesis underscores its innovative potential owing to its low toxicity, suggesting applicability across several areas and paving the way for future research. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms, 2nd Edition)

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12 pages, 256 KiB

Open AccessReview

Source Control and Antibiotics in Intra-Abdominal Infections

by Raffaele Bova, Giulia Griggio, Carlo Vallicelli, Giorgia Santandrea, Federico Coccolini, Luca Ansaloni, Massimo Sartelli, Vanni Agnoletti, Francesca Bravi and Fausto Catena

Antibiotics 2024, 13(8), 776; https://doi.org/10.3390/antibiotics13080776 - 16 Aug 2024

Viewed by 1389

Abstract

Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23–38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones [...] Read more.

Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23–38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones of management of IAIs and are associated with a more favorable clinical outcome. The aim of source control is to reduce microbial load by removing the infection source and it is achievable by using a wide range of procedures, such as definitive surgical removal of anatomic infectious foci, percutaneous drainage and toilette of infected collections, decompression, and debridement of infected and necrotic tissue or device removal, providing for the restoration of anatomy and function. Damage control surgery may be an option in selected septic patients. Intra-abdominal infections can be classified as uncomplicated or complicated causing localized or diffuse peritonitis. Early clinical evaluation is mandatory in order to optimize diagnostic testing and establish a therapeutic plan. Prognostic scores could serve as helpful tools in medical settings for evaluating both the seriousness and future outlook of a condition. The patient’s conditions and the potential progression of the disease determine when to initiate source control. Patients can be classified into three groups based on disease severity, the origin of infection, and the patient’s overall physical health, as well as any existing comorbidities. In recent decades, antibiotic resistance has become a global health threat caused by inappropriate antibiotic regimens, inadequate control measures, and infection prevention. The sepsis prevention and infection control protocols combined with optimizing antibiotic administration are crucial to improve outcome and should be encouraged in surgical departments. Antibiotic and antifungal regimens in patients with IAIs should be based on the resistance epidemiology, clinical conditions, and risk for multidrug resistance (MDR) and Candida spp. infections. Several challenges still exist regarding the effectiveness, timing, and patient stratification, as well as the procedures for source control. Antibiotic choice, optimal dosing, and duration of therapy are essential to achieve the best treatment. Promoting standard of care in the management of IAIs improves clinical outcomes worldwide. Further trials and stronger evidence are required to achieve optimal management with the least morbidity in the clinical care of critically ill patients with intra-abdominal sepsis. Full article

(This article belongs to the Special Issue Antibiotics in the Critically Ill Patient)

13 pages, 1384 KiB

Open AccessArticle

Anti-Biofilm and Anti-Inflammatory Properties of the Truncated Analogs of the Scorpion Venom-Derived Peptide IsCT against Pseudomonas aeruginosa

by Pornpimon Jantaruk, Kittitat Teerapo, Supattra Charoenwutthikun, Sittiruk Roytrakul and Duangkamol Kunthalert

Antibiotics 2024, 13(8), 775; https://doi.org/10.3390/antibiotics13080775 - 16 Aug 2024

Viewed by 1360

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen in humans and a frequent cause of severe nosocomial infections and fatal infections in immunocompromised individuals. Its ability to form biofilms has been the main driving force behind its resistance to almost all conventional antibiotics, thereby limiting [...] Read more.

Pseudomonas aeruginosa is an opportunistic pathogen in humans and a frequent cause of severe nosocomial infections and fatal infections in immunocompromised individuals. Its ability to form biofilms has been the main driving force behind its resistance to almost all conventional antibiotics, thereby limiting treatment efficacy. In an effort to discover novel therapeutic agents to fight P. aeruginosa-associated biofilm infections, the truncated analogs of scorpion venom-derived peptide IsCT were synthesized and their anti-biofilm properties were examined. Among the investigated peptides, the IsCT-Δ6-8 peptide evidently showed the most potential anti-P. aeruginosa biofilm activity and the effect was not due to bacterial growth inhibition. The IsCT-Δ6-8 peptide also exhibited inhibitory activity against the production of pyocyanin, an important virulence factor of P. aeruginosa. Furthermore, the IsCT-Δ6-8 peptide significantly suppressed the production of inflammatory mediators nitric oxide and interleukin-6 in P. aeruginosa LPS-induced macrophages. Due to its low cytotoxicity to mammalian cells, the IsCT-Δ6-8 peptide emerges as a promising candidate with significant anti-biofilm and anti-inflammatory properties. These findings highlight its potential application in treating P. aeruginosa-related biofilm infections. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Bioactive Peptides and Their Derivatives)

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21 pages, 3702 KiB

Open AccessArticle

Genetic Characterization, Antibiotic Resistance, and Virulence Genes Profiling of Bacillus cereus Strains from Various Foods in Japan

by Marwa Nabil Sayed Abdelaziz, Mahmoud Gamaleldin Zayda, Aye Thida Maung, Mohamed El-Telbany, Tahir Noor Mohammadi, Su Zar Chi Lwin, Khin Zar Linn, Chen Wang, Lu Yuan, Yoshimitsu Masuda, Ken-ichi Honjoh and Takahisa Miyamoto

Antibiotics 2024, 13(8), 774; https://doi.org/10.3390/antibiotics13080774 - 16 Aug 2024

Viewed by 1335

Abstract

Bacillus cereus sensu stricto is a foodborne pathogen that causes food poisoning. Their spore and biofilm-forming abilities persist in various environments and foods. This study investigated the prevalence, virulence, antibiotic resistance, and genetic diversity of B. cereus s. s. strains isolated from various [...] Read more.

Bacillus cereus sensu stricto is a foodborne pathogen that causes food poisoning. Their spore and biofilm-forming abilities persist in various environments and foods. This study investigated the prevalence, virulence, antibiotic resistance, and genetic diversity of B. cereus s. s. strains isolated from various food samples. Of 179 samples, 22.34% were positive for B. cereus s. s., with significantly high detection rates in milk products and raw chicken meat. Forty strains were isolated from positive samples. Matrix-assisted laser desorption ionization/time of flight mass spectrometry analysis revealed nine distinct clusters and multi-locus sequence typing revealed 34 sequence types including 23 novel sequences, demonstrating high genetic diversity among the isolates. PCR analysis revealed that all the strains contained at least one toxin gene, but none contained the cytK gene. Antibiotic resistance tests revealed that all isolates were classified as multidrug-resistant, with high resistance levels, particularly to β-lactam antibiotics and vancomycin, but were susceptible to gentamicin. All isolates showed variations in biofilm formation. This study highlights the significant public health risk due to B. cereus s. s. and underscores the need for stringent monitoring and control measures in food production to manage antimicrobial resistance and ensure food safety. Full article

(This article belongs to the Special Issue Infectious Disease Testing and Pathogenic Bacterial Virulence Identification)

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18 pages, 1879 KiB

Open AccessArticle

Phylogenetic Diversity, Antibiotic Resistance, and Virulence of Escherichia coli Strains from Urinary Tract Infections in Algeria

by Anfal Kara, Chiara Massaro, Giovanni M. Giammanco, Rosa Alduina and Naouel Boussoualim

Antibiotics 2024, 13(8), 773; https://doi.org/10.3390/antibiotics13080773 - 15 Aug 2024

Viewed by 1150

Abstract

Urinary tract infections (UTIs) caused by Escherichia coli represent a significant public health concern due to the high virulence and antimicrobial resistance exhibited by these pathogens. This study aimed to analyze the phylogenetic diversity and antibiotic resistance profiles of Uropathogenic E. coli (UPEC) [...] Read more.

Urinary tract infections (UTIs) caused by Escherichia coli represent a significant public health concern due to the high virulence and antimicrobial resistance exhibited by these pathogens. This study aimed to analyze the phylogenetic diversity and antibiotic resistance profiles of Uropathogenic E. coli (UPEC) strains isolated from UTI patients in Algeria, focusing on virulence factors such as extended β-lactamase (ESBL) production, biofilm formation, and hemolytic activity. Phylogenetic grouping of 86 clinical imipenem resistant E. coli isolates showed the prevalence of group B2 (48.9%), followed by groups E (22.1%), unknown (12.8%), A (8.1%), and B1 (4.7%), and Clade I, D, Clade I, or Clade II (1.2%). The highest resistance rates were observed towards amoxicillin (86.04%), ticarcillin (82.55%), piperacillin (73.25%), nitrofurantoin (84.88%), and trimethoprim-sulfamethoxazole (51.16%). Notably, 69.8% of UPEC strains were multidrug-resistant (MDR) and 23.2% were extensively drug-resistant (XDR). Additionally, 48.9%, 42%, and 71% of strains demonstrated ESBL production, hemolytic activity, and weak biofilm production, respectively. Continuous monitoring and characterization of UPEC strains are essential to track the spread of the most resistant and virulent phylogenetic groups over time, facilitating rapid therapeutic decisions to treat infections and prevent the emergence of new resistant organisms, helping choose the most effective antibiotics and reducing treatment failure. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance)

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17 pages, 1033 KiB

Open AccessReview

Antimicrobial Regimens in Cement Spacers for Periprosthetic Joint Infections: A Critical Review

by Symeon Naoum, Christos Koutserimpas, Ioannis Pantekidis, Vasileios Giovanoulis, Enejd Veizi, Maria Piagkou, Petros Ioannou, George Samonis, Aglaia Domouchtsidou, Andreas G. Tsantes and Dimitrios V. Papadopoulos

Antibiotics 2024, 13(8), 772; https://doi.org/10.3390/antibiotics13080772 - 15 Aug 2024

Cited by 1 | Viewed by 1509

Abstract

Antibiotic-loaded cement spacers (ALCSs) are essential for treating periprosthetic joint infections (PJIs) by providing mechanical support and local antibiotic delivery. The purpose of this review is to comprehensively examine the various types of spacers utilised in the management of periprosthetic joint infections (PJIs), [...] Read more.

Antibiotic-loaded cement spacers (ALCSs) are essential for treating periprosthetic joint infections (PJIs) by providing mechanical support and local antibiotic delivery. The purpose of this review is to comprehensively examine the various types of spacers utilised in the management of periprosthetic joint infections (PJIs), including both static and articulating variants and to analyse the fundamental principles underlying spacer use, their clinical benefits, the selection and administration of antimicrobial agents, appropriate dosages, and potential adverse effects. Articulating spacers, which allow joint mobility, often yield better outcomes than static ones. Spacer pharmacokinetics are vital for maintaining therapeutic antibiotic levels, influenced by cement porosity, mixing techniques, and the contact area. Antibiotic choice depends on heat stability, solubility, and impact on cement’s mechanical properties. Mechanical properties are crucial, as spacers must withstand physical stresses, with antibiotics potentially affecting these properties. Complications, such as tissue damage and systemic toxicity, are discussed, along with mitigation strategies. Future advancements include surface modifications and novel carriers to enhance biofilm management and infection control. Full article

(This article belongs to the Special Issue Osteoarticular Infections: New Challenges and Current Concepts in Antibiotic Therapy)

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9 pages, 197 KiB

Open AccessArticle

Do Organism Profile and Resistance Patterns Change between First and Subsequent Two-Stage Revision for Periprosthetic Joint Infection?

by Helmut Ahrens, Amelie Constanze Steinicke, Georg Gosheger, Jan Schwarze, Sebastian Bockholt, Burkhard Moellenbeck and Christoph Theil

Antibiotics 2024, 13(8), 771; https://doi.org/10.3390/antibiotics13080771 - 15 Aug 2024

Viewed by 721

Abstract

Increasing antibiotic resistance has been reported as an issue in the treatment of periprosthetic joint infection (PJI). A repeat two-stage revision for recurrent PJI is at high risk of reinfection. However, it is unclear if the microorganism profile plays a role with potentially [...] Read more.

Increasing antibiotic resistance has been reported as an issue in the treatment of periprosthetic joint infection (PJI). A repeat two-stage revision for recurrent PJI is at high risk of reinfection. However, it is unclear if the microorganism profile plays a role with potentially more resistant or polymicrobial infections. This is a retrospective, single-center analysis of two-stage revisions performed between 2011 and 2017. We identified 46 patients who underwent a repeat resection arthroplasty for recurrent PJI of the same joint after a previous two-stage revision of the same joint at the same department. All microbiological findings were analyzed focusing on microbiological spectrum and resistance testing as well as the potential impact on reinfection-free survival. The most common organism found at the time of recurrent PJI were coagulase-negative Staphylococci (39%) followed by Gram-negative organisms (28%). The risk of polymicrobial infections, difficult-to-treat resistant organisms, and Gram-negative infections increased significantly. Among staphylococcal infections, there was a high percentage of methicillin-resistant species and resistance to oral antibiotics. Patients with Gram-negative organisms had a reduced infection-free survivorship, while resistant organisms were not associated with decreased survival. Patients who undergo a repeat two-stage revision for recurrent PJI have more polymicrobial and resistant organisms, although the impact on survivorship is unclear. Full article

(This article belongs to the Special Issue Prevention and Antibiotic Treatment of Periprosthetic Joint Infection)

11 pages, 253 KiB

Open AccessArticle

Cefiderocol-Based Regimen for Acinetobacter NDM-1 Outbreak

by Giovanna Travi, Francesco Peracchi, Marco Merli, Noemi Lo Re, Elisa Matarazzo, Livia Tartaglione, Alessandra Bielli, Giorgia Casalicchio, Fulvio Crippa, Chiara S. Vismara and Massimo Puoti

Antibiotics 2024, 13(8), 770; https://doi.org/10.3390/antibiotics13080770 - 15 Aug 2024

Viewed by 973

Abstract

Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol. Thirty-eight patients were colonized and/or infected. Thirteen patients [...] Read more.

Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol. Thirty-eight patients were colonized and/or infected. Thirteen patients developed a systemic infection. A clinical cure was achieved in 10 (83%) patients, one VAP and 9 BSIs, at day 7. In vitro, the activity of cefiderocol does not appear to match in vivo effectiveness using currently available commercial tests. Despite high clinical cures, overall mortality remains high in severely ill patients. Cefiderocol may be considered in this specific setting, though the implementation of susceptibility tests and infection control measures is mandatory. Full article

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

11 pages, 513 KiB

Open AccessArticle

Clostridioides difficile Infection: Use of Inflammatory Biomarkers and Hemogram-Derived Ratios to Predict Mortality Risk in Hospitalized Patients

by Giuseppe Guido Maria Scarlata, Angela Quirino, Carmen Costache, Dan Alexandru Toc, Nadia Marascio, Marta Pantanella, Daniel Corneliu Leucuta, Abdulrahman Ismaiel, Dan Lucian Dumitrascu and Ludovico Abenavoli

Antibiotics 2024, 13(8), 769; https://doi.org/10.3390/antibiotics13080769 - 15 Aug 2024

Viewed by 1115

Abstract

Background: Clostridioides difficile infection (CDI) is a significant cause of mortality, especially in healthcare environments. Reliable biomarkers that can accurately predict mortality in CDI patients are yet to be evaluated. Our study aims to evaluate the accuracy of several inflammatory biomarkers and hemogram-derived [...] Read more.

Background: Clostridioides difficile infection (CDI) is a significant cause of mortality, especially in healthcare environments. Reliable biomarkers that can accurately predict mortality in CDI patients are yet to be evaluated. Our study aims to evaluate the accuracy of several inflammatory biomarkers and hemogram-derived ratios in predicting mortality in CDI patients, such as the neutrophil-to-lymphocyte ratio (NLR), the systemic immune-inflammation index (SII), the platelet-to-neutrophil ratio (PNR), the derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), and procalcitonin (PCT). Results: NLR showed a sensitivity of 72.5% and a specificity of 58.42% with an area under curve (AUC) = 0.652. SII had a sensitivity of 77.5%, a specificity of 54.74%, and an AUC = 0.64. PNR, neutrophils, dNLR, and lymphocytes had lower AUCs which ranged from 0.595 to 0.616, with varied sensitivity and specificity. CRP, leukocytes, and platelets showed modest predictive values with AUCs below 0.6. PCT had a sensitivity of 100%, a low specificity of 7.41%, and an AUC = 0.528. Methods: We conducted a retrospective analysis of CDI patients from two different hospital settings in Italy and Romania during the COVID-19 pandemic, from 1 January 2020 to 5 May 2023. Statistical analyses included t-tests, Wilcoxon rank-sum tests, χ2 tests, and multivariate logistic regression to identify predictors of mortality. ROC analysis assessed the accuracy of biomarkers and hemogram-derived ratios. A p value < 0.05 was considered significant. Conclusions: Neutrophils, dNLR, NLR, SII, and PNR are valuable biomarkers for predicting mortality in CDI patients. Understanding these predictors can improve risk stratification and clinical outcomes for CDI patients. Full article

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

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16 pages, 2619 KiB

Open AccessArticle

Innovative Alignment-Based Method for Antiviral Peptide Prediction

by Daniela de Llano García, Yovani Marrero-Ponce, Guillermin Agüero-Chapin, Francesc J. Ferri, Agostinho Antunes, Felix Martinez-Rios and Hortensia Rodríguez

Antibiotics 2024, 13(8), 768; https://doi.org/10.3390/antibiotics13080768 - 14 Aug 2024

Viewed by 2819

Abstract

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenges of viral infections and their growing resistances to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but [...] Read more.

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenges of viral infections and their growing resistances to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but supervised multi-query similarity search models (MQSSMs) integrated into the StarPep toolbox. Rigorous testing and validation across diverse AVP datasets confirmed the models’ robustness and reliability. The top-performing model, M13+, demonstrated impressive results, with an accuracy of 0.969 and a Matthew’s correlation coefficient of 0.71. To assess their competitiveness, the top five models were benchmarked against 14 publicly available machine-learning and deep-learning AVP predictors. The MQSSMs outperformed these predictors, highlighting their efficiency in terms of resource demand and public accessibility. Another significant achievement of this study is the creation of the most comprehensive dataset of antiviral sequences to date. In general, these results suggest that MQSSMs are promissory tools to develop good alignment-based models that can be successfully applied in the screening of large datasets for new AVP discovery. Full article

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

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15 pages, 1068 KiB

Open AccessArticle

Multidrug-Resistant Staphylococcus aureus Colonizing Pigs and Farm Workers in Rio de Janeiro State, Brazil: Potential Interspecies Transmission of Livestock-Associated MRSA (LA-MRSA) ST398

by Joana Talim, Ianick Martins, Cassio Messias, Hellen Sabino, Laura Oliveira, Tatiana Pinto, Julia Albuquerque, Aloysio Cerqueira, Ítalo Dolores, Beatriz Moreira, Renato Silveira, Felipe Neves and Renata Rabello

Antibiotics 2024, 13(8), 767; https://doi.org/10.3390/antibiotics13080767 - 14 Aug 2024

Viewed by 1034

Abstract

Multidrug-resistant (MDR) Staphylococcus aureus has been increasingly isolated from pigs and people in close contact with them, especially livestock-associated methicillin-resistant S. aureus (LA-MRSA). In this cross-sectional study, we investigated S. aureus colonization in pigs and farm workers, their resistance profile, and genetic background [...] Read more.

Multidrug-resistant (MDR) Staphylococcus aureus has been increasingly isolated from pigs and people in close contact with them, especially livestock-associated methicillin-resistant S. aureus (LA-MRSA). In this cross-sectional study, we investigated S. aureus colonization in pigs and farm workers, their resistance profile, and genetic background to estimate interspecies transmission potential within farms from Rio de Janeiro state, Brazil, between 2014 and 2019. We collected nasal swabs from 230 pigs and 27 workers from 16 and 10 farms, respectively. Five MDR strains were subjected to whole genome sequencing. Fourteen (6.1%) pigs and seven (25.9%) humans were colonized with S. aureus, mostly (64–71%) MDR strains. Resistance to clindamycin, erythromycin, penicillin, and tetracycline was the most common among the pig and human strains investigated. MDR strains shared several resistance genes [blaZ, dfrG, fexA, lsa(E), and tet(M)]. Pig and human strains recovered from the same farm shared the same genetic background and antimicrobial resistance profile. LA-MRSA ST398-SCCmecV-t011 was isolated from pigs in two farms and from a farm worker in one of them, suggesting interspecies transmission. The association between pig management practices and MDR S. aureus colonization might be investigated in additional studies. Full article

(This article belongs to the Special Issue Use of Antibiotics in Animals and Antimicrobial Resistance)

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15 pages, 793 KiB

Open AccessReview

Practical Application of Aztreonam-Avibactam as a Treatment Strategy for Ambler Class B Metallo-β-Lactamase Producing Enterobacteriaceae

by Darren W. Wong

Antibiotics 2024, 13(8), 766; https://doi.org/10.3390/antibiotics13080766 - 14 Aug 2024

Viewed by 1429

Abstract

Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) [...] Read more.

Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) remain a critical challenge with decidedly fewer effective options. One intriguing option for these MBL pathogens is the combination of ceftazidime-avibactam with aztreonam. While clinical experience with this regimen is limited, in vitro studies are promising, and limited case reports describe success with this regimen; however, significant challenges preclude widespread adoption of this novel treatment regimen. A systemic literature review was performed to offer recommendations based on current evidence for a practical strategy on how to best integrate the use of aztreonam with avibactam combination therapy. Full article

(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)

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12 pages, 629 KiB

Open AccessArticle

Exploring the Antimicrobial Resistance Profile of Salmonella typhi and Its Clinical Burden

by Muhammad Asghar, Taj Ali Khan, Marie Nancy Séraphin, Lena F. Schimke, Otavio Cabral-Marques, Ihtisham Ul Haq, Zia-ur-Rehman Farooqi, Susana Campino, Ihsan Ullah and Taane G. Clark

Antibiotics 2024, 13(8), 765; https://doi.org/10.3390/antibiotics13080765 - 14 Aug 2024

Viewed by 2219

Abstract

Background: Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar’s hospital [...] Read more.

Background: Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar’s hospital population. Methodology: A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by S. typhi infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). Results: The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0–11 years) (429/2747, 15.6%). Compared to children, the risk of S. typhi infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42–0.66), adulthood (19–59 years; aOR = 0.30; 95% CI: 0.25–0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04–0.18) (p < 0.001). Compared to males, the risk of S. typhi infection was lower in females (aOR = 0.67; 95% CI = 0.56–0.80; p = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16–1.63; p = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43–0.73; p = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04–0.11, p = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive S. typhi isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). Conclusions: This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of S. typhi in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial. Full article

(This article belongs to the Special Issue Epidemiology of Clinically Relevant Bacteria and Antimicrobial Resistance)

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18 pages, 2360 KiB

Open AccessArticle

Antimicrobial Properties and Cytotoxicity of LL-37-Derived Synthetic Peptides to Treat Orthopedic Infections

by Vincenzo Pennone, Elisa Angelini, David Sarlah and Arianna B. Lovati

Antibiotics 2024, 13(8), 764; https://doi.org/10.3390/antibiotics13080764 - 14 Aug 2024

Viewed by 1163

Abstract

Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This [...] Read more.

Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This study aimed to synthesize and evaluate LL-37-derived antimicrobial peptides (AMPs) for antibacterial efficacy and toxicity. Several truncated LL-37 analogues were created and tested against 18 bacterial strains, both ATCC and orthopedic clinical isolates, using MIC and MBC assays. Synergy with antibiotics and resistance development were also analyzed, alongside cytotoxicity on NIH-3T3 fibroblasts and hemolytic activity assessments. Six AMPs were synthesized, with FK-16 and GF-17 emerging as the most effective. The MIC values ranged from 4.69 to 18.75 µg/mL and 2.34 to 18.75 µg/mL, respectively, against S. epidermidis and S. aureus, with the MBC values matching the MIC values. Cytotoxicity tests showed no toxicity at concentrations below 75 µg/mL for GF-17 and 150 µg/mL for FK-16. Hemolytic activity was below 1% at 18.75 µg/mL for GF-17 and 75 µg/mL for FK-16. These AMPs showed no synergistic effects with antibiotics and no resistance development. FK-16 and GF-17 effectively removed biofilms, particularly against S. epidermidis. Incorporating these AMPs into surgical materials (hydrogels, cements, etc.) could enhance infection control in orthopedic procedures, warranting further in vivo studies. Full article

(This article belongs to the Special Issue Prevention, Diagnostic and Antibiotic Treatment of Periprosthetic Joint and Fracture Related Infection, 2nd Edition)

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51 pages, 24336 KiB

Open AccessReview

An Insight into Rational Drug Design: The Development of In-House Azole Compounds with Antimicrobial Activity

by Daniel Ungureanu, Ovidiu Oniga, Cristina Moldovan, Ioana Ionuț, Gabriel Marc, Anca Stana, Raluca Pele, Mihaela Duma and Brîndușa Tiperciuc

Antibiotics 2024, 13(8), 763; https://doi.org/10.3390/antibiotics13080763 - 13 Aug 2024

Viewed by 1311

Abstract

Antimicrobial resistance poses a major threat to global health as the number of efficient antimicrobials decreases and the number of resistant pathogens rises. Our research group has been actively involved in the design of novel antimicrobial drugs. The blueprints of these compounds were [...] Read more.

Antimicrobial resistance poses a major threat to global health as the number of efficient antimicrobials decreases and the number of resistant pathogens rises. Our research group has been actively involved in the design of novel antimicrobial drugs. The blueprints of these compounds were azolic heterocycles, particularly thiazole. Starting with oxadiazolines, our research group explored, one by one, the other five-membered heterocycles, developing more or less potent compounds. An overview of this research activity conducted by our research group allowed us to observe an evolution in the methodology used (from inhibition zone diameters to minimal inhibitory concentrations and antibiofilm potential determination) correlated with the design of azole compounds based on results obtained from molecular modeling. The purpose of this review is to present the development of in-house azole compounds with antimicrobial activity, designed over the years by this research group from the departments of Pharmaceutical and Therapeutical Chemistry in Cluj-Napoca. Full article

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

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14 pages, 896 KiB

Open AccessArticle

Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from bla_VIM- to bla_NDM-harbouring Isolates in a Greek Tertiary Care Hospital

by Efthymia Protonotariou, Georgios Meletis, Nikoletta Vlachodimou, Andigoni Malousi, Areti Tychala, Charikleia Katsanou, Aikaterini Daviti, Paraskevi Mantzana and Lemonia Skoura

Antibiotics 2024, 13(8), 762; https://doi.org/10.3390/antibiotics13080762 - 12 Aug 2024

Viewed by 989

Abstract

Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of [...] Read more.

Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from bla_VIM- to bla_NDM-harbouring isolates that occurred in our hospital since then. Between January 2023 and February 2024, 139 isolates tested positive for carbapenemase production with the NG-Test CARBA 5 immunochromatographic assay. Eight isolates were processed with the Hybrispot antimicrobial resistance direct flow chip molecular assay, and the first NDM-producing isolate was further analyzed through whole genome sequencing and bioinformatics analysis. Multiple resistance genes were detected by molecular techniques in accordance with the extensively drug-resistant phenotype. The isolate that was subjected to whole-genome sequencing belonged to the P. aeruginosa high-risk clone ST308, and the bla_NDM was located in the chromosome in accordance with previously reported data. During the study period, NDM-producing isolates were increasingly detected, and only five months after their emergence, they overcame VIM producers. Our results indicate the potential of this new clone to spread rapidly and predominate within healthcare institutions, further restricting the already limited treatment options. Full article

(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)

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11 pages, 1810 KiB

Open AccessArticle

A Hunt for the Resistance of Haemophilus influnezae to Beta-Lactams

by Mélanie Denizon, Eva Hong, Aude Terrade, Muhamed-Kheir Taha and Ala-Eddine Deghmane

Antibiotics 2024, 13(8), 761; https://doi.org/10.3390/antibiotics13080761 - 12 Aug 2024

Viewed by 1082

Abstract

Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition [...] Read more.

Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition of beta-lactamase, which was first detected in 1980. Modifications of the ftsI gene encoding the penicillin-binding protein 3, PBP3, also involved in resistance to beta-lactams, appeared in 1991. These modifications (G490E, A502V, R517H, and N526K) were associated with resistance to amoxicillin that was not relieved by a beta-lactamase inhibitor (clavulanic acid), but the isolates retained susceptibility to third-generation cephalosporins (3GC). The modeling of the PBP3 structure suggested that these modifications may reduce the accessibility to the PBP3 active site. Other modifications appeared in 1998 and were associated with resistance to 3GC (S357N, M377I, S385T, and L389F). Modeling of the PBP3 structure suggested that they lie near the S379xN motif of the active site of PBP3. Overall resistance to amoxicillin was detected among 25 isolates (30.8%) of this collection. Resistance to sulfonamides was predicted by a genomic approach from the sequences of the folP gene (encoding the dihydropteroate synthase) due to difficulties in interpreting phenotypic anti-microbial testing and found in 13 isolates (16.0%). Our data suggest a slower spread of resistance to sulfonamides, which may be used for the treatment of H. influnezae infections. Genomic analysis may help in the prediction of antibiotic resistance, inform structure–function analysis, and guide the optimal use of antibiotics. Full article

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

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Antibiotics, Volume 13, Issue 8 (August 2024) – 110 articles

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