Antibiotics

20 pages, 1023 KiB

Open AccessArticle

Synergistic Antibiofilm Effects of Chestnut and Linden Honey with Lavender Essential Oil Against Multidrug-Resistant Otitis Media Pathogens

by Virág D. Ángyán, Viktória L. Balázs, Marianna Kocsis, Béla Kocsis, Györgyi Horváth, Ágnes Farkas and Lilla Nagy-Radványi

Antibiotics 2025, 14(2), 146; https://doi.org/10.3390/antibiotics14020146 - 2 Feb 2025

Abstract

Background/Objectives: Bacterial resistance to antibiotics is a major problem in healthcare, complicated by the ability of bacteria to form biofilms. Complementary therapy for infectious diseases can rely on natural substances with antibacterial activity, e.g., essential oils and honeys. The aim of the study [...] Read more.

Background/Objectives: Bacterial resistance to antibiotics is a major problem in healthcare, complicated by the ability of bacteria to form biofilms. Complementary therapy for infectious diseases can rely on natural substances with antibacterial activity, e.g., essential oils and honeys. The aim of the study was to investigate the effects of linden and chestnut honeys, lavender essential oil, and their combinations against the multidrug-resistant otitis media pathogens Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Streptococcus pneumoniae. The efficacy of these natural substances was compared with each other and antibiotics used in clinical practice. Methods: Microscopic pollen analysis and physicochemical traits were used to confirm the botanical origin of honey samples. The antibiotic sensitivity of bacteria was tested with a disk diffusion assay. Minimum inhibitory concentrations were determined using a microdilution assay. A 24 h immature biofilm eradication test was performed with a crystal violet assay. The efficacy of combinations was tested with a checkerboard titration method. The DNA release of damaged bacterial cells was measured using a membrane degradation assay. Results: Lavender essential oil displayed more potent antibacterial activity compared to the honey samples. However, honey–essential oil combinations showed higher inhibition rates for biofilm eradication, with P. aeruginosa being the most resistant bacterium. The combined use of chestnut honey and lavender oil resulted in a higher degree of membrane degradation in a shorter time, and their synergistic effect was proven with checkerboard titration. Conclusions: The combination of linden or chestnut honey with lavender essential oil was shown to be effective in the eradication of a 24 h immature biofilm formed by H. parainfluenzae, M. catarrhalis, and S. pneumoniae. Full article

(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)

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21 pages, 3320 KiB

Open AccessArticle

Relationship Between CRISPR–Cas Systems and Acquisition of Tetracycline Resistance in Non-Clinical Enterococcus Populations in Bulgaria

by Maria Pandova, Yoana Kizheva and Petya Hristova

Antibiotics 2025, 14(2), 145; https://doi.org/10.3390/antibiotics14020145 - 2 Feb 2025

Abstract

Non-clinical enterococci are relatively poorly studied by means of acquired antibiotic resistance to tetracycline and by the distribution, functionality and role of their CRISPR systems. Background: In our study, 72 enterococcal strains, isolated from various non-clinical origins, were investigated for their phenotypic and [...] Read more.

Non-clinical enterococci are relatively poorly studied by means of acquired antibiotic resistance to tetracycline and by the distribution, functionality and role of their CRISPR systems. Background: In our study, 72 enterococcal strains, isolated from various non-clinical origins, were investigated for their phenotypic and genotypic (tet(M), tet(O), tet(S), tet(L), tet(K), tet(T) and tet(W)) tetracycline resistance. Methods: The genetic determinants for HGT (MGEs (Int-Tn and prgW), inducible pheromones (cpd, cop and cff), aggregation substances (agg, asa1, prgB and asa373) and CRISPR–Cas systems were characterized by PCR and whole-genome sequencing. Results: Four tet genes (tetM, tetO, tetS and tetT) were detected in 39% (n = 28) of our enterococcal population, with tetM (31%) being dominant. The gene location was linked to the Tn6009 transposon. All strains that contained tet genes also had genes for HGT. No tet genes were found in E. casseliflavus and E. gilvus. In our study, 79% of all tet-positive strains correlated with non-functional CRISPR systems. The strain E. faecalis BM15 was the only one containing a combination of a functional CRISPR system (cas1, cas2, csn2 and csn1/cas9) and tet genes. The CRISPR subtype repeats II-A, III-B, IV-A2 and VI-B1 were identified among E. faecalis strains (CM4-II-A, III-B and VI-B1; BM5-IV-A2, II-A and III-B; BM12 and BM15-II-A). The subtype II-A was the most present. These repeats enclosed a great number of spacers (1–10 spacers) with lengths of 31 to 36 bp. One CRISPR locus was identified in plasmid (p.Firmicutes1 in strain E. faecalis BM5). We described the presence of CRISPR loci in the species E. pseudoavium, E. pallens and E. devriesei and their lack in E. gilvus, E. malodoratus and E. mundtii. Conclusions: Our findings generally describe the acquisition of foreign DNA as a consequence of CRISPR inactivation, and self-targeting spacers as the main cause. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution)

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22 pages, 3030 KiB

Open AccessReview

Bioactive Compounds as Alternative Approaches for Preventing Urinary Tract Infections in the Era of Antibiotic Resistance

by Chiara Cipriani, Marco Carilli, Marta Rizzo, Martino Tony Miele, Paola Sinibaldi-Vallebona, Claudia Matteucci, Pierluigi Bove and Emanuela Balestrieri

Antibiotics 2025, 14(2), 144; https://doi.org/10.3390/antibiotics14020144 - 1 Feb 2025

Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. They occur in the urinary system when a microorganism, commonly present on the perineal skin or rectum, reaches the bladder through the urethra, and adheres to the luminal surface of uroepithelial [...] Read more.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide. They occur in the urinary system when a microorganism, commonly present on the perineal skin or rectum, reaches the bladder through the urethra, and adheres to the luminal surface of uroepithelial cells, forming biofilms. The treatment of UTIs includes antibiotics, but their indiscriminate use has favored the development of multidrug-resistant bacteria strains, which represent a serious challenge to today’s microbiology. The pathogenesis of the infection and antibiotic resistance synergistically contribute to hindering the eradication of the disease while favoring the establishment of persistent infections. The repeated requirement for antibiotic treatment and the limited therapeutic options have further contributed to the increase in antibiotic resistance and the occurrence of potential relapses by therapeutic failure. To limit antimicrobial resistance and broaden the choice of non-antibiotic preventive approaches, this review reports studies focused on the bacteriostatic/bactericidal activity, inhibition of bacterial adhesion and quorum sensing, restoration of uroepithelial integrity and immune response of molecules, vitamins, and compounds obtained from plants. To date, different supplementations are recommended by the European Association of Urology for the management of UTIs as an alternative approach to antibiotic treatment, while a variety of bioactive compounds are under investigation, mostly at the level of in vitro and preclinical studies. Although the evidence is promising, they are far from being included in the clinical practice of UTIs. Full article

(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)

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21 pages, 1578 KiB

Open AccessArticle

Pooled Antibiotic Susceptibility Testing for Polymicrobial UTI Performs Within CLSI Validation Standards

by Richard A. Festa, Frank R. Cockerill, Rick L. Pesano, Emery Haley, Natalie Luke, Mohit Mathur, Xiaofei Chen, Jim Havrilla, Michael Percaccio, Jesus Magallon, Shane Erickson, Mandana Ghashghaie, Alain Rosas and David Baunoch

Antibiotics 2025, 14(2), 143; https://doi.org/10.3390/antibiotics14020143 - 1 Feb 2025

Abstract

Background/Objectives: Urinary tract infections (UTIs) pose an increasing risk of antimicrobial resistance, and novel diagnostic tests have been developed to address the limitations of standard urine culture in these cases. It is important that these novel tests be validated for agreement and error [...] Read more.

Background/Objectives: Urinary tract infections (UTIs) pose an increasing risk of antimicrobial resistance, and novel diagnostic tests have been developed to address the limitations of standard urine culture in these cases. It is important that these novel tests be validated for agreement and error rates against the standard antibiotic susceptibility testing (AST) methods. Methods: Polymicrobial (≥two non-fastidious microorganisms) consecutive clinical urine specimens submitted for UTI diagnostic testing were included in this analysis. Specimens were tested with Pooled Antibiotic Susceptibility Testing (P-AST) and with broth microdilution/disk diffusion (BMD/DD) in parallel. Performance characteristics, such as essential agreement (EA%), very major errors (VMEs), and major errors (MEs), were assessed using Clinical and Laboratory Standards Institute (CLSI) standards. Specimens with P-AST-resistant and BMD/DD consensus-sensitive results were assessed for heteroresistance. Real-world clinical sample data were used to assess associations between increasing organism counts and average “sensitive” antibiotic count per sample. Results: The essential agreement between P-AST and standard isolate AST was ≥90%, VMEs were <2.0%, and MEs were <3.0%, meeting the CLSI guidelines for AST verification and validation studies. When heteroresistance was accounted for, overall VMEs and MEs were both <1.5%. The presence of additional non-fastidious organisms dropped the number of average “sensitive” antibiotics from 9.8 with one organism to 2.5 with five or more organisms. The presence of fastidious organisms did not have any meaningful impact. Conclusions: P-AST, a component of the Guidance^® UTI assay (Pathnostics, Irvine, CA, USA), performed within CLSI standards for AST in polymicrobial UTI diagnostic urine specimens. Full article

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

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11 pages, 1547 KiB

Open AccessReview

What Do We Know About Bacterial Infections in Hidradenitis Suppurativa?—A Narrative Review

by Zuzanna Świerczewska and Wioletta Barańska-Rybak

Antibiotics 2025, 14(2), 142; https://doi.org/10.3390/antibiotics14020142 - 1 Feb 2025

Abstract

Background/Objectives: Hidradenitis suppurativa is an inflammatory skin condition of the pilosebaceous unit of a chronic, painful, and progressive nature. It affects intertriginous parts of the body, including the axillae, groin, submammary region, and anogenital region. The risk of infection in HS patients [...] Read more.

Background/Objectives: Hidradenitis suppurativa is an inflammatory skin condition of the pilosebaceous unit of a chronic, painful, and progressive nature. It affects intertriginous parts of the body, including the axillae, groin, submammary region, and anogenital region. The risk of infection in HS patients is not well understood. Thus, presenting the most recent findings in the study of bacterial infections in relation to hidradenitis suppurativa was the objective of this review. Methods: The presented article is a narrative review. The PubMed and Scopus databases were searched for articles applicable to this review. All types of study design were included in this review. Results: Among reported infections in patients with HS, Fournier’s gangrene, osteomyelitis, Clostridium difficile infection, and biofilm were significant. Attention should also be paid to post-procedural infections. Conclusions: A wide range of bacterial infections, from localized purulent infections to serious systemic consequences, can affect patients with HS. Comorbid diseases like diabetes mellitus and obesity change the cutaneous microbiota and produce a pro-inflammatory systemic milieu, which makes the disease more severe and makes HS patients more susceptible to infections. Additionally, those with untreated or unmanaged HS are more likely to experience infectious complications. Full article

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20 pages, 352 KiB

Open AccessReview

Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health

by Gualtiero Alvisi, Antonio Curtoni, Rossella Fonnesu, Aurora Piazza, Caterina Signoretto, Giorgia Piccinini, Davide Sassera and Paolo Gaibani

Antibiotics 2025, 14(2), 141; https://doi.org/10.3390/antibiotics14020141 - 1 Feb 2025

Abstract

Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided [...] Read more.

Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided into three classes (A, B, and D) according to the Ambler classification system. Among these, KPC (class A), NDM, VIM, IMP (class B), and OXA-48-like (class D) represent the most important carbapenemases in terms of diffusion and clinical impact. CPE diffusion has been observed worldwide, with current endemicity in multiple territories around the world. In this context, the clonal spread and plasmid-mediated transmission of carbapenemases have contributed to the global spread of CPE worldwide and to the diffusion of carbapenemases among different Enterobacterales species. In recent years, novel molecules showing excellent in vitro and in vivo activity have been developed against CPE. However, the recent emergence of novel traits of resistance to these molecules has already been reported in several cases, mitigating the initial promising results. This review aims to provide an updated description of the major classes of carbapenemases, their global distribution, and future perspectives to limit the diffusion of CPEs. Full article

(This article belongs to the Special Issue Genomic Analysis of Drug-Resistant Pathogens)

12 pages, 5804 KiB

Open AccessReview

Psychrobacter Infections in Humans—A Narrative Review of Reported Cases

by Petros Ioannou, Afroditi Ziogou, Alexios Giannakodimos, Ilias Giannakodimos, Andreas G. Tsantes and George Samonis

Antibiotics 2025, 14(2), 140; https://doi.org/10.3390/antibiotics14020140 - 1 Feb 2025

Abstract

Background: Psychrobacter species are aerobic, Gram-negative, spherical-to-rod-shaped, psychrophilic bacteria that belong to the Moraxellaceae family. In spite of their uncommon manifestation in the general population, infections due to Psychrobacter spp. are increasingly identified especially in immunocompromised individuals or patients with severe comorbidities. Objectives: [...] Read more.

Background: Psychrobacter species are aerobic, Gram-negative, spherical-to-rod-shaped, psychrophilic bacteria that belong to the Moraxellaceae family. In spite of their uncommon manifestation in the general population, infections due to Psychrobacter spp. are increasingly identified especially in immunocompromised individuals or patients with severe comorbidities. Objectives: This review aims to analyze all reported instances of Psychrobacter spp. infections in humans, with an emphasis on data pertaining to epidemiology, microbiology, antimicrobial resistance, treatment strategies, and mortality outcomes. Methods: A narrative review was performed through a literature search of PubMed/MedLine and Scopus databases. Results: In total, 12 articles offered data on 12 patients infected with Psychrobacter spp. Their mean age was 33.41 years, while 63.64% of them were male. Immunosuppression was the predominant risk factor (33.3%). Bacteremia was the most commonly observed type of infection (41.6%), followed by meningitis, skin infection, and conjunctivitis. Psychrobacter immobilis was the most usually identified species (33.3%). The pathogen exhibited sensitivity to most antimicrobials. The most widely administered antimicrobials included cephalosporins (70%), followed by aminopenicillins and vancomycin (40%, respectively). The clinical outcome depended primarily on the infection site; mortality rate was high (44.4%), especially in cases of bacteremia (50%). Conclusion: Due to the potential of Psychrobacter spp. to cause serious infection, clinicians and laboratory professionals should consider it in the differential diagnosis in patients with infections by Gram-negative spherical bacteria, particularly in patients with significant comorbidities and immunodeficiency, in order to accurately establish the diagnosis and proceed to the right treatment. Full article

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14 pages, 983 KiB

Open AccessArticle

Could a Reduced Dose of 8 g of Continuous Infusion Fosfomycin Be Considered as Effective as and Safer than a Standard 16 g Dose When Combined with High-Dose Daptomycin in the Treatment of Staphylococcal osteoarticular Infections?

by Pier Giorgio Cojutti, Sara Tedeschi, Eleonora Zamparini, Giacomo Fornaro, Manuel Zagarrigo, Massimiliano De Paolis, Pierluigi Viale and Federico Pea

Antibiotics 2025, 14(2), 139; https://doi.org/10.3390/antibiotics14020139 - 1 Feb 2025

Abstract

Background: Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections (OIs), but hypernatremia and hypokalemia due to sodium overload are important issues. The aim of this study was to assess the likelihood of attaining a pharmacokinetic/pharmacodynamic (PK/PD) [...] Read more.

Background: Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections (OIs), but hypernatremia and hypokalemia due to sodium overload are important issues. The aim of this study was to assess the likelihood of attaining a pharmacokinetic/pharmacodynamic (PK/PD) target of AUC/MIC > 66.6 and/or of 70%t > MIC with continuous infusion (CI) fosfomycin at the recommended vs. reduced dose in patients with OIs receiving combination therapy with high-dose daptomycin. Adverse events were also evaluated. Methods: Patients with OIs treated with 8–10 mg/kg daily daptomycin plus CI fosfomycin, and who had a ≥1 TDM assessment of CI fosfomycin, were retrospectively included in the high-dose (16 g daily) or reduced-dose (<16 g daily) groups. The attainment of the PK/PD targets of 70%t > MIC and AUC/MIC > 66.6 up to an MIC of 32 mg/L was calculated. A CART analysis was used to identify a cut-off of fosfomycin AUC that indicated occurrence of hypernatremia and/or hypokalemia. Results: A total of 44 and 39 patients were included in the high- and reduced-dose groups, respectively. The two groups did not differ in terms of demographic characteristics, underlying infectious diseases and microbiological isolates. No differences between groups in attaining both PK/PD targets up to an MIC of 32 mg/L and in C-reactive protein reduction at the end of treatment were observed. Fosfomycin AUC > 8245 mg × h/L and >8326 mg × h/L were associated with hypernatremia and hypokalemia, respectively. Conclusions: CI fosfomycin at 8 g daily may reach optimal PK/PD target attainment with better safety than the recommended 16 g daily dose in patients with preserved renal function. Targeting fosfomycin AUC at 2131–8326 mg × h/L or steady-state concentration at 88.8–347 mg/L may be adequate for optimizing drug pharmacodynamics up to an MIC of 32 mg/L and minimizing the risk of hypernatremia and hypokalemia. Full article

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23 pages, 1127 KiB

Open AccessReview

Evaluating the Efficacy of Secondary Metabolites in Antibiotic-Induced Dysbiosis: A Narrative Review of Preclinical Studies

by Corina Andrei, Anca Zanfirescu, Victor-Pierre Ormeneanu and Simona Negreș

Antibiotics 2025, 14(2), 138; https://doi.org/10.3390/antibiotics14020138 - 1 Feb 2025

Abstract

Background/Objectives: Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate [...] Read more.

Background/Objectives: Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy. Methods: A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included “gut microbiota”, “antibiotics”, and “secondary metabolites”. Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized. Results: Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation. Conclusions: Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)

14 pages, 864 KiB

Open AccessArticle

Prevalence and Antimicrobial Resistance Patterns of Escherichia coli in the Environment, Cow Dung, and Milk of Selangor Dairy Farms

by Yuvaneswary Veloo, Sakshaleni Rajendiran, Zunita Zakaria, Rohaida Ismail, Salina Abdul Rahman, Rozaihan Mansor and Syahidiah Syed Abu Thahir

Antibiotics 2025, 14(2), 137; https://doi.org/10.3390/antibiotics14020137 - 1 Feb 2025

Abstract

Background/Objectives: The increasing threat of antimicrobial resistance (AMR) to global public health urgently needs attention. Misuse of antimicrobials in sectors such as dairy farming has led to the emergence and spread of resistant bacteria and genes. This study investigated AMR patterns and profiles [...] Read more.

Background/Objectives: The increasing threat of antimicrobial resistance (AMR) to global public health urgently needs attention. Misuse of antimicrobials in sectors such as dairy farming has led to the emergence and spread of resistant bacteria and genes. This study investigated AMR patterns and profiles of Escherichia coli (E. coli) from various sources, including soil, effluent, cow dung, and milk. Methods: A total of 192 samples were collected, comprising environmental samples (soil and effluent), cow dung samples, and milk samples from eight dairy farms in Selangor, Malaysia. The spread plate method was employed to isolate E. coli, and all the isolates were subjected to Gram staining to identify Gram-negative, rod-shaped bacteria. The Vitek^® 2 system was used for E. coli identification and susceptibility testing. Results: The prevalence of E. coli identified in the eight farms was 66.1%. A total of 360 E. coli isolates were successfully isolated, and 19.7% of the isolates presented AMR with ampicillin exhibiting the highest resistance (18.3%), followed by trimethoprim–sulfamethoxazole (8.9%). Additionally, 8.9% of them were multidrug resistant, which could be divided into 16 patterns. For the extended spectrum beta-lactamase screening, nine isolates were positive. Conclusions: This finding emphasizes the rise in resistant isolates in the growing dairy industry and underscores the urgency of addressing the potential reservoir of AMR. Therefore, essential measures such as continuous surveillance and effective antimicrobial stewardship programs are crucial for regulating veterinary antimicrobial use. Research on the mechanisms driving the development and dissemination of AMR is imperative for addressing One Health concerns. Full article

(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach, 2nd Edition)

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27 pages, 7343 KiB

Open AccessArticle

Cannabidiol (CBD) Acts as an Antioxidant on Gardnerella vaginalis, Resulting in Reduced Metabolic Activity, Loss of Survivability, and Elimination of Biofilms

by Ronit Vogt Sionov, Maya Korem, Itzhack Polacheck and Doron Steinberg

Antibiotics 2025, 14(2), 136; https://doi.org/10.3390/antibiotics14020136 - 1 Feb 2025

Abstract

Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an [...] Read more.

Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an anti-inflammatory compound that also has antibacterial activities against several Gram-positive and certain Gram-negative bacteria. Objectives: Since G. vaginalis is an opportunistic pathogenic Gram-variable bacterium, we investigated its response to CBD. Methods: The antibacterial activity of CBD was studied by broth dilution assay, changes in intracellular ATP levels, and the ability of bacteria to recover on chocolate agar plates. The antibiofilm activity was investigated by MTT metabolic assay, crystal violet staining, and HR-SEM. Flow cytometric analyses were performed to measure changes in membrane potential, membrane perforation, and metabolic activity. Reactive oxygen species (ROS) production was analyzed using the nitro blue tetrazolium (NBT) reagent. Gene expression was determined by semi-quantitative real-time PCR, while protein composition was determined by LC-MS/MS analysis. Results: We observed that G. vaginalis clinical isolates exhibited high susceptibility to CBD with a minimum inhibitory concentration (MIC) of 2.5 µg/mL CBD. CBD induced rapid membrane hyperpolarization and caused cytoplasmic leakage of ATP without increasing propidium iodide uptake. This was accompanied by reduced metabolic activity and loss of survivability. Proteomic analysis revealed decreased expression of some ribosomal-associated proteins. CBD exhibited antioxidant activity by reducing intracellular ROS levels in a dose-dependent manner. The antibacterial effect was neutralized by the free radical scavenger α-tocopherol, suggesting the involvement of radicals in executing the antibacterial effect. Importantly, CBD not only prevented the biofilm formation of G. vaginalis but also reduced the metabolic activity and biofilm biomass of preformed, mature biofilms. Real-time PCR analysis of G. vaginalis treated with CBD for 6 h showed an increase in the expression of biofilm-associated genes, suggesting that the antibiofilm activity of CBD is mainly due to its antibacterial effect. CBD did not alter the ability of G. vaginalis to adhere to HeLa cervical carcinoma cells and CBD-treated bacteria were still phagocytosed by RAW264.7 macrophages. Conclusions: Our study shows that CBD exhibits antibacterial and antibiofilm activities against G. vaginalis clinical isolates and is thus a potential drug for the treatment of vaginosis caused by this bacterium. Full article

(This article belongs to the Special Issue Antimicrobial and Antibiofilm Activity by Natural Compounds)

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19 pages, 1376 KiB

Open AccessArticle

Pharmaco-Epidemiological Study and Correlation Between Antibiotic Resistance and Antibiotic Consumption in a Tunisian Teaching Hospital from 2010 to 2022

by Yosr Kasbi, Fatma Sellami, Asma Ferjani, Aimen Abbassi and Ilhem Boutiba Ben Boubaker

Antibiotics 2025, 14(2), 135; https://doi.org/10.3390/antibiotics14020135 - 1 Feb 2025

Abstract

The exponential rise of bacterial resistance poses a threat to antibiotic efficacy, with a great impact on public health. This study aims to analyze the correlation between antibiotic consumption and the emergence of bacterial resistance. Conducted retrospectively at Charles Nicolle Hospital in Tunis, [...] Read more.

The exponential rise of bacterial resistance poses a threat to antibiotic efficacy, with a great impact on public health. This study aims to analyze the correlation between antibiotic consumption and the emergence of bacterial resistance. Conducted retrospectively at Charles Nicolle Hospital in Tunis, Tunisia, from 2010 to 2022, this study was based on STKMED^® software for antibiotic consumption data, hospital administrative records for the number of hospitalization days, and SIRSCAN^® software for bacteriological data. Data processing was performed using Excel^® software version 2019, and analysis was conducted using SPSS23^®. In 2022, consumption was almost evenly split between the two major “AWaRe” groups, with 49.33% for “Access” and 46.89% for “Watch”, and the consumption of the “Reserve” group also increased, accounting for 3.77% of the total. Bacterial resistances, notably carbapenem-resistant Klebsiella pneumoniae, increased. Seventy-four significant correlations were identified, including those between carbapenem consumption and resistance in Escherichia coli and Klebsiella pneumoniae strains. However, no significant correlation was observed with imipenem-resistant Pseudomonas aeruginosa strains. The significant correlations between the emergence of bacterial resistance and antibiotic use, particularly with antibiotics in the “Watch” and “Reserve” groups, underscore the urgent need to continue efforts to combat this threat through rational antibiotic use. Full article

(This article belongs to the Special Issue Antibiotic Use and the Emergence of Antibiotic Resistance in Clinical Settings)

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19 pages, 1314 KiB

Open AccessReview

The Role of Artificial Intelligence and Machine Learning Models in Antimicrobial Stewardship in Public Health: A Narrative Review

by Flavia Pennisi, Antonio Pinto, Giovanni Emanuele Ricciardi, Carlo Signorelli and Vincenza Gianfredi

Antibiotics 2025, 14(2), 134; https://doi.org/10.3390/antibiotics14020134 - 30 Jan 2025

Abstract

Antimicrobial resistance (AMR) poses a critical global health threat, necessitating innovative approaches in antimicrobial stewardship (AMS). Artificial intelligence (AI) and machine learning (ML) have emerged as transformative tools in this domain, enabling data-driven interventions to optimize antibiotic use and combat resistance. This comprehensive [...] Read more.

Antimicrobial resistance (AMR) poses a critical global health threat, necessitating innovative approaches in antimicrobial stewardship (AMS). Artificial intelligence (AI) and machine learning (ML) have emerged as transformative tools in this domain, enabling data-driven interventions to optimize antibiotic use and combat resistance. This comprehensive review explores the multifaceted role of AI and ML models in enhancing antimicrobial stewardship efforts across healthcare systems. AI-powered predictive analytics can identify patterns of resistance, forecast outbreaks, and guide personalized antibiotic therapies by leveraging large-scale clinical and epidemiological data. ML algorithms facilitate rapid pathogen identification, resistance profiling, and real-time monitoring, enabling precise decision making. These technologies also support the development of advanced diagnostic tools, reducing the reliance on broad-spectrum antibiotics and fostering timely, targeted treatments. In public health, AI-driven surveillance systems improve the detection of AMR trends and enhance global monitoring capabilities. By integrating diverse data sources—such as electronic health records, laboratory results, and environmental data—ML models provide actionable insights to policymakers, healthcare providers, and public health officials. Additionally, AI applications in antimicrobial stewardship programs (ASPs) promote adherence to prescribing guidelines, evaluate intervention outcomes, and optimize resource allocation. Despite these advancements, challenges such as data quality, algorithm transparency, and ethical considerations must be addressed to maximize the potential of AI and ML in this field. Future research should focus on developing interpretable models and fostering interdisciplinary collaborations to ensure the equitable and sustainable integration of AI into antimicrobial stewardship initiatives. Full article

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11 pages, 244 KiB

Open AccessArticle

Risk Factors for Clostridium difficile Infection in Inpatients: A Four-Year (2017–2020) Retrospective Study

by Chu-Hsuan Hsia, Hsiu-Yueh Su and Yi-Wen Chien

Antibiotics 2025, 14(2), 133; https://doi.org/10.3390/antibiotics14020133 - 29 Jan 2025

Abstract

Background: Clostridium difficile infection (CDI) impact on healthcare systems is concerning due to high treatment cost and increased hospitalization time. We found that the incidence rate of CDI increased annually at Taipei Medical University Hospital (TMUH). The study aimed to establish monitoring indicators [...] Read more.

Background: Clostridium difficile infection (CDI) impact on healthcare systems is concerning due to high treatment cost and increased hospitalization time. We found that the incidence rate of CDI increased annually at Taipei Medical University Hospital (TMUH). The study aimed to establish monitoring indicators for hospitalized patients receiving antibiotics to prevent CDI occurrences. Methods: A case–control study was conducted to identify the risk factors of CDI among patients who were admitted to TMUH and tested for C. difficile. Patient demographics, patient history, and laboratory data were collected and analyzed. Results: Nutrition Risk Screening 2002 score (NRS 2002) in CDI patients was significantly lower than in non-CDI patients (3.1 ± 1.7 vs. 3.5 ± 1.6). The percentage of tube feeding in CDI patients was significantly lower than in non-CDI patients (23.0% vs. 36.7%), whereas parenteral nutrition was higher (8.8% vs. 3.8%). Age (OR = 1.03, p = 0.00), NRS 2002 score (OR =0.86, p = 0.05), comorbidity with cardiovascular disease (OR = 1.73, p = 0.03) or pulmonary disease (OR = 3.72, p = 0.00), patients with tube feeding (OR = 2.02, p = 0.01), and the number of medications (OR = 1.15, p < 0.01) were significant predictors of CDI. Conclusion: This study revealed that nutritional factors, including NRS 2002 scores and feeding routes, were associated with CDI, emphasizing the importance of nutritional factors as key predictors in managing and preventing CDI. Full article

(This article belongs to the Special Issue Healthcare-Associated Infections (HAIs): Prevention, Control and Surveillance)

31 pages, 5237 KiB

Open AccessReview

State of the Art of Antimicrobial and Diagnostic Stewardship in Pediatric Setting

by Daniele Donà, Elisa Barbieri, Giulia Brigadoi, Cecilia Liberati, Samantha Bosis, Elio Castagnola, Claudia Colomba, Luisa Galli, Laura Lancella, Andrea Lo Vecchio, Marianna Meschiari, Carlotta Montagnani, Maia De Luca, Stefania Mercadante and Susanna Esposito

Antibiotics 2025, 14(2), 132; https://doi.org/10.3390/antibiotics14020132 - 27 Jan 2025

Abstract

Antimicrobial stewardship programs (ASPs) and diagnostic stewardship programs (DSPs) are essential strategies for effectively managing infectious diseases and tackling antimicrobial resistance (AMR). These programs can have a complementary impact, i.e., ASPs optimize antimicrobial use to prevent resistance, while DSPs enhance diagnostic accuracy to [...] Read more.

Antimicrobial stewardship programs (ASPs) and diagnostic stewardship programs (DSPs) are essential strategies for effectively managing infectious diseases and tackling antimicrobial resistance (AMR). These programs can have a complementary impact, i.e., ASPs optimize antimicrobial use to prevent resistance, while DSPs enhance diagnostic accuracy to guide appropriate treatments. This review explores the current landscape of ASPs and DSPs in pediatric care, focusing on key factors, influencing their development, implementation, and evaluation across various settings. A multidisciplinary approach is necessary, involving multiple healthcare professionals to support comprehensive stewardship practices in pediatric care. No single intervention suits all settings, or even the same setting, in different countries; interventions must be tailored to each specific context, considering factors such as hospital capacity, patient complexity, and the parent–child dynamic. It is essential to educate caregivers on optimal antibiotic use through clear, concise messages adapted to their socioeconomic status and level of understanding. The cost-effectiveness of ASPs and DSPs should also be assessed, and standardized metrics should be employed to evaluate success in pediatric settings, focusing on outcomes beyond just antibiotic consumption, such as AMR rates. This manuscript further discusses emerging opportunities and challenges in ASP implementation, offering insights into future research priorities. These include large-scale studies to evaluate the long-term impact of ASPs, cost-effectiveness assessments of pediatric-specific diagnostic tools, and the integration of artificial intelligence to support clinical decision making. Addressing these areas will enhance the effectiveness and sustainability of ASPs, contributing to global efforts to combat AMR and improve pediatric health outcomes. Full article

(This article belongs to the Special Issue Inappropriate Use of Antibiotics in Pediatrics)

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29 pages, 595 KiB

Open AccessReview

The Impact of Wastewater on Antimicrobial Resistance: A Scoping Review of Transmission Pathways and Contributing Factors

by Maria Clara La Rosa, Andrea Maugeri, Giuliana Favara, Claudia La Mastra, Roberta Magnano San Lio, Martina Barchitta and Antonella Agodi

Antibiotics 2025, 14(2), 131; https://doi.org/10.3390/antibiotics14020131 - 26 Jan 2025

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is a global issue driven by the overuse of antibiotics in healthcare, agriculture, and veterinary settings. Wastewater and treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The One Health approach emphasizes the [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is a global issue driven by the overuse of antibiotics in healthcare, agriculture, and veterinary settings. Wastewater and treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The One Health approach emphasizes the interconnectedness of human, animal, and environmental health in addressing AMR. This scoping review analyzes wastewater’s role in the AMR spread, identifies influencing factors, and highlights research gaps to guide interventions. Methods: This scoping review followed the PRISMA-ScR guidelines. A comprehensive literature search was conducted across the PubMed and Web of Science databases for articles published up to June 2024, supplemented by manual reference checks. The review focused on wastewater as a source of AMR, including hospital effluents, industrial and urban sewage, and agricultural runoff. Screening and selection were independently performed by two reviewers, with conflicts resolved by a third. Results: Of 3367 studies identified, 70 met the inclusion criteria. The findings indicated that antibiotic residues, heavy metals, and microbial interactions in wastewater are key drivers of AMR development. Although WWTPs aim to reduce contaminants, they often create conditions conducive to horizontal gene transfer, amplifying resistance. Promising interventions, such as advanced treatment methods and regulatory measures, exist but require further research and implementation. Conclusions: Wastewater plays a pivotal role in AMR dissemination. Targeted interventions in wastewater management are essential to mitigate AMR risks. Future studies should prioritize understanding AMR dynamics in wastewater ecosystems and evaluating scalable mitigation strategies to support global health efforts. Full article

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14 pages, 618 KiB

Open AccessReview

Antimicrobial Stewardship Programs in Pediatric Intensive Care Units: A Systematic Scoping Review

by Cecilia Liberati, Giulia Brigadoi, Elisa Barbieri, Carlo Giaquinto and Daniele Donà

Antibiotics 2025, 14(2), 130; https://doi.org/10.3390/antibiotics14020130 - 26 Jan 2025

Abstract

Objectives: We aimed to summarize the current state of antimicrobial stewardship (ASP) and diagnostic stewardship programs (DSPs) implemented in pediatric intensive care units (PICUs). Methods: Embase, MEDLINE, Scopus and the Cochrane Library were searched, including studies from 1 January 2007 to [...] Read more.

Objectives: We aimed to summarize the current state of antimicrobial stewardship (ASP) and diagnostic stewardship programs (DSPs) implemented in pediatric intensive care units (PICUs). Methods: Embase, MEDLINE, Scopus and the Cochrane Library were searched, including studies from 1 January 2007 to 20 February 2024. Studies were included in the review if they assessed the implementation of an ASP or a DSP in a PICU. Identified references were downloaded into Rayyan software, and data were extracted using a standardized data collection form. Results: 18 studies were included; 13 described an ASP intervention, and 5 described a diagnostic stewardship intervention. Most studies were retrospective and adopted a persuasive strategy for ASP, reporting positive effects on antimicrobial consumption. However, studies were dramatically heterogeneous in terms of intervention type, outcomes and metrics used, limiting the possibility of a broader comparison. Diagnostic stewardship studies included mainly the impact of biomarkers and pathogen testing panels without significant impact on antibiotic prescription patterns. Antimicrobial resistance changes were not described by the majority of studies. Conclusions: the implementation of ASP in PICUs is still limited, with significant variability in the metrics used to evaluate outcomes. To enhance the effectiveness of these programs, it is crucial to harmonize reporting metrics to allow an adequate comparison of results and to find the best strategies to inform ASP in PICUs. Full article

(This article belongs to the Special Issue Inappropriate Use of Antibiotics in Pediatrics)

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20 pages, 3185 KiB

Open AccessArticle

Development of a Spectrophotometric Assay for the Cysteine Desulfurase from Staphylococcus aureus

by Emily Sabo, Connor Nelson, Nupur Tyagi, Veronica Stark, Katelyn Aasman, Christine N. Morrison, Jeffrey M. Boyd and Richard C. Holz

Antibiotics 2025, 14(2), 129; https://doi.org/10.3390/antibiotics14020129 - 26 Jan 2025

Abstract

Background/Objectives: Antibiotic-resistant Staphylococcus aureus represents a growing threat in the modern world, and new antibiotic targets are needed for its successful treatment. One such potential target is the pyridoxal-5′-phosphate (PLP)-dependent cysteine desulfurase (SaSufS) of the SUF-like iron–sulfur (Fe-S) cluster biogenesis [...] Read more.

Background/Objectives: Antibiotic-resistant Staphylococcus aureus represents a growing threat in the modern world, and new antibiotic targets are needed for its successful treatment. One such potential target is the pyridoxal-5′-phosphate (PLP)-dependent cysteine desulfurase (SaSufS) of the SUF-like iron–sulfur (Fe-S) cluster biogenesis pathway upon which S. aureus relies exclusively for Fe-S synthesis. The current methods for measuring the activity of this protein have allowed for its recent characterization, but they are hampered by their use of chemical reagents which require long incubation times and may cause undesired side reactions. This problem highlights a need for the development of a rapid quantitative assay for the characterization of SaSufS in the presence of potential inhibitors. Methods: A spectrophotometric assay based on the well-documented absorbance of PLP intermediates at 340 nm was both compared to an established alanine detection assay and used to effectively measure the activity of SaSufS incubated in the absence and presence of the PLP-binding inhibitors, D-cycloserine (DCS) and L-cycloserine (LCS) as proof of concept. Methicillin-resistant S. aureus strain LAC was also grown in the presence of these inhibitors. Results: The Michaelis–Menten parameters k_cat and K_m of SaSufS were determined using the alanine detection assay and compared to corresponding intermediate-based values obtained spectrophotometrically in the absence and presence of the reducing agent tris(2-carboxyethyl)phosphine (TCEP). These data revealed the formation of both an intermediate that achieves steady-state during continued enzyme turnover and an intermediate that likely accumulates upon the stoppage of the catalytic cycle during the second turnover. The spectrophotometric method was then utilized to determine the half maximal inhibitory concentration (IC₅₀) values for DCS and LCS binding to SaSufS, which are 2170

\pm

920 and 62

\pm

23 μM, respectively. Both inhibitors of SaSufS were also found to inhibit the growth of S. aureus. Conclusions: Together, this work offers a spectrophotometric method for the analysis of new inhibitors of SufS and lays the groundwork for the future development of novel antibiotics targeting cysteine desulfurases. Full article

(This article belongs to the Section Mechanisms and Structural Biology of Antibiotic Action)

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11 pages, 1629 KiB

Open AccessArticle

Circulation of a Unique Klebsiella pneumoniae Clone, ST147 NDM-1/OXA-48, in Two Diverse Hospitals in Calabria (Italy)

by Emanuele Nicitra, Morena Terrana, Dafne Bongiorno, Saveria Dodaro, Francesca Greco, Sonia Greco, Nadia Marascio, Maria Vittoria Mauro, Marta Pantanella, Grete Francesca Privitera, Angela Quirino, Francesca Serapide, Enrico Maria Trecarichi, Valeria Vangeli, Antonio Mastroianni, Giovanni Matera, Alessandro Russo and Stefania Stefani

Antibiotics 2025, 14(2), 128; https://doi.org/10.3390/antibiotics14020128 - 26 Jan 2025

Abstract

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae has become endemic in Europe, including in Italy, where its prevalence has risen dramatically, primarily due to epidemic clones harboring metallo-enzymes. This study aims to investigate the dissemination of K. pneumoniae strains co-producing OXA-48 and NDM-1 between two hospitals [...] Read more.

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae has become endemic in Europe, including in Italy, where its prevalence has risen dramatically, primarily due to epidemic clones harboring metallo-enzymes. This study aims to investigate the dissemination of K. pneumoniae strains co-producing OXA-48 and NDM-1 between two hospitals in southern Italy using molecular analyses. Methods: A total of 49 K. pneumoniae strains, predominantly co-producing OXA-48 and NDM-1, were collected between March and December 2023. Antibiotic susceptibility testing was conducted following EUCAST guidelines. Whole-genome sequencing (Illumina MiSeq) and bioinformatics tools (CARD, CLC Genomics Workbench) were used to identify resistance and virulence genes, capsule loci, and phylogenetic relationships. Results: All isolates exhibited multidrug-resistant or extensively drug-resistant profiles, including resistance to ceftazidime/avibactam and meropenem/vaborbactam. Genomic analysis revealed diverse resistance genes such as bla_OXA-48, bla_NDM-1, bla_CTX-M-15, and bla_SHV variants. Virulence genes associated with capsules, fimbriae, and siderophores were widespread. Most strains were classified as ST147 by MLST and contained various plasmids known to carry antimicrobial resistance. Phylogenetic analysis confirmed their clonal relatedness, highlighting the intra-hospital dissemination of high-risk clones. Conclusions: High-risk K. pneumoniae clones, particularly ST147, pose significant challenges in healthcare settings due to the extensive antimicrobial resistance driven by plasmid-borne resistance genes, including those that co-produce carbapenemases, like bla_NDM-1 and bla_OXA-48. Molecular monitoring of these clones is essential for improving targeted infection control strategies, mitigating the spread of multidrug-resistant pathogens, and managing their clinical impact effectively. Full article

(This article belongs to the Special Issue Antibiotics Resistance and Molecular Epidemiology of Carbapenem-Resistance Bacteria)

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