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Search Results (542)

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15 pages, 1535 KB  
Article
Antibiofilm Inhibitor Ferulic Acid as an Antibacterial Synergist Against Escherichia coli
by Zhijin Zhang, Jing Xu, Xiaojuan Wei, Rongbin Hu, Zhen Zhu, Zixuan Shang, Weiwei Wang, Bing Li, Yubin Bai and Jiyu Zhang
Biomolecules 2025, 15(9), 1253; https://doi.org/10.3390/biom15091253 - 29 Aug 2025
Viewed by 70
Abstract
Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that [...] Read more.
Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that has been proven to possess various biological activities, including anti-inflammatory, antioxidant, and antitumor properties. This study evaluated the inhibitory effect of FA on the biofilm formation of E. coli through crystal violet (CV) staining and scanning electron microscopy (SEM) and investigated the synergistic effect of FA with antibiotics, using the alamar blue (AB) assay. In addition, the regulatory effect of FA on the transcription of biofilm-related genes was analyzed using qRT-PCR technology. The results showed that FA could significantly inhibit biofilm formation, reduce the production of extracellular polymeric substances (EPS), and weaken bacterial motility, without affecting bacterial growth and metabolic activity. qRT-PCR analysis revealed that FA significantly downregulated the expression of curli-related gene csgD, flagella-related genes (flhC, flhD, and motA), and type I fimbriae gene fimA, while upregulating the transcription of c-di-GMP-related genes (pdeR, pdeA, and dosP). It is noteworthy that FA exhibits significant synergistic antibacterial effects when combined with clinically commonly used antibiotics, including sodium fosfomycin, ceftriaxone, gentamicin, and tetracycline, with the most prominent synergistic effect observed in the combination of FA and sodium fosfomycin. These results confirm that FA possesses notable anti-biofilm activity and novel synergistic antibacterial properties, providing a potential therapeutic strategy for treating E. coli infections. Full article
(This article belongs to the Special Issue Novel Mechanisms of Bacterial Antibiotic Resistance)
24 pages, 2071 KB  
Article
Increased Antimicrobial Consumption, Isolation Rate, and Resistance Profiles of Multi-Drug Resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii During the COVID-19 Pandemic in a Tertiary Healthcare Institution
by Predrag Savic, Ljiljana Gojkovic Bukarica, Predrag Stevanovic, Teodora Vitorovic, Zoran Bukumiric, Olivera Vucicevic, Nenad Milanov, Vladimir Zivanovic, Ana Bukarica and Milos Gostimirovic
Antibiotics 2025, 14(9), 871; https://doi.org/10.3390/antibiotics14090871 - 29 Aug 2025
Viewed by 213
Abstract
Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter [...] Read more.
Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in the Management of Bloodstream Infections)
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19 pages, 1288 KB  
Review
Syphilis and the Eye: Clinical Features, Diagnostic Challenges, and Evolving Therapeutic Paradigms
by Zizhen Ye, Mingming Yang, Yaru Zou, Jing Zhang, Jiaxin Deng, Yuan Zong, Kyoko Ohno-Matsui and Koju Kamoi
Pathogens 2025, 14(9), 852; https://doi.org/10.3390/pathogens14090852 - 27 Aug 2025
Viewed by 370
Abstract
Syphilis is a systemic infection with a broad spectrum of ocular involvement that can affect every segment of the eye. Clinical presentations range from interstitial keratitis, conjunctivitis, episcleritis, and scleritis to anterior, intermediate, and posterior uveitis; acute syphilitic posterior placoid chorioretinitis; retinitis; retinal [...] Read more.
Syphilis is a systemic infection with a broad spectrum of ocular involvement that can affect every segment of the eye. Clinical presentations range from interstitial keratitis, conjunctivitis, episcleritis, and scleritis to anterior, intermediate, and posterior uveitis; acute syphilitic posterior placoid chorioretinitis; retinitis; retinal vasculitis; neuroretinitis; optic neuritis; exudative retinal detachment; and optic nerve dysfunction. These manifestations may occur at any stage of infection and are frequently nonspecific, contributing to diagnostic delays. Diagnosis requires a high index of suspicion and is established by combined non-treponemal and treponemal serologic testing, with cerebrospinal fluid analysis when neurosyphilis is suspected. Multimodal imaging, including optical coherence tomography, fluorescein angiography, fundus autofluorescence, and visual field testing, enhances the detection of subclinical and atypical diseases. Management mandates prompt intravenous penicillin G, with adjunctive corticosteroids to mitigate Jarisch–Herxheimer reactions and control inflammation; ceftriaxone or doxycycline serve as alternatives for penicillin-allergic patients. Long-term follow-up with serial serologies and neurologic evaluation is essential to detect relapse or progression to neurosyphilis. Despite effective therapy, diagnostic delays contribute to irreversible visual loss in a significant proportion of cases. This review integrates current knowledge on ocular syphilis, emphasizing its varied presentations and the importance of early recognition to prevent vision-threatening complications, and calls for multidisciplinary, mechanism-based research to optimize outcomes. We conducted a literature search in Pubmed and Embase for articles published between 2000 and 2025, using the terms “ocular syphilis,” “syphilitic uveitis,” and “neurosyphilis,” with a focus on epidemiology, clinical features, diagnostics, therapeutics, and co-infections. Full article
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11 pages, 1621 KB  
Article
Veillonella parvula as a Causative Agent of Discitis: Insights from a Clinical Case and Literature Overview
by Giulio D’Agati, Lorena Mignone, Antonella Bartolone, Giuseppa Sciortino, Teresa Maria Assunta Fasciana, Cinzia Calà, Silvia Bonura, Francesco Carini, Luca Pipitò and Antonio Cascio
Antibiotics 2025, 14(9), 854; https://doi.org/10.3390/antibiotics14090854 - 24 Aug 2025
Viewed by 413
Abstract
Background/Objectives: Veillonella species are Gram-negative, non-motile, non-fermentative, obligate anaerobic cocci. They are typically considered commensals of the oral cavity, respiratory tract, genitourinary tract, and gastrointestinal tract. It may be a rare cause of dental infections and discitis/spondylodiscitis. Methods: We report the case of [...] Read more.
Background/Objectives: Veillonella species are Gram-negative, non-motile, non-fermentative, obligate anaerobic cocci. They are typically considered commensals of the oral cavity, respiratory tract, genitourinary tract, and gastrointestinal tract. It may be a rare cause of dental infections and discitis/spondylodiscitis. Methods: We report the case of an 80-year-old patient diagnosed with discitis caused by Veillonella parvula, isolated from blood. In addition, we performed a comprehensive literature review summarizing all reported cases of discitis or spondylodiscitis caused by Veillonella species. Results: In our case, antimicrobial susceptibility testing was performed using the Kirby–Bauer disc diffusion method. Based on the results, the patient was treated with amoxicillin/clavulanate, which led to a favourable clinical outcome. A review of the literature revealed that, to date, only 14 cases of spondylodiscitis or discitis caused by Veillonella spp. have been reported. Potential risk factors for Veillonella spp. bacteremia were identified in only 9 cases. The most commonly affected site was the lumbar or lumbosacral spine. Magnetic resonance imaging was consistently regarded as the diagnostic gold standard. Most patients presented with localized pain. The overall therapeutic approach generally consisted of an initial course of intravenous antibiotics, typically ceftriaxone administered either as monotherapy or in combination with metronidazole, followed by an oral regimen with amoxicillin/clavulanate, given alone or alongside metronidazole. Conclusions: Spondylodiscitis due to V. parvula remains extremely rare. Although antimicrobial susceptibility patterns remain heterogeneous, beta-lactams, particularly amoxicillin/clavulanate, appear effective in most cases, and treatment regimens typically involve an initial intravenous phase followed by oral therapy. Full article
(This article belongs to the Special Issue Diagnosis and Antimicrobial Therapy of Osteoarticular Infection)
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25 pages, 1259 KB  
Review
Cerebrovascular Disease as a Manifestation of Tick-Borne Infections: A Narrative Review
by David Doyle, Samuel Kim, Alexis Berry, Morgan Belle, Nicholas Panico, Shawn Kaura, Austin Price, Taylor Reardon and Margaret Ellen
J. Vasc. Dis. 2025, 4(3), 33; https://doi.org/10.3390/jvd4030033 - 21 Aug 2025
Viewed by 524
Abstract
Background/Objectives: Tick-borne diseases (TBDs) are increasingly recognized as causes of both systemic and neurologic illness. While their impact on vascular health is established, their role in cerebrovascular disease remains underexplored. This review aims to synthesize clinical evidence linking TBDs with cerebrovascular events, [...] Read more.
Background/Objectives: Tick-borne diseases (TBDs) are increasingly recognized as causes of both systemic and neurologic illness. While their impact on vascular health is established, their role in cerebrovascular disease remains underexplored. This review aims to synthesize clinical evidence linking TBDs with cerebrovascular events, focusing on mechanisms of injury, pathogen-specific associations, and treatment outcomes. Methods: A narrative review was conducted using Boolean keyword searches across PubMed, Scopus, EMBASE, and Web of Science. Relevant literature on ischemic and hemorrhagic stroke, cerebral vasculitis, and stroke mimics associated with TBDs was examined. The review included case reports, observational studies, and mechanistic research. Pathogen-specific data and disease characteristics were extracted and summarized. Results: Several tick-borne pathogens were associated with cerebrovascular complications. Borrelia burgdorferi was most commonly implicated and typically presented with large-vessel vasculitis. Rickettsia, Ehrlichia, and Anaplasma species caused endothelial injury through immune-mediated inflammation. Powassan virus and Crimean–Congo hemorrhagic fever virus exhibited central nervous system involvement and hemorrhagic potential. Babesia species contributed to vascular injury through thrombocytopenia and embolic complications. Neuroimaging frequently demonstrated multifocal stenoses and vessel wall inflammation. Antimicrobial treatment, particularly with doxycycline or ceftriaxone, was often effective, especially when administered early. Supportive care for stroke symptoms varied by presentation and underlying pathogen. Conclusions: Cerebrovascular disease caused by tick-borne pathogens is an underrecognized but potentially reversible condition. Despite diverse etiologies, most pathogens share a final common pathway of endothelial dysfunction. Early recognition and targeted antimicrobial therapy, combined with supportive stroke care, are essential to improving patient outcomes. Full article
(This article belongs to the Topic Diagnosis and Management of Acute Ischemic Stroke)
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11 pages, 525 KB  
Article
Susceptibility of Neisseria gonorrhoeae to Zoliflodacin and Quinolones in Hyogo Prefecture, Japan
by Takashi Yurube, Katsumi Shigemura, Yurino Kobayashi, Taishi Maeda, Nami Nishimura, Ayaka Yamada, Kotoko Kotani, Saki Horii, Hiroyuki Yoshida and Kayo Osawa
Pathogens 2025, 14(8), 831; https://doi.org/10.3390/pathogens14080831 - 21 Aug 2025
Viewed by 296
Abstract
The DNA synthesis inhibitor zoliflodacin (ZFD) is expected to be effective against strains resistant to therapeutic agents for Neisseria gonorrhoeae infection. In addition to ZFD, we investigated the susceptibility of N. gonorrhoeae strains to ceftriaxone (CTRX), ciprofloxacin (CPFX), garenoxacin (GRNX), and sitafloxacin (STFX). [...] Read more.
The DNA synthesis inhibitor zoliflodacin (ZFD) is expected to be effective against strains resistant to therapeutic agents for Neisseria gonorrhoeae infection. In addition to ZFD, we investigated the susceptibility of N. gonorrhoeae strains to ceftriaxone (CTRX), ciprofloxacin (CPFX), garenoxacin (GRNX), and sitafloxacin (STFX). Minimum inhibitory concentration values for ZFD and four other drugs were determined for 147 strains of N. gonorrhoeae isolated at medical institutions in Hyogo Prefecture, Japan, from 2015 to 2022. Amino acid alterations in gyrA, gyrB, parC, and parE were examined by polymerase chain reaction and sequencing analysis. Sequence type (ST) was determined for epidemiological analysis, and N. gonorrhoeae strains were classified. The non-susceptibility rate was not observed in CTRX. The lowest non-susceptibility rate was observed in ZFD (39.5%) compared to CPFX (80.3%), GRNX (83.7%), and STFX (65.3%) (all p < 0.0001). The most common amino acid alterations in gyrA and parC had non-susceptibility rates exceeding 80% to quinolones except ZFD, suggesting that these alterations may have influenced the resistance trend. STs were different between isolates in 2015 and those in 2020 and later. ZFD showed potent antimicrobial activity against N. gonorrhoeae strains that are highly resistant to quinolones. It may become a new option in the treatment of gonococcal infections. Full article
(This article belongs to the Special Issue Cutting-Edge Research on Pathogenic Neisseria)
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14 pages, 1029 KB  
Article
Molecular Characterization and Antimicrobial Resistance of Salmonella from Chicken Meat and Water in Retail Markets of Chitwan, Nepal
by Saroj Parajuli, Hom Bahadur Basnet, Rabin Raut and Rebanta Kumar Bhattarai
Appl. Microbiol. 2025, 5(3), 81; https://doi.org/10.3390/applmicrobiol5030081 - 9 Aug 2025
Viewed by 377
Abstract
Salmonella is a zoonotic foodborne pathogen that affects poultry health and reaches consumers through the food chain via contaminated products. A cross-sectional study was conducted to isolate and identify Salmonella and to detect antibiotic resistance genes in Salmonella isolates from retail meat shops [...] Read more.
Salmonella is a zoonotic foodborne pathogen that affects poultry health and reaches consumers through the food chain via contaminated products. A cross-sectional study was conducted to isolate and identify Salmonella and to detect antibiotic resistance genes in Salmonella isolates from retail meat shops in Chitwan, Nepal. The antimicrobial susceptibility test was carried out using the Kirby–Bauer disc diffusion method. Antibiotic resistance genes were detected by using multiplex polymerase chain reaction (PCR). A total of 216 samples, chicken meat (108) and water (108), were tested for the presence of Salmonella. Out of the 216 samples tested, 38 samples were positive, giving an overall prevalence of 17.59%. A higher prevalence of Salmonella was found in meat samples, 29.62% (32/108), compared with the water samples, 5.55% (6/108), which was statistically significant (p < 0.05). The antibiogram profile showed maximum resistance to doxycycline (88%), followed by tetracycline (86%), erythromycin (79%), ampicillin + sulbactam (76%), ceftriaxone (22%), levofloxacin (21%), gentamicin (18%), chloramphenicol (13%), and amikacin (15%). The prevalence of the tetB gene and ere(A) gene was 23.68% (9/38) and 18.42% (7/38), respectively, and the association was statistically non-significant (p > 0.05). However, mcr1, catA1, and blaTEM genes were not detected. The study recommends integrated surveillance encompassing human health, food safety, and animal health under the ‘One Health’ approach, highlighting the need for effective strategies involving poultry farms, retail meat shops, and consumers to minimize contamination and reduce the transmission of Salmonella along the food chain from primary production to consumption on a global scale. Full article
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8 pages, 912 KB  
Article
Methenamine as an Alternative Treatment of Neisseria gonorrhoeae Urethritis? An In Vitro and In Vivo Study in Galleria mellonella
by Izumo Kanesaka, Saïd Abdellati, Sheeba Santhini Manoharan-Basil and Chris Kenyon
Venereology 2025, 4(3), 13; https://doi.org/10.3390/venereology4030013 - 1 Aug 2025
Viewed by 305
Abstract
Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then [...] Read more.
Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then assessed the in vivo efficacy of methenamine-hippurate against N. gonorrhoeae using the Galleria mellonella infection model. Results: We found that all the gonococcal isolates had a methenamine-hippurate MIC of 300 mg/L. This MIC was not higher in isolates with higher ceftriaxone MICs. No toxicity of methenamine at the doses tested was found, and doses as low as 200 mg/kg were effective in the G. mellonella model. Conclusions: Further studies in mice and humans are required to assess if methenamine-hippurate could be used to treat gonococcal urethritis alone or in combination with other agents such as ceftriaxone. Full article
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16 pages, 306 KB  
Article
Antibiotic Use in Pediatric Care in Ghana: A Call to Action for Stewardship in This Population
by Israel Abebrese Sefah, Dennis Komla Bosrotsi, Kwame Ohene Buabeng, Brian Godman and Varsha Bangalee
Antibiotics 2025, 14(8), 779; https://doi.org/10.3390/antibiotics14080779 - 1 Aug 2025
Viewed by 787
Abstract
Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable [...] Read more.
Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable population. This was the objective behind this study. Methods: The medical records of all pediatric patients (under 12 years) admitted and treated with antibiotics at a Ghanaian Teaching Hospital between January 2022 and March 2022 were extracted from the hospital’s electronic database. The prevalence and appropriateness of antibiotic use were based on antibiotic choices compared with current guidelines. Influencing factors were also assessed. Results: Of the 410 admitted patients, 319 (77.80%) received at least one antibiotic. The majority (68.65%; n = 219/319) were between 0 and 2 years, and males (54.55%; n = 174/319). Ceftriaxone was the most commonly prescribed antibiotic (20.69%; n = 66/319), and most of the systemic antibiotics used belonged to the WHO Access and Watch groups, including a combination of Access and Watch groups (42.90%; n = 136/319). Neonatal sepsis (24.14%; n = 77/319) and pneumonia (14.42%; n = 46/319) were the most common diagnoses treated with antibiotics. Antibiotic appropriateness was 42.32% (n = 135/319). Multivariate analysis revealed ceftriaxone prescriptions (aOR = 0.12; CI = 0.02–0.95; p-value = 0.044) and surgical prophylaxis (aOR = 0.07; CI = 0.01–0.42; p-value = 0.004) were associated with reduced antibiotic appropriateness, while a pneumonia diagnosis appreciably increased this (aOR = 15.38; CI = 3.30–71.62; p-value < 0.001). Conclusions: There was high and suboptimal usage of antibiotics among hospitalized pediatric patients in this leading hospital. Antibiotic appropriateness was influenced by antibiotic type, diagnosis, and surgical prophylaxis. Targeted interventions, including education, are needed to improve antibiotic utilization in this setting in Ghana and, subsequently, in ambulatory care. Full article
20 pages, 15855 KB  
Article
Resistance Response and Regulatory Mechanisms of Ciprofloxacin-Induced Resistant Salmonella Typhimurium Based on Comprehensive Transcriptomic and Metabolomic Analysis
by Xiaohan Yang, Jinhua Chu, Lulu Huang, Muhammad Haris Raza Farhan, Mengyao Feng, Jiapeng Bai, Bangjuan Wang and Guyue Cheng
Antibiotics 2025, 14(8), 767; https://doi.org/10.3390/antibiotics14080767 - 29 Jul 2025
Viewed by 500
Abstract
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, [...] Read more.
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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15 pages, 1411 KB  
Article
Enhancing Antibiotic Effect by Photodynamic: The Case of Klebsiella pneumoniae
by Koteswara Rao Yerra and Vanderlei S. Bagnato
Antibiotics 2025, 14(8), 766; https://doi.org/10.3390/antibiotics14080766 - 29 Jul 2025
Viewed by 431
Abstract
Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in [...] Read more.
Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm2 LED emitting at 660 nm with an energy of 15 J/cm2. The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log10 to 2 Log10 CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log10 to 6 Log10 CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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14 pages, 384 KB  
Article
Outbreak Caused by VIM-1- and VIM-4-Positive Proteus mirabilis in a Hospital in Zagreb
by Branka Bedenić, Gernot Zarfel, Josefa Luxner, Andrea Grisold, Marina Nađ, Maja Anušić, Vladimira Tičić, Verena Dobretzberger, Ivan Barišić and Jasmina Vraneš
Pathogens 2025, 14(8), 737; https://doi.org/10.3390/pathogens14080737 - 26 Jul 2025
Viewed by 426
Abstract
Background/objectives: Proteus mirabilis is a frequent causative agent of urinary and wound infections in both community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESCs) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpCs). Recently, carbapenem-resistant isolates of [...] Read more.
Background/objectives: Proteus mirabilis is a frequent causative agent of urinary and wound infections in both community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESCs) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpCs). Recently, carbapenem-resistant isolates of P. mirabilis emerged due to the production of carbapenemases, mostly belonging to Ambler classes B and D. Here, we report an outbreak of infections due to carbapenem-resistant P. mirabilis that were observed in a psychiatric hospital in Zagreb, Croatia. The characteristics of ESBL and carbapenemase-producing P. mirabilis isolates, associated with an outbreak, were analyzed. Materials and methods: The antibiotic susceptibility testing was performed by the disk-diffusion and broth dilution methods. The double-disk synergy test (DDST) and inhibitor-based test with clavulanic and phenylboronic acid were applied to screen for ESBLs and p-AmpCs, respectively. Carbapenemases were screened by the modified Hodge test (MHT), while carbapenem hydrolysis was investigated by the carbapenem inactivation method (CIM) and EDTA-carbapenem-inactivation method (eCIM). The nature of the ESBLs, carbapenemases, and fluoroquinolone-resistance determinants was investigated by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). Selected isolates were subjected to molecular characterization of the resistome by an Inter-Array Genotyping Kit CarbaResisit and whole-genome sequencing (WGS). Results: In total, 20 isolates were collected and analyzed. All isolates exhibited resistance to amoxicillin alone and when combined with clavulanic acid, cefuroxime, cefotaxime, ceftriaxone, cefepime, imipenem, ceftazidime–avibactam, ceftolozane–tazobactam, gentamicin, amikacin, and ciprofloxacin. There was uniform susceptibility to ertapenem, meropenem, and cefiderocol. The DDST and combined disk test with clavulanic acid were positive, indicating the production of an ESBL. The MHT was negative in all except one isolate, while the CIM showed moderate sensitivity, but only with imipenem as the indicator disk. Furthermore, eCIM tested positive in all of the CIM-positive isolates, consistent with a metallo-β-lactamase (MBL). PCR and sequencing of the selected amplicons identified VIM-1 and VIM-4. The Inter-Array Genotyping Kit CarbaResist and WGS identified β-lactam resistance genes blaVIM, blaCTX-M-15, and blaTEM genes; aminoglycoside resistance genes aac(3)-IId, aph(6)-Id, aph(3″)-Ib, aadA1, armA, and aac(6′)-IIc; as well as resistance genes for sulphonamides sul1 and sul2, trimethoprim dfr1, chloramphenicol cat, and tetracycline tet(J). Conclusions: This study revealed an epidemic spread of carbapenemase-producing P. mirabilis in two wards in a psychiatric hospital. Due to the extensively resistant phenotype (XDR), therapeutic options were limited. This is the first report of carbapenemase-producing P. mirabilis in Croatia. Full article
(This article belongs to the Special Issue Emerging and Neglected Pathogens in the Balkans)
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13 pages, 413 KB  
Article
A Retrospective Cohort Study of Leptospirosis in Crete, Greece
by Petros Ioannou, Maria Pendondgis, Eleni Kampanieri, Stergos Koukias, Maria Gorgomyti, Kyriaki Tryfinopoulou and Diamantis Kofteridis
Trop. Med. Infect. Dis. 2025, 10(8), 209; https://doi.org/10.3390/tropicalmed10080209 - 25 Jul 2025
Viewed by 621
Abstract
Introduction: Leptospirosis is an under-recognized zoonosis that affects both tropical and temperate regions. While it is often associated with exposure to contaminated water or infected animals, its presentation and epidemiology in Mediterranean countries remain incompletely understood. This retrospective cohort study investigates the clinical [...] Read more.
Introduction: Leptospirosis is an under-recognized zoonosis that affects both tropical and temperate regions. While it is often associated with exposure to contaminated water or infected animals, its presentation and epidemiology in Mediterranean countries remain incompletely understood. This retrospective cohort study investigates the clinical and epidemiological profile of leptospirosis in Crete, Greece, a region where data are scarce. Methods: All adult patients with laboratory-confirmed leptospirosis admitted to three major public hospitals in Crete, Greece, between January 2019 and December 2023 were included in the analysis. Diagnosis was made through serologic testing along with compatible clinical symptoms. Results: A total of 17 patients were included. Their median age was 48 years, with a predominance of males (70.6%). Notably, more than half of the patients had no documented exposure to classic risk factors such as rodents or standing water. Clinical presentations were varied but commonly included fever, fatigue, acute kidney injury, and jaundice. Of the patients who underwent imaging, most showed hepatomegaly. The median delay from symptom onset to diagnosis was 11 days, underscoring the diagnostic challenge in non-endemic areas. Ceftriaxone was the most frequently administered antibiotic (76.5%), often in combination with tetracyclines or quinolones. Despite treatment, three patients (17.6%) died, all presenting with severe manifestations such as ARDS, liver failure, or shock. A concerning increase in cases was noted in 2023. Conclusions: Leptospirosis can present with severe and potentially fatal outcomes even in previously healthy individuals and in regions not traditionally considered endemic. The relatively high mortality and disease frequency noted emphasize the importance of maintaining a high index of suspicion. Timely diagnosis and appropriate antimicrobial therapy are essential to improving patient outcomes. Additionally, the need for enhanced public health awareness, diagnostic capacity, and possibly environmental surveillance to control this neglected but impactful disease better, should be emphasized. Full article
(This article belongs to the Special Issue Leptospirosis and One Health)
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9 pages, 234 KB  
Article
Should Cefoxitin Non-Susceptibility in Ceftriaxone-Susceptible E. coli and K. pneumoniae Prompt Concerns Regarding Plasmid-Mediated AmpC Resistance? A Genomic Characterization and Summary of Treatment Challenges in Singapore
by Jonathan Jinpeng Foo, Ying Ying Ong, Clement Kin Ming Tsui, David C. Lye, De Partha Pratim, Nurhidayah Binte Mohamed Yazid, Swaine L. Chen, Shawn Vasoo and Tat Ming Ng
Antibiotics 2025, 14(7), 722; https://doi.org/10.3390/antibiotics14070722 - 18 Jul 2025
Viewed by 625
Abstract
Objectives: Plasmid-mediated AmpC beta-lactamases represent a growing clinical concern in Enterobacterales, with challenges in diagnostic approaches, limited data on clinical outcomes, and our incomplete understanding of their regulatory mechanisms warranting the need for further investigation. Methods: This retrospective study examined the genomic [...] Read more.
Objectives: Plasmid-mediated AmpC beta-lactamases represent a growing clinical concern in Enterobacterales, with challenges in diagnostic approaches, limited data on clinical outcomes, and our incomplete understanding of their regulatory mechanisms warranting the need for further investigation. Methods: This retrospective study examined the genomic and clinical characteristics of cefoxitin-non-susceptible, ceftriaxone-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates collected from a tertiary hospital in Singapore. Whole-genome sequencing was performed to detect ampC genes, subtypes, and associated regulatory elements. Results: Among 108 cefoxitin-non-susceptible isolates, only 15 (13.9%) harboured plasmid-mediated ampC, suggesting that cefoxitin non-susceptibility alone in ceftriaxone susceptible isolates was not predictive of ampC carriage. All plasmid-ampC isolates were from the blaDHA-1 subtype and carried ampR, a known transcriptional regulator of inducible beta-lactamase expression. Notably, five non-ampC carrying Klebsiella isolates displayed truncations in ompK35 and ompK36, which could potentially contribute to reduced cefoxitin susceptibility via porin loss. Conclusions: These findings underscore the limited diagnostic utility of cefoxitin susceptibility testing for detecting plasmid-mediated ampC producers and highlight the clinical relevance of regulatory genes such as ampR in mediating inducible resistance. The routine incorporation of molecular diagnostics or genome sequencing may be necessary to improve detection accuracy and inform antimicrobial stewardship strategies. Full article
11 pages, 1010 KB  
Case Report
A Puerperal Patient with Leukopenia During Vancomycin Administration: A Case Report and Review of the Literature
by Lidija Tulic, Katarina Ivanovic, Ivan Tulic, Svetlana Vrzic-Petronijevic, Stefan Ivanovic, Danijela Bratic and Miloš Petronijevic
Int. J. Mol. Sci. 2025, 26(14), 6584; https://doi.org/10.3390/ijms26146584 - 9 Jul 2025
Cited by 1 | Viewed by 499
Abstract
Antibiotic therapy is essential for managing bacterial infections, but rare yet serious hematological complications such as leukopenia and agranulocytosis may occur. These conditions, although uncommon, require timely diagnosis and intervention, particularly in vulnerable populations such as postpartum patients. This case report describes a [...] Read more.
Antibiotic therapy is essential for managing bacterial infections, but rare yet serious hematological complications such as leukopenia and agranulocytosis may occur. These conditions, although uncommon, require timely diagnosis and intervention, particularly in vulnerable populations such as postpartum patients. This case report describes a 31-year-old puerperal woman who developed agranulocytosis after extended antibiotic treatment for a presumed multidrug-resistant infection. Initially treated with ceftriaxone and metronidazole, her therapy was later escalated to include ciprofloxacin, amoxicillin–clavulanic acid, and vancomycin. Enterococcus spp. and Staphylococcus aureus were isolated from multiple sites, although no systemic infection was confirmed. Bone marrow findings were consistent with agranulocytosis in the recovery phase. Despite improvements in infection markers, her leukocyte count progressively declined, reaching a nadir of 1.61 × 109/L on the 19th day of therapy. Granulocyte-colony stimulating factor (G-CSF) therapy was initiated, resulting in hematological recovery. The patient was discharged with normal inflammatory markers and leukocyte counts. This case highlights the importance of diagnostic precision, rational antibiotic use, and timely hematologic assessment during prolonged antimicrobial treatment. Full article
(This article belongs to the Special Issue Drug Treatment for Bacterial Infections)
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