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14 pages, 263 KiB  
Article
Impact of Antibiotic Prophylaxis Duration on the Incidence of Healthcare-Associated Infections in Elective Colorectal Surgery
by Vladimir Nikolic, Ljiljana Markovic-Denic, Boris Tadić, Milan Veselinović, Ivan Palibrk, Milorad Reljić, Predrag Sabljak, Lidija Masic, Svetozar Mijuskovic, Stefan Kmezic, Djordje Knezevic, Slavenko Ostojić, Jelena Đokić-Kovač and Andrija Antic
Antibiotics 2025, 14(8), 791; https://doi.org/10.3390/antibiotics14080791 (registering DOI) - 4 Aug 2025
Abstract
Background/Objectives: Antibiotic prophylaxis is a key component of infection prevention strategies. This study aimed to evaluate whether the duration of antibiotic prophylaxis influences the incidence of HAIs in patients undergoing elective colorectal surgery. Methods: This prospective cohort study included 278 adult [...] Read more.
Background/Objectives: Antibiotic prophylaxis is a key component of infection prevention strategies. This study aimed to evaluate whether the duration of antibiotic prophylaxis influences the incidence of HAIs in patients undergoing elective colorectal surgery. Methods: This prospective cohort study included 278 adult patients who underwent elective colorectal surgery at a single tertiary care center. Patients were categorized into two groups based on the duration of antibiotic prophylaxis: one day or more than one day. Data on demographics, clinical characteristics, perioperative variables, and infection outcomes were collected. Results: The overall incidence of HAIs was 16.9%, with no significant difference between patients receiving one-day versus extended antibiotic prophylaxis. However, traditional multivariate analysis showed that prophylaxis lasting more than one day was independently associated with a significantly lower risk of HAI (RR = 0.30, 95% CI: 0.12–0.75, p = 0.010) and surgical site infections (RR = 0.24, 95% CI: 0.08–0.72, p = 0.011). After adjusting for confounders using propensity score matching, this association was no longer statistically significant. No significant association was found between prophylaxis duration and urinary tract infections. Regarding antibiotic selection, first-generation cephalosporins were the most commonly used agents, accounting for 78.8% of prophylactic prescriptions. This was followed by fluoroquinolones (14.4%) and third-generation cephalosporins (5.0%). All patients received metronidazole, a nitroimidazole-class antimicrobial, in combination with the above agents. Conclusions: One day of prophylactic antibiotics may be sufficient in SSI prevention in patients undergoing elective colorectal surgery. The use of extended antibiotic prophylaxis beyond one day should be considered for high-risk patients at high risk of infection, particularly those requiring ICU care. Full article
11 pages, 593 KiB  
Article
Burden of Streptococcus pyogenes and emm12 Type in Severe Otitis Media Among Children
by Alexandra S. Alexandrova, Adile A. Muhtarova, Vasil S. Boyanov and Raina T. Gergova
Microbiol. Res. 2025, 16(8), 181; https://doi.org/10.3390/microbiolres16080181 - 3 Aug 2025
Abstract
Streptococcus pyogenes (GAS) is a leading cause of acute otitis media (AOM) and its complications. This study aimed to evaluate the antimicrobial resistance of all isolated bacterial agents recovered from children with AOM and to perform the emm typing of GAS isolates. Antibiotic [...] Read more.
Streptococcus pyogenes (GAS) is a leading cause of acute otitis media (AOM) and its complications. This study aimed to evaluate the antimicrobial resistance of all isolated bacterial agents recovered from children with AOM and to perform the emm typing of GAS isolates. Antibiotic susceptibility testing was evaluated according to EUCAST criteria. Phenotyping and genotyping were performed for the macrolide-resistant GAS isolates. All GAS isolates were subjected to emm typing. Among the 103 AOM cases considered, we identified GAS isolates (39.4%), Staphylococcus aureus (26.6%), Haemophilus influenzae (13.8%), Streptococcus pneumoniae (11.7%), Moraxella catarrhalis (7.4%), and Serratia marcescens (1.1%). GAS exhibited 32.4% macrolide resistance and 10.8% clindamycin resistance. The M phenotype and mefE gene (18.9%) were the most common, followed by cMLSB (10.8% with ermB), a combination of mefA and ermB (8.1%), and iMLSB (2.7% with ermA). The most prevalent emm types were emm12 (27.0%), emm1 (21.6%), and emm3 (16.2%). The most common GAS emm types identified among AOM patients in this study are found worldwide and are associated with invasive infections in various countries. This may influence the virulence and invasive potential of these strains. Full article
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12 pages, 1739 KiB  
Article
Tailored Levofloxacin Incorporated Extracellular Matrix Nanoparticles for Pulmonary Infections
by Raahi Patel, Ignacio Moyano, Masahiro Sakagami, Jason D. Kang, Phillip B. Hylemon, Judith A. Voynow and Rebecca L. Heise
Int. J. Mol. Sci. 2025, 26(15), 7453; https://doi.org/10.3390/ijms26157453 (registering DOI) - 1 Aug 2025
Viewed by 146
Abstract
Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to [...] Read more.
Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article
(This article belongs to the Special Issue The Advances in Antimicrobial Biomaterials)
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25 pages, 7784 KiB  
Article
Diversity in the Common Fold: Structural Insights into Class D β-Lactamases from Gram-Negative Pathogens
by Clyde A. Smith and Anastasiya Stasyuk
Pathogens 2025, 14(8), 761; https://doi.org/10.3390/pathogens14080761 (registering DOI) - 1 Aug 2025
Viewed by 155
Abstract
Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops [...] Read more.
Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops (the P-loop, Ω-loop, and newly designated B-loop) that surround the active site. While each of these loops is known to influence enzyme function, their coordinated roles have not been fully elucidated. To investigate the significance of their interplay, we compared the sequences and crystal structures of 40 DBLs from clinically relevant Gram-negative pathogens and performed molecular dynamics simulations on selected representatives. Combined structural and dynamical analyses revealed a strong correlation between B-loop architecture and carbapenemase activity in the pathogens Klebsiella and Acinetobacter, particularly regarding loop length and spatial organization. These findings emphasize the B-loop’s critical contribution, in concert with the P- and Ω-loops, in tuning active site versatility, substrate recognition, catalytic activity, and structural stability. A deeper understanding of how these motifs and loops govern DBL function may inform the development of novel antibiotics and inhibitors targeting this class of enzymes. Full article
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26 pages, 89199 KiB  
Article
Light-Responsive PLGA Microparticles for On-Demand Vancomycin Release and Enhanced Antibacterial Efficiency
by Mishal Pokharel, Abid Neron, Amit Kumar Dey, Aishwarya Raksha Siddharthan, Menaka Konara, Md Mainuddin Sagar, Tracie Ferreira and Kihan Park
Pharmaceutics 2025, 17(8), 1007; https://doi.org/10.3390/pharmaceutics17081007 - 1 Aug 2025
Viewed by 428
Abstract
Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) [...] Read more.
Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 μm) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article
(This article belongs to the Special Issue Nano-Based Delivery Systems for Topical Applications)
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6 pages, 3862 KiB  
Case Report
Gastric Sarcina ventriculi: A Report on Two Cases
by Yaomin Chen, Yu Liu and Zhiyan Fu
Reports 2025, 8(3), 128; https://doi.org/10.3390/reports8030128 - 1 Aug 2025
Viewed by 144
Abstract
Background and Clinical SignificanceSarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. [...] Read more.
Background and Clinical SignificanceSarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. Case Presentation: We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution and clearance of Sarcina ventriculi upon follow-up examinations. Conclusions: This report explores the pathogenicity of Sarcina ventriculi by documenting its presence in symptomatic patients without other identifiable pathogens and demonstrating complete symptom resolution following targeted therapy. These findings raise the possibility of Sarcina ventriculi’s pathogenic potential under specific clinical conditions, suggesting it may act as more than a benign colonizer. Full article
(This article belongs to the Section Gastroenterology)
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16 pages, 306 KiB  
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 (registering DOI) - 1 Aug 2025
Viewed by 177
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
13 pages, 1321 KiB  
Article
Intravitreal Povidone-Iodine Injection and Low-Dose Antibiotic Irrigation for Infectious Endophthalmitis: A Retrospective Case Series
by Yumiko Machida, Hiroyuki Nakashizuka, Hajime Onoe, Yorihisa Kitagawa, Naoya Nakagawa, Keisuke Miyata, Misato Yamakawa, Yu Wakatsuki, Koji Tanaka, Ryusaburo Mori and Hiroyuki Shimada
Pharmaceutics 2025, 17(8), 995; https://doi.org/10.3390/pharmaceutics17080995 (registering DOI) - 31 Jul 2025
Viewed by 194
Abstract
Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the [...] Read more.
Background/Objectives: Infectious endophthalmitis is a vision-threatening complication of intraocular surgery and intravitreal injections. Standard treatment involves intravitreal antibiotics; however, concerns regarding multidrug resistance and vancomycin-associated hemorrhagic occlusive retinal vasculitis (HORV) highlight the need for alternative antimicrobial strategies. This study aimed to evaluate the clinical efficacy and safety of a protocol combining intravitreal injection of 1.25% povidone-iodine (PI) with intraoperative irrigation using low concentrations of vancomycin and ceftazidime. Methods: We retrospectively analyzed 11 eyes from patients diagnosed with postoperative or injection-related endophthalmitis. Six of the eleven cases received an initial intravitreal injection of 1.25% PI, followed by pars plana vitrectomy with irrigation using balanced salt solution PLUS containing vancomycin (20 μg/mL) and ceftazidime (40 μg/mL). A second intravitreal PI injection was administered at the end of surgery in all cases. Additional PI injections were administered postoperatively based on clinical response. Clinical outcomes included best-corrected visual acuity (BCVA), microbial culture results, corneal endothelial cell density, and visual field testing. Results: All eyes achieved complete infection resolution without recurrence. The mean BCVA improved significantly from 2.18 logMAR at baseline to 0.296 logMAR at final follow-up (p < 0.001). No adverse events were observed on specular microscopy or visual field assessment. The protocol was well tolerated, and repeated PI injections showed no signs of ocular toxicity. Conclusions: This combination protocol provides a safe and effective treatment strategy for infectious endophthalmitis. It enables rapid and complete infection resolution while minimizing the risks associated with intravitreal antibiotics. These findings support further investigation of this protocol as a practical and globally accessible alternative to standard intravitreal antimicrobial therapy. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Ocular Diseases)
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18 pages, 7265 KiB  
Case Report
New Neonatal and Prenatal Approach to Home Therapy with Amoxicillin, Rifaximin, and Anti-Inflammatory Drugs for Pregnant Women with COVID-19 Infections—Monitoring of Fetal Growth as a Prognostic Factor: A Triple Case Series (N.A.T.H.A.N.)
by Carlo Brogna, Grazia Castellucci, Elrashdy M. Redwan, Alberto Rubio-Casillas, Luigi Montano, Gianluca Ciammetti, Marino Giuliano, Valentina Viduto, Mark Fabrowski, Gennaro Lettieri, Carmela Marinaro and Marina Piscopo
Biomedicines 2025, 13(8), 1858; https://doi.org/10.3390/biomedicines13081858 - 30 Jul 2025
Viewed by 369
Abstract
Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have [...] Read more.
Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article
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24 pages, 5828 KiB  
Article
Removal of Rifampicin and Rifaximin Antibiotics on PET Fibers: Optimization, Modeling, and Mechanism Insight
by Elena Fasniuc-Pereu, Elena Niculina Drăgoi, Dumitru Bulgariu, Maria-Cristina Popescu and Laura Bulgariu
Polymers 2025, 17(15), 2089; https://doi.org/10.3390/polym17152089 - 30 Jul 2025
Viewed by 197
Abstract
The removal of antibiotics from aqueous media along with their recovery is still an open research topic, due to their practical and economical importance. Adsorption allows these two objectives to be achieved, provided that the adsorbent used is chemically and mechanically stable and [...] Read more.
The removal of antibiotics from aqueous media along with their recovery is still an open research topic, due to their practical and economical importance. Adsorption allows these two objectives to be achieved, provided that the adsorbent used is chemically and mechanically stable and has a low preparation cost. In this study, PET (polyethylene terephthalate) fibers, obtained by mechanically processing PET waste, were used for the adsorption of rifampicin (RIF) and rifaximin (RIX) antibiotics from aqueous media. The experimental adsorption capacity of PET fibers for the two antibiotics (RIF and RIX) was determined at different pH values (2.0–6.5), adsorbent dose (0.4–20.0 g/L), contact time (5–1440 min), initial antibiotic concentration (4.0–67.0 mg/L), and temperature (10, 22, and 50 °C); the experimental values of these parameters were analyzed using a neuro-evolutive technique (ANE) combining sequential deep learning (DL) models with a differential evolution algorithm. The obtained optimal ANN-DL algorithm was then used to obtain the optimal models for the adsorption of RIF and RIX on PET fibers, which should adequately describe the adsorption dynamics for both antibiotics. The adsorption processes are spontaneous and endothermic (ΔG < 0, ΔH > 0) and are described by the Langmuir model (R2 > 0.97) and the pseudo-second order kinetic model (R2 > 0.99). The retention of RIF and RIX on the surface of PET fibers occurs through physicochemical interactions, and the FTIR spectra and microscopic images support this hypothesis. The presence of inorganic anions in the aqueous solution leads to an increase in the adsorption capacities of RIF (max. 7.6 mg/g) and RIX (max. 3.6 mg/g) on PET fibers, which is mainly due to the ordering of water molecules in the solution. The experimental results presented in this study allowed for the development of the adsorption mechanism of RIF and RIX on PET fibers, highlighting the potential practical applications of these adsorption processes. Full article
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20 pages, 15855 KiB  
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 290
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 KiB  
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 145
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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18 pages, 7222 KiB  
Article
Assessing Risks and Innovating Traceability in Campania’s Illegal Mussel Sale: A One Health Perspective
by Valeria Vuoso, Attilio Mondelli, Carlotta Ceniti, Iolanda Venuti, Giorgio Ciardella, Yolande Thérèse Rose Proroga, Bruna Nisci, Rosa Luisa Ambrosio and Aniello Anastasio
Foods 2025, 14(15), 2672; https://doi.org/10.3390/foods14152672 - 29 Jul 2025
Viewed by 286
Abstract
The illegal sale of mussels is a persistent problem for food safety and public health in the Campania region, where bivalve molluscs are often sold without traceability, evading regulatory controls. In this study, ten batches of mussels seized from unauthorized vendors were analyzed [...] Read more.
The illegal sale of mussels is a persistent problem for food safety and public health in the Campania region, where bivalve molluscs are often sold without traceability, evading regulatory controls. In this study, ten batches of mussels seized from unauthorized vendors were analyzed to evaluate their microbiological safety and trace their geographical origin. High loads of Escherichia coli, exceeding European regulatory limits (Regulation (EC) No 2073/2005), were detected in all samples. In addition, Salmonella Infantis strains resistant to trimethoprim-sulfamethoxazole and azithromycin were isolated, raising further concerns about antimicrobial resistance. Of the 93 Vibrio isolates, identified as V. alginolyticus and V. parahaemolyticus, 37.63% showed multidrug resistance. Approximately 68.57% of the isolates were resistant to tetracyclines and cephalosporins. The presence of resistance to last-resort antibiotics such as carbapenems (11.43%) is particularly alarming. Near-infrared spectroscopy, combined with chemometric models, was used to obtain traceability information, attributing a presumed origin to the seized mussel samples. Of the ten samples, seven were attributed to the Phlegraean area. These findings have provided valuable insights, reinforcing the need for continuous and rigorous surveillance and the integration of innovative tools to ensure seafood safety and support One Health approaches. Full article
(This article belongs to the Section Food Quality and Safety)
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16 pages, 317 KiB  
Review
Combination Antibiotic Therapy for Orthopedic Infections
by Eric Bonnet and Julie Lourtet-Hascoët
Antibiotics 2025, 14(8), 761; https://doi.org/10.3390/antibiotics14080761 - 29 Jul 2025
Viewed by 254
Abstract
Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may [...] Read more.
Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
14 pages, 384 KiB  
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 253
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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