Antibiotics

13 pages, 3990 KiB

Open AccessArticle

Protective Effects of Luteolin on Glaesserella parasuis-Induced Injury: An In Vitro Study with Porcine Vascular Endothelial Cells

by Pu Guo, Xuwen Liu, Xiaoyi Li, Awais Ihsan, Zhongyuan Wu, Shulin Fu, Chun Ye, Yinsheng Qiu, Xu Wang, Qirong Lu and Yu Liu

Antibiotics 2025, 14(8), 824; https://doi.org/10.3390/antibiotics14080824 (registering DOI) - 12 Aug 2025

Abstract

Background: Glaesserella parasuis (GPS) is a conditional pathogen that colonizes the upper respiratory tract in pigs and causes Glässer’s disease, resulting in high morbidity and mortality in piglets. GPS infection increases the vascular endothelial permeability, but the mechanism has not been fully [...] Read more.

Background: Glaesserella parasuis (GPS) is a conditional pathogen that colonizes the upper respiratory tract in pigs and causes Glässer’s disease, resulting in high morbidity and mortality in piglets. GPS infection increases the vascular endothelial permeability, but the mechanism has not been fully elucidated. Luteolin (Lut) is a naturally occurring flavonoid found in plants such as vegetables, herbs, and fruits, but its potential to treat the increased vascular endothelial permeability caused by GPS infection has not been evaluated. Results: This study revealed that GPS infection induces increased vascular endothelial permeability in porcine iliac artery endothelial cells (PIECs) by increasing the gene expressions of tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8, and IL-1β, and by regulating F-actin cytoskeleton reorganization. Mechanistically, GPS infection or Cluster of differentiation 44 (CD44) overexpression significantly increased the expressions of vascular-endothelial-permeability-related proteins (CD44; vascular endothelial growth factor (VEGFA); matrixmetalloProteinase-3 (MMP-3); MMP-9; and SRC proto-oncogene, non-receptor tyrosine kinase (c-Src)) and increased the vascular endothelial permeability; these changes were alleviated by a Lut treatment or CD44 silencing in the PIECs. Conclusions: This study comprehensively illustrates the potential targets and molecular mechanism of Lut in alleviating the GPS-induced increase in vascular endothelial permeability. The CD44 pathway and Lut may be an effective target and antibiotic alternative, respectively, to prevent the increased vascular endothelial permeability caused by GPS. Full article

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17 pages, 1453 KiB

Open AccessArticle

Unique Regulation of Sed-1 β-Lactamase in Citrobacter sedlakii: Insights on Resistance to Third-Generation Cephalosporin

by Mako Watanabe, Ryuichi Nakano, Keizo Yamamoto, Akiyo Nakano, Yuki Suzuki, Kai Saito, Satoko Nakashima, Kentaro Endo, Kazuya Narita and Hisakazu Yano

Antibiotics 2025, 14(8), 823; https://doi.org/10.3390/antibiotics14080823 (registering DOI) - 12 Aug 2025

Abstract

Background: The Citrobacter genus harbors class C (AmpC) and class A β-lactamases. Citrobacter freundii produces an inducible AmpC β-lactamase controlled by the LysR-type transcriptional regulator AmpR and cytosolic amidase AmpD. Citrobacter sedlakii produces the class A β-lactamase Sed-1, whose expression is believed to [...] Read more.

Background: The Citrobacter genus harbors class C (AmpC) and class A β-lactamases. Citrobacter freundii produces an inducible AmpC β-lactamase controlled by the LysR-type transcriptional regulator AmpR and cytosolic amidase AmpD. Citrobacter sedlakii produces the class A β-lactamase Sed-1, whose expression is believed to be regulated by the transcriptional regulator SedR and AmpD. Objectives:C. sedlakii NR2807, isolated in Japan, is resistant to third-generation cephalosporins and displays extended-spectrum β-lactamase characteristics. Here, we sought to understand the mechanism for successful resistance to third-generation cephalosporins by investigating the regulators controlling Sed-1 production. Methods: Plasmids containing bla_Sed-1 and sedR (pCR2807) or truncated sedR (pCR2807ΔSedR) were constructed and introduced into Escherichia coli. Antibiotic-resistant mutants of NR2807 were obtained, and enzyme kinetics were assessed. Results: The AmpD mutant (pCR2807/ML4953) showed an 8-fold increase in cefotaxime MIC and an 8.46-fold increase in Sed-1 activity compared to the wild-type (pCR2807/ML4947). However, induction of pCR2807/ML4947 also led to a 1.32-fold higher Sed-1 activity, indicating semi-inducibility. Deletion of sedR (pCR2807ΔSedR/ML4947) led to a 4-fold decrease in cefotaxime MIC and 1.93-fold lower Sed-1 activity, confirming SedR as an activator. While wild-type C. sedlakii ATCC51115 is susceptible to third-generation cephalosporins, the AmpD mutation in NR2807 led to Sed-1 overproduction and resistance to this class of antibiotics. Finally, mutagenesis revealed that amino acid substitution in Sed-1 conferred resistance to ceftazidime and extended-spectrum β-lactamase characteristics. Conclusions: Sed-1 producers, though usually susceptible to third-generation cephalosporins, may develop extended-spectrum β-lactamase traits due to AmpD or Sed-1 mutations, thereby requiring careful monitoring. Full article

(This article belongs to the Special Issue Genomic Characterization of Antimicrobial Resistance and Evolution Mechanism of Bacteria)

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14 pages, 663 KiB

Open AccessArticle

Diagnostic Accuracy of Presepsin and Its Impact on Early Antibiotic De-Escalation in Burn-Related Sepsis

by Seontai Park, Dohern Kym, Jaechul Yoon, Yong Suk Cho and Jun Hur

Antibiotics 2025, 14(8), 822; https://doi.org/10.3390/antibiotics14080822 - 11 Aug 2025

Abstract

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a [...] Read more.

Background/Objectives: Despite overlapping inflammatory responses and frequent culture-negative results in severe burn patients, early and accurate sepsis diagnosis remains challenging. We aimed to evaluate the diagnostic performance of seven candidate biomarkers and their clinical utility, particularly in culture-negative cases. Methods: We conducted a prospective diagnostic accuracy study (January 2021–December 2022; N = 221) in the burn intensive care unit, applying a two-step feature selection to 41 candidate variables. Seven top biomarkers—presepsin, procalcitonin (PCT), albumin, C-reactive protein (CRP), prothrombin time (PT), hematocrit (Hct), and D-dimer—were measured at the moment of clinical sepsis suspicion, concurrently with blood cultures and prior to empirical antibiotic administration, within ±2 h of Sequential Organ Failure Assessment (SOFA). Diagnostic performance was evaluated using a Receiver Operating Characteristic (ROC) curve analysis to determine the area under the curve (AUC), Youden index-derived cut-offs, decision curve analysis, and Net Reclassification Improvement (NRI). Results: Presepsin achieved the highest overall AUC (0.810; 95% CI, 0.742–0.878) and outperformed other markers in culture-negative cases (AUC, 0.846 vs. 0.604; p = 0.015). In the decision curve analysis, presepsin and PCT maintained the largest net benefits at high thresholds, although PT, D-dimer, and Hct also retained smaller positive benefits. Patients were stratified into high- vs. low-risk groups for survival analysis using Youden index cut-offs; Cox regression confirmed PCT (Hazard Ratio 3.78; p < 0.001) and PT (HR 2.12; p = 0.018) as a significant mortality predictor, with presepsin showing borderline significance (HR 3.14; p = 0.055). Conclusions: The high rate of culture-negative sepsis reflects early antibiotic use suppressing culture yield rather than resistance patterns alone. Presepsin’s rapid rise and preserved accuracy under pre-sampling antibiotics suggest its value for early sepsis detection and antimicrobial stewardship. Future work will incorporate polymicrobial and multidrug-resistant bloodstream infection profiles to refine biomarker utility. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Infection Prevention in Intensive Care Unit)

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14 pages, 5087 KiB

Open AccessArticle

Clinical Characteristics and Follow-Up of Children with Primary Haematogenous Osteomyelitis and Septic Arthritis: Eight Years of Experience from Hungary

by Szofia Hajósi-Kalcakosz, Erzsébet Varga, Dorottya Őri, Csaba Ráskai, Borbála Zsigmond, Beáta Visy, Ferenc Fekete, Andrea Horváth, Orsolya Dobay and Bálint Gergely Szabó

Antibiotics 2025, 14(8), 821; https://doi.org/10.3390/antibiotics14080821 - 11 Aug 2025

Abstract

Introduction: Paediatric acute haematogenous bone and joint infections (BJIs) are serious conditions. This study aimed to analyse the characteristics of paediatric acute haematogenous osteomyelitis (AHO) and septic arthritis (SA) in Hungary, with a focus on causative pathogens, clinical outcomes, and long-term complications. Methods [...] Read more.

Introduction: Paediatric acute haematogenous bone and joint infections (BJIs) are serious conditions. This study aimed to analyse the characteristics of paediatric acute haematogenous osteomyelitis (AHO) and septic arthritis (SA) in Hungary, with a focus on causative pathogens, clinical outcomes, and long-term complications. Methods: A retrospective cohort study was conducted at a Hungarian tertiary referral centre between 2015 and 2022. Children aged 18 years or younger diagnosed with acute haematogenous osteomyelitis (AHO) or septic arthritis (SA) within two months of symptom onset were included. Exclusion criteria were chronic infection, post-operative infections, or wound-related infections. Complicated AHO was defined by intraosseous abscess or necrosis confirmed radiologically or intraoperatively. The primary outcome was surgical intervention beyond 30 days after diagnosis; secondary outcomes included long-term complications. Results: Forty patients were included (77.5% male, median age 8.7 years). AHO was diagnosed in 8 patients (20.0%), complicated AHO in 22 (55.0%), and SA in 10 (25.0%). MRI had the highest diagnostic sensitivity (97.0%). Pathogens were identified in 72.5% of cases; Staphylococcus aureus (S. aureus) was most common (57.5%), followed by Salmonella and Streptococcus pyogenes (5% each). Surgery was required in 90.0% of SA cases, 77.2% of complicated AHO, and 37.5% of uncomplicated AHO. Long-term complications occurred in 10%, mainly with S. aureus and complicated AHO. Conclusions: Paediatric BJIs, especially due to S. aureus, often require surgery and cause long-term sequelae. Full article

(This article belongs to the Special Issue Bone and Joint Infections: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research)

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14 pages, 4501 KiB

Open AccessArticle

The Small Molecule Inhibitor of the Type III Secretion System Fluorothiazinone Affects Flagellum Surface Presentation and Restricts Motility in Gram-Negative Bacteria

by Alexey Slonov, Mariam Abdulkadieva, Egor Kalinin, Natalya Bondareva, Lydia Kapotina, Svetlana Andreevskaya, Natalia Shevlyagina, Anna Sheremet, Elena Sysolyatina, Vladimir Zhukhovitsky, Mikhail Vasiliev, Oleg Petrov, Svetlana Ermolaeva, Nailya Zigangirova and Alexander Gintsburg

Antibiotics 2025, 14(8), 820; https://doi.org/10.3390/antibiotics14080820 - 11 Aug 2025

Abstract

Background/Objectives: Fluorothiazinone (FT), a small molecule of the 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-one class, is known to inhibit the type III secretion system (T3SS) in Gram-negative bacteria and has shown therapeutic potential in animal models and clinical trials. Given the evolutionary relationship between the T3SS and the [...] Read more.

Background/Objectives: Fluorothiazinone (FT), a small molecule of the 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-one class, is known to inhibit the type III secretion system (T3SS) in Gram-negative bacteria and has shown therapeutic potential in animal models and clinical trials. Given the evolutionary relationship between the T3SS and the bacterial flagellar apparatus, this study aimed to investigate the effects of FT on bacterial motility and flagellum assembly. Methods: Motility was assessed in Pseudomonas aeruginosa, Proteus mirabilis, pathogenic Escherichia coli, and Listeria monocytogenes using a semisolid agar assay and a microfluidic motility system. The mechanism of FT’s action was further examined through time-course analysis, Western blotting of surface flagella proteins, and transmission electron microscopy (TEM). Results: FT inhibited motility of P. aeruginosa, P. mirabilis, and E. coli in a dose-dependent manner, while L. monocytogenes motility remained unaffected. The inhibitory effect was not immediate but delayed 2–3 h post FT addition. Western blotting revealed the absence of surface flagella in EHEC grown with FT, and TEM confirmed structural disruption of flagella in P. mirabilis. Conclusions: FT selectively inhibits flagellum-based motility in Gram-negative bacteria. Obtained data suggested FT interference with flagellum biosynthesis rather than disruption of rotation. Motility inhibition can contribute to FT therapeutic effects on Gram-negative bacterial infections. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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9 pages, 257 KiB

Open AccessArticle

Clonal Diversity of Extraintestinal Pathogenic Escherichia coli Strains Isolated from Canine Urinary Tract Infections in Brazil

by Luciana Sartori, João Pedro Rueda Furlan, Fábio Parra Sellera, Fernanda Borges Barbosa, Yohanna Carvalho dos Santos Aoun Chikhani, Gabriel Gandolfi and Terezinha Knöbl

Antibiotics 2025, 14(8), 819; https://doi.org/10.3390/antibiotics14080819 - 10 Aug 2025

Abstract

Background/Objectives: Extraintestinal pathogenic Escherichia coli (ExPEC) strains, particularly those belonging to phylogenetic group B2, are clinically significant due to their frequent involvement in urinary tract infections (UTIs) and display antimicrobial resistance profiles. While the association of phylogroup B2 E. coli with human urinary [...] Read more.

Background/Objectives: Extraintestinal pathogenic Escherichia coli (ExPEC) strains, particularly those belonging to phylogenetic group B2, are clinically significant due to their frequent involvement in urinary tract infections (UTIs) and display antimicrobial resistance profiles. While the association of phylogroup B2 E. coli with human urinary tract infections is well established, the growing number of reports of ExPEC strains in canine UTIs highlights their clinical relevance in small animal medicine and raises concerns about their potential role in zoonotic transmission. This study investigated the microbiological and genomic features of E. coli strains isolated from dogs with UTIs in São Paulo, Brazil. Methods: Between March and May 2023, a total of 60 E. coli strains from canine UTIs were screened for antimicrobial susceptibility and phylotyping. Accordingly, four strains (6.6%) were identified as multidrug-resistant (MDR) or belonging to phylogroup B2 and, therefore, were submitted for characterization by whole-genome sequencing. Results: The four E. coli strains exhibited diverse antimicrobial resistance profiles, including resistance to third- and fourth-generation cephalosporins and fluoroquinolones. Phylogenetic groups B1, B2, and G, and sequence types (ST) 73, ST224, ST1193, and ST12960 were identified. The resistome included clinically important β-lactam resistance genes, such as bla_CTX-M-55 and bla_CMY-2, as well as mutations in the quinolone-resistance-determining region. Virulence factors associated with ExPEC pathogenesis, including adhesion, iron acquisition, immune evasion, and toxin, were detected. Plasmid sequences were identified as carrying antimicrobial resistance and virulence genes, highlighting the potential for horizontal gene transfer. Conclusions: Our findings underscore the importance of genomic surveillance in companion animals to better understand the epidemiology of ExPEC strains and monitor the spread of MDR strains. Full article

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

18 pages, 1458 KiB

Open AccessArticle

Colistin-Resistant Escherichia coli Isolated from Houseflies and Feces of Cattle and Pigs at a Slaughterhouse in Lima, Peru

by Andrea Carhuallanqui, Lorena Villafana, Rosa Gonzalez-Veliz, José F. Cobo-Díaz, Avelino Álvarez-Ordoñez and Daphne Doris Ramos-Delgado

Antibiotics 2025, 14(8), 818; https://doi.org/10.3390/antibiotics14080818 - 10 Aug 2025

Abstract

Background: Pigs and cattle have been implicated as reservoirs of antimicrobial resistance genes (ARGs) that can spread to humans, and houseflies are considered potential carriers of bacteria with ARGs that could contribute to their spread to the environment, including food, animals, and humans. [...] Read more.

Background: Pigs and cattle have been implicated as reservoirs of antimicrobial resistance genes (ARGs) that can spread to humans, and houseflies are considered potential carriers of bacteria with ARGs that could contribute to their spread to the environment, including food, animals, and humans. Methods: In this study, 107, 145, and 127 Escherichia coli strains were isolated from houseflies, pigs, and cattle, respectively, from a slaughterhouse in Lima, Peru. Antimicrobial susceptibility testing was performed using the Kirby–Bauer method, where thirteen antibiotics were used. Strains were also plated on CHROMagar COL-APSE agar, and colistin’s minimum inhibitory concentration (MIC) was determined. Colistin-resistant E. coli strains were subjected to whole genome sequencing. Results: 7.8% (8/107), 1.38% (2/145), and 0.79% (1/127) of E. coli strains isolated from houseflies, pigs, and cattle, respectively, were resistant to colistin (MIC ≥ 4 µg/mL). ARGs associated with resistance to more than 6 different antibiotic classes were identified, including tetracyclines, beta-lactams, fluoroquinolones, nitroimidazoles, trimethoprim and amphenicols. Conclusions: This study suggests that flies could contribute to the dissemination of ARG carrying bacteria and shows the potential risk of animals and meat production systems as reservoirs of ARG carrying bacteria. Full article

(This article belongs to the Special Issue Virulence, Antimicrobial Resistance and Biofilm Production in Veterinary, Zoonotic and Food-Related Pathogens)

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21 pages, 3124 KiB

Open AccessArticle

Prevalence and Characterization of the Antimicrobial Resistance and Virulence Profiles of Staphylococcus aureus in Ready-to-Eat (Meat, Chicken, and Tuna) Pizzas in Mansoura City, Egypt

by Sara Amgad Elsalkh, Amira Ibrahim Zakaria, Samir Mohammed Abd-Elghany, Kálmán Imre, Adriana Morar and Khalid Ibrahim Sallam

Antibiotics 2025, 14(8), 817; https://doi.org/10.3390/antibiotics14080817 - 10 Aug 2025

Abstract

Introduction: Staphylococcus aureus is a high-priority foodborne pathogen contributing to several food poisoning outbreaks. Methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA), pose significant public health concerns due to their potential for serious illness, antibiotic resistance, and transmission within both healthcare and [...] Read more.

Introduction: Staphylococcus aureus is a high-priority foodborne pathogen contributing to several food poisoning outbreaks. Methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA), pose significant public health concerns due to their potential for serious illness, antibiotic resistance, and transmission within both healthcare and community settings. These bacteria can cause numerous infections, ranging from skin and soft tissue infections to life-threatening conditions like bloodstream infections, pneumonia, and endocarditis. Although several publications are concerned with Staphylococcus aureus contamination in ready-to-eat (RTE) food products, little published data is available about its prevalence in pizza, which is widely distributed and consumed worldwide. Methods: The current study is intended to determine the prevalence, virulence genes, and antimicrobial resistance profiles of S. aureus in three hundred ready-to-eat pizza samples (100 each of meat, chicken, and canned tuna pizzas) collected from different restaurants in Mansoura City, Egypt. The typical colonies on Baird–Parker selective agar supplemented with egg yolk tellurite emulsion were counted and further confirmed based on Gram staining, coagulase testing, catalase testing, carbohydrate fermentation, and thermostable nuclease production. The genomic DNA of the confirmed coagulase-positive isolates was prepared and subjected to PCR analyses for detecting the nuc gene, mecA (methicillin resistance gene), and vancomycin resistance gene (vanA), as well as six selected S. aureus virulence genes: sea, seb, sec, sed, hla, and tsst. The antimicrobial resistance profile of the S. aureus isolates was determined against 16 antimicrobial agents belonging to six classes using the agar disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines (CLSI), except for oxacillin and vancomycin, which were assessed using the MIC test. Results: The results revealed that 56% (56/100), 56% (56/100), and 40% (40/100) of chicken, meat, and canned tuna pizzas were positive for S. aureus, with an overall prevalence of 50.7% (152/300). All 560 isolates (100%) were verified as S. aureus based on molecular confirmation of the nuc gene. Interestingly, 48.6% (272/560) and 8.6% (48/560) of the isolates tested were identified as methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA) through detection of mecA and vanA genes, respectively. Among the S. aureus isolates tested, the hla gene was detected in 87.1% (488/560), while the enterotoxin genes sea, seb, sec, and sed were identified in 50% (280/560), 78.6% (440/560), 9.8% (55/560), and 24.5% (137/560) of isolates, respectively. All recovered isolates (n = 560) were classified as multidrug-resistant and were resistant to penicillin, oxacillin, and ampicillin. Moreover, 77% (431/560), 24% (134/560), 8% (45/560), and 8.6% (48/560) of isolates were resistant to cefotaxime, ciprofloxacin, azithromycin, and vancomycin, respectively. Conclusions: The current study emphasizes that ready-to-eat pizza is highly contaminated with multidrug-resistant S. aureus, highlighting the urgent need for rationalizing antibiotic use in both veterinary and human medicine to prevent the transmission of resistant bacteria through the food chain. Additionally, strict adherence to good hygienic practices throughout all stages of the food chain is essential to minimize overall contamination and enhance food safety. Full article

(This article belongs to the Special Issue The Antimicrobial Resistance in the Food Chain)

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17 pages, 1848 KiB

Open AccessArticle

Phenotypic Characterization of pilA, pilB, and pilD Mutants of Acinetobacter baumannii 5075: Impacts on Growth, Biofilm Formation, and Tazobactam Response

by Joel H. Salinas, Jr., Fatma Pinar Gordesli-Duatepe, Angelica Diaz-Sanchez and Nehal I. Abu-Lail

Antibiotics 2025, 14(8), 816; https://doi.org/10.3390/antibiotics14080816 - 9 Aug 2025

Abstract

Background/Objectives: The Type IV pilus assembly system in Acinetobacter baumannii is a major determinant of its pathogenicity, playing a role in surface-associated functions via the biogenesis of Type IV pili (T4P). Tazobactam (TAZ) is a well-characterized β-lactamase inhibitor, primarily used in combination with [...] Read more.

Background/Objectives: The Type IV pilus assembly system in Acinetobacter baumannii is a major determinant of its pathogenicity, playing a role in surface-associated functions via the biogenesis of Type IV pili (T4P). Tazobactam (TAZ) is a well-characterized β-lactamase inhibitor, primarily used in combination with β-lactam antibiotics such as piperacillin (PIP) to counteract bacterial resistance mechanisms. While A. baumannii resistance to β-lactam antibiotics has been well studied, the influence of T4P on its susceptibility to TAZ remains largely unexplored. For this reason, we investigated how multidrug-resistant A. baumannii 5075 (AB5075) responds to TAZ by assessing the roles of pilA, pilB, and pilD in bacterial growth and biofilm formation under direct TAZ exposure, with a focus on phenotypic characterization rather than molecular mechanisms. Methods: Bacterial growth kinetics were quantified by measuring the optical densities of cell suspensions and the colony forming units per volume (CFUs/mL) at different time intervals. Time-kill assays and microtiter dish biofilm formation assays were used to evaluate how effectively TAZ can inhibit growth and biofilm formation, respectively. Results: Time–kill assays confirmed that 32 µg/mL of TAZ inhibited growth in both wild-type (WT) and mutant strains, with the pilD mutant showing initial resistance before eventual inhibition. Biofilm assays showed that the pilA mutant had the highest biofilm formation at 8 h, surpassing the WT strain. A prolonged 32 µg/mL of TAZ exposure (24–36 h) significantly reduced biofilm production across all strains, with inhibition rates reaching 89% for the WT, 82% for the pilA mutant, 91% for the pilB mutant, and 86% for the pilD mutant. Conclusion: These findings deepen our understanding of the strain-specific roles of T4P components in growth and biofilm regulation in AB5075, and highlight the potential of TAZ as a therapeutic strategy against biofilm-associated infections. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)

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19 pages, 972 KiB

Open AccessReview

Effects of Antiseptic Formulations on Oral Microbiota and Related Systemic Diseases: A Scoping Review

by Angela Angjelova, Elena Jovanova, Alessandro Polizzi, Rosalia Leonardi and Gaetano Isola

Antibiotics 2025, 14(8), 815; https://doi.org/10.3390/antibiotics14080815 - 8 Aug 2025

Abstract

Background: Oral antiseptic formulations are widely used as adjuncts in oral hygiene to reduce pathogenic microorganisms and prevent oral diseases. While these agents are effective in controlling biofilm, their broader effects may disrupt the oral microbiota’s balance, potentially contributing to systemic health implications. [...] Read more.

Background: Oral antiseptic formulations are widely used as adjuncts in oral hygiene to reduce pathogenic microorganisms and prevent oral diseases. While these agents are effective in controlling biofilm, their broader effects may disrupt the oral microbiota’s balance, potentially contributing to systemic health implications. The complex relationship between antiseptic use, microbial composition, and systemic outcomes remains insufficiently mapped. Objective: This scoping review aimed to explore and map the current evidence regarding the impact of antiseptic formulations on oral microbiota composition and to examine their potential associations with systemic diseases. Methods: A comprehensive literature search was performed using PubMed, Scopus, and Web of Science up to June 2025. Studies were included if they investigated antiseptic formulations commonly used in oral healthcare—such as chlorhexidine, essential oils, and cetylpyridinium chloride—and reported effects on oral microbiota and/or systemic health. Eligible study types included human clinical trials, observational studies, in vitro, and animal studies. Two reviewers independently screened and selected studies, with disagreements resolved by consensus. Data extraction focused on study design, antiseptic agents, microbial outcomes, and systemic implications. A total of 12 studies were included and charted. Results: The included studies demonstrated that oral antiseptics effectively reduce pathogenic microorganisms and improve clinical outcomes in oral diseases such as gingivitis and periodontitis. However, several studies also reported alterations in commensal microbial communities, suggesting a potential for dysbiosis. Some studies indicated possible links between antiseptic-induced microbial changes and systemic conditions, including cardiovascular and respiratory diseases. Conclusions: The evidence highlights a dual effect of antiseptic formulations: while beneficial in controlling oral pathogens, they may disrupt microbial homeostasis with possible systemic consequences. Further research is needed to evaluate long-term effects and develop targeted, microbiota-preserving oral hygiene strategies. Full article

(This article belongs to the Special Issue Antimicrobial Therapy in Oral Diseases)

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15 pages, 680 KiB

Open AccessArticle

Does Bovine Raw Milk Represent a Potential Risk for Vancomycin-Resistant Enterococci (VRE) Transmission to Humans?

by Elisa Massella, Simone Russo, Anita Filippi, Chiara Anna Garbarino, Matteo Ricchi, Patrizia Bassi, Elena Toschi, Camilla Torreggiani, Giovanni Pupillo, Gianluca Rugna, Valentina Carta, Cristina Bertasio, Andrea Di Cesare, Tomasa Sbaffi, Giulia Borgomaneiro and Andrea Luppi

Antibiotics 2025, 14(8), 814; https://doi.org/10.3390/antibiotics14080814 - 8 Aug 2025

Abstract

Background/Objectives: Vancomycin-resistant enterococci (VRE) are significant nosocomial pathogens worldwide, potentially transmitted by food-producing animals and related products. This study investigates the epidemiological role of bovine raw milk in the transmission of VRE to humans. Methods: Bulk milk samples were screened for [...] Read more.

Background/Objectives: Vancomycin-resistant enterococci (VRE) are significant nosocomial pathogens worldwide, potentially transmitted by food-producing animals and related products. This study investigates the epidemiological role of bovine raw milk in the transmission of VRE to humans. Methods: Bulk milk samples were screened for van gene presence using a multiplex PCR. Mastitogenic enterococci isolated from individual milk samples were tested for antimicrobial susceptibility using the broth microdilution method. Strains not susceptible to vancomycin were whole genome sequenced. Results: Overall, vanC genes were detected in 299/1026 (29.14%) bulk milk samples. Specifically, vanC1 was found in 204 samples (19.88%) and vanC2/3 in 57 samples (5.56%), with both detected simultaneously in 38 samples (3.70%). Clinically significant vanA and vanB genes were not identified. A total of 163 mastitogenic Enterococcus strains were isolated from individual milk samples. Eight different Enterococcus species were detected, with E. faecium (104/163, 63.80%) and E. faecalis (34/163, 20.86%) being the most common. Multidrug resistance was observed in 106/163 (65.03%) isolates. The most common resistance frequencies were to ciprofloxacin and erythromycin (102/163, 62.58% both), followed by quinupristin/dalfopristin (93/163, 57.06%), linezolid (65/163, 39.88%), tetracycline (58/163, 35.58%), daptomycin (46/163, 28.22%), chloramphenicol (33/163, 20.25%), ampicillin, tigecycline, and high-dosage gentamycin (8/163, 4.91% all). Resistance to teicoplanin was not observed. Two vancomycin non-susceptible strains were identified: one vanC2/3 E. casseliflavus and one vanC1 E. gallinarum. Whole genome sequencing confirmed the presence of the complete vanC gene cluster and several virulence genes in both strains. Conclusions: Our findings suggest that while raw milk is unlikely to be a source of vancomycin resistance genes of highest clinical importance (vanA or vanB), it may contribute to the spread of vanC enterococci, which are increasingly associated with human infections. Full article

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25 pages, 846 KiB

Open AccessReview

The Current Landscape of Antibiotic Use and Antimicrobial Resistance in Japan: Focusing on Common Infections Including Uncomplicated Urinary Tract Infection and Gonorrhea

by Daisuke Fukuda, Yutaka Handa, Yoko Kayama, Kenji Fujii, Shinya Kawamatsu, Yoshiaki Kawano, Ivo Vojtek, Danielle Powell, Aruni Mulgirigama and Yoshiaki Gu

Antibiotics 2025, 14(8), 813; https://doi.org/10.3390/antibiotics14080813 - 8 Aug 2025

Abstract

Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged [...] Read more.

Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged a national environment conducive to mitigation measures. However, tackling AMR remains difficult. From an epidemiological perspective, this challenge now extends beyond severe infections, impacting common community-acquired infections, including uncomplicated urinary tract infections (uUTls) and gonorrhea. In uUTIs, the rising prevalence of extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli diminishes the effectiveness of current, routinely used oral antibiotics, necessitating an exploration into innovative solutions. Similarly, the growing resistance of Neisseria gonorrhoeae to antibiotics such as azithromycin raises concerns about the efficacy of current therapeutic options for gonorrhea, which is a highly prevalent sexually transmitted infection. In Japan, since the removal of azithromycin as the recommended first-line treatment, there are no oral first-line antibiotics available to treat gonorrhea. Therefore, novel oral antibiotics are urgently needed for both serious and commonly occurring community-acquired infections. This narrative review discusses the limited availability of novel antibiotics in Japan, the distinctive features of the Japanese antibiotic repertoire and AMR epidemiology, and potential alternative oral treatments for community-acquired infections, including uUTIs and gonorrhea. Japan has been making significant advances toward tackling the AMR crisis through an updated national action plan, AMR policy changes, and innovative approaches to developing novel antibiotics. Substantial international cooperation and the engagement of diverse industry sectors are essential to address the pressing issue of AMR. Full article

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18 pages, 3219 KiB

Open AccessArticle

Antimicrobial Activity of Lacticaseibacillus rhamnosus CRL 2244 Extracts Against Community- and Hospital-Acquired Staphylococcus aureus

by Cecilia Rodriguez, Briea Gasca, Vyanka Mezcord, Robert A. Bonomo, Gauri Rao, Nicholas T. Salzameda and Maria Soledad Ramirez

Antibiotics 2025, 14(8), 812; https://doi.org/10.3390/antibiotics14080812 - 8 Aug 2025

Abstract

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) remains a critical public health concern due to its multidrug resistance and capacity to form persistent infections, particularly in the context of implanted medical devices. Alternative therapeutic strategies that target bacterial virulence instead of viability are increasingly explored. [...] Read more.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) remains a critical public health concern due to its multidrug resistance and capacity to form persistent infections, particularly in the context of implanted medical devices. Alternative therapeutic strategies that target bacterial virulence instead of viability are increasingly explored. This study aimed to evaluate the antimicrobial and antivirulence activity of an extract derived from Lacticaseibacillus rhamnosus CRL 2244 against two MRSA strains—USA300 and M86—and to elucidate its effects on bacterial physiology and gene expression under host-mimicking conditions. Methods: Antimicrobial activity was assessed using agar diffusion, MIC, and time-kill assays. Scanning electron microscopy of cells exposed to the extract confirmed decreased cellular density and morphological changes. Phenotypic assays evaluated biofilm formation, staphyloxanthin production, and adhesion to fibronectin. RT-qPCR analyzed transcriptional responses. Viability was assessed in the presence of human serum and type I collagen. Results: The CRL 2244 extract demonstrated bactericidal activity with up to 6-log₁₀ CFU/mL reduction at 1× MIC. In USA300, the extract reduced the expression of hla, lukAB, fnbA, and icaA, correlating with decreased staphyloxanthin levels. In M86, a significant reduction in biofilm formation and repression of lukAB, nucA, and fnbA were observed. Adhesion to fibronectin was impaired in both strains. The extract showed no cytotoxicity in human serum but reduced viability in collagen-enriched conditions. Conclusions: The Lcb. rhamnosus CRL 2244 extract modulates MRSA virulence in a strain-specific manner, targeting key regulatory and structural genes without inducing cytotoxic effects. Full article

(This article belongs to the Collection Staphylococcus— Molecular Pathogenesis, Virulence Regulation and Antibiotics Resistance)

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20 pages, 1404 KiB

Open AccessArticle

Bacteriophage PCSE1 as a Potential Strategy Against Salmonella Enteritidis in Liquid Egg Products

by Márcia Braz, Carla Pereira, Gabriela Matos, Jorge A. Saraiva, Carmen S. R. Freire and Adelaide Almeida

Antibiotics 2025, 14(8), 811; https://doi.org/10.3390/antibiotics14080811 - 8 Aug 2025

Abstract

Background/Objectives: The consumption of liquid egg products is rising. While thermal pasteurization improves safety and shelf life, it can affect product quality. Furthermore, egg products continue to cause many foodborne illnesses, especially those caused by Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella [...] Read more.

Background/Objectives: The consumption of liquid egg products is rising. While thermal pasteurization improves safety and shelf life, it can affect product quality. Furthermore, egg products continue to cause many foodborne illnesses, especially those caused by Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Bacteriophages (or phages) are an effective alternative to specifically fight foodborne bacteria. This study aimed to evaluate (i) the stability of phage vB_SeEM_UALMA_PCSE1 (PCSE1) under different conditions of temperature and pH; (ii) the effect of multiplicity of infection (MOI) and temperature on phage efficacy; (iii) the bactericidal effect of phage PCSE1 against S. Enteritidis in liquid whole eggs compared to thermal pasteurization; and (iv) the effect of both treatments on the physicochemical and functional properties of liquid whole eggs. Methods: For this, stability tests, bacterial growth inhibition assays in culture media and liquid eggs, and physicochemical and functional analyses were conducted. Results: Phage PCSE1 was (i) stable at pH 7 and 8, and at 4, 25, and 37 °C for 56 days; (ii) effectively prevented S. Enteritidis growth in TSB (reduction of 1.8, 4.5, and 4.5 log colony-forming units (CFU)/mL at 4, 10, and 25 °C, respectively, relative to the bacterial control); (iii) controlled S. Enteritidis in liquid whole eggs at 25 °C (reduction of 5.8 log CFU/mL relative to the bacterial control) comparable to pasteurization (reduction of 5.2 log CFU/mL); and (iv) preserved eggs’ properties, contrarily to pasteurization. Conclusions: These findings suggest PCSE1 is a promising strategy to fight S. Enteritidis in liquid egg products, though further studies on shelf-life are needed. Full article

(This article belongs to the Section Bacteriophages)

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27 pages, 1208 KiB

Open AccessReview

Staphylococcus aureus in Bovine Mastitis: A Narrative Review of Prevalence, Antimicrobial Resistance, and Advances in Detection Strategies

by Rahima Touaitia, Nasir Adam Ibrahim, Abdelaziz Touati and Takfarinas Idres

Antibiotics 2025, 14(8), 810; https://doi.org/10.3390/antibiotics14080810 - 8 Aug 2025

Abstract

Bovine mastitis, particularly that caused by Staphylococcus aureus, presents a major challenge to dairy production worldwide due to its economic impact, animal welfare concerns, and zoonotic potential. This narrative review synthesizes current literature on the epidemiology, pathogenesis, resistance patterns, and control strategies [...] Read more.

Bovine mastitis, particularly that caused by Staphylococcus aureus, presents a major challenge to dairy production worldwide due to its economic impact, animal welfare concerns, and zoonotic potential. This narrative review synthesizes current literature on the epidemiology, pathogenesis, resistance patterns, and control strategies related to S. aureus-associated mastitis in dairy cattle. It highlights the pathogen’s virulence mechanisms, such as biofilm formation, immune evasion, and toxin production, that facilitate persistent infections. The review compiles global prevalence data, revealing significant geographic variation and disparities between clinical and subclinical cases. Antimicrobial resistance, especially the emergence of methicillin-resistant S. aureus (MRSA), is extensively examined alongside resistance gene profiles. Diagnostic approaches, including culture, PCR, MALDI-TOF MS, and AI-based systems, are evaluated for their sensitivity and field applicability. Additionally, the review addresses public health implications, zoonotic risks, and One Health perspectives, culminating in an exploration of prevention strategies, including improved hygiene, vaccination, dry cow therapy, and AI-driven herd management. The findings emphasize the urgent need for integrated surveillance, precision diagnostics, and targeted interventions to mitigate the burden of S. aureus mastitis. Full article

(This article belongs to the Special Issue Detection of Bacteria and Antibiotics Surveillance in Livestock)

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9 pages, 680 KiB

Open AccessCase Report

Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA) Bacteremia—Case Report

by Beverly Buffart, Philippe Clevenbergh, Alina Stiuliuc, Ioannis Raftakis, Mony Hing, Véronique Yvette Miendje Deyi, Olivier Denis, Delphine Martiny and Nicolas Yin

Antibiotics 2025, 14(8), 809; https://doi.org/10.3390/antibiotics14080809 - 7 Aug 2025

Abstract

Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In [...] Read more.

Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In this report, we present a rare case of BORSA bacteremia and discuss potential approaches to improve its detection and management. Case presentation: A 39-year-old woman with systemic lupus erythematosus was admitted for a suspected exacerbation, complicated by multiple serositis and nephritis. She was on chronic treatment with methylprednisolone and hydroxychloroquine. On admission, she was afebrile. Laboratory investigations revealed elevated C-reactive protein and increased D-dimer levels. Later, she developed a septic peripheral venous thrombophlebitis, and treatment was adjusted to amoxicillin–clavulanate. Blood cultures grew S. aureus, prompting a switch to intravenous oxacillin based on a negative penicillin-binding protein 2a test. A discrepancy in the antimicrobial susceptibility test was observed, with cefoxitin showing susceptibility and oxacillin resistance. Further characterizations were carried out, confirming a BORSA infection. Treatment was switched to linezolid and ciprofloxacin with good recovery. Conclusions: This case highlights the complexity of managing a patient with an uncommon and poorly documented infection. The lack of data on BORSA infections and the difficulties in detecting and treating them led to a prolonged delay in the appropriate management of this patient. Full article

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17 pages, 704 KiB

Open AccessReview

Marine Antimicrobial Peptides: Emerging Strategies Against Multidrug-Resistant and Biofilm-Forming Bacteria

by Rita Magalhães, Dalila Mil-Homens, Sónia Cruz and Manuela Oliveira

Antibiotics 2025, 14(8), 808; https://doi.org/10.3390/antibiotics14080808 - 7 Aug 2025

Abstract

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from [...] Read more.

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from marine organisms, have emerged as promising antimicrobial candidates due to their broad-spectrum activity, structural diversity, and distinctive mechanisms of action. Unlike conventional antibiotics, AMPs can disrupt microbial membranes, inhibit biofilm formation, and even modulate immune responses, making them highly effective against resistant bacteria. This review highlights the potential of marine AMPs as next-generation therapeutics, emphasizing their efficacy against multidrug-resistant pathogens and biofilm-associated infections. Furthermore, marine AMPs show promise in combating persister cells and disrupting quorum sensing pathways, offering new strategies for tackling chronic infections. Despite their potential, challenges such as production scalability and limited clinical validation remain; nevertheless, the use of new technologies and bioinformatic tools is accelerating the discovery and optimization of these peptides, paving the way for bypassing these challenges. This review consolidates current findings on marine AMPs, advocating for their continued exploration as viable tools in the fight against antimicrobial resistance. Full article

(This article belongs to the Section Antimicrobial Peptides)

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19 pages, 1684 KiB

Open AccessArticle

Effectiveness of Implementing Hospital Wastewater Treatment Systems as a Measure to Mitigate the Microbial and Antimicrobial Burden on the Environment

by Takashi Azuma, Miwa Katagiri, Takatoshi Yamamoto, Makoto Kuroda and Manabu Watanabe

Antibiotics 2025, 14(8), 807; https://doi.org/10.3390/antibiotics14080807 - 7 Aug 2025

Abstract

Background: The emergence and spread of antimicrobial-resistant bacteria (ARB) has become an urgent global concern as a silent pandemic. When taking measures to reduce the impact of antimicrobial resistance (AMR) on the environment, it is important to consider appropriate treatment of wastewater from [...] Read more.

Background: The emergence and spread of antimicrobial-resistant bacteria (ARB) has become an urgent global concern as a silent pandemic. When taking measures to reduce the impact of antimicrobial resistance (AMR) on the environment, it is important to consider appropriate treatment of wastewater from medical facilities. Methods: In this study, a continuous-flow wastewater treatment system using ozone and ultraviolet light, which has excellent inactivation effects, was implemented in a hospital in an urban area of Japan. Results: The results showed that 99% (2 log₁₀) of Gram-negative rods and more than 99.99% (>99.99%) of ARB comprising ESBL-producing Enterobacterales were reduced by ozone treatment from the first day after treatment, and ultraviolet light-emitting diode (UV-LED) irradiation after ozone treatment; UV-LED irradiation after ozonation further inactivated the bacteria to below the detection limit. Inactivation effects were maintained throughout the treatment period in this study. Metagenomic analysis showed that the removal of these microorganisms at the DNA level tended to be gradual in ozone treatment; however, the treated water after ozone/UV-LED treatment showed a 2 log₁₀ (>99%) removal rate at the end of the treatment. The residual antimicrobials in the effluent were benzylpenicillin, cefpodoxime, ciprofloxacin, levofloxacin, azithromycin, clarithromycin, doxycycline, minocycline, and vancomycin, which were removed by ozone treatment on day 1. In contrast, the removal of ampicillin and cefdinir ranged from 19% to 64% even when combined with UV-LED treatment. Conclusions: Our findings will help to reduce the discharge of ARB and antimicrobials into rivers and maintain the safety of aquatic environments. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Wastewater Treatment Plants)

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9 pages, 235 KiB

Open AccessArticle

Ceftazidime-Avibactam Plus Aztreonam for the Treatment of Blood Stream Infection Caused by Klebsiella pneumoniae Resistant to All Beta-Lactame/Beta-Lactamase Inhibitor Combinations

by Konstantinos Mantzarlis, Efstratios Manoulakas, Dimitrios Papadopoulos, Konstantina Katseli, Athanasia Makrygianni, Vassiliki Leontopoulou, Periklis Katsiafylloudis, Stelios Xitsas, Panagiotis Papamichalis, Achilleas Chovas, Demosthenes Makris and George Dimopoulos

Antibiotics 2025, 14(8), 806; https://doi.org/10.3390/antibiotics14080806 - 7 Aug 2025

Abstract

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and [...] Read more.

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Helen Giamarellou—Outstanding Contributions in the Fields of Antimicrobial Resistance and Difficult-to-Treat Resistance Pathogens)

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