Antibiotics

17 pages, 8522 KB

Open AccessArticle

Combating Carbapenem-Resistant Enterobacterales: Comparative In Vitro Efficacy of Aztreonam–Avibactam and Ceftazidime–Avibactam and Distribution of Carbapenemase Genes

by Melike Yaşar Duman, Mervenur Kanat, Elif Seren Tanrıverdi, Feriha Çilli and Şöhret Aydemir

Antibiotics 2026, 15(8), 724; https://doi.org/10.3390/antibiotics15080724 (registering DOI) - 25 Jul 2026

Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge, particularly in settings where metallo-β-lactamases are prevalent. Aztreonam–avibactam (AZA) may provide activity against metallo-β-lactamase-producing isolates, whereas ceftazidime–avibactam (CZA) has limited activity against the isolates that harbor these enzymes. This study aimed to evaluate the [...] Read more.

Background: Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge, particularly in settings where metallo-β-lactamases are prevalent. Aztreonam–avibactam (AZA) may provide activity against metallo-β-lactamase-producing isolates, whereas ceftazidime–avibactam (CZA) has limited activity against the isolates that harbor these enzymes. This study aimed to evaluate the in vitro activity of aztreonam–avibactam and ceftazidime–avibactam against invasive carbapenem-resistant Enterobacterales isolates and to characterize the distribution of carbapenemase genes in a tertiary-care center in Türkiye. Methods: A total of 100 non-duplicate CRE isolates recovered from blood cultures and sterile body fluids between January 2024 and January 2026 were included. Species identification and routine antimicrobial susceptibility testing were performed using MALDI-TOF MS and an automated system. CZA and AZA MICs were determined by gradient diffusion testing, whereas CZA–aztreonam synergy was assessed separately using a disk/gradient diffusion-based method. Carbapenemase genes were detected by real-time PCR. Whole-genome sequencing was performed for the two AZA-resistant Escherichia coli isolates. Results: The isolate collection was dominated by Klebsiella pneumoniae (87.0%), and most isolates were recovered from blood cultures (80.0%). CZA susceptibility was observed in 31.0% of isolates, with MIC_50/90 values of 256/256 mg/L. In contrast, AZA showed high in vitro activity, with 98.0% of isolates categorized as susceptible and MIC_50/90 values of 0.25/0.50 mg/L. CZA–aztreonam synergy was detected in 98.0% of isolates. Qualitative CZA–aztreonam synergy testing did not fully concord with direct AZA MIC-based susceptibility categorization: one AZA-resistant isolate showed a positive synergy result, whereas one synergy-negative isolate remained AZA-susceptible. Carbapenemase genes were detected in 99.0% of isolates; bla_NDM was the most frequent gene (81.0%), followed by bla_OXA-48 (72.0%), bla_KPC (14.0%), and bla_VIM (4.0%). The most common carbapenemase profile was bla_NDM + bla_OXA-48 (62.0%). bla_NDM carriage was strongly associated with CZA resistance, and CZA MICs were significantly higher among bla_NDM-positive isolates. The two AZA-resistant E. coli isolates belonged to ST500 and ST410, and both carried a YRIK insertion in PBP3; one of them additionally showed ompF disruption associated with a 4 bp insertion. Conclusions: AZA demonstrated potent in vitro activity against invasive CRE isolates in this setting, whereas CZA activity was substantially limited, likely reflecting the high prevalence of bla_NDM and frequent carbapenemase co-carriage. These findings support the potential value of AZA in regions with emerging metallo-β-lactamase predominance and highlight the importance of local molecular surveillance to guide antimicrobial strategies. Full article

(This article belongs to the Special Issue Resistance, Treatment and Prevention of ESKAPE Pathogens)

► Show Figures

Graphical abstract

13 pages, 675 KB

Open AccessArticle

Five-Year Evolution of the Microbiological Landscape of Diabetic Foot Infections (2021–2025): Rising Polymicrobial Gram-Negative Predominance and Emergence of Resistant Enterobacterales at a Single Large-Volume Outpatient Centre

by Magdalena Maj and Leszek Czupryniak

Antibiotics 2026, 15(8), 723; https://doi.org/10.3390/antibiotics15080723 - 24 Jul 2026

Abstract

Background/Objectives: Diabetic foot infections (DFI) drive most non-traumatic lower-limb amputations, and empirical regimens must track local microbiology, which is itself evolving under broad-spectrum antibiotic pressure. Methods: We retrospectively analysed all consecutive bacterial cultures from clinically infected diabetic foot lesions at a single Polish [...] Read more.

Background/Objectives: Diabetic foot infections (DFI) drive most non-traumatic lower-limb amputations, and empirical regimens must track local microbiology, which is itself evolving under broad-spectrum antibiotic pressure. Methods: We retrospectively analysed all consecutive bacterial cultures from clinically infected diabetic foot lesions at a single Polish outpatient centre over 2021–2025. Isolates were identified by MALDI-TOF mass spectrometry and susceptibility was interpreted under contemporaneous EUCAST breakpoints (v12.0–v15.0). Results: A total of 274 cultures yielded 443 isolates (polymicrobial index 1.62). Staphylococcus aureus remained the most common pathogen but fell from 55.0% to 38.9% of cultures, while Enterobacterales rose from 36.1% to 47.7% of all isolates. Proteus mirabilis and Streptococcus agalactiae emerged as major contributors, and Enterobacter hormaechei showed an apparent increase (the apparent rise in E. hormaechei reflects, at least in part, improved species-level identification rather than a true increase in incidence). Methicillin-resistant S. aureus was first documented in 2025 (6/38; 15.8%). P. mirabilis showed deteriorating activity against trimethoprim–sulfamethoxazole and ciprofloxacin, the first meropenem-resistant isolate appeared in 2025, and two carbapenem-non-susceptible Enterobacterales were also detected (2/18 carbapenem-tested isolates in 2025; 11%). Conclusions: The DFI profile has shifted from an S. aureus-dominated Gram-positive ecology toward a polymicrobial, increasingly Gram-negative one, with the first documentation of MRSA (on reintroduction of routine oxacillin testing) and of carbapenem-non-susceptible Enterobacterales. Empirical policy for moderate-to-severe DFI should reliably cover Enterobacterales and methicillin-resistant Gram-positives while preserving carbapenems and glycopeptides through active stewardship. Full article

(This article belongs to the Special Issue Diabetic Foot Infection and Clinical Infections: New Insights in Diagnosis and Treatment)

► Show Figures

Figure 1

14 pages, 8093 KB

Open AccessArticle

Characterization of blaNDM-1 and blaOXA-23-Type Carbapenemases in Acinetobacter baumannii Isolated from Post-Surgical Patients

by Sana Gul, Nawab Ali, Muhammad Qasim, Maali Alahmad, Muhammad Saeed Khan, Zull E. Nourain, Sadir Zaman, Yar Muhammad and Waheed Ullah

Antibiotics 2026, 15(8), 722; https://doi.org/10.3390/antibiotics15080722 - 24 Jul 2026

Abstract

Background: Acinetobacter baumannii is an important opportunistic pathogen responsible for healthcare-associated infections, particularly among critically ill, intensive care unit (ICU), and post-surgical patients. The emergence of carbapenem-resistant A. baumannii (CRAB) has become a major therapeutic challenge worldwide because of its multidrug-resistant nature [...] Read more.

Background: Acinetobacter baumannii is an important opportunistic pathogen responsible for healthcare-associated infections, particularly among critically ill, intensive care unit (ICU), and post-surgical patients. The emergence of carbapenem-resistant A. baumannii (CRAB) has become a major therapeutic challenge worldwide because of its multidrug-resistant nature and limited treatment options. Despite the increasing prevalence of CRAB in Pakistan, information regarding the molecular characterization of carbapenem resistance genes among isolates recovered from surgical site infections (SSIs) remains limited. Methods: A cross-sectional study was conducted from November 2023 to February 2024 at Khalifa Gul Nawaz Hospital, Bannu, Khyber Pakhtunkhwa, Pakistan. A total of (n = 118) surgical wound specimens were collected from patients with clinically diagnosed SSIs. A. baumannii isolates were identified using standard biochemical tests and confirmed by 16S rRNA gene sequencing. In vitro antimicrobial susceptibility was determined by Kirby–Bauer disk diffusion according to CLSI 2024 guidelines. In addition, the concentration-dependent inhibition-zone response of imipenem and meropenem against carbapenem-resistant isolates was evaluated using an agar well diffusion assay. Molecular detection of blaNDM-1 and blaOXA-23 was performed by polymerase chain reaction (PCR), and representative amplicons were subjected to Sanger sequencing for further analysis. Results: In the current study, the total number of (n = 118) wound specimens from healthcare-associated patients were processed, in which A. baumannii-positive isolates (n = 23, 19.5%) were documented. Its prevalence was higher in males (69.6%) compared to females, and was strongly associated (78.2%) with elderly patients (aged 51–68 years). In vitro susceptibility testing revealed that 91.3% of isolates harbored multidrug-resistant (MDR) attributes. Antimicrobial susceptibility profiling revealed high levels of multidrug resistance, with 82.6% of isolates resistant to imipenem and meropenem, as well as 100% resistance to aztreonam and gentamicin. Colistin showed the highest activity, with 87.0% of isolates remaining susceptible. In the agar well diffusion assay, measurable inhibition of the carbapenem-resistant isolates by imipenem and meropenem occurred only at higher concentrations. Molecular screening of resistance genes identified blaOXA-23 in 60.9% and blaNDM-1 in 30.4% of isolates. Co-expression of both genes was detected in some (n = 4) isolates. Among the selected MDR isolates included in the gene resistance analysis, imipenem and meropenem resistance were recorded in 9/14 blaOXA-23-positive isolates and 5/7 blaNDM-1-positive isolates. Conclusions: This study substantiates an escalated incidence of carbapenem-resistant, MDR A. baumannii in post-surgical infections. blaOXA-23 were documented as the predominant carbapenemase gene, with co-expression of blaNDM-1 in a substantial proportion of isolates. These findings provide an important phenotypic and molecular characterization of selected carbapenemase genes in healthcare-associated infections, highlighting the exigency for strengthened antimicrobial stewardship and infection control strategies in the hospitals of the region. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens, 2nd Edition)

► Show Figures

Figure 1

23 pages, 13289 KB

Open AccessArticle

Towards Antimicrobial Formulations of Repurposed Drugs and Cationic Surfactants: Efficacy, Cytotoxicity on Human Cell Lines, and Ecotoxicity in Aquatic Models

by Alida Monreal, Diego Ballestero, Cristina Yus, Iman Mattar, Gracia Mendoza, Elisa Langa, Mª Rosa Pino-Otín and Manuel Arruebo

Antibiotics 2026, 15(8), 721; https://doi.org/10.3390/antibiotics15080721 - 24 Jul 2026

Abstract

Background: Antimicrobial combination therapies outperform traditional monotherapies by offering additive or synergetic effects, a broader spectrum of activity, enhanced efficacy against polymicrobial infections, and a reduced risk of resistance development and infection relapse. Methods: Herein, we have combined the chemotherapeutic antibiotic alkylating agent [...] Read more.

Background: Antimicrobial combination therapies outperform traditional monotherapies by offering additive or synergetic effects, a broader spectrum of activity, enhanced efficacy against polymicrobial infections, and a reduced risk of resistance development and infection relapse. Methods: Herein, we have combined the chemotherapeutic antibiotic alkylating agent mitomycin C (MMC) with the wide-spectrum antiseptic octenidine hydrochloride (OCT). The non-specific mode of action via membrane disruption of the latter, together with the DNA-alkylating ability of the former, is here combined to produce bactericidal antibiotic-like mixtures against clinical isolates of Methicillin-resistant Staphylococcus aureus and uropathogenic Escherichia coli. The concentrations required for both antimicrobials to inhibit or eradicate bacterial biofilms as well as intracellular persisters are also determined here. The cytotoxicity of the selected combinations on eukaryotic cells was also evaluated in traditional 2D cultures and in 3D-fibroblast spheroids to mimic a physiologically relevant microenvironment present in topical infections. Finally, the ecotoxicity of the studied compounds was also evaluated through standardized bioassays using representative microorganisms commonly employed in environmental toxicity assessments such as Daphnia magna (D. magna) and Aliivibrio fischeri (A. fischeri). Results: Compared to monotherapy, these environmentally friendly antibiotic-like combinations at specific concentrations may achieve additive antimicrobial effects against planktonic, sessile, and intracellular pathogenic strains. However, the ecotoxicological response was bioindicator-dependent: the OCT–MMC combination reduced toxicity in A. fischeri, but not in D. magna, where toxicity was comparable to OCT alone, indicating OCT as the main driver. Thus, any reduction in ecotoxicity appears species-specific. Nonetheless, the use of lower doses may help minimize selective pressure for resistance. Conclusions: Collectively, these findings demonstrate that selected MMC–OCT combinations achieve antibacterial efficacy against planktonic, sessile, and intracellular pathogenic bacteria while preserving the viability of eukaryotic cells and exhibiting minimal toxicity toward standard ecotoxicological model organisms. Further studies are needed to guarantee the safe use of this combination at selected doses and to guarantee its non-systemic absorption after topical administration. Full article

(This article belongs to the Special Issue Advances in Antimicrobial Compounds: Exploring Natural, Synthetic, and Repositioned Drugs)

► Show Figures

Graphical abstract

14 pages, 2088 KB

Open AccessArticle

Comparison of Urinary Isolate Distribution and Antimicrobial Resistance Profiles in Kidney Transplant Recipients and Non-Transplant Nephrology Patients

by Büşra Çalışır, Abdullah İbrahim Çalışır, Safa Şanda, Nazmiye Ülkü Tüzemen, Abdülmecit Yıldız, Alparslan Ersoy and Cüneyt Özakın

Antibiotics 2026, 15(8), 720; https://doi.org/10.3390/antibiotics15080720 - 24 Jul 2026

Abstract

Background/Objectives: Urinary tract infections (UTIs) are common infectious complications in kidney transplant recipients (KTRs) and non-transplant nephrology patients. However, direct culture-based comparisons of urinary isolate distribution and antimicrobial resistance profiles between KTRs and non-transplant nephrology (NTN) patients remain limited. This study compared urinary [...] Read more.

Background/Objectives: Urinary tract infections (UTIs) are common infectious complications in kidney transplant recipients (KTRs) and non-transplant nephrology patients. However, direct culture-based comparisons of urinary isolate distribution and antimicrobial resistance profiles between KTRs and non-transplant nephrology (NTN) patients remain limited. This study compared urinary isolates recovered from urine cultures with significant growth and their in vitro antimicrobial resistance profiles in hospitalized KTRs and NTN patients. Methods: In this retrospective culture-based study, urine culture results from patients hospitalized in the nephrology and kidney transplantation units between 1 January 2024 and 31 December 2025 were reviewed. Urinary isolate distribution, in vitro antimicrobial resistance profiles, and extended-spectrum β-lactamase (ESBL) production were compared between the two. Results: A total of 397 patients with at least one urine culture showing significant growth were included, comprising 220 KTRs and 177 NTN patients. Enterobacterales were significantly more frequent among KTRs than among NTN patients (77.2% vs. 41.1%, p < 0.001). Escherichia coli was the predominant urinary isolate in both groups. In contrast, Candida spp. (26.8% vs. 3.2%, p < 0.001), Enterococcus spp. (15.8% vs. 7.7%, p < 0.001), and non-fermenting Gram-negative bacteria (9.4% vs. 3.4%, p = 0.001) were more frequently recovered from NTN patients. Among E. coli isolates, resistance to gentamicin (p = 0.006) and ertapenem (p = 0.001) was significantly higher in the NTN group. Likewise, Klebsiella pneumoniae isolates from NTN patients showed significantly higher resistance to third-generation cephalosporins, aminoglycosides, and carbapenems (p < 0.05). ESBL production was also more frequent in NTN patients than in KTRs (55.7% vs. 41.9%, p = 0.013). Conclusions: Hospitalized KTRs and NTN patients exhibited distinct urinary isolate distributions and in vitro antimicrobial resistance profiles. These findings should be interpreted as culture-based epidemiological data rather than as differences in clinically confirmed UTI burden. Stratified local surveillance may help contextualize urinary isolate and susceptibility patterns across hospitalized nephrology populations. Full article

(This article belongs to the Special Issue Antibiotic Surveillance and Rational Use in Special Populations: Enhancing Stewardship for Vulnerable Groups)

► Show Figures

Figure 1

30 pages, 6560 KB

Open AccessReview

How Should Bacteriological Sampling Be Stratified in Paediatric Septic Arthritis? A Narrative Review with a Proposed Risk-Stratified Framework

by Pablo Rodriguez, Maxime Schilliger, Ahmer Khan, Giacomo De Marco, Oscar Vazquez, Andreas Tsoupras, Ardian Ramadani, Christina Steiger, Romain Dayer and Dimitri Ceroni

Antibiotics 2026, 15(8), 719; https://doi.org/10.3390/antibiotics15080719 - 24 Jul 2026

Abstract

Joint aspiration remains the gold standard and an urgent step in the diagnosis of paediatric septic arthritis (SA). Unlike in acute haematogenous osteomyelitis, it has both diagnostic and therapeutic value. No previous review has specifically addressed when bacteriological sampling is essential and when [...] Read more.

Joint aspiration remains the gold standard and an urgent step in the diagnosis of paediatric septic arthritis (SA). Unlike in acute haematogenous osteomyelitis, it has both diagnostic and therapeutic value. No previous review has specifically addressed when bacteriological sampling is essential and when it may reasonably be omitted. The bacteriological profile in children is highly age-dependent: Kingella kingae predominates before 4 years of age, whereas Staphylococcus aureus—including Panton–Valentine leukocidin (PVL)-producing and methicillin-resistant (MRSA) strains—predominates thereafter. We critically review the evidence through nine clinical questions and propose a conceptual risk-stratified framework in which the sampling approach is tailored to age and clinical context. In children younger than 4 years with a positive oropharyngeal K. kingae PCR and a mild clinical presentation—defined as CRP < 20 mg/L, absence of fever, and preserved weight-bearing—non-invasive confirmation may be sufficient. This proposal is explicitly hypothesis-generating: it is derived from observational data, it has not been validated prospectively, and it is not endorsed by current PIDS/IDSA or ESPID guidance. A positive oropharyngeal PCR alone is never sufficient, given the 10–12% asymptomatic carriage rate and the limited reliability of the Kocher–Caird criteria in this age group; the decision requires a cluster of concordant findings together with mandatory clinical and laboratory reassessment at 48–72 h and a low threshold for escalation to arthrocentesis. In children older than 4 years, arthrocentesis under general anaesthesia remains the standard approach, with pathogen identification and antimicrobial susceptibility testing as the primary microbiological determinants of therapy and toxin profiling as an adjunctive investigation in selected cases. Full article

► Show Figures

Figure 1

15 pages, 1281 KB

Open AccessArticle

Pediatric Urinary Antimicrobial Resistance Patterns in a Tertiary Hospital of Northern Greece: A Retrospective Laboratory-Based Surveillance Study

by Zafeiris Tsinaris, Theodouli Stergiopoulou, Paraskevi Mantzana, Areti Tychala, Olga Vasilaki, Georgia Kagkalou, Maria Stamou, Georgios Meletis, Efthymia Protonotariou, Assimina Galli-Tsinopoulou and Lemonia Skoura

Antibiotics 2026, 15(8), 718; https://doi.org/10.3390/antibiotics15080718 - 24 Jul 2026

Abstract

Background/Objectives: Antimicrobial resistance in pediatric urinary tract infections (UTIs) is a growing concern. We evaluated resistance patterns of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa urinary isolates in a tertiary care Greek hospital from 2015 through 12 September 2025. Methods: We retrospectively [...] Read more.

Background/Objectives: Antimicrobial resistance in pediatric urinary tract infections (UTIs) is a growing concern. We evaluated resistance patterns of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa urinary isolates in a tertiary care Greek hospital from 2015 through 12 September 2025. Methods: We retrospectively analyzed pediatric urinary isolates collected from 2015 through September 2025. Antibiotic analysis was restricted to EUCAST UTI-relevant organism-drug pairs. Resistance was summarized for the prespecified antibiotics, and presumptive ESBL and carbapenem resistance phenotypes were assessed. Results: Among 776 isolates (567 E. coli, 104 K. pneumoniae, 105 P. aeruginosa), E. coli showed the lowest resistance among non-carbapenem options to nitrofurantoin (0.4%), amikacin (1.2%), and gentamicin (7.8%), and the highest to trimethoprim (98.8%), ampicillin (53.5%), and trimethoprim-sulfamethoxazole (31.5%). K. pneumoniae had the lowest resistance among non-carbapenem options to amikacin (8.6%) and gentamicin (15.5%), with high cephalosporin resistance (oral cefuroxime 40.9%, intravenous cefuroxime 39.7%). Presumptive ESBL and carbapenem resistance in K. pneumoniae were 42.3% and 20.2%, respectively. Corresponding prevalences in E. coli were 12.4% and 0.7%. P. aeruginosa retained low resistance to meropenem (1.9%) and piperacillin-tazobactam (2.1%). No age or sex association with the presumptive resistance phenotypes remained significant after false-discovery-rate adjustment. Conclusions: E. coli showed very high ampicillin resistance, low resistance to gentamicin and amikacin, and moderate resistance to guideline-relevant cephalosporins. P. aeruginosa retained low resistance to key antipseudomonal agents. K. pneumoniae showed the highest burden of cephalosporin resistance and of presumptive ESBL and carbapenem resistance phenotypes. These data support guideline-based empirical coverage more strongly for E. coli than for K. pneumoniae in this setting. Full article

(This article belongs to the Special Issue Prevention and Antimicrobial Surveillance of Hospital-Associated Infections)

► Show Figures

Figure 1

13 pages, 1739 KB

Open AccessArticle

Bile Microbiology and Risk Factors Associated with Antibiotic Resistance Patterns in Patients Taken to Laparoscopic Cholecystectomy: A Prospective Cohort Study

by Isabella Van-Londoño, Camilo Ramírez-Giraldo, Samir Moreno-Martinez, Carlos Rodriguez-Barbosa, Maria Gabriela Robayo-Romero, Eliana Maldonado, Susana Rojas López and Andrés Isaza-Restrepo

Antibiotics 2026, 15(8), 717; https://doi.org/10.3390/antibiotics15080717 - 24 Jul 2026

Abstract

Objectives: To evaluate bile culture microbiology and factors associated with resistance patterns in patients taken to laparoscopic cholecystectomy to better guide empiric antibiotic therapy. Methods: Prospective cohort study with a logistic regression model in a middle-income public hospital network of two [...] Read more.

Objectives: To evaluate bile culture microbiology and factors associated with resistance patterns in patients taken to laparoscopic cholecystectomy to better guide empiric antibiotic therapy. Methods: Prospective cohort study with a logistic regression model in a middle-income public hospital network of two institutions. Inclusion criteria were patients taken to laparoscopic cholecystectomy over 18 years of age due to benign biliary disease without other concomitant surgical procedures taken to bile culture and antibiogram testing to evaluate bile culture positivity considered as a “resistant pattern”. Results: 226 cultures tested positive for at least one microorganism, and 218 were included in the study. Overall, bile cultures classified as resistant were associated with age, comorbidities, acute signs of cholecystitis, and longer antibiotic therapy. Bile microorganisms found consisted mostly of Enterobacteriaceae. In the logistic regression model, previous ERCP, Charlson comorbidity index and duration of antibiotic therapy yielded as statistically significant (p 0.03, p 0.003 and 0.004, respectively) for presenting resistant patterns. Conclusions: Patients taken to laparoscopic cholecystectomy have a higher probability of being resistant to empirical therapy for managing acute cholecystitis if they had a higher Charlson comorbidity index, previous ERCP and longer preoperative antibiotic therapy, and thus intraoperative cultures should be considered for guided antibiotic therapy. Trial registration number: NCT06314399. Full article

► Show Figures

Figure 1

25 pages, 2930 KB

Open AccessArticle

Exploratory Pharmacokinetic Characterization of Enrofloxacin and Ciprofloxacin in Plasma and Interstitial Fluid of Dogs: Nonlinear Mixed-Effects Modeling and PK/PD Target Attainment Analysis

by Patrik Mag, Zoltán Somogyi, Andrea Kertenics, Márton Kovács, Pál Szabó and Ákos Jerzsele

Antibiotics 2026, 15(8), 716; https://doi.org/10.3390/antibiotics15080716 - 23 Jul 2026

Abstract

Background: Assessment of antimicrobial exposure at the site of infection is essential for pharmacokinetic/pharmacodynamic (PK/PD)-guided antimicrobial therapy, yet plasma concentrations may not adequately reflect extracellular target-site exposure. This study characterized the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in plasma and interstitial [...] Read more.

Background: Assessment of antimicrobial exposure at the site of infection is essential for pharmacokinetic/pharmacodynamic (PK/PD)-guided antimicrobial therapy, yet plasma concentrations may not adequately reflect extracellular target-site exposure. This study characterized the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in plasma and interstitial fluid (ISF) following high-dose oral enrofloxacin administration in dogs and evaluated PK/PD target attainment using nonlinear mixed-effects (NLME) modeling and Monte Carlo simulation. Methods: Nine healthy Beagle dogs were enrolled and received a single oral dose of enrofloxacin (target dose 20 mg/kg). Following exclusion of one dog after vomiting, pharmacokinetic analyses included plasma data from eight dogs and interstitial fluid (ISF) data from six dogs. Serial plasma samples and protein-free ISF samples collected over 24 h by in vivo ultrafiltration were analyzed using LC–MS/MS. Non-compartmental and population pharmacokinetic analyses were performed separately for plasma and ISF data. Final population models were used to simulate 5000 virtual individuals for probability of target attainment (PTA) analyses across a range of minimum inhibitory concentrations (MICs) using established AUC_0–24/MIC and C_max/MIC targets. Results: Both enrofloxacin and ciprofloxacin exhibited delayed peak concentrations and greater overall exposure in ISF than in plasma. For enrofloxacin, mean AUC_0–24 was higher in ISF than in plasma (44.9 vs. 21.6 µg × h/mL). Exploratory population pharmacokinetic models adequately described the plasma and ISF concentration-time data. Monte Carlo simulations showed consistently higher PTA in ISF than in plasma. For the more conservative AUC_0–24/MIC targets (≥100 and ≥125), the MIC associated with ≥90% PTA for enrofloxacin was four-fold higher in ISF than in plasma (0.125 vs. 0.03 µg/mL). Conclusions: High-dose oral enrofloxacin produced sustained extracellular exposure, resulting in more favorable PK/PD target attainment in ISF than in plasma. These findings indicate that plasma pharmacokinetics alone may not accurately reflect target-site antimicrobial exposure and support further evaluation of ISF-based pharmacokinetic data for PK/PD-guided optimization of fluoroquinolone therapy in dogs. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)

► Show Figures

Figure 1

11 pages, 501 KB

Open AccessArticle

Clinical Outcomes and Healthcare Resource Utilization Results Among Hospitalized Adults with Cystic Fibrosis Treated with Ceftolozane/Tazobactam: A SPECTRA Real-World Subgroup Analysis

by Emre Yucel, Alex Soriano, Florian Thalhammer, Stefan Kluge, Mike Allen, Jessica Levy, Huina Yang and Sunny Kaul

Antibiotics 2026, 15(8), 715; https://doi.org/10.3390/antibiotics15080715 - 23 Jul 2026

Abstract

Background: Patients with cystic fibrosis (CF) experience recurrent infections requiring repeated antimicrobial therapy, leading to high rates of multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) and contributing substantially to disease-related mortality. Ceftolozane/tazobactam (C/T) is an innovative therapy used to treat resistant Gram-negative [...] Read more.

Background: Patients with cystic fibrosis (CF) experience recurrent infections requiring repeated antimicrobial therapy, leading to high rates of multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) and contributing substantially to disease-related mortality. Ceftolozane/tazobactam (C/T) is an innovative therapy used to treat resistant Gram-negative infections, with enhanced activity against P. aeruginosa infections. Methods: The Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA) was a multicenter, retrospective real-world study of hospitalized adults who received ≥48 h of C/T across seven countries. Medical record data were collected for up to 6 months before treatment and 30 days after the final C/T dose (or death). This subgroup analysis describes clinical outcomes and healthcare resource utilization (HCRU) among hospitalized adults with CF who received C/T for an index infection. Results: Of 64 patients with CF, 53.1% had MDR P. aeruginosa. Clinical success was achieved in 78.1% of patients, with highest and lowest success rates in patients treated with C/T as second (100%) and sixth or later (40.0%) treatment. Microbial eradication was reported in 10.9% of patients. In-hospital mortality occurred in 14.1% of patients, with the lowest percentage in patients treated with C/T as first or second line treatment (0.0%) and the highest in patients treated with C/T sixth or later (40.0%). Median LOS was 31.5 days. Readmission (30-day all-cause) occurred in 10.9% of patients. Conclusions: In this SPECTRA subgroup analysis, C/T was associated with favorable real-world clinical outcomes among hospitalized adults with CF treated for an index infection. Interpretation is limited by the retrospective design, heterogeneous infection indications/sites, and limited interpretability of microbiologic endpoints in CF. Full article

► Show Figures

Figure 1

11 pages, 429 KB

Open AccessArticle

Comparative Analysis of Methicillin-Susceptible Staphylococcus aureus and Streptococcal Native Joint Septic Arthritis: Clinical Characteristics and Outcomes

by Jungok Kim, Eun-Jeong Joo, Ki-Ho Park, Bomi Kim and Mi Suk Lee

Antibiotics 2026, 15(7), 714; https://doi.org/10.3390/antibiotics15070714 - 22 Jul 2026

Abstract

Background/Objectives: This study aimed to evaluate and compare the clinical characteristics and outcomes of patients with methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal native joint septic arthritis (NJSA). Methods: This retrospective multicenter study included adult patients with NJSA from three tertiary care [...] Read more.

Background/Objectives: This study aimed to evaluate and compare the clinical characteristics and outcomes of patients with methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal native joint septic arthritis (NJSA). Methods: This retrospective multicenter study included adult patients with NJSA from three tertiary care hospitals between 2004 and 2023. Patients were categorized into three groups based on bacterial virulence and differences among streptococcal species: MSSA, non-viridans streptococci, and viridans streptococci. Results: A total of 213 NJSA cases were identified, comprising 164 MSSA, 35 non-viridans streptococcal, and 14 viridans streptococcal cases. Non-viridans streptococcal NJSA exhibited significantly more acute clinical features associated with systemic inflammation, including frequent fever, leukocytosis, thrombocytopenia, elevated C-reactive protein levels, higher total bilirubin levels, and acute kidney injury, compared to MSSA and viridans streptococcal NJSA. The clinical presentations were similar between the MSSA and viridans streptococcal groups. The non-viridans streptococcal group showed a higher incidence of concomitant bacteremia, but a lower proportion of positive joint culture results. Treatment approaches were consistent across the groups, except for a shorter duration of antibiotic therapy in the viridans group. Treatment failure rates were comparable: 9.8% for MSSA, 14.3% for non-viridans streptococci, and 21.4% for viridans streptococci. Conclusions: This study highlights the heterogeneous nature of streptococcal NJSA, with non-viridans streptococci presenting more aggressive clinical manifestations despite similar treatment responses across groups. These findings challenge conventional views on streptococci as a less virulent pathogen than MSSA and emphasize the need for diagnostic and management strategies tailored to the unique pathogenic traits of these bacteria. Full article

(This article belongs to the Special Issue Diagnostics and Antibiotic Therapy in Bone and Joint Infections)

► Show Figures

Figure 1

17 pages, 2700 KB

Open AccessArticle

Molecular Characterisation and Descriptive Analysis of Carbapenemase-Producing Enterobacterales: Striking Epidemiological Changes

by Estíbaliz Ugalde Zárraga, Matxalen Vidal-García, Mikel Urrutikoetxea-Gutiérrez, Elena Eraso, Itziar Angulo López and José Luis Díaz de Tuesta del Arco

Antibiotics 2026, 15(7), 713; https://doi.org/10.3390/antibiotics15070713 - 22 Jul 2026

Abstract

Background/Objectives: Klebsiella pneumoniae complex, Escherichia coli, and Enterobacter cloacae complex are considered the most prevalent carbapenemase-producing (CP) Enterobacterales in Spain. However, temporal changes in carbapenemase distribution, clonal diversity, and the mobile genetic elements (MGEs) involved in their dissemination have not been [...] Read more.

Background/Objectives: Klebsiella pneumoniae complex, Escherichia coli, and Enterobacter cloacae complex are considered the most prevalent carbapenemase-producing (CP) Enterobacterales in Spain. However, temporal changes in carbapenemase distribution, clonal diversity, and the mobile genetic elements (MGEs) involved in their dissemination have not been systematically characterised in our region. To address this knowledge gap, this study investigated the epidemiology of these organisms over a seven-year period. Methods: CP Enterobacterales isolates recovered between 2019 and 2025 from rectal screening swabs and clinical specimens (blood, urine, respiratory, wound, and sterile fluid samples) were included. All 297 isolates underwent phenotypic characterisation. Carbapenemase detection and sequence type (ST) assignment were performed for the 282 isolates available for molecular analysis. Following the gradual implementation of long-read whole-genome sequencing (WGS) beginning in 2022, MGEs associated with carbapenemase dissemination were characterised, and selected high-risk clones were analysed by SNP-based phylogenetic analysis. Results: Fifty isolates were recovered from ICU admission rectal screening, and 247 from clinical samples. Although the proportion of CP Enterobacterales among Enterobacterales isolates remained stable throughout the study period, significant changes were observed between 2019 and 2022 and between 2023 and 2025 in carbapenemase types, with a statistically significant increase in metallo-β-lactamases (MBLs) (p < 0.001), as well as in species distribution. Furthermore, predominant plasmid replicons associated with the dissemination of MBL genes were characterised. A K. pneumoniae ST147 clone co-harbouring bla_OXA-48 and bla_NDM-1 emerged and expanded significantly during the study period (p < 0.05). In addition, an ST225 NDM-1 clone was identified. SNP-based phylogenetic analysis revealed distinct genetic clusters within both lineages. Conclusions: Temporal shifts in the epidemiology of CP Enterobacterales, including the emergence and expansion of high-risk clones, were observed. High-resolution genomic analyses provided additional insight into the genetic relationships among circulating lineages. Full article

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

► Show Figures

Figure 1

24 pages, 15330 KB

Open AccessArticle

Skin Infection Pathogenicity Associated with a Canine Microbiome Resident: Polygenic Architecture of Virulence Factors in Staphylococcus pseudintermedius

by Aqib Javaid, Nazia Tabassum, Abirami Karthikeyan, Tae-Hee Kim, Young-Mog Kim and Fazlurrahman Khan

Antibiotics 2026, 15(7), 712; https://doi.org/10.3390/antibiotics15070712 - 22 Jul 2026

Abstract

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This [...] Read more.

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This study aimed to identify the genomic determinants of SSTI pathogenic potential in S. pseudintermedius and to determine whether pathogenicity is driven by single, major-effect virulence genes or by polygenic genome-wide genetic architecture. Using accessory gene-based and unitig-based genome-wide association studies (GWASs), employing a linear mixed model, across a genetically diverse collection of S. pseudintermedius isolates spanning multiple phylogenetic clades, we found that disease and carriage isolates showed no phylogenetic clustering. SSTI pathogenicity exhibited high narrow-sense heritability. Surface-associated LPXTG-anchored proteins, particularly spsF, harbored the strongest associations, with additional signals in iron metabolism (narH, sufB) and oxidative stress tolerance (ahpC). Random Forest classification validated GWAS signals. SSTI pathogenicity in S. pseudintermedius reflects a polygenic architecture driven by cumulative variation across surface-associated, metabolic, and stress-response loci, shifting focus from single virulence genes to genome-wide genetic variation. Full article

(This article belongs to the Special Issue Companion Animals: Antimicrobial Resistance in Bacterial and Fungal Pathogens Associated with Skin and Ear Infections)

► Show Figures

Figure 1

25 pages, 21300 KB

Open AccessArticle

Ranalexin-1G: A Promising Antimicrobial Peptide Targeting Virulence and Host–Pathogen Interactions in Pseudomonas aeruginosa In Vitro Models

by Marina Acunzo, Carla Zannella, Rosa Giugliano, Laura Di Clemente, Carla Capasso, Annalisa Chianese, Maria Andriolo, Federica Donadio, Emanuela Esposito, Alessandra Monti, Nunzianna Doti, Teresa Maria Assunta Fasciana, Anna Giammanco, Massimiliano Galdiero and Anna De Filippis

Antibiotics 2026, 15(7), 711; https://doi.org/10.3390/antibiotics15070711 - 22 Jul 2026

Abstract

Background: Lung infections represent a major cause of morbidity and mortality in patients with cystic fibrosis (CF) and are predominantly associated with chronic infection by Pseudomonas aeruginosa. The clinical management of CF lung disease is increasingly compromised by the emergence of multidrug-resistant [...] Read more.

Background: Lung infections represent a major cause of morbidity and mortality in patients with cystic fibrosis (CF) and are predominantly associated with chronic infection by Pseudomonas aeruginosa. The clinical management of CF lung disease is increasingly compromised by the emergence of multidrug-resistant strains, biofilm formation, and the expression of multiple virulence determinants. Antimicrobial peptides (AMPs), evolutionarily conserved effectors of innate immunity, have emerged as promising therapeutic candidates due to their ability to exert both bactericidal and anti-virulence activities. In this study, we investigated the antimicrobial and mechanistic effects of Ranalexin-1G, an AMP derived from the skin secretion of Rana grylio, against P. aeruginosa, for which its antibacterial activity has not previously been reported in the literature. Methods: Antibacterial activity was determined against the reference strain and three clinical isolates of P. aeruginosa by broth microdilution assays, time-kill kinetics and anti-biofilm assays, while peptide-mediated modulation of virulence was evaluated through transcriptional analysis of key virulence-associated genes by RT-PCR. The impact of Ranalexin-1G on host–pathogen interactions was further assessed using bacterial invasion assays in human bronchial epithelial cells (BEAS-2B). Results: Ranalexin-1G exerted a rapid bactericidal effect within 6 h at non-cytotoxic concentrations and displayed modest anti-biofilm effects, with greater efficacy in inhibiting biofilm formation. Mechanistically, peptide treatment resulted in a reduction in the expression of selected genes involved in biofilm formation and virulence, including those associated with alginate biosynthesis and type III secretion system-mediated cytotoxicity. Consistently, Ranalexin-1G markedly impaired bacterial invasion of epithelial cells, indicating interference with early host–pathogen interaction processes. Notably, the peptide displayed robust antimicrobial activity against multidrug-resistant P. aeruginosa clinical isolates from CF patients. Conclusions: Collectively, these findings suggest that Ranalexin-1G acts through a dual mechanism involving direct bactericidal activity and modulation of selected virulence pathways, supporting further investigation of its potential as an anti-virulence and host-directed approach for the treatment of chronic P. aeruginosa infections in cystic fibrosis. Full article

(This article belongs to the Special Issue New Insights Toward the Development of Novel Inhibitors of S. aureus and P. aeruginosa Factors)

► Show Figures

Figure 1

30 pages, 544 KB

Open AccessReview

Current Recommendations, Antibiotic Resistance, and Emerging Treatments for Gram-Positive Ocular Infections in the United States

by Inès Fenniri and Camille André

Antibiotics 2026, 15(7), 710; https://doi.org/10.3390/antibiotics15070710 - 22 Jul 2026

Abstract

Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009–2020), methicillin resistance reached 45.9% of intraocular Staphylococcus [...] Read more.

Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009–2020), methicillin resistance reached 45.9% of intraocular Staphylococcus aureus and 47.9% of coagulase-negative staphylococci (CoNS), with multidrug resistance exceeding 70% among methicillin-resistant intraocular isolates. While new antibiotics have been approved for systemic infections, vancomycin remains the standard of care for severe Gram-positive ocular infections. However, its ophthalmic use is constrained by limited ocular surface tolerability, physical incompatibility with intravitreal ceftazidime, and an association with hemorrhagic occlusive retinal vasculitis. To address this gap and further stimulate the development of next-generation targeted therapies in ophthalmology, this review focuses on current recommendations and new vancomycin alternative treatments for Gram-positive ocular infections in the antibiotic resistance era. This review details the current antimicrobial recommendations for the most frequent ocular infections, followed by the epidemiology and molecular mechanisms of resistance in S. aureus, CoNS, and S. pneumoniae. Finally, this review discusses new drugs that represent promising alternatives to vancomycin in ophthalmology. Full article

(This article belongs to the Special Issue Antimicrobial Treatment and Antibiotic Use in Ophthalmology)

31 pages, 1402 KB

Open AccessArticle

Occurrence of Phenotypic Multidrug-Resistant E. coli in Kentucky (USA) Surface Waters and Exploration of Sentinel Antibiotics for One Health Surveillance

by Jason W. Marion and S. Travis Altheide

Antibiotics 2026, 15(7), 709; https://doi.org/10.3390/antibiotics15070709 - 21 Jul 2026

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is a global public health threat, and surface waters may serve as surveillance locations for multidrug-resistant (MDR) bacteria within communities. This study explored MDR E. coli in Kentucky (USA) surface waters, primarily evaluating non-susceptibility to tetracycline, for assessing [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is a global public health threat, and surface waters may serve as surveillance locations for multidrug-resistant (MDR) bacteria within communities. This study explored MDR E. coli in Kentucky (USA) surface waters, primarily evaluating non-susceptibility to tetracycline, for assessing MDR associations. Methods: Surface water samples were collected from 47 sites in East-Central Kentucky during 2022 and 2024. Isolates were obtained using selective differential media, with and without tetracycline (TE) supplementation, targeting E. coli and TE-resistant E. coli. Species identification and antimicrobial susceptibility testing against 21 antibiotics representing 13 categories was performed with recovered presumptive E. coli isolates. MDR was defined as non-susceptibility to at least one antibiotic in three or more antimicrobial categories. Results: Of 151 isolates, 130 (86%) were identified as E. coli. Overall, 25% and 13% of recovered E. coli isolates from media with and without TE had MDR phenotypes, respectively, which included one isolate with non-susceptibility to 10 of 12 designated antibiotic categories. MDR prevalence was higher among incidentally recovered Enterobacter spp. (100%) than E. coli. TE non-susceptibility occurred in 100% and 18% of E. coli isolates recovered from TE-treated and untreated media, respectively. Ampicillin non-susceptibility occurred in 28% and 16% of E. coli isolates from TE-treated and untreated media. Among this non-random set of recovered isolates, ampicillin and cefazolin non-susceptibility demonstrated potential for MDR E. coli prediction. TE-treated media did not significantly improve MDR E. coli recovery. Conclusions: MDR E. coli and one potentially extensively drug-resistant (XDR) E. coli isolate were recoverable from Kentucky surface waters. Ampicillin and cefazolin non-susceptibility demonstrated potential as sentinel markers for informing screening media development for AMR surveillance in Kentucky waters. Full article

(This article belongs to the Special Issue Antibiotic Resistance: The Role of Aquatic Environments)

► Show Figures

Figure 1

10 pages, 554 KB

Open AccessArticle

Physicochemical Stability of Aztreonam/Avibactam in Elastomeric Devices for Outpatient Parenteral Antimicrobial Therapy

by Cristina Toro Blanch, Xabier Larrea Urtaran, Raquel Aguilar Salmerón, Alba Prat Riera, Laura Gómez, Anna Costa Pou, Beatriz Fernández-Rubio, Laura Herrera-Hidalgo and Carles Quiñones Ribas

Antibiotics 2026, 15(7), 708; https://doi.org/10.3390/antibiotics15070708 - 21 Jul 2026

Abstract

Background/Objectives: Outpatient Parenteral Antimicrobial Therapy (OPAT) programs provide a safe and cost-effective strategy for administering intravenous antimicrobials in the home setting. Aztreonam/avibactam (ATM/AVI) is a reserve antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria. The aim of this study was to [...] Read more.

Background/Objectives: Outpatient Parenteral Antimicrobial Therapy (OPAT) programs provide a safe and cost-effective strategy for administering intravenous antimicrobials in the home setting. Aztreonam/avibactam (ATM/AVI) is a reserve antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria. The aim of this study was to evaluate the physicochemical stability of ATM/AVI in elastomeric pumps for OPAT use. Methods: ATM/AVI was diluted in a 0.9% sodium chloride solution to a concentration of 25/8.33 mg/mL and stored in elastomeric pumps (Infusor LV 10 mL/h, 240 mL; Baxter Healthcare S.A, Zurich, Switzerland). The devices were maintained at 4 °C for 14 days and at 25, 32, and 37 °C for 48 h. Three independent elastomeric devices were prepared for each temperature condition and sampled in duplicate at each time point. Solutions were considered stable if the color, clarity, and pH remained unchanged and if the percentage of intact drug remained ≥90%, as determined via UHPLC-MS/MS. Results: ATM/AVI in polyisoprene elastomeric devices remained physicochemically stable for up to 14 days under refrigerated conditions and for 48 h at 25 °C, 32 °C, and 37 °C. Conclusions: ATM/AVI solutions demonstrated prolonged stability under the evaluated conditions, supporting their potential use in OPAT programs via 24 h continuous infusion. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

► Show Figures

Figure 1

29 pages, 6401 KB

Open AccessArticle

Suppression of Quorum Sensing and Virulence Factors by Meloxicam and Celecoxib in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

by Reham Ali, Ramadan A. El-Domany and Mona I. Shaaban

Antibiotics 2026, 15(7), 707; https://doi.org/10.3390/antibiotics15070707 - 21 Jul 2026

Abstract

Background: Staphylococcus aureus is a major cause of life-threatening infections, and increasing antimicrobial resistance necessitates alternative therapeutic strategies. This study evaluated the antiquorum sensing and antivirulence activities of selected nonsteroidal anti-inflammatory drugs (NSAIDs) against S. aureus clinical isolates by targeting the accessory [...] Read more.

Background: Staphylococcus aureus is a major cause of life-threatening infections, and increasing antimicrobial resistance necessitates alternative therapeutic strategies. This study evaluated the antiquorum sensing and antivirulence activities of selected nonsteroidal anti-inflammatory drugs (NSAIDs) against S. aureus clinical isolates by targeting the accessory gene regulator (agr). Methods: Antimicrobial susceptibility and virulence factor production were evaluated in 56 S. aureus clinical isolates. The MICs of six NSAIDs (Diclofenac, ketoprofen, ketorolac, meloxicam, indomethacin and celecoxib) were determined by broth microdilution, and the effects of sub-MICs (½ and ¼ MIC) on virulence factors were assessed. The expression of agrA, hlb, and hld was analyzed by qRT-PCR, and molecular docking was performed to evaluate interactions with AgrA receptor. Results: Among the isolates, high resistance rates were accompanied with cefoxitin, ceftazidime, and cefepime. Hemolysin, protease, and lipase production were detected in 42.86%, 89.28%, and 94.64% of isolates, respectively. Meloxicam and celecoxib at sub-MIC levels significantly reduced hemolysin, protease, and lipase activities. Additionally, both drugs markedly downregulated agrA expression by 88.9–95.3% and significantly reduced hlb and hld expression by 90.5–99.9% without affecting bacterial growth. Molecular docking demonstrated favorable binding interactions with AgrA. Conclusions: Meloxicam and celecoxib could be promising adjunctive therapies against S. aureus through suppression of the Agr-regulated virulence traits. Full article

► Show Figures

Figure 1

15 pages, 4337 KB

Open AccessArticle

Changes in the Gut Microbiome Following Perioperative Prophylactic Cefazolin Administration in Patients Undergoing Orthopedic Surgery: A Longitudinal Prospective Study

by Dokyun Kim, Woo-Suk Lee, Kyoung Hwa Lee, Min Hyuk Choi, Jun Sung Hong, Yu Jin Park, Jihoon G. Yoon, Kwangjun Lee and Seok Hoon Jeong

Antibiotics 2026, 15(7), 706; https://doi.org/10.3390/antibiotics15070706 - 21 Jul 2026

Abstract

Introduction: Cefazolin is a first-generation cephalosporin with a moderate antimicrobial spectrum and the ability to induce the production of beta-lactamases by bacterial hosts. We investigated the effect of prophylactic cefazolin administration on the gut microbiome in patients undergoing orthopedic surgery. Methods: A total [...] Read more.

Introduction: Cefazolin is a first-generation cephalosporin with a moderate antimicrobial spectrum and the ability to induce the production of beta-lactamases by bacterial hosts. We investigated the effect of prophylactic cefazolin administration on the gut microbiome in patients undergoing orthopedic surgery. Methods: A total of 42 patients were included in this study, and fecal samples were collected before cefazolin administration, within 3 days after administration, and 1 month after surgery. Shotgun whole-metagenome sequencing was performed with DNA extracted from fecal samples to assess the taxonomic composition and antimicrobial resistance genes (ARGs). Results: Within 3 days after perioperative prophylactic cefazolin administration, both the diversity indices and the Gut Microbiome Health Index were significantly decreased. Furthermore, a decrease in two beneficial anaerobic Gram-positive taxa, Ruminococcus and Fusicatenibacter, and an increase in Enterobacterales was observed. The relative abundances of ARGs related to fluoroquinolone and beta-lactam antimicrobials including penicillin, cephalosporin, carbapenem, and monobactam, were also significantly increased. The changes in the taxonomic composition and resistome related to perioperative cefazolin administration partially reverted after one month. Conclusions: Our findings suggest that even perioperative administration of a single-class antimicrobial agent could be related to the decrease of the gut microbiome diversity with potentially unfavorable taxonomic changes and lead to an increase in ARGs. Full article

► Show Figures

Figure 1

Journal Description

Antibiotics

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI