Antibiotics

18 pages, 513 KiB

Open AccessReview

Physiologically Based Pharmacokinetic Modeling of Antibiotics in Children: Perspectives on Model-Informed Precision Dosing

by Ryota Tanaka, Kei Irie and Tomoyuki Mizuno

Antibiotics 2025, 14(6), 541; https://doi.org/10.3390/antibiotics14060541 (registering DOI) - 24 May 2025

Abstract

The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict [...] Read more.

The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict PK behavior. In pediatric populations, PBPK modeling accounts for developmental changes in organ function, making it particularly useful for optimizing antibiotic dosing across different age groups, from neonates to adolescents. In recent decades, PBPK modeling has been widely applied to predict antibiotic disposition in pediatric patients for various clinical and research purposes. Model-informed precision dosing (MIPD) is an evolving approach that enhances traditional therapeutic drug monitoring by integrating multiple information sources into a mathematical framework. By incorporating PBPK modeling, MIPD could offer a more optimized antibiotic dosing that accounts for PK/PD parameters at the site of infection, improving therapeutic outcomes while minimizing toxicity. This review summarizes currently published pediatric PBPK modeling studies on antibiotics, covering various objectives such as evaluating drug–drug interactions, PK/PD analyses in targeted tissues, predicting PK in specific populations (e.g., maternal/fetal, renal impairment, obesity), and PK predictions for preterm neonates. Based on these reports, the review discusses the implications of PBPK modeling for MIPD in pediatric antibiotic therapy. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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17 pages, 2217 KiB

Open AccessArticle

Identification and Antibiotic Resistance of Isolates from Poultry Meat and Poultry Meat By-Products Exhibiting Characteristic Salmonella Morphology on Chromogenic Agar

by Sarah Panera-Martínez, Cristina Rodríguez-Melcón, Camino González-Machado, Carlos Alonso-Calleja and Rosa Capita

Antibiotics 2025, 14(6), 540; https://doi.org/10.3390/antibiotics14060540 (registering DOI) - 24 May 2025

Abstract

Background/Objectives: The main objective of this research work was to identify and determine the antibiotic resistance of the false-positive isolates on chromogenic agar when analyzing Salmonella in chicken meat. Methods: A total of 234 samples of chicken meat (carcasses, cuts and [...] Read more.

Background/Objectives: The main objective of this research work was to identify and determine the antibiotic resistance of the false-positive isolates on chromogenic agar when analyzing Salmonella in chicken meat. Methods: A total of 234 samples of chicken meat (carcasses, cuts and preparations) were studied using buffered peptone water for primary enrichment, Rappaport–Vassiliadis soy broth for secondary enrichment and Salmonella Chromogen Agar Set as a selective solid medium. Colonies with a morphology characteristic of Salmonella (one isolate per sample) were identified by matrix-assisted laser desorption ionization and time-of-flight mass spectrometry (MALDI-TOF). Results: Colonies with a characteristic morphology of Salmonella were detected in 71 samples. Only five isolates (7.0% of the total) corresponded to the genus Salmonella. Other genera detected were Hafnia (three isolates; 4.2% of the total), Escherichia (22; 31.0%), Klebsiella (19; 26.8%), Proteus (6; 8.5%) and Pseudomonas (16; 22.5%). The 66 isolates of these last five genera were tested for susceptibility to a panel of 42 antibiotics of clinical importance by disc diffusion. All isolates presented multiple resistances, to between 4 and 29 antibiotics, all of them having a multi drug-resistant (MDR) phenotype except for one Pseudomonas strain, with an extensively drug-resistant (XDR) phenotype. Conclusions: These results highlight the low selectivity of this method, with the specific culture media under test, for the detection of Salmonella in poultry meat. The considerable prevalence of antibiotic resistance observed suggests a need to improve control measures throughout the poultry meat production chain to prevent this food from becoming a reservoir of bacteria with resistance to multiple antibiotics. Full article

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15 pages, 339 KiB

Open AccessArticle

Antibiotics Resistance Profile of Clinical Isolates of Pseudomonas aeruginosa Obtained from Farwaniya Hospital in Kuwait Using Phenotypic and Molecular Methods

by Rawan Saad Althaferi, Wadha Ahmed Alfouzan and Abu Salim Mustafa

Antibiotics 2025, 14(6), 539; https://doi.org/10.3390/antibiotics14060539 (registering DOI) - 24 May 2025

Abstract

Background/Objectives: The World Health Organization has recognized Pseudomonas aeruginosa as a multidrug-resistant bacterium that presents public health concerns. This study aimed to evaluate the prevalence of MDR P. aeruginosa isolates along with their susceptibility profiles and determine the genetic basis of resistance. Methods: [...] Read more.

Background/Objectives: The World Health Organization has recognized Pseudomonas aeruginosa as a multidrug-resistant bacterium that presents public health concerns. This study aimed to evaluate the prevalence of MDR P. aeruginosa isolates along with their susceptibility profiles and determine the genetic basis of resistance. Methods: A total of 100 P. aeruginosa isolates were cultured on MacConkey agar with various specimens from patients admitted to ICUs and wards. Species identification was performed for each isolate using the VITEK^® 2 system. Each isolate was tested for susceptibility to specific antibiotics by the broth microdilution method. The resistance genes were detected by molecular methods, i.e., PCR and Sangar sequencing. Results: Among the 100 P. aeruginosa isolates tested phenotypically, 33 MDR P. aeruginosa isolates were detected. The aminoglycoside group of antibiotics showed the least resistance against P. aeruginosa, with increasing resistance to carbapenems and ciprofloxacin. The most prevalent detected genes responsible for resistance were blaVEB, blaVIM, aac (6′)-Ib, and qnr S. DNA sequencing results for the MDR isolates showed that 14 isolates had Thr-83> Ile mutation in gyrA, and 12 isolates had Ser-87>Leu mutation in parC genes. Conclusions: We conclude that the low rates of resistance to certain antibiotics, such as amikacin and piperacillin-tazobactam, seem encouraging to be effective for the treatment of Pseudomonas infections. Furthermore, the prominent mechanisms of resistance to fluoroquinolones in clinical strains of P. aeruginosa include mutations in gyrA and parC genes. These findings highlight the necessity of molecular diagnostics in guiding therapy and the potential need for broader surveillance. Full article

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15 pages, 6488 KiB

Open AccessArticle

Efficacy of Endolysin LysAB1245 Combined with Colistin as Adjunctive Therapy Against Colistin-Resistant Gram-Negative Bacteria

by Rosesathorn Soontarach, Supayang Piyawan Voravuthikunchai, Potjanee Srimanote and Sarunyou Chusri

Antibiotics 2025, 14(6), 538; https://doi.org/10.3390/antibiotics14060538 - 23 May 2025

Abstract

Background: Colistin resistance among Gram-negative nosocomial pathogens is an increasing concern. The bacteriophage-encoded lytic enzyme endolysin LysAB1245, which targets bacterial peptidoglycan, was evaluated as a potential antibacterial agent in combination with colistin as a therapeutic approach. Methods: Clinical isolates of Acinetobacter baumannii and [...] Read more.

Background: Colistin resistance among Gram-negative nosocomial pathogens is an increasing concern. The bacteriophage-encoded lytic enzyme endolysin LysAB1245, which targets bacterial peptidoglycan, was evaluated as a potential antibacterial agent in combination with colistin as a therapeutic approach. Methods: Clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, along with two reference strains, were used to assess the antibacterial activity of LysAB1245 and colistin, individually and in combination. Antibacterial susceptibility was assessed by broth microdilution. Synergistic interactions were determined using checkerboard assays and confirmed by time-kill kinetics. Resistance development was assessed after several rounds of exposure to each agent, either alone or in combination. Results: In this study, the synergistic activity of the LysAB1245/colistin combination therapy was found in some clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, resulting in a reduction in the MICs of both LysAB1245 and colistin. The bactericidal effects, with a significant, more than 3-log reduction in CFU/mL (p < 0.01), were observed in representative synergistic isolates within 4 h of treatment with the combination of LysAB1245 at 1/4 × MIC and colistin at 1/4 × MIC. Scanning electron microscope micrographs confirmed bacterial cell damage upon treatment with the combination. Additionally, treatment with LysAB1245 in combination with colistin had no effect on the development of bacterial resistance after multiple passages. Conclusions: Combining LysAB1245 with a last-resort antibiotic like polymyxins (colistin) could be used as a promising new antibacterial strategy for preventing and controlling antibiotic-resistant Gram-negative bacteria. Full article

15 pages, 474 KiB

Open AccessArticle

Antimicrobial Susceptibility Patterns of Staphylococcus spp. Isolates from Mastitic Cases in Romanian Buffaloes from Western Romania

by János Degi, Viorel Herman, Ionica Iancu, Corina Badea, Cristian Zaha, Petru Eugen Mergheș, Vlad Iorgoni, Bogdan-Alexandru Florea, Romeo Teodor Cristina and Diana Maria Degi

Antibiotics 2025, 14(6), 537; https://doi.org/10.3390/antibiotics14060537 - 23 May 2025

Abstract

Mastitis is defined as mammary gland inflammation and is one of the most common and economically significant diseases affecting dairy cows. Bacteria are the most frequently reported agents responsible for mastitis, while other pathogens are often overlooked due to insufficient routine investigation. Incomplete [...] Read more.

Mastitis is defined as mammary gland inflammation and is one of the most common and economically significant diseases affecting dairy cows. Bacteria are the most frequently reported agents responsible for mastitis, while other pathogens are often overlooked due to insufficient routine investigation. Incomplete diagnoses can result in inappropriate antimicrobial treatments, treatment failures, antimicrobial resistance, the spread of pathogens, and the recurrence of mastitis. Background/Objectives: This study aimed to investigate the presence of Staphylococcus spp. associated with Romanian buffalo mastitis on dairy farms in Western Romania via a bacteriological analysis of mastitis milk and determine antimicrobial susceptibility profiles. Methods: Bacterial culture was performed according to the guidelines described by the National Mastitis Council. Vitek 2 Compact systems (Bio Mérieux, France), with the GP ID cards, were used to confirm the species of the isolates. Antibiotic susceptibility testing was conducted by utilizing Vitek^® 2 preset antimicrobial card AST-GP79 Gram-positive Livestock WW. Results: Of all the milk samples (n = 115) analyzed, 83 were positive for Staphylococcus spp. (72.17%) and were evaluated for their antimicrobial susceptibility profiles. The most common microorganism found was S. aureus (n = 46; 55.42%), followed by S. hyicus (n = 28; 33.73%) and S. schleiferi (n = 9; 10.84%). These pathogens demonstrated significant resistance to the tetracycline, neomycin, benzylpenicillin, and erythromycin. Conclusions: Current control measures for mastitis caused by S. aureus are ineffective. A better understanding of the virulence factors in Romanian buffalo-adapted strains of S. aureus, their pathogenesis, and host immunological responses is essential for developing effective and sustainable non-antibiotic control tools such as vaccines, prophylactic therapies, and other innovative approaches. Full article

(This article belongs to the Special Issue Perspective on the Role of Farm Animals in the Transmission of Antimicrobial Resistance from a One Health Approach)

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11 pages, 370 KiB

Open AccessArticle

Description of Two Resistance-Nodulation-Cell Division Efflux Systems Involved in Acquired Antibiotic Resistance: AxySUV in Achromobacter xylosoxidans and AinCDJ in Achromobacter insuavis

by Arnaud Magallon, Julien Bador, Thomas Garrigos, Caroline Demeule, Anaïs Chapelle, Véronique Varin, Catherine Neuwirth and Lucie Amoureux

Antibiotics 2025, 14(6), 536; https://doi.org/10.3390/antibiotics14060536 - 23 May 2025

Abstract

Background/Objectives: Achromobacter xylosoxidans and Achromobacter insuavis are emerging opportunistic pathogens. Several Resistance-Nodulation-cell Division (RND) efflux systems are involved in intrinsic or acquired antibiotic resistance (AxyABM, AxyXY-OprZ, and AxyEF-OprN). The aim of this study was to explore the resistance mechanisms in one-step mutants in [...] Read more.

Background/Objectives: Achromobacter xylosoxidans and Achromobacter insuavis are emerging opportunistic pathogens. Several Resistance-Nodulation-cell Division (RND) efflux systems are involved in intrinsic or acquired antibiotic resistance (AxyABM, AxyXY-OprZ, and AxyEF-OprN). The aim of this study was to explore the resistance mechanisms in one-step mutants in which the efflux systems described to date are not involved: one mutant of A. insuavis AXX-A (AXX-A-Do1) and two mutants of A. xylosoxidans CIP102236 (CIP102236-El9 and CIP102236-Eo4) selected on fluoroquinolones. Methods: In vitro mutants were compared to parental isolates by WGS. RT–qPCR and gene inactivation were used to explore the role of the new efflux systems detected. Results: In the A. insuavis AXX-A mutant (AXX-A-Do1), WGS showed a substitution in the putative regulator of the new RND efflux system AinCDJ. The transporter gene ainD was 79-fold overexpressed in AXX-A-Do1, compared to its parental strain. The inactivation of ainD in AXX-A-Do1 led to a decrease in MICs of (8-fold), levofloxacin (8-fold), cefepime (≥8-fold), meropenem (4-fold), doripenem (4-fold), doxycycline (4-fold), minocycline (4-fold), tigecycline (4-fold) and chloramphenicol (≥8-fold). The MICs values obtained were similar to those of the parental strain AXX-A. The same approach allowed the detection of the new efflux system AxySUV in A. xylosoxidans CIP102236 mutants, in which substitutions in the putative AxySUV regulator were associated with the overexpression of the transporter gene axyU. axyU inactivation in the mutants led to a decrease in MICs of ciprofloxacin (8- to 16-fold), levofloxacin (4- to 8-fold), doripenem (4-fold), doxycycline (4-fold), minocycline (4-fold), and chloramphenicol (≥4-fold). Interestingly, axySUV is present in only about 50% of available A. xylosoxidans genomes, whereas ainCDJ is detected in all A. insuavis genomes. Conclusions: This study demonstrated that AinCDJ overproduction is involved in the acquired resistance of A. insuavis to cefepime, meropenem, doripenem, fluoroquinolones, minocycline, doxycycline, tigecycline, and chloramphenicol and that AxySUV overproduction is involved in the acquired resistance of A. xylosoxidans to meropenem, fluoroquinolones, minocycline, doxycycline, and chloramphenicol. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Multidrug-Resistant (MDR) Gram-Negative Bacteria, 2nd Edition)

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12 pages, 790 KiB

Open AccessArticle

A Retrospective Study of the Impact of the COVID-19 Pandemic on the Utilization and Quality of Antibiotic Use in a Tertiary Care Teaching Hospital in Low-Resource Settings

by Vedrana Barišić, Tijana Kovačević, Maja Travar, Ana Golić Jelić, Pedja Kovačević, Dragana Milaković and Ranko Škrbić

Antibiotics 2025, 14(6), 535; https://doi.org/10.3390/antibiotics14060535 - 23 May 2025

Abstract

Background/Objectives: Improper use of systemic antibiotics remains a significant concern in hospital settings, contributing to increased antimicrobial resistance and suboptimal clinical outcomes. The COVID-19 pandemic exacerbated this issue. This study aimed to evaluate long-term trends in antibiotic utilization in low-resource settings at a [...] Read more.

Background/Objectives: Improper use of systemic antibiotics remains a significant concern in hospital settings, contributing to increased antimicrobial resistance and suboptimal clinical outcomes. The COVID-19 pandemic exacerbated this issue. This study aimed to evaluate long-term trends in antibiotic utilization in low-resource settings at a tertiary care teaching hospital, focusing specifically on the changes before, during, and after the COVID-19 pandemic. Methods: This retrospective observational study analyzed antibiotic utilization data from the University Clinical Centre of the Republic of Srpska over ten years (2015–2024). Antibiotic consumption was expressed in defined daily doses (DDD) per 100 bed-days, and compared across three periods: pre-COVID-19 (2015–2019), COVID-19 (2020–2022), and post-COVID-19 (2023–2024). Additionally, antibiotic use was categorized according to the WHO AWaRe classification. Results: Antibiotic utilization peaked during the COVID-19 period, with the highest rate observed in 2021 (91.5 DDD/100 bed-days), despite a decrease in hospital admissions. The most frequently used antibiotics were cephalosporins, penicillins, and metronidazole. A significant increase in the use of azithromycin, meropenem, piperacillin/tazobactam, vancomycin, and colistin was noted during the COVID-19 and post-COVID-19 periods (p < 0.05), along with a notable decline in penicillin use. Watch and Reserve antibiotic use rose significantly (p < 0.05), while Access group use fell from 67% to 49.2%. Conclusions: These findings underscore the lasting impact of the COVID-19 pandemic on antibiotic prescribing patterns and emphasize the urgent need for strengthened antimicrobial stewardship efforts to ensure rational antibiotic use and combat antimicrobial resistance. Full article

(This article belongs to the Special Issue Epidemiology and Treatment of Microbial Infections in Respiratory Diseases)

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15 pages, 4743 KiB

Open AccessArticle

Bioactive Calcium Silico-Phosphate Glasses Doped with Mg²⁺ and/or Zn²⁺: Biocompatibility, Bioactivity and Antibacterial Activity

by Laura-Nicoleta Dragomir, Cristina-Daniela Ghiţulică, Andreia Cucuruz, Andreea Lazar, Georgeta Voicu and Sorina Dinescu

Antibiotics 2025, 14(6), 534; https://doi.org/10.3390/antibiotics14060534 - 22 May 2025

Abstract

Bioactive glasses in the SiO₂-CaO-P₂O₅ system represent emerging materials for hard-tissue-regeneration applications. This article focuses on the synthesis, characterization, and biological interaction of glasses doped with Mg²⁺ and/or Zn²⁺, with an emphasis on their effects [...] Read more.

Bioactive glasses in the SiO₂-CaO-P₂O₅ system represent emerging materials for hard-tissue-regeneration applications. This article focuses on the synthesis, characterization, and biological interaction of glasses doped with Mg²⁺ and/or Zn²⁺, with an emphasis on their effects on biomineralization, antibacterial behavior, and interactions with preosteoblasts from the MC3T3-E1 cell line. The bioglasses were synthesized using the sol-gel method, and the vitreous nature remained predominant even after thermal treatment at 600 °C for 2 h. From an in vitro perspective, the synthesized bioglasses demonstrated strong cell adhesion and proliferation (notably in the case of Mg²⁺ doping), low cytotoxicity, and antibacterial properties (especially in Zn²⁺-doped samples). Additionally, the simultaneous doping with Mg²⁺ and Zn²⁺ of the bioactive glass matrix is a prospective strategy for developing biomaterials with a “dual” biological characteristics–both osteoinductive and antibacterial. Full article

(This article belongs to the Special Issue Nanotechnology-Based Antimicrobials and Drug Delivery Systems)

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11 pages, 898 KiB

Open AccessArticle

Blood Culture Contamination Creep Independent of COVID-19 Pandemics: An Interrupted Time-Series Analysis

by Samo Jeverica, Jani Dernič, Peter Golob, Alenka Stepišnik, Bojan Novak, Tomaž Gantar, Lea Papst, Anamarija Juriševič Dodič, Darja Barlič Maganja, Jan Zmazek and Mladen Gasparini

Antibiotics 2025, 14(6), 533; https://doi.org/10.3390/antibiotics14060533 - 22 May 2025

Abstract

Background/Objectives: Our study aimed to assess longitudinal trends in blood culture contamination in a regional secondary care teaching hospital before and after the COVID-19 pandemic and to evaluate differences in the interpretation of trends using two distinct quasi-experimental statistical methods, including interrupted [...] Read more.

Background/Objectives: Our study aimed to assess longitudinal trends in blood culture contamination in a regional secondary care teaching hospital before and after the COVID-19 pandemic and to evaluate differences in the interpretation of trends using two distinct quasi-experimental statistical methods, including interrupted time-series analysis. Methods: We analyzed data from a 10-year period spanning from 2015 to 2024, encompassing 147,733 admissions and 634,158 patient-days, as well as a total of 25,068 blood cultures. The (i) blood culture contamination rate, (ii) contaminant proportion, (iii) single blood culture rate, and (iv) first-to-second bottle contamination ratio were calculated. Results: The observed usage rate of blood cultures per 1000 patient-days was 38.9. The contamination rate of blood cultures increased from 0.9% to 1.5% (p = 0.001) in the post-COVID-19 period, accompanied by a rise in the proportion of contaminant bacteria from 9.8% to 14.2% (p = 0.016). Additionally, the proportion of single blood culture collections increased from 23.1% to 33.6% (p < 0.001). Finally, the overall first-to-second bottle contamination ratio was 1.54, while the ratio in the post-COVID-19 period was 1.92. Conclusions: In a low-COVID-19-burden secondary care teaching hospital setting, blood culture contamination rates have progressively increased over the past decade, irrespective of the pandemic. These findings underscore the importance of sustained vigilance in infection prevention and control practices, strict adherence to blood culture collection protocols, and the ongoing need for staff training. Full article

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

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10 pages, 424 KiB

Open AccessArticle

Two-Year Follow-Up Shows Gentamicin-Coated Tibial Nails Reduce Infection Rates in Open Tibial Fractures

by Álvaro I. Zamorano, Matías A. Vaccia, Carlos F. Albarrán, Rodrigo I. Parra, Tomás Turner, Ignacio A. Rivera, Tomás Errázuriz, Andrés Oyarzún, Osvaldo A. Garrido, Pablo F. Suárez, Pierluca Zecchetto and Luis A. Bahamonde

Antibiotics 2025, 14(6), 532; https://doi.org/10.3390/antibiotics14060532 - 22 May 2025

Abstract

Introduction: Open tibial fractures carry a high risk of fracture-related infection (FRI), and prevention typically relies on early antibiotics and debridement. However, achieving optimum local antibiotic concentration remains challenging. Gentamicin-coated intramedullary nails (GCN) have been developed to prevent biofilm formation, showing short-term [...] Read more.

Introduction: Open tibial fractures carry a high risk of fracture-related infection (FRI), and prevention typically relies on early antibiotics and debridement. However, achieving optimum local antibiotic concentration remains challenging. Gentamicin-coated intramedullary nails (GCN) have been developed to prevent biofilm formation, showing short-term efficacy without interfering with fracture healing. Medium- and long-term data on GCN use are limited. This study aimed to assess the effectiveness and safety of GCN in medium-term follow-up. Methods: A prospective cohort study of patients with open tibial fractures was treated with GCN under a standardized protocol, with a minimum follow-up of 24 months. Patients with traumatic amputations, protocol infringement, or loss of follow-up were excluded. The analysis assessed overall FRI incidence by Gustilo–Anderson (GA) classification. Results: Of 907 patients, 139 were included, with 2 lost to follow-up. The overall FRI incidence was 8.8%, the average healing time was 34.3 weeks, and the non-union rate was 2.2%. FRI incidence by GA classification was 0% in GA I, 2.9% in GA II, 2.9% in GA IIIA, 44.4% in GA IIIB, and 33.3% in GA IIIC. External fixation (EF) was required in 45.2% of cases, with 16.1% developing FRI (14.3% in GA II, 2.8% in GA IIIA, 50% in GA IIIB, and 33.3% in GA IIIC). In non-EF cases, FRI occurred in 2.7% of patients (2.9% in GA IIIA and 25% in GA IIIB). No adverse effects were reported due to locally administered gentamicin. Conclusions: In the medium term, GCN has consistently demonstrated safety and efficacy in preventing FRI in open tibial fractures, particularly in GA IIIA cases, even with the use of temporary EF. These findings highlight its potential as a valuable tool in managing open tibial fractures. However, further studies with long-term outcomes are needed to evaluate its effectiveness in GA IIIB and IIIC fractures. Full article

(This article belongs to the Special Issue Prevention, Diagnostic and Antimicrobial Treatment of Periprosthetic Joint Infection—Proven Meets Innovative, Complementary Approaches)

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14 pages, 1004 KiB

Open AccessArticle

Therapeutic Drug Monitoring-Based Population Pharmacokinetics of Amikacin in Patients at a Teaching Hospital

by Nadine Arnold Steffens, Estevan Sonego Zimmermann, Francine Johansson Azeredo, Rafael Linden, Luis Junior Finatto, Roberta Zilles Hahn, Alexandre Vargas Schwarzbold, Liliane Souto Pacheco and Natália Brucker

Antibiotics 2025, 14(6), 531; https://doi.org/10.3390/antibiotics14060531 - 22 May 2025

Abstract

Background: Amikacin is still an essential antimicrobial to treat life-threatening infections, including multidrug-resistant microorganisms. The effectiveness of treatment has been correlated with the Cmax/MIC ratio, with a ratio of 8 being recommended, which is difficult to reach in some patients. Appropriate antibiotic [...] Read more.

Background: Amikacin is still an essential antimicrobial to treat life-threatening infections, including multidrug-resistant microorganisms. The effectiveness of treatment has been correlated with the Cmax/MIC ratio, with a ratio of 8 being recommended, which is difficult to reach in some patients. Appropriate antibiotic exposure is important for knowing the disposition of the drug in the population. Objectives: We aimed to integrate therapeutic drug monitoring and a populational pharmacokinetic model to assess an optimal dose regimen and respective plasma exposure. Methods: Plasma levels of amikacin in peaks and troughs were determined by LC-MS/MS. The pharmacokinetic parameter was estimated to use nonlinear mixed effect modeling in Monolix^® software. The probability of target attainment was also determined using the Simulx™ software. Results: A total of 39 patients were enrolled. A one-compartment model with proportional error model best described amikacin pharmacokinetic parameters, providing a Cl of 1.49 L/h and Vc of 23.18 L. The model developed could characterize the pharmacokinetic profile in Brazilian patients who underwent therapeutic drug monitoring. Conclusions: Amikacin therapeutic drug monitoring should be associated with population pharmacokinetic analysis in dose optimization and individualization, helping maintain appropriate drug exposure in special populations such as critically ill patients. This strategy may contribute to enhancing clinical outcomes. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antibiotics in the Hospital Environment)

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15 pages, 2035 KiB

Open AccessArticle

Comprehensive Genomic Analysis of Pseudomonas aeruginosa PSU9449 Isolated from a Clinical Case in Thailand

by Thitaporn Dechathai, Kamonnut Singkhamanan, Thunchanok Yaikhan, Sarunyou Chusri, Rattanaruji Pomwised, Monwadee Wonglapsuwan and Komwit Surachat

Antibiotics 2025, 14(6), 530; https://doi.org/10.3390/antibiotics14060530 - 22 May 2025

Abstract

Background/Objectives: Pseudomonas aeruginosa is one of the most significant multidrug-resistant bacteria. It poses considerable challenges in terms of treatment and causes hospital-acquired infections that lead to high morbidity and mortality. Colonization by P. aeruginosa in a patient without clinical signs of infection [...] Read more.

Background/Objectives: Pseudomonas aeruginosa is one of the most significant multidrug-resistant bacteria. It poses considerable challenges in terms of treatment and causes hospital-acquired infections that lead to high morbidity and mortality. Colonization by P. aeruginosa in a patient without clinical signs of infection is a concern in hospital settings, as it is an opportunistic pathogen and can potentially be a multidrug-resistant strain. The objective of this study was to characterize and provide a detailed genomic analysis of this strain of the P. aeruginosa PSU9449 genome, an isolate obtained from a patient at Songklanagarind Hospital, Thailand. Methods: Whole-genome sequencing (WGS) and bioinformatics analysis were employed to examine the genomic features of P. aeruginosa PSU9449. We performed sequence type (ST) determination through multilocus sequence typing (MLST), identified antimicrobial resistance genes (ARGs), virulence factor genes (VFGs), and analyzed the presence of mobile genetic elements (MGEs). Additionally, we compared the PSU9449 genome with strains from neighboring countries to understand its phylogenetic relationship. Results: The P. aeruginosa PSU9449 genome contained five insertion sequences and several ARGs, including fosA, aph (3’)-IIb, bla_OXA-50, and catB7. It also harbored VFGs related to flagella (fli, fle, and flg), the type 6 secretion system (hcpA, tssA, and las), and the type 3 secretion system (exoS, exoU, and exoT). MLST identified PSU9449 as ST3777, which was reported in Thailand for the first time. Phylogenetic analysis based on core gene SNPs revealed that PSU9449 was closely related to P. aeruginosa HW001G from Malaysia and P. aeruginosa MyJU45 from Myanmar, forming a distinct clade. Conclusions: This study presents a comprehensive genomic analysis of P. aeruginosa PSU9449, shedding light on its genetic characteristics, antimicrobial resistance profile, and virulence potential. Interestingly, ST3777, the novel STs from the published genomes of P. aeruginosa in Thailand, were assigned in this study. The findings enhance valuable insights into the expanding knowledge of P. aeruginosa PSU9449 and highlight the importance of ongoing surveillance of its genetic diversity. Full article

(This article belongs to the Special Issue Genetics and Antimicrobial Resistance in Pathogens of Hospital Importance)

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3 pages, 663 KiB

Open AccessCorrection

Correction: Hegazy et al. Terazosin Interferes with Quorum Sensing and Type Three Secretion System and Diminishes the Bacterial Espionage to Mitigate the Salmonella Typhimurium Pathogenesis. Antibiotics 2022, 11, 465

by Wael A. H. Hegazy, Ibrahim M. Salem, Hadil Faris Alotaibi, El-Sayed Khafagy and Doaa Ibrahim

Antibiotics 2025, 14(6), 529; https://doi.org/10.3390/antibiotics14060529 - 22 May 2025

Abstract

In the original publication, there was a mistake in Figure 2C as published [...] Full article

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23 pages, 1395 KiB

Open AccessReview

Breaking Through Resistance: A Comparative Review of New Beta-Lactamase Inhibitors (Avibactam, Vaborbactam, Relebactam) Against Multidrug-Resistant Superbugs

by Ilias Karaiskos, Irene Galani, George L. Daikos and Helen Giamarellou

Antibiotics 2025, 14(5), 528; https://doi.org/10.3390/antibiotics14050528 - 21 May 2025

Abstract

The introduction of new β-lactam–β-lactamase inhibitors (BLBLIs), such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam, expands our therapeutic options against carbapenem-resistant Gram-negative bacteria, including those pathogens for which therapeutic options are limited. These new combinations are active against ESBL-, AmpC-, and KPC-producing Enterobacterales, with the [...] Read more.

The introduction of new β-lactam–β-lactamase inhibitors (BLBLIs), such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam, expands our therapeutic options against carbapenem-resistant Gram-negative bacteria, including those pathogens for which therapeutic options are limited. These new combinations are active against ESBL-, AmpC-, and KPC-producing Enterobacterales, with the exception of ceftazidime/avibactam, which is active in vitro against OXA-48. However, one drawback that must be taken seriously by the clinician is that they are ineffective against metallo-β-lactamases as well as Acinetobacter baumannii. The recent introduction of aztreonam/avibactam marks a significant advancement in our therapeutic armamentarium against metallo-β-lactamase-producing pathogens. The question to be answered is whether there is a preferred, newer BLBLI combination for the treatment of KPC-producing Enterobacterales infections. This review provides a thorough analysis of the similarities and differences between these new combinations to identify the most effective treatment options. The present review aims to provide clinicians with a detailed understanding of each BLBLI treatment option to guide the optimal use of these new agents for the effective treatment of difficult infections caused by carbapenemase-producing Enterobacterales infections. This review is based on literature retrieved from PubMed, Scopus, Web of Science, and the Cochrane Library. 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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17 pages, 1315 KiB

Open AccessArticle

Cefiderocol Antimicrobial Susceptibility Testing by Disk Diffusion: Influence of Agar Media and Inhibition Zone Morphology in K. pneumoniae Metallo-β-lactamase

by Maciej Saar, Anna Wawrzyk, Dorota Pastuszak-Lewandoska and Filip Bielec

Antibiotics 2025, 14(5), 527; https://doi.org/10.3390/antibiotics14050527 - 21 May 2025

Abstract

Accurate antimicrobial susceptibility testing (AST) of cefiderocol remains a diagnostic challenge, especially in infections caused by metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae. While disk diffusion offers a cost-effective alternative to broth microdilution, it is highly sensitive to factors such as media composition and the [...] Read more.

Accurate antimicrobial susceptibility testing (AST) of cefiderocol remains a diagnostic challenge, especially in infections caused by metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae. While disk diffusion offers a cost-effective alternative to broth microdilution, it is highly sensitive to factors such as media composition and the presence of atypical colony morphology. The objective of this study was to evaluate how different agar media and interpretations of isolated colonies affect the performance and reliability of cefiderocol AST by disk diffusion. A total of 50 clinical K. pneumoniae MBL isolates were tested using disk diffusion on Columbia with blood, MacConkey, and chromogenic agars from three manufacturers. Inhibition zones were compared with MICs from broth microdilution. Statistical analyses included paired t-tests and Spearman correlation to assess media effects and zone morphology impact. Variability in inhibition zone diameters was observed between media, notably with chromogenic agar. The most consistent results were obtained using Graso Biotech and Thermo Fisher Columbia with blood agar. Isolated colonies were observed in over half the samples and, depending on how they were interpreted, led to major changes in classification accuracy. Up to 64% of results fell into the EUCAST area of technical uncertainty (ATU), and categorical agreement varied across media and interpretive criteria. Disk diffusion for cefiderocol may be used in resource-limited settings but only if rigorously standardized using validated media, consistent zone reading, and ATU-aware interpretive strategies. In borderline cases or when morphological anomalies are present, broth microdilution should be considered the sole reliable method. Clinical microbiologists are advised to exercise caution with ambiguous results and seek expert or confirmatory testing when needed. Full article

(This article belongs to the Special Issue Preventing Antimicrobial Resistance in Hospitals: Infection Control and Antibiotic Use)

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27 pages, 2293 KiB

Open AccessReview

Combatting Pseudomonas aeruginosa with β-Lactam Antibiotics: A Revived Weapon?

by Dylan W. Zhao and Christopher T. Lohans

Antibiotics 2025, 14(5), 526; https://doi.org/10.3390/antibiotics14050526 - 20 May 2025

Abstract

Pseudomonas aeruginosa is a significant threat to public health as an aggressive, opportunistic pathogen. The use of β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems remains a front-line treatment against P. aeruginosa. However, the widespread use of β-lactams has led to [...] Read more.

Pseudomonas aeruginosa is a significant threat to public health as an aggressive, opportunistic pathogen. The use of β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems remains a front-line treatment against P. aeruginosa. However, the widespread use of β-lactams has led to the emergence of β-lactam-resistant isolates that significantly increase the economic burden and risk of mortality in patients. With the declining productivity of the antibiotic discovery pipeline, research has investigated synergistic agents to revive the use of β-lactam antibiotics against β-lactam-resistant P. aeruginosa. In this review, we summarize the mechanism of β-lactam antibiotics and provide an overview of major mechanisms associated with β-lactam resistance in P. aeruginosa. We then describe the background and use of three promising classes of agents that have shown extensive beneficial effects with β-lactam antibiotics against P. aeruginosa, namely β-lactamase inhibitors, bacteriophages, and antimicrobial peptides. The current understanding of the mechanisms of these synergistic agents is discussed. Lastly, we provide an overview of the current barriers impeding antibiotic development, and offer a glimpse into recent advances of artificial intelligence-based discovery that may serve as a new foundation for antimicrobial discovery and treatment. Full article

(This article belongs to the Special Issue Innovations in Antibacterial Agents: Combating Resistance, Improving Efficacy and Exploring New Mechanisms)

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Graphical abstract

16 pages, 1593 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Staphylococcus aureus Isolates from Domestic Pigeons in Hungary in 2022

by Ádám Kerek, Ábel Szabó and Ákos Jerzsele

Antibiotics 2025, 14(5), 525; https://doi.org/10.3390/antibiotics14050525 - 20 May 2025

Abstract

Background: Antimicrobial resistance (AMR) is a critical global health threat, affecting both human and veterinary medicine. Pigeons are increasingly recognized as potential reservoirs of antibiotic-resistant bacteria due to their widespread presence in urban and rural environments. The aim of this study was [...] Read more.

Background: Antimicrobial resistance (AMR) is a critical global health threat, affecting both human and veterinary medicine. Pigeons are increasingly recognized as potential reservoirs of antibiotic-resistant bacteria due to their widespread presence in urban and rural environments. The aim of this study was to determine the antimicrobial susceptibility profiles of Staphylococcus aureus isolates from pigeons in Hungary. Methods: A total of 73 S. aureus isolates were collected from pigeons across seven regions of Hungary in 2022. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Statistical analysis included correlation heatmaps, hierarchical clustering, network analysis, decision tree modeling, and Monte Carlo simulations. Results: The multidrug-resistant (MDR) prevalence rate was alarmingly high at 80.8%. Very high resistance rates were observed for doxycycline (97.3%), enrofloxacin (87.7%), and amoxicillin (84.9%). By contrast, low resistance rates were detected for vancomycin (5.5%) and imipenem (8.2%). Decision tree modeling identified tiamulin, enrofloxacin, and amoxicillin-clavulanate resistance as the most significant predictors of MDR status. Monte Carlo simulations predicted a mean MDR prevalence of 78.5%, indicating that the dominance of MDR strains is not merely a random phenomenon but part of a broader epidemiological pattern. Conclusions: These findings confirm that pigeons may serve as critical reservoirs of MDR S. aureus strains, posing a potential risk to public and animal health. Continued monitoring, the genetic characterization of resistant strains, and the development of effective control strategies are urgently needed. This study provides a foundation for future research aimed at understanding the biological, ecological, and epidemiological roles of pigeon-associated MDR strains. Full article

(This article belongs to the Special Issue Perspective on the Role of Farm Animals in the Transmission of Antimicrobial Resistance from a One Health Approach)

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15 pages, 1727 KiB

Open AccessSystematic Review

Helicobacter pylori Antibiotic Resistance in Russia: A Systematic Review and Meta-Analysis

by Dmitrii N. Andreev, Alsu R. Khurmatullina, Igor V. Maev, Dmitry S. Bordin, Andrey V. Zaborovskiy, Sayar R. Abdulkhakov, Yury A. Kucheryavyy, Filipp S. Sokolov and Petr A. Beliy

Antibiotics 2025, 14(5), 524; https://doi.org/10.3390/antibiotics14050524 - 19 May 2025

Abstract

Objective: This systematic review and meta-analysis aims to evaluate the temporal changes in Helicobacter pylori antibiotic resistance in Russia based on studies published over the past 15 years. Materials and Methods: We conducted a comprehensive literature search in MEDLINE/PubMed, EMBASE, the [...] Read more.

Objective: This systematic review and meta-analysis aims to evaluate the temporal changes in Helicobacter pylori antibiotic resistance in Russia based on studies published over the past 15 years. Materials and Methods: We conducted a comprehensive literature search in MEDLINE/PubMed, EMBASE, the Russian Science Citation Index, and Google Scholar, following the PRISMA 2020 guidelines. Our meta-analysis was pre-registered in PROSPERO (CRD 420251025636). The inclusion criteria included original research, published in English or Russian in 2011–2024, involving antibiotic susceptibility testing in treatment-naive Russian adults using validated diagnostic methods. Two independent researchers selected studies and extracted data using standardized procedures, with methodological quality assessed via the Newcastle–Ottawa Scale. Pooled resistance rates were calculated using fixed/random-effects models in MedCalc 23.1.5 and Python 3.9.21, with meta-regression investigating temporal trends and subgroup analyses examining regional and methodological variations. Results: We identified 16 studies comprising 1206 H. pylori isolates. The pooled analysis of studies (2011–2025) revealed an overall clarithromycin resistance rate of 15.236%, with a significant temporal increase from 11.903% pre-2015 to 21.024% in 2020–2024 (p = 0.0049). Metronidazole showed consistently high pooled resistance (33.309%), while amoxicillin (1.828%), levofloxacin (19.014%), tetracycline (1.328%), and rifampicin (5.803%) maintained low resistance rates, and dual clarithromycin–metronidazole resistance was observed in 2.793% of isolates. Regional disparities were notable in the two largest cities of Russia, with 18.763% clarithromycin resistance in Moscow versus 28.540% in Saint-Petersburg. Conclusions: Russia surpasses the Maastricht VI Consensus resistance threshold for clarithromycin (15%), necessitating revision of empirical treatment strategies. The significant increase in clarithromycin resistance, potentially exacerbated by antibiotic use during the COVID-19 pandemic, underscores the urgent need for resistance-guided therapies and ongoing national surveillance programs to optimize H. pylori management. Full article

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11 pages, 1029 KiB

Open AccessArticle

Public Awareness and Perceptions of Antibiotic Use in Human and Veterinary Medicine in Serbia

by Gordana Belamarić, Dejana Vuković, Zoran Bukumirić, Rada Sandić Spaho and Gordana Marković

Antibiotics 2025, 14(5), 523; https://doi.org/10.3390/antibiotics14050523 - 19 May 2025

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is a growing global health threat, requiring an approach that integrates human, animal, and environmental health. Public awareness and responsible antibiotic use are key to combating AMR. This study examines the knowledge, attitudes, and practices related to antibiotic [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is a growing global health threat, requiring an approach that integrates human, animal, and environmental health. Public awareness and responsible antibiotic use are key to combating AMR. This study examines the knowledge, attitudes, and practices related to antibiotic use among the general population in Serbia, exploring their impact on antimicrobial stewardship efforts. Methods: A cross-sectional study was conducted in December 2022 using a three-stage stratified random sample of the Serbian population. The Eurobarometer questionnaire was utilized with permission from the European Commission. Statistical analyses included multivariate ordinal logistic regression to identify predictors of desirable attitudes and behaviors related to antibiotic use. Results: Almost two-thirds of respondents (61.6%) reported not receiving any advice on rational antibiotic use, underscoring the need for education of the general population and raising awareness. A Higher Antibiotic Knowledge Score was associated with a 60% greater likelihood of favorable attitudes and a 21% greater likelihood of rational antibiotic use. Pharmacists were identified as the primary source of antibiotic-related information for the general population in Serbia, but there is limited public interest and awareness of antibiotic use in animals, as well as of the bans on using antibiotics to stimulate growth in farm animals within the EU. Conclusions: Through targeted educational interventions, strengthening interdisciplinary collaboration and AMR control measures is necessary for human and veterinary medicine. Although pharmacists are the primary source of information about antibiotics for the population in Serbia, collaboration with physicians and their empowerment should be introduced to strengthen antimicrobial stewardship further. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Food Animals and Human — a One Health Perspective)

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