Antibiotics

19 pages, 1413 KB

Open AccessArticle

Incorporating Sales Value into Weight-Based Veterinary Antimicrobial Use Surveillance: An Analysis of Veterinary Antimicrobial Sales Data in Japan, 2011–2024

by Yuta Hosoi, Mari Matsuda, Michiko Kawanishi, Saki Harada, Shunya Okamura, Tetsuo Asai and Hideto Sekiguchi

Antibiotics 2026, 15(9), 908; https://doi.org/10.3390/antibiotics15090908 - 15 Sep 2026

Abstract

Background/Objectives: Veterinary antimicrobial surveillance has been developed mainly around weight-based indicators, whereas the monetary dimension of antimicrobial sales has been less commonly reported. The Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) records both sales volume and sales value, enabling the quantity and monetary [...] Read more.

Background/Objectives: Veterinary antimicrobial surveillance has been developed mainly around weight-based indicators, whereas the monetary dimension of antimicrobial sales has been less commonly reported. The Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) records both sales volume and sales value, enabling the quantity and monetary dimensions of antimicrobial sales to be examined together. The objective of this study was to assess whether examining sales value alongside sales volume could provide additional surveillance information on their temporal trends and distributions across antimicrobial classes and animal species. Methods: We extracted annual veterinary antimicrobial sales data for 2011–2024 from publicly available JVARM reports. We summarized sales volume and sales value overall, by antimicrobial class, by animal category, and by antimicrobial class within each animal category. We examined their joint patterns using two-dimensional volume–value positioning and standardized annual class-specific trajectories and estimated class-specific elasticity and marginal effects using an implied unit price calculated as sales value divided by sales volume. Results: Total sales volume increased from 794 tonnes in 2011 to a peak of 859 tonnes in 2017 and then declined to 745 tonnes in 2024, whereas total sales value increased overall from JPY 19.1 billion in 2011 to JPY 28.7 billion in 2024. In 2024, tetracyclines remained the dominant class by volume at 292 tonnes, whereas cephalosporins, macrolides, and fluoroquinolones were the leading classes by sales value at JPY 4.73, 4.55, and 4.54 billion, respectively. In 2024, pigs ranked first among animal sectors in both sales volume and sales value, at 363 tonnes and JPY 10.28 billion, respectively. Dogs and cats accounted for only 8.6 tonnes but ranked second in sales value at JPY 7.32 billion. The volume–value plots illustrated contrasting positions of antimicrobial classes: tetracyclines, macrolides, and penicillins were located in the high-volume/high-value quadrant; sulfonamides in the high-volume/low-value quadrant; and cephalosporins and fluoroquinolones in the low-volume/high-value quadrant. Standardized trajectories showed concordant movement for some classes but marked divergence for others, most notably tetracyclines, for which sales volume declined while sales value increased. Cephalosporins and fluoroquinolones showed relatively weak proportional responsiveness, with elasticity estimates of −0.70 and −1.00 and marginal effect estimates of −0.03 and −0.05 kg per JPY/g. In contrast, sulfonamides and penicillins showed stronger proportional responsiveness, with elasticity estimates of −1.65 and −1.67, respectively. Conclusions: The joint analysis of sales volume and sales value revealed differences between the two measures in temporal trajectories and the relative prominence of antimicrobial classes and animal sectors. Veterinary antimicrobial use surveillance may therefore benefit from analyzing sales value alongside established sales volume measures, as this approach provides complementary market context. Full article

(This article belongs to the Special Issue Research Advances in Antimicrobial Stewardship, Residues and Resistance in Veterinary and Environmental Science)

16 pages, 1307 KB

Open AccessArticle

Impact of a Multifaceted Antimicrobial Stewardship Program on Antimicrobial Use and Prescription Quality in a Pediatric Intensive Care Unit: An Interrupted Time-Series Study

by Laura Fernández-Vallespin, Elena Fresán-Ruiz, Maria Goretti López-Ramos, Ángela Pieras-López, Eneritz Velasco-Arnaiz and Iolanda Jordan

Antibiotics 2026, 15(9), 907; https://doi.org/10.3390/antibiotics15090907 - 15 Sep 2026

Abstract

Background: Inappropriate antibiotic use contributes to antimicrobial resistance. Evidence regarding the impact of antimicrobial stewardship programs (ASPs) in pediatric intensive care units (PICUs) remains limited. The study aims to evaluate the impact of a multidisciplinary prospective post-prescription review and feedback (PPRF) ASP in [...] Read more.

Background: Inappropriate antibiotic use contributes to antimicrobial resistance. Evidence regarding the impact of antimicrobial stewardship programs (ASPs) in pediatric intensive care units (PICUs) remains limited. The study aims to evaluate the impact of a multidisciplinary prospective post-prescription review and feedback (PPRF) ASP in a European PICU on antimicrobial use and prescription quality (PQ). Methods: A prospective quasi-experimental study was conducted using interrupted time-series analysis to evaluate antimicrobial use trends before (July 2018–December 2020) and after (January 2021–March 2025) the implementation of a multifaceted ASP, integrated within a hospital-wide ASP, in a tertiary 24-bed medical–surgical PICU in Barcelona, Spain. Antimicrobial use was measured as days of therapy per 100 patient-days (DOT/100 PD) and per 100 discharges (DOT/100 D) and was analyzed by WHO AWaRe group and by individual drug. PQ was evaluated by means of cross-sectional point-prevalence surveys (PPSs). Results: During the study-period, median monthly activity in the PICU remained stable: 475 patient-days (IQR: 396–534) and 113 patients discharged (IQR: 102–124). Following ASP implementation, total antibiotic consumption significantly decreased, with an immediate reduction of 18.2 DOT/100 patient-days (p = 0.006) and a sustained monthly decline of 0.73 DOT/100 patient-days (p = 0.028). The COVID-19 pandemic did not significantly affect overall antibiotic consumption. Access and Reserve antibiotic use decreased significantly after ASP implementation, whereas Watch antibiotic use remained unchanged. Overall antifungal consumption was not significantly modified, although a transient increase was observed during the pandemic. At the individual drug level, several antibiotics demonstrated significant immediate decreases after ASP implementation. Prescription quality remained high (>88% optimal prescriptions), and PICU length of stay and mortality were unchanged. Conclusions: Implementation of a multidisciplinary PPRF-based ASP in a tertiary PICU was associated with a sustained reduction in antibiotic exposure without compromising prescription quality or clinical safety. These data support the effectiveness of collaborative stewardship in one of the most complex pediatric healthcare settings. Full article

(This article belongs to the Special Issue Antimicrobial Prescribing, Population Use and Resistance, Impact in Global Health, 3rd Edition)

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17 pages, 1926 KB

Open AccessArticle

Clinical, Microbiological and Genomic Characterization of OXA-48-Producing Klebsiella pneumoniae ST395 Circulating in a Secondary-Care Hospital in North-Eastern Italy, 2024–2025

by Simone Giuliano, Chiara Moreal, Michela Bulfoni, Jacopo Angelini, Valeria Fox, Nicolò Gualandi, Cinzia Lombardo, Francesco Curcio, Corrado Pipan, Carlo Federico Perno, Francesco Serino, Paolo Cesselli, Carlo Tascini and Paolo Gaibani

Antibiotics 2026, 15(9), 906; https://doi.org/10.3390/antibiotics15090906 - 14 Sep 2026

Abstract

Background/Objectives: This study aimed to characterize the epidemiology, resistance, virulence determinants, and genomic relatedness of OXA-48-producing Klebsiella pneumoniae in a secondary-care hospital in north-eastern Italy, and to assess the in vitro activity of cefepime-based β-lactam/β-lactamase inhibitor combinations. Methods: We performed a retrospective observational [...] Read more.

Background/Objectives: This study aimed to characterize the epidemiology, resistance, virulence determinants, and genomic relatedness of OXA-48-producing Klebsiella pneumoniae in a secondary-care hospital in north-eastern Italy, and to assess the in vitro activity of cefepime-based β-lactam/β-lactamase inhibitor combinations. Methods: We performed a retrospective observational study of consecutive, non-duplicate isolates (September 2024–January 2025). Susceptibility testing was performed using VITEK^® 2 and MIC TestStrip. All isolates underwent single-read Nanopore whole-genome sequencing, with assembly and in silico detection of resistance genes, porin alterations, plasmid replicons and virulence loci. Core-genome single-nucleotide polymorphism analysis with recombination filtering assessed genetic relatedness. Results: Thirteen isolates were recovered from elderly, highly comorbid inpatients, mainly from urine (46.2%) and rectal/fecal screening (38.5%). Twelve patients were classified as colonized, whereas one patient had an infection due to OXA-48-producing K. pneumoniae, with the organism recovered from both blood and urine cultures. All belonged to sequence type 395 and carried blaOXA-48 and blaCTX-M-15, together with a truncated OmpK35 and an OmpK36 loop-3 GD insertion. The yersiniabactin locus ybt16 within integrative conjugative element ICEKp12 was detected in 92.3% of isolates. Core-genome analysis showed high genomic similarity among isolates, consistent with local circulation of an ST395 lineage. Although yersiniabactin may contribute to iron acquisition and bacterial fitness, its presence alone does not establish a hypervirulent phenotype or predict clinical virulence. In the absence of aerobactin, salmochelin, rmpADC, and rmpA2, and without phenotypic virulence testing, these isolates should be regarded as yersiniabactin-positive but non-hypervirulent based on their genomic profile. Core-genome analysis indicated close genetic relatedness among the isolates, consistent with possible local clonal circulation. In a subset, cefepime/enmetazobactam and especially cefepime/zidebactam substantially reduced cefepime minimum inhibitory concentrations. Conclusions: We identified a multidrug-resistant OXA-48-producing K. pneumoniae ST395 lineage circulating locally, predominantly in colonization contexts. Active screening and genomic surveillance may support infection control and inform the potential role of emerging cefepime-based inhibitor combinations. Full article

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

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11 pages, 1980 KB

Open AccessArticle

Hairy Roots Cultures from the Slow-Growing and Protected Panax ginseng, Leontopodium alpinum and Gynostemma pentaphyllum as an Alternative Source of Antimicrobials

by Olivier Braissant, Virginie Flury, Muriel Jobin and Sophie Hu

Antibiotics 2026, 15(9), 905; https://doi.org/10.3390/antibiotics15090905 - 14 Sep 2026

Abstract

Background/Objectives: Although the potential of hairy roots in secondary metabolite including antimicrobal production has been demonstrated in many laboratories, the scale-up to industrial production might lead to undesired phenomena affecting the final products. Methods: Here, the hairy root cultures of a [...] Read more.

Background/Objectives: Although the potential of hairy roots in secondary metabolite including antimicrobal production has been demonstrated in many laboratories, the scale-up to industrial production might lead to undesired phenomena affecting the final products. Methods: Here, the hairy root cultures of a pilot plant was investigated for antimicrobial properties. Methanolic extract of Panax ginseng Mey., Leontopodium alpinum Cass., and Gynostemma pentaphyllum Thunb. that are slow-growing, hard-to-cultivate and endangered species, were tested for antimicrobial activity using isothermal microcalorimetry and the Kirby–Bauer assay. Results: Antimicrobial effects were detected for P. ginseng and L. alpinum extract with a minimum inhibitory concentration (MIC) at 3.6 mg·mL⁻¹ and 15 mg·mL⁻¹ respectively. G. pentaphyllum showed only minimal inhibition at high concentration and appeared to act as a prebiotic at sub-inhibitory concentrations instead. The Kirby–Bauer assays supported these results. Conclusions: Industrial callus culture and hairy root production are a valuable alternative to the use of field-grown plants for the production of antimicrobials and other metabolites. Effects similar to those of their field-harvested counterpart described in many pharmacopeias were observed. Finally, isothermal microcalorimetry provides a valuable tool as it can rapidly, quantitatively and accurately monitor antimicrobial efficacy even in dark or cloudy samples. Full article

(This article belongs to the Special Issue Innovations in Plant-Based Antibiotic and Antiviral Agents)

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12 pages, 2531 KB

Open AccessArticle

L-AmB as the Real First-Line Therapy for Paediatric Visceral Leishmaniasis: A Multicentre Retrospective Study from an Endemic Area of Southern Italy

by Ottavia Avola, Daniela Cuzzubbo, Martina Cinnirella, Lucia Gozzo, Piera Samperi, Maria Licciardello, Vito Miraglia, Filippo Greco, Martino Ruggieri, Silvia Marino, Milena La Spina, Mattia Comella, Antonino Trizzino, Andrea Di Cataldo and Giovanna Russo

Antibiotics 2026, 15(9), 904; https://doi.org/10.3390/antibiotics15090904 - 14 Sep 2026

Abstract

Background/Objectives: visceral leishmaniasis (VL) remains an important zoonotic disease in endemic Mediterranean regions, where children represent one of the populations at highest risk of developing symptomatic infection. Although pentavalent antimonials have historically been considered first-line therapy for VL, their use in Italy has [...] Read more.

Background/Objectives: visceral leishmaniasis (VL) remains an important zoonotic disease in endemic Mediterranean regions, where children represent one of the populations at highest risk of developing symptomatic infection. Although pentavalent antimonials have historically been considered first-line therapy for VL, their use in Italy has become increasingly limited because of restricted availability, safety concerns, and the widespread adoption of liposomal amphotericin B (L-AmB). Methods: this multicentre retrospective observational study evaluated the contemporary management of paediatric VL in three tertiary referral centres in Catania, Southern Italy, between January 2016 and December 2025. Results: 19 children were included, with a mean age of 4.13 years. The most common clinical manifestations were prolonged fever, pancytopenia, and hepatosplenomegaly. Three different L-AmB regimens were identified, with the 10 mg/kg/day for two consecutive days schedule representing the most frequently adopted protocol. L-AmB was well tolerated; three patients (15.8%) experienced disease relapse during follow-up, all of whom responded successfully to additional L-AmB treatment, resulting in an overall clinical cure rate of 100%. Notably, no patient received pentavalent antimonials, reflecting their complete replacement in routine clinical practice. Conclusions: these findings provide real-world evidence that L-AmB has effectively become the contemporary first-line treatment and standard of care for paediatric VL in an endemic Mediterranean setting, highlighting the discrepancy between historical therapeutic paradigms and current clinical practice. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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15 pages, 1231 KB

Open AccessArticle

Antibiotic Escalation Following Rapid Multiplex PCR Pneumonia Panel Testing in Intensive Care Patients with Severe Pneumonia: A Retrospective Cohort Study

by Soo Kyun Jung, Keum Ju Choi and Eun Jin Kim

Antibiotics 2026, 15(9), 903; https://doi.org/10.3390/antibiotics15090903 - 14 Sep 2026

Abstract

Background/Objectives: Severe community-acquired pneumonia (CAP) can be fatal and requires the rapid and appropriate administration of antibiotics. Rapid multiplex PCR pneumonia panels are widely used tools for antimicrobial de-escalation and stewardship; however, their role in driving antibiotic escalation in severe pneumonia requiring intensive [...] Read more.

Background/Objectives: Severe community-acquired pneumonia (CAP) can be fatal and requires the rapid and appropriate administration of antibiotics. Rapid multiplex PCR pneumonia panels are widely used tools for antimicrobial de-escalation and stewardship; however, their role in driving antibiotic escalation in severe pneumonia requiring intensive care is less well characterized. Methods: We retrospectively analyzed 288 adults with severe CAP who were admitted to the intensive care unit (ICU) of a tertiary hospital and underwent lower-respiratory BioFire FilmArray Pneumonia Panel (BFPP) testing between April 2023 and September 2024. The primary outcome was antibiotic escalation, defined as addition of an agent or a change to broader-spectrum therapy after the BFPP result, and its associated factors. Secondary outcomes were in-hospital mortality, hospital and ICU length of stay (LOS), and ventilator duration according to the antibiotic escalation. Results: Patients were elderly (median 72 years old; 60.8% male) and critically ill (median SOFA 8; median APACHE-II 19; shock 49.0%; mechanical ventilation 56.9%). The panel was positive in 66.3% of cases, and results were obtained with a median turnaround time of 2 h versus 67 h for sputum culture. After the panel, antibiotics were escalated in 34.0% of cases, de-escalated in 2.8%, discontinued in 0.7%, and unchanged in 62.5%. Escalation was independently associated with resistance gene detection (adjusted odds ratio [aOR] 3.15, 95% CI 1.71–5.82), panel positivity (aOR 1.97, 95% CI 1.02–3.80), and SOFA score (aOR 1.10 per point, 95% CI 1.01–1.19). Thirty-day mortality, in-hospital mortality, hospital LOS, ICU LOS, and ventilator duration did not differ between escalation and non-escalation groups. Conclusions: In severe CAP requiring intensive care and managed with a comparatively narrow initial empirical regimen, panel testing was predominantly followed by antibiotic escalation rather than de-escalation, particularly when resistance genes were detected. No statistically measurable difference in clinical outcomes was observed, but the study was not powered to exclude any clinically meaningful benefit or harm of escalation. Full article

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

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16 pages, 712 KB

Open AccessArticle

Antifungal Susceptibility Patterns in Respiratory Tract Candidiasis and Risk Factors Among HIV-Infected Adults in South West Cameroon

by Emile Valery Lyonga Bekende, Valantine Ngum Ndze, Erastus N. Nembo, Joseph Fokam, Taku Nadesh Ashukem, Nicoline Fri Tanih, Krisztián Bányai and Anna Longdoh Njunda

Antibiotics 2026, 15(9), 902; https://doi.org/10.3390/antibiotics15090902 - 14 Sep 2026

Abstract

Background: Respiratory tract candidiasis, primarily caused by Candida species, is a prevalent opportunistic fungal infection in individuals with HIV/AIDS. A high HIV viral load is considered a significant risk factor for developing respiratory fungal infection. This study aimed to identify the yeast [...] Read more.

Background: Respiratory tract candidiasis, primarily caused by Candida species, is a prevalent opportunistic fungal infection in individuals with HIV/AIDS. A high HIV viral load is considered a significant risk factor for developing respiratory fungal infection. This study aimed to identify the yeast species isolated from sputum samples of HIV-positive and HIV-negative adults, determine their antifungal susceptibility patterns, and investigate associated risk factors. Methods: A hospital-based comparative cross-sectional study was conducted from March to May 2022. Sputum samples were collected from 190 HIV-positive and 190 HIV-negative participants. Candida and other yeast species were isolated and identified, followed by antifungal sensitivity testing. Results: Of the 190 specimens from each group, 77 (40.53%) from HIV patients and 12 (6.31%) from HIV-negative participants tested positive for yeasts. Candida albicans was the most prevalent species, found in 52 (67.53%) HIV-positive patients and 12 (100%) HIV-negative patients. This was followed by Nakaseomyces glabratus (15.58%), Pichia kudriavzevii (9.09%), Candida tropicalis (6.49%), and Candida parapsilosis (1.29%) in HIV-positive patients. Notably, all 12 isolates from HIV-negative participants demonstrated 100% sensitivity to all ten tested antifungal drugs. In contrast, isolates from HIV patients showed significant resistance to fluconazole and ketoconazole (32.5% each). High viral load (p < 0.001), dermatophyte infection (p < 0.001), and antiretroviral (ARV) regimen (p = 0.030) were significantly associated with respiratory tract fungal infections in HIV patients. Conclusions: Based on this exploratory study, respiratory mycosis is frequent in HIV-positive patients in Cameroon, and identified fungi show increased resistance to azoles. While these results must be interpreted with care due to the sample size relative to the high national HIV prevalence, they suggest that public health education is needed to improve awareness. These preliminary findings prompt a review by health authorities concerning the use of fluconazole for prophylaxis in HIV-positive patients in Cameroon. Full article

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22 pages, 7410 KB

Open AccessArticle

Antibiotic Consumption Patterns in Three Romanian Hospitals: A Five-Year Retrospective Study

by Radu-Daniel Duvlea, Robert Viorel Ancuceanu, Ana-Maria Ispas and Adriana-Elena Tăerel

Antibiotics 2026, 15(9), 901; https://doi.org/10.3390/antibiotics15090901 - 13 Sep 2026

Abstract

Background: Monitoring antibiotic consumption represents an important objective for antimicrobial stewardship programs in hospitals. The aim of this study was to analyze antibiotic consumption patterns in three Romanian hospitals. Methods: A five-year retrospective study was conducted using monthly pharmacy consumption data from [...] Read more.

Background: Monitoring antibiotic consumption represents an important objective for antimicrobial stewardship programs in hospitals. The aim of this study was to analyze antibiotic consumption patterns in three Romanian hospitals. Methods: A five-year retrospective study was conducted using monthly pharmacy consumption data from three Romanian hospitals for the years 2018, 2019, 2023, 2024, and 2025. Antibiotic consumption was quantified using defined daily doses (DDD) per 100 bed-days. Antibiotics were grouped using the World Health Organization AWaRe (Access, Watch, Reserve) classification. Results: The analysis revealed statistically significant differences in overall antibiotic consumption among the three hospitals (p < 0.001). A significant annual correlation between hospitalization days and antibiotic consumption was observed for some years in two of the facilities. Post hoc analysis confirmed statistically significant differences across all AWaRe category pairwise comparisons. Watch antibiotics had the highest consumption rates (over 60%). By therapeutic classes, the highest overall consumption was for cephalosporins, fluoroquinolones, penicillins, and carbapenems. Cefuroxime accounted for the highest cumulative consumption, followed by ceftriaxone, meropenem, vancomycin, ciprofloxacin, and metronidazole. Conclusions: Antibiotic consumption differed among the participating hospitals and study years. Monitoring antibiotic consumption provides valuable information on hospital antibiotic utilization patterns and can support evidence-based antimicrobial stewardship in hospitals. Full article

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16 pages, 1011 KB

Open AccessArticle

Receptor Structure Shapes Host Range but Incompletely Predicts High Activity in Klebsiella pneumoniae Phage Cocktails

by Roman B. Gorodnichev, Anastasiia O. Krivulia, Maryam O. Sidorskaia, Maria A. Kornienko, Narina K. Abdraimova, Maja V. Malakhova, Marina V. Zaychikova, Dmitry A. Bespiatykh and Egor A. Shitikov

Antibiotics 2026, 15(9), 900; https://doi.org/10.3390/antibiotics15090900 - 12 Sep 2026

Abstract

Background. Rational design of phage cocktails typically relies on the lytic spectrum. However, susceptibility criteria vary widely among studies, ranging from qualitative lysis in spot tests to quantitative endpoints based on serial-dilution titration or efficiency of plating. Methods. We investigated this discrepancy using [...] Read more.

Background. Rational design of phage cocktails typically relies on the lytic spectrum. However, susceptibility criteria vary widely among studies, ranging from qualitative lysis in spot tests to quantitative endpoints based on serial-dilution titration or efficiency of plating. Methods. We investigated this discrepancy using four commercial phage cocktails and two capsule-specific monophages against a clinically representative collection of 448 Klebsiella pneumoniae isolates comprising 56 capsule types, collected in 2018–2025 from 12 medical centers. Using a modified Gratia titration assay, we defined host range (HR) as specific lysis at any dilution and putative therapeutic applicability (PTA) as lysis at dilutions corresponding to ≥10⁶ plaque-forming units per mL. Results. We identified a systematic discrepancy between these two measures of cocktail efficacy. HR coverage reached 64%, whereas PTA was significantly lower, with a median HR–PTA difference of 36%. This discrepancy persisted for capsule-specific monophages tested against KL2 isolates (n = 69), indicating that neither nominal capsule matching nor low component titres fully explained the loss of activity. This pattern provides indirect functional evidence that post-adsorption barriers contribute to the HR–PTA discrepancy, although adsorption and intracellular antiphage mechanisms were not assessed directly. Capsule type was the principal and most robust predictor of efficacy, whereas spatiotemporal factors, including year and medical centre, had only a weak effect on PTA. Conclusions. Capsule matching can therefore help estimate population-level coverage but does not fully predict high-titre activity. Phage selection should incorporate serial-dilution testing rather than rely on spot-test lysis alone. Cocktail design should account for both receptor coverage and functional activity against representative isolates within individual capsule types. Full article

(This article belongs to the Special Issue Bacteriophage Therapy: A Renaissance Weapon—Recent Developments and Application, 3rd Edition)

32 pages, 1370 KB

Open AccessReview

Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical Pipeline

by Melanie Kempf Hansen and Lars Østergaard

Antibiotics 2026, 15(9), 899; https://doi.org/10.3390/antibiotics15090899 - 12 Sep 2026

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is an urgent global threat, with bacteria developing resistance against most antibiotics currently in clinical use. Non-traditional antibacterials—including bacteriophages, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), live biotherapeutic products (LBPs) and anti-virulence small molecules—act through mechanisms distinct from traditional antibiotics [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is an urgent global threat, with bacteria developing resistance against most antibiotics currently in clinical use. Non-traditional antibacterials—including bacteriophages, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), live biotherapeutic products (LBPs) and anti-virulence small molecules—act through mechanisms distinct from traditional antibiotics and may exhibit mechanism-dependent differences in the propensity for resistance development. Despite growing interest, the landscape of non-traditional candidates in active clinical development against WHO priority pathogens has not been recently systematically mapped. This review aimed to characterize the current non-traditional antibacterial clinical pipeline targeting pathogens on the WHO Bacterial Priority Pathogens List (BPPL) 2024. Methods: Candidates were identified from the WHO antibacterial clinical pipeline report (October 2025) and verified through the Global AMR R&D Hub, ClinicalTrials.gov, and targeted searches of peer-reviewed publications, conference abstracts, and company communications. Candidates were included if they showed documented clinical activity since January 2023. Results: Twenty-seven candidates met the inclusion criteria, of which 20 remain in active clinical development and seven have been discontinued or paused or have unverified status. The pipeline is dominated by bacteriophages and markedly skewed toward carbapenem-resistant Pseudomonas aeruginosa (CRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with few or no candidates targeting carbapenem-resistant Acinetobacter baumannii (CRAB), Shigella or Salmonella. Conclusions: Non-traditional antibacterials represent a promising but underfunded and unevenly distributed pipeline—with public and philanthropic investment in antibacterial R&D totaling just $2.51 billion across 2017–2023, a seven-year total, against an estimated $251–276 billion in global pharmaceutical R&D spending in a single recent year. Realizing their potential will require substantially greater investment and more deliberate prioritization toward the WHO priority pathogens currently underserved by the non-traditional pipeline. Full article

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20 pages, 1596 KB

Open AccessArticle

Anthranilate Reduces Pseudomonas aeruginosa Infection Severity through an Antibiotic-Independent Anti-Virulence Mechanism

by Huiyan Li, Min-Hee Kang, Wen-Xin Niu, Eunsoo Kim and Joon-Hee Lee

Antibiotics 2026, 15(9), 898; https://doi.org/10.3390/antibiotics15090898 - 11 Sep 2026

Abstract

Background/Objectives: Antibiotic resistance is a growing global health challenge, especially with tricky bacteria like Pseudomonas aeruginosa. Anthranilate, previously identified as a signaling molecule in P. aeruginosa, modulates various pathogenicity-related phenotypes by reducing virulence factor production, inhibiting biofilm formation, and increasing antibiotic [...] Read more.

Background/Objectives: Antibiotic resistance is a growing global health challenge, especially with tricky bacteria like Pseudomonas aeruginosa. Anthranilate, previously identified as a signaling molecule in P. aeruginosa, modulates various pathogenicity-related phenotypes by reducing virulence factor production, inhibiting biofilm formation, and increasing antibiotic susceptibility. Based on these good properties as an anti-virulence agent, this study evaluated the actual therapeutic potential of anthranilate using mouse skin infection and lung infection models. Specifically, the efficacy of anthranilate in a standalone treatment was investigated without reliance on conventional antibiotics. Methods: The therapeutic efficacy of anthranilate was evaluated in murine skin and lung infection models of P. aeruginosa. Anthranilate was administered as a standalone treatment, and its effects on bacterial burden, inflammatory responses, and tissue lesion progression were assessed and compared with those of gentamicin treatment. Results: Anthranilate effectively reduced bacterial suppuration, mitigated inflammatory responses, and suppressed lesion progression in infected skin and lung tissues. Notably, anthranilate alone produced therapeutic effects comparable to those of gentamicin. Conclusions: These findings highlight its potential of standalone treatment as an alternative to traditional antibiotics and offer a novel anti-virulence strategy that minimizes selective pressure for resistance development. Full article

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

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19 pages, 1831 KB

Open AccessArticle

Pairwise Growth Dynamics of Environmental Escherichia coli and Enterococcus Isolates with Contrasting Antibiotic Susceptibility Phenotypes: Influence of Temperature

by Athanasios Tsiartsafis and Foteini F. Parlapani

Antibiotics 2026, 15(9), 897; https://doi.org/10.3390/antibiotics15090897 - 11 Sep 2026

Abstract

Background/Objectives: Environmental bacterial isolates with contrasting, previously established antimicrobial-susceptibility phenotypes may differ in growth under antibiotic-free conditions, but such differences can reflect strain background and temperature. This study characterized the monoculture population development and growth kinetics of predefined pairs of naturally occurring, genetically [...] Read more.

Background/Objectives: Environmental bacterial isolates with contrasting, previously established antimicrobial-susceptibility phenotypes may differ in growth under antibiotic-free conditions, but such differences can reflect strain background and temperature. This study characterized the monoculture population development and growth kinetics of predefined pairs of naturally occurring, genetically distinct environmental Escherichia coli, Enterococcus faecalis, and Enterococcus faecium isolates selected from a broader previously characterized collection. Methods: Nine isolates were grown separately in a controlled nutrient-enriched seawater model at 12, 22, and 30 °C, representing low, intermediate, and high water-temperature conditions relevant to the Thermaic Gulf. Growth was described using the Baranyi–Roberts model. Within each predefined strain pair and temperature, population development over time was assessed by two-way mixed-design ANOVA with Greenhouse–Geisser correction and Šídák-adjusted time-point comparisons. Temperature dependence of μ_max was summarized using Ratkowsky and Arrhenius models. Results: Population-development patterns differed between paired isolates in all pair–temperature comparisons except MA60–T640 at 30 °C, but the direction and degree of the differences varied among pairs and sampling times. Fitted μ_max did not always correspond directly to observed population development, as illustrated by SB10–T280. SB10 had a higher μ_max at all three temperatures while remaining at lower absolute population levels during early-to-mid growth. Conclusions: The selected environmental isolate pairs did not show a uniform direction of difference associated with antimicrobial-susceptibility phenotype. Population-development patterns were pair- and time-specific and differed among the tested temperature conditions, while fitted μ_max did not always reflect observed population development. These findings provide a temperature-resolved basis for interpreting the growth behaviour of selected environmental isolates with contrasting antimicrobial-susceptibility phenotypes under controlled nutrient-enriched marine conditions across temperatures relevant to warming shellfish-production environments. Full article

(This article belongs to the Special Issue Monitoring the Dissemination of Antibiotic Resistance in Environments)

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20 pages, 791 KB

Open AccessArticle

Analytical and Clinical Evaluation of a Fully Automated Direct-from-Whole-Blood Multiplex PCR Assay Using Large-Volume Reverse Elution for Rapid Bloodstream Infection Diagnosis

by Chi-Sheng Tai, Hsing-Yi Chung, Tai-Han Lin, Chih-Kai Chang, Cherng-Lih Perng, Hung-Sheng Shang and Ming-Jr Jian

Antibiotics 2026, 15(9), 896; https://doi.org/10.3390/antibiotics15090896 - 11 Sep 2026

Abstract

Background/Objectives: Prompt identification of bloodborne pathogens and their antimicrobial resistance is critical for effective sepsis management. Direct molecular testing of blood offers faster results than blood culture; however, its clinical utility has been limited by suboptimal sensitivity and procedural complexity. This study evaluated [...] Read more.

Background/Objectives: Prompt identification of bloodborne pathogens and their antimicrobial resistance is critical for effective sepsis management. Direct molecular testing of blood offers faster results than blood culture; however, its clinical utility has been limited by suboptimal sensitivity and procedural complexity. This study evaluated an automated rapid multiplex PCR assay (BPID^® system) and compared its performance with gold-standard methods. Methods: This was a preliminary, single-centre diagnostic-agreement study. Forty-three whole-blood samples were collected from patients with suspected bloodstream infection at Tri-Service General Hospital, Taipei, Taiwan, between January 2025 and January 2026, and were analysed. Three molecular methods and two culture-based methods were compared: the BPID^® system, a Qiagen^®-based workflow, the BioFire^® FilmArray^® BCID2 panel, blood culture, and MALDI-TOF MS identification. Positive percent agreement (PPA) was calculated at the organism level against a composite reference standard. Analytical sensitivity (limit of detection, LoD) was assessed in whole blood spiked with serial dilutions of ten reference organisms. Results: The composite reference standard yielded 47 reference-positive organisms across 42 samples. The BPID^® system achieved a PPA of 95.74% (95% CI, 85.8–98.8), numerically similar to the post-culture BCID2 panel (93.62%; p = 1.00, exact McNemar test), and higher than the Qiagen^® workflow (72.34%; p = 0.001), blood culture (72.34%; p = 0.007), and MALDI-TOF MS (74.47%; p = 0.013). In a sensitivity analysis using a composite reference standard from which the index test was excluded, 46 organisms remained reference-positive and the PPA of the BPID^® system was 95.65% (44/46; 95% CI, 85.5–98.8), again numerically similar to the BCID2 panel (93.48%; p = 1.00). For antimicrobial resistance determinants covered by both panels, the BPID^® system reproduced the BCID2 determinant profile in all 16 specimens in which such a determinant was reported (100%), versus 10 of 16 specimens (62.5%) for the Qiagen^® method. Confirmed LoD values for the BPID^® system were 0.67–20.81 CFU/mL, an 8.8- to 24.3-fold improvement over the Qiagen^® method (6.51–224.61 CFU/mL). Conclusions: The automated BPID^® system substantially improves PCR-based diagnostic sensitivity for bacteremia and, by operating directly on whole blood, removes the culture-incubation step that post-culture molecular panels require. Because the study was not designed as an equivalence or non-inferiority trial and evaluated only 43 specimens, the similar agreement observed for the BPID^® system and the BCID2 panel should not be interpreted as demonstrated equivalence; these findings should be regarded as a preliminary clinical evaluation requiring confirmation in larger multicentre studies that also enrol culture-negative and uninfected controls. Full article

(This article belongs to the Special Issue Surveillance of Carbapenem-Resistant Microbes and Strategies to Combat Them)

14 pages, 1983 KB

Open AccessArticle

Behaviour of K. pneumoniae|Carbapenems in Several European Countries According to Clustering Time-Series Health Data with Generalised Affinity Coefficient

by Ana Paula Nascimento, Mónica Vieira, Cristina Prudêncio and Helena Bacelar-Nicolau

Antibiotics 2026, 15(9), 895; https://doi.org/10.3390/antibiotics15090895 - 11 Sep 2026

Abstract

Background/Objectives: Antimicrobial resistance (AMR) constitutes a major public health and economic burden in contemporary society. This work aims to identify the patterns and temporal trends of Klebsiella pneumoniae resistance to carbapenems across several European countries. Methods: Data on K. pneumoniae resistance [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) constitutes a major public health and economic burden in contemporary society. This work aims to identify the patterns and temporal trends of Klebsiella pneumoniae resistance to carbapenems across several European countries. Methods: Data on K. pneumoniae resistance to carbapenems in several countries from 2005 to 2021 (with data available up to 2023) were retrieved from the public ECDC website in 2023. Agglomerative Hierarchical Cluster Analysis (HCA), based on the new generalised affinity coefficient, was applied to the estimated ARIMA models. Results: The dendrogram at the cut-off presented four clusters: the first cluster with Slovenia, Luxembourg, Italy and Estonia; the second cluster with Romania, Malta, Greece, Portugal and Spain; the third cluster Denmark, France and Czechia; and finally the fourth cluster with Lithuania, Cyprus, Finland, Austria, Belgium and Slovakia. Although the resistance values showed an increasing trend over the years in clusters II and III, the increase was more pronounced in cluster II. Conclusions: The application of data analysis, for the first time, using HCA based on a new similarity coefficient, namely, the generalised affinity coefficient, enables the evaluation of time-series patterns in different regions and enables the identification of clusters of countries showing similar temporal patterns of antimicrobial resistance. Carbapenem resistance in K. pneumoniae among countries belonging to cluster II showed increasing trends throughout the study period. Full article

(This article belongs to the Special Issue Advances in Antimicrobial Action and Resistance)

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16 pages, 404 KB

Open AccessArticle

Early Outcomes After Discontinuing Routine Gentamicin Irrigation During AMS 800 Artificial Urinary Sphincter Implantation: A Single-Centre Retrospective Before–After Cohort Study

by Michał Andrzej Skrzypczyk, Anna Pliszka, Łukasz Białek, Marta Rydzińska, Wojciech Karoń, Jakub Dobruch and Artur Lemiński

Antibiotics 2026, 15(9), 894; https://doi.org/10.3390/antibiotics15090894 - 11 Sep 2026

Abstract

Background/Objectives: Routine local gentamicin irrigation has been used during artificial urinary sphincter (AUS) implantation despite limited procedure-specific evidence. We evaluated early outcomes after its calendar-defined discontinuation. Methods: This single-centre retrospective before–after cohort included 173 uncoated AMS 800 procedures in 164 men: [...] Read more.

Background/Objectives: Routine local gentamicin irrigation has been used during artificial urinary sphincter (AUS) implantation despite limited procedure-specific evidence. We evaluated early outcomes after its calendar-defined discontinuation. Methods: This single-centre retrospective before–after cohort included 173 uncoated AMS 800 procedures in 164 men: 59 under a gentamicin-containing local protocol and 114 after gentamicin withdrawal. Saline device immersion and Betadine-containing intraoperative irrigation of the operative field and both wounds continued in both periods. Clinician-recorded surgical-site infection (SSI) within 90 days was the antimicrobial outcome of greatest direct relevance. Complete explantation within 90 days for SSI and/or urethral erosion was an exploratory device-related endpoint; all-cause complications at 30 and 90 days were secondary safety outcomes. Results: SSI occurred after 1/59 (1.7%) gentamicin-protocol and 2/114 (1.8%) gentamicin-free procedures (risk difference +0.1 percentage points, 95% confidence interval −7.4 to +4.7; p = 1.000). Erosion occurred after 0/59 and 4/114 (3.5%) procedures; all four led to complete explantation. The explantation endpoint occurred after 1/59 versus 4/114 procedures (risk difference +1.8 percentage points, 95% confidence interval −5.8 to +7.2; p = 0.662). Thirty-day all-cause complications occurred after 14/59 versus 16/114 procedures and 90-day complications after 15/59 versus 26/114. Conclusions: No statistically significant between-period difference was detected in SSI, exploratory device-related explantation, or broad all-cause complications. Sparse events, wide confidence intervals and calendar-defined exposure amid concurrent era changes preclude conclusions regarding equivalence or absence of clinically relevant benefit or harm. Full article

(This article belongs to the Special Issue Current Challenges in Antimicrobial Stewardship)

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17 pages, 5954 KB

Open AccessArticle

Antimicrobial Resistance and Genomic Characterization of a Novel ST181 Streptococcus parasuis Clinical Isolate from Human Pleural Fluid

by Zhenghao Jie, Hongyu Lei, Yuhui Tian, Fekadu Gutema Wegi, Weijiang Liu, Long Ye, Xiaojun Tan, Jingfang Zhou, Jiayi Pan, Shaofang Lin, Pishun Li, Xiaofeng Zheng and Xuxia Cui

Antibiotics 2026, 15(9), 893; https://doi.org/10.3390/antibiotics15090893 - 11 Sep 2026

Abstract

Background/Objectives: Streptococcus parasuis is an under-recognized member of the Streptococcus suis complex that can be misidentified by routine diagnostic methods. Human clinical isolates remain sparsely characterized. This study investigated the antimicrobial phenotype, genomic features, population position, and larval pathogenicity of a human [...] Read more.

Background/Objectives: Streptococcus parasuis is an under-recognized member of the Streptococcus suis complex that can be misidentified by routine diagnostic methods. Human clinical isolates remain sparsely characterized. This study investigated the antimicrobial phenotype, genomic features, population position, and larval pathogenicity of a human pleural-fluid isolate. Methods: Strain HUGSPH was recovered during the care of a patient with pneumonia. Hybrid whole-genome sequencing (WGS), average nucleotide identity analysis, multilocus sequence typing (MLST), core-genome phylogenetics, comparative pan-genomics, and an exploratory host-origin association analysis were performed. Minimum inhibitory concentrations (MICs) were determined using the VITEK 2 Compact system with an AST-ST03 card, and virulence was evaluated in Galleria mellonella larvae. Results: Genome-based analysis confirmed HUGSPH as S. parasuis and assigned it to the novel sequence type (ST) 181. The isolate clustered within a predominantly human-origin phylogenetic clade. Because species-specific clinical breakpoints are unavailable, the MICs were interpreted provisionally using explicitly stated surrogate Clinical and Laboratory Standards Institute (CLSI) criteria; erythromycin, clindamycin, and levofloxacin were categorized as resistant under those criteria. Several predicted antimicrobial-resistance-associated genes were detected. In a restricted comparison of seven human-origin and nine swine-origin genomes, eight genes were present in all included human-origin isolates and absent from all included swine-origin isolates, whereas metQ, metP, and metN showed the reciprocal pattern. HUGSPH caused dose-dependent larval mortality, reaching 100% at 10⁷ colony-forming units (CFU) by 96 h. Conclusions: HUGSPH expands the genomic record of human clinical S. parasuis and highlights the diagnostic and surveillance relevance of antimicrobial resistance in this species. The susceptibility categories, source-associated genes, and larval phenotype require validation by reference susceptibility testing, broader phylogenetically balanced collections, comparative strains, and mammalian models. Full article

(This article belongs to the Special Issue Advances in Streptococcus spp. Research: Pathogenicity, Resistance, and Clinical Implications)

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19 pages, 11468 KB

Open AccessArticle

Physiological and Horticultural Responses of HLB-Affected ‘Valencia’ Orange Trees to Trunk-Injected Oxytetracycline and Streptomycin Formulations Differing in Adjuvant and pH

by Igor Silva, Jorge Pereira, Swadeshmukul Santra and Ute Albrecht

Antibiotics 2026, 15(9), 892; https://doi.org/10.3390/antibiotics15090892 - 11 Sep 2026

Abstract

Background/Objectives: Trunk injection of oxytetracycline (OTC) can suppress Candidatus Liberibacter asiaticus (CLas) and improve the productivity of citrus trees affected by huanglongbing (HLB), a devastating bacterial disease, but conventional acidic formulations may cause phytotoxicity and exacerbate trunk injury. This study evaluated [...] Read more.

Background/Objectives: Trunk injection of oxytetracycline (OTC) can suppress Candidatus Liberibacter asiaticus (CLas) and improve the productivity of citrus trees affected by huanglongbing (HLB), a devastating bacterial disease, but conventional acidic formulations may cause phytotoxicity and exacerbate trunk injury. This study evaluated a proprietary adjuvant intended to stabilize OTC at higher pH and assessed streptomycin (STM) as an alternative or complement to OTC. Methods: Two commercial field trials with HLB-affected ‘Valencia’ sweet orange trees compared a 2 × 4 factorial combination of two formulations, adjuvant/high-pH and no-adjuvant/low-pH, and four antibiotic treatments: none, OTC, STM, and OTC + STM. Tree growth, canopy health, phytotoxicity, CLas load, external wound responses, fruit drop, yield, and fruit quality were evaluated. Results: Tree growth and canopy health were not affected by treatment. The adjuvant/high-pH formulation caused severe canopy phytotoxicity in trial 1 and increased wound width, wound length, and bark cracking in both trials, compared to the control. OTC and OTC + STM generally reduced fruit drop, increased yield, and improved fruit quality attributes though effects on CLas were moderate and not consistent. STM alone provided no consistent therapeutic or horticultural benefit, and OTC + STM were not consistently superior to OTC alone. Conclusions: OTC was the primary effective component to mitigate HLB in affected citrus trees. The adjuvant/high-pH formulations did not affect OTC efficacy but caused tree injury, even in the absence of OTC. Novel trunk-injection formulations must balance chemical stability and delivery with plant tissue compatibility and safety to meet commercial viability. Full article

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15 pages, 4776 KB

Open AccessReview

Shiga Toxin-Producing Escherichia coli in Animal Reservoirs, Serotype Diversity, Virulence Profiles, and Antimicrobial Resistance Trends (2020–2026): A Scoping Review

by Katarzyna Kosznik-Kwaśnicka, Agnieszka Necel, Tomasz Jarzembowski and Lidia Piechowicz

Antibiotics 2026, 15(9), 891; https://doi.org/10.3390/antibiotics15090891 - 11 Sep 2026

Abstract

Background/Objectives: Shiga toxin-producing Escherichia coli (STEC) are important zoonotic pathogens associated with gastrointestinal infections and hemolytic–uremic syndrome (HUS). Increasing serotype diversity, emergence of hybrid strains, and growing antimicrobial resistance complicate surveillance and treatment. This review summarizes recent data on STEC isolated from [...] Read more.

Background/Objectives: Shiga toxin-producing Escherichia coli (STEC) are important zoonotic pathogens associated with gastrointestinal infections and hemolytic–uremic syndrome (HUS). Increasing serotype diversity, emergence of hybrid strains, and growing antimicrobial resistance complicate surveillance and treatment. This review summarizes recent data on STEC isolated from major animal reservoirs between 2020 and 2026. Methods: We comparatively analyzed peer-reviewed, open-access studies investigating STEC from cattle, sheep, goats, poultry, wildlife, and related animal products. We extracted and evaluated data on serotypes, virulence genes, hybrid pathotypes, and antimicrobial resistance determinants. Results: High serotype diversity was observed across all reservoirs, with non-O157 STEC frequently predominating over O157:H7. Ruminant isolates commonly carried stx2 and additional virulence determinants associated with severe human disease, confirming cattle and small ruminants as major reservoirs of highly pathogenic STEC. Poultry-associated isolates showed greater variability in virulence profiles but frequently exhibited high rates of multidrug resistance. Hybrid strains combining virulence traits characteristic of multiple E. coli pathotypes were increasingly reported. Livestock-associated STEC commonly carried resistance determinants against β-lactams, tetracyclines, sulfonamides, quinolones, and polymyxins, whereas wildlife isolates generally showed lower rates of resistance. Conclusions: Animal-associated STEC populations demonstrate increasing genomic diversity, pathogenic potential, and antimicrobial resistance. The growing prevalence of non-O157 and hybrid strains highlights the limitations of traditional serotype-focused surveillance and emphasizes the need for integrated One Health monitoring strategies. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Bacterial Isolates of Animal Origin)

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2 pages, 133 KB

Open AccessEditorial

Editorial: Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy

by Darko Modun

Antibiotics 2026, 15(9), 890; https://doi.org/10.3390/antibiotics15090890 - 11 Sep 2026

Abstract

Clinical guidelines for antimicrobial pharmacotherapy are crucial tools, built upon extensive research and expert consensus, designed to optimize the treatment of infections [...] Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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