Antimicrobial Susceptibility Profiles of Commensal spp. Isolates from Chickens in Hungarian Poultry Farms Between 2022 and 2023
Antimicrobial resistance is one of the greatest challenges of our time, urging researchers in both veterinary and public health to engage in collaborative efforts, thereby fostering the One Health approach. Infections caused by species can not only lead to significant diseases in poultry but also pose serious threats to human life, particularly in hospital (nosocomial) infections; therefore, it is crucial to identify their antimicrobial resistance.
The Introduction of the Global Traditional, Complementary, and Integrative Healthcare (TCIH) Research Agenda on Antimicrobial Resistance and Its Added Value to the WHO and the WHO/FAO/UNEP/WOAH 2023 Research Agendas on Antimicrobial Resistance
: Given the magnitude and urgency of the global antimicrobial resistance (AMR) problem and the insufficiency of strategies to reduce antimicrobial use, there is a need for novel strategies. Traditional, Complementary, and Integrative Healthcare (TCIH) provides strategies and solutions that contribute to reducing (inappropriate) antimicrobial use, preventing or treating infections in both human and veterinary medicine, and may contribute to promoting the health/resilience of humans and animals and reducing AMR. The aims of this study were to present the core results of a global TCIH research agenda for AMR and its added value to two existing global AMR research agendas published in 2023. : A survey, interviews, and consensus meetings among network members, as an adapted version of the nominal group technique, were executed to develop the global TCIH research agenda. A comparison of the global TCIH research agenda with the two existing global AMR research agendas was performed. The TCIH additions to these two existing global AMR research agendas were determined. : The global TCIH research agenda adds to 19 of 40 research priorities of the World Health Organization (WHO) AMR research agenda 2023 and three of the five pillars of the WHO/Food and Agriculture Organization of the United Nations (FAO)/United Nations Environment Programme (UNEP)/World Organisation for Animal Health (WOAH) research agenda 2023. In addition, the TCIH research agenda adds two new research themes with four new research priorities and three new research priorities to already existing themes of the two global AMR research agendas. : The global TCIH research agenda fits with and adds to two global AMR research agendas and can be used as an additional strategy to reduce AMR and (inappropriate) use of antibiotics.
Antibiotic Prescription Practice and Resistance Patterns of Bacterial Isolates from a Neonatal Intensive Care Unit: A Retrospective Study from Jordan
: Neonatal sepsis is a systemic inflammation in neonates caused by bacteria, viruses, or fungi that can progress into severe conditions. In developing countries, neonatal sepsis is a major cause of mortality and a major public health issue with a high prevalence. This study aims to evaluate the antibiotic prescription practice and resistance patterns of bacterial isolates from the neonatal intensive care unit (NICU) at the largest governmental hospital in Amman, Jordan. : This was a retrospective cross-sectional study. The antibiotic prescription practice and resistance patterns of bacterial isolates from the NICU at Al Basheer Government Hospital in Amman, Jordan, were evaluated. The hospital's microbiology lab database and medical records were the sources of the retrospective data collection. : A total of 266 neonates treated with antibiotics were assessed. The findings showed that most neonates had late-onset sepsis (LOS) (65.4%). The penicillin group of antibiotics (ampicillin) was the most highly prescribed first empiric antibiotic for LOS and early-onset sepsis (EOS) (61.7%). Aminoglycosides (60.9%) were the most prescribed antibiotics as a second empiric treatment for EOS and LOS. The culture results showed that resistance to antibiotics was as follows: 15.4% of the culture samples were resistant to penicillin ( and ), 13.9% were resistant to cefotaxime ( and ), 13.2% were resistant to cefoxitin ( and ), and 12.4% were resistant to oxacillin ( and ). : This retrospective study sheds light on the antibiotic prescription practice and resistance patterns of bacterial isolates from newborns with sepsis. The results highlight the high rates of antibiotic resistance. These findings underline the urgent need for improved antibiotic stewardship and infection control strategies to prevent resistance from spreading further.
A VersaTile Approach to Reprogram the Specificity of the R2-Type Tailocin Towards Different Serotypes of and
Phage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the target range of a selected R2 tailocin from , the process is labor-intensive, limiting broader application. We introduce a VersaTile-driven R2 tailocin engineering and screening platform to scale up RBP grafting. This platform achieved three key milestones: (I) engineering R2 tailocins specific to serogroups O26, O103, O104, O111, O145, O146, and O157; (II) reprogramming R2 tailocins to target, for the first time, the capsule and a new species, specifically the capsular serotype K1 of and K11 and K63 of ; (III) creating the first bivalent tailocin with a branched RBP and cross-species activity, effective against both K1 and K11. Over 90% of engineered tailocins were effective, with clear pathways for further optimization identified. This work lays the groundwork for a scalable platform for the development of engineered tailocins, marking an important step towards making R2 tailocins a practical therapeutic tool for targeted bacterial infections.
Evaluation of Cinnamon Essential Oil and Its Emulsion on Biofilm-Associated Components of Clinical Strains
, one of the most dangerous pathogens, is able to form biofilm structures and aggravate its treatment. For that reason, new antibiofilm agents are in need, and new sources of antibiofilm compounds are being sought from plants and their products. Cinnamon essential oil is associated with a wide spectrum of biological activities, but with a further improvement of its physicochemical properties it could provide even better bioavailability. The aim of this work was the evaluation of the antibiofilm properties of cinnamon essential oil and its emulsion.
Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children
Clindamycin resistance among community-associated methicillin-resistant (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children's hospital.
Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes
The increasing prevalence of drug-resistant tuberculosis (TB) underscores the urgent need for novel antimicrobial agents.
Thromboelastometry-Based Profiling of Haemostatic Alterations in Neonatal Sepsis by Causative Pathogens
: Neonatal sepsis is a serious condition with high mortality, especially in premature and low-birth-weight neonates. This study aims to examine whether the haemostatic profile of neonates with sepsis defers depending on the type of bacteria (Gram-positive or Gram-negative), by using the method of Rotational Thromboelastometry (ROTEM). : This single-centre prospective cohort study was conducted on 128 neonates with sepsis, including 95 cases caused by Gram-negative pathogens and 33 cases caused by Gram-positive bacteria. All participants were hospitalised in the Neonatal Intensive Care Unit (NICU). ROTEM parameters were compared between neonates with Gram-positive and Gram-negative infections. : The ROTEM parameters were found to be significantly different between neonates suffering from Gram-positive versus Gram-negative infections, with Gram-positive pathogens associated with an increased clotting potential compared to Gram-negative pathogens. This is reflected in the higher ROTEM values such as A10, α-angle, and MCF in the EXTEM and INTEM assays. Multivariant analysis showed that Gram-positive infections were linked to increased clot thickness at 10 min (coefficient: 8.9, CI: 2.8-15.0, = 0.004), higher maximum clot stability (coefficient: 10.4, CI: 4.3-16.6, = 0.001), and a bigger α-angle (coefficient: 8.0, CI: 2.7-13.2, = 0.003). Similar findings were observed in the INTEM assay parameters. : Neonatal sepsis caused by Gram-positive bacteria leads to a hypercoagulable haemostatic state, whereas neonates with sepsis caused by Gram-negative bacteria exhibit a more hypocoagulable profile and a higher incidence of haemorrhagic episodes. These findings provide valuable insights into the haemostatic disorders associated with sepsis, and may aid in developing an individualised approach for the treatment of those disorders, dependent on and adapted for the specific type of causative organism.
Oral Antibacterial Drug Prescribing in Primary Care Out-of-Hours Services: A Scoping Review
The rapid spread of antimicrobial resistance (AMR) presents a critical threat to global health. Primary care plays a significant role in this crisis, with oral antibacterial drugs among the most prescribed medications. Antibacterial prescribing rates are often high and complicated in out-of-hours (OOH) services, including weekdays outside regular hours, weekends, and holidays, potentially exacerbating AMR. This review aims to identify the existing literature on oral antibacterial drug prescribing within primary care OOH services.
Antibiotic Residues in Animal Products from Some African Countries and Their Possible Impact on Human Health
This review investigates the levels of antibiotic residues in animal products, types of antibiotics, and their possible impact on human health in Africa. The literature search involved the use of a systematic survey using data that were published from Africa from 2015 to 2024. The search terms used the Boolean operators with keywords such as antibiotics, antibiotic residues, antibiotics in animal products in Africa, and impact on human health. Only research conducted in Africa was used in the present study. The findings showed that the most prevalent groups of antibiotic residues were aminoglycoside, macrolides, β-lactams, fluoroquinolones, tetracyclines sulfonamides, and phenicols. Tetracycline showed the most prevalent antibiotic residue with 43% mostly from East Africa, followed by sulfonamides at 19%, and β-lactams at 16%; most of the antibiotic residue levels were higher than the World Health Organization permissible limit. Noncompliance with withdrawal periods and maximum residue limits for antibiotics used in food-producing animals may lead to negative outcomes such as allergic reactions, teratogenicity, carcinogenicity, microbiome alterations, and, most notably, antibiotic resistance. As a result, there is a need for constant monitoring of antibiotic residues in animal products in addition to the consideration of alternatives to antibiotics in order to avoid their health implications.
Evaluation of Antimicrobial Performance of Calcium Dihydroxide (Ca(OH)) Coating on Ti for Potential Metallic Orthopedic Implant Applications
Orthopedic implant infections are rare but represent a significant problem for patients, surgeons, and the healthcare systems. This is because these infections cause severe and persistent pain and, in some cases, may require revision of the implant, among other things. Thus, there is strong interest in the use of antimicrobial coatings on orthopedic implants. Here, we investigate electrochemically deposited Ca(OH) antimicrobial coating for its potential to be used on metallic orthopedic implants. A triphenyl tetrazolim chloride (TTC) assay and isothermal microcalorimetry (IMC) were used to determine the reduction in microbial activity on three sets of Ti parts (discs and screws): uncoated, coated with hydroxyapatite (HA), and coated with Ca(OH). Using the TTC assay, a ~70% reduction in the growth of bacteria on Ca(OH)-coated discs was found, and using IMC, bacterial growth on these discs showed a decreased rate and an increased lag phase up to 25 h. Each of these sets of results was statistically superior to the corresponding results obtained using the other sets of parts. The present results suggest that the Ca(OH) coating may have potential for use on metallic orthopedic implants.
RETRACTED: Kanan et al. Empowering Low- and Middle-Income Countries to Combat AMR by Minimal Use of Antibiotics: A Way Forward. 2023, , 1504
The journal retracts the article "Empowering Low- and Middle-Income Countries to Combat AMR by Minimal Use of Antibiotics: A Way Forward" [...].
Chemical Characterization and Antimicrobial Activity of Essential Oils and Nanoemulsions of and
This study aimed to develop gel nanoemulsions (NEs) of Brazilian essential oils (EOs) from and , as well as to perform chemical characterization and investigate the antimicrobial activity of the EOs and NEs. : The main chemical compounds of EO were curzerene (34.80%) and germacrene B (11.92%), while those of EO were β-caryophyllene (25.92%), β-selinene (22.64%), and γ-selinene (19.13%). The NEs of and had droplet sizes of 105.30 and 99.50 nm and polydispersity index (PDI) values of 0.32 and 0.43, respectively. The NEs remained stable for 30 days of storage at 25 °C, with droplet sizes of 104.7 and 103.8 nm, PDI values below 0.50, and no phase separation. The NE of exhibited inhibition zones ranging from 8.41 to 15.13 mm against the Gram-positive bacterium and the Gram-negative bacteria , , and . Additionally, the NE of showed the largest inhibition zones against (20.97 mm) and (15.20 mm), along with low minimum inhibitory concentration (MIC) values (0.54-1.22 mg/mL) and minimal bactericidal concentration (MBC) values (4.84-11.02 mg/mL) against these pathogenic yeasts. The NE of demonstrated low MIC (1.26 mg/mL) and MBC (11.35 mg/mL) values for . The time-growth inhibition assay also suggests the effectiveness of the NE against the tested pathogens and , highlighting its potential as a novel alternative therapeutic agent.
PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance
Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects. First, we discuss the importance of drug concentration management for enhancing efficacy while preventing toxicity, considering various patient populations, including pediatric and elderly patients with their unique physiological characteristics. Second, we analyze different PK modeling approaches: the classic top-down approach exemplified by population PK analysis, the bottom-up approach represented by physiologically based PK modeling, and hybrid models combining both approaches for enhanced predictive performance. Third, we explore clinical applications, including nomogram-based dosing strategies, Bayesian estimation, and emerging artificial intelligence applications, for real-time dose optimization. Critical challenges in implementing PK/PD simulation are addressed, particularly the selection of appropriate PK models, the optimization of PK/PD indices, and considerations concerning antimicrobial concentrations at infection sites. Understanding these principles and challenges is crucial for optimizing antimicrobial therapy and combating AMR through improved dosing strategies.
Antimicrobial Resistance Genes in Clinical Strains from Livestock and Poultry in Shandong Province, China During 2015-2020
Antimicrobial resistant (AMR) () isolated from animals may lead to antibiotic treatment failure and economic losses to farmers. The co-existence of antimicrobial resistant genes (ARGs) in the same isolate presents a major challenge for the prevention and control of infection in multidrug-resistant (MDR) Gram-negative organisms. There have been a lot of studies on the antibiotic resistance of in livestock and poultry, but few of them have focused on clinical pathogens. The aim of this study was to explore the genetic characteristics, co-occurrence, and correlations between ARGs of isolated from the pathological tissues of livestock and poultry in Shandong Province, East China during 2015-2020. A total of 158 strains were collected and subjected to antimicrobial susceptibility testing and sequencing by whole-genome Next Generation Sequencing (NGS). MDR strains accounted for 46.20% of the 158 strains with the highest resistant rate of ciprofloxacin (71.52%). In addition, strains with and were found in chickens, while three strains with were found in pigs. In addition, the most common serotypes detected were the O serotype (76/158) and H serotype (36/158). Moreover, seventy-one STs were found and the most common STs were ST10 (6.33%), ST155 (6.33%), and ST101 (5.69%). The genetic environment analysis of the phylogroups revealed that belonging to phylogroup B1, phylogroup A, and phylogroup C constituted 39.87%, 27.85%, and 15.19%, respectively. Through the correlation analysis, genes were observed to have certain relationships with ARGS such as , , , and . This study demonstrates the high prevalence and gene diversity of MDR isolated from a clinic in Shandong Province, East China. We predicted the transmission risk of animal-borne -bearing and -harboring to public health and provided insight into the relationship of co-existence or co-transfer between with ARGS. These relationships present a great challenge for the infection control of MDR Gram-negative organisms.
Sources and Transmission Routes of Carbapenem-Resistant : Study Design and Methodology of the SAMPAN Study
: The global spread of carbapenem-resistant (CRPA) warrants collaborative action. Guidance should come from integrated One Health surveillance; however, a surveillance strategy is currently unavailable due to insufficient knowledge on the sources and transmission routes of CRPA. The aim of the SAMPAN study ("A Smart Surveillance Strategy for Carbapenem-resistant ") is to develop a globally applicable surveillance strategy. : First, an international cross-sectional study will be conducted to investigate CRPA in clinical and environmental settings in Rotterdam (The Netherlands), Rome (Italy), and Jakarta (Indonesia). Screening cultures and risk factor questionnaires will be taken from healthy individuals and patients upon hospital admission. Clinical CRPA isolates will also be included. Additionally, samples will be taken twice from wet hospital environments and monthly from the hospitals' (drinking) water system, hospital and municipal wastewater treatment plants, and receiving rivers. Whole-genome sequencing will be performed to characterize CRPA isolates and determine the genetic relatedness among the isolates from different reservoirs. Findings from the cross-sectional study, combined with expert elicitation using a Delphi method, will serve as the input for the surveillance strategy. : The SAMPAN study will provide a broader understanding of the sources and transmission routes of CRPA. Therewith, the development of a globally applicable smart surveillance strategy will be made possible, delivering information that is needed to guide actions against the spread of CRPA.
Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility
Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. Recent studies investigating antimicrobial susceptibility in mammalian cell culture media, a more host-mimicking environment, demonstrate that exposure to host factors significantly alters susceptibility profiles. One such factor is bicarbonate, an abundant ion in the mammalian bloodstream/tissues. Importantly, bicarbonate sensitizes methicillin-resistant (MRSA) to early-generation β-lactams used for the treatment of methicillin-susceptible (MSSA). This "NaHCO-responsive" phenotype is widespread among US MRSA USA300/CC8 bloodstream and skin and soft tissue infection isolates. Translationally, β-lactam therapy has proven effective against NaHCO-responsive MRSA in both ex vivo simulated endocarditis vegetation (SEV) and in vivo rabbit infective endocarditis (IE) models. Mechanistically, bicarbonate appears to influence expression and PBP2a production/localization, as well as key elements for PBP2a functionality, including the PBP2a chaperone PrsA, components of functional membrane microdomains (FMMs), and wall teichoic acid (WTA) synthesis. The NaHCO-responsive phenotype highlights the critical role of host factors in shaping antibiotic susceptibility, emphasizing the need to incorporate more physiological conditions into AST protocols.
Bacteriocin-Producing Staphylococci and Mammaliicocci Strains for Agro-Food and Public Health Applications with Relevance of Micrococcin P1
Antimicrobial-producing strains and their bacteriocins hold great promise for the control of bacterial diseases, being an attractive alternative to antibiotics. Thus, the aim of this study was to evaluate the inhibitory activity of 15 bacteriocin-producing staphylococci and mammaliicocci (BP-S/M) strains and their pre-purified extracts with butanol (BT) against a collection of 27 harmful or zoonotic strains (including Gram-positive/-negative bacteria and molds) with relevance in the public health and agro-food fields. These indicators (excluding Gram-negative strains) were grouped into seven categories based on their potential application areas: dairy livestock mastitis, avian pathogen zoonoses, swine zoonoses, food safety, aquaculture, wine making, and mushroom cultivation. In addition, cross-immunity assays between the BP-S/M strains were carried out to identify potential strain combinations to enhance their activity against pathogens. Finally, the hemolytic and gelatinase activities were tested in the BP-S/M strains. A strong inhibitory capacity of the BP-S/M strains was verified against relevant Gram-positive indicators, such as methicillin-resistant , , and , among others, while no activity was detected against Gram-negative ones. Interestingly, several BT extracts inhibited the two mold indicators included in this study as representants of mushroom pathogens. The Micrococcin P1 producer C5835 (>60% of indicators were intensively inhibited by all the methods) can be proposed as a potential candidate for the control of bacterial diseases in the aforementioned categories alone or in combination with other BP-S/M strains (mainly with X2969). In this regard, five potential combinations of BP-S/M strains that enhanced their activity against specific pathogens were detected.
The Prevalence and Risk Factors Associated with the Presence of Antibiotic Residues in Milk from Peri-Urban Dairy Cattle Farms in Kathmandu, Nepal
The presence of antibiotic residues (ARs) in animal products such as milk can be an important driver of antimicrobial resistance in commensal and pathogenic bacteria. Previous studies on ARs in Nepal have demonstrated the presence of ARs in milk samples but without further characterization of the samples for risk factor analysis. This study aimed to quantify the prevalence and risk factors for the presence of ARs in 140 peri-urban dairy farms in Kathmandu, Nepal, included in a cross-sectional survey in 2019 to estimate farm-level AR prevalence. Our results reveal the presence of ARs of sulfamethazine (61%), sulfamethoxazole (53%), ciprofloxacin (46%), and enrofloxacin (42%). Furthermore, of those samples positive for sulfamethazine, sulfamethoxazole, and ciprofloxacin, 81%, 42%, and 42%, respectively, exceeded the maximum residue limit (MRL). While samples taken from farms where staff administered antibiotics were less likely to have single drug residues and multidrug residues (two, three, and four drugs), farms with more workers were more likely to have single residues. Moreover, samples from farms with a higher number of calves and milking cows were more likely to contain single and multiple residues exceeding the MRL, while milk from farms with higher numbers of dry cows and farmers reported by a visiting chemist were less likely to have multidrug residues exceeding the MRL. High-performance liquid chromatography was conducted on bulk milk samples from farms for an AR analysis, revealing positive results. Additionally, a structured questionnaire and direct farmer interviews were used to collect data on farm biosecurity and farming practices, animal health and hygiene, antibiotic usage (AMU), and attitudes and practices towards antibiotic stewardship. Ultimately, this study provides evidence on the role of modifiable ARs risk factors in the peri-urban milk industry of Kathmandu, which can serve as a foundation for developing improved antimicrobial stewardship guidelines and designing intervention measures to reduce the public health risk posed by ARs in milk sold in Kathmandu, Nepal.
Pharmacodynamic Profiling of Amoxicillin: Targeting Multidrug-Resistant Gram-Positive Pathogens and in Canine Clinical Isolates
The rising threat of antimicrobial resistance (AMR) is a global concern in both human and veterinary medicine, with multidrug-resistant (MDR) pathogens such as and presenting significant challenges. : This study evaluates the effectiveness of amoxicillin against these MDR pathogens in canine isolates using pharmacokinetic and pharmacodynamic parameters. : Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and mutation prevention concentration (MPC) were assessed. Additionally, time-kill assays and post-antibiotic effect (PAE) assessments were performed. Epidemiological cutoff (ECOFF) values were established for both species to guide therapy. : had a higher resistance rate (35.89%) than (15.27%), with MIC50 values of 0.50 μg/mL and 0.25 μg/mL, respectively. The MPC analysis revealed that required higher antibiotic concentrations (16.11 μg/mL) to prevent mutations compared to (2.20 μg/mL). Time-kill assays indicated that higher amoxicillin dosages caused faster bacterial reduction. The PAE analysis showed extended post-treatment bacterial suppression at elevated doses, particularly against . : Species-specific amoxicillin dosing strategies are necessary due to differing resistance and susceptibility profiles between and . High-dose amoxicillin therapy is recommended to achieve optimal therapeutic outcomes for resistant SA, while slightly adjusted dosing can manage infections. These findings provide essential insights for veterinary antimicrobial stewardship, underscoring the need for tailored therapeutic approaches to minimize AMR development while ensuring effective infection control.
Correction: Kirkegaard-Biosca et al. Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria. 2024, , 874
[...].