Frontiers in antibiotics最新文献

Antimicrobial resistance (AMR) in poultry production poses a growing public health threat due to the emergence of multidrug-resistant (MDR) bacteria and the risk of transmission to humans through direct or indirect contact with these germs. In Tunisia, limited data on antibiotic use and veterinary prescribing practices hinder the development of effective AMR mitigation strategies, particularly in a sector with high antibiotic consumption. A cross-sectional study was conducted among veterinarian prescribers in avian medicine in Tunisia to assess their antibiotic prescribing behaviours and related practices and to evaluate their potential contribution to AMR emergence and spread. The most frequently reported first and second-line antibiotics were enrofloxacin (20/52 and 14/52), florfenicol (14/52 and 14/52), and doxycycline (7/52 and 6/52). Colistin (10/52) was the most used third-line antibiotic. These antibiotics were often administered without microbiological confirmation. Although 69% had access to accredited labs, 42% relied on rapid antimicrobial susceptibility tests (RASTs). Waste management practices were inadequate, with 50% disposing of biological waste in regular trash and 42% discarding expired antibiotics into the environment. Additionally, 77% reported frequent farmer self-medication. These findings highlight the urgent need for targeted training, improved surveillance, and the application of the One Health approach to tackle AMR in Tunisia's poultry sector.

Introduction: Clostridium perfringens strains may cause foodborne illness, and 95% of human infections are linked to the consumption of contaminated meat, including chicken products. In poultry, C. perfringens infection may cause necrotic enteritis, and infections are associated with high mortality rates partially due to antibiotic resistance, which hampers efficient treatment. In-vitro screening approaches of alternative treatment options, for instance, specific phages, represent a promising strategy for the selection of novel interventions to combat infections.

Material and methods: In this study, we explored the application of a C. perfringens strain LMG 11264-specific phage #7 introduced at 10⁴ pfu/mL to inhibit the growth of C. perfringens at 10⁶ cfu/mL compared to two antibiotics (amoxicillin at 10 µg/mL and clindamycin at 10 µg/mL) within complex chicken cecal microbiota in vitro. Samples for gDNA isolation, qPCR, and metagenome sequencing were taken at the beginning and after 24 and 48 h of incubation.

Results: The C. perfringens strain LMG 11264 proliferated within the untreated complex microbiota and reached levels of approximately 10⁸ and 10⁹ genome equivalents per mL after 24 and 48 h of incubation, respectively. The phage intervention with phage #7 inhibited the growth of C. perfringens LMG 11264 significantly; the inhibitory effects were similar to those exerted by the antibiotic intervention with amoxicillin and stronger than the inhibitory effects with clindamycin. In the absence of the C. perfringens challenge, we found a significant effect of amoxicillin (p = 0.040) or clindamycin (p = 0.000017) compared to the untreated control after 24 h of incubation, and the phage addition did not affect the alpha diversity expressed as Chao index significantly (p = 1). In addition, the endogenous C. perfringens in the chicken microbiota appeared insensitive to phage #7. The phage titer of phage #7 only increased in the presence of the inoculated C. perfringens strain LMG 11264. In conclusion, the i-screen model can be implemented to test the efficacy and specificity of phage therapy in vitro.

Background: Environmental coliform bacteria are frequently the cause of subclinical mastitis (SCM), a serious health issue in the dairy industry. Extended-spectrum β-lactamase (ESBL)-producing coliforms in livestock are a serious public health concern, particularly in environments where people and animals coexist. With an emphasis on their zoonotic and One Health implications, this study sought to evaluate the incidence of SCM and the occurrence of ESBL-producing coliforms in ruminants in Plateau State, Nigeria.

Methods: The California Mastitis Test (CMT) was used to screen 287 milk samples that were taken from cows, ewes, and does. Standard microbiological methods were used to identify the bacterial isolates from CMT-positive samples. The presence of resistance genes (bla _TEM and bla _CTX-M) was ascertained by PCR, and ESBL production was confirmed phenotypically. Phylogenetic analysis showed genetic diversity and possible horizontal gene transfer among isolates.

Results: Out of 287 milk samples, 79 (27.5%) had subclinical mastitis through the CMT, with a higher prevalence recorded in does 18(22.8%) while ewes and cows recorded 23(29.1%), and 38(48.1%) respectively. Of the 79 CMT-positive samples, the following isolates were identified: Citrobacter freundii (6.3%), Klebsiella pneumoniae (21.6%), K. oxytoca (2.5%), K. aerogenes (6.3%), and E. coli, being the most prevalent in cows (71%). Through PCR, 46 isolates expressed two important ESBL genes, bla _TEM and bla _CTX-M.

Conclusion: A possible zoonotic reservoir for antibiotic resistance in Nigeria is highlighted by the increased frequency of ESBL-producing coliforms in ruminants with SCM. These results highlight the necessity of implementing integrated One Health initiatives, such as public education, surveillance, and antimicrobial stewardship, in order to reduce the risk of resistant pathogen transmission from animals to people.

The development of medical countermeasures against pathogens of biodefense concern remains critical to protecting military and public health. This review compares data detailing antibacterial activity and efficacy for a selection of antibiotics evaluated against potential bacterial biothreat pathogens. The human safety and tolerability of these formulations were also considered. This review includes finafloxacin, levofloxacin, delafloxacin, omadacycline, gepotidacin, tebipenem and sulopenem. The selection criteria of these antibiotics were 1) the availability of an oral formulation, 2) the regulatory status (licensed by a regulatory authority or in an advanced stage of development) and 3) the availability of publicly available information on the biodefence pathogens of concern. We hope to highlight approved or advanced clinical candidates that have significant and unique potential in the biodefense space which may be deployed to protect both the public and warfighter against these bacterial infections.

Background: Rising antimicrobial resistance (AMR) necessitates innovative metrics, such as days of antibiotic spectrum coverage (DASC), to optimize antibiotic stewardship. This study evaluated antibiotic use in an Indian trauma center using DASC, defined daily doses (DDD), and the World Health Organization (WHO) Access, Watch, Reserve (AWaRe) classification.

Methods: This retrospective cohort study analyzed data from 1,812 adult inpatients (mean age: 35 years; 70% male; 80% with polytrauma) admitted to a 250-bed Level-1 Trauma Center at the All India Institute of Medical Sciences (AIIMS), India, from August to October 2022. We measured days of therapy (DOT), DDD, and DASC for 46 antibiotics across 12 pathogens [e.g., methicillin-susceptible Staphylococcus aureus (MSSA), carbapenem-resistant Enterobacteriaceae]. DASC scores were developed through expert consensus and local antibiogram data, and validated using Pearson's correlation with DOT (R = 0.43, p < 0.1) and DDD (R = 0.21). Differences in antibiotic usage between the ICU and ward were analyzed using a t-test in R software.

Results: Total antibiotic consumption was 81,064.6 g (3,142 DDD/1,000 patient-days). The Watch group antibiotics dominated usage (37%, 16,018.6 g), resulting in a low Access-to-Watch ratio (0.47). ICU settings showed higher DDD values (326 vs. 193/1,000 patient-days, p < 0.05) and DASC/DOT ratios (mean: 3; 95% CI: 2.73-4.01). Piperacillin-tazobactam accounted for the largest share of the Watch category use (5,952.9 g). DASC values (mean 4401.5, 95% CI: 3592-5211.1) showed a moderate correlation with DOT (R = 0.43, p < 0.1), offering spectrum-specific insights.

Conclusions: Excessive use of the Watch group antibiotics contributes significantly to AMR. However, DASC's novel, spectrum-focused approach offers a transformative tool for antibiotic stewardship, supporting targeted de-escalation and improved benchmarking. These findings underscore the urgent need for policy reforms to enforce adherence to the WHO AWaRe classification in Indian centers, potentially reducing AMR-related mortality (30% higher with resistant infections). Integrating DASC into global Antimicrobial stewardship (AMS) programs may redefine antibiotic prescribing practices and help mitigate the AMR crisis.

Background: Antibiotic resistance (ABR) to commonly used antibiotics is significant in sub-Saharan Africa (SSA). In SSA, Chad has one of the highest antimicrobial resistance (AMR) rates. The link between ABR and antibiotic consumption (ABC) is well-established. However, no ABC-related studies have been conducted in Chad recently. The purpose of this study is to examine the trajectory of ABC in Chad from 2017 to 2021, using the World Health Organization's (WHO) Access, Watch, and Reserve (AWaRe) antibiotic classification.

Methods: A descriptive retrospective study was conducted in N'Djamena, using antibiotic import and distribution data collected from the General Directorate of Pharmacy and four wholesale distributors of medicines. The defined daily doses (DDDs) and the mean relative change (MRC) were used to compute the results. Results were presented in terms of tables and graphs. The results were compared to the WHO's guidelines for ABC use via the AWaRe categorization.

Results: Between 2017 and 2021, an average ABC of 2.5 doses per inhabitant per year was observed, peaking in 2020 at 5.3 doses per inhabitant. In terms of DDD, the ten most commonly consumed antibiotics during the time, in descending order, were amoxicillin, ampicillin, sulfamethoxazole/trimethoprim, doxycycline, ciprofloxacin, phenoxymethyl-penicillin, erythromycin, ceftriaxone, azithromycin, and gentamicin. However, the MRC analysis detected an increase in benzathine benzyl penicillin, benzylpenicillin, ampicillin, amoxicillin+clavulanic acid, flucloxacillin, ceftriaxone, cefixime, cefpodoxime and cefalexin, cotrimoxazole, ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, and azithromycin. Controversially, amoxicillin, cefotaxime, doxycycline, erythromycin, and moxifloxacin had a lower MRC from 2017 to 2021. Although 90% of the ABC are from the "Access" group, the "Watch" group has increased over time.

Conclusions: Our findings indicated a significant ABC in the Chadian population from 2017 to 2021, which may elucidate the country's elevated ABR. On average, 90% of ABC were categorized in the "Access" group, although utilization of the Watch group increased over time. This requires the prompt implementation of the monitoring system for ABC at all tiers in Chad.

Introduction: Antimicrobial resistance (AMR) can spread in microorganisms through the transfer of antimicrobial resistance genes (ARGs). Livestock husbandry is one of the pathways for AMR emergence and transmission. Chicken manure contains valuable nutrients for agricultural field fertilization and can be used as input material for biogas production by anaerobic digestion (AD). However, usually, chicken manure also contains quite high levels of ARGs. In this study, we investigated the presence and temporal dynamics of ARGs against different antibiotic classes in chicken manure and anaerobic digestate as a source of AMR spread.

Methods: To get an overview of the ARG profiles, we quantified the abundances of 374 ARGs by high-throughput (HT)-PCR. We studied eight selected ARGs (tetA, tetX, sul1, sul2, lnuF, emrD, aadA, and tnpA) using qPCR in chicken manure from different flocks and animal ages and in digestate from different AD time points.

Results: Chicken manure showed higher amounts of ARGs compared to digestate, which was characterized by a higher ARG diversity. We observed that the effect of chicken age differed between the flocks. ARG abundances in digestate from different time points and different treatment conditions did not exhibit major changes.

Conclusion: The flocks' variability had no relevant effect on ARG abundances in chicken manure, likely due to similar growth conditions. However, manure ARG content increased with the age of the chickens. In our experimental batch setup, AD was more effective in reducing AMR microorganisms than reducing ARGs. Further investigations on process optimization or the application of pre-treatment methods could enhance ARG reduction. Notably, pre-mixing chicken manure with material from a biogas plant prior to processing resulted in a lower ARG load compared to untreated chicken manure.

Background: Antibiotic-resistant bacteria are becoming a significant global concern. To combat the spread of resistance or reverse multidrug resistance, developing novel antimicrobials and/or resistance modulators is essential. This study aimed to evaluate the synergistic effects of the methanolic extract of Pandanus fascicularis fruits (MEPFF) in combination with azithromycin against multidrug-resistant bacteria.

Methods: Phytochemical analysis along with the determination of total phenolic content (TPC), total flavonoid content (TFC), and total antioxidant capacity (TAC) of MEPFF, was performed using standard procedure. The extract's DPPH free radical scavenging activity was assessed to evaluate its potential antioxidant activity. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MEPFF against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa were determined, followed by an analysis of the synergistic effect with azithromycin, as well as the activity of azithromycin alone. Subsequently, the drug-likeness, antibacterial activity, and toxicological properties were analyzed using in silico tools.

Results: The quantitative investigation found terpenoids, flavonoids, tannins, phenolics, saponins, cardiac glycosides, and alkaloids in MEPFF. The TFC, TPC, and TAC of MEPFF were found at 183 ± 9.54 mg QE, 248.33 ± 11.06 mg GAE, and 95.33 ± 8.33 mg AAE/gm extract. The extract showed significant antioxidant activity in the DPPH experiment, with an IC50 value of 12.13±0.53 µg/ml. Azithromycin and the extract together have far greater antibacterial action against all four bacterial strains. The minimal inhibitory concentration (MIC) is 3.67 ± 1.15 to 5.83 ± 0.76 mg/mL, while the minimum bactericidal concentration (MBC) is 4.33 ± 1.26 to 7.33 ± 1.04 mg/mL. In silico studies revealed that pandamarilactone-1, nonpandamarilactone-B, and thiamine had the best docking energy (-9.9, -8.9, and -8.5 kcal/mol), suggesting most active compounds against MPh-II protein.

Conclusion: The extract enhances antibiotic therapy and suggests that the aforesaid synergistic drug-herb combinations may treat MDR bacterial infections.

Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB patients for risk of all-cause mortality, relapse, or lung damage, no evidence was found on TB-associated cancer or cardiovascular disease. In addition to monitoring microbiologic outcomes, clinical trials and treatment cohorts need to capture patient-centered health dimensions more broadly. Finally, we highlight key research gaps and opportunities to evaluate non-microbiological biomarkers, aiming to improve patient monitoring and enable stratified approaches to tuberculosis management.