Antibiotics-Basel最新文献

Background: Antimicrobials are crucial for animal health and food security. However, their overuse in animals can lead to the emergence of resistant microorganisms. Antimicrobial resistance (AMR) poses a global public health threat that impacts both animal and human health. The objective of this study was to estimate the antimicrobial consumption (AMC) of veterinary antimicrobials at the national level using import data from January to December 2021, available from the Uganda National Drug Authority (NDA).

Methods: The World Organization for Animal Health (WOAH) methodology was applied using the Anatomical Therapeutic Chemical classification codes for veterinary medicines.

Results: Approximately 88,387.37 kg (88.39 tonnes) of veterinary antimicrobials were consumed in 2021. Parenteral veterinary antimicrobials accounted for 63.8% (56,375.65 kg) and oral veterinary antibacterials accounted for 36.2% (32,011.71 kg). Tetracyclines were the single most consumed veterinary antimicrobial class, accounting for 62.7% of total consumption. Oxytetracycline was the most consumed antibacterial (58.4%), followed by sulphadiazine + trimethoprim (11.1%), penicillin g/dihydrostreptomycin (7.4%), penicillin G procaine + dihydrostreptomycin (6.8%), and tetracycline (3.5%), respectively. Out of all imported veterinary antimicrobials, 76% belonged to the World Health Organization (WHO)'s Highly Important Antimicrobials (HIA) category, 16% to the Critically Important (CIA), and 9% to the Highest Priority Critically Important (HPCIA) categories. Imported colistin accounted for 0.1% of total veterinary consumption.

Conclusions: This study contributes to understanding antimicrobial consumption in Uganda's livestock sector and, for the NDA, leaves in place a system for routine surveillance at a national level. We recommend strict regulatory oversight on the importation and use of colistin and macrolides to address AMR.

Background/Objectives: Pasteurella multocida commonly colonizes the bovine respiratory tract and can occasionally cause intramammary infections. Here, eight P. multocida isolates from clinical cases of bovine mastitis were investigated for their molecular characteristics as well as phenotypic and genotypic antimicrobial resistance (AMR) properties. Methods: The isolates originated from quarter milk samples obtained in Germany for diagnostic purposes. Antimicrobial susceptibility testing (AST) by broth microdilution was performed according to the Clinical and Laboratory Standards Institute. Closed whole-genome sequences were generated by hybrid assembly of Illumina MiSeq short-reads and Oxford Nanopore MinION long-reads, followed by consecutive sequence analysis. Results: The P. multocida isolates belonged either to capsular:lipopolysaccharide type A:3 (n = 7) or A:6 (n = 1), and multi-locus sequence types 1 (n = 7) or 7 (n = 1). Seven isolates carried AMR genes, such as mef(C), mph(G), strA, strB, aphA1, aadA31, tet(H), tet(Y), floR, catA3, and sul2, as part of an integrative and conjugative element (ICE). These mobile genetic elements, 58,382-78,401 bp in size, were highly similar to the ICEs Tn7406 or Tn7407 that have been previously described in bovine Mannheimia haemolytica and P. multocida, respectively. Moreover, the isolates showed elevated minimal inhibitory concentrations corresponding to the identified AMR determinants. Conclusions: Molecular typing and ICE organization suggest the bovine respiratory tract as reservoir of the investigated mastitis-associated P. multocida. Horizontal cross-genus transfer of multidrug-resistance-mediating ICEs seems to occur under in vivo conditions among different pathogens from cattle in Germany, which underlines the importance of pathogen identification followed by AST for successful bovine mastitis therapy.

Background: Bloodstream infections affect up to 20% of pediatric cancer patients receiving intensive care, contributing significantly to morbidity and mortality, with infection-related mortality rates reported to be as high as 16%.

Methods: The identification of microorganisms directly from whole blood is difficult due to several factors, such as interference from host genomic material, low bacterial load, the endogenous components of whole blood and exogenous substances, which can interfere with the identification process. Nevertheless, rapid microbial diagnosis remains of paramount importance in these patients.

Results and conclusion: Here, we present the first case of bacterial pathogen identification directly from whole blood using MALDI-TOF mass spectrometry in an onco-hematological pediatric patient affected by sepsis and admitted to Bambino Gesù Children's Hospital (IRCCS) in Rome, Italy.

Clostridioides difficile (C. difficile), once considered a predominantly nosocomial pathogen, is increasingly implicated in community-acquired infections (CA-CDIs). This study investigates the prevalence, ribotypes, and antimicrobial susceptibility of C. difficile in Irish pork products and abattoirs, with a focus on the potential public health implications. A total of 180 retail pork products and 150 pig carcase swabs from three abattoirs were examined, alongside 30 environmental lairage samples. The C. difficile isolates were characterised through ribotyping and tested in terms of antimicrobial susceptibility. No C. difficile was isolated from the retail pork, while the carcase swabs yielded a low recovery rate (0.66%). However, the lairage areas were contaminated with C. difficile (33%), and six different ribotypes were identified, including the clinically relevant RT078. The ribotypes exhibited susceptibility to the antibiotics used to treat C. difficile infection (CDI) (fidaxomicin, vancomycin, and metronidazole) but showed resistance to tetracycline (9%) and ciprofloxacin (100%). These findings align with the international findings on antimicrobial resistance in C. difficile and suggest that strict EU food safety standards could mitigate retail pork contamination risks. Nevertheless, the environmental exposure during slaughtering and handling processes presents potential transmission risks for workers.

Background: Approximately 71% of antibiotics in England are prescribed in general practice settings. Whilst there are various impactful training resources available to support clinicians in antimicrobial stewardship (AMS) activities, implementation, reach, and uptake affect how successful they are nationally. This case study explores the feasibility, acceptability, and usefulness of embedding the TARGET (Treat Antibiotics Responsibly, Guidance, Education and Tools) AMS training into a local incentive scheme.

Method: Black Country Integrated Care Board (ICB) invited a representative from all associated general practises to a TARGET AMS training event; attendance was linked to a local incentive scheme. Data were collected via a pre- and post-workshop survey capturing TARGET toolkit knowledge, AMS attitudes and behaviours, training feedback, and intention to implement AMS behaviours. Descriptive analyses were conducted.

Results: 157 and 101 attendees completed the pre- and post-session surveys, respectively. In total, 89% agreed that attending the session was a good use of their time. The proportions of attendees stating an intention to use the TARGET toolkit and implement a range of AMS strategies following the session were high (TARGET Toolkit: >82%, AMS strategies: >90%). Most attendees planned to implement these actions within 3 months (47%) or within 3-6 months (30%).

Conclusion: Results suggest that embedding the training into a local incentive scheme is a viable implementation approach in extending training reach. Although the impact on prescribing rates is not yet available, the high engagement and intention to implement AMS strategies observed should inspire confidence in this approach to training implementation.

Antimicrobial resistance (AMR) has emerged as one of the major challenges for human health, with a remarkable burden of mortality, morbidity, and healthcare-associated costs [...].

Non-clinical enterococci are relatively poorly studied by means of acquired antibiotic resistance to tetracycline and by the distribution, functionality and role of their CRISPR systems. Background: In our study, 72 enterococcal strains, isolated from various non-clinical origins, were investigated for their phenotypic and genotypic (tet(M), tet(O), tet(S), tet(L), tet(K), tet(T) and tet(W)) tetracycline resistance. Methods: The genetic determinants for HGT (MGEs (Int-Tn and prgW), inducible pheromones (cpd, cop and cff), aggregation substances (agg, asa1, prgB and asa373) and CRISPR-Cas systems were characterized by PCR and whole-genome sequencing. Results: Four tet genes (tetM, tetO, tetS and tetT) were detected in 39% (n = 28) of our enterococcal population, with tetM (31%) being dominant. The gene location was linked to the Tn6009 transposon. All strains that contained tet genes also had genes for HGT. No tet genes were found in E. casseliflavus and E. gilvus. In our study, 79% of all tet-positive strains correlated with non-functional CRISPR systems. The strain E. faecalis BM15 was the only one containing a combination of a functional CRISPR system (cas1, cas2, csn2 and csn1/cas9) and tet genes. The CRISPR subtype repeats II-A, III-B, IV-A2 and VI-B1 were identified among E. faecalis strains (CM4-II-A, III-B and VI-B1; BM5-IV-A2, II-A and III-B; BM12 and BM15-II-A). The subtype II-A was the most present. These repeats enclosed a great number of spacers (1-10 spacers) with lengths of 31 to 36 bp. One CRISPR locus was identified in plasmid (p.Firmicutes1 in strain E. faecalis BM5). We described the presence of CRISPR loci in the species E. pseudoavium, E. pallens and E. devriesei and their lack in E. gilvus, E. malodoratus and E. mundtii. Conclusions: Our findings generally describe the acquisition of foreign DNA as a consequence of CRISPR inactivation, and self-targeting spacers as the main cause.

Background/objectives: Bacterial resistance to antibiotics is a major problem in healthcare, complicated by the ability of bacteria to form biofilms. Complementary therapy for infectious diseases can rely on natural substances with antibacterial activity, e.g., essential oils and honeys. The aim of the study was to investigate the effects of linden and chestnut honeys, lavender essential oil, and their combinations against the multidrug-resistant otitis media pathogens Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Streptococcus pneumoniae. The efficacy of these natural substances was compared with each other and antibiotics used in clinical practice.

Methods: Microscopic pollen analysis and physicochemical traits were used to confirm the botanical origin of honey samples. The antibiotic sensitivity of bacteria was tested with a disk diffusion assay. Minimum inhibitory concentrations were determined using a microdilution assay. A 24 h immature biofilm eradication test was performed with a crystal violet assay. The efficacy of combinations was tested with a checkerboard titration method. The DNA release of damaged bacterial cells was measured using a membrane degradation assay.

Results: Lavender essential oil displayed more potent antibacterial activity compared to the honey samples. However, honey-essential oil combinations showed higher inhibition rates for biofilm eradication, with P. aeruginosa being the most resistant bacterium. The combined use of chestnut honey and lavender oil resulted in a higher degree of membrane degradation in a shorter time, and their synergistic effect was proven with checkerboard titration.

Conclusions: The combination of linden or chestnut honey with lavender essential oil was shown to be effective in the eradication of a 24 h immature biofilm formed by H. parainfluenzae, M. catarrhalis, and S. pneumoniae.

Background/objectives: The increasing threat of antimicrobial resistance (AMR) to global public health urgently needs attention. Misuse of antimicrobials in sectors such as dairy farming has led to the emergence and spread of resistant bacteria and genes. This study investigated AMR patterns and profiles of Escherichia coli (E. coli) from various sources, including soil, effluent, cow dung, and milk.

Methods: A total of 192 samples were collected, comprising environmental samples (soil and effluent), cow dung samples, and milk samples from eight dairy farms in Selangor, Malaysia. The spread plate method was employed to isolate E. coli, and all the isolates were subjected to Gram staining to identify Gram-negative, rod-shaped bacteria. The Vitek^® 2 system was used for E. coli identification and susceptibility testing.

Results: The prevalence of E. coli identified in the eight farms was 66.1%. A total of 360 E. coli isolates were successfully isolated, and 19.7% of the isolates presented AMR with ampicillin exhibiting the highest resistance (18.3%), followed by trimethoprim-sulfamethoxazole (8.9%). Additionally, 8.9% of them were multidrug resistant, which could be divided into 16 patterns. For the extended spectrum beta-lactamase screening, nine isolates were positive.

Conclusions: This finding emphasizes the rise in resistant isolates in the growing dairy industry and underscores the urgency of addressing the potential reservoir of AMR. Therefore, essential measures such as continuous surveillance and effective antimicrobial stewardship programs are crucial for regulating veterinary antimicrobial use. Research on the mechanisms driving the development and dissemination of AMR is imperative for addressing One Health concerns.

Background: Daptomycin plus fosfomycin combination therapy is a valuable strategy for treating staphylococcal osteoarticular infections (OIs), but hypernatremia and hypokalemia due to sodium overload are important issues. The aim of this study was to assess the likelihood of attaining a pharmacokinetic/pharmacodynamic (PK/PD) target of AUC/MIC > 66.6 and/or of 70%t > MIC with continuous infusion (CI) fosfomycin at the recommended vs. reduced dose in patients with OIs receiving combination therapy with high-dose daptomycin. Adverse events were also evaluated. Methods: Patients with OIs treated with 8-10 mg/kg daily daptomycin plus CI fosfomycin, and who had a ≥1 TDM assessment of CI fosfomycin, were retrospectively included in the high-dose (16 g daily) or reduced-dose (<16 g daily) groups. The attainment of the PK/PD targets of 70%t > MIC and AUC/MIC > 66.6 up to an MIC of 32 mg/L was calculated. A CART analysis was used to identify a cut-off of fosfomycin AUC that indicated occurrence of hypernatremia and/or hypokalemia. Results: A total of 44 and 39 patients were included in the high- and reduced-dose groups, respectively. The two groups did not differ in terms of demographic characteristics, underlying infectious diseases and microbiological isolates. No differences between groups in attaining both PK/PD targets up to an MIC of 32 mg/L and in C-reactive protein reduction at the end of treatment were observed. Fosfomycin AUC > 8245 mg × h/L and >8326 mg × h/L were associated with hypernatremia and hypokalemia, respectively. Conclusions: CI fosfomycin at 8 g daily may reach optimal PK/PD target attainment with better safety than the recommended 16 g daily dose in patients with preserved renal function. Targeting fosfomycin AUC at 2131-8326 mg × h/L or steady-state concentration at 88.8-347 mg/L may be adequate for optimizing drug pharmacodynamics up to an MIC of 32 mg/L and minimizing the risk of hypernatremia and hypokalemia.