Antibiotics-Basel最新文献

Background/Objectives: Milk and dairy products are among the most relevant foods both nutritionally and commercially. Costa Rica stands out as one of the main producers and consumers of dairy products in Central America. However, in recent years, the use of antibiotics in the livestock industry has increased, with implications for public health and food security, generating a need to monitor residues of these drugs in food. The present research focuses on developing a liquid chromatography method for the simultaneous quantification of penicillin G (PEN) and cloxacillin (CLO) in raw and commercial bovine milk, as well as in various dairy products, including fresh cheese and liquid yogurt. Methods/Results: During the validation of the methodology, average sensitivities of (960 ± 8)·10¹ mg L^-1 and (1580 ± 9)·10¹ mg L^-1 were achieved for PEN and CLO, respectively. Determination coefficients of 0.9995 and 0.9998 were also achieved, respectively. The limits of detection (LOD) and quantification (LOQ) for PEN and CLO were (0.330 ± 0.025) mg L^-1 and (0.65 ± 0.12) mg L^-1, (1.10 ± 0.083) mg L^-1 and (2.2 ± 0.4) mg L^-1, respectively, on both accounts. Recoveries were 68-77%, 92-106%, and 78-112% for PEN and 57-79%, 99-114%, and 95-120% for CLO in milk, cheese, and yogurt, respectively, across all three concentration levels evaluated. The precision of the method, in terms of reproducibility, was assessed for liquid yogurt (3-12% RSD_R for PEN and 4-12% RSD_R for CLO) and in cheese (8-14% RSD_R for PEN and 4-12% RSD_R for CLO). Nineteen bovine milk samples from the Cartago area were evaluated, including commercial and milk samples. Additionally, cheese (n = 17) and yogurt samples (n = 8) were analyzed. Conclusions: None of the samples showed detectable signals of the antibiotics. In addition, antibiotic sensitivity testing was performed on n = 9 Lactic Acid Bacteria (LAB) strains isolated from the raw milk samples, revealing the presence of some resistant traits to several antibiotics, including β-lactams.

Background: Infected pancreatic necrosis (IPN) is a serious complication of moderate-to-severe acute pancreatitis (AP), associated with high morbidity, intensive care unit (ICU) admission, organ failure, and mortality. Initial management relies on antibiotics and drainage of walled-off necrosis (WON). In the context of increasing multidrug-resistant (MDR) bacteria, identifying risk factors for MDR emergence is crucial. The impact of fungal infections (FIs) on outcomes also remains unclear. This study aimed to identify risk factors associated with the emergence of MDR bacteria and FIs during intervention for IPN.

Methods: This retrospective study included 71 consecutive patients undergoing intervention for suspected IPN or symptomatic WON.

Results: At first intervention, IPN was confirmed in 52 patients (73%), MDR bacteria in 19 (27%), extensively drug-resistant (XDR) bacteria in 4 (5.6%), and FI in 21 (30%). After all interventions, MDR/XDR bacteria and fungi were detected in 25 (35%)/11 (15.5%) and 42 (59%) patients, respectively. Independent risk factors for MDR emergence were the number of antibiotic changes (b, 1.70; 95% CI 1.18-2.43; p = 0.004) and need for nutritional support (NS) (b, 5.69; 95% CI 1.52-20.50; p = 0.010). No independent factor was associated with FI. The 180-day mortality did not differ across groups. The 90-day cumulative ICU admission rate was higher in IPN vs. non-IPN (63.1% vs. 29.4%, p = 0.030) and in MDR vs. non-MDR (72.2% vs. 37.1%, p = 0.005).

Conclusions: Antibiotic changes and NS were independently associated with MDR emergence in IPN. No independent factors were linked to FI. ICU admission was significantly higher in IPN and MDR cases.

Background. Antibiotic resistance is a growing global health challenge, complicating the management of infections. Aminoglycosides are increasingly associated with resistance, raising the risk of clinical complications and mortality in severe infections. This study aimed to characterize the epidemiological profile of 135 aminoglycoside-resistant clinical strains collected in Setif between 2021 and 2023. Methods. Antibiotic susceptibility testing was performed according to EUCAST guidelines, and phenotypic assays were conducted to assess key virulence traits, including biofilm formation and enzyme production. Results. Aminoglycoside resistance was more frequently observed in female patients (55.6%) and was found to be predominant among adults (68.1%). Urinary tract infections represented the main clinical presentation (76.3%), with Escherichia coli being the most common isolate (40.7%). High resistance rates were detected for amoxicillin (83%), amoxicillin-clavulanic acid (80%), cephalexin (74.8%), cefixime (71.1%), trimethoprim-sulfamethoxazole (74.8%), and gentamicin (72.6%). Conversely, chloramphenicol (53.3%), imipenem (47.4%), amikacin (47.4%), and piperacillin-tazobactam (31.1%) remained comparatively more effective. Multidrug resistance involving seven antibiotics occurred in 25.6% of isolates, with notable cross-resistance patterns between gentamicin and β-lactam antibiotics (5 out of 22). Genotypic analysis showed that 43% of isolates carried at least one β-lactamase gene, whereas 9.6% harbored a qnr determinant. Regarding virulence factors, isolates with low biofilm-forming ability were found to be the most common (62.96%). Conclusion. In conclusion, this study revealed substantial variations in aminoglycoside resistance in Setif, shaped by demographic, clinical, and bacteriological factors.

Background/Objectives: In traditional contrast-based meta-analyses of randomized concurrent controlled trials (RCCTs), topical antibiotic prophylaxis (TAP) appears more effective than either antiseptic-based or non-antimicrobial-based interventions for preventing ventilator-associated pneumonia (VAP). The objective here is to use arm-based methods to determine whether this effectiveness translates towards achieving VAP-zero, both overall and specifically for VAP in association with Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter species among the same RCCTs. Methods: Data were extracted from RCCTs sourced primarily from Cochrane reviews of VAP prevention interventions. Arms-based and contrast-based methods of meta-analyses of the VAP prevention effect size and the VAP incidence per 100 patients receiving mechanical ventilation were obtained using random effects methods. Results: The VAP prevention intervention effect sizes derived by contrast-based versus arms-based meta-analyses were similar for each of the three broad types of interventions. The overall VAP prevention effect of antibiotic-based interventions by contrast-based and arms-based methods were 0.39 (95% confidence interval 0.33 to 0.46; n = 28) versus 0.39 (95% confidence interval 0.32 to 0.47; n = 28), respectively. Surprisingly, the arms-based analysis revealed that the summary VAP incidence, both overall and for each of Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter species within antibiotic intervention groups, were similar to the respective summary incidences within intervention groups of non-antimicrobial RCCTs. Conclusions: VAP-zero, both overall and in association with specific microbial sub-types, has remained elusive using antimicrobial-based interventions. This inference was not evident from a contrast-based analysis.

Background/Objectives: Antimicrobial resistance in food-animal environments threatens sustainable production and public health, yet small farms remain poorly characterized as potential reservoirs of antimicrobial resistant bacteria. To address this, we investigated the prevalence and antimicrobial resistance profiles of Escherichia coli, Klebsiella spp., and Enterococcus spp. from small-scale cattle farms in Tennessee, USA. Methods: Over one year, 153 environmental samples (soil, manure, water) were collected from 17 farms. Target bacteria were isolated and confirmed using selective agar, biochemical tests, and PCR, and tested against 12 antibiotics using the Kirby-Bauer disk diffusion test. Multiple Antibiotic Resistance Index (MARI) and multidrug resistance (MDR) profiles were summarized. A complementary farmer survey of 26 farmers captured veterinary access, antibiotic use, manure handling, record keeping, and awareness of antimicrobial resistance. Results: Prevalence was highest for Enterococcus spp. (41.8%), followed by E. coli (23.5%) and Klebsiella spp. (12.4%). Seasonal variation was significant for E. coli and Enterococcus (p < 0.05). Winter manure yielded highest detection of E. coli (55.6%) and Enterococcus (53.8%), whereas Klebsiella peaked in Fall soil (19.1%). Resistance patterns varied across species, with Enterococcus showing consistent resistance to all three. E. coli frequently resisted erythromycin, ampicillin, and azithromycin; and Klebsiella commonly resisted erythromycin, ampicillin, and cefotaxime, though some of these reflect intrinsic resistance rather than acquired clinical resistance. MARI values were 0.92 in manure and soil, identifying them as high-risk reservoirs. We identified 29 distinct MDR pattern. Bipartite network visualization highlighted "resistance hubs" around erythromycin, ampicillin, and vancomycin, particularly in Enterococcus. In our study, 76.9% of farmers consulted veterinarians before antibiotic use, 57.7% kept written antibiotic records, and 65.4% were aware of AMR as a public health issue. Small-scale cattle farms are potential reservoirs of multidrug resistant commensal bacteria. Conclusions: These findings provide an evidence-based foundation to guide targeted antimicrobial stewardship and promote sustainable management practices in small-scale food animal farms.

Background/Objectives: The salmon industry plays an important role in the Chilean economy, positioning the country as the second-largest producer of salmonids worldwide after Norway. However, this rapid growth has led to an increase in outbreaks of infectious diseases, which cause significant economic losses to the industry. The pathogen that most affects the salmon industry is the bacterium Piscirickettsia salmonis, accounting for 43.1% of infection-related deaths. In the search for new treatment alternatives against P. salmonis, we have previously reported that the effect of co-incubating silybin at sub-IC50 concentrations decreases the intracellular presence of P. salmonis in SHK-1 cells. Methods: This article evaluates the effect of silybin on the immune response and oxidative stress of SHK-1 cells infected with P. salmonis, as well as the reduction in intracellular bacterial replication during the first 72 h of infection. Furthermore, we assess the ability of silybin administration to modulate the immune response in S. salar and protect against P. salmonis infection. Results: The results show that co-incubation of silybin during infection in SHK-1 cells modulates the expression levels of the genes gsh-px, cat, tnf-α, and il-1β and also decreases the levels of intracellular ROS generated by the infection. Furthermore, the mechanism of action of silybin in SHK-1 cells is related to interference with the intracellular replication of P. salmonis after 72 h of infection and not to adherence or internalization of the bacteria. Finally, silybin is able to generate protection in S. salar infected with P. salmonis independently of stimulation of the immune response. Conclusions: In conclusion, silybin administration may be an effective treatment against P. salmonis in salmonids; however, further studies are needed to clarify the mechanism of action.

Background: After imipenem was introduced in clinical practice, neurologic adverse effects led to recommendations against its use in patients with neurologic conditions. However, these conclusions were drawn without considering pharmacokinetic variations in such patients. Furthermore, animal studies lack the use of clinically relevant doses and supporting morphological studies in both naïve and disease models. Objectives: We aim to study the effects of imipenem in the hippocampus of naïve animals, evaluating potential behavioral and morphological alterations. Methods: Naïve Wistar rats received a 10-day course of intraperitoneal imipenem (40 mg/kg) while controls received a saline injection. After that, they were put through the Morris water maze, elevated plus maze, open-field test, and then euthanized. We analyzed neurogenesis (using doublecortin immunoreactivity), astrogliosis, and the γ-Aminobutyric acid (GABA)ergic system (using parvalbumin (PV), calretinin (CR) and calbindin (CB) immunoreactive (IR) neurons) in the hippocampus. Results: Interestingly, our results showed no significant alterations in both short and long-term memory, nor in anxiety. There were also no significant changes in the neuronal density of doublecortin-immunoreactive (IR) neurons nor in astrogliosis. Furthermore, the areal density of PV- and CR-IR was preserved in all hippocampal subfields. The density of CB-IR neurons also showed no changes in the dentate gyrus, CA3, and subiculum; however, a significant increase was found in the CA1 region. Conclusions: Our results indicate that in naïve individuals, a clinically relevant dose of imipenem does not seem to cause overt behavioral deficits or widespread morphological alterations in the hippocampus. However, a specific increase in the CB-IR neuronal population in the CA1 region highlights a localized cellular alteration/plasticity induced by the imipenem. Hence, pharmacokinetic factors seem to be the potential contributors of imipenem side effects. Further studies should focus on this as a possible cause and focus on individuals with brain diseases.

Background/objectives: Inappropriate use of antibiotics contributes to the rise in antibiotic-resistant bacteria and can result in adverse drug effects for individuals. Informed discussions between patients and general practitioners (GPs) can help ensure that treatment decisions about antibiotic use align with the best health outcomes for individuals.

Methods: We implemented a set of information resources designed to support clinical discussions and decision-making for patients with common infections in primary care. A suite of patient information sheets, which had been co-designed with primary care providers and consumers, were implemented in eight general practices in metropolitan Melbourne and regional Victoria, from August to November 2020.

Results: Post-implementation evaluation, conducted through interviews with 15 primary care providers and 13 patients, revealed that the information sheets were simple, easy to use and generated discussion within consultations. GPs reported using the sheets to reinforce their decision-making during consultations with patients, reduce potential conflict, provide alternatives to antibiotic prescriptions, and offer patients a written summary of management recommendations. Patients found the sheets informative and that they made it easier to understand their diagnosis and to manage their conditions. Both GPs and patients agreed that the content was relevant and effectively enhanced patients' knowledge of disease conditions, treatment options, and when to seek medical advice and were facilitators of meaningful conversations during consultations.

Conclusion: These resources are acceptable in Australian primary care and publicly available for use by GPs, pharmacists and patients in Australia.

Background: Albendazole, mebendazole, and ivermectin are effective against adult Trichinella spiralis but show limited efficacy against encapsulated muscle stage larvae. This limitation highlights the need for improved experimental approaches to evaluate anthelmintic activity at this stage and to identify alternative therapeutic candidates. Methods: Seven antiparasitic drugs, albendazole (ABZ), miltefosine (MLT), ivermectin (IVM), tribendimidine (TBD), praziquantel (PZQ), artesunate (ART), and mefloquine (MEQ), were evaluated for in vitro activity against T. spiralis muscle larvae. Larval viability was quantified using a tetrazolium salt XTT assay to determine IC₅₀ values and compare with microscopic assessments. Based on in vitro activity, TBD was selected for in vivo evaluation in a mouse model, where efficacy was assessed by muscle larval burden and histopathological changes. Results: TBD, MEQ, IVM, and ABZ exhibited measurable in vitro efficacies against T. spiralis larvae, with TBD showing the lowest IC₅₀ value at 135.2 μM. XTT formazan absorbance correlated strongly with larval number and incubation time. In vivo, TBD treatment significantly reduced larval burdens in diaphragm and gastrocnemius muscles and was associated with reduced collagen capsule thickness, inflammation, and fibrosis compared with ABZ-treated controls. Conclusions: This study validated an assay for quantitative evaluation of T. spiralis muscle larvae and demonstrates robust in vitro and in vivo activity of TBD against this stage.

Background/objectives: Staphylococcus aureus virulence is tightly regulated by the agr (accessory gene regulator) quorum-sensing system. Targeting AgrC, the histidine kinase receptor that serves as a core regulator of agr signaling, represents a promising antivirulence strategy that circumvents conventional bactericidal pressure.

Methods: In this study, structure-based virtual screening using AutoDock Vina was performed, followed by molecular dynamics simulations, to identify potent analogs of known AgrC inhibitors.

Results: A cyclo[Ala-Phe-OLeu-Phe-D-Leu] exhibiting high binding affinity and stable receptor interaction was selected for further evaluation. Antimicrobial susceptibility testing confirmed that the compound did not inhibit bacterial growth. However, at a concentration of 16 µg/mL, it significantly inhibited hemolytic activity with high reproducibility, and the inhibition rate reached 77.60%. Quantitative reverse transcription PCR (RT-qPCR) demonstrated that the compound decreased some key AgrC-mediated genes, including agrC, agrA, saeS, hla, spa, fnbA, and lukS.

Conclusions: These findings identify a promising cyclic pentapeptide inhibitor of AgrC that effectively attenuates S. aureus virulence without exerting bactericidal pressure. This work provides a valuable lead compound and offers novel insights for the development of advanced, safe, and effective antivirulence therapeutics.