-
Clinical Medicine (London, England) Jun 2024We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these...
OBJECTIVES
We aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin.
METHODS
Opportunistic, prospective observational study of usual clinical care, between 16/05/23 and 14/08/23, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history.
RESULTS
Of the 123 patients admitted with a PenA (or sensitivity record) and exposed to a penicillin, data were collected for 50. Their PenA records were grouped follows: eligible for DDL 34 (68%), eligible for DOC 11 (22%), high risk 4 (8%) and unable to obtain history 1 (2%). In 14/50 (28%) patients there was no evidence of a current PenA assessment in the medical notes.
CONCLUSIONS
Using the allergy risk tool, most patients with penA records were exposed to penicillin appropriately. However, patients meeting high risk criteria were also exposed to penicillin when the tool excluded them. PenA assessment needs to be carried out with appropriate training and governance structures in place.
PubMed: 38944245
DOI: 10.1016/j.clinme.2024.100225 -
Phytochemistry Jun 2024The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was...
The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was found to grow vigorously in an intact Pinus koraiensis seed, it is inferred that the strain may develop unique mechanisms associated with the biosynthesis of rare metabolites. Further fermentation of the strain on solid rice medium yielded thirteen undescribed compounds, including three andrastin-type meroterpenoids (1-3), two α- pyrone polyketides (4 and 5), and eight sesquicarane derivatives (6-13), along with seven known compounds (14-20). Their structures were determined by detailed analysis of the spectroscopic and spectrometric data (NMR and HRESIMS), in addition to comparisons of the experimental and calculated ECD data for absolute configurational assignments. The hemiacetal moiety in compounds 1 and 2 and the 3α-hydroxy group in compound 3 were rarely found in the andrastin-type meroterpenoid family. The sesquicaranes belong to a small group of sesquiterpenoid that are rarely reported. Bioassay study showed that compound 1 exhibited inhibitory effects against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 with MIC values of 64 and 32 μg/mL, respectively. In addition, compounds 1 and 3 displayed weak DPPH radical scavenging activities. The andrastins and sesquicaranes in this study enriched the structural diversity of these classes of terpenoids. Of note, this study is the first report on the metabolites of a fungus isolated from P. koraiensis seed.
PubMed: 38944099
DOI: 10.1016/j.phytochem.2024.114202 -
BMC Microbiology Jun 2024Lactobacillus plantarum has been found to play a significant role in maintaining the balance of intestinal flora in the human gut. However, it is sensitive to commonly...
BACKGROUND
Lactobacillus plantarum has been found to play a significant role in maintaining the balance of intestinal flora in the human gut. However, it is sensitive to commonly used antibiotics and is often incidentally killed during treatment. We attempted to identify a means to protect L. plantarum ATCC14917 from the metabolic changes caused by two commonly used antibiotics, ampicillin, and doxycycline. We examined the metabolic changes under ampicillin and doxycycline treatment and assessed the protective effects of adding key exogenous metabolites.
RESULTS
Using metabolomics, we found that under the stress of ampicillin or doxycycline, L. plantarum ATCC14917 exhibited reduced metabolic activity, with purine metabolism a key metabolic pathway involved in this change. We then screened the key biomarkers in this metabolic pathway, guanine and adenosine diphosphate (ADP). The exogenous addition of each of these two metabolites significantly reduced the lethality of ampicillin and doxycycline on L. plantarum ATCC14917. Because purine metabolism is closely related to the production of reactive oxygen species (ROS), the results showed that the addition of guanine or ADP reduced intracellular ROS levels in L. plantarum ATCC14917. Moreover, the killing effects of ampicillin and doxycycline on L. plantarum ATCC14917 were restored by the addition of a ROS accelerator in the presence of guanine or ADP.
CONCLUSIONS
The metabolic changes of L. plantarum ATCC14917 under antibiotic treatments were determined. Moreover, the metabolome information that was elucidated can be used to help L. plantarum cope with adverse stress, which will help probiotics become less vulnerable to antibiotics during clinical treatment.
Topics: Lactobacillus plantarum; Metabolomics; Anti-Bacterial Agents; Ampicillin; Doxycycline; Reactive Oxygen Species; Purines; Stress, Physiological; Metabolic Networks and Pathways; Adenosine Diphosphate; Humans
PubMed: 38943061
DOI: 10.1186/s12866-024-03385-3 -
Environmental Monitoring and Assessment Jun 2024Solar Fenton is an important and extensively used advanced oxidation process (AOP) to degrade pharmaceutical pollutants. The objective of this study was to evaluate the...
Solar Fenton is an important and extensively used advanced oxidation process (AOP) to degrade pharmaceutical pollutants. The objective of this study was to evaluate the performance of simultaneous degradation of the mixed pollutants (amoxicillin, acetaminophen, and ciprofloxacin) for an aqueous solution using the solar Fenton process. Operating parameters such as pH, iron doses, HO doses, pollutant concentrations, and time were studied. From the experimental results, the ideal conditions were obtained for the removal of mixed pollutants such as pH 3, Fe 0.04 mM, HO 4 mM, the concentration of the mixed pollutants 5 mg/L, solar radiation 400 W/m, and time 10 min, respectively. The pseudo-first-order kinetics were utilized to investigate the degradation efficacy of the mixed pollutants. The result of the study indicates that the degradation efficiency was > 99% for the mixed pollutants. A maximum of 63% mineralization was observed, and hydroxyl radical scavenger effects were studied. The best optimal conditions were applied to assess the spiked wastewater (municipal wastewater (MWW) and hospital wastewater (HWW)). The highest elimination rates for AMX, ACET, and CIP were observed as 65%, 89%, and 85% for MWW and 76%, 92%, and 80% for HWW, respectively. The degraded by-products were detected by LC-ESI-MS in the water matrix (aqueous solution and spiked wastewater), and ECOSAR analysis was performed for the transformed products. The study concluded that the solar Fenton technique is promising and effective for the removal of mixed pollutants from the water matrix.
Topics: Water Pollutants, Chemical; Hydrogen Peroxide; Kinetics; Iron; Waste Disposal, Fluid; Sunlight; Wastewater; Oxidation-Reduction; Ciprofloxacin; Acetaminophen; Amoxicillin
PubMed: 38942963
DOI: 10.1007/s10661-024-12837-2 -
Clinical Therapeutics Jun 2024Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy...
PURPOSE
Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA.
METHODS
This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity.
FINDINGS
There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events.
IMPLICATIONS
Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.
PubMed: 38942719
DOI: 10.1016/j.clinthera.2024.05.007 -
The Science of the Total Environment Jun 2024Since the discovery of antibiotics, penicillin has remained the top choice in clinical medicine. With continuous advancements in biotechnology, penicillin production has... (Review)
Review
Since the discovery of antibiotics, penicillin has remained the top choice in clinical medicine. With continuous advancements in biotechnology, penicillin production has become cost-effective and efficient. Genetic engineering techniques have been employed to enhance biosynthetic pathways, leading to the production of new penicillin derivatives with improved properties and increased efficacy against antibiotic-resistant pathogens. Advances in bioreactor design, media formulation, and process optimization have contributed to higher yields, reduced production costs, and increased penicillin accessibility. While biotechnological advances have clearly benefited the global production of this life-saving drug, they have also created challenges in terms of waste management. Production fermentation broths from industries contain residual antibiotics, by-products, and other contaminants that pose direct environmental threats, while increased global consumption intensifies the risk of antimicrobial resistance in both the environment and living organisms. The current geographical and spatial distribution of antibiotic and penicillin consumption dramatically reveals a worldwide threat. These challenges are being addressed through the development of novel waste management techniques. Efforts are aimed at both upstream and downstream processing of antibiotic and penicillin production to minimize costs and improve yield efficiency while lowering the overall environmental impact. Yield optimization using artificial intelligence (AI), along with biological and chemical treatment of waste, is also being explored to reduce adverse impacts. The implementation of strict regulatory frameworks and guidelines is also essential to ensure proper management and disposal of penicillin production waste. This review is novel because it explores the key remaining challenges in antibiotic development, the scope of machine learning tools such as Quantitative Structure-Activity Relationship (QSAR) in modern biotechnology-driven production, improved waste management for antibiotics, discovering alternative path to reducing antibiotic use in agriculture through alternative meat production, addressing current practices, and offering effective recommendations.
PubMed: 38942308
DOI: 10.1016/j.scitotenv.2024.174236 -
International Journal of Surgery Case... Jun 2024Actinomycosis is a rare, chronic bacterial infection caused by Actinomyces species. While it commonly affects the cervicofacial region, thorax, and abdomen, appendicular...
INTRODUCTION AND IMPORTANCE
Actinomycosis is a rare, chronic bacterial infection caused by Actinomyces species. While it commonly affects the cervicofacial region, thorax, and abdomen, appendicular involvement is extremely uncommon. This case report details the presentation, diagnosis, and management of a 45-year-old female patient with acute appendicitis secondary to actinomycosis.
CASE PRESENTATION
A 45-year-old woman, with an 8-year intrauterine device history, presented with three-day right iliac fossa pain, vomiting, and stable vital signs. Laboratory tests revealed an inflammatory syndrome. Suspecting acute appendicitis, a CT scan confirmed a swollen 10 mm appendix. Laparoscopic surgery revealed a phlegmonous appendix, leading to an uncomplicated appendectomy. Pathological examination confirmed actinomycotic granules, supporting the diagnosis of actinomycosis appendicitis. The patient received 18 million units of intravenous penicillin G daily for 6 weeks followed by a 6-month course of oral amoxicillin (1 g three times daily) thereafter, showing favorable progression with no symptoms. Normal clinical and ultrasound follow-ups were observed at one year.
CLINICAL DISCUSSION
Appendiceal actinomycosis is a rare condition. Women, especially those with intrauterine contraceptives, experience an increase in cases due to chronic inflammation. Typically underdiagnosed, actinomycosis mimics other conditions, presenting with nonspecific symptoms. Laboratory results offer limited assistance, and histological confirmation is crucial. Histopathological examination is mandatory for diagnosis confirmation. Management involves surgical resection and prolonged penicillin-based antibiotics, providing a favorable prognosis with low mortality.
CONCLUSION
This case underscores the importance of considering rare etiologies, such as actinomycosis, in the differential diagnosis of appendicitis. Timely recognition and management are crucial for optimal patient outcomes.
PubMed: 38941730
DOI: 10.1016/j.ijscr.2024.109975 -
Alternative Therapies in Health and... Jun 2024Hepatocellular carcinoma (HCC) presents a challenging global health concern due to its high incidence and limited treatment efficacy. Understanding the molecular...
BACKGROUND
Hepatocellular carcinoma (HCC) presents a challenging global health concern due to its high incidence and limited treatment efficacy. Understanding the molecular pathways driving HCC development is crucial for advancing therapeutic strategies and improving patient outcomes.
OBJECTIVE
This study aims to assess the impact of Salinomycin on the Wnt/β-catenin signaling pathway in hepatocellular carcinoma, exploring its role in tumor migration and angiogenesis. Additionally, to explore the therapeutic potential of targeting this pathway for improving HCC treatment outcomes.
METHODS
This study employed an in vitro experimental design to investigate the role of the Wnt/β-catenin signaling pathway in HCC progression. HepG2 cells were cultured in RPMI 1640 medium supplemented with 10% serum, penicillin (100 U/ml), and streptomycin (100 μg/ml). The cells were divided into experimental and control groups for comparative analysis. Salinomycin was administered to inhibit Wnt/β-catenin pathway activation. The primary outcome measures included the evaluation of cell migration and tumor angiogenesis using cell migration assays and vascular endothelial growth factor (VEGF) expression analysis, respectively. Statistical analysis was performed using the two-tailed Student's t test, with significance set at P < .05.
RESULTS
Salinomycin treatment led to a dose-dependent decrease in HCC cell proliferation, with optical density values decreasing as the concentration of Salinomycin increased. Cell migration assays showed inhibited migration in cells treated with Salinomycin compared to controls. Western blot analysis revealed decreased levels of β-catenin and increased levels of DVL in Salinomycin-treated cells, indicating inhibition of the Wnt/β-catenin pathway. Furthermore, VEGF expression decreased after Salinomycin treatment, implicating the pathway in tumor angiogenesis. Statistical analysis, including Student's t-test, confirmed significant differences between control and experimental groups (P < .05).
CONCLUSION
The Wnt/β-catenin signaling pathway plays a significant role in the migration and angiogenesis of HCC when treated with Salinomycin.
PubMed: 38940798
DOI: No ID Found -
Photochemistry and Photobiology Jun 2024The purpose of this study was to evaluate the effects of 635 nm diode laser with different powers on undifferentiated mesenchymal stem cells obtained from buccal fat...
The purpose of this study was to evaluate the effects of 635 nm diode laser with different powers on undifferentiated mesenchymal stem cells obtained from buccal fat pad. Human buccal fat stem cells were cultured in DMEM containing 10% FBS, penicillin, and streptomycin under 5% CO and 95% humidity. Cells were cultured in 96-well plate and 24 h later, laser irradiation with 635 nm diode laser was performed in four groups of 200, 300, 400, and 500 mW powers in addition to the control group with the same energy density of 4 J/cm. MTT and flow cytometry assay was performed to evaluate cell proliferation and viability on 2 and 4 days after irradiation. Alizarin red assay and real-time PCR (OPN, OCN, ALP, and RUNX-2 genes) was performed to evaluate osteogenic differentiation. According to the MTT assay, none of the mentioned powers of 635 nm diode laser had significant effect on cell proliferation. Cells irradiated with power of 400 mW and 500 mW significantly showed a greater number of necrotic cells compared to the control group in Day 4. Cells irradiated with 300 mW power significantly exhibited a greater amount of nodule formation compared to all groups. Results of this study indicated that 635 nm diode laser with energy density of 4 J/cm has a positive effect inducing osteogenic differentiation when applying with a power of 300 mW in buccal fat pad mesenchymal stem cells.
PubMed: 38940369
DOI: 10.1111/php.13992 -
Advances in Pharmacological and... 2024Gonococcal infections present a notable public health issue, and the major approach for treatment involves using -lactam antibiotics that specifically target...
Investigation into the Interaction between Penicillin-Resistant and Penicillin-Susceptible Gonococcal Penicillin-Binding Protein 2 and Target Phenolic Ligands through Molecular Docking Studies and Structure-Activity Relationship Analysis.
Gonococcal infections present a notable public health issue, and the major approach for treatment involves using -lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in . This study examines the influence of flavonoids, namely, rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research starts by clarifying the structural effects of certain mutations, such as the insertion of an aspartate residue at position 345 (Asp-345a), in the PBP2. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely, P551S and F504L, have a significant impact on the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasising rutin's exceptional binding affinity and its potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments, namely, in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in . Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant bacteria. The verified simulation outcomes establish a basis for the creation of potent inhibitors and medicinal therapies to combat infectious illnesses.
PubMed: 38938595
DOI: 10.1155/2024/2585922