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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 -
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 -
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 -
Renal Failure Dec 2024The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced...
OBJECTIVES
The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced epilepsy could be based on two main factors: neurotoxicity caused by drug accumulation after renal failure and an abnormal gut microbiota (GM).
METHODS
A chronic renal failure (CRF) model in mice was established, and then different doses of cefoperazone/sulbactam were injected to induce epilepsy in mice. Normal mouse feces for fecal microbiota transplantation (FMT) were collected. We observed the changes in feces, mental state, and activity of each group of mice. After killing, we collected kidneys and colon for H&E staining. We collected mouse feces for the 16S RNA sequencing of bacteria.
RESULTS
All CRF mice injected with different concentrations of cefoperazone/sulbactam experienced grade-V seizures and eventually died, whereas normal control mice did not. However, after FMT intervention, the time of epilepsy onset and death in mice was delayed. Early FMT intervention resulted in more mice surviving ( = .0359). Moreover, the villi in the mucosal of group-CS layer fell off, goblet cells missed, and crypts disappeared. The mucosal layer and submucosa were clearly separated. The morphology of intestinal tissue of the CFS and FS group was improved. After FMT, the changes of the GM were observed.
CONCLUSIONS
The GM may be involved in the epilepsy induced by cefoperazone/sulbactam in CRF mice. FMT can delay the onset of epilepsy in CRF mice induced by cefoperazone/sulbactam, and the earlier the intervention, the better the effect.
Topics: Animals; Cefoperazone; Sulbactam; Mice; Gastrointestinal Microbiome; Disease Models, Animal; Kidney Failure, Chronic; Epilepsy; Male; Anti-Bacterial Agents; Fecal Microbiota Transplantation; Feces
PubMed: 38938213
DOI: 10.1080/0886022X.2024.2371551 -
BMC Infectious Diseases Jun 2024Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection.
METHODS
Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions.
RESULTS
Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period.
CONCLUSIONS
Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.
Topics: Humans; Helicobacter Infections; Male; Female; Helicobacter pylori; Middle Aged; Immunoglobulins; Adult; Anti-Bacterial Agents; Treatment Outcome; Aged; Drug Therapy, Combination; Clarithromycin; Amoxicillin; Young Adult; Antibodies, Bacterial
PubMed: 38937679
DOI: 10.1186/s12879-024-09498-4 -
Semergen Jun 2024Self-reported penicillin allergy is highly prevalent. Different studies estimate that 10% of the population is labeled as such. This label, confirmed or suspected,...
Self-reported penicillin allergy is highly prevalent. Different studies estimate that 10% of the population is labeled as such. This label, confirmed or suspected, forces us to take precautions and replace the antibiotic treatment of choice (frequently beta-lactams) with other 2nd or 3rd choice alternatives with worse overall results: side effects, resistance, costs, etc. The penicillin allergy label, once placed, remains in the medical record. It is only confirmed in less than 5% of patients, either because it has been placed inappropriately or because over time the sensitivity decreases and may disappear. Penicillin Allergy Decision Rule -PEN-FAST- is a validated and simple clinical prediction rule that estimates the risk of presenting an allergic reaction. Its use, together with algorithms that involve primary care in the study and delabeling of low-risk patients, can change our clinical practice.
PubMed: 38936101
DOI: 10.1016/j.semerg.2024.102280