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Plant Molecular Biology Jan 2024Plant U-box E3 ligases PUB20 and PUB21 are flg22-triggered signaling components and negatively regulate immune responses. Plant U-box proteins (PUBs) constitute a class...
Plant U-box E3 ligases PUB20 and PUB21 are flg22-triggered signaling components and negatively regulate immune responses. Plant U-box proteins (PUBs) constitute a class of E3 ligases that are associated with various stress responses. Among the class IV PUBs featuring C-terminal Armadillo (ARM) repeats, PUB20 and PUB21 are closely related homologs. Here, we show that both PUB20 and PUB21 negatively regulate innate immunity in plants. Loss of PUB20 and PUB21 function leads to enhanced resistance to surface inoculation with the virulent bacterium Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). However, the resistance levels remain unaffected after infiltration inoculation, suggesting that PUB20 and PUB21 primarily function during the early defense stages. The enhanced resistance to Pst DC3000 in PUB mutant plants (pub20-1, pub21-1, and pub20-1/pub21-1) correlates with extensive flg22-triggered reactive oxygen production, strong MPK3 activation, and enhanced transcriptional activation of early immune response genes. Additionally, PUB mutant plants (except pub21-1) exhibit constitutive stomatal closure after Pst DC3000 inoculation, implying the significant role of PUB20 in stomatal immunity. Comparative analyses of flg22 responses between PUB mutants and wild-type plants reveals that the robust activation of the pattern-induced immune responses may enhance resistance against Pst DC3000. Notably, the hypersensitivity responses triggered by RPM1/avrRpm1 and RPS2/avrRpt2 are independent of PUB20 and PUB21. These results suggest that PUB20 and PUB21 knockout mutations affect bacterial invasion, likely during the early stages, acting as negative regulators of plant immunity.
Topics: Innate Immunity Recognition; Arabidopsis; Immunity, Innate; Plant Proteins; Penicillin V; Ligases
PubMed: 38265485
DOI: 10.1007/s11103-023-01409-6 -
Analytical Methods : Advancing Methods... Jan 2024: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with...
: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with toxicity and antimicrobial resistance. Probenecid has shown significant potential in enhancing the serum exposure of phenoxymethylpenicillin, thereby allowing for lower doses of phenoxymethylpenicillin to achieve similar pharmacokinetic/pharmacodynamic (PK/PD) targets. We developed a triple quadrupole liquid chromatography mass spectrometry (TQ LC/MS) analysis of, phenoxymethylpenicillin, benzylpenicillin and probenecid using benzylpenicillin-d7 and probenecid-d14 as IS in single low-volumes of human serum, with improved limit of quantification to support therapeutic drug monitoring. : Sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using TQ LC/MS. The mobile phase consisted of 55% methanol in water + 0.1% formic acid, with a flow rate of 0.4 mL min. Antibiotic stability was assessed at different temperatures. : Chromatographic separation was achieved within 2 minutes, allowing simultaneous measurement of phenoxymethylpenicillin, benzylpenicillin and probenecid in a single 15 μL blood sample. Validation indicated linearity over the range 0.0015-10 mg L, with accuracy of 96-102% and a LLOQ of 0.01 mg L. All drugs demonstrated good stability under different storage conditions. : The developed method is simple, rapid, accurate and clinically applicable for the quantification of phenoxymethylpenicillin, benzylpenicillin and probenecid in tandem.
Topics: Humans; Penicillin V; Probenecid; Tandem Mass Spectrometry; Anti-Bacterial Agents; Penicillin G
PubMed: 38189092
DOI: 10.1039/d3ay01816d -
Acta Obstetricia Et Gynecologica... Mar 2024Antibiotics are often prescribed during pregnancy. Assessing the current state of prenatal antibiotic use is therefore imperative for optimizing prescribing and...
INTRODUCTION
Antibiotics are often prescribed during pregnancy. Assessing the current state of prenatal antibiotic use is therefore imperative for optimizing prescribing and identifying emerging research priorities. The study aimed to describe recent trends and patterns in antibiotic use during pregnancy among women who gave birth in Sweden, including user characteristics.
MATERIAL AND METHODS
Population-based descriptive study using linked nationwide registers. All pregnancies delivered in Sweden from 2007 to 2019 were included. Prevalence of use was defined as the percentage of pregnancies during which at least one prescription forantibiotics was filled. Temporal trends in the prevalence of antibiotic use by calendar year, trimester and weeks of gestation were assessed from time series graphs.
RESULTS
Prescriptions for systemic antibiotics were filled in 20.7% of 1 434 431 pregnancies overall, decreasing from 24.7% in 2007 to 18.0% in 2019. Phenoxymethylpenicillin (8.5%), pivmecillinam (6.5%), nitrofurantoin (4.7%), amoxicillin (1.6%) and cefadroxil (1.5%) use were the most prevalent. Their use decreased over the 13-year period, except for pivmecillinam, which increased from 4.0% to 7.4%. Prevalence of use was highest in the second trimester (9.5%), with weekly trends peaking at 13 and 34 weeks of gestation. Compared with non-users, antibiotic users more often belonged to the youngest and oldest age strata, carried multipleton pregnancies, had delivered before, had attained a lower education level and smoked in early pregnancy. A higher body mass index, asthma, chronic renal disease and diabetes mellitus were more prevalent among antibiotic users than among non-users.
CONCLUSIONS
Although outpatient antibiotic use during pregnancy in Sweden has been declining, one in five pregnancies was exposed to systemic antibiotics.
Topics: Pregnancy; Female; Humans; Anti-Bacterial Agents; Amdinocillin Pivoxil; Sweden; Amoxicillin; Penicillin V
PubMed: 38108616
DOI: 10.1111/aogs.14741 -
Gels (Basel, Switzerland) Nov 2023This research explores the integration of DUT-67 metal organic frameworks into polyethyleneimine-based hydrogels to assemble a composite system with enough mechanical...
Linear Polyethyleneimine-Based and Metal Organic Frameworks (DUT-67) Composite Hydrogels as Efficient Sorbents for the Removal of Methyl Orange, Copper Ions, and Penicillin V.
This research explores the integration of DUT-67 metal organic frameworks into polyethyleneimine-based hydrogels to assemble a composite system with enough mechanical strength, pore structure and chemical affinity to work as a sorbent for water remediation. By varying the solvent-to-modulator ratio in a water-based synthesis path, the particle size of DUT-67 was successfully modulated from 1 μm to 200 nm. Once DUT-67 particles were integrated into the polymeric hydrogel, the composite hydrogel exhibited enhanced mechanical properties after the incorporation of the MOF filler. XPS, NMR, TGA, FTIR, and FT Raman studies confirmed the presence and interaction of the DUT-67 particles with the polymeric chains within the hydrogel network. Adsorption studies of methyl orange, copper(II) ions, and penicillin V on the composite hydrogel revealed a rapid adsorption kinetics and monolayer adsorption according to the Langmuir's model. The composite hydrogel demonstrated higher adsorption capacities, as compared to the pristine hydrogel, showcasing a synergistic effect, with maximum adsorption capacities of 473 ± 21 mg L, 86 ± 6 mg L, and 127 ± 4 mg L, for methyl orange, copper(II) ions, and penicillin V, respectively. This study highlights the potential of MOF-based composite hydrogels as efficient adsorbents for environmental pollutants and pharmaceuticals.
PubMed: 37998999
DOI: 10.3390/gels9110909 -
Polymers Nov 2023This paper describes a new methodology for carrying out quantitative extraction of cloxacillin from drinking and river water samples using a molecularly imprinted...
This paper describes a new methodology for carrying out quantitative extraction of cloxacillin from drinking and river water samples using a molecularly imprinted polymer (MIP) as a selective sorbent for solid-phase extraction (MISPE). Several polymers were synthesized via thermal polymerization using cloxacillin as a template, methacrylic acid (MAA) as a functional monomer, ethyleneglycoldimethacrylate (EGDMA) as a cross-linker and different solvents as porogens. Binding characteristics of the adequate molecularly imprinted and non-imprinted (NIP) polymers were evaluated via batch adsorption assays following the Langmuir and Freundlich isotherms and Scatchard assays. The parameters related to the extraction approach were studied to select the most appropriate polymer for cloxacillin determination. Using the optimized MIP as the SPE sorbent, a simple sample treatment methodology was combined with high-performance liquid chromatography (HPLC) to analyze cloxacillin residues in drinking and river water. Under the optimum experimental conditions, the MISPE methodology was validated using spiked samples. The linearity for cloxacillin was assessed within the limits of 0.05-1.5 µg L and the recovery percentage was higher than 98% (RSD < 4%). The limits of detection and limits of quantification were 0.29 and 0.37 µg L and 0.8 and 0.98 µg L for drinking and river water, respectively. The selectivity of MIP against other ß-lactam antibiotics with similar structures (oxacillin, cefazoline, amoxicillin and penicillin V) was studied, obtaining a good recovery higher than 85% for all except cefazoline. The proposed MISPE-HPLC methodology was successfully applied for the detection of cloxacillin in drinking water from Canal de Isabel II (Madrid) and river water from the Manzanares River (Madrid).
PubMed: 37959993
DOI: 10.3390/polym15214314 -
Environmental Technology Nov 2023The soil application of hydrothermally treated penicillin V fermentation residue (PFR) is attractive but challenged, due to the concern of the resistance risk in soil...
The soil application of hydrothermally treated penicillin V fermentation residue (PFR) is attractive but challenged, due to the concern of the resistance risk in soil related to residual antibiotics. In this study, a lab-scale incubation experiment was conducted to investigate the influence of penicillin V on antibiotic resistance genes (ARGs) in PFR-amended soil via qPCR. The introduced penicillin V in soil could not be persistent, and its degradation occurred mainly within 2 days. The higher number of soil ARGs was detected under 108 mg/kg of penicillin V than lower contents (≤54 mg/kg). Additionally, the relative abundance of ARGs was higher in soil spiked with penicillin V than that in blank soil, and the great increase in the relative abundance of soil ARGs occurred earlier under 108 mg/kg of penicillin V than lower contents. The horizontal gene transfer might contribute to the shift of ARGs in PFR-amended soil. The results indicated that the residual penicillin V could cause the proliferation of soil ARGs and should be completely removed by hydrothermal treatment before soil application. The results of this study provide a comprehensive understanding of the resistance risk posed by penicillin V during the application of hydrothermally pretreated PFR.
PubMed: 37955258
DOI: 10.1080/09593330.2023.2283807 -
European Journal of Pediatrics Dec 2023This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to... (Review)
Review
This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A β-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates. Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.
Topics: Child; Adult; Humans; Streptococcus pyogenes; Streptococcal Infections; Pharyngitis; Anti-Bacterial Agents; Hypersensitivity
PubMed: 37819417
DOI: 10.1007/s00431-023-05211-w -
Innere Medizin (Heidelberg, Germany) Dec 2023Drug-mediated immune hemolysis is a rare but potentially life-threatening condition. Based on a case of penicillin-induced immune hemolysis, a structured literature... (Review)
Review
BACKGROUND
Drug-mediated immune hemolysis is a rare but potentially life-threatening condition. Based on a case of penicillin-induced immune hemolysis, a structured literature review of case reports and studies on penicillin-mediated Drug-Induced Immune Hemolytic Anemia (DIIHA) was carried out.
CASE REPORT
A 28-year-old male patient presented to the emergency department with gross hematuria and non-specific abdominal complaints. The patient had a 10-day history of respiratory infection with bacterial tonsillitis, treated orally with penicillin V on an outpatient basis. Laboratory diagnostics detected pathologically altered direct and indirect hemolysis parameters. After stopping the medication, the patient's condition could be stabilized.
CONCLUSION
Diagnosis of penicillin-mediated immune hemolysis requires structured cooperation between clinic and laboratory, as clinical and serological findings may be highly variable with the risk of misdiagnosis. Due to the rarity of the disease, this case report is intended to raise awareness with respect to the triad of abrupt drop in hemoglobin levels in connection with drug therapy and in combination with a strongly positive direct Coombs test.
Topics: Male; Humans; Adult; Hemolysis; Hematuria; Penicillins; Anemia, Hemolytic; Coombs Test
PubMed: 37493757
DOI: 10.1007/s00108-023-01555-5 -
Current Pediatric Reviews Jul 2023Group A ß-hemolytic streptococcus (GABHS) is the leading bacterial cause of acute pharyngitis in children and adolescents worldwide.
BACKGROUND
Group A ß-hemolytic streptococcus (GABHS) is the leading bacterial cause of acute pharyngitis in children and adolescents worldwide.
OBJECTIVE
This article aims to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of GABHS pharyngitis.
METHODS
A search was conducted in December 2022 in PubMed Clinical Queries using the key term "group A β-hemolytic streptococcal pharyngitis". This review covers mainly literature published in the previous ten years.
RESULTS
Children with GABHS pharyngitis typically present with an abrupt onset of fever, intense pain in the throat, pain on swallowing, an inflamed pharynx, enlarged and erythematous tonsils, a red and swollen uvula, enlarged tender anterior cervical lymph nodes. As clinical manifestations may not be specific, even experienced clinicians may have difficulties diagnosing GABHS pharyngitis solely based on epidemiologic or clinical grounds alone. Patients suspected of having GABHS pharyngitis should be confirmed by microbiologic testing (e.g., culture, rapid antigen detection test, molecular point-of-care test) of a throat swab specimen prior to the initiation of antimicrobial therapy. Microbiologic testing is generally unnecessary in patients with pharyngitis whose clinical and epidemiologic findings do not suggest GABHS. Clinical score systems such as the Centor score and McIssac score have been developed to help clinicians decide which patients should undergo diagnostic testing and reduce the unnecessary use of antimicrobials. Antimicrobial therapy should be initiated without delay once the diagnosis is confirmed. Oral penicillin V and amoxicillin remain the drugs of choice. For patients who have a non-anaphylactic allergy to penicillin, oral cephalosporin is an acceptable alternative. For patients with a history of immediate, anaphylactic-type hypersensitivity to penicillin, oral clindamycin, clarithromycin, and azithromycin are acceptable alternatives.
CONCLUSION
Early diagnosis and antimicrobial treatment are recommended to prevent suppurative complications (e.g., cervical lymphadenitis, peritonsillar abscess) and non-suppurative complications (particularly rheumatic fever) as well as to reduce the severity of symptoms, to shorten the duration of the illness and to reduce disease transmission.
PubMed: 37493159
DOI: 10.2174/1573396320666230726145436 -
Journal of Clinical Nursing Nov 2023Increasing number of nurse prescribers could be part of a solution to the shortage of physicians, improve access to treatment and curb the rise in healthcare costs;...
BACKGROUND
Increasing number of nurse prescribers could be part of a solution to the shortage of physicians, improve access to treatment and curb the rise in healthcare costs; however, readmissions after nurse prescribers' appointments are under-researched.
AIMS
To describe and compare clients' initial appointments with nurse prescribers and physicians. In addition, client readmissions within 60 days in the target organisation after nurse prescribers' and physicians' appointments were investigated.
DESIGN
Retrospective register-based follow-up study.
METHODS
Data included client appointments (n = 3986) with nurse prescribers and physicians, and clients' readmissions (n = 9038) from 1 January 2018 to 31 December 2019 from one hospital district in Finland. Data were analysed statistically using frequencies, percentages, rate ratios and cross-tabulation. STROBE checklist was used.
RESULTS
Initial appointments including trimethoprim, pivmecillinam, phenoxymethyl penicillin, chloramphenicol, fusidic acid and cephalexin prescriptions with nurse prescribers (n = 36) were 2131, and physicians (n = 140) 1855. On average, client readmissions (within 60 days) per initial appointment were 2.10 after appointments with nurse prescribers and 2.46 after physicians. After initial appointments, including phenoxymethyl penicillin prescriptions, with nurse prescribers, clients had more readmissions in all age groups than after initial appointments with physicians. However, in all, after initial appointments with physicians, clients had a higher proportion of readmissions.
CONCLUSION
Clients have fewer readmissions after appointments with nurse prescribers than physicians, including the same prescriptions. Nurse prescribers' skills may not have been fully utilised. Physicians treated many patients whose diseases nurse prescribers might have been able to treat based on the nurse prescribers' rights. However, physician clients may have more demanding service requirements.
Topics: Humans; Retrospective Studies; Follow-Up Studies; Patient Readmission; Penicillin V; Drug Prescriptions
PubMed: 37485967
DOI: 10.1111/jocn.16837