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The Journal of Chemical Physics Feb 2023Three-dimensional crystalline frameworks with nanoscale periodicity are valuable for many emerging technologies, from nanophotonics to nanomedicine. DNA nanotechnology...
Three-dimensional crystalline frameworks with nanoscale periodicity are valuable for many emerging technologies, from nanophotonics to nanomedicine. DNA nanotechnology has emerged as a prime route for constructing these materials, with most approaches taking advantage of the structural rigidity and bond directionality programmable for DNA building blocks. Recently, we have introduced an alternative strategy reliant on flexible, amphiphilic DNA junctions dubbed C-stars, whose ability to crystallize is modulated by design parameters, such as nanostructure topology, conformation, rigidity, and size. While C-stars have been shown to form ordered phases with controllable lattice parameter, response to stimuli, and embedded functionalities, much of their vast design space remains unexplored. Here, we investigate the effect of changing the chemical nature of the hydrophobic modifications and the structure of the DNA motifs in the vicinity of these moieties. While similar design variations should strongly alter key properties of the hydrophobic interactions between C-stars, such as strength and valency, only limited differences in self-assembly behavior are observed. This finding suggests that long-range order in C-star crystals is likely imposed by structural features of the building block itself rather than the specific characteristics of the hydrophobic tags. Nonetheless, we find that altering the hydrophobic regions influences the ability of C-star crystals to uptake hydrophobic molecular cargoes, which we exemplify by studying the encapsulation of antibiotic penicillin V. Besides advancing our understanding of the principles governing the self-assembly of amphiphilic DNA building blocks, our observations thus open up new routes to chemically program the materials without affecting their structure.
Topics: Crystallization; Nanostructures; Nanotechnology; Anti-Bacterial Agents; DNA
PubMed: 36859089
DOI: 10.1063/5.0132484 -
Current Opinion in Infectious Diseases Apr 2023Recurrent cellulitis is a challenging clinical condition affecting up to 47% of patients after the first episode, especially those with predisposing risk factors. The... (Review)
Review
PURPOSE OF REVIEW
Recurrent cellulitis is a challenging clinical condition affecting up to 47% of patients after the first episode, especially those with predisposing risk factors. The purpose of this review is to describe the state of the art of literature evidence and to highlight recent developments in its management.
RECENT FINDINGS
Recurrent cellulitis can occur after successful treatment of cellulitis. Conditions that commonly increase the risk of cellulitis include local and systemic modifiable and nonmodifiable factors. A rigorous approach to the management of risk factors and treatment of acute infection is important as the risk of recurrence rises with repeated episodes. Risk factors, if present, need to be targeted in association with antibiotic prophylaxis. Penicillin V is the preferred antibiotic for prevention but other antibiotics and new drugs can be considered in cases of β-lactam allergy, intolerance, or failure.
SUMMARY
Recurrent cellulitis is associated with short term and long-term morbidity as well as significant healthcare costs. Management of underlying predisposing conditions is crucial to prevent recurrence in addition with evaluation of pharmacological measures, but specialized and multidisciplinary skills are needed. More efforts are needed to prevent and treat this underestimated problem.
Topics: Humans; Cellulitis; Anti-Bacterial Agents; Antibiotic Prophylaxis; Penicillin V; Secondary Prevention; Chronic Disease; Recurrence
PubMed: 36853755
DOI: 10.1097/QCO.0000000000000903 -
Environmental Monitoring and Assessment Feb 2023The continued frequent detection of pharmaceuticals in the environment is of major concern due to potential human and ecological risks. This study evaluated 30...
The continued frequent detection of pharmaceuticals in the environment is of major concern due to potential human and ecological risks. This study evaluated 30 antibiotics from 8 classes: sulphonamides (SAs), penicillins (PNs), fluoroquinolones (FQs), macrolides (MLs), lincosamides (LINs), nitroimidazoles (NIs), diaminopyrimidines (DAPs), salfones and 4 anthelmintics benzimidazoles (BZs) in surface water and sediments from River Sosiani in Eldoret, Kenya. Samples were collected during the wet and dry seasons and subjected to solid phase extraction using HLB cartridges. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was used for the simultaneous quantification of the compounds. Chromatographic separation was on a reversed-phase Zorkax Eclipse Plus C18 column eluted in a gradient program and compounds detected by mass spectrometer operated in a positive electrospray ionization (+ ESI) mode. Twenty-eight antibiotics were detected in water where 22 had a 100% detection frequency and the remaining 4 showed detection frequencies ranging from 5 to 47%. Three BZs had a 100% detection frequency. Detectable concentrations of the pharmaceuticals in water ranged between 0.1 and 247 ng L and 0.01 and 974 µg kg in the sediments. The sulfonamide, sulfamethoxazole, had the highest concentration in water (247 ng L), whereas penicillin G showed the highest concentrations in sediments (414-974 µg kg). Quantified pharmaceuticals decreased in the order SAs > DAPs > FQs > ATs > PNs ≈ MCs ≈ LNs > NIs in water, and followed the order PNs > BZs > FQs > MLs > DAPs ≈ LNs > NIs > SAs in sediments. Risk quotients (RQ) showed that sulfamethoxazole and ciprofloxacin were of high ecological risk in the surface water (RQ values of 1.11 and 3.24, respectively), whereas penicillin V, ampicillin, penicillin G, norfloxacin, enrofloxacin, erythromycin, tylosin, and lincomycin were of medium ecological risk in the aquatic system. The findings show high prevalence of pharmaceuticals in surface water and sediments and are therefore potential ecological hazards. Such information is vital when devising mitigation strategies.
Topics: Humans; Kenya; Chromatography, Liquid; Rivers; Tandem Mass Spectrometry; Environmental Monitoring; Anti-Bacterial Agents; Penicillins; Fluoroquinolones; Sulfamethoxazole; Macrolides; Nitroimidazoles; Benzimidazoles; Pharmaceutical Preparations
PubMed: 36849593
DOI: 10.1007/s10661-023-11022-1 -
JAC-antimicrobial Resistance Feb 2023The intestinal microbiota functions as a reservoir of antibiotic resistance.
BACKGROUND
The intestinal microbiota functions as a reservoir of antibiotic resistance.
OBJECTIVES
To evaluate penicillin V (phenoxymethylpenicillin) effects on the faecal microbiota with focus on beta-lactam resistance.
METHODS
We included 31 primary care patients with group A streptococcal pharyngotonsillitis treated with penicillin V for 5 (800 mg × 4) or 10 days (1000 mg × 3). Twenty-nine patients contributed with three faecal swab samples each. The faecal specimens were collected at the start of penicillin V treatment, after the last dose and at follow-up 7-9 days after completed treatment. Samples were inoculated semiquantitatively on selective screening agar plates to study beta-lactam resistance, species shifts among Enterobacterales and enterococci, and colonization with spp. and . Representative colonies were identified using MALDI-TOF. Results were analysed by non-parametric statistical methods.
RESULTS
An increase in the proportion of patients colonized with ampicillin-resistant Enterobacterales, from 52% to 86% ( = 0.007), and Enterobacterales with decreased susceptibility to third-generation cephalosporins, from 32% to 52% ( = 0.034), was observed between the first and second samples. This increase was no longer significant at follow-up. New colonization with ampicillin-resistant Enterobacterales species and non-Enterobacterales Gram-negative species was observed, and persisted at follow-up.
CONCLUSIONS
Following treatment with penicillin V, we observed decreased susceptibility to ampicillin and third-generation cephalosporins, and prolonged colonization with non- Gram-negative species. These findings challenge the perception that penicillin V has limited ecological effect on the intestinal microbiota, and emphasizes the importance of avoiding even narrow-spectrum antimicrobials when possible.
PubMed: 36816747
DOI: 10.1093/jacamr/dlad006 -
British Dental Journal Jan 2023
Topics: Penicillin V; Penicillins
PubMed: 36639456
DOI: 10.1038/s41415-023-5442-4 -
Journal of the American Society For... Jan 2023Enzyme kinetics is normally assessed by performing individual kinetic measurements using batch-type reactors (test tubes, microtiter plates), in which enzymes are mixed...
Enzyme kinetics is normally assessed by performing individual kinetic measurements using batch-type reactors (test tubes, microtiter plates), in which enzymes are mixed with different substrates. Some drawbacks of conventional methods are the large amounts of experimental materials, long analysis times, and limitations of spectrophotometry. Therefore, we have developed a method for facile determination of enzyme kinetics using online flow-based mass spectrometry. A concentration ramp of substrate or product was created by dynamically adjusting flow rates of pumps delivering stock solution of substrate and diluent. Precise kinetic measurements were performed by reaction product quantification and initial rate calculation. In the presence of ascending substrate concentrations, the rate of a target enzyme (penicillinase)-catalyzed hydrolysis was varied. By measuring the reaction product continuously, Michaelis constants () could be calculated. The enzyme kinetic measurements for hydrolysis of penicillins were conducted based on this simple, rapid, and low sample consumption online flow device. In the homogeneous reaction, the values for amoxicillin, ampicillin, penicillin G, and penicillin V were 254.9 ± 14.5, 29.2 ± 0.3, 2.6 ± 0.1, and 5.4 ± 0.1 μM, respectively. In the heterogeneous reaction, the values for amoxicillin, ampicillin, penicillin G, and penicillin V were 408.9 ± 75.1, 114.4 ± 8.0, 21.8 ± 0.7, and 83.3 ± 4.8 μM, respectively. Apart from enzyme assay, the showcased method for the generation of temporal concentration ramps can be utilized to perform rapid quantity calibrations for mass spectrometric analyses.
Topics: Penicillin V; Kinetics; Ampicillin; Penicillin G; Amoxicillin; Mass Spectrometry
PubMed: 36515652
DOI: 10.1021/jasms.2c00283 -
Health Science Reports Nov 2022Penicillin V prophylaxis protects children living with sickle cell disease (SCD) from bacteria infections especially . However, the uptake of penicillin V prophylaxis is...
BACKGROUND AND AIMS
Penicillin V prophylaxis protects children living with sickle cell disease (SCD) from bacteria infections especially . However, the uptake of penicillin V prophylaxis is difficult to assess and often poor among SCD patients. Therefore, this study sought to investigate oral penicillin V prophylaxis adherence among SCD children using urine assay and self-reported methods and the associated factors.
METHODS
The study employed an analytical cross-sectional design in the assessment of penicillin V prophylaxis adherence using both urine assay and self-reported methods. Multiple logistic regression analysis was used to determine the factors associated with penicillin V prophylaxis adherence. A value < 0.05 was considered statistically significant.
RESULTS
Among the 421 SCD patients recruited, penicillin V prophylaxis adherence was observed to be 30.0% and 68.0% for the objective and subjective methods of assessment, respectively. For the objective method of assessment, being cared for by grandparents increased the odds of penicillin V adherence (adjusted odds ratio [aOR] = 3.68, confidence interval [CI] = 1.03-13.15). However, SCD patients within the ages of 10-14 years (aOR = 0.36, CI = 0.17-0.80), >14 years (aOR = 0.17, CI = 0.05-0.61), SCD patient cared for by married caregivers/parents (aOR = 0.32, CI = 0.14-0.72), SCD patient cared for by divorced caregivers/parents (aOR = 0.23, CI = 0.07-0.75), SCD patients taking homemade (herbal) preparations for the treatment of SCD (aOR = 0.42, CI = 0.21-0.83), and inappropriate intake of penicillin V prophylaxis (aOR = 0.27, CI = 0.11-0.67) reduced the odds of penicillin V adherence. For the subjective method of assessment, taking homemade preparation (herbal) for the treatment of SCD (aOR = 0.52, CI = 0.30-0.89) and inappropriate intake of penicillin V (aOR = 0.32, CI = 0.17-0.60) reduced the odds of penicillin V adherence.
CONCLUSION
This study reports a relatively low adherence rate of penicillin V prophylaxis among children living with SCD. Educating and counseling both SCD patients and/or caregivers on the need to be adherent to penicillin V prophylaxis could prevent complications that may arise from nonadherence.
PubMed: 36439045
DOI: 10.1002/hsr2.953 -
BMC Infectious Diseases Nov 2022Sore throat is a common reason for prescribing antibiotics in primary care, and 10 days of treatment is recommended for patients with pharyngotonsillitis with group A... (Randomized Controlled Trial)
Randomized Controlled Trial
Clinical course of pharyngotonsillitis with group A streptococcus treated with different penicillin V strategies, divided in groups of Centor Score 3 and 4: a prospective study in primary care.
BACKGROUND
Sore throat is a common reason for prescribing antibiotics in primary care, and 10 days of treatment is recommended for patients with pharyngotonsillitis with group A streptococcus (GAS). Our group recently showed that penicillin V (PcV) four times daily for 5 days was non-inferior in clinical outcome to PcV three times daily for 10 days. This study compares duration, intensity of symptoms, and side effects in patients with a Centor Score (CS) of 3 or 4 respectively, after treatment with PcV for 5 or 10 days and evaluates whether all patients with pharyngotonsillitis with a CS of 3 or 4 should be treated for 5 days or if severity of symptoms or CS suggest a longer treatment period.
METHOD
Data on symptoms and recovery from patient diaries from 433 patients included in a RCT comparing PcV 800 mg × 4 for 5 days or PcV 1 g × 3 for 10 days was used. Patients six years and older with CS-3 or CS-4 and positive rapid antigen detection test for GAS-infection were grouped based on CS and randomized treatment. Comparisons for categorical variables were made with Pearson's chi-squared test or Fisher's exact test. Continuous variables were compared with the Mann-Whitney U test.
RESULTS
Patients with CS-3 as well as patients with CS-4 who received PcV 800 mg × 4 for 5 days self-reported that they recovered earlier compared to patients with CS-3 or CS-4 who received treatment with PcV 1 g × 3 for 10 days. In addition, the throat pain as single symptom was relieved 1 day earlier in patients with CS-4 and 5 days of treatment compared to patients with CS-4 and 10 days of treatment. No differences in side effects between the groups were found.
CONCLUSION
Intense treatment with PcV four times a day for 5 days seems clinically beneficial and strengthens the suggestion that the 4-dose regimen with 800 mg PcV for 5 days may be the future treatment strategy for GAS positive pharyngotonsillitis irrespectively of CS-3 or CS-4. Trail registration ClinicalTrials.gov ID: NCT02712307 (3 April 2016).
Topics: Humans; Penicillin V; Pharyngitis; Primary Health Care; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis
PubMed: 36368940
DOI: 10.1186/s12879-022-07830-4 -
Frontiers in Pediatrics 2022Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal...
Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two variants, NM_000152.5: c.842G>C, p.(Arg281Pro) and NM_000152.5: c.2560C>T, p.(Arg854) in , and homozygosity for the variant causative of SCA, consistent with his diagnosis. An acute neonatal presentation of hypotonia and cardiomyopathy required ERT with alglucosidase alfa infusions preceded by immune tolerance induction (ITI), as well as chronic red blood cell transfusions and penicillin V potassium prophylaxis for treatment of IOPD and SCA. Clinical course was further complicated by multiple respiratory infections. We review the current guidelines and interventions taken to optimize his care and the pitfalls of those guidelines when treating patients with concomitant conditions. To the best of our knowledge, no other case reports of the concomitance of these two disorders was found. This report emphasizes the importance of newborn screening, early intervention, and treatment considerations for this complex patient presentation of IOPD and SCA.
PubMed: 36245745
DOI: 10.3389/fped.2022.944178 -
Ecotoxicology and Environmental Safety Nov 2022We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats....
We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats. Male 1.5-year-old Fischer 344 ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure system for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. particulate matter with aerodynamic diameter of ≤2.5 µm (PM) pollution). Lung functions, antibiotics, drugs, and metals in lungs were examined and linked to lung and fecal microbiome analyses by high-throughput sequencing analysis of 16 s ribosomal (r)DNA. Rats were exposed to 8.7 μg/m PM, 10.1 ppb NO, 1.6 ppb SO, and 23.9 ppb O in average during the study period. Air pollution exposure decreased forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory volume in 20 ms (FEV), and FEF at 25∼75% of FVC (FEF). Air pollution exposure increased antibiotics and drugs (benzotriazole, methamphetamine, methyl-1 H-benzotriazole, ketamine, ampicillin, ciprofloxacin, pentoxifylline, erythromycin, clarithromycin, ceftriaxone, penicillin G, and penicillin V) and altered metals (V, Cr, Cu, Zn, and Ba) levels in lungs. Fusobacteria and Verrucomicrobia at phylum level were increased in lung microbiome by air pollution, whereas increased alpha diversity, Bacteroidetes and Proteobacteria and decreased Firmicutes at phylum level were occurred in intestinal microbiome. Lung function decline was correlated with increasing antibiotics, drugs, and metals in lungs as well as lung and intestinal microbiome dysbiosis. The antibiotics, drugs, and Cr, Co, Ca, and Cu levels in lung were correlated with lung and intestinal microbiome dysbiosis. The lung microbiome was correlated with intestinal microbiome at several phylum and family levels after air pollution exposure. Our results revealed that antibiotics, drugs, and metals in the lung caused lung and intestinal microbiome dysbiosis in ageing rats exposed to air pollution, which may lead to lung function decline.
Topics: Male; Rats; Animals; Gastrointestinal Microbiome; Dysbiosis; Anti-Bacterial Agents; Environmental Exposure; Air Pollution; Particulate Matter; Lung; Metals; Aging; Air Pollutants
PubMed: 36244167
DOI: 10.1016/j.ecoenv.2022.114164