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ACS Omega Jun 2024[This corrects the article DOI: 10.1021/acsomega.0c02813.].
[This corrects the article DOI: 10.1021/acsomega.0c02813.].
PubMed: 38947840
DOI: 10.1021/acsomega.4c04009 -
ACS Omega Jun 2024Penicillin V (phenoxy methyl penicillin) is highly sought after among natural penicillins because of its exceptional acid stability and effectiveness against common skin...
Penicillin V (phenoxy methyl penicillin) is highly sought after among natural penicillins because of its exceptional acid stability and effectiveness against common skin and respiratory infections. Given its wide-ranging therapeutic uses, there is a need to establish a greener method for its maximum recovery to reduce the carbon footprint. Here, we have identified and validated optimized operational conditions for resin-based penicillin V recovery. It was observed that Amberlite XAD4 had the highest penicillin V hydrophobic adsorption capacity among the other screened resins. Kinetic and isothermal studies using linear and nonlinear regression analysis showed that the adsorption process well fitted with pseudo-second-order kinetics ( = 0.9816) and the Freundlich adsorption isotherm model ( = 0.9871). Adsorption equilibrium was attained within 4 h, while maximum adsorption was observed at 3 mg/mL penicillin V concentration. Furthermore, the optimized extraction protocol was compared with the conventional butyl acetate-based downstream processing. Under optimum conditions resin-based penicillin V recovery was 2-fold higher as compared to the solvent extraction method and the resin could be reused for over six cycles without compromising the yield. These findings signify substantial progress toward the development of an environmentally sustainable approach for penicillin V recovery and a potentially viable method for extractive fermentation.
PubMed: 38911711
DOI: 10.1021/acsomega.4c00251 -
Clinical Microbiology and Infection :... Jun 2024While most countries recommend amoxicillin for pediatric pneumonia, there is a long tradition of treatment with penicillin V (PcV) in Sweden, thus not empirically...
OBJECTIVES
While most countries recommend amoxicillin for pediatric pneumonia, there is a long tradition of treatment with penicillin V (PcV) in Sweden, thus not empirically covering Haemophilus influenzae. There are, however, large regional differences in treatment practice. The aim was to compare clinical outcomes (treatment failure and severe complications), in children aged 1 to 59 months treated with PcV versus amoxicillin for pneumonia.
METHODS
This population-based emulated target trial included all children born in Sweden between 2001-2021, utilizing national health, sociodemographic, and population registers. All pneumonia cases from hospitals and pediatric outpatient clinics in children aged 1 to 59 months treated as outpatients with PcV or amoxicillin between July 2005-December 2021, were identified. Adjusted odds ratios (aOR)s and 95% confidence intervals (CI)s for treatment failure (new dispensed antibiotic prescription or pneumonia associated hospitalization day 1-14) and severe complications (lung complications, invasive bacterial disease, admission to intensive care unit or death day 1-28) were calculated with logistic regression analysis.
RESULTS
PcV was prescribed in 14,766 cases, and amoxicillin in 10,566. Treatment failure occurred in 7.7% with PcV versus 4.7% with amoxicillin, aOR 1.76 (95% CI: 1.54-2.00). Severe complications were rare, with no significant difference between PcV and amoxicillin (0.3% vs. 0.2%, aOR 0.96, 95% CI: 0.53-1.73). Sensitivity and interaction analyses showed consistent results.
CONCLUSIONS
PcV treatment compared to amoxicillin, was associated with an increased risk for treatment failure but not for severe complications. The absolute risks for adverse outcomes were low in both groups suggesting a minor role of H. influenzae in pediatric pneumonia.
PubMed: 38889864
DOI: 10.1016/j.cmi.2024.06.008 -
Journal of Clinical Periodontology May 2024To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics.
AIM
To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics.
MATERIALS AND METHODS
Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis.
RESULTS
A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups.
CONCLUSIONS
Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.
PubMed: 38699828
DOI: 10.1111/jcpe.13994 -
Annals of Allergy, Asthma & Immunology... Mar 2024Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited.
BACKGROUND
Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited.
OBJECTIVE
To evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported.
METHODS
A total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed.
RESULTS
PEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered.
CONCLUSION
PEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.
PubMed: 38561050
DOI: 10.1016/j.anai.2024.03.022 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2024We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine...
We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine phenoxymethylpenicillin. The antimicrobial agents for treatment were selected on the basis of their activity against a disease agent, the group A β-hemolytic strain Streptococcus pyogenes BS1 isolated from a patient. The bacterium was susceptible in vitro to β-lactams, with largest zones conditioned by penicillin G and benzathine phenoxymethylpenicillin discs, to fluoroquinolones and to cephems, with exception of cefazolin. Lincosamide clindamycin, macrolide spiramycin, aminoglycoside gentamicin, erythromycin, tetracycline and combination of sulfamethoxazole and trimethoprim were inactive against this bacterium. The Streptococcus pyogenes BS1 demonstrated intermediate susceptibility to the cephalosporin cephalexin, fluoroquinolone lomefloxacin and glycopeptide vancomycin. Non-antibiotic preparations were evaluated against Streptococcus pyogenes BS1 also. Among them "Stomatidin", "Chlorophyllipt", and phages of "Pyofag" were more effective than "Decatylen", "Decasan" and "Furadonin" in vitro. The antimicrobial applications of "Stomatidin", "Chlorophyllipt" and phages of "Pyofag" in the patient were less effective compared to the result of antibiotic benzathine phenoxymethylpenicillin treatment. Complete recovery of the patient was achieved with use of this antibiotic and Calendula flower extract as an local anti-inflammatory agent.
Topics: Adolescent; Humans; Anti-Bacterial Agents; Anti-Infective Agents; Ethylenediamines; Penicillin V; Streptococcus pyogenes; Tonsillitis
PubMed: 38431823
DOI: 10.36740/WLek202401122 -
International Microbiology : the... Feb 2024A filamentous fungus Penicillium rubens is widely recognized for producing industrially important antibiotic, penicillin at industrial scale.
BACKGROUND
A filamentous fungus Penicillium rubens is widely recognized for producing industrially important antibiotic, penicillin at industrial scale.
OBJECTIVE
To better comprehend, the genetic blueprint of the wild-type P. rubens was isolated from India to identify the genetic/biosynthetic pathways for phenoxymethylpenicillin (penicillin V, PenV) and other secondary metabolites.
METHOD
Genomic DNA (gDNA) was isolated, and library was prepared as per Illumina platform. Whole genome sequencing (WGS) was performed according to Illumina NovoSeq platform. Further, SOAPdenovo was used to assemble the short reads validated by Bowtie-2 and SAMtools packages. Glimmer and GeneMark were used to dig out total genes in genome. Functional annotation of predicted proteins was performed by NCBI non-redundant (NR), UniProt, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases. Moreover, secretome analysis was performed by SignalP 4.1 and TargetP v1.1 and carbohydrate-active enzymes (CAZymes) and protease families by CAZy database. Comparative genome analysis was performed by Mauve 2.4.0. software to find genomic correlation between P. rubens BIONCL P45 and Penicillium chrysogenum Wisconsin 54-1255; also phylogeny was prepared with known penicillin producing strains by ParSNP tool.
RESULTS
Penicillium rubens BIONCL P45 strain was isolated from India and is producing excess PenV. The 31.09 Mb genome was assembled with 95.6% coverage of the reference genome P. chrysogenum Wis 54-1255 with 10687 protein coding genes, 3502 genes had homologs in NR, UniProt, KEGG, and GO databases. Additionally, 358 CAZymes and 911 transporter coding genes were found in genome. Genome contains complete pathways for penicillin, homogentisate pathway of phenyl acetic acid (PAA) catabolism, Andrastin A, Sorbicillin, Roquefortine C, and Meleagrin. Comparative genome analysis of BIONCL P45 and Wis 54-1255 revealed 99.89% coverage with 2952 common KEGG orthologous protein-coding genes. Phylogenetic analysis revealed that BIONCL P45 was clustered with Fleming's original isolate P. rubens IMI 15378.
CONCLUSION
This genome can be a helpful resource for further research in developing fermentation processes and strain engineering approaches for high titer penicillin production.
PubMed: 38388812
DOI: 10.1007/s10123-024-00491-0 -
International Journal of Biological... Mar 2024Metallo-β-lactamases (MβLs) stand as significant resistant mechanism against β-lactam antibiotics in Gram-negative bacteria. The worldwide dissemination of New Delhi...
Metallo-β-lactamases (MβLs) stand as significant resistant mechanism against β-lactam antibiotics in Gram-negative bacteria. The worldwide dissemination of New Delhi metallo-β-lactamases (NDMs) intensifies antimicrobial resistance, posing severe threats to human health due to the absence of inhibitors available in clinical therapy. L3, a flexible β-hairpin loop flanking the active site in MβLs, has been proven to wield influence over the reaction process by assuming a crucial role in substrate recognition and intermediate stabilization. In principle, it potentially retards product release from the enzyme, consequently reducing the overall turnover rate although the details regarding this aspect remain inadequately elucidated. In this study, we crystallized NDM-1 in complex with three penicillin substrates, conducted molecular dynamics simulations, and measured the steady-state kinetic parameters. These analyses consistently unveiled substantial disparities in their interactions with loop L3. We further synthesized a penicillin V derivative with increased hydrophobicity in the R1 side chain and co-crystallized it with NDM-1. Remarkably, this compound exhibited much stronger dynamic interplay with L3 during molecular dynamics simulation, showed much lower K and k values, and demonstrated moderate inhibitory capacity to NDM-1 catalyzed meropenem hydrolysis. The data presented here may provide a strategic approach for designing mechanism-based MβL inhibitors focusing on structural elements external to the enzyme's active center.
Topics: Humans; Penicillins; beta-Lactams; Catalytic Domain; Hydrolysis; beta-Lactamases; Anti-Bacterial Agents
PubMed: 38336327
DOI: 10.1016/j.ijbiomac.2024.130041 -
The Journal of Antimicrobial... Apr 2024Managing drug-food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Managing drug-food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics.
METHODS
We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices.
RESULTS
Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor).
CONCLUSIONS
Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.
Topics: Humans; Cefaclor; beta Lactam Antibiotics; Cefuroxime; Penicillin V; Cephradine; Biological Availability; Antacids; Streptococcus pneumoniae; Anti-Bacterial Agents; beta-Lactams; Monobactams; Minerals; Microbial Sensitivity Tests
PubMed: 38334389
DOI: 10.1093/jac/dkae028 -
Infectious Disorders Drug Targets Jan 2024Actinomyces species are commensal oral cavity flora that can cause jaw osteomyelitis. Osteomyelitis of the jaw by Actinomyces is rare, and its presentation can be...
BACKGROUND
Actinomyces species are commensal oral cavity flora that can cause jaw osteomyelitis. Osteomyelitis of the jaw by Actinomyces is rare, and its presentation can be confused with many different pathologies.
CASE PRESENTATION
This is the case of a 61-year-old female with breast cancer and on chemotherapy as well as non-invasive carcinoma of the tongue who initially presented to the dentist with white spots in the right mandible near the incisors associated with right mandible pain and swelling. Actinomyces-induced osteomyelitis of the mandible was diagnosed. The patient was treated with penicillin V for 6 weeks along with a course of hyperbaric oxygen therapy, which resulted in the complete resolution of the infection.
CONCLUSION
In summary, jaw osteomyelitis caused by Actinomyces should always be part of the differential diagnosis; as these organisms are commensal flora, the symptoms manifested are nonspecific, and such a diagnosis could be easily missed, resulting in delay of care and disease progression.
PubMed: 38299277
DOI: 10.2174/0118715265275102231217155015