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ACS Omega Jun 2024Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate...
Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone , to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds -) were synthesized and assayed in vitro. The results on the ability of derivatives - to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound , a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein.
PubMed: 38911797
DOI: 10.1021/acsomega.4c02984 -
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 -
Journal of the Medical Library... Jan 2024In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not...
In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming's laboratory in its original location at St. Mary's Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.
Topics: History, 20th Century; Humans; Penicillins; History, 19th Century; Anti-Bacterial Agents; London
PubMed: 38911526
DOI: 10.5195/jmla.2024.1780 -
BMC Infectious Diseases Jun 2024In the last two decades, a significant increase in the number of Clostridioides difficile infection (CDI) cases has been observed. It is understandable to attempt to... (Observational Study)
Observational Study
BACKGROUND
In the last two decades, a significant increase in the number of Clostridioides difficile infection (CDI) cases has been observed. It is understandable to attempt to determine the factors that can predict the severity of the course of the infection and identify patients at risk of death. This study aimed to analyze the factors affecting the incidence and mortality of CDI in inpatient treatment at the University Clinical Hospital in Wrocław in 2016-2018.
METHODS
Statistical analysis of data obtained from patients' medical records was performed. Only patients with symptoms of infection and infection confirmed by laboratory tests were enrolled in the study. When analyzing the number of deaths, only adult patients who died in hospital wards were included. The quantitative data including laboratory tests, used antibiotics and Nutritional Risk Screening (NRS) were assessed. Also, the qualitative data such as sex, year of hospitalization, occurrence of diarrhoea on admission to the hospital, presence of additional diseases, as wee ad the use of antibacterial drugs or proton pump blockers and ranitidine during hospitalization were analyzed.
RESULTS
A total of 319 adult CDI patients (178 women and 141 men) were enrolled of which 80 people died (50 women and 30 men). The mean age of the patients was 72.08 ± 16.74 years. Over the entire period studied, the morbidity was 174 cases per 100,000 hospitalizations while mortality was 25.08%. The group of deceased patients was characterized by: older age (by 9.24 years), longer duration of hospitalization (by 10 days), reduced albumin levels (Rho = -0.235, p < 0.001), higher urea levels, use of more antibiotics, higher risk of malnutrition in NRS (Rho = 0.219, p < 0.001), higher incidence of sepsis, heart failure, stroke, hypothyroidism. Pneumonia was diagnosed twice as often. It was also shown that deceased patients were significantly more likely to take penicillin and fluoroquinolones.
CONCLUSIONS
In this study, the morbidity was lower, but mortality was higher compared to similar hospitals in Poland. CDI patients were characterized by older age, multimorbidity, extended hospitalization, and the use of broad-spectrum antibiotics. Risk factors for death included advanced age, prolonged hospital stays, lower albumin, higher urea, malnutrition, and comorbidities like heart failure, stroke, pneumonia, sepsis, and hypothyroidism. Increased antibiotic use, particularly penicillin and fluoroquinolones, was associated with a higher mortality risk.
Topics: Humans; Male; Female; Clostridium Infections; Aged; Poland; Middle Aged; Aged, 80 and over; Hospitals, University; Clostridioides difficile; Hospitalization; Incidence; Risk Factors; Anti-Bacterial Agents; Adult
PubMed: 38910242
DOI: 10.1186/s12879-024-09495-7 -
Journal of Oral and Maxillofacial... Jun 2024Traditional mandibular reconstruction has relied on the use of vascularized and non-vascularized autografts. The use of allografts and tissue engineering modalities has...
BACKGROUND
Traditional mandibular reconstruction has relied on the use of vascularized and non-vascularized autografts. The use of allografts and tissue engineering modalities has risen as an alternative.
PURPOSE
The purpose of this study was to determine the success of a cellular bone matrix (CBM) allograft composed of lineage committed bone forming cells for mandibular tissue engineering and reconstruction.
STUDY DESIGN, SETTING, SAMPLE
A retrospective cohort study was implemented using data from subjects treated with a CBM at the University of Louisville from 2019 to 2023. Subjects were excluded if they were not treated with a CBM, data were not complete, or postoperative follow-up time was less than 3 months.
PREDICTOR VARIABLES
The predictor variables were composed of heterogenous variables grouped into the following categories: demographics (age, sex), medical history (history of penicillin [PCN] allergy, history of diabetes mellitus [DM] and tobacco use), etiology (benign tumor, ballistic trauma, nonballistic trauma, odontogenic cyst, osteomyelitis/ medication-related osteonecrosis of the jaw), mandibular resection length (cm) and type (marginal, segmental), delayed versus immediate reconstruction, and whether an autograft (proximal tibia) with platelet-rich fibrin was used in combination with the CBM.
MAIN OUTCOME VARIABLE
The primary outcome variable was graft success (yes or no). Success was defined as bony union and defect fill (demonstrated on panoramic radiograph) and mandibular stability (based on postoperative clinical examination at 3 months).
COVARIATES
Not applicable.
ANALYSES
Descriptive statistics were calculated for each variable. To measure the associations between the risk factors and graft success, Fisher's exact test for categorical variables and the Wilcoxon rank sum test for numeric data were used. A P value of <.05 was considered significant.
RESULTS
The sample included 38 subjects. The median age of all subjects was 46 (interquartile range 32.6) years. Overall, 28 (73.7%) cases were successful. Subjects with a reported PCN allergy or a history of DM had significantly lower success (2, 7.1% with PCN allergy or DM) compared to those who did not (P = .008, PCN allergy; P = .03, DM).
CONCLUSIONS AND RELEVANCE
This is the largest case series of CBM based mandibular reconstruction relative to the available maxillofacial surgery literature. The clinician should consider confirmation of PCN allergy so PCN-type antibiotics can be used. CBMs may be an alternative to autografts.
PubMed: 38909627
DOI: 10.1016/j.joms.2024.05.040 -
Medicina 2024Mushrooms containing amatoxins generate the highest number of fatal mycete poisonings on the planet. These toxins are produced not only by Amanita species, such as the...
Mushrooms containing amatoxins generate the highest number of fatal mycete poisonings on the planet. These toxins are produced not only by Amanita species, such as the well-known Amanita phalloides, but also by other genera, including Lepiota. In this work we report the treatment of a 51-year-old male patient weighing 79 kg who was referred to the hospital after 36 h of ingesting mushrooms. The mushrooms were identified as Lepiota brunneoincarnata, found for the first time in Argentina. The patient presented general malaise, nausea and repeated vomiting, abdominal pain, and diarrhea. Thanks to a quick anamnesis and early and accurate identification of the fungus, he was administered a nasogastric tube and serial activated charcoal. Additionally, N-acetylcysteine, phytomenadione and penicillin G EV were administered. The patient was discharged 11 days after admission. This case highlights the importance of obtaining a correct and sufficient anamnesis on fungi, enabling rapid analysis of them, and initiation of timely treatment for intoxication. Once again, the importance of having Toxicological Information and Advice Centers (CIAT) with experience and knowledge of micetisms is demonstrated.
Topics: Male; Middle Aged; Humans; Mushroom Poisoning; Argentina; Treatment Outcome
PubMed: 38907978
DOI: No ID Found -
Gut Jun 2024This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for infection in patients with penicillin...
BACKGROUND AND AIMS
This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for infection in patients with penicillin allergy.
METHODS
In this randomised controlled trial, treatment-naïve adults with infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.
RESULTS
300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).
CONCLUSIONS
VT dual therapy demonstrated efficacy and safety as a first-line treatment for infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.
TRIAL REGISTRATION NUMBER
ChiCTR2300074693.
PubMed: 38906695
DOI: 10.1136/gutjnl-2024-332640 -
International Journal of Food... Jun 2024Pre-cut fresh fruits and vegetables are highly appealing to consumers for their convenience, however, as they are highly susceptible to microbial contamination in...
Pre-cut fresh fruits and vegetables are highly appealing to consumers for their convenience, however, as they are highly susceptible to microbial contamination in processing, the potential risks of foodborne illnesses to public health are not negligible. This study aimed to assess the prevalence, antibiotic susceptibility and molecular characteristics of major foodborne pathogens (Listeria monocytogenes, Escherichia coli, Staphylococcus aureus and Salmonella) isolated from fresh-cut fruits and vegetables in Beijing, China. 86 stains were isolated from 326 samples, with S. aureus being the highest prevalence (15.38 %), followed by E. coli (9.23 %) and L. monocytogenes (1.85 %), while no Salmonella was detected. The prevalence by type of food indicated that fruit trays and mixed vegetables were more susceptible to contamination by pathogens. 98 % of S. aureus were resistant to at least of one antibiotic, and showed a high resistance rate to benzylpenicillin (90 %) and oxacillin (48 %). Among 25 E. coli isolates, 57.67 % of which exhibited multi-drug resistance, with common resist to trimethoprim/sulfamethoxazole (66.67 %) and ampicillin (63.33 %). A total of 9 sequence types (STs) and 8 spa types were identified in 35 S. aureus isolates, with ST398-t34 being the predominant type (42.86 %). Additionally, analysis of 25 E. coli isolates demonstrated significant heterogeneity, characterized by 22 serotypes and 18 STs. Genomic analysis revealed that 5 and 44 distinct antibiotic resistance genes (ARGs) in S. aureus and E. coli, respectively. Seven quinolone resistance-determining regions (QRDRs) mutations were identified in E. coli isolates, of which GyrA (S83L) was the most frequently detected. All the S. aureus and E. coli isolates harbored virulence genes. ARGs in S. aureus and E. coli showed a significant positive correlation with plasmids. Furthermore, one L. monocytogenes isolate, which was ST101 and serogroupIIc from watermelon sample, harbored virulence genes (inlA and inlB) and LIPI-1 pathogenic islands (prfA, plcA, hly and actA), which posed potential risks for consumer's health. This study focused on the potential microbial risk of fresh-cut fruits and vegetables associated with foodborne diseases, improving the scientific understanding towards risk assessment related to ready-to-eat foods.
PubMed: 38905809
DOI: 10.1016/j.ijfoodmicro.2024.110804 -
Die Anaesthesiologie Jul 2024The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All... (Review)
Review
The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show a negative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play a central role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and a risk stratification for the identification of patients with a penicillin allergy. This overview article presents a possible delabelling algorithm within the framework of the clarification of a beta-lactam antibiotic allergy. The focus is on a structured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score.
Topics: Drug Hypersensitivity; Humans; Penicillins; Anti-Bacterial Agents; Anaphylaxis; Algorithms
PubMed: 38904675
DOI: 10.1007/s00101-024-01425-1 -
Stomatologiia 2024Was to determine the presence of an amoxicillin-based antibiotic in bone implant biopsies by Raman spectroscopy in an experiment.
THE AIM OF THE STUDY
Was to determine the presence of an amoxicillin-based antibiotic in bone implant biopsies by Raman spectroscopy in an experiment.
MATERIALS AND METHODS
Experimental animals (=10, a miniature pig of the Svetlogorsk breed) were divided into 2 groups of 5 animals. Groups 1 and 2 were injected with amoxicillin 2 ml per 20 kg of body weight 30 minutes before dental implantation surgery, then group 2 was additionally injected with 1 ml per 20 kg of body weight for 5 days. Each animal has 6 implants installed. On the 1st, 3rd, 7th, 14th day, an implant-bone biopsy was removed from each animal, micro-preparations were made and Raman spectroscopy was performed to assess the peak matching of the Raman spectrum.
RESULTS
In animals of the 1st and 2nd groups, the main peak of the Raman spectrum, which is closest to the values of the antibiotic spectrum of interest to us, is located closer to 1448 cm and 1446 cm, respectively. At the same time, in both observations, the peaks relate to the spectrum of bone tissue, which cannot indicate the content of an antibiotic in the drug.
CONCLUSION
No scattering spectra corresponding to the antibiotic molecule were found in any animal from both groups, regardless of the mode of administration and dosage of amoxicillin. The detected peaks corresponded to bone tissue without an antibiotic.
Topics: Spectrum Analysis, Raman; Animals; Amoxicillin; Swine; Anti-Bacterial Agents; Biopsy; Dental Implants; Swine, Miniature; Bone and Bones; Dental Implantation
PubMed: 38904552
DOI: 10.17116/stomat20241030315