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RSC Advances Mar 2024In this study, we designed and synthesized a number of novel 1,2,3-triazole-piperazin-benzo[][1,4]thiazine 1,1-dioxide derivatives and investigated their antibacterial...
In this study, we designed and synthesized a number of novel 1,2,3-triazole-piperazin-benzo[][1,4]thiazine 1,1-dioxide derivatives and investigated their antibacterial and hemolytic activity. When compared to the lead chemical, dicloxacillin, the majority of the compounds demonstrated acceptable activity. Among them, the most promising compounds 6e, 6g, 6i, 8d, and 8e exhibited excellent antibacterial activity against the methicillin-susceptible (MSSA), methicillin-resistant (MRSA), and vancomycin-resistant (VRSA) with MIC values of 1.56 ± 0.22 to 12.5 ± 1.75 μg mL, respectively, The percentage of hemolysis ranged from 21.3 μg mL to 33.8 μg mL. Out of the six compounds (6i, 6e, 6f, 6g, 8e, 8d) tested compound 8e and 8d displayed minimal or negligible hemolytic activity across all the tested concentrations 29.6% and 30.2% recorded at 100 μg mL concentration respectively. docking studies were performed to evaluate the molecular interactions of 6e, 6f, 6g, 6i, 8d, and 8e compounds with Human, Mouse and Bovine TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1) and observed that three of the compounds (6i, 8d, and 8i) had appreciable binding energies ranging from -8.5 to -9.0 Kcal mol. Finally, the pharmacokinetic profile was predicted for potent compounds 8d, 8e and 6i using SWISS/ADME, All compounds investigated in this study adhered to Lipinski's rule of five with slight deviation in molecular weight (8d and 8e).
PubMed: 38500620
DOI: 10.1039/d3ra07509e -
Antibiotics (Basel, Switzerland) Feb 2024First-line treatments for methicillin-susceptible (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to...
BACKGROUND
First-line treatments for methicillin-susceptible (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia.
METHODS
This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality.
RESULTS
We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, = 0.57) or 90-day all-cause mortality (24% vs. 22%, = 0.82). No severe adverse reactions were associated with either antibiotic.
CONCLUSIONS
Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.
PubMed: 38391562
DOI: 10.3390/antibiotics13020176 -
Case Reports in Dermatology 2023Fungal infections can be challenging to diagnose, but doctors of every specialty may encounter this issue. They can be mistaken for other common dermatoses such as...
Fungal infections can be challenging to diagnose, but doctors of every specialty may encounter this issue. They can be mistaken for other common dermatoses such as eczema or psoriasis and inadvertently be treated with topical corticosteroids or calcineurin inhibitors. This may lead to tinea incognita, a term used to describe a fungal infection with an altered clinical appearance, which may confuse the clinician even further. This case report presents a 54-year-old previously healthy man with a 4-month history of a painful and pruritic rash in the genitoinguinal region. The patient's general practitioner had unsuccessfully attempted to treat the rash with topical terbinafine, econazole-triamcinolone, and betamethasone-fusidic acid, in addition to peroral dicloxacillin capsules. On examination, there were multiple red-bluish nodules and pustules coalescing into infiltrating erythematous plaques on both thighs and in the pubic region. Fungal cultures were negative, but the clinical features together with the history of prolonged use of combined topical steroids and antifungals raised suspicion of a deep fungal infection. Histopathological skin examination revealed deep suppurative and granulomatous folliculitis with ruptured hair follicles which was consistent with a diagnosis of Majocchi's granuloma. Treatment with itraconazole capsules was initiated, and after a 16-week course of systemic antifungal therapy, the rash resolved. In conclusion, our case report presents a case of Majocchi's granuloma, which is a great mimicker, especially for non-dermatologists. It is therefore important that the diagnosis is considered as a differential diagnosis, even though a patient has previously been treated with a topical antifungal.
PubMed: 37899944
DOI: 10.1159/000533475 -
Tidsskrift For Den Norske Laegeforening... Oct 2023While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions.
BACKGROUND
While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions.
CASE PRESENTATION
A man in his forties contacted his general practitioner because of increasing functional dyspnoea. He had completed a course of dicloxacillin a few months previously for a skin abscess on his abdomen. Bloodwork revealed severe anaemia (haemoglobin 5.4 g/dL), which required transfusion. Subsequent testing excluded iron and vitamin deficiency anaemia, haemolysis and malignancy. Initial bone marrow biopsy was of suboptimal quality. However, repeat tissue sample supported a diagnosis of pure red cell aplasia. The patient improved with ciclosporin treatment, which was gradually tapered.
INTERPRETATION
Pure red cell aplasia should be considered in patients with new onset isolated anaemia with severe reticulocytopenia. Diagnosis depends on obtaining representative tissue from bone marrow biopsy. It is difficult to conclude for this patient whether the aetiology of his pure red cell aplasia was idiopathic or secondary to recent dicloxacillin use.
Topics: Humans; Male; Anemia; Bone Marrow; Dicloxacillin; Neoplasms; Red-Cell Aplasia, Pure; Adult
PubMed: 37874056
DOI: 10.4045/tidsskr.23.0022 -
Microorganisms Jun 2023is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to...
is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to characterize the probiotic potential, based on the biochemical and genomic functionality, of LBUX23, isolated from neonates' feces. LBUX23 contains one circular genome of 2,287,838 bp with a G+C content of 60.05%, no plasmids, no CRISPR-Cas operon, possesses 56 tRNAs, 9 rRNAs, 1 tmRNA and 1776 coding sequences (CDSs). It has chromosomally encoded resistance genes to ampicillin and dicloxacillin, non-hemolytic activity, and moderate inhibition of ATCC 25922 and to some emergent pathogen's clinical strains. LBUX23 was able to utilize lactose, sucrose, fructooligosaccharides (FOS), and lactulose. The maximum peak of bacterial growth was observed in sucrose and FOS at 6 h; in lactose and lactulose, it was shown at 8 h. LBUX23 can survive in gastrointestinal conditions (pH 4 to 7). A decrease in survival (96.5 and 93.8%) was observed at pH 3 and 3.5 during 120 min. , , and genes could be involved in this tolerance. LBUX23 can also survive under primary and secondary glyco- or tauro-conjugated bile salts, and a mixture of bile salts due to the high extracellular bile salt hydrolase (BSH) activity (67.3 %), in taurocholic acid followed by taurodeoxycholic acid (48.5%), glycocholic acid (47.1%), oxgall (44.3%), and glycodeoxycholic acid (29.7%) probably due to the presence of the and genes which form an operon (start: 119573 and end: 123812). Low BSH activity was determined intracellularly (<7%), particularly in glycocholic acid; no intracellular activity was shown. LBUX23 showed antioxidant effects in DPPH radical, mainly in intact cells (27.4%). In the case of hydroxyl radical scavenging capacity, cell debris showed the highest reduction (72.5%). In the cell-free extract, superoxide anion radical scavenging capacity was higher (90.5%). The genome of LBUX23 contains , , , and genes, which could be involved in this activity. Regarding adherence, it showed adherence up to 5% to Caco-2 cells. LBUX23 showed in vitro potential probiotic properties, mainly in BSH activity and antioxidant capacity, which indicates that it could be a good candidate for antioxidant or anti-cholesterol tests using in vivo models.
PubMed: 37512821
DOI: 10.3390/microorganisms11071648 -
Tropical Medicine and Infectious Disease Jun 2023Snakebite envenoming is an occupational hazard in remote rural areas of South Thailand, where the highest incidence of snakebites is reported. In this work, a...
Snakebite envenoming is an occupational hazard in remote rural areas of South Thailand, where the highest incidence of snakebites is reported. In this work, a hospital-based retrospective study of snakebite patients from 2012 to 2022 at Fort Wachirawut Hospital and Fort Thepsatrisrisunthon Hospital, located in Nakhon Si Thammarat province, Thailand was conducted. Data from the laboratory investigation, physical examinations of snakebite victims, and clinical management, including pharmacological and non-pharmacological treatments, were evaluated. A total of 54 snakebite victims were included. The median age of patients was 49 years (IQR, 28 to 63). Males accounted for 74.1% of all participants. The majority of patients were bitten by Malayan pit vipers (68.5%), followed by unidentified snakes (18.5%), other non-venomous snakes (7.4%), and cobras (5.6%). The most common clinical manifestations were swelling (90.2%) and local pain (73.2%). One patient experienced respiratory failure following an envenoming by an unidentified venomous snake. No deaths were observed in this study. In total, 24 patients received antivenom administration (44.4%), most of whom were from Fort Wachirawut Hospital. Patients who were administered antivenom showed a median admission duration of three days (IQR, 3 to 4), compared with two days (IQR, one to three) for those who did not receive antivenom treatment ( < 0.001). In addition, paracetamol and prophylactic antibiotics, namely, amoxicillin-clavulanate and dicloxacillin, were the most common pharmacotherapies following snakebites. Overall, it was observed that these two community hospitals undertook appropriate clinical management under the standard guidelines for snakebite patients. This might be due to the effective emergency management, facilities, and clinical consultations. Finally, the management process in the medical teams also plays a crucial role in minimizing the severity of snakebite outcomes.
PubMed: 37505642
DOI: 10.3390/tropicalmed8070346 -
Microorganisms May 2023Skin and soft tissue infections are one of the main causes of consultations worldwide. The objective was to determine the treatment of a group of patients with...
Skin and soft tissue infections are one of the main causes of consultations worldwide. The objective was to determine the treatment of a group of patients with uncomplicated skin and soft tissue infections in Colombia. Follow-up study of a cohort of patients with skin infections who were treated in the Colombian Health System. Sociodemographic, clinical and pharmacological variables were identified. Treatments were evaluated using clinical practice guidelines for skin infections. A total of 400 patients were analyzed. They had a median age of 38.0 years and 52.3% were men. The most commonly used antibiotics were cephalexin (39.0%), dicloxacillin (28.0%) and clindamycin (18.0%). A total of 49.8% of the subjects received inappropriate antibiotics, especially those with purulent infections (82.0%). Being cared for in an outpatient clinic (OR: 2.09; 95% CI: 1.06-4.12), presenting pain (OR: 3.72; 95% CI: 1.41-9.78) and having a purulent infection (OR: 25.71; 95% CI: 14.52-45.52) were associated with a higher probability of receiving inappropriate antibiotics. Half of patients with uncomplicated skin and soft tissue infections were treated with antibiotics that were not recommended by clinical practice guidelines. This inappropriate use of antibiotics occurred in the vast majority of patients with purulent infections because the antimicrobials used had no effect on methicillin-resistant .
PubMed: 37374871
DOI: 10.3390/microorganisms11061369 -
Pathogens (Basel, Switzerland) Apr 2023A case of severe mortality in farmed was investigated to characterize the causative agent. We identified the bacterial strain as isolated from the gut of infected by...
A case of severe mortality in farmed was investigated to characterize the causative agent. We identified the bacterial strain as isolated from the gut of infected by biochemical assay, scanning electron microscopy and 16S rRNA gene sequence analysis. The in vivo challenge experiment showed that the LD of was 2.2 × 10 CFU/fish. Virulence gene investigation revealed that the isolated possesses Aerolysin, Cytotoxic enterotoxin, Serine protease, Dnase and Type III secretion system genes. The isolated strain was resistant to two antibiotics (ampicillin and dicloxacillin) while susceptible to 22 other antibiotics. The study further revealed that induced both stresses along with non-specific and specific immune responses marked by elevated cortisol HSP70, HSP90 and IgM levels in the treated fingerlings. Although the bacterial pathogen enhances the immune response, the negative effect on fish, including stress, and high mortality, create concern and a need for management in farms. The knowledge gained from this study would facilitate future research aimed at assessing the pathogenicity of , with an emphasis on microbial disease management in other farmed fish species.
PubMed: 37111485
DOI: 10.3390/pathogens12040598 -
Euro Surveillance : Bulletin Europeen... Mar 2023From October 2022 through January 2023, nine patients with NDM-5/OXA-48-carbapenemase-producing ST79 were detected in Denmark and subsequently one patient in Iceland....
From October 2022 through January 2023, nine patients with NDM-5/OXA-48-carbapenemase-producing ST79 were detected in Denmark and subsequently one patient in Iceland. There were no nosocomial links between patients, but they had all been treated with dicloxacillin capsules. An NDM-5/OXA-48-carbapenemase-producing ST79, identical to patient isolates, was cultured from the surface of dicloxacillin capsules in Denmark, strongly implicating them as the source of the outbreak. Special attention is required to detect the outbreak strain in the microbiology laboratory.
Topics: Humans; Iceland; Dicloxacillin; Disease Outbreaks; Denmark
PubMed: 36862098
DOI: 10.2807/1560-7917.ES.2023.28.9.2300108 -
BMJ Open Feb 2023Lesional skin of atopic dermatitis (AD) is often colonised by and the bacterial abundance increases during a flare. However, the role of and the skin microbiome in the...
Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study.
INTRODUCTION
Lesional skin of atopic dermatitis (AD) is often colonised by and the bacterial abundance increases during a flare. However, the role of and the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.
METHODS AND ANALYSIS
This clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologous , staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.
ETHICS AND DISSEMINATION
The scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov: NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT05578482, EudraCT 2021-006883-2.
Topics: Adult; Humans; Dermatitis, Atopic; Staphylococcus aureus; Skin; Immunity; Denmark
PubMed: 36806068
DOI: 10.1136/bmjopen-2022-068395