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Acta Orthopaedica Dec 2016Background and purpose - Acute kidney injury is a known complication of antibiotic use. Antibiotic prophylaxis is essential to prevent periprosthetic infections after...
Background and purpose - Acute kidney injury is a known complication of antibiotic use. Antibiotic prophylaxis is essential to prevent periprosthetic infections after total hip replacement. We experienced a rise in the incidence of acute kidney injury (AKI), and in an effort to solve this problem, we changed our antibiotic prophylaxis protocol. We investigated whether removing gentamicin from our antibiotic protocol would cause fewer and less severe cases of renal impairment. Patients and methods - We performed a retrospective study involving 136 cases of total hip replacement, with 66 patients receiving dicloxacillin and gentamicin and 70 patients receiving dicloxacillin alone. Results - We found less cases of AKI in the dicloxacillin group (p = 0.03): the mean creatine level in the dicloxacillin/gentamicin group was 126 (25-422) μmol/L whereas it was 93 (39-278) μmol/L in the group that received dicloxacillin alone. We also found that cases were less severe in the dicloxacillin group than in the dicloxacillin/gentamicin group (p = 0.02). The relative risk of developing AKI was 3 times higher if dicloxacillin and gentamicin were both used (p = 0.02). Interpretation - After removing gentamicin, there were fewer and less severe cases of acute kidney injury.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Arthroplasty, Replacement, Hip; Denmark; Dicloxacillin; Female; Gentamicins; Humans; Incidence; Male; Middle Aged; Prognosis; Retrospective Studies; Surgical Wound Infection
PubMed: 27648882
DOI: 10.1080/17453674.2016.1231008 -
BMC Clinical Pharmacology Sep 2002It is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may...
BACKGROUND
It is generally assumed that the tissue exchange of antibiotics is flow limited (complete equilibration between the capillary and the tissue water). This assumption may not be valid if there is a large amount of plasma protein binding because the effective capillary permeability depends on the product of the intrinsic capillary permeability (PS) and the fraction of solute that is free in the blood (fwB). PKQuest, a new generic physiologically based pharmacokinetic software routine (PBPK), provides a novel approach to modeling capillary permeability in which the only adjustable parameter is the PS of muscle.
METHODS
All the results were obtained by applying PKQuest to previously published human pharmacokinetic data.
RESULTS
The PKQuest analysis suggests that the highly protein bound antibiotics dicloxacillin and ceftriaxone have a significant capillary permeability limitation. The human muscle capillary PS of inulin, dicloxacillin and ceftriaxone was 0.6, 13 and 6 ml/min/100 gm, respectively. The ceftriaxone protein binding is non-linear, saturating at high plasma concentrations. The experimental ceftriaxone data over a wide range of intravenous inputs (0.15 to 3 gms) was well described by PKQuest. PKQuest is the first PBPK that includes both permeability limitation and non-linear binding.
CONCLUSIONS
Because of their high degree of plasma protein binding, dicloxacillin and ceftriaxone appear to have a diffusion limited exchange rate between the blood and tissue and are not flow limited as had been previously assumed. PKQuest and all the examples are freely available at http:\\www.pkquest.com.
Topics: Adult; Anti-Bacterial Agents; Blood Proteins; Capillary Permeability; Ceftriaxone; Dicloxacillin; Female; Humans; Inulin; Male; Protein Binding
PubMed: 12323078
DOI: 10.1186/1472-6904-2-7 -
British Medical Journal Nov 1970Flucloxacillin, a new isoxazole penicillin, is active against penicillinase-producing strains of Staphylococcus aureus and is well absorbed in man after oral and... (Comparative Study)
Comparative Study
Flucloxacillin, a new isoxazole penicillin, is active against penicillinase-producing strains of Staphylococcus aureus and is well absorbed in man after oral and intramuscular administration. Compared with isoxazole penicillins in current clinical use-namely, oxacillin, cloxacillin, and dicloxacillin-flucloxacillin has proved as active against Gram-positive cocci, including penicillin-resistant staphylococci. The extent of binding of flucloxacillin to the protein of human serum was similar to that of oxacillin and cloxacillin and less than that of dicloxacillin. In man flucloxacillin given orally produced total and free serum levels higher than those obtained with oxacillin and cloxacillin; total serum levels similar to those of dicloxacillin, and free levels greater than those of dicloxacillin. Similarly, after intramuscular injection the free serum levels of flucloxacillin were higher than those of oxacillin, cloxacillin, and dicloxacillin.
Topics: Administration, Oral; Blood Proteins; Cloxacillin; Dicloxacillin; Fasting; Humans; Hydrogen-Ion Concentration; Injections, Intramuscular; Microbial Sensitivity Tests; Oxacillin; Oxazoles; Penicillins; Protein Binding; Staphylococcus; Streptococcus
PubMed: 5481218
DOI: 10.1136/bmj.4.5733.455 -
Drug Metabolism and Disposition: the... Aug 2008We have investigated several in silico and in vitro methods to improve our ability to predict potential drug interactions of antibiotics. Our focus was to identify those...
We have investigated several in silico and in vitro methods to improve our ability to predict potential drug interactions of antibiotics. Our focus was to identify those antibiotics that activate pregnane X receptor (PXR) and induce CYP3A4 in human hepatocytes and intestinal cells. Human PXR activation was screened using reporter assays in HepG2 cells, kinetic measurements of PXR activation were made in DPX-2 cells, and induction of CYP3A4 expression and activity was verified by quantitative polymerase chain reaction, immunoblotting, and testosterone 6beta-hydroxylation in primary human hepatocytes and LS180 cells. We found that in HepG2 cells CYP3A4 transcription was activated strongly (> 10-fold) by rifampin and troleandomycin; moderately (> or = 7-fold) by dicloxacillin, tetracycline, clindamycin, griseofulvin, and (> or = 4-fold) erythromycin; and weakly (> 2.4-fold) by nafcillin, cefaclor, sulfisoxazole, and (> 2-fold) cefadroxil and penicillin V. Similar although not identical results were obtained in DPX-2 cells. CYP3A4 mRNA and protein expression were induced by these antibiotics to differing extents in both liver and intestinal cells. CYP3A4 activity was significantly increased by rifampin (9.7-fold), nafcillin and dicloxacillin (5.9-fold), and weakly induced (2-fold) by tetracycline, sufisoxazole, troleandomycin, and clindamycin. Multiple pharmacophore models and docking indicated a good fit for dicloxacillin and nafcillin in PXR. These results suggest that in vitro and in silico methods can help to prioritize and identify antibiotics that are most likely to reduce exposures of medications (such as oral contraceptive agents) which interact with enzymes and transporters regulated by PXR. In summary, nafcillin, dicloxacillin, cephradine, tetracycline, sulfixoxazole, erythromycin, clindamycin, and griseofulvin exhibit a clear propensity to induce CYP3A4 and warrant further clinical investigation.
Topics: Anti-Bacterial Agents; Base Sequence; Cell Line; Cytochrome P-450 CYP3A; DNA Primers; Enzyme Induction; Genes, Reporter; Humans; In Vitro Techniques; Intestines; Liver; Pregnane X Receptor; RNA, Messenger; Receptors, Steroid
PubMed: 18505790
DOI: 10.1124/dmd.108.020701 -
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 -
Drug Design, Development and Therapy 2017Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against...
BACKGROUND
Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and low level of toxicity. The objective of this study was to obtain optimal dosing regimen of oral administration of dicloxacillin by analyzing the pharmacokinetic (PK) index in healthy volunteers and in vitro antibacterial activity by using Monte Carlo simulation.
MATERIALS AND METHODS
A total of 867 clinical isolates from community-onset infections were collected from 31 secondary hospitals in People's Republic of China. The minimum inhibitory concentration (MIC) values of dicloxacillin were determined by the agar dilution method. Based on the MICs and the PK parameters of different dosage regimens, Monte Carlo simulation was performed to simulate the PK/pharmacodynamic indices of 250 mg once-daily (qd), 500 mg qd, 1,000 mg qd, 2,000 mg qd, 250 mg every 6 hours (q6h), and 500 mg q6h, respectively. The probability of target attainment was estimated at each MIC value, and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens.
RESULTS
Dicloxacillin showed poor antibacterial activity against , , and . Resistance to dicloxacillin was observed in 7.5% of coagulase-negative (CNS) isolates and 9.2% of other isolates, whereas 1.5% of methicillin-sensitive (MSSA) was resistant to dicloxacillin. Multiple-dose regimens could obtain higher CFR than single-dose regimens against and . However, all dosing regimens against MSSA achieved CFR ≥$90%. Meanwhile, dosing regimen of 2,000 mg qd, 250 mg q6h, and 500 mg q6h could achieve >90% of CFR for CNS. For other isolates, multiple-dose regimens achieved CFR ≥90%.
CONCLUSION
Dicloxacillin has a significant antibacterial activity against MSSA, CNS, and other isolates. The simulation results suggest that dicloxacillin 250 mg q6h and 500 mg q6h dosing regimens may be recommended for clinical applications, especially for community-onset infections.
Topics: Administration, Oral; Anti-Bacterial Agents; Bacteria; Community-Acquired Infections; Computer Simulation; Dicloxacillin; Drug Resistance, Bacterial; Healthy Volunteers; Humans; Microbial Sensitivity Tests; Monte Carlo Method
PubMed: 28721014
DOI: 10.2147/DDDT.S139632 -
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 -
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 -
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 -
Efficient detection and assessment of human exposure to trace antibiotic residues in drinking water.Water Research May 2020Human exposure to antibiotic residues in drinking water has not been well evaluated. This study is the first attempt to simultaneously and efficiently identify and...
Human exposure to antibiotic residues in drinking water has not been well evaluated. This study is the first attempt to simultaneously and efficiently identify and quantify 92 antibiotic residues in filtered tap water (multistage filtration at the tap) (n = 36) collected from 10 areas of a large city in southern China, 10 Chinese brands of bottled/barreled water (n = 30) and six foreign brands of bottled water (n = 18) obtained from the Chinese market. The average and median concentrations of all the detected antibiotic compounds was 182 and 92 ng/L in filtered tap water, 180 and 105 ng/L in Chinese brands of bottled/barreled water, and 666 and 146 ng/L in foreign brands of bottled water, respectively. A total of 58 antibiotics were detected in the filtered tap water, and 45 and 36 antibiotics were detected in the Chinese and foreign brands of bottled water, respectively. More types of antibiotics were detected in Chinese brands of bottled water than in the other bottled waters. In addition, Chinese waters had high roxithromycin concentrations, while the foreign brands of bottled water had high concentrations of dicloxacillin. The average and median values of the estimated overall daily intake of all the detected antibiotics were 4.3 and 2.3 ng/kg/day when only filtered tap water was drunk, 4.0 and 2.5 ng/kg/day when Chinese brands of bottled water was drunk, and 16.0 and 4.9 ng/kg/day when foreign brands of bottled water was drunk. Further study is needed to develop a more comprehensive estimation of human exposure to antibiotic residues in the environment and a more in-depth understanding of the potential hazard of ingested antibiotic residues to the human microbiome.
Topics: Anti-Bacterial Agents; China; Cities; Drinking Water; Humans
PubMed: 32200333
DOI: 10.1016/j.watres.2020.115699