ABSTRACT
The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.
Subject(s)
Anti-Bacterial Agents , Drug Stability , Emulsions , Ophthalmic Solutions , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Emulsions/chemistry , Ophthalmic Solutions/chemistry , Hydrolysis , Castor Oil/chemistry , Cefuroxime/chemistry , Cefuroxime/administration & dosage , Cefuroxime/pharmacokinetics , Vancomycin/chemistry , Vancomycin/administration & dosage , Surface-Active Agents/chemistry , Chemistry, Pharmaceutical/methods , Suspensions , Water/chemistry , Solubility , Polysorbates/chemistry , Olive Oil/chemistry , Hexoses/chemistry , Drug Carriers/chemistryABSTRACT
OBJECTIVES: Therapeutic drug monitoring (TDM) of ß-lactam antibiotics in critically ill patients may benefit dose optimisation, thus improving therapeutic outcomes. However, rapidly and accurately detecting these antibiotics in blood remains a challenge. This research group recently developed a thermometric biosensor called the New Delhi metallo-ß-lactamase-1 (NDM-1) biosensor, which detects multiple classes of ß-lactam antibiotics in spiked plasma samples. METHODS: This study assessed the NDM-1 biosensor's effectiveness in detecting plasma concentrations of ß-lactam antibiotics in treated patients. Seven patients receiving cefuroxime were studied. Plasma samples collected pre- and post-antibiotic treatment were analysed using the NDM-1 biosensor and compared with liquid chromatography coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The biosensor detected plasma samples without dilution, and a brief pre-treatment using a polyvinylidene fluoride filter significantly lowered matrix effects, reducing the running time to 5-8 minutes per sample. The assay's linear range for cefuroxime (6.25-200 mg/L) covered target concentrations during the trough phase of pharmacokinetics in critically ill patients. The pharmacokinetic properties of cefuroxime in treated patients determined by the NDM-1 biosensor and the UPLC-MS/MS were comparable, and the cefuroxime plasma concentrations measured by the two methods showed statistically good consistency. CONCLUSION: These data demonstrate that the NDM-1 biosensor assay is a fast, sensitive, and accurate method for detecting cefuroxime plasma concentrations in treated patients and highlights the NDM-1 biosensor as a promising tool for on-site TDM of ß-lactam antibiotics in critically ill patients.
Subject(s)
Anti-Bacterial Agents , Biosensing Techniques , Cefuroxime , Drug Monitoring , Tandem Mass Spectrometry , beta-Lactamases , Humans , beta-Lactamases/blood , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/blood , Cefuroxime/blood , Cefuroxime/therapeutic use , Drug Monitoring/methods , Biosensing Techniques/methods , Male , Middle Aged , Female , Aged , Chromatography, Liquid/methods , Plasma/chemistry , Critical IllnessABSTRACT
In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic ß-lactam antibiotics and ß-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g-1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 - 0.2 ng mL-1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3-105.4 % for intra-day and 90.6-103.5 % for inter-day, with low relative standard deviations of 1.3-7.2 % and 4.9-10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.
Subject(s)
Cefoperazone , Cefuroxime , Hydrophobic and Hydrophilic Interactions , Limit of Detection , Nanotubes , Silicon Dioxide , Solid Phase Extraction , Sulbactam , Cefoperazone/blood , Cefoperazone/chemistry , Humans , Sulbactam/blood , Sulbactam/chemistry , Solid Phase Extraction/methods , Silicon Dioxide/chemistry , Nanotubes/chemistry , Cefuroxime/blood , Cefuroxime/chemistry , Clay/chemistry , Adsorption , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/chemistry , Polyethyleneimine/chemistry , Chromatography, High Pressure Liquid/methods , Reproducibility of ResultsABSTRACT
A 36-year-old male patient presented with a decrease in vision after undergoing scleral suturing for a left eye injury caused by an iron hook, combined with intravitreal injection of cefuroxime. Ocular examination revealed extensive gray-white edematous areas in the macular region, along with focal serous shallow retinal detachment in the posterior pole. Following admission, comprehensive ophthalmic examinations were conducted, leading to the diagnosis of toxic retinal damage in the left eye. Treatment with oral corticosteroids and interventions to improve microcirculation were initiated, resulting in improved visual acuity. At the six-month follow-up, the patient's visual acuity had recovered to 0.5.
Subject(s)
Cefuroxime , Humans , Male , Adult , Cefuroxime/adverse effects , Cefuroxime/administration & dosage , Intravitreal Injections , Anti-Bacterial Agents/adverse effects , Retinal Detachment , RetinaABSTRACT
After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.
Subject(s)
Cefuroxime , Floxacillin , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Cefuroxime/analysis , Cefuroxime/pharmacokinetics , Cefuroxime/blood , Chromatography, High Pressure Liquid/methods , Linear Models , Reproducibility of Results , Floxacillin/analysis , Floxacillin/pharmacokinetics , Floxacillin/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacokinetics , Bone and Bones/chemistry , Bone and Bones/metabolism , Synovial Membrane/chemistry , Synovial Membrane/metabolism , Limit of DetectionABSTRACT
Mycobacterium abscessus (Mab) affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, Mab poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual ß-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with ß-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)]. The sulopenem-CXM combination yielded low minimum inhibitory concentration (MIC) values for 54 clinical Mab isolates and ATCC19977 (MIC50 and MIC90 ≤0.25 µg/mL). Similar synergistic effects were observed in time-kill studies conducted at concentrations achievable in clinical settings. Sulopenem-CXM outperformed monotherapy, yielding ~1.5 Log10 CFU/mL reduction during 10 days. Addition of BLIs enhanced this antibacterial effect, resulting in an additional reduction of CFUs (~3 Log10 for sulopenem-CXM and AVI and ~4 Log10 for sulopenem-DUR). Exploration of the potential mechanisms of the synergy focused on their interactions with L,D-transpeptidases (Ldts; LdtMab1-LdtMab4), penicillin-binding-protein B (PBP B), and D,D-carboxypeptidase (DDC). Acyl complexes, identified via mass spectrometry analysis, demonstrated the binding of sulopenem with LdtMab2-LdtMab4, DDC, and PBP B and CXM with LdtMab2 and PBP B. Molecular docking and mass spectrometry data suggest the formation of a covalent adduct between sulopenem and LdtMab2 after the nucleophilic attack of the cysteine residue at the ß-lactam carbonyl carbon, leading to the cleavage of the ß-lactam ring and the establishment of a thioester bond linking the LdtMab2 with sulopenem. In conclusion, we demonstrated the biochemical basis of the synergy of sulopenem-CXM with or without BLIs. These findings potentially broaden the selection of oral therapeutic agents to combat Mab. IMPORTANCE: Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination ß-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.
Subject(s)
Anti-Bacterial Agents , Cefuroxime , Drug Synergism , Microbial Sensitivity Tests , Mycobacterium abscessus , Mycobacterium abscessus/drug effects , Anti-Bacterial Agents/pharmacology , Humans , Cefuroxime/pharmacology , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/drug therapy , beta-Lactamase Inhibitors/pharmacology , Molecular Docking Simulation , ProhibitinsABSTRACT
AIM: Our antimicrobial guidelines (AGs) were changed in 2021 to recommend once-daily ceftriaxone in place of three-times-daily cefuroxime as preferred cephalosporin. This analysis sought to assess the effects of this on incidence of Clostridioides difficile infection (CDI), third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and resource utilisation. METHOD: Before and after analysis of 30-day CDI and 3GCR-E incidence following receipt of cefuroxime/ceftriaxone pre- and post-AG change. Total nursing time and waste production relating to cefuroxime/ceftriaxone delivery were calculated pre- and post-change. RESULTS: CDI incidence was 0.6% pre- and 1.0% post-change (adjusted odds ratio [aOR] 1.44, p=0.07) and 3GCR-E incidence 3.5% and 3.1% (aOR 0.90, p=0.33). Mean per-quarter estimated nursing administration time decreased from 2,065 to 1,163 hours (902 nurse-hour reduction) and antibiotic-related waste generation from 1,131kg to 748kg (383kg reduction). Overall days of therapy per-quarter of cefuroxime/ceftriaxone were unchanged between periods. CONCLUSION: This simplification of our AG from a three-times-daily to a once-daily antibiotic resulted in considerable savings for our hospital (roughly 1.7 full-time equivalent nurses and over a tonne of waste yearly), with no significant increases in CDI or 3GCR-E. The impact of dosing schedules on non-antibiotic-spectrum factors, such as nursing time and resource usage, is worthy of consideration when designing AGs.
Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Ceftriaxone , Cefuroxime , Humans , Cefuroxime/therapeutic use , Cefuroxime/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Ceftriaxone/therapeutic use , Ceftriaxone/administration & dosage , Male , Female , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Middle Aged , Incidence , Aged , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Practice Guidelines as Topic , Drug Administration ScheduleABSTRACT
This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.
Subject(s)
Anaphylaxis , Drug Hypersensitivity , Male , Humans , Female , Middle Aged , Cefuroxime/adverse effects , Anaphylaxis/chemically induced , Anaphylaxis/complications , Retrospective Studies , Drug Hypersensitivity/etiology , Skin Tests/adverse effectsABSTRACT
BACKGROUND: Helicobacter pylori infection and its associated diseases represent a significant global health concern. Patients who cannot use amoxicillin pose a therapeutic challenge and necessitate alternative medications. Preliminary research indicates that cefuroxime demonstrates promising potential for eradicating H. pylori infection, and there is a lack of comprehensive review articles on the use of cefuroxime. MATERIALS AND METHODS: This study conducts a thorough systematic literature review and synthesis. A comprehensive systematic search was conducted in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data up to January 13, 2024. The search strategy utilized the following keywords: (Cefuroxime) AND (Helicobacter pylori OR Helicobacter nemestrinae OR Campylobacter pylori OR Campylobacter pylori subsp. pylori OR Campylobacter pyloridis OR H. pylori OR Hp) for both English and Chinese language publications. Sixteen studies from five different countries or regions were included in final literature review. RESULTS: Analysis results indicate that H. pylori is sensitive to cefuroxime, with resistance rates similar to amoxicillin being relatively low. Regimens containing cefuroxime have shown favorable eradication rates, which were comparable to those of the regimens containing amoxicillin. Regarding safety, the incidence of adverse reactions in cefuroxime-containing eradication regimens was comparable to that of amoxicillin-containing regimens or other bismuth quadruple regimens, with no significant increase in allergic reactions in penicillin-allergic patients. Regarding compliance, studies consistently report high compliance rates for regimens containing cefuroxime. CONCLUSION: Cefuroxime can serve as an alternative to amoxicillin for the patients allergic to penicillin with satisfactory efficacies, safety, and compliance.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Cefuroxime/therapeutic use , Anti-Bacterial Agents/adverse effects , Drug Therapy, Combination , Amoxicillin/therapeutic use , Bismuth/adverse effects , Penicillins/therapeutic use , Treatment Outcome , Proton Pump Inhibitors/therapeutic useABSTRACT
PURPOSE: To study the incidence, predictive factors, etiology, and visual consequences of postoperative endophthalmitis (PE) in relation to 3 intracameral (IC) antibiotic regimes. SETTING: Swedish National Cataract Register entries from 2011 through 2017. DESIGN: Observational retrospective study. METHODS: PE incidence, influencing factors, bacteriology, and visual outcome were analyzed regarding the 3 major prophylactic IC protocols. RESULTS: The overall incidence of PE was 0.023% or 177 cases in 764 513 cataract procedures. Analyzed per IC regime, the rates of PE were 0.024% (126 cases in 514 916 surgeries) for cefuroxime, 0.020% (25 cases in 122 340 surgeries) for moxifloxacin, and 0.017% (20 cases in 121 045 surgeries) for combined cefuroxime-ampicillin. Incidences were not statistically significantly different from one another. Gram-positive bacteria caused 89.0% of culture positive cases. Enterococci as pathogens were significantly more frequent with IC cefuroxime than with moxifloxacin, P = .006, or cefuroxime-ampicillin, P < .001, while streptococci other than enterococci were more common with moxifloxacin than with cefuroxime, P < .001. Bacterial susceptibility to the given antibiotics was demonstrated in 21.3% of PE cases treated with cefuroxime, which was statistically significantly lower than proportions found with cefuroxime-ampicillin, 60.0%, P = .015, or with moxifloxacin, 88.2%, P < .001. Visual outcome worse than 20/200 was similar in the groups ranging from 42.0% to 53.7%. CONCLUSIONS: No statistically significant differences in PE incidence or visual outcome results between treatment groups were demonstrated. However, differences in etiology and bacterial sensitivity were found between the prophylactic IC treatments.
Subject(s)
Anti-Bacterial Agents , Cataract Extraction , Endophthalmitis , Eye Infections, Bacterial , Registries , Endophthalmitis/epidemiology , Endophthalmitis/microbiology , Endophthalmitis/prevention & control , Humans , Sweden/epidemiology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Incidence , Eye Infections, Bacterial/epidemiology , Eye Infections, Bacterial/microbiology , Cataract Extraction/adverse effects , Aged , Male , Female , Antibiotic Prophylaxis , Cefuroxime/therapeutic use , Postoperative Complications/epidemiology , Visual Acuity , Anterior Chamber/drug effects , Middle Aged , Aged, 80 and over , Moxifloxacin/therapeutic useABSTRACT
OBJECTIVES: We aimed to identify the prevalence, bacterial isolates, antimicrobial susceptibility profile, and factors associated with asymptomatic bacteriuria (ASB) in patients with type 2 diabetes mellitus (T2DM) in rural southwestern Nigeria. METHODS: We performed a hospital-based cross-sectional study of patients with T2DM and ASB. Demographic and clinical data were collected using questionnaires. Urine samples were cultured using standard laboratory procedures, and bacterial colonies were isolated and antimicrobial sensitivity was performed using the disc diffusion technique. Relationships between variables were assessed using adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Of the 280 participants, 73 (26.1%) had ASB (95% CI: 20.9%-31.2%). The most commonly identified isolate was E. coli (45/73; 61.7%), 100.0% of which were sensitive to cefuroxime but resistant to ciprofloxacin. Female sex (AOR, 6.132; 95% CI: 2.327-16.157), living below the poverty line (AOR, 2.066; 95% CI: 1.059-4.029), uncontrolled blood glucose (AOR, 2.097; 95% CI: 1.000-4.404), and a history of indwelling urethral catheterization (AOR, 14.521; 95% CI: 4.914-42.908) were associated with ASB. CONCLUSION: The findings suggest that cefuroxime should be used as an empirical treatment, pending urine culture and sensitivity, and that efforts should be made to prevent ASB in rural southwestern Nigeria.
Subject(s)
Anti-Infective Agents , Bacteriuria , Diabetes Mellitus, Type 2 , Humans , Female , Bacteriuria/drug therapy , Bacteriuria/epidemiology , Bacteriuria/microbiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Cross-Sectional Studies , Escherichia coli , Cefuroxime , Nigeria/epidemiologyABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most ß-lactams, the first-line treatment for methicillin-susceptible S. aureus. A phenotype termed "NaHCO3-responsiveness" has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care ß-lactams in the presence of physiologically relevant concentrations of NaHCO3, in vitro and ex vivo; moreover, such "NaHCO3-responsive" isolates can be effectively cleared by ß-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO3 exposure on NaHCO3-responsive MRSA is to repress WTA synthesis. This NaHCO3 effect mimics the phenotype of tarO-deficient MRSA, including sensitization to the PBP2-targeting ß-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO3 exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO3 and/or TCP enhanced susceptibility to CFX in vitro, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an ex vivo simulated endocarditis vegetations (SEV) model, in NaHCO3-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO3), pre-exposure to TCP prior to infection sensitized the NaHCO3-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO3 is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific ß-lactam agents.
Subject(s)
Endocarditis, Bacterial , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Anti-Bacterial Agents/pharmacology , Cefuroxime/pharmacology , Bicarbonates/pharmacology , Staphylococcus aureus , beta-Lactams/pharmacology , Endocarditis, Bacterial/drug therapy , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapyABSTRACT
BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the preplanned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.
Subject(s)
Antibiotic Prophylaxis , Cefuroxime , Spinal Fusion , Surgical Wound Infection , Humans , Spinal Fusion/adverse effects , Spinal Fusion/methods , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Male , Female , Antibiotic Prophylaxis/methods , Middle Aged , Case-Control Studies , Cefuroxime/administration & dosage , Cefuroxime/therapeutic use , Aged , Retrospective Studies , Anti-Bacterial Agents/administration & dosage , Adult , Time FactorsABSTRACT
Environmental conditions can lead to changes in the physical and chemical structures of drug products. In this study, the stability of cefuroxime tablets stored under adverse conditions was evaluated based on total directional-hemispherical reflectance (THR). The THR value was measured before and after the tablets' exposure to stress factors (temperature of 45 °C and UV radiation). Each measurement was performed three times within seven spectral bands at the beginning of the experiment (day 0), and then on days 1, 2, 3, 5, and 7. In addition, hyperspectral profiles (400-1030 nm) were analyzed on days 0 and 7. A significant decrease in THR values in all wavelength ranges was observed when day 7 vs. day 0 were compared, especially for spectral bands of 335-380 nm and 1700-2500 nm (Δ = 0.220, p < 0.001 and Δ = 0.171, p < 0.001, respectively). The hyperspectral analysis confirmed a decrease in the reflectance after the end of stress conditions in the visible light range (400-700 nm) compared to tablets before the experiment. This may indicate that more radiation entered the tablets. In conclusion, the THR of cefuroxime tablets decreases during the exposure to heat and UV radiation, which may result from some physicochemical changes that have occurred during storage.
Subject(s)
Cefuroxime , Ultraviolet Rays , Cefuroxime/chemistry , Temperature , Light , TabletsABSTRACT
BACKGROUND: The selection of prophylactic antibiotics for preventing post-operative pulmonary infections in smoking patients undergoing video-assisted thoracoscopic lung surgery (VATLS) is not clear. METHODS: In this retrospective cohort study, the outcomes of 572 smoking patients undergoing VATLS with prophylactic cefazolin/cefuroxime or other antibiotics were analyzed. Patients were classified as cefazolin/cefuroxime group and the control group. A 1:1 propensity score matching was also performed. RESULTS: The primary outcome of the incidence of post-operative pulmonary infection did not differ significantly between the two groups (23.7% vs 30.5%, RR = 0.777, 95%CI 0.564 ~ 1.070 p = 0.113). Similarly, secondary outcomes including the incidence of post-operative fever, the white blood cell count and neutrophils on the 3rd day after the surgery, and time for blood routine test recovery were all found without significant difference between the two groups. In the multivariate logistic regression model, no association was found between prophylactic use of cefazolin/cefuroxime and post-operative pulmonary infections after controlling other possible confounding factors (OR = 0.685, 95%CI 0.441 ~ 1.065, p = 0.093). CONCLUSIONS: Prophylactic use of cefazolin/cefuroxime was not associated with more adverse clinical outcomes among smoking populations undergoing VATLS when compared with broad-spectrum antibiotics and the two drugs are still feasible for peri-operative prophylactic use for smoking population before the surgery.
Subject(s)
Cefazolin , Pneumonia , Humans , Cefazolin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Cefuroxime , Retrospective Studies , Propensity Score , Thoracic Surgery, Video-Assisted , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Lung , Smoking , Antibiotic Prophylaxis , Surgical Wound Infection/epidemiologyABSTRACT
Nobiletin (NOB) exhibits significant biological activities and may be a potential dietary treatment for antibiotic-associated gut dysbiosis. In this study, mice were gavaged with 0.2 mL day-1 of 12.5 g L-1 cefuroxime (LFX) and 10 g L-1 levofloxacin (LVX) for a duration of 10 days, accompanied by 0.05% NOB to investigate the regulatory effect and potential mechanisms of NOB on antibiotic-induced intestinal microbiota disorder and intestinal barrier dysfunction. Our results indicated that dietary NOB improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins (TJs) and the number of goblet cells. Furthermore, dietary NOB reduced the levels of serum lipopolysaccharide (LPS) and pro-inflammatory factors (TNF-α and IL-1ß), thereby facilitating the restoration of the intestinal mucosal barrier. Additionally, dietary NOB increased the abundance of beneficial bacteria f_Lachnospiraceae and regulated the metabolic disorders of short-chain fatty acids (SCFAs) and bile acids (BAs). Notably, NOB supplementation resulted in elevated levels of butyric acid and lithocholic acid (LCA), which contributed to the repair of the intestinal mucosal barrier function and the maintenance of intestinal homeostasis. Collectively, our results propose a healthy dietary strategy for the prevention or mitigation of antibiotic-associated gut dysbiosis by dietary NOB.
Subject(s)
Flavones , Gastrointestinal Microbiome , Intestinal Diseases , Animals , Mice , Cefuroxime/adverse effects , Levofloxacin/adverse effects , Dysbiosis/chemically induced , Intestinal Diseases/microbiology , Anti-Bacterial Agents/adverse effectsABSTRACT
BACKGROUND: The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI). METHODS: We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is "remission" at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries. DISCUSSION: In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime. TRIAL REGISTRATION: ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022).
Subject(s)
Antibiotic Prophylaxis , Neoplasms , Orthopedic Procedures , Humans , Antibiotic Prophylaxis/methods , Cefuroxime , Neoplasms/surgery , Neoplasms/drug therapy , Orthopedic Procedures/adverse effects , Prospective Studies , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Vancomycin/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. METHODS: To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. RESULTS: This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. CONCLUSIONS: Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.
Subject(s)
Cefuroxime , Models, Biological , Humans , Pregnancy , Female , Software , Amniotic Fluid , MusclesABSTRACT
Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this phenomenon are still not fully understood. This study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), this study found that the WT/ΔSR1039 mutants caused a two-fold increase in sensitivity to ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a two-fold increase in sensitivity to cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P<0.01), and changed the oxidative stress level of bacteria to reduce their survival rate (P<0.001). Subsequently, this study explored the molecular mechanisms by which sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby regulating the expression of pore protein gene ompD indirectly and negatively to increase bacterial sensitivity to ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce resistance to cefuroxime, and reduced the expression of type-III-secretion-system-related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These results provide new insights into Hfq-sRNA-mRNA regulation of the resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies.
Subject(s)
Dysentery, Bacillary , RNA, Small Untranslated , Shigella , Humans , Shigella sonnei/genetics , Virulence/genetics , HeLa Cells , Cefuroxime/metabolism , Shigella flexneri/genetics , Dysentery, Bacillary/microbiology , Ampicillin/pharmacology , Ampicillin/metabolism , Drug Resistance, Microbial , Gentamicins , RNA, Messenger , RNA, Small Untranslated/genetics , RNA, Small Untranslated/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolismABSTRACT
BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). METHODS: We reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. RESULTS: In the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. CONCLUSION: The use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.