BACKGROUND: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin amongst guidelines. However, there is variability amongst guidelines for maximal ST NICs of cephalosporins.
OBJECTIVE: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants.
METHODS: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at six increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm than negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted.
RESULTS: A total of 747 participants with a median age of 64 (IQR 54-72), 52% males, 85% White, and 92% Non-Hispanic underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/ml): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely non-irritant close or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data.
CONCLUSIONS: Our results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared to previously published nonirritant concentrations, we propose a 2 to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.

UNASSIGNED: The incidence of microorganisms with extended-spectrum beta-lactamase (ESBL) is on the rise, posing a significant public health concern. The current application of machine learning (ML) focuses on predicting bacterial resistance to optimize antibiotic therapy. This study employs ML to forecast the occurrence of bacteria that generate ESBL and demonstrate resistance to multiple antibiotics (MDR).
UNASSIGNED: Six popular ML algorithms were initially trained on antibiotic resistance test patient reports (n = 489) collected from Al-Hussein/Salt Hospital in Jordan. Trained outcome models predict ESBL and multidrug resistance profiles based on microbiological and patients\' clinical data. The results were utilized to select the optimal ML method to predict ESBL\'s most associated features.
UNASSIGNED: Escherichia coli (E. coli, 82%) was the most commonly identified microbe generating ESBL, displaying multidrug resistance. Urinary tract infections (UTIs) constituted the most frequently observed clinical diagnosis (68.7%). Classification and Regression Trees (CART) and Random Forest (RF) classifiers emerged as the most effective algorithms. The relevant features associated with the emergence of ESBL include age and different classes of antibiotics, including cefuroxime, ceftazidime, cefepime, trimethoprim/ sulfamethoxazole, ciprofloxacin, and gentamicin. Fosfomycin nitrofurantoin, piperacillin/tazobactam, along with amikacin, meropenem, and imipenem, had a pronounced inverse relationship with the ESBL class.
UNASSIGNED: CART and RF-based ML algorithms can be employed to predict the most important features of ESBL. The significance of monitoring trends in ESBL infections is emphasized to facilitate the administration of appropriate antibiotic therapy.

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.

BACKGROUND: Aminopenicillins are recommended agents for non-invasive Haemophilus influenzae infections. One of the mechanisms of resistance to β-lactams is the alteration of the transpeptidase region of penicillin binding protein 3 (PBP3) which is caused by mutations in the ftsI gene. It was shown that exposure to beta-lactams has a stimulating effect on increase of prevalence of H. influenzae strains with the non-enzymatic mechanism of resistance.
OBJECTIVE: The aim of our study was to compare the mutational potential of ampicillin and cefuroxime in H. influenzae strains, determination of minimum inhibitory concentration and the evolution of mutations over time, focusing on amino acid substitutions in PBP3.
METHODS: 30 days of serial passaging of strains in liquid broth containing increasing concentrations of ampicillin or cefuroxime was followed by whole-genome sequencing.
RESULTS: On average, cefuroxime increased the minimum inhibitory concentration more than ampicillin. The minimum inhibitory concentration was increased by a maximum of 32 fold. Substitutions in the PBP3 started to appear after 15 days of passaging. In PBP3, cefuroxime caused different substitutions than ampicillin.
CONCLUSIONS: Our experiment observed differences in mutation selection by ampicillin and cefuroxime. Selection pressure of antibiotics in vitro generated substitutions that do not occur in clinical strains in the Czech Republic.

UNASSIGNED: Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes remain unclear.
UNASSIGNED: This study aimed to investigate the post-marketing safety of cefuroxime, particularly concerning formulations and routes.
UNASSIGNED: A retrospective pharmacovigilance study of cefuroxime was conducted using the data from Food and Drug Administration Adverse Event Reporting System database.
UNASSIGNED: The clinical characteristics and concomitant drugs reported with cefuroxime were investigated. Adverse event signals of cefuroxime were identified based on four disproportionality algorithms. The signal differences of cefuroxime across formulations and routes were further examined.
UNASSIGNED: A total of 1810 adverse event reports associated with cefuroxime were identified, and 181 cefuroxime-associated signals were detected. Compared with tablets, injections were more likely to cause preferred terms \'blood pressure decreased\' and \'anaphylactic shock\'. In addition, system organ class \'eye disorders\' significantly increased when cefuroxime was administered intraocularly, underscoring the importance of exercising caution regarding ocular toxicity.
UNASSIGNED: The adverse events associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.
Post-marketing safety concerns with cefuroxime.
UNASSIGNED: Cefuroxime is a commonly used antibiotic. This study investigated the safety of cefuroxime using Food and Drug Administration Adverse Event Reporting System database.
UNASSIGNED: We analyzed the clinical characteristics and concomitant drugs reported with cefuroxime. Then, we detected the signals of cefuroxime. We further examined the signal differences of cefuroxime across formulations and routes.
UNASSIGNED: We retrieved 1810 reports and identified 181 signals associated with cefuroxime. In comparison to tablets, injections had a higher likelihood of causing decreased blood pressure and anaphylactic shock. Furthermore, the administration of cefuroxime intraocularly increased the possibility of experiencing eye disorders.
UNASSIGNED: The signals associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.

OBJECTIVE: Therapeutic drug monitoring (TDM) of β-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-β-lactamase-1 (NDM-1) biosensor, which detects multiple classes of β-lactam antibiotics in spiked plasma samples.
METHODS: This study assessed the NDM-1 biosensor\'s effectiveness in detecting plasma concentrations of β-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.
CONCLUSIONS: 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 β-lactam antibiotics in critically ill patients.

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.

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 β-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with β-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 β-lactam carbonyl carbon, leading to the cleavage of the β-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.
OBJECTIVE: 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 β-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.

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.
患者男性，36岁。因左眼被铁钩击伤行左眼巩膜清创缝合联合玻璃体内注入头孢呋辛后视力下降就诊。眼部检查发现黄斑区可见大片状灰白色水肿区，后极部视网膜局限性浆液性浅脱离。入院完善眼科辅助检查，诊断为左眼中毒性视网膜病变。经口服糖皮质激素、改善微循环等治疗，患者视力提高。随访6个月，患者视力恢复至0.5。.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.