Antibiotics-Basel最新文献

Background/Objectives: Cefazolin is commonly administered for surgical antibiotic prophylaxis. This review aims to examine whether target unbound plasma and tissue cefazolin concentrations are reached following prophylactic administration across multiple surgical subtypes. The primary outcome was a lower limit of cefazolin concentration variability (mean-SD, lower quartile, or lower range) in unbound plasma and/or tissue > 2 mg·L^-1, the epidemiological cut-off (ECOFF) value for Staphylococcus aureus at skin incision and/or closure. Methods: Prisma 2020 guidelines were followed, and the protocol is registered in PROSPERO (CRD42021080289). A literature search using MEDLINE (PubMed), Embase, CENTRAL, CINAHL, and further databases was performed to identify studies in which prophylactic cefazolin was administered to adult surgical patients (≥18 years old) undergoing elective surgery, and unbound plasma and tissue concentrations were measured at skin incision and closure. Exclusion criteria included languages other than English, emergency surgery, cefazolin being administered for any reason other than surgical site prophylaxis, and whether patients received any cefazolin within the 48 h prior to the prophylactic dose. The search was repeated in August 2025 to ensure currency. A narrative assessment of the methodological quality was performed. The data were synthesised in a narrative and tabular form, and the certainty of the evidence was assessed using the GRADE approach. Results: A total of 37 studies with 1102 patients met the inclusion criteria. Twelve bariatric studies and 378 patients, 9 cardiac studies and 197 patients, 8 obstetric studies and 277 patients, 6 orthopaedic studies and 176 patients, 3 abdominal surgery studies and 62 patients, and 1 vascular study and 12 patients were included. Two studies met the inclusion criteria for both bariatric and abdominal surgery. The lower limit of variability of the unbound plasma concentration was consistently >2 mg·L^-1. The reported lower limits of variability in tissue concentrations of bariatric surgery were conflicting. Only one study in cardiac surgery assessed the current dosing regimens. The lower range of variability of tissue concentrations was consistently >2 mg·L^-1 in the orthopaedic, obstetric, abdominal, and vascular surgery subtypes. Conclusions: The current dosing approaches in the obstetric, orthopaedic, abdominal, and vascular surgery groups are reassuring for achieving effective concentrations, although the overall data are sparse. It is unclear if increased dosing is warranted in bariatric surgery patients, and further investigations in cardiac surgery with current dosing regimens are required.

Introduction: Globally, microbial infections are projected to be among the leading causes of death by 2050 due to rising drug resistance. Antimicrobials are vital for treating both animals and humans worldwide. However, their overuse and misuse accelerate drug resistance, posing a serious threat to public health. Coumarin is a naturally occurring compound contributing health-beneficial features in drug discovery. Its high solubility in organic solvents, high bioavailability, simple structure, low toxicity, and low molecular weight make it an ideal candidate for combining with other pharmacophores to develop new therapeutic agents. This compound exhibits several biological activities, including antimicrobial, anticancer, anti-inflammatory, antidiabetic, neuroprotective, and anticoagulant effects, motivating medicinal researchers to hybridize it with other compounds to enhance its pharmacological efficacy. Hybridization of different pharmacophores via suitable linkers, including cleavable and non-cleavable ones, is a promising approach in drug development, resulting in new therapeutics with improved biological activity. Therefore, the hybridization of coumarin with other pharmacophores has become an interesting paradigm for medicinal scientists. Aim: This review aims to summarize the existing scientific literature on coumarin-based hybrid compounds with antimicrobial capabilities and discuss the structure-activity relationship (SAR) of these hybrids to potentially guide future research on and development of coumarin-based drugs for microbial treatment. Material and Methods: The review focuses on open-access literature about coumarin hybrid drugs available through searching tools such as Google, Google Scholar, ScienceDirect, and Scopus, published from 2024 to 2025. Results: Coumarin hybrids exhibit promising antimicrobial activity, particularly against S. aureus and C. albicans. The SAR reveals that halogenation, bulky aromatics, nitro, and hydroxyl groups enhance the interaction of the coumarin rings with amino acid residues. Conclusions: The reported coumarin hybrids showed a promising antimicrobial activity, with structural modifications influencing their activity. Hence, more studies, including more pre-clinical and clinical evaluations, are recommended for these hybrid compounds.

Background: Prevention of hospital-onset Clostridioides difficile infection (HO-CDI) is a priority for hospitals. In addition to standard infection control measures, some probiotics show promise in reducing HO-CDI incidence. However, prior research has produced mixed results. Methods: Retrospective, observational cohort study of HO-CDI incidence among inpatients treated with or without BioK+ probiotic prophylaxis. BioK+, a probiotic with three Lactobacilli strains, was administered to patients on antibiotics with high risk for HO-CDI. BioK+ was continued for 5 days after antibiotics were discontinued, or the patient was discharged. The primary outcome was HO-CDI incidence. Results: Out of 494 eligible patients on high-risk antibiotics, 343 patients received BioK+ probiotics. No cases of HO-CDI were identified in patients who received BioK+, compared to three cases among patients not on BioK+ (p = 0.028). In the baseline period (1 April 2021-31 March 2022) the HO-CDI incidence density was 5.62 per 10,000 bed-days. In the BioK+ probiotic period (1 April 2022-31 March 2023), the incidence density was 2.22 cases per 10,000 patient days (p = 0.03). Conclusions: When bundled with standard infection control practices, the use of BioK+ probiotics was associated with a statistically significant decreased incidence of HO-CDI among patients prescribed high-risk antibiotics.

Background/Objectives: Antimicrobial resistance (AMR) represents a major global health challenge, driving the need for rapid and accurate diagnostic tools. Novel molecular assays, including multiplex PCR and DNA microarray-based systems, have emerged to detect antimicrobial resistance genes (ARGs) alongside bacterial identification. Methods: In this study, we evaluated the performance of the HybriSpot12 PCR AUTO (HS12a) system and the MDR Direct Flow Chip (MDR-FC) Kit-an automatic microarray assay based on reverse hybridization-for the detection of ARGs directly from positive blood culture (PBC) samples. A total of 111 Gram-negative bacterial isolates (92 Enterobacterales, 14 Acinetobacter baumannii, and 6 Pseudomonas spp.), previously characterized by whole-genome sequencing (WGS), were each used to generate a PBC, which was then analyzed with the HS12a/MDR-FC assay. Results: We demonstrated perfect agreement for the detection of macrolide resistance genes across all bacterial species and high agreement for genes conferring resistance to sulfonamides and β-lactams. In contrast, aminoglycoside resistance genes showed only moderate agreement, with minor discrepancies observed in Klebsiella pneumoniae and Escherichia coli, largely attributable to specific SNP variations. Conclusions: The HS12a/MDR-FC assay includes 51 ARGs, though not all were represented in our isolate set, and some false negatives were observed. Despite these limitations, its broad coverage and rapid turnaround remain advantageous compared to other rapid assays with fewer targets. Future refinements should aim at broader gene coverage, inclusion of key mutations, and detection of emerging variants, making this approach a promising tool for rapid AMR surveillance and antimicrobial stewardship.

Background and Objectives:Helicobacter pylori (H. pylori) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic resistance, particularly to clarithromycin and fluoroquinolones, represent a major therapeutic challenge. The objective of this study was to determine the prevalence of resistance-associated mutations in H. pylori-positive gastric biopsy samples from western Romania. Materials and Methods: We conducted a prospective study from January to December 2024, enrolling 138 patients undergoing gastroscopy. Biopsies were collected from the gastric antrum, and H. pylori infection was confirmed using the rapid urease test (RUT). Positive samples were further analyzed with the GenoType HelicoDR assay to detect mutations in the 23S rRNA gene (clarithromycin resistance) and gyrA gene (fluoroquinolone resistance). Clinical, demographic, and endoscopic data were also collected. Results:H. pylori infection was confirmed in 41.3% of the patients (57), of whom 63.2% (36) were treatment-naïve and 36.8% (21) had prior eradication therapy. Among treatment-naïve patients, clarithromycin resistance was identified in 19.4%, whereas previously treated patients showed a markedly higher resistance rate of 47.6% (p = 0.018). All clarithromycin-resistant cases carried the A2147G (23S MUT3) mutation. Fluoroquinolone resistance was present in 13.9% of naïve patients and increased to 23.8% in those with prior eradication therapy, with resistance linked to gyrA mutations at codons 87 (N87K) and 91 (D91 variants). Combined resistance to both antibiotics was observed only in a subset of previously treated patients. Conclusions: Primary resistance to clarithromycin in western Romania exceeds the 15% threshold defined by international guidelines, making clarithromycin-based triple therapy unsuitable as an empirical first-line option. The findings support the use of bismuth quadruple therapy as the preferred empirical regimen in this region. Also, molecular testing proved effective for rapid identification of resistance-associated mutations.

While many paediatric patients have a penicillin allergy label, most do not have a true allergy. The penicillin allergy label is associated with a lifetime risk of avoidable use of broad-spectrum antibiotics, higher healthcare costs, and poorer clinical outcomes. In this review, we present different types of penicillin allergies, de-labelling approaches, and significance on paediatric patients. We also discuss parental perspectives regarding penicillin de-labelling in the emergency setting. We highlight that despite the challenges posed by barriers such as overcrowding and the need for quick patient turnover in the PED, the availability of resources and expertise in managing potential allergic reactions makes the PED an ideal environment where PCN de-labelling can be both feasible and effective. We show that further education of both parents and healthcare professionals is essential to overcoming misconceptions, alleviating safety concerns, fostering trust in the de-labelling process, and normalising de-labelling in the PED.

Introduction:Streptococcus suis is a zoonotic pathogen of great relevance to the swine industry, characterized by high genetic diversity and multiple serovars (SVs) with varying clinical prevalence. Biofilm formation represents a key factor in its virulence, antimicrobial resistance and infection persistence. Methods: We integrated gene expression profiling of biofilm-associated genes by RT-qPCR and antimicrobial susceptibility in planktonic and mature biofilm against five antibiotics in S. suis field isolates belonging to SV1, SV2, SV7 and SV9. Results: Expression of quorum sensing and adhesion genes (luxS, fbps, sadP and srtA) was significantly higher in SV2, the poorest biofilm formers, and inversely correlated with biofilm biomass, suggesting these factors act during early biofilm establishment. Correlation analysis indicated coordinated regulation among genes involved in quorum sensing, adhesion and capsule synthesis. Antimicrobial susceptibility testing revealed a high frequency of non-wild type phenotypes in planktonic cells for tetracycline, erythromycin and clindamycin (>80%), while ampicillin and ciprofloxacin were less frequent. Mature biofilms exhibited a significant increase in antimicrobial tolerance for all antibiotics tested, with SV2 showing the greatest susceptibility. Conclusions: These data highlight serovar-specific biofilm regulation patterns and enhanced drug tolerance in established S. suis biofilms.

Background: Due to the rising incidence of ESBL-producing bacterial infections, the use of carbapenems has increased over recent decades. Carbapenems are part of the group of last-resort antimicrobials and are used widely as empirical therapy, which is contributing to the growing rate of antimicrobial resistance (AMR). De-escalation has been proven to be a successful tool in antimicrobial stewardship programmes (ASPs) in minimising the occurrence of AMR and decreasing the use of antimicrobials. The purpose of the study was to find the reasons why prescribers do not de-escalate from empiric carbapenem therapy.

Methods: This retrospective quantitative study was conducted in a private hospital in South Africa. The infection markers and cultures of these patients were considered.

Results: De-escalation was practiced in 17% of the patients. Empiric carbapenem therapy was started in 11.2% of patients and the most prescribed carbapenem was ertapenem (62.4%). Cultures were available in 71.1% of the study population. De-escalation was not performed in 83% of patients, mostly since their infection markers decreased with carbapenem therapy (45.9%) or because of culture unavailability (28.9%).

Conclusion: The study came to the conclusion that prescribers do not want to de-escalate once their patients are improving on current treatment or if there are no cultures available.

Background: Cefiderocol (CFD) is a novel cephalosporin targeting multidrug-resistant Gram-negative bacterial (GNB) infections. It mimics siderophores to enter into GNB through iron transport receptors. However, evidence on its use in Hospital at Home (HaH) and outpatient parenteral antibiotic therapy (OPAT) programs remains scarce. Objectives: The primary objective was to evaluate feasibility and efficacy of CFD in HaH setting. The secondary objective was to assess its safety. Methods: A retrospective, observational study was conducted across six Spanish centers between January 2023 and December 2024. Adult patients with documented GNB infections treated with CFD in HaH units were included. Demographic, clinical and microbiological data, treatment characteristics, and outcomes were collected. Statistical analysis was descriptive; no inferential or correlation tests were performed. Results: 27 patients were included; 70.4% were male, with a median age of 69 years. Most infections were nosocomial (65.4%), particularly skin and soft tissue (37%). Septic shock occurred in 14.8% of patients. Pseudomonas aeruginosa (66.7%) and Klebsiella pneumoniae (14.8%) were the most frequent pathogens involved, with Verona Integron-encoded metallo-B-lactamase (VIM, 50%) being the predominant resistance mechanism. CFD was used as a first-line therapy in 63% of cases and in combination with other antibiotics in 40.7%. Median treatment duration was 21.7 days. Administration was mainly via peripherally inserted central catheters (PICC, 33.3%) and electronic pumps (52%). Adverse effects occurred in 7.4% of patients, leading to discontinuation in one case. A total of 88.8% of patients achieved clinical success, with 7.7% recurrence within a month. Escalation of care occurred in 7.7% and 19.2% were readmitted within a month after HaH discharge. No infection-related deaths were reported. Conclusions: CFD is a feasible, safe, and effective treatment for difficult-to-treat GNB infections in HaH settings.

Backgrounds/Objectives: This study aimed to quantify biofilm production and characterize the distribution of the biofilm-associated ica genes (icaA, icaD, icaB, icaC, icaR) in coagulase-negative staphylococci (CoNS) isolates, and to assess the association between these genes and antibiotic resistance profiles. Methods: A total of 121 CoNS isolates collected at Ümraniye Training and Research Hospital between 1 January and 30 August 2024 were identified by VITEK 2 Compact and MALDI-TOF MS. Biofilm production was quantified using the microtiter plate assay, and the presence of ica genes was determined by quantitative real-time PCR (qPCR). Antimicrobial susceptibility testing (AST) was performed with the VITEK 2 Compact (bioMérieux), and minimum inhibitory concentrations (MICs) were interpreted according to EUCAST criteria. Results:S. epidermidis was found to have the highest biofilm production capacity among the CoNS isolates, followed by S. haemolyticus. The icaA gene was detected in 99.17% of isolates, followed by icaR (70.24%), icaD (55.37%), and both icaB and icaC (28.92% each). The highest resistance rates were observed for oxacillin (85.8%) and erythromycin (85.1%), while all isolates remained susceptible to linezolid, daptomycin, and vancomycin. Conclusions: The high prevalence of ica genes in CoNS isolates indicates that biofilm formation plays a critical role in the pathogenesis of these species. The findings reveal that CoNS have a strong biofilm production potential, which is a decisive factor in their pathogenicity. However, the high methicillin resistance rates emerge as one of the main factors limiting the effectiveness of current treatment options. Therefore, future studies need to focus on the development of anti-biofilm approaches and alternative therapeutic strategies.