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Calcium silicate cements (CSCs) are often used in endodontics despite some limitations related to their physical properties and antibacterial efficacy. This study aimed to develop and demonstrate the viability of a series of CSCs that were produced by sol-gel method and further modified with mesoporous bioactive glass nanoparticles (MBGNs) and collagen, for endodontic therapy. Calcium silicate (CS) particles and MBGNs were synthesized by the sol-gel method, and their elemental, molecular, and physical microstructure was characterized. Three CSCs were developed by mixing the CS with distilled water (CS+H 2 O), 10 mg/mL collagen solution (CS+colH 2 O), and MBGNs (10 %) (CSmbgn+colH 2 O). The mixing (MT) and setting (ST) times of the CSCs were determined, while the setting reaction was monitored in real-time. Antibacterial efficacy against Enterococcus faecalis (E. faecalis) and regenerative potential on dental pulp stem cells (DPSCs) were also analyzed. The CS+H 2 O displayed a ST comparable to commercial products, while CSmbgn+colH 2 O achieved the longest MT of 68 s and the shortest ST of 8 min. All the experimental CSCs inhibited the growth of E. faecalis. Additionally, compared to the control group, CSCs supported cell proliferation and spreading and mineralized matrix production, regardless of their composition. Tested CSCs presented potential as candidates for pulp therapy procedures. Future research should investigate the pulp regeneration mechanisms alongside rigorous antibacterial evaluations, preferably with multi-organism biofilms, executed over extended periods. [Display omitted] • Novel dental cements developed from calcium silicate, bioactive glass and collagen. • 10 % bioactive glass nanoparticles shorten the setting time of calcium silicate cement. • Developed calcium silicate cements are antimicrobial against E. faecalis. • Modest regeneration effect of mesoporous bioactive glass and collagen inclusion. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and antibiotic therapy in patients with sepsis reduce morbidity and mortality, thus pre-hospital management is likely to affect patient outcomes. Pre-hospital administration may increase the risk of unnecessary use of broad-spectrum antibiotics, but identification of an infectious focus enables more targeted antibiotic therapy. The aim of this study was to investigate how paramedics, with or without the assistance of general practitioners, can administer empiric intravenous antibiotic treatment against sepsis in a timely manner. Methods: Cohort study of patients with suspected sepsis that received pre-hospital intravenous antibiotics and were transported to hospital. The setting was mainly rural with long average distance to hospital. Patients received targeted antibiotic treatment after an assessment based on clinical work-up supported by scoring systems. Patients were prospectively included from May 2018 to August 2022. Results are presented as median or absolute values, and chi-square tests were used to compare categorical data. Results: We included 328 patients. Median age was 76 years (IQR 64, 83) and 48.5% of patients were female. 30-days all-cause mortality was 10.4%. In cases where a suspected infectious focus was determined, the hospital discharge papers confirmed the pre-hospital diagnosis focus in 195 cases (79.3%). The presence of a general practitioner during the pre-hospital assessment increased the rate of correctly identified infectious focus from 72.6% to 86.1% (p = 0.009). Concordance between pre-hospital identification of a tentative focus and discharge diagnosis was highest for lower respiratory tract (p = 0.02) and urinary tract infections (p = 0.03). Antibiotic treatment was initiated 44 min (median) after arrival of ambulance, and median transportation time to hospital was 69 min. Antibiotic therapy was started 76 min (median) before arrival at hospital. Conclusions: Pre-hospital identification of infectious focus in suspected sepsis was feasible, and collaboration with primary care physicians increased level of diagnostic accuracy. This allowed initiation of intravenous focus-directed antibiotics more than one hour before arrival in hospital in a rural setting. The effect of pre-hospital therapy on timing was much stronger than in previous studies from more urban areas. [ABSTRACT FROM AUTHOR]

Objective(s): Silver nanoparticles (AgNPs) can be considered as the new antibacterial agents. The antibacterial effects of synthesized AgNPs from Iranian pistachio hulls on several antibiotic-resistant bacteria were assessed in this study. Materials and Methods: In an experimental study, AgNPs were synthesized by reducing Ag+ ions using pistachio hulls. Several methods characterized the qualities of AgNPs. Antibacterial activities of the AgNPs against six gram-positive and gram-negative standard bacteria and 30 multidrug-resistant (MDR) clinical isolates were investigated by well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) methods. Results: The aqueous extract of pistachio hulls had an acceptable potential to synthesize AgNPs, and the formed nanoparticles displayed suitable size and acceptable stability in solutions. Antibacterial activities of the AgNPs were detected against two standard strains, Escherichia coli, and Staphylococcus aureus, with growth inhibition zones of 13 and 11 mm, respectively. MIC were 10 mg/ml for E. coli and 20 mg/ml for S. aureus. MBC for both bacteria was the same as MIC. MIC and MBC AgNPs against 15 methicillin-resistant S. aureus (MRSA) isolates ranged from 40 to 10 mg/ml. In extended-spectrum beta-lactamase (ESBL) E. coli isolates, 11 and 3 isolates have MIC equal to 20 and 10 mg/ml, respectively. Three ESBL E. coli isolates had 10, 5 and 2.5 mg/ml MBC; in other isolates, MBC and MIC were the same. Conclusion: The green synthesis of AgNPs using pistachio hull can replace common chemical and physical methods. AgNPs displayed antibacterial activities, and they could replace some antibiotics. [ABSTRACT FROM AUTHOR]

Objectives Pharmacodynamic parameters evaluated under conditions that simulate an infection site volume and microbial load might reveal hidden risks of resistance selection and subsequent treatment failure. The study aimed to investigate the predictive potential of MICs determined at various conditions on the antimicrobial effect and emergence of resistance. Methods We assessed meropenem MICs (microdilution: 0.2 mL, 5 × 105 cfu/mL; macrodilution: 2 mL, 5 × 105 cfu/mL), MICHVs (220 mL, 5 × 105 cfu/mL), MICHIs (0.2 mL, 5 × 107 cfu/mL) and MICHVIs (220 mL, 5 × 107 cfu/mL) for five Klebsiella pneumoniae strains and analysed these values alongside the results of experiments in a dynamic in vitro model. A clinically relevant meropenem dosing regimen was simulated and the starting bacterial inocula were 106 and 108 cfu/mL. Results The effectiveness of meropenem agreed with MICHVs for the 106 cfu/mL inoculum and with MICHIs or MICHVIs for the 108 cfu/mL inoculum. Strains characterized as resistant according to these values grew during meropenem exposure, and resistant mutants were selected. Conclusions Our results suggest that MICHV-based parameters may be suitable for predicting antibacterial effects and the risk of resistance development when the inoculum is 106 cfu/mL, while MICHI- or MICHVI-based parameters are suitable for these purposes when the inoculum is 108 cfu/mL. Also, the correlation between resistance selection and the MICHI-based parameter was as high as one that corresponds with a mutant prevention concentration (MPC)-based parameter; this suggests that the MPC can be replaced by the more easily determined alternative parameter MICHI. [ABSTRACT FROM AUTHOR]

Objectives Klebsiella pneumoniae is a significant pathogen with increasing resistance and high mortality rates. Conventional antibiotic susceptibility testing methods are time-consuming. Next-generation sequencing has shown promise for predicting antimicrobial resistance (AMR). This study aims to develop prediction models using whole-genome sequencing data and assess their feasibility with metagenomic next-generation sequencing data from clinical samples. Methods On the basis of 4170 K. pneumoniae genomes, the main genetic characteristics associated with AMR were identified using a LASSO regression model. Consequently, the prediction model was established, validated and optimized using clinical isolate read simulation sequences. To evaluate the efficacy of the model, clinical specimens were collected. Results Four predictive models for amikacin, ciprofloxacin, levofloxacin, and piperacillin/tazobactam, initially had positive predictive values (PPVs) of 92%, 98%, 99%, 94%, respectively, when they were originally constructed. When applied to clinical specimens, their PPVs were 96%, 96%, 95%, and 100%, respectively. Meanwhile, there were negative predictive values (NPVs) of 100% for ciprofloxacin and levofloxacin, and 'not applicable' (NA) for amikacin and piperacillin/tazobactam. Our method achieved antibacterial phenotype classification accuracy rates of 95.92% for amikacin, 96.15% for ciprofloxacin, 95.31% for levofloxacin and 100% for piperacillin/tazobactam. The sequence-based prediction antibiotic susceptibility testing (AST) reported results in an average time of 19.5 h, compared with the 67.9 h needed for culture-based AST, resulting in a significant reduction of 48.4 h. Conclusions These preliminary results demonstrated that the performance of prediction model for a clinically significant antimicrobial–species pair was comparable to that of phenotypic methods, thereby encouraging the expansion of sequence-based susceptibility prediction and its clinical validation and application. [ABSTRACT FROM AUTHOR]

Self-medication without a medical or dental prescription is an action that leads to a significant problems associated with the overuse of medication in Brazil. The inappropriate use of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) leads to problems related to microbial agent resistance and gastrointestinal complications. The purpose of this study was to elucidate the patterns of antibiotic and NSAIDs consumption among the adult population of Brazil. The questionnaire was answered by 400 people residing in Brazil who had access to the link in the year 2023. The findings showed that approximately 89.5% of the volunteers had used NSAIDs, and 32.2% had used antibiotics whether or not these medications had been prescribed by doctors or dentists. It was noted that a large proportion of the adverse effects reported by the volunteers involved symptoms related to gastrointestinal complaints. There was a high prevalence of NSAIDs consumption in the studied population, which is consistent with the high frequency of risk of adverse reactions caused by these drugs, particularly in the gastrointestinal tract. In relation to antibiotics, it was observed that the non-prescription consumption of these medications by the population was considered high, reaching one-third of the total number of volunteers who consumed such medications. [ABSTRACT FROM AUTHOR]

The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects. [ABSTRACT FROM AUTHOR]

AbstractBackgroundAimMethodsResultsConclusionAntibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship.To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group.This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate).The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96–0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62–0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70–1.76). The decline in clinic consultations was largest for consultations involving children aged 0–10 years (RR = 0.53, 95%CI: 0.51–0.56).Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care. [ABSTRACT FROM AUTHOR]

Background: Glycopeptides for ampicillin-susceptible Enterococcus faecalis/faecium bacteremia are readily prescribed depending on the severity of the condition. However, there is limited data on the outcomes of glycopeptide use compared to ampicillin-containing regimens for ampicillin-susceptible E. faecalis/faecium bacteremia. From an antibiotic stewardship perspective, it is important to determine whether the use of glycopeptides is associated with improved clinical outcomes in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. Methods: This retrospective cohort study was conducted at a university-affiliated hospital between January 2010 and September 2019. We collected data from patients with positive blood cultures for Enterococcus species isolates. The clinical data of patients who received ampicillin-containing regimens or glycopeptides as definitive therapy for ampicillin-susceptible E. faecalis/faecium bacteremia were reviewed. Multivariate logistic regression analysis was performed to identify risk factors for 28-day mortality. Results: Ampicillin-susceptible E. faecalis/faecium accounted for 41.2% (557/1,353) of enterococcal bacteremia cases during the study period. A total of 127 patients who received ampicillin-containing regimens (N = 56) or glycopeptides (N = 71) as definitive therapy were included in the analysis. The 28-day mortality rate was higher in patients treated with glycopeptides (19.7%) than in those treated with ampicillin-containing regimens (3.6%) (p = 0.006). However, in the multivariate model, antibiotic choice was not an independent predictor of 28-day mortality (adjusted OR, 3.7; 95% CI, 0.6–23.6). Conclusions: Glycopeptide use was not associated with improved mortality in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. This study provides insights to reduce the inappropriate use of glycopeptides in ampicillin-susceptible E. faecalis/faecium bacteremia treatment and promote antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Introduction Bloodstream infections are a significant threat to soldiers wounded in combat and contribute to preventable deaths. Novel and combination therapies that can be delivered on the battlefield or in lower roles of care are urgently needed to address the threat of bloodstream infection among military personnel. In this manuscript, we tested the antibacterial capability of silver ions (Ag+), with long-appreciated antibacterial properties, against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) pathogens. Materials and Methods We used the GENESYS (RAIN LLC) device to deliver Ag+ to Gram-positive and Gram-negative ESKAPEE organisms grown in broth, human blood, and serum. Following the Ag+ treatment, we quantified the antibacterial effects by quantifying colony-forming units. Results We found that Ag+ was bactericidal against 5 Gram-negative organisms, K pneumoniae, A baumannii, P aeruginosa , E cloacae , and E coli , and bacteriostatic against 2 Gram-positive organisms, E faecium and S aureus. The whole blood and serum inhibited the bactericidal activity of Ag+ against a common agent of bloodstream infection, P aeruginosa. Finally, when Ag+ was added in conjunction with antibiotic in the presence of whole blood, there was no significant effect of Ag+ over antibiotic alone. Conclusions Our results confirmed that Ag+ has broad-spectrum antibacterial properties. However, the therapeutic value of Ag+ may not extend to the treatment of bloodstream infections because of the inhibition of Ag+ activity in blood and serum. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e. 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e. ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e. methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e. PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605 , MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e. 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes. [ABSTRACT FROM AUTHOR]

Background and aims: One essential plant-based strategy to deal with infections is antimicrobial synergism, which can make antimicrobials more efficient. The aim of this study was to investigate the interaction between these extracts and two widely used antibiotics, meropenem and gentamicin, on two multidrug-resistant (MDR) bacteria, K. pneumoniae and A. baumannii, in vitro. Methods: Different concentrations of Rosa damascena Mill., Malva sylvestris L., and Zataria multiflora Boiss. hydroalcoholic extracts (2-fold serial dilution from 131072 to 256 μg/mL) were administered against two MDR bacteria, and their combination with gentamicin and meropenem (serial dilution from 32 to 0.015 μg/mL) was investigated by the resazurin-based microdilution and the checkerboard method. The phytochemical properties of the extracts were also examined, and the total phenolic content (TPC), total flavonoid content (TFC), anthocyanin content, and antioxidant capacity of the extracts were determined. Results: Z. multiflora and R. damascena showed high antibacterial activity, and their minimal inhibitory concentrations on Acinetobacter baumannii were 1024 and 2048 μg/mL, respectively. Z. multiflora also had high TFC, TPC, and antioxidant activity and demonstrated additive interaction with meropenem and gentamicin with fractional inhibitory concentrations of 1 and 0.75, respectively. Conclusion: We suggest the potency of Z. multiflora-antibiotic combinations in treating MDR A. baumannii after future clinical studies. [ABSTRACT FROM AUTHOR]

Blue light in the visible spectrum naturally fights bacteria and effectively deactivates various Gram-positive and Gram-negative bacteria and fungi using photodynamic processes. It works against drug-resistant strains within these species and is gentler on mammalian cells than ultraviolet rays or chemicals. This study evaluated blue light as an affordable way to sanitize surfaces in poultry settings, such as eggs and litter. The study used an light-emitting diode array to remove harmful Escherichia coli and Staphylococcus aureus from these items and observed how blue light affected their survival rates. Blue light (455 nm) at 30 mW/cm2 for one hour decreased the survival of S. aureus and E. coli on solid agar plates to 29.88% and 21.04%, respectively, compared to non-irradiated cultures. Similarly, on untreated surfaces (such as plastic used for feeding and drinking), the survival rates dropped to 25.8% and 15.6%, respectively. The survival percentages on treated eggs were 50% (S. aureus) and 36.47% (E. coli) and 49% (S. aureus) and 48.2% (E. coli) on treated litter. Hence, blue light technology offers a promising alternative to traditional antimicrobial methods by leveraging specific wavelengths to target microbial cells. This approach can significantly reduce the microbial load in poultry environments, enhancing food safety and animal health. This paper reports the first use of blue light as an antibacterial within poultry research in Iraq, offering a fresh approach to disinfection in this field. [ABSTRACT FROM AUTHOR]

Globally, it is estimated that more than 50% of antibiotics are obtained without a prescription. The main purpose of this study is to determine the knowledge and practice of primary caregivers about self-medication in children with antibiotics, as studies on self-medication is lacking in India, also, it will help is assessing parents' knowledge and attitude towards self medication. This cross-sectional study conducted in the urban community of Shastri Nagar, Patna, aimed to evaluated antibiotic use in children aged 0-12. From January 2023 to March 2023, 173 caregivers were randomly selected through house visits. Data collection used a pre-tested questionnaire, ensuring confidentiality. In this study of 173 participants, caregivers in an urban community demonstrated varying knowledge regarding antibiotic use in children. Mothers and postgraduates possessed better awareness of antibiotic consequences. Fathers exhibited better understanding of side effects. Knowledge on antibiotics' action was seen among mothers, those aged 30-39, with family income of Rs. 20,000-40,000 and those with family members in medical field. Fathers had more incorrect beliefs about antibiotics treating viral infections. Common conditions for self-medication included cough/cold, fever and diarrhea, with hospitals being the primary source of antibiotics. Majority obtained information from pharmacies but awareness about antibiotic course completion and versatility was limited. Caregivers' antibiotic knowledge varied; mothers and postgraduates were more aware, while fathers understood side effects better. [ABSTRACT FROM AUTHOR]

The use of antimicrobials in patients receiving end-of-life (EOL) care, which is generally defined as supportive care provided to patients anticipated to live less than 1 year, has been actively debated in the realm of palliative care medicine due to the nebulous nature of the topic. In this article, we explore the use of antimicrobial use near EOL as it relates to both the ethical and practical issues that face physicians. We also discuss the reasons underlying the scarcity of prospective studies on this topic. [ABSTRACT FROM AUTHOR]

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Objective: The goal of this study is the detection of the P. aeruginosa isolate for production the protease, the optimal conditions for produce, extraction, purification and characterization of the enzyme and study the synergistic effect of protease with antibiotics on S. aureus. Methods: Among (110) isolates from clinical sources, only (74) isolates identified as P. aeruginosa isolated from Baghdad hospitals. Detection of the optimal isolate for production the protease enzyme and the optimal conditions its produce, purification of enzyme by using ammonium sulfate, ion exchange chromatography and gel filtration, enzyme characterization of PH and temperature activity and stability, the study of synergistic effect of protease with antibiotics on S. aureus. Results: The optimal conditions to produce protease is pH (8), (37)°C, (BHI) broth, and during (48 hrs.). The precipitation saturation ratio (80%). Ion-exchanges (DEAE and CM) Cellulose and Gel filtration have specific activity ((121.25), (161.6), (660.53)) units/mg)) respectively. The characterization done by pH and temperature activity purified protease was active in (138.51 units/ml) at pH (8), and stable in pH (8), the temperature for protease activity is (158.21 units/ml) at (37)°C. The synergistic effect of purified protease with antibiotics on S. aureus in-vitro, was detected using the agar diffusion method, the effectiveness of the prepared hydrogel types, the results showed S. aureus was more sensitive isolate to prepare (Gel & Protease & Ceftriaxone) the diameter of the inhibition zone reached (44 mm), the synergistic effect we noticed when using a (Gel & Ceftriaxone & Protease) healing was observed in time (five days) with wound healing without effect. Conclusion: In this study, it was discovered that mixing (protease + hydrogel + Ceftriaxone) accelerates the wound healing without leaving traces. [ABSTRACT FROM AUTHOR]

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α‐dihydrotestosterone (5α‐DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin‐ and 5α‐DHT‐differentiated hamster sebocytes. Ozenoxacin showed a dose‐dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl‐CoA desaturase‐1, and perilipin‐1 mRNA, all important factors involved in sebum synthesis, in a dose‐dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin‐ and 5α‐DHT‐treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin‐containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum‐inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management. [ABSTRACT FROM AUTHOR]

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.

Gulf War (GW) veterans show gastrointestinal disturbances and gut dysbiosis. Prolonged antibiotic treatments commonly employed in veterans, especially the use of fluoroquinolones and aminoglycosides, have also been associated with dysbiosis. This study investigates the effect of prolonged antibiotic exposure on risks of adverse renal pathology and its association with gut bacterial species abundance in underlying GWI and aims to uncover the molecular mechanisms leading to possible renal dysfunction with aging. Using a GWI mouse model, administration of a prolonged antibiotic regimen involving neomycin and enrofloxacin treatment for 5 months showed an exacerbated renal inflammation with increased NF-κB activation and pro-inflammatory cytokines levels. Involvement of the high mobility group 1 (HMGB1)-mediated receptor for advanced glycation end products (RAGE) activation triggered an inflammatory phenotype and increased transforming growth factor-β (TGF-β) production. Mechanistically, TGF-β- induced microRNA-21 upregulation in the renal tissue leads to decreased phosphatase and tensin homolog (PTEN) expression. The above event led to the activation of protein kinase-B (AKT) signaling, resulting in increased fibronectin production and fibrosis-like pathology. Importantly, the increased miR-21 was associated with low levels of Lachnospiraceae in the host gut which is also a key to heightened HMGB1-mediated inflammation. Overall, though correlative, the study highlights the complex interplay between GWI, host gut dysbiosis, prolonged antibiotics usage, and renal pathology via miR-21/PTEN/AKT signaling.

Antibiotic-resistant bacteria present an emerging challenge to human health. Their prevalence has been increasing across the globe due in part to the liberal use of antibiotics that has pressured them to develop resistance. Those bacteria that acquire mobile genetic elements are especially concerning because those plasmids may be shared readily with other microbes that can then also become antibiotic resistant. Serious infections have recently been related to the contamination of preservative-free eyedrops with extensively drug-resistant (XDR) isolates of Pseudomonas aeruginosa, already resulting in three deaths. These drug-resistant isolates cannot be managed with most conventional antibiotics. We sought to identify alternatives to conventional antibiotics for the lysis of these XDR isolates and identified multiple bacteriophages (viruses that attack bacteria) that killed them efficiently. We found both jumbo phages (>200 kb in genome size) and non-jumbo phages that were active against these isolates, the former killing more efficiently. Jumbo phages effectively killed the three separate XDR P. aeruginosa isolates both on solid and liquid medium. Given the ongoing nature of the XDR P. aeruginosa eyedrop outbreak, the identification of phages active against them provides physicians with several novel potential alternatives for treatment.

Antimicrobial resistance in Neisseria gonorrhoeae is an urgent global health issue. The objectives of the study were to use a global collection of 12,936 N. gonorrhoeae genomes from the PathogenWatch database to evaluate different machine learning models to predict ceftriaxone susceptibility/decreased susceptibility using 97 mutations known to be associated with ceftriaxone resistance. We found the random forest classifier model had the highest performance. The analysis also reported the relative contributions of different mutations within the ML model predictions, allowing for the identification of the mutations with the highest importance for ceftriaxone resistance. A machine learning model retrained with the top five mutations performed similarly to the model using all 97 mutations. These results could aid in the development of molecular tests to detect resistance to ceftriaxone in N. gonorrhoeae. Moreover, this approach could be applied to building and evaluating machine learning models for predicting antimicrobial resistance in other pathogens.

Infectious conjunctivitis outbreaks remain a public health burden. This study focuses on the pathogen and antimicrobial resistance (AMR) profiles identified in Niger. Sixty-two patients with acute infectious conjunctivitis who presented to health posts were enrolled from December 2021 to May 2022. Nasal and conjunctival swabs were obtained from each patient. Unbiased RNA deep sequencing (RNA-seq) was used to identify associated pathogens. A pathogen was identified in 39 patients (63%; 95% CI, 50-74). Of those, an RNA virus was detected in 23 patients (59%; 95% CI, 43-73). RNA viruses were diverse and included human coronaviruses (HCoVs): SARS-CoV-2, HCoV-229E, HCoV-HKU1, and HCoV-OC43. A DNA virus was identified in 11 patients (28%; 95% CI, 17-44). Of those, four patients had a coinfection with an RNA virus and two patients had a coinfection with both an RNA virus and a bacterium. DNA viruses were predominantly human herpesvirus (cytomegalovirus, Epstein-Barr virus, human herpesvirus 8) and human adenovirus species B, C, and F. Eighteen patients (46%; 95% CI, 32-61) had a bacteria-associated infection that included Haemophilus influenza, Haemophilus aegyptius, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella spp. Antimicrobial resistance determinants were detected in either the conjunctiva or nasal samples of 20 patients (32%; 95% CI, 22-45) and were found to be more diverse in the nose (Shannon alpha diversity, 1.12 [95% CI, 1.05-1.26] versus 1.02 [95% CI, 1.00-1.05], P = 0.01). These results suggest the potential utility of leveraging RNA-seq to surveil pathogens and AMR for ocular infections.

Abstract Background Early diagnosis and antibiotic therapy in patients with sepsis reduce morbidity and mortality, thus pre-hospital management is likely to affect patient outcomes. Pre-hospital administration may increase the risk of unnecessary use of broad-spectrum antibiotics, but identification of an infectious focus enables more targeted antibiotic therapy. The aim of this study was to investigate how paramedics, with or without the assistance of general practitioners, can administer empiric intravenous antibiotic treatment against sepsis in a timely manner. Methods Cohort study of patients with suspected sepsis that received pre-hospital intravenous antibiotics and were transported to hospital. The setting was mainly rural with long average distance to hospital. Patients received targeted antibiotic treatment after an assessment based on clinical work-up supported by scoring systems. Patients were prospectively included from May 2018 to August 2022. Results are presented as median or absolute values, and chi-square tests were used to compare categorical data. Results We included 328 patients. Median age was 76 years (IQR 64, 83) and 48.5% of patients were female. 30-days all-cause mortality was 10.4%. In cases where a suspected infectious focus was determined, the hospital discharge papers confirmed the pre-hospital diagnosis focus in 195 cases (79.3%). The presence of a general practitioner during the pre-hospital assessment increased the rate of correctly identified infectious focus from 72.6% to 86.1% (p = 0.009). Concordance between pre-hospital identification of a tentative focus and discharge diagnosis was highest for lower respiratory tract (p = 0.02) and urinary tract infections (p = 0.03). Antibiotic treatment was initiated 44 min (median) after arrival of ambulance, and median transportation time to hospital was 69 min. Antibiotic therapy was started 76 min (median) before arrival at hospital. Conclusions Pre-hospital identification of infectious focus in suspected sepsis was feasible, and collaboration with primary care physicians increased level of diagnostic accuracy. This allowed initiation of intravenous focus-directed antibiotics more than one hour before arrival in hospital in a rural setting. The effect of pre-hospital therapy on timing was much stronger than in previous studies from more urban areas.

Objective To investigate the clinical effect and mechanism of compound azintamide combined with bifidobacteria triple viable capsules in the prevention and treatment of antibiotic-associated diarrhea (AAD) in the elderly. Methods A retrospective analysis was performed for 62 elderly patients with or comorbid with infectious diseases who were admitted to Department of Geriatrics, Taian 88 Hospital, from October 2019 to February 2021 and received intravenous drip of antibiotics, and according to the treatment method, they were divided into observation group with 32 patients (treated with compound azintamide combined with bifidobacteria triple viable capsules) and control group with 30 patients (treated with bifidobacteria triple viable capsules alone). The drugs were used in addition to antibiotics for 14 d. The two groups were compared in terms of the incidence rate of AAD, time to the onset of diarrhea, number of times of diarrhea per day, and duration of diarrhea during treatment, as well as related biochemical parameters before treatment and on day 14 of treatment, including hemoglobin (Hb), plasma albumin (Alb), total protein (TP), and the serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and complement C3 and C4. Results Compared with the control group, the observation group had a significantly lower incidence rate of AAD during treatment (χ2=5.77,P

Objective Chronic obstructive pulmonary disease (COPD) is associated with exacerbations and high risk of serious outcomes. Our goal was to determine the appropriateness of the emergency department (ED) management of COPD exacerbations. Methods This observational cohort study incorporated a health records review and included COPD exacerbation cases seen at two large academic EDs. We included all patients with the primary diagnosis of COPD exacerbation. From the electronic medical record, demographic and clinical data were abstracted, and the Ottawa COPD Risk Score (OCRS) was calculated for each. Short-term serious outcomes included intensive care unit admission, intubation, myocardial infarction, noninvasive positive pressure ventilation (NIV), and death at 30 days. Cases were judged for appropriateness of treatment according to explicit indications and standards developed a priori. Results We enrolled 500 cases with mean age of 71.9 years, 51.2% female patients, 50.2% admitted, and 4.4% death. The calculated OCRS score was ≥2 for 70.8% of patients. The treatments provided were inhaled β-agonists (82.6%), inhaled anticholinergics (76.6%), corticosteroids (75.2%), antibiotics (71.0%), oxygen (63.8%), NIV (8.8%), and intubation (0.6%). Overall, 50.0% of cases were judged to have had inadequate management due to missing treatments. Specifically, the proportion of missing treatments were inhaled β-agonist (17.0%), inhaled anticholinergic (22.6%), corticosteroids (24.4%), antibiotics (12.8%), and NIV (2.0%). Conclusion Adequate treatment of COPD exacerbation was lacking in 50.0% of patients in these two large academic EDs. Concerning were the number of patients not receiving corticosteroids or antibiotics. Implementation of explicit treatment standards should lead to improved patient care of this common and serious condition.

Abstract The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects.

Background Antibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship.Aim To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group.Methods This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate).Results The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96–0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62–0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70–1.76). The decline in clinic consultations was largest for consultations involving children aged 0–10 years (RR = 0.53, 95%CI: 0.51–0.56).Conclusion Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care.

Abstract Background Glycopeptides for ampicillin-susceptible Enterococcus faecalis/faecium bacteremia are readily prescribed depending on the severity of the condition. However, there is limited data on the outcomes of glycopeptide use compared to ampicillin-containing regimens for ampicillin-susceptible E. faecalis/faecium bacteremia. From an antibiotic stewardship perspective, it is important to determine whether the use of glycopeptides is associated with improved clinical outcomes in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. Methods This retrospective cohort study was conducted at a university-affiliated hospital between January 2010 and September 2019. We collected data from patients with positive blood cultures for Enterococcus species isolates. The clinical data of patients who received ampicillin-containing regimens or glycopeptides as definitive therapy for ampicillin-susceptible E. faecalis/faecium bacteremia were reviewed. Multivariate logistic regression analysis was performed to identify risk factors for 28-day mortality. Results Ampicillin-susceptible E. faecalis/faecium accounted for 41.2% (557/1,353) of enterococcal bacteremia cases during the study period. A total of 127 patients who received ampicillin-containing regimens (N = 56) or glycopeptides (N = 71) as definitive therapy were included in the analysis. The 28-day mortality rate was higher in patients treated with glycopeptides (19.7%) than in those treated with ampicillin-containing regimens (3.6%) (p = 0.006). However, in the multivariate model, antibiotic choice was not an independent predictor of 28-day mortality (adjusted OR, 3.7; 95% CI, 0.6–23.6). Conclusions Glycopeptide use was not associated with improved mortality in patients with ampicillin-susceptible E. faecalis/faecium bacteremia. This study provides insights to reduce the inappropriate use of glycopeptides in ampicillin-susceptible E. faecalis/faecium bacteremia treatment and promote antimicrobial stewardship.

BACKGROUND: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter VOS, formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. METHODS: Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1-2, 3-4, ≥5); (ii) baseline creatinine clearance (50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. RESULTS: Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. CONCLUSIONS: In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.