Renal Function and Its Impact on the Concentration of Ceftazidime-Avibactam: A cross-sectional study.

OBJECTIVES: This study measured the effect of renal function on the plasma concentrations of ceftazidime and avibactam in critically ill patients. We also sought to measure the concentration ratio of ceftazidime to avibactam. METHODS: This was a cohort study at a tertiary referral centre in Italy, on patients treated with continuous infusion of ceftazidime-avibactam (CAZ-AVI) between November 2019 and December 2023. The association between creatine clearance (CrCl) and free plasma ceftazidime and avibactam concentration, as well as CAZ-AVI ratio was explored to assess correlation and potential risk to fail to achieve target therapeutic concentration. RESULTS: 52 patients, predominantly male (75%), with a median age of 68.5 years were included. Our analyses provided strong evidence for inverse correlation between CrCl and both free-CAZ (r=-0.627; R2=0.3936; P<0.001) and free-AVI plasma concentration (r=-0.619; R2=0.3832; P<0.001). Overall CrCl alone could explain about 40% of overall variation of either free-CAZ and free-AVI. Linear models suggest that free-CAZ and free-AVI concentration drop of about 7.31% and 9.23% for each 10 point increase of CrCl, respectively. . Assessment of the CAZ-AVI ratio supports a direct linear association with CrCl suggesting that free-AVI concetration is more affected by CrCl variation than free-CAZ concentration. Patients with CrCl ≥130 mL/min showed a significantly higher risk of suboptimal drug exposure (i.e. less than 4 times the MIC) both to CAZ and AVI. CONCLUSION: The findings emphasize the need for individualized dosing strategies of CAZ-AVI based on renal function, for antibiotics used in critically ill patients. The study suggests that underdosing in patients with high CrCl is likely to be common and as such could affect drug effectiveness.

Rising trend of dentist-prescribed antibiotics in Brazil: 2011-2021.

OBJECTIVES: To describe the trends in antibiotic prescribing by dental practitioners and to investigate the relationship between these trends and some factors of public oral health services in Minas Gerais (MG), Brazil. METHODS: This was a time-series analysis of antibiotics prescribed by dental practitioners between January 2011 and December 2021. The outcome variables were number of defined daily doses (DDD) and DDD/1000 population/year in a sample of cities in MG. Covariates were public oral healthcare factors, such as coverage, estimates of dental procedures, and frequency of dental pain. Linear time-series regression models were used to examine trends and the influence of covariates on antibiotic prescribing. RESULTS: Overall, the number of prescriptions increased by 334.69% between 2011 and 2021, with amoxicillin being the most commonly prescribed drug (78.53%). The number of DDD for all antibiotics increased from 17,147.13 to 77,346.67 and the average DDD/1000 inhabitants/year was 126.66 (SD: 130.28). The linear time-series regression model showed that for each one-year increase, the average log DDD/1000 inhabitants increased by 0.35 (standard error = 0.07, p < 0.001). No covariates were found to be associated with the outcome. CONCLUSIONS: In Minas Gerais, Brazil, a significant upward trend was observed in the number of prescriptions and the number of DDD of antibiotics prescribed by dental practitioners. No influence of factors related to public oral healthcare services on the outcome was observed, thereby emphasizing the need for further research on factors influencing medication use in dental practice.

Primary Caregiver Knowledge about Self-Medication of Antibiotics in Children Aged 0-12 Years.

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 post-graduates 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 post-graduates were more aware, while fathers understood side effects better.

Trends and geographical variations in outpatient antimicrobial consumption in Ireland in relation to socio-economic deprivation.

Background: Different factors have been associated with changes in antimicrobial consumption rates in Ireland, however the relationship between socio-economic deprivation and antimicrobial consumption has not been explored. The presented ecological analysis explores the temporal and geographical variation in outpatient antimicrobial consumption and socio-economic deprivation in Ireland from January 2015 to March 2022. Method: Deprivation index (DI) was used as a socio-economic proxy. A multilevel mixed model was applied to explore temporal variation and analyse the longitudinal antimicrobial consumption (DID) in relation to DI. Furthermore, maps were generated based on antimicrobial consumption rates, and spatial autocorrelation analyses were carried out to study geographical variation in antimicrobial consumption rates. Results: The antimicrobial consumption rates per month varied from 26.2 DID (January 2015) to 22.1 DID (March 2022) showing an overall reduction of 16 %. Overall, total antimicrobial consumption in the multilevel model showed a consistent correlation with higher DI score (6.6 (95%CI 3.9 to 9.3)), and winter season (3.6 (95%CI 3.2 to 3.9)). In contrast, before COVID-19 showed significant lower antimicrobial consumption rates compared to during COVID-19 (-4.0 (95%CI -4.7 to -3.23)). No consistent trends were observed for geographical variation between areas. Conclusion: Antimicrobial consumption rates decreased from 2015 to 2021 in Ireland. No geographical patterns were observed in antimicrobial consumption rates but associations between deprivation and antimicrobial consumption rates were observed.

Antimicrobial spectrum against wound pathogens and cytotoxicity of star-arranged poly-l-lysine-based antimicrobial peptide polymers.

Introduction. As growing numbers of patients are at higher risk of infection, novel topical broad-spectrum antimicrobials are urgently required for wound infection management. Robust pre-clinical studies should support the development of such novel antimicrobials.Gap statement. To date, evidence of robust investigation of the cytotoxicity and antimicrobial spectrum of activity of antimicrobial peptides (AMP)s is lacking in published literature. Using a more clinical lens, we address this gap in experimental approach, building on our experience with poly-l-lysine (PLL)-based AMP polymers.Aim. To evaluate the in vitro bactericidal activity and cytotoxicity of a PLL-based 16-armed star AMP polymer, designated 16-PLL10, as a novel candidate antimicrobial.Methods. Antimicrobial susceptibilities of clinical isolates and reference strains of ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogens, to 16-PLL10 were investigated. Human erythrocyte haemolysis and keratinocyte viability assays were used to assess toxicity. Modifications were made to 16-PLL10 and re-evaluated for improvement.Results. Minimum bactericidal concentration of 16-PLL10 ranged from 1.25 µM to ≥25 µM. At 2.5 µM, 16-PLL10 was broadly bactericidal against ESKAPE strains/wound isolates. Log-reduction in colony forming units (c.f.u.) per millilitre after 1 h, ranged from 0.3 (E. cloacae) to 5.6 (K. pneumoniae). At bactericidal concentrations, 16-PLL10 was toxic to human keratinocyte and erythrocytes. Conjugates of 16-PLL10, Trifluoroacetylated (TFA)-16-PLL10, and Poly-ethylene glycol (PEG)ylated 16-PLL10, synthesised to address toxicity, only moderately reduced cytotoxicity and haemolysis.Conclusions. Due to poor selectivity indices, further development of 16-PLL10 is unlikely warranted. However, considering the unmet need for novel topical antimicrobials, the ease of AMP polymer synthesises/modification is attractive. To support more rational development, prioritising clinically relevant pathogens and human cells, to establish selective toxicity profiles in vitro, is critical. Further characterisation and discovery utilising artificial intelligence and computational screening approaches can accelerate future AMP nanomaterial development.

Clinical outcome of ampicillin or ampicillin/sulbactam versus glycopeptides in ampicillin-susceptible Enterococcus faecalis/faecium bacteremia: a 10-year retrospective cohort study.

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.

Impact of antibiotic changes on hospital stay and treatment duration in community-acquired pneumonia.

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.

ATP synthase of E. coli: F1-ATPase activity is functionally decoupled from the proton-transporting complex (FO) by tributyltin.

The F-type ATP synthase/ATPase (FOF1) is important for cellular bioenergetics in eukaryotes and bacteria. We recently showed that venturicidins, a class of macrolides that inhibit the proton transporting complex (FO), can also induce time-dependent functional decoupling of F1-ATPase from FO on membranes from Escherichia coli and Pseudomonas aeruginosa. This dysregulated ATPase activity could deplete bacterial ATP levels and contribute to venturicidin's capacity to enhance the bactericidal action of aminoglycosides antibiotics. We now show that a distinct type of FO inhibitor, tributyltin, also can decouple FOF1-ATPase activity of E. coli membranes. In contrast to the action of venturicidins, decoupling by tributyltin is not dependent on ATP, indicating mechanistic differences. Tributyltin disrupts the coupling role of the ε subunit of F1 but does not induce dissociation of the F1-ATPase complex from membrane-embedded FO. Understanding such decoupling mechanisms could support development of novel antibacterial compounds that target dysregulation of FOF1 functions.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

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.

The impact of the COVID-19 pandemic on antibiotic prescription rates in out-of-hours primary care - a register-based study in Denmark.

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.

Retrospective study on penicillin allergy delabeling and evaluation of an antibiotic allergy assessment tool.

BACKGROUND: It has been reported that 95 % of patients labeled as penicillin-allergic may be mislabeled. However, the process of delabeling has not advanced due to a shortage of allergy specialists capable of conducting accurate assessments. To address this issue, The Antibiotics Allergy Assessment Tool (AAAT) has been proposed as a tool to evaluate patients who can be delabeled by non-specialists. OBJECTIVE: This study aims to identify patients who can be delabeled and to evaluate patients who are likely to be delabeled using AAAT. METHODS: Patients admitted to the hospital between January 1, 2017, and December 31, 2021, with documented penicillin allergy labels were included in the study. Patients who demonstrated tolerance to labeled antibiotics or were labeled without explicit allergy declarations were defined as delabeling. Subsequently, patients who did not meet the criteria for delabeling were evaluated for their potential to be delabeled using the AAAT, retrospectively. RESULTS: 530 patients were selected, of which 62 (11.7 %) were delabeled. The AAAT evaluation of the remaining patients indicated that at least an additional 137 (25.8 %) patients could potentially be delabeled. CONCLUSION: The use of AAAT demonstrated the potential to delabel approximately third as many patients without the need for specialist evaluation. To promote broader delabeling efforts in the future, prospective studies should investigate the safety and effectiveness of evaluation tools such as the AAAT.

Cost comparison analysis of continuous versus intermittent antimicrobial therapy infusions in inpatient and outpatient care: real-world data from Finland.

OBJECTIVE: This study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care pathways. DESIGN: Retrospective real-world data informed a cost comparison analysis that compared costs and nursing hours between infusion of antibiotics via EIP versus CII across eight care pathways in inpatient or outpatient care during infection episodes. Real-world data were obtained from patients treated within a year with parenteral antimicrobial therapy in Päijät-Häme Region, Finland. SETTING: Inpatient care with hospital admission and outpatient care at hospital at home in Päijät-Häme Region in Finland. PARTICIPANTS: 3778 patients with a total of 4214 infection episodes treated with intravenous antimicrobial therapy. INTERVENTIONS: Eight treatment strategies with various combinations of EIP and CII administered in inpatient or outpatient care. PRIMARY AND SECONDARY OUTCOME MEASURES: Direct costs and nursing time. RESULTS: Skin and soft tissue infections accounted for the highest number of episodes treated with EIP overall (30.8%; 74 out of 240 episodes) and in outpatient care specifically (53.3%; 128 out of 240 episodes). Compared with inpatient care costs with CII (€4590 per episode), treating skin and soft tissue infections in outpatient care with EIP or CII incurred only 24% (€1104) and 35% (€1620) of the costs, respectively. Across all treatment strategies and infections studied, the use of EIP consistently required less nursing time. The highest nursing time in the outpatient care was observed in sepsis episodes treated with CII (37 hours with CII vs 7 hours with EIP per episode). CONCLUSION: Delivery of antimicrobial therapy using continuous infusions with EIP instead of CII can significantly decrease the nursing time and cost in both inpatient and outpatient care. For skin and soft tissue infections and sepsis, the utilisation of EIP is a cost-saving option in outpatient care compared with the use of CII.

Ethical and Practical Issues with the Use of Antimicrobial Agents during the End of Life.

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.

Ozenoxacin suppresses sebum production by inhibiting mTORC1 activation in differentiated hamster sebocytes.

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.

C-reactive protein point-of-care testing in primary care-broader implementation needed to combat antimicrobial resistance.

This study presents the perspective of an international group of experts, providing an overview of existing models and policies and guidance to facilitate a proper and sustainable implementation of C-reactive protein point-of-care testing (CRP POCT) to support antibiotic prescribing decisions for respiratory tract infections (RTIs) with the aim to tackle antimicrobial resistance (AMR). AMR threatens to render life-saving antibiotics ineffective and is already costing millions of lives and billions of Euros worldwide. AMR is strongly correlated with the volume of antibiotics used. Most antibiotics are prescribed in primary care, mostly for RTIs, and are often unnecessary. CRP POCT is an available tool and has been proven to safely and cost-effectively reduce antibiotic prescribing for RTIs in primary care. Though established in a few European countries during several years, it has still not been implemented in many European countries. Due to the complexity of inappropriate antibiotic prescribing behavior, a multifaceted approach is necessary to enable sustainable change. The effect is maximized with clear guidance, advanced communication training for primary care physicians, and delayed antibiotic prescribing strategies. CRP POCT should be included in professional guidelines and implemented together with complementary strategies. Adequate reimbursement needs to be provided, and high-quality, and primary care-friendly POCT organization and performance must be enabled. Data gathering, sharing, and discussion as incentivization for proper behaviors should be enabled. Public awareness should be increased, and healthcare professionals' awareness and understanding should be ensured. Impactful use is achieved when all stakeholders join forces to facilitate proper implementation.

[Intracranial epidural abscess associated to sinusitis with positive response to medical treatment]. / Absceso epidural intracraneal asociado a sinusitis con respuesta al tratamiento médico.

Epidural abscesses are rare intracranial infections. They can occur from neurosurgical procedures, or head and neck infections. Successful treatment usually requires a combination of drainage procedure and antibiotic therapy. We present the case of a young patient with an intracranial epidural abscess and meningitis secondary to sinusitis who received only corticosteroids and antibiotic therapy, with good evolution.

Los abscesos epidurales son infecciones intracraneales de baja frecuencia. Pueden ocurrir derivados de procedimientos neuroquirúrgicos, o infecciones de cabeza y cuello. El tratamiento exitoso generalmente requiere la combinación de un procedimiento de drenaje y antibioticoterapia. Se presenta el caso de un paciente joven, con un absceso epidural intracraneal y meningitis, secundario a sinusitis que recibió solo tratamiento con corticoides y antibioticoterapia con buena evolución.

Antibiotic use in public hospitals in Vietnam between 2018 and 2022: a retrospective study.

OBJECTIVE: To assess the patterns of antibiotic consumption and expenditure in Vietnam. DESIGN: This was a cross-sectional study. SETTING: This study used data of antibiotic procurement that was publicly announced from 2018 to 2022 as a proxy for antibiotic consumption. PARTICIPANTS: This study included winning bids from 390 procurement units in 63 provinces in Vietnam for 5 years with a total expenditure of US$ 12.8 billions that represented for approximately 20-30% of the national funds spend on medicines. INTERVENTIONS: Antibiotics were classified by WHO AWaRe (Access, Watch and Reserve) classification. OUTCOME MEASURES: The primary outcomes were the proportions of antibiotic consumptions in number of defined daily doses (DDD) and expenditures. RESULTS: There was a total of 2.54 million DDDs of systemic antibiotics, which accounted for 24.7% (US $3.16 billions) of total expenditure for medicines purchased by these public health facilities. The overall proportion of Access group antibiotics ranges from 40.9% to 53.8% of the total antibiotic consumption over 5 years. CONCLUSION: This analysis identifies an unmet target of at least 60% of the total antibiotic consumption being Access group antibiotics and an unreasonable share of expenditure for non-essential antibiotics in public hospitals in Vietnam.

Prolonged Beta-Lactam Infusions in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections. STUDY DESIGN: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia. RESULTS: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis. CONCLUSIONS: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies.

Sol-gel-derived calcium silicate cement incorporating collagen and mesoporous bioglass nanoparticles for dental pulp therapy.

OBJECTIVE: 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. METHODS: 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+H2O), 10 mg/mL collagen solution (CS+colH2O), and MBGNs (10 %) (CSmbgn+colH2O). 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. RESULTS: The CS+H2O displayed a ST comparable to commercial products, while CSmbgn+colH2O 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. SIGNIFICANCE: 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.