Observational, retrospective real-world evidence study demonstrates safety, performance and usefulness of antimicrobial central venous catheters.

OBJECTIVE: To collect real-world data to demonstrate the safety and performance of Arrowg+ard Blue® /Arrowg+ard Blue Plus® (AGB/AGB+) central venous catheters (CVCs). METHODS: This observational, retrospective study involved patients who required AGB/AGB+ CVCs at designated general hospitals in USA (22), UK (19) and Germany (2). Data were extracted from electronic medical records. There were no specific inclusion/exclusion criteria. Primary endpoint was successful treatment without an adverse event (AE). Secondary endpoint was rate of AEs. RESULTS: In total, 384 cases were included from 43 centres and most patients (74%) were >35 years of age. A success rate of 99%, and an overall AE rate of 0.8% were observed. Moreover, the overall infection rate was lower than typically reported for standard catheters. In addition, power injection of contrast media was successful in all 51 cases. CONCLUSIONS: This study indicates the AGB/AGB+ CVCs perform as intended with a high success rate and few AEs. Further large-scale, controlled studies are required to confirm our findings.

Effectiveness of pharmacist-led antimicrobial stewardship programs in perioperative settings: A systematic review and meta-analysis.

OBJECTIVE: We sought to characterize and evaluate the effectiveness of pharmacist-led AMS interventions in improving antimicrobial use and subsequent surgical site infections (SSI) in perioperative settings. METHODS: A systematic review and meta-analysis was conducted by searching PubMed, Embase and CINAHL. Two independent reviewers extracted the data using the Descriptive Elements of Pharmacist Intervention Characterization Tool and undertook quality assessment using the Crowe Critical Appraisal. A meta-analysis was conducted using a random-effect model. RESULTS: Eleven studies were included in this review. Pharmacists were found to have various roles in AMS, including educational sessions, ward rounds, audits and feedback, and guidelines development. The discussion of interventions lacked details on the development. A meta-analysis revealed that pharmacist-led AMS programs in perioperative settings was associated with a significant improvement in antibiotic selection (OR 4.29; 95 % CI 2.52-7.30), administration time (OR 4.93; 95 % CI 2.05-11.84), duration (OR 5.27; 95 % CI 1.58-17.55), and SSI (OR 0.51; 95 % CI 0.34-0.77). CONCLUSION: Pharmacist-led AMS programs were effective in improving antimicrobial prescribing while reducing SSI; however most studies were of moderate quality. Studies lacked the utilization of theory to develop interventions, therefore, it is not clear whether theory-derived interventions are more effective than those without a theoretical element. High-quality, multicomponent, theory-derived, interventional studies using appropriate methodology and standardized data collection, are needed.

Antimicrobial use in laboratory rodent facilities in Australia and New Zealand- a cross-sectional survey of veterinarians and facility managers.

This cross-sectional study surveyed veterinarians and facility managers to characterise the use of antimicrobials in laboratory rodent facilities within Australia and New Zealand. Most facilities (71%) reported routine administration of antimicrobials. The indications for antibiotic use reflected those described in publications and differed significantly to reasons for use in non-laboratory animals. Antimicrobials used include those of critical importance to human health, and access to these drugs is unregulated, as prescription-only classes are ordered through research catalogues, without human or veterinary physician prescriptions. The ways in which antimicrobials are used in Australian and New Zealand rodent facilities are likely contributing to antimicrobial resistance within rodent populations, particularly as they are largely administered in drinking water, risking subtherapeutic dosing. Much antimicrobial use reported is unnecessary and could be replaced with changes to husbandry and handling. The generation of resistance in both pathogenic and commensal microbes may also represent a work health and safety issue for humans working with these animals. Reported disposal of antimicrobials included discharge into wastewater, without inactivation, and some respondents reported disposal of substrate, or soiled bedding, nesting material, and disposable enrichment items, from treated animals and medicated feed into landfill, without prior inactivation. Environmental contamination with resistant microbes and antimicrobials is a significant driver of antimicrobial resistance. As such, significant opportunities exist to implement judicious and responsible use of antimicrobials within research rodent facilities in Australia and New Zealand, with a particular focus on instituting aseptic surgery, optimising dosing regimens, and inactivation of medicated water and substrate before disposal.

A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing.

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Comparison of antimicrobial therapy termination in febrile and afebrile patients with acute cholangitis after drainage.

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

Surveillance of Antimicrobial Use in Long-Term Care Facilities: An Antimicrobial Mapping Survey.

OBJECTIVES: To explore antimicrobial management processes in Australian residential aged care facilities (RACFs), including antimicrobial prescribing, supply, administration, and documentation to inform surveillance activities. DESIGN: Voluntary, online cross-sectional survey. SETTING AND PARTICIPANTS: The survey was disseminated to all South Australian RACFs (n = 237) seeking participation from an infection prevention and control lead (preferred respondent), a nurse or senior RACF staff member, or an aged care pharmacist. METHODS: The survey was open during May-June 2023. Questions aimed to understand clinical and medication management systems, sources of antimicrobial prescription and supply, management by external health care providers and documentation of antimicrobial administration. A process map of antimicrobial management in RACFs was developed. RESULTS: Of the 54 RACFs included in the analysis (29.5% response rate), most used an electronic clinical documentation system (74.1%) or a hybrid electronic paper-based system (22.2%). Medication charts were either electronic (81.0%), hybrid (5.6%), or paper-based (13.0%). Antimicrobials were prescribed by the resident's usual general practitioner, but also by locums, hospital or specialist physicians, nurse practitioners, virtual care physicians, and dentists. Oral, topical, and inhaled antimicrobial formulations were usually supplied by community pharmacies, and intravenous formulations were predominately supplied by hospitals for administration by outreach nurses. Almost all RACFs (96.2%) had imprest stock of antimicrobials that included both oral and intravenous formulations. Antimicrobials were predominately administered by an enrolled nurse or a registered nurse. CONCLUSIONS AND IMPLICATIONS: Antimicrobial management in RACFs is complex, particularly during care transitions. Multiple prescribers and sources of antimicrobials, use of different systems for clinical documentation, particularly by external health care providers, and clinical governance relating to imprest supplies were identified as key areas where medication management could be improved. Addressing these gaps will facilitate comprehensive, real-time antimicrobial surveillance in Australian RACFs.

Bioadhesive Polymeric Films Containing Rhamnolipids, An Innovative Antimicrobial Topical Formulation.

Acne affects most of the world's population, causing an impact on the self-esteem of adolescents and young adults. One of the causes is the presence of the bacteria Cutibacterium acnes which are part of the natural microbiota of the skin. Topical treatments consist of anti-inflammatory and antibiotics, which could select resistant strains. Alternatives to the antibiotic are biocomposites that have antimicrobial activity like biosurfactants which are produced by bacteria. An innovative way of applying these compounds is bioadhesive polymeric films that adhere to the skin and release the active principle topically. Rhamnolipids have great potential to be used in the treatment of acne because they present antimicrobial activity against C. acnes in low and safe concentrations (MIC of 15.62 µg/mL, CBM of 31.25 µg/mL and CC50 of 181.93 µg/mL). Four films with different rhamnolipids concentrations (0.0; 0.1; 0.2; and 0.3%, w/w) were obtained as to visual appearance, mass variation, thickness, density, solubility, pH, water vapor transmission, mechanical properties (folding endurance, bioadhesion strength, tensile strength, elongation at break and Young's modulus), scanning electron microscopy and infrared. The results show that these formulations had a homogeneous appearance; elastic mechanical properties; pH similar to human skin and bioadhesive. The polymeric films containing rhamnolipids were effective against C. acnes, in the in vitro test, at the three concentrations tested, the film with the highest concentration (0.3%, w/w) being the most promising for presenting the highest antimicrobial activity. Thus, the polymeric film containing rhamnolipids has the potential to be used in the treatment of acne.

Human ß-defensins: The multi-functional natural peptide.

The increasing threat of antibiotic resistance among pathogenic microorganisms and the urgent demand for new antibiotics require immediate attention. Antimicrobial peptides exhibit effectiveness against microorganisms, fungi, viruses, and protozoa. The discovery of human ß-defensins represents a major milestone in biomedical research, opening new avenues for scientific investigation into the innate immune system and its resistance mechanisms against pathogenic microorganisms. Multiple defensins present a promising alternative in the context of antibiotic abuse. However, obstacles to the practical application of defensins as anti-infective therapies persist due to the unique properties of human ß-defensins themselves and serious pharmacological and technical challenges. To overcome these challenges, diverse delivery vehicles have been developed and progressively improved for the conjugation or encapsulation of human ß-defensins. This review briefly introduces the biology of human ß-defensins, focusing on their multistage structure and diverse functions. It also discusses several heterologous systems for producing human ß-defensins, various delivery systems created for these peptides, and patent applications related to their utilization, concluding with a summary of current challenges and potential solutions.

Safety and efficacy of outpatient parenteral antimicrobial therapy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy. METHODS: We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy. We included studies without restrictions on language or publication year. Eligibility was reviewed independently by two assessors, and data extraction was cross validated. We evaluated bias risk via the Cochrane tool and determined the evidence certainty using GRADE. Meta-analysis was conducted using a random effects model. The protocol of this review was registered on PROSPERO (CRD42023460389). RESULT: Thirteen RCTs, involving 1,310 participants were included. We found no difference in mortality (Risk Ratio [RR] 0.54, 95% Confidence Interval [CI] 0.23 to 1.26; P = 0.93), treatment failure (RR 1.0, CI 0.59 to 1.72; P = 0.99), adverse reaction related to antimicrobials (RR 0.89, CI 0.69 to 1.15; P = 0.38), and administration device (RR 0.58, CI 0.17 to 1.98; P = 0.87) between outpatient and inpatient parenteral antimicrobial therapy. The overall body of evidence had a low level of certainty. CONCLUSION: Existing evidence suggests OPAT is a safe and effective alternative to inpatient treatment. Further RCTs are warranted for a thorough comparison of inpatient and outpatient parenteral antimicrobial therapy with a high level of certainty.

Influence of the COVID-19 pandemic on the defined daily dose of antimicrobials in patients requiring elective and emergency surgical procedures.

BACKGROUND: The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital. METHODS: A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed. RESULTS: A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption. CONCLUSIONS: The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years.

Pioneering Topical Ointment Intervention for Unprecedented Antimicrobial and Diabetic Wound Management with Phenylpropanoids and Nano-Silver.

Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating phenylpropanoids-Eugenol and Cinnamaldehyde-with positively-charged silver nanoparticles was synthesized. The process began with the synthesis and characterization of nano-silver, aimed at ensuring the effectiveness and safety of the nanoparticles in biological applications. Subsequent experiments determined the minimum inhibitory concentration (MIC) against pathogens such as Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. These MIC values of all three active leads guided the strategic formulation of an ointment base, which effectively integrated the bioactive components. Evaluations of this nano-ointment revealed enhanced antimicrobial activity against both clinical and reference bacterial strains and it maintained stability after freeze-thaw cycles. Furthermore, the ointment demonstrated superior in-vitro diabetic wound healing capabilities and significantly promoted angiogenesis, as shown by enhanced blood vessel formation in the Chorioallantoic Membrane assay. These findings underscore the formulation's therapeutic potential, marking a significant advance in the use of nanotechnology for topical wound care.

Development and characterization of an emulgel based on a snail slime useful for dermatological applications.

Snail slime is an interesting material for effective dermatological use (e.g. wounds). Its properties are stricly connected to the origin. In this paper a snail slime, deriving from the species Helix aspersa Muller and obtained from a company, was deeply characterized and then properly formulated. The slime, obtained by Donatella Veroni method, was firstly submitted to NMR analysis in order to evaluate the chemical composition. The main molecules found are glycolate and allantoin, well known for their activities in wound healing promotion. In vitro experiments performed on keratinocytes, revealed the snail slime ability to promote cellular well-being. Moreover, the microbiological analysis showed high activity against many strains involved in wounds infections such as gram+ (e.g. S. aureus, S. pyogenes), gram- (e.g. P. aeruginosa, E. coli) and the yeast C. albicans. The effect on skin elasticity was evaluated as well by the instrument Cutometer® dualMPA580. The snail slime was then formulated as hydrophilic gel, using a combination of corn starch and sodium hyaluronate as polymers, then used as external water phase of an O/W emulgel. The formulation is physically stable and easily spreadable and demonstrated antimicrobial activity as observed for slime alone, suggesting its suitability to be used for wound treatment.

When Should Patients at the End of Life Get Antimicrobials?

Although antimicrobial medications are commonly prescribed to patients at the end of life (EOL), clinicians might not discuss the benefits and harms of antimicrobials with their patients in the advance care planning process. This commentary on a case discusses challenges and strategies in antimicrobial decision making for patients at the EOL. As antimicrobial use can harm some patients, and as antimicrobial resistance remains an urgent public health issue, this article advocates for ethical reasoning to guide antimicrobial decision making for patients at the EOL.

Safety of carrageenan-based gels as preventive microbicides: a narrative review.

BACKGROUND: Carrageenan-containing gels researched for the prevention of sexually transmitted infections (STIs) have shown promising results for human papillomavirus prevention in women, but not in men. We conducted a narrative review to assess the safety of these gels for genital use. METHODS: We searched PubMed using MeSH terms and keywords on 5 November 2023. Title/abstract of articles were screened to identify relevant ones. Full-text screening determined eligibility: empirical study evaluating safety of carrageenan-containing gel(s) for genital use. RESULTS: Of the 125 identified records, 15 were eligible, comprising 14 (10 randomised controlled trials and 4 cohorts) unique study populations. Studies included women only (n=11), men only (n=1) or both (n=3); number of participants ranged from 4 to 6202. Safety was assessed for vaginal (n=13), penile (n=3) and anal use (n=2). Most studies assessed safety of Carraguard (53%), followed by Divine9 (14%), and one each of iota-carrageenan gel, lambda-carrageenan gel, Carvir, PC-6500 (griffithsin and carrageenan) and PC-1005 (MIV-150/zinc acetate/carrageenan). Safety assessment relied on self-report (80.0%), testing for STIs (53.3%), investigator-identified genital findings (93.3%) and/or testing for changes in genital flora (60.0%). Adverse events (AEs) were described by investigators as mostly mild, (mostly) comparable between groups, not observed and/or not significant for vaginal and penile use. Only one study, assessing anal use of carrageenan, reported a significantly higher proportion of AEs in the carrageenan compared with placebo group. CONCLUSIONS: Carrageenan-based gels are generally well tolerated for vaginal and penile, but not anal use. Studies on carrageenan gel's safety for anal use are scarce.

Antimicrobial-coated sutures versus non-coated sutures in reducing surgical site infection: an updated systematic review and meta-analysis.

BACKGROUND: Antimicrobial-coated sutures are one of the strategies to avoid surgical site infection (SSI) caused by microbial colonization on the surface of surgical sutures. AIM: To investigate the effectiveness of antimicrobial-coated sutures in reducing SSI and develop the latest systematic evaluation evidence for clinical SSI prevention and the use of antimicrobial-coated sutures. METHODS: The databases of MEDLINE, Embase, CINAHL, Cochrane, African Index Medicus, and WHO Global Health were searched from October 10th, 1990 to March 3rd, 2023 with language restricted to English, Spanish, and French. Meta-analysis was used to evaluate the impact of antimicrobial-coated sutures on SSI and whether their effectiveness is influenced by the type of sutures or wounds. Subgroup analyses were conducted based on type of sutures and wounds. Finally, quality of the retrieved evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). FINDINGS: Twenty-six randomized control trials (RCTs) and nine observational studies (OBSs) met the inclusion criteria. Antimicrobial sutures significantly reduced SSI risk (RCTs: odds ratio: 0.74; 95% confidence interval: 0.63-0.87; P = 0.0002; OBSs: OR: 0.61; 95% CI: 0.48-0.76; P < 0.0001). Only subgroup analysis of Polydioxanone Suture (PDS) Plus vs PDS, Vicryl Plus vs Vicryl and mixed wounds revealed consistent results in favour of antimicrobial-coated sutures. According to GRADE, the quality of RCT evidence is moderate, while that of OBS evidence is low. CONCLUSION: Antimicrobial-coated sutures are effective in reducing the risk of postoperative SSI among a large number of surgical patients. However, the available evidence is of moderate/low quality and many studies had conflicts of interest.

Making a case for outpatient parenteral antimicrobial therapy (OPAT).

In the wake of the COVID-19 pandemic, and its negative impact on both acute and elective care and decline in available inpatient resources, there is an imperative to maximize safe and effective alternatives to inpatient hospital care. Properly governed outpatient parenteral antimicrobial therapy (OPAT) services embed the principles of antimicrobial stewardship (AMS) (including use of early oral therapy) and support admission avoidance and early discharge for a growing range of patient groups with complex infections through well-organized multidisciplinary team working. Expansion of OPAT aligns with the UK's national strategy to deliver care closer to home and cost-effectively maximize use of inpatient resources. OPAT serves as an exemplar to other ambulatory services and presents opportunities for developing and assuring AMS strategies within the rapidly developing hospital-at-home and virtual ward environments.

Buriti oil as an alternative to the use of antimicrobials in broiler diets.

The objective of this study was to evaluate the effects and economic viability of diets containing different levels of antibiotic and buriti oil (BO) on performance, carcass and cut yields, and relative weight of organs of broilers. A total of 432 one- to 42-day-old male chicks were distributed in a completely randomized experimental design with six treatments, each consisting of six replicates of 12 birds. The treatments consisted of one diet with antibiotic without BO, one diet without antibiotic (DWA) without BO, and four DWA containing increasing levels of BO (0.2, 0.4, 0.6, and 0.8%). Average weight and weight gain (WG) of broilers fed with DWA + BO were similar to those of birds fed control diet. Feed intake and feed conversion (FC) were not different among treatments. Relative weight of pancreas linearly increased in the birds fed diets containing BO. The inclusion of 0.45 and 0.40% of BO in the diets promoted the improvement of WG and FC, respectively. Cost of feed management, ratio, gross margin, and gross income did not differ among treatments. It was concluded that the inclusion of 0.45% of BO in diets without antibiotics is economically feasible and allows recovering the performance of broilers.

Antimicrobial photodynamic therapy in the nonsurgical treatment of periodontitis in patients with HIV infection: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis (SRM) was to evaluate the effectiveness of the adjunctive use of antimicrobial photodynamic therapy (aPDT) in non-surgical periodontal treatment (NSPT) in subjects with Human Immunodeficiency Virus (HIV) and periodontitis. This SRM was registered in PROSPERO (CRD42023410180) and followed the guidelines of PRISMA 2020. Searches were performed in different electronic databases. Risk of bias was performed using the Cochrane Risk of Bias tool (RoB 2.0) for randomized clinical trials (RCT). Meta-analysis was performed using Rev Man software. The mean difference (MD) measure of effect was calculated, the random effect model was applied with a 95% confidence interval, and heterogeneity was tested by the I2 index. The certainty of the evidence was rated using GRADE. A total of 1118 records were screened, and four studies were included. There was a greater reduction in the microbial load of periodontopathogens after NSPT with aPDT. Meta-analysis showed that probing depth (post 3 and 6 months) and clinical attachment loss (post 6 months) were lower for the aPDT-treated group than the NSPT alone: MD -0.39 [-0.74; -0.05], p = 0.02; MD -0.70 [-0.99; -0.41], p < 0.0001; MD -0.84 [-1,34; -0.34], p = 0.0001, respectively. Overall, the studies had a low risk of bias and, the certainty of evidence was rated as moderate. It is suggested that aPDT is a promising adjuvant therapy, showing efficacy in the reduction of the microbial load and in some clinical parameters of individuals with periodontitis and HIV.