Identifying AWaRe indicators for appropriate antibiotic use: a narrative review.

INTRODUCTION: Quality indicators (QIs) are widely used tools for antibiotic stewardship programmes. The Access, Watch, Reserve (AWaRe) system has been developed by the WHO to classify antibiotics based on their spectrum of activity and potential selection of antibiotic resistance. This review aimed to identify existing indicators for optimal antibiotic use to inform the development of future AWaRe QIs. METHODS: A literature search was performed in PubMed. We included articles describing QIs for hospital and primary healthcare antibiotic use. We extracted information about (i) the type of infection; (ii) setting; (iii) target for quality assessment; and (iv) methodology used for the development. We then identified the indicators that reflected the guidance provided in the AWaRe system. RESULTS: A total of 773 indicators for antibiotic use were identified. The management of health services and/or workers, the consumption of antibiotics, and antibiotic prescribing/dispensing were the principal targets for quality assessment. There was a similar distribution of indicators across primary and secondary care. For infection-specific indicators, about 50% focused on respiratory tract infections. Only a few QIs included information on review treatment or microbiological investigations. Although only 8 (1%) indicators directly cited the AWaRe system in the wording of the indicators, 445 (57.6%) indicators reflected the guidance provided in the AWaRe book. CONCLUSIONS: A high number of indicators for appropriate antibiotic use have been developed. However, few are currently based directly on the WHO AWaRe system. There is a clear need to develop globally applicable AWaRe based indicators that can be integrated into antibiotic stewardship programmes.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

A Narrative Review of Recent Antibiotic Prescribing Practices in Ambulatory Care in Tanzania: Findings and Implications.

Background and objectives: There are concerns with the current prescribing practices of antibiotics in ambulatory care in Tanzania, including both the public and private sectors. These concerns need to be addressed as part of the national action plan (NAP) of Tanzania to reduce rising antimicrobial resistance (AMR) rates. Issues and concerns include high rates of prescribing of antibiotics for essentially self-limiting conditions. Consequently, there is a need to address this. As a result, the aims of this narrative review were to comprehensively summarize antibiotic utilization patterns particularly in ambulatory care and their rationale in Tanzania and to suggest ways forward to improve future prescribing practices. Materials and Methods: We undertook a narrative review of recently published studies and subsequently documented potential activities to improve future prescribing practices. Potential activities included instigating quality indicators and antimicrobial stewardship programs (ASPs). Results: Published studies have shown that antibiotics are being excessively prescribed in ambulatory care in Tanzania, in up to 95% to 96.3% of presenting cases depending on the sector. This is despite concerns with their appropriateness. High rates of antibiotic prescribing are not helped by variable adherence to current treatment guidelines. There have also been concerns with extensive prescribing of 'Watch' antibiotics in the private sector. Overall, the majority of antibiotics prescribed across the sectors, albeit inappropriately, were typically from the 'Access' group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than 'Watch' antibiotics to limit AMR. The inappropriate prescribing of antibiotics in ambulatory care is linked to current knowledge regarding antibiotics, AMR, and ASPs among both prescribers and patients. Recommended activities for the future include improved education for all groups, the instigation of updated quality indicators, and the regular monitoring of prescribing practices against agreed-upon guidelines and indicators. Education for healthcare professionals on ASPs should start at undergraduate level and continue post qualification. Community advocacy on the rational use of antibiotics should also include social media activities to dispel misinformation. Conclusion: The quality of current prescribing practices of antibiotics in ambulatory care is sub-optimal in Tanzania. This needs to be urgently addressed.

A Narrative Review of Antibiotic Prescribing Practices in Primary Care Settings in South Africa and Potential Ways Forward to Reduce Antimicrobial Resistance.

There are concerns with the current prescribing of antibiotics in both the private and public primary care settings in South Africa. These concerns need to be addressed going forward to reduce rising antimicrobial resistance (AMR) rates in South Africa. Concerns include adherence to current prescribing guidelines. Consequently, there is a need to comprehensively summarise current antibiotic utilization patterns from published studies as well as potential activities to improve prescribing, including indicators and antimicrobial stewardship programs (ASPs). Published studies showed that there was an appreciable prescribing of antibiotics for patients with acute respiratory infections, i.e., 52.9% to 78% or more across the sectors. However, this was not universal, with appreciable adherence to prescribing guidelines in community health centres. Encouragingly, the majority of antibiotics prescribed, albeit often inappropriately, were from the 'Access' group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than 'Watch' antibiotics to limit AMR. Inappropriate prescribing of antibiotics in primary care is not helped by concerns with current knowledge regarding antibiotics, AMR and ASPs among prescribers and patients in primary care. This needs to be addressed going forward. However, studies have shown it is crucial for prescribers to use a language that patients understand when discussing key aspects to enhance appropriate antibiotic use. Recommended activities for the future include improved education for all groups as well as regularly monitoring prescribing against agreed-upon guidelines and indicators.

Immunological characterization of an Italian PANDAS cohort.

This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A ß-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology.

Ongoing Strategies to Improve Antimicrobial Utilization in Hospitals across the Middle East and North Africa (MENA): Findings and Implications.

Antimicrobial resistance (AMR) is an increasing global concern, increasing costs, morbidity, and mortality. National action plans (NAPs) to minimize AMR are one of several global and national initiatives to slow down rising AMR rates. NAPs are also helping key stakeholders understand current antimicrobial utilization patterns and resistance rates. The Middle East is no exception, with high AMR rates. Antibiotic point prevalence surveys (PPS) provide a better understanding of existing antimicrobial consumption trends in hospitals and assist with the subsequent implementation of antimicrobial stewardship programs (ASPs). These are important NAP activities. We examined current hospital consumption trends across the Middle East along with documented ASPs. A narrative assessment of 24 PPS studies in the region found that, on average, more than 50% of in-patients received antibiotics, with Jordan having the highest rate of 98.1%. Published studies ranged in size from a single to 18 hospitals. The most prescribed antibiotics were ceftriaxone, metronidazole, and penicillin. In addition, significant postoperative antibiotic prescribing lasting up to five days or longer was common to avoid surgical site infections. These findings have resulted in a variety of suggested short-, medium-, and long-term actions among key stakeholders, including governments and healthcare workers, to improve and sustain future antibiotic prescribing in order to decrease AMR throughout the Middle East.

Current rates of purchasing of antibiotics without a prescription across sub-Saharan Africa; rationale and potential programmes to reduce inappropriate dispensing and resistance.

INTRODUCTION: Antimicrobial resistance (AMR) is a global concern. Currently, the greatest mortality due to AMR is in Africa. A key driver continues to be high levels of dispensing of antibiotics without a prescription. AREAS COVERED: A need to document current rates of dispensing, their rationale and potential ways forward including antimicrobial stewardship programmes (ASPs). A narrative review was undertaken. The highest rates of antibiotic purchasing were in Eritrea (up to 89.2% of antibiotics dispensed), Ethiopia (up to 87.9%), Nigeria (up to 86.5%), Tanzania (up to 92.3%) and Zambia (up to 100% of pharmacies dispensing antibiotics without a prescription). However, considerable variation was seen with no dispensing in a minority of countries and situations. Key drivers of self-purchasing included high co-payment levels for physician consultations and antibiotic costs, travel costs, convenience of pharmacies, patient requests, limited knowledge of antibiotics and AMR and weak enforcement. ASPs have been introduced in some African countries along with quality targets to reduce inappropriate dispensing, centering on educating pharmacists and patients. EXPERT OPINION: ASP activities need accelerating among community pharmacies alongside quality targets, with greater monitoring of pharmacists' activities to reduce inappropriate dispensing. Such activities, alongside educating patients and healthcare professionals, should enhance appropriate dispensing of antibiotics and reduce AMR.

Hemoadsorption for severe MIS-C in critically ill children, should we consider it as a therapeutic opportunity?

Multisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic. MIS-C affects children and the young usually after a mild or asymptomatic COVID-19 infection. MIS-C has a high tropism for the cardiovascular system with need for inotropes and vasopressor support in 62% of cases. As of today a mortality from 1.5% to 1.9% related to MIS-C is reported. Hemoadsorption via the inflammatory mediator adsorber CytoSorb (CytoSorbents Europe, Berlin Germany) has been used as adjunctive therapy with the aim to restore the host response in septic shock and other hyper-inflammatory syndromes. We present the clinical experience of an adolescent boy with a refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, treated with hemoadsorption, and continuous kidney replacement therapy (CKRT) in combination with immunomodulatory therapies. The therapeutic strategy resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response. Treatment appeared to be safe and feasible. Our findings are in line with previously published clinical cases on Cytosorb use in MIS-C showing the beneficial role of the hemoperfusion with Cytosorb in severe MIS-C to manage the cytokine storm. We provide an analysis and comparison of recent evidence on the use of hemoadsorption as an adjuvant therapy in critically ill children with severe forms of MIS-C, suggesting this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygentation (ECMO) and other mechanical cardiocirculatory supports.

Role of Hemoperfusion With CytoSorb Associated With Continuous Kidney Replacement Therapy on Renal Outcome in Critically III Children With Septic Shock.

Introduction: Sepsis-associated acute kidney injury (SA-AKI) represents a relevant cause of mortality and morbidity in critically ill children. Since with the "inflammatory theory" the authors have been witnessed an important role of inflammatory mediators in the pathophysiology and in the prognosis of SA-AKI, making the need of adjunctive therapies in association with kidney replacement therapies mandatory. Hemoperfusion with CytoSorb is a safe and well-tolerated therapy in septic shock: the very high surface area of the absorber means it is able to efficiently remove cytokines and other medium size molecules involved in cytokine storm, thus playing a synergistic effect with Continuous Kidney Replacement Therapy (CKRT). Materials and Methods: We retrospectively analyzed data from a cohort of eight critically ill children treated from January 2018 to March 2020 describing the impact of CKRT plus hemoperfusion with CytoSorb on renal outcome in critically ill children with septic shock. Results: We evidenced a significant reduction in interleukin (IL)-6 an IL-10 after hemoperfusion with CytoSorb in our pediatric population. Furthermore, we were able to show a significant improvement of creatinine and blood urea nitrogen (BUN) after blood purification and at pediatric intensive care units (PICU) discharge. We have observed a median of 2.5 CKRT days after stop of hemoperfusion (Q1 0.25; Q3 18.75). None of our patients required CKRT 30 days after PICU discharge (PICU-D). None of them developed CKD. Conclusion: Hemoperfusion with CytoSorb is a valuable therapeutic option in combination with CKRT in SA-AKI. More studies are warranted to confirm our results and in particular to define the role of this adjuvant therapy as a preemptive strategy to protect renal function in pediatric septic shock.

Rare TACI Mutation in a 3-Year-Old Boy With CVID Phenotype.

Common variable immunodeficiency (CVID) is the most common and clinically relevant primary immunodeficiency (PID). Genetic basis of CVID remains largely unknown. However, in a minority of CVID patients, a number of distinct genetic defects affecting the normal processes of B cell maturation and differentiation into memory B cells have now been identified, resulting in markedly reduced serum levels of immunoglobulin G (IgG) and low immunoglobulin A (IgA) or immunoglobulin M (IgM), with impaired antibody responses, despite the presence of normal levels of B cells. Patients with CVID develop recurrent and chronic infections of respiratory and gastrointestinal tracts, autoimmune diseases, lymphoproliferative complications, malignancies, and granulomatous disease. We report the case of a boy admitted to our unit for the first time at the age of three for reduced gamma globulin levels and a clinical history positive for two episodes of pneumonia. Our patient incompletely met ESID diagnostic criteria for CVID, but molecular genetic analysis, a NGS panel including 47 PID-associated genes was performed in the proband and in his parents, revealing the presence of a heterozygous nucleotide substitution in exon 4 (c.579C>A) of TNFRSF13B encoding TACI. This mutation has been described only in two CVID adult patients and in a child with selective IgA deficiency (sIgAD). We highlighted the same mutation in the asymptomatic mother and detected two extra heterozygous mutations of RIG1 and LIG1. We promptly started intravenous immunoglobulin (IVIG) therapy with good tolerance. Despite the diagnosis of CVID remains clinical, in this case report we underline the importance of considering and planning genetic workup in all subjects with unclear diagnosis and of reporting new molecular diagnosis especially in case of rare mutations.

Polymer-Based Black Phosphorus (bP) Hybrid Materials by in Situ Radical Polymerization: An Effective Tool To Exfoliate bP and Stabilize bP Nanoflakes.

Black phosphorus (bP) has been recently investigated for next generation nanoelectronic multifunctional devices. However, the intrinsic instability of exfoliated bP (the bP nanoflakes) toward both moisture and air has so far overshadowed its practical implementation. In order to contribute to fill this gap, we report here the preparation of new hybrid polymer-based materials where bP nanoflakes (bPn) exhibit a significantly improved stability. The new materials have been prepared by different synthetic paths including: (i) the mixing of conventionally liquid-phase exfoliated bP (in dimethyl sulfoxide, DMSO) with poly(methyl methacrylate) (PMMA) solution; (ii) the direct exfoliation of bP in a polymeric solution; (iii) the in situ radical polymerization after exfoliating bP in the liquid monomer (methyl methacrylate, MMA). This last methodology concerns the preparation of stable suspensions of bPn-MMA by sonication-assisted liquid-phase exfoliation (LPE) of bP in the presence of MMA followed by radical polymerization. The hybrids characteristics have been compared in order to evaluate the bP dispersion and the effectiveness of the bPn interfacial interactions with polymer chains aimed at their long-term environmental stabilization. The passivation of the bPn is particularly effective when the hybrid material is prepared by in situ polymerization. By using this synthetic methodology, the nanoflakes, even if with a gradient of dispersion (size of aggregates), preserve their chemical structure from oxidation (as proved by both Raman and 31P-solid state NMR studies) and are particularly stable to air and UV light exposure. The feasibility of this approach, capable of efficiently exfoliating bP while protecting the bPn, has been then verified by using different vinyl monomers (styrene and N-vinylpyrrolidone), thus obtaining hybrids where the nanoflakes are embedded in polymer matrices with a variety of intriguing thermal, mechanical, and solubility characteristics.

X-Ray Fluorescence Analysis and Self-Organizing Maps Classification of the Etruscan Gold Coin Collection at the Monetiere of Florence.

The "Monetiere" of Florence hosts the most important collection of Etruscan coins in the world. In the framework of the longstanding collaboration between the Monetiere and the Applied Laser and Spectroscopy Laboratory in Pisa, the Etruscan gold coin collection of the museum was studied. The measurements were performed at the Monetiere, using a portable energy-dispersive X-ray fluorescence (XRF) instrument. The quantitative determination of the gold alloys used for the realization of the coins was obtained applying the fundamental parameters method to the XRF spectra; as a result, using the self-organizing maps method, we were able to classify the coins in four main groups. The main parameter determining the classification is the quantity of silver in the alloy. The results obtained shed some light about the origin of the coins under study.

Micro-Laser-Induced Breakdown Spectroscopy (Micro-LIBS) Study on Ancient Roman Mortars.

The laser-induced breakdown spectroscopy (LIBS) technique was used for analyzing the composition of an ancient Roman mortar (5th century A.D.), exploiting an experimental setup which allows the determination of the compositions of binder and aggregate in few minutes, without the need for sample treatment. Four thousand LIBS spectra were acquired from an area of 10 mm2, with a 50 µm lateral resolution. The elements of interest in the mortar sample (H, C, O, Na, Mg, Al, Si, K, Ca, Ti, Mn, Fe) were detected and mapped. The collected data graphically shown as compositional images were interpreted using different statistical approaches for the determination of the chemical composition of the binder and aggregate fraction. The methods of false color imaging, blind separation, and self-organizing maps were applied and their results are discussed in this paper. In particular, the method based on the use of self-organizing maps gives well interpretable results in very short times, without any reduction in the dimensionality of the system.

Discovering "The Italian Flag" by Fernando Melani (1907-1985).

In the occasion of the celebrations for the 150th anniversary of the founding of Italy (1861-2011), it was decided to analyse the artwork "The Italian Flag" (La Bandiera Italiana) created by the artist Fernando Melani (Pistoia, 1907-1985), one of the precursors of the Poor Art artistic movement in Italy. This project is a follow-up to a previous study which was mainly focused on the pigments and dyes found in his home-studio. The main goal of this paper is to identify a correct diagnostic plan, based on the use of a combination of non-invasive and micro-invasive methodologies, in order to determine the state of preservation and define the best conservation procedures for a contemporary artwork. Visible, infrared and infrared false colour images as well as the Fibre Optic Reflectance Spectroscopy (FORS) technique were applied in situ to analyse The Italian Flag. Laser Induced Breakdown Spectroscopy (LIBS), Fourier Transform Infrared (FT-IR) and micro-Raman spectroscopies, Pyrolysis-Gas Chromatography/Mass Spectroscopy (Py-GC/MS), High Performance Liquid Chromatography with Diode Arrays Detection (HPLC-DAD) and Mass Spectrometric Detection (HPLC-ESI-Q-ToF) were all applied to three small samples detached from the three painted (green-blue, white and red-yellow, respectively) areas of the flag. The combination of the data obtained with all these techniques made possible a comprehensive understanding of both the chemical composition and physical behaviour of the materials used by the artist and supported curators in defining the preventive conservation of this artwork.