BACKGROUND: Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient de-labelling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and non-allergist de-labelling.
OBJECTIVE: To assess the safety of de-labelling low-risk adults by means of dDC in primary care.
METHODS: We searched MEDLINE, EMBASE and the Conchrane Library databases, from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal was performed by one reviewer and we pooled the results in a meta-analysis.
RESULTS: Out of 2,138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated de-labelling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely de-labelled. Ten patients (<1%) developed an immediate reaction: three had self-limiting reactions, and seven needed antihistaminics, steroids, epinephrine and/or salbutamol.
CONCLUSIONS: No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of one recent report, these studies are of low to moderate quality. Non-specialist de-labelling is promising but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.

Inappropriate antibiotic choice or duration of therapy for urinary tract infections (UTIs) in outpatients is common and is a major contributor to antibiotic overuse. Most studies on outpatient antibiotic stewardship for UTIs follow a pre-design or post-design with a multifaceted intervention; these trials generally have found improvement in appropriateness of antibiotic use for UTI. Audit and feedback was one of the most commonly employed strategies across these trials but may not be sustainable. Future research on antibiotic stewardship for UTIs in outpatients should measure both effectiveness and implementation success.

Navigating antibiotics at the end of life is a challenge for infectious disease (ID) physicians who remain deeply committed to providing patient-centered care and engaging in shared decision making. ID physicians, who often see patients in both inpatient and outpatient settings and maintain continuity of care for patients with refractory or recurrent infections, are ideally situated to provide guidance that aligns with patients\' goals and values. Complex communication skills, including navigating difficult emotions around end-of-life care, can be used to better direct shared decision making and assist with antibiotic stewardship.

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This study aimed to summarize the screened articles on antibiotic shortages, compare them with the Hungarian Health Authority database, and identify the overlapping substances in shortages and handling practices. A systematic analysis was conducted using the provided keywords to filter out appropriate studies and incorporate them into this review. The studies were searched in the following databases: Reaxys, PubMed, Ovid, ScienceDirect, and Embase. The search time interval was 2000-2023, with the following keywords used: \"antibiotic\", \"shortage\", and \"in clinic\". The shortage data for Hungary were collected and integrated within the specified timeframe. This was achieved through a comprehensive screening method to ensure comparability between the data from the literature review and the database. Based on the comparison, we have identified two groups of ingredients, the overlapping and not-overlapping ingredients. The mitigation practices were also categorized and evaluated to recommend good shortage management practices for Hungarian decision-makers and healthcare professionals. Our key conclusion was to enhance a shortage risk-based approach, including the legislative, health authority, and healthcare professionals responsible for therapeutic protocol and procuring or producing the necessary product. A widely approved shortage risk-based framework should be created to mitigate the impacts, including communication protocols, individual therapy planning, compounding of magistral products, and antimicrobial stewardship programs. The most common mitigation strategy is the substitution with available alternatives, but besides, a good understanding and implementation of antimicrobial stewardship programs is also crucial.

UNASSIGNED: A growing emphasis on antibiotic stewardship has led to extensive literature regarding antibiotic use in spine surgery for surgical prophylaxis and the treatment of spinal infections.
UNASSIGNED: This article aims to review principles of antibiotic stewardship, evidence-based guidelines for surgical prophylaxis and ways to optimize antibiotics use in the treatment of spinal infections.
UNASSIGNED: A narrative review of several society guidelines and spine surgery literature was conducted.
UNASSIGNED: Antibiotic stewardship in spine surgery requires multidisciplinary investment and consistent evaluation of antibiotic use for drug selection, dose, duration, drug-route, and de-escalation. Developing effective surgical prophylaxis regimens is a key strategy in reducing the burden of antibiotic resistance. For treatment of primary spinal infection, the diagnostic work-up is vital in tailoring effective antibiotic therapy. The future of antibiotics in spine surgery will be highly influenced by improving surgical technique and evidence regarding the role of bacteria in the pathogenesis of degenerative spinal pathology.
UNASSIGNED: Incorporating evidence-based guidelines into regular practice will serve to limit the development of resistance while preventing morbidity from spinal infection. Further research should be conducted to provide more evidence for surgical site infection prevention and treatment of spinal infections.

To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics.
We performed 2 different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analyzed the articles and collected variables of efficacy, safety, and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed.
The selected studies analyzed questionnaires, allergy delabeling, intradermal tests, and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favor of pharmaceutical intervention. In the study of Kwiatkowski et al., cefazolin use increased in surgical patients after pharmacist intervention (65% vs 28%; P < .01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, P <.01) and (8.79-4.24, P = .016), pre- and post-intervention, respectively, increasing antibiotic de-escalations (P = < .01). In another quasi-experimental study, the prescription of restricted use antibiotics decreased (42.5% vs 17.9%, P < .01)and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, P < .01)in another study. Other study showed that the mean time per interview was 5.2 min per patient. No adverse events were reported in any study.
The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe, and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabeling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second-line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.

Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the \"One Health approach.\" Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed-lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity. Graphical AbstractThe graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.

Clostridioides difficile infection (CDI) has become the most common healthcare-associated infection in the United States, with considerable morbidity, mortality, and healthcare costs. Assessing new preventive strategies is vital. We present a literature review of studies evaluating a strategy of screening and isolation of asymptomatic carriers in hospital settings. Asymptomatic detection of C. difficile is reported in ~ 10-20% of admitted patients. Risk factors for carriage include recent hospitalization, previous antibiotics, older age, lower functional capacity, immunosuppression, and others. Asymptomatic C. difficile carriers of toxigenic strains are at higher risk for progression to CDI. They are also shedders of C. difficile spores and may contribute to the persistence and transmission of this bacterium. Screening for asymptomatic carriers at hospital admission can theoretically reduce CDI by isolating carriers to reduce transmission, and implementing antibiotic stewardship measures targeting carriers to prevent progression to clinical illness. Several observational studies, summarized in this review, have reported implementing screening and isolation strategies, and found a reduction in CDI rates. Nevertheless, the data are still limited to a few observational studies, and this strategy is not commonly practiced. Studies supporting screening were performed in North America, coinciding with the period of dominance of the 027/BI/NAP1 strain. Additional studies evaluating screening, followed by infection control and antibiotic stewardship measures, are needed.

To analyze the role played by the clinical pharmacist and its impact in antibiotic stewardship facing suspected allergy to beta-lactam antibiotics.
We performed two different independent bibliographic searches. A total of 35 articles were found, and the final number included in the study was 12. We analysed the articles and collected variables of efficacy, safety and applicability of evaluation tools applied to patients with suspected allergy to beta-lactams. Also, the variation in the consumption and prescription profile of alternative antibiotics was analyzed.
The selected studies analysed questionnaires, allergy delabeling, intradermal tests and oral challenge tests performed by pharmacists. Significant differences in the efficacy endpoint were found in 4 studies in favour of pharmaceutical intervention. In the study of Kwiatkowski et al, cefazolin use increased in surgical patients after pharmacist intervention (65 vs. 28%; p < 0.01). In a quasi-experimental study, the mean defined daily dose of aztreonam and the mean days of therapy per 1000 patients/day decreased (21.23 vs 9.05, p <0.01) and (8.79-4.24, p = 0.016), pre and post-intervention, respectively, increasing antibiotic de-escalations (p ≤ 0.01). In another quasi-experimental study, the prescription of restricted-use antibiotics decreased (42.5% vs. 17.9%, p < 0.01) and the use of pre-surgical prophylactic antibiotics alternative to cefazolin (81.9% vs 55.9%, p<0.01) in another study. Other study showed that the mean time per interview was 5.2 minutes per patient. No adverse events were reported in any study.
The pharmacist intervention in the evaluation of the patient with suspected allergy to beta-lactams is effective, safe and feasible to implement on daily clinical practice. The standardization of protocols to clarify the history of allergies and development of evaluation tools represent simple screenings to perform delabelling or refer to the Immunoallergology service, improving penicilins use and reducing the need for second line antibiotics. More studies are needed to standardize the desensitization tests made by pharmacists. However, despite these results, the involvement and leadership of the pharmacist in this area is limited and constitutes a future challenge for the profession.