Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic resistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating antibiotic efficacy and resistance. This review delves into the intricate relationship between gut microbiota, antibiotic therapy, and resistance and discusses the potential applications of gut microbiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demonstrated the potential for tailored antibiotic regimens that minimize collateral damage to commensal bacteria and reduce the risk of resistance. Adjuvant therapies, such as probiotics, prebiotics, and synbiotics, have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field, including the need for standardized methodologies, ethical considerations, and interdisciplinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes. Antibiotic resistance has emerged as a significant concern for public health, which is likely to jeopardize the efficacy of life-saving antimicrobial treatments ,2. The iAmidst these concerns, the gut microbiota has gained significant attention as a crucial modulator of host health and disease . The humThe intricate interplay between the gut microbiota and the host immune system is essential to maintain homeostasis for the optimal functioning of an individual. Imbalances in this interplay have been linked to a range of diseases, including infectious diseases . TherefoFurthermore, newer research has highlighted the potential of the gut microbiota to overcome antibiotic resistance through competitive exclusion, colonization resistance, and modulation of host immune responses -17. The The present review presents an extensive overview of the molecular mechanisms underlying the influence of gut microbiota on the selection of antibiotic therapy and the alleviation of antibiotic resistance. The article emphasizes the clinical significance, hurdles, and potential research pathways concerning gut microbiota in the context of infectious diseases. The knowledge in this review will improve clinical decision-making and help design innovative therapeutic strategies.Gut microbiota and antibiotic therapy selectionThe gut microbiota can significantly influence the efficacy and toxicity of orally administered antibiotics as it plays a crucial role in modulation of their pharmacokinetics and pharmacodynamics. Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs, while pharmacodynamics deals with the relationship between drug concentration and its effect on the body . Both asThe gut microbiota also influences the absorption of antibiotics by metabolizing the drug or altering the intestinal environment, which can lead to changes in drug bioavailability . For insClostridiodes difficile infection. A study by Buffie et al. reported that the administration of a single clindamycin dose resulted in a significant reduction in the diversity of the intestinal microbiota for a minimum of 28 days. Moreover, it caused a long-term reduction of approximately 90% of the normal microbial taxa present in the cecum [One of the key examples illustrating the impact of the gut microbiota on antibiotic therapy selection is the interaction between the gut microbiota and the antibiotic vancomycin. The gut microbiota can modulate the pharmacokinetics and pharmacodynamics of vancomycin by altering its absorption, distribution, and metabolism, as well as its ability to elicit an immune response . Furtherhe cecum .Staphylococcus aureus, which acquires antibiotic resistance easily. Even the most susceptible S. aureus survives and persists the antibiotic therapy. It requires prolonged surgical interventions and treatments. They tolerate high concentrations of antibiotics, display the phenotype of arrested growth, and are are linked with recurrent and chronic infections [S. aureus in reaction to acid stress, paving to a general infectious population. They persist also due to molecular reprogramming, such as ribosomal protein upregulation, downregulation of virulence, amino acid pathways, cell division, ATP levels, lowered aconitase activity, and accretion of insoluble proteins used in translation, transcription, and energy production. They showed that a directed antipersister therapy by the use of retinoid byproducts and antibiotics helps to eliminate persistiors to some extent [An example of persisters is fections . Huemer e extent .Clostridium difficile, an etiological factor for severe diarrhea and colitis [Furthermore, it has been shown that the gut microbiota can contribute to antibiotic-related toxicity. Antibiotics can disrupt the gut microbiota, which leads to the overgrowth of pathogenic bacteria, such as  colitis . In addi colitis . For exa colitis .Use of diagnostic techniques in understanding the role of gut microbiota in antibiotic therapyThe recent advancements in various molecular techniques, such as metagenomics, transcriptomics, and metabolomics, have significantly contributed to our understanding of the role of gut microbiota in antibiotic therapy selection. Metagenomics has enabled the sequencing and analysis of the total genomic content of microbiota, which facilitate the identification of specific bacterial taxa and their functional genes . This apAntibiotic resistance mitigation by gut microbiotaThe gut microbiota has been shown to play a significant role in the development and mitigation of antibiotic resistance . AntibioCompetitive ExclusionBifidobacterium and Lactobacillus species produce antimicrobial compounds that directly target pathogenic bacteria, which further restricts their growth and minimizes the emergence of resistance [One of the mechanisms through which the gut microbiota mitigates antibiotic resistance is competitive exclusion where beneficial commensal bacteria in the gut prevent the colonization and growth of resistant pathogens . Beneficsistance .Colonization ResistanceColonization resistance is a crucial mechanism that aids in reducing antibiotic resistance by impeding the colonization of pathogens in the gut through the production of antimicrobial agents and alteration of the local environment . The comThe use of narrow-spectrum antibiotics can preserve colonization resistance and minimize the emergence of antibiotic resistance . CertainCitrobacter rodentium and E. coli may be in rivalry for the absorption of monosaccharides. However, some pathogenic microbes may use gastrointestinal nutrients that commensals cannot digest. For instance, ethanolamine is a nitrogen and carbon source for Enterohaemorrhagic E. coli (EHEC), Salmonella typhimurium, Klebsiella, C. difficile, Listeria monocytogenes , and Pseudomonas, but it cannot be utilized by a maximum of the commensal species [E. coli [E. coli, and might fail to form a colony in the gut [Mechanisms of colonization resistance: There are two types of mechanisms in colonization resistance: direct and indirect. The direct mechanism is characterized by the ability of gut microbiota to limit colonization by intestinal pathogens, or the over progression of these pathogens after embedding, and those liberated from the host. Dietary complex carbohydrates and mucins are crucial colonic nutritious means to which commensal types have adapted through definite metabolic paths . Enterop species . Particu[E. coli . Interes the gut . Cell wall-active bactericidal polypeptides produced by the commensal microbes generally are called bacteriocins. Bacteriocins produced by the Gram-negative bacteria are named microcins, and they have a fine spectrum of action restricted to new Gram-negative microbes . MicrociIn indirect mechanisms, host and commensal flora interactions result in colonization resistance indirectly. This happens through RegIIIγ and angiotensin-4 , bile acid metabolism, and epithelial barrier mechanism. The production of antimicrobial peptides is regulated by the microbes. Microbiota can stimulate the production of RegIIIγ by stimulating toll-like receptors (TLRs), mainly TLR-4, through the lipopolysaccharides . In the C. difficile spores, while secondary bile acids are well known to cause an inhibition in the growth of toxin-producing vegetative C. difficile [Clostridium scindens can convert chenodeoxycholic acid and cholic acid (primary bile acids) to lithocholic acid and deoxycholic acid (secondary bile acids). As a result, C. scindens increase resistance to infections by C. difficile in both human patients and animals through secondary bile acid-dependent functions [In the case of bile acid metabolisms, reabsorption of primary bile acids occurs in the terming ileum; however, only a small fraction reaches the large intestine, where the subset of colonic bacteria converts primary bile acids into secondary bile acids. Different bile acids affect differently on the vegetative growth and germination process. For example, taurocholic acid, a primary bile acid, has an impact on germination induction in the ifficile . Clostriunctions .Use of Diagnostic Techniques in Antibiotic Resistance Mitigation by Gut MicrobiotaThe role of different molecular techniques has been instrumental in studying the role of gut microbiota in mitigating antibiotic resistance. Metagenomic analyses can identify the presence and abundance of antibiotic resistance genes within the gut microbiota . TranscrFurthermore, recent advances in NGS technologies, such as long-read sequencing and metagenomic assembly, have enabled the identification and characterization of novel antibiotic resistance genes and mobile genetic elements that contribute to the spread of antibiotic resistance within the gut microbiota . These tProbiotics, Prebiotics, and Fecal Microbiota Transplantation (FMT)C. difficile infections and reducing the prevalence of antibiotic-resistant bacteria in the gut [Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) carriage compared with controls [The modulation of gut microbiota is a promising strategy for mitigating antibiotic resistance. Probiotics, prebiotics, and fecal microbiota transplantation (FMT) are potential interventions that can be used for this purpose. Probiotics are living microorganisms that when consumed in appropriate quantities bestow a health benefit on the host by enhancing the resistance of gut microbiota against pathogenic organisms and antibiotic-induced perturbations . Prebiot the gut . A randocontrols .C. difficile infection on the gut microbiota. Additionally, the application of bacteriophages has been proposed as an alternative to conventional antibiotics with the potential to specifically target resistant bacteria without disrupting the overall gut microbial community . Figure Clinical applications of gut microbiota research for antibiotic therapy selectionBy understanding the complex interactions between the gut microbiota, antibiotics, and host immune responses, clinicians can attain greater acuity in antibiotic selection and implement measures to attenuate resistance. Furthermore, recent advances in omics technologies have facilitated the development of rapid diagnostic tools that can assess the gut microbiota's composition and function, providing real-time information to guide clinical decision-making . Gut micLactobacillus rhamnosus probiotic alongside antibiotic treatment for bacterial vaginosis resulted in higher cure rates and fewer recurrences compared to the antibiotic treatment alone [Moreover, research into the use of probiotics, prebiotics, and synbiotics as adjuvant therapies has shown promise in improving antibiotic efficacy and reducing resistance development. In a randomized, double-blind, placebo-controlled trial, Reid et al. demonstrated that the administration of a nt alone . Similarnt alone . The intFurthermore, the implementation of gut microbiota-based diagnostics and therapeutics in clinical settings faces several practical barriers, such as the need for specialized equipment, trained personnel, and rigorous quality control measures, to ensure the accuracy and reproducibility of results . FurtherCurrent challenges and future directionsThe investigation of gut microbiota has the potential to significantly influence the selection of antibiotic therapy and the mitigation of resistance. However, the field faces various challenges. One such challenge is the standardization of techniques and interpretation of results as the field currently lacks universally accepted methodologies and reporting standards. The inconsistency in sample collection, processing, sequencing, and data analysis can result in variations in findings, which obstruct the translation of research outcomes into clinical practice . To addrFuture research directions in the field include investigating the role of the gut microbiota in antibiotic stewardship and optimizing personalized medicine approaches. Antibiotic stewardship programs could greatly benefit from a better understanding of the role of the gut microbiota in antibiotic response and resistance development . By incoThe emerging field of gut microbiota research holds tremendous potential for revolutionizing antibiotic therapy selection and resistance mitigation strategies. The intricate interplay between the gut microbiota, antibiotic therapy, and antibiotic resistance underscores the importance of incorporating this research into clinical practice. By addressing the challenges and future directions associated with this field, including standardization of methodologies, ethical considerations, and interdisciplinary collaboration, we can pave the way for the integration of gut microbiota research into antibiotic therapy and resistance mitigation efforts. Harnessing the power of gut microbiota research can not only optimize antibiotic use and preserve the efficacy of these lifesaving drugs but also significantly contribute to combating the global threat of antibiotic resistance. Furthermore, the development and validation of novel diagnostic tools, therapeutic interventions, and predictive models will facilitate the practical implementation of gut microbiota research findings in clinical settings. By maintaining an agile and responsive research environment, the scientific community can swiftly adapt to new findings and challenges, driving the field of gut microbiota research forward and making significant strides toward better antibiotic therapy selection and resistance mitigation.


It is unclear which stewardship metrics are most effective for audit and feedback to outpatient clinicians. In this study, we explored a metric that captures antibiotic-prescribing for all respiratory tract diagnoses to determine if it could serve as an appropriate metric for feedback.We performed a retrospective cohort study of in-person visits to the 7 walk-in clinics, including 3 Urgent Care locations, within University of Iowa Health Care during 2018-2022. Visits were categorized as respiratory visits (RVs) if a respiratory tract diagnosis was coded and the patient lacked complicating factors, such as a concomitant non-respiratory infection or certain comorbidities. We built a hierarchical logistic regression model that adjusted for antibiotic appropriateness tiers (1-3) to identify factors associated with antibiotic-prescribing for RVs. Using Spearman’s correlation, we compared the frequency at which clinicians prescribed antibiotics for RVs and other types of visits.There were 331,496 visits, and 96,546 (29.1%) led to an antibiotic prescription; 44,498 (46.1%) of these were for RVs (Tables 1 and 2). At the clinician-level (n=89), the mean frequency of antibiotic-prescribing for RVs was 36.4% (standard deviation 11.6). Factors at the visit-level associated with an increased odds of antibiotic use for RVs included age ≥ 65  and having at least one comorbidity . The frequency at which a clinician prescribed antibiotics for RVs was strongly correlated with antibiotic use for all visits . Clinicians who more often prescribed antibiotics for RVs also more often prescribed antibiotics for respiratory infections that are always viral , sinusitis , and non-streptococcal pharyngitis . There was no correlation between antibiotic-prescribing for RVs and the frequency of return visits within 30 days .A metric that quantifies the frequency of antibiotic-prescribing for all respiratory tract diagnoses correlated strongly with clinicians who over-use antibiotics for walk-in visits. Future studies should assess whether this type of metric is acceptable to clinicians and an effective tool for feedback.Daniel J. Livorsi, MD, Merck: Grant/Research Support Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant


Antibiotics are most commonly used in outpatient setting when compared to inpatient setting. Inappropriate antibiotics prescribing in dental and ophthalmic outpatient setting without following any proper guidelines has been identified as a potential driver for antimicrobial resistance especially in the developing world. As there is no sufficient data in India regarding efficient prophylactic use of antibiotics in dental and ophthalmic department, this study is aimed to address this by assessing the antibiotic prophylaxis among outpatients.This retrospective observational study was conducted in the Dental and Ophthalmic outpatient’s department in a tertiary care hospital in South India for 3 months from April 2022 to June 2022. The data regarding the Antibiotic prophylaxis were collected from records of the patients’ prescription and analyzed using simple statistics.A total of 395 prescriptions are collected. Mean age was found to be 53.5 years. The key findings are summarized in Table 1 below.85% of patients were prescribed with antibiotics in Dental OP whereas 90% of patients were prescribed with antibiotics in Ophthalmic OP in which 56% of patients were found to have inappropriate duration of Antibiotic therapy. Understanding the current patterns of antibiotic prophylaxis in outpatient setting is necessary to implement antibiotic stewardship and large multicentric studies in the future will help to reduce unnecessary antibiotic use in the developing world.All Authors: No reported disclosures


A practice guide to help nursing homes set up an antimicrobial stewardship (AMS) program was developed based on experiences gained during a project at one of the largest providers of elderly care in the South-east of the Netherlands. The guideline for the implementation of AMS in Dutch hospitals served as a starting point and were tailored to the unique characteristics of a nursing home setting. This practice guide offers recommendations and practical tools while emphasizing the importance of establishing a multidisciplinary approach to oversee AMS efforts. The recommendations and practical tools address various elements of AMS, including the basic conditions to initiate an AMS program and a comprehensive approach to embed an AMS program. This approach involves educating nurses and caregivers, informing volunteers and residents/their representatives, and the activities of an antibiotic team (A-team). The practice guide also highlights a feasible work process for the A-team. This process aims to achieve a culture of continuous learning and improvement that can enhance the overall quality of antibiotic prescribing rather than making individual adjustments to client prescriptions. Overall, this practice guide aims to help nursing homes establish an AMS program through collaborative efforts between involved physicians, pharmacists, clinical microbiologists, and infection control practitioners. The involved physician plays a crucial role in instilling a sense of urgency and developing a stepwise strategy. Antimicrobial resistance is widely recognized as a crucial concern. Antibiotic use and antimicrobial resistance in long-term care facilities (LTCFs) are substantial due to the significant use of antibiotics . SeveralSince 2015, it has been mandatory for Dutch hospitals to implement an antimicrobial stewardship (AMS) program to enhance the quality of antibiotic use. Consequently, a practice guide was developed to facilitate this process . HoweverTo investigate the implementation of an AMS program that tailors hospital recommendations to NHs, a project was conducted in one of the largest providers of nursing home care in the South‒East region of the Netherlands. The project group comprised the following members: a medical director and an elderly care physician from the provider of nursing home care, a pharmacist responsible for medication supply, a clinical microbiologist from the medical microbiology laboratory providing diagnostics to the organization, an infection control practitioner offering services to the elderly care organization, a representative from a national committee focused on optimizing antibiotic use (Dutch Working Party on Antibiotic Policy (Dutch acronym is SWAB)), representatives from a national institute working on the development and dissemination of information and solutions for medication use, and an administrative support staff member. During the 14-month project, the AMS approach was formulated, and an A-team was established. Antibiotic treatment protocols for the most common infections in nursing home residents were revised at the regional level, including urinary tract infections (UTIs), lower respiratory tract infections (LRTIs) and skin and soft tissue infections (SSTIs). Scorecards for data collection and assessment were developed to evaluate all antibiotic prescriptions in 4 out of 28 nursing homes. A new rule regarding the use of urine dipstick tests was implemented, and it was required that culture be conducted in accordance with the guideline . A standThe nursing home facilities met the international definition for nursing homes: ‘A nursing home is a facility with a domestic-styled environment that provides 24-hour functional support and care for persons who require assistance with activities of daily living (ADLs) and who often have complex health needs and increased vulnerability. Residents within a nursing home may stay relatively brief for respite purposes, short term (rehabilitative), or long term, and may also receive palliative/hospice and end-of-life care’ . MoreoveThe lessons learned from this project have been compiled into recommendations, which are presented in the current practice guide to help NHs set up an AMS program.To establish an AMS program, certain basic conditions must be met. The extent to which these conditions are met contributes to the success of the program.One of the crucial conditions is the commitment of the board of directors. This board needs to have a clear vision of the necessity of an AMS program and be willing to allocate the necessary human and financial resources.Another essential condition is ensuring that the human and financial resources required for an AMS program are both adequate and appropriate for the NH. Consequently, assign this specific task to a physician. The baseline situation determines the amount of resources needed, which may vary depending on factors such as existing contracts between cooperating parties and the ability to embed AMS topics into regular processes and meetings. Consider establishing service agreements in which AMS is an integral part of the services for a clinical microbiologist, a pharmacist, and an infection control practitioner who are not employees of the organization. Additionally, having up-to-date treatment protocols and written guidelines for appropriate antibiotic prescribing are needed to easily generate overviews of antibiotic prescriptions. Furthermore, ensuring that physicians mention the indication for the antibiotic prescription in the prescription system will reduce the time investment required for the program. If NHs already have high compliance rates regarding antibiotic prescribing, implementing the program will require less effort. Changes in microbiology culture policies may have financial implications. Finally, purchasing education materials and adapting them may require substantial financial investment and time investment from healthcare workers.To implement an AMS program, it is crucial to form a project team consisting of professionals with relevant expertise. The team should include, at least, a physician who provides medical care to the residents, a pharmacist who supplies the medication to the NH, and a clinical microbiologist of the medical microbiology laboratory that delivers microbiological diagnostic to the NH and has knowledge on local/regional resistance data. To ensure efficient decision-making and create organisation-wide conditions for the success of an AMS program, it is recommended to appoint a medical director or member of the management team to the project team. If this is not feasible, one of the project team members should be authorized on behalf of the management team to determine the responsibilities of each member of the project team. It is also advisable to appoint a healthcare professional to the project team who is well-versed in the nursing home organisation and has received appropriate training in infection control and antibiotic resistance, such as an infection control practitioner.Overall, a comprehensive approach to embedding an AMS program within a NH creates collaboration with and engagement of relevant stakeholders. It incorporates strategies that support the program’s sustainability and success.The implementation of an aligned AMS and infection control program and bringing both policy topics under the responsibility of one committee  can help achieve the following objectives: (1) Prevent the development of antibiotic resistance through appropriate use of antibiotics, (2) Detect the presence and transmission of (drug-resistant) bacteria, and (3) Prevent transmission of (drug-resistant) bacteria through hygiene and infection control measures.Establishing an A-team comprising a physician, pharmacist, and clinical microbiologist can facilitate the development and revision of antibiotic treatment protocols as well as the monitoring of antibiotic use. It is also advised to examine the feasibility of regional collaborations in certain aspects . It can be highly valuable to add an infection control practitioner to the A-team to coordinate the activities. The A-team’s composition allows for a collaborative approach to optimize antibiotic use and promote appropriate prescribing.To obtain physicians’ support for the AMS program, they must be involved from the start. Utilizing existing meetings, such as PTAMs or staff meetings, can be an effective way to keep colleagues informed about the program’s progress, A-team activities, and antibiotic treatment protocols. The A-team may also use these meetings to discuss issues related to antibiotic choices in treatment protocols, deviations from protocols, or experiences from previous cases, which could result in topics for additional education. Such education can increase physician competence and willingness to adhere to antibiotic treatment protocols.It is recommended to provide education on antibiotic use and antibiotic resistance to nurses and carers for various reasons. These healthcare workers are often the first to recognize signs and symptoms of an infection and serve as the primary contact for residents and their representatives. They play a crucial role in relaying information about residents’ conditions to physicians, who do not see residents every day. In addition, they are responsible for carrying out protocols. For example, protocols depicting the use of infection control measures and measures to reduce the risk of a urinary tract infection (UTI) or (aspiration) pneumonia. Often, they also inform residents/their representatives about antibiotic prescriptions. It is important to discuss the feasibility of different modes of education, such as e-learning, which can reach a large target group with relatively little effort, or group discussion training led by an infection control practitioner. Arrangements should also be made regarding whether healthcare workers will receive training during work or during personal time and whether they will have the opportunity to gain accreditation points.In nursing homes, volunteers play an important role in the provision of care, e.g., supporting individual and group activities, assisting caregivers with practical tasks such as serving coffee and tea, aiding in cooking and serving dishes, and offering social and emotional support to residents. This group should be adequately informed about infection control. Specifically, the provision of information on hand hygiene, appropriate measures to take in the event of signs or symptoms of an infection, and food preparation (cooking and serving) should be considered. It is recommended to use reliable, publicly accessible sources of information for the dissemination of general information on infections and antibiotic resistance.In addition to the fact that residents and their representatives should always be able to consult nurses, carers, or physicians, it is recommended to offer them information through various media such as paper copies (folders/newsletters), audio recordings, and video presentations so that they can absorb the information at their convenience. It is imperative to contact the residents’ council of the nursing home to ascertain their information requirements  and determine the most effective way to convey the information to them. The residents’ council should also support the implementation of an AMS program. Similar to volunteers, it is also recommended for this target group to use reliable, publicly accessible sources of information.It is important to define the activities of an A-team, which is responsible for promoting appropriate antibiotic use.It is important to define the responsibilities and authority of the A-team, which include the following: (1) maintaining treatment protocols up-to-date in accordance with (inter)national guidelines, regional resistance data, and culturing policy, and (2) monitoring compliance with treatment protocols based on predetermined selection criteria. Moreover, the A-team derives its authority from its expertise in the field of antibiotics, making its opinion highly valued. In case of deviations from treatment protocols or the A-team’s opinion, prescribing physicians need to state the reason for the deviation in the residents’ record. It is also important to emphasize that although the A-team plays a crucial role in antibiotic management, the ultimate responsibility for prescribing antibiotics remains of the individual physician.The working process employed in hospitals will usually not be applicable in NHs. Therefore, it is essential to identify a working process that fits within the NH setting. Based on the project we carried out, we recommend a periodic retrospective review of antibiotic prescriptions for discussion in the A-team. Ideally, in an onsite meeting prior to regularly scheduled plenary meetings . This approach enables A-team members to gain insight into the prescribing behaviour of the preceding months and discuss deviations or issues identified during the plenary meeting. This approach aims to achieve a learning effect for the prescription of antibiotics in the future for all residents. As a consequence, sustainable improvement of the overall quality of antibiotic treatments can be achieved.To evaluate the activities of the A-team, the following questions could be posed to fellow physicians: (a) How feasible do you consider the treatment protocols to be? (b) If it comes to UTIs, do you think that the nurses adhere to the policy that dipstick tests may only be used after consultation with the physician? (c) What aspects of the A-team’s work process are you satisfied with? (d) Are there any bottlenecks or areas for improvement in the work process of the A-team? (e) Do you agree with the policy regarding culturing? (f) Did you change your prescribing behaviour of antibiotics?To optimize antibiotic prescriptions in NHs, it is recommended to focus on the most common infections, namely, UTIs, lower respiratory tract infections (LRTIs), and skin- and soft-tissue infections (SSTIs). Selection criteria that could be used to identify prescriptions for discussion in the A-team include: (a) prescriptions lacking an indication in the prescription system; (b) prescriptions lacking a (preliminary) stop date in the prescription system; (c) prescriptions with a duration exceeding 7 days; (d) prescriptions for intramuscular or intravenous antibiotics (if applicable); (e) prescriptions for antibiotics other than the first choice based on the applied treatment protocols; (f) prescriptions for combinations of substances, such as amoxicillin + fluoroquinolone; (g) prescriptions for antibiotics regulated for the treatment of particularly resistant microorganisms; and (h) on request of the prescriber.To determine the time investment required for A-team activities, it is recommended to analyse the volume of prescriptions over a period of one to two months based on the predetermined selection criteria. Priority may be given to one or more of the predetermined selection criteria depending on the results of the analysis. In the prioritization, factors to consider could include (but are not limited to) the severity and frequency of deviations from the treatment protocols, as well as selection criteria where improvement can be achieved quickly and easily.We advise to oblige physicians to note the indication for an antibiotic in the prescription system. Prescription systems always offer a free text field that can be used, but often it is possible to add a required field for this information. Adding the indication makes it easier to analyse prescription data in relation to infection types and treatment protocols and saves time for the A-team. In addition, complete and correct registration of kidney function, contraindications, over-the-counter (OTC) medication, intolerances, etc. is essential for pharmacists to intervene when necessary.To ensure optimal functioning of the A-team, it is recommended to define the tasks of each team member. In addition to the A-team’s responsibility for keeping the treatment protocols up-to-date, the following elaboration provides an example of the tasks assigned to each A-team member in monitoring compliance with treatment protocols. The pharmacist generates summaries of antibiotic prescriptions, including the name of the antibiotic, dosage, and duration, based on predetermined criteria. They also review the prescription for potential side effects, toxicity and interactions with other medications used by the resident. The elderly care physician records relevant data from the resident’s medical record on a registration form see Fig.  and requ*Partly based on the scoring system for the appropriateness of antimicrobial therapy from Willemsen et al. [and adapted to the nursing home setting.n et al.  and adapA summary of the recommendations and their elaboration is included in Table In this practice guide, we present a feasible approach for NHs to implement an AMS program. This approach is rooted in the ‘Practical Guide Antimicrobial Stewardship in the Netherlands’ , which iThis approach can be adapted to local or regional collaborations between NHs, pharmacies, and clinical microbiologists. With the described working process of the A-team, we aim to achieve a learning effect for future antibiotic prescriptions for all residents, thereby enhancing the overall quality of the prescriptions. Moreover, the presence of a peer-review system in which physicians review their colleagues’ prescribing behaviour is expected to encourage greater attention to prescribing practices.The hospital practice guide  publisheIn recent years, several systematic reviews have collectively indicated that the implementation of an AMS program has the potential to optimize antimicrobial use in LTCFs –24. The Another crucial aspect to be noted is that in the USA, it became mandatory by law to integrate AMS into infection control programs in NHs in 2016. A survey conducted in NHs showed that the implementation of all seven core elements increased from 43% to 2016  to 71% iIn general, it is crucial to facilitate NHs in implementing an AMS program. NHs should have the flexibility to choose an approach that aligns with their organizational structure. Our current practice guide offers practical tools for establishing an AMS program, which can be considered separate parts of a toolbox. The local context determines the most effective way to utilize the A-team and implement the AMS program’s tools. The involved physician should play a significant role in creating a sense of urgency, prioritizing program elements, and proposing a step-by-step approach. In the Netherlands, the Dutch Association of Elderly Care Physicians has endorsed the role of elderly care physicians in infection control and antibiotic resistance in its general guideline .Given the lessons learned from our project, we recommend retrospectively reviewing antibiotic prescriptions by the A-team until EMR, pharmacy, and laboratory systems are appropriately configured to enable automatic feedback upon an antibiotic prescription at the individual level of residents. Subsequently, the results of these reviews should be periodically discussed during regular meetings, such as PTAMs. This approach has two limitations. First, this approach precludes the possibility of individual client adjustments. Second, our focus is limited to residents who receive antibiotics, whereas those who do not receive antibiotics, even when it may be indicated, are excluded. Therefore, we recommend conducting repeated prevalence studies on antibiotic use among all residents.In conclusion, the development of tailored AMS programs that are feasible in NHs can be facilitated by collaborative efforts between physicians, pharmacists, clinical microbiologists and infection control practitioners, preferably on a regional level.


Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING  aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice. Antibiotics are essential and life-saving medicines. However, improper use is pervasive. Ensuring appropriate antibiotic prescribing is a fundamental aspect of good clinical practice . Since SThere are also substantial disparities in antibiotic usage worldwide. Whereas some regions face the challenge of excessive antibiotic use, other areas suffer from limited access to essential antibiotics . This coEffective antibiotic treatment is an essential component of universal healthcare. There is a global collective responsibility to use antibiotics appropriately to maintain their effectiveness. Pharmaceutical companies have few incentives to develop new antibiotics due to numerous scientific, regulatory, and financial barriers –8. Thus,Antibiotics are used commonly in acute care hospitals for the treatment of both community- and hospital-acquired infections (HAIs), as well as for surgical prophylaxis . HoweverClostridioides difficile infection: [CDI]) and the selection and transmission of antimicrobial-resistant bacteria in individual patients within and across hospitals, countries, and globally [Optimizing inpatient antibiotic prescribing results in improved treatment effectiveness and patient safety, minimizes the risk of antibiotic-associated infections .We present 10 core principles for the appropriate use of antibiotics, which clinicians should always follow in their clinical practice   settings can support responsible and effective antibiotic use, mitigate the risks of adverse effects and AMR, and promote better patient outcomes in their clinical practices. To enhance awareness and promote best practices, we developed impactful iconography that conveys salient messaging, facilitates implementation, and enhances the retention and application of recommended principles and practices.AMR occurs as bacteria, viruses, fungi, and parasites evolve antimicrobial defense mechanisms that reduce treatment efficacy and increase the risk of treatment failure, disease progression, severe illness, or death. However, misuse and overuse of antimicrobial agents, combined with ineffective infection prevention and control (IPC) practices, are recognized as major drivers of the increasing prevalence of AMR  Fig. 3)3).Fig. 3Although antibiotic-resistant infections are a recognized public health threat, and this call to action addresses the appropriate use of antibacterial agents, less is known about the burden of AMR fungal infections . Fungal Candida auris has emerged worldwide as a multidrug-resistant (MDR) pathogen [C. auris is spreading at an alarming rate [C. auris have increased to the point of higher prevalence than the common fungal pathogen, C. albicans, at some centers [Candida auris is uniquely challenging due to five factors: high transmissibility leading to widespread outbreaks in numerous hospitals worldwide [C. auris by microbiology laboratories [C. auris is associated with biofilm formation and production of proteinases and phospholipases [Recently, pathogen –19 whosepathogen . Data puing rate  since iting rate  as an ining rate . Infecti centers . Candidaorldwide , 26; a borldwide ; environorldwide , 29; difratories , 30–32. olipases , 33, in Bacteria may be intrinsically resistant to one or more classes of antibiotics or may acquire such resistance. Bacteria have developed different resistance mechanisms to avoid antibiotic action Fig. . In addi“Heteroresistance” describes the presence of subpopulations of bacterial cells with higher levels of antibiotic resistance than those of the rest of the population in the same culture . Recent Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa, and Enterobacter spp. [Escherichia coli, Mycobacterium tuberculosis and Neisseria gonorrhoeae are currently among the most prevalent bacterial pathogens affected by AMR issues.Infections caused by AMR bacteria pose a global challenge . In 2008ter spp. . The lisIn 2012, the European Centre for Disease Prevention and Control (ECDC) and the CDC developed standardized nomenclature to describe acquired resistance profiles in bacteria . MDR wasAMR is a complex and multifaceted issue that involves not only humans, but also animals and the environment , 43. On In 2015, the WHO published the Global Action Plan on Antimicrobial Resistance . Its fivAcientobacter spp. Langford et al. reported that more than 60% of patients with COVID-19 who had a bacterial infection harbored a highly resistant organism [There is increasing evidence that the pandemic accelerated the emergence and spread of AMR at least in hospital settings  particulorganism . Howeverorganism , 56.E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa) were found to be responsible for 929,000 deaths due to AMR and 3.57 million deaths total. Notably, methicillin-resistant S. aureus (MRSA) alone caused more than 100,000 deaths in 2019. AMR bacterial infections were associated with the highest infection-related mortality rates in sub-Saharan Africa, with 99 deaths/100,000 people. By comparison, in high-income countries, AMR was associated with 56 deaths/100,000 individuals. However, Murray et al. may have underestimated the true burden of AMR [Alarming levels of AMR have been reported in all countries, regardless of their average income level . The 201n of AMR . Modern n of AMR .The true burden of AMR in low- and middle-income countries (LMICs) would remain unknown unless surveillance is resourced adequately . In partThe COVID-19 pandemic has demonstrated that morbidity and mortality from infectious diseases disproportionately impact upon certain populations . The meaAn important report from India (the ‘Chennai Declaration’) was published in November 2012, representing a major national step forward as a landmark commitment to antibiotic stewardship, with international importance and global implications . Althougin the high AMR-impact scenario, an additional 24 million people could be pushed into extreme poverty by 2030" [Recognizing the gravity of AMR, the United Kingdom commissioned in 2014 a comprehensive analysis of this global problem . The stuby 2030" . Althougby 2030"  will be urgent public health and socio-economic problem" that may have global effects but could have a greater impact on LMICs. Acknowledging AMR as a shared responsibility, they committed together to "taking further urgent and tangible action" to address the issue. Among the actions, they pledged to establish new or improved national integrated surveillance systems on AMR and antibiotic use in human beings, animal husbandry, farming, and environmental sectors; promotion of appropriate antimicrobial use through stewardship; strengthening implementation of IPC programs across the One Health spectrum; and strengthening the research and development pipeline for new antibiotics. This approach aims to achieve optimal health outcomes for people, animals, and the environment, while considering the diverse socioeconomic, political, and cultural contexts affecting AMR [In 2022, the Group of Seven  issued the G7 Health Ministers’ Declaration . Their cting AMR , includiting AMR . As effeting AMR . Preservting AMR , 71.On 13 June 2023, the European Council adopted a resolution calling for stronger EU action to combat AMR in human and animal health and the environment, employing a 'One Health' approach to AMR. The resolution encourages the prudent use of antimicrobial agents in human and animal health through a series of voluntary measures, with the aim of reducing AMR .Antibiotic prophylaxis refers to the antibiotic administration to patients without signs of infection, in order to prevent its occurrence. Empiric antibiotic therapy is prescribed to treat known or suspected infections based on the patient's symptoms and likely causative pathogens before definitive diagnostic test results, including antibiotic susceptibility testing, are available. Targeted antibiotic therapy is initiated based on microbial identification and susceptibility test results to identify the specific pathogen and ensure that the most effective , least toxic, and narrowest spectrum antibiotic is used as therapy. Optimal targeted therapy requires early identification and characterization of bacteria. However, despite advancements in rapid microbial diagnostics, the turnaround time for microbiologic testing and reporting can still take up to 72 h, if it is available at all. As a result, clinicians often initiate empiric antibiotic therapies that can have negative consequences for patients' health and exacerbate the risk of AMR [Healthcare workers (HCWs) play a crucial role in combatting AMR . Unfortuk of AMR .Although antibiotic decision-making is reported to be driven by different determinants in medical versus surgical settings , hospitadiagnostic stewardship); emphasizing the importance of prescribing antibiotics only when needed; to the right patient and clinical situation, at the right time, in the right dose and interval, and for the correct duration [All clinicians must strive for improvement by incorporating antibiotic stewardship principles into daily practice . Antimicduration –84. ASPsduration , 86. Diaduration , encouraduration , and impAlthough 15 years have passed since the CDC, the Society for Healthcare Epidemiology of America (SHEA), and the Infectious Diseases Society of America (IDSA) published joint guidelines for the development of institutional ASPs, best practices for ASPs are still being defined and are likely to vary based on local practice patterns, policy, and available resources . The preThus, we present the following 10 principles for the appropriate use of antibiotics. These principles should be adhered to by all HCWs in their clinical practices, and they should be considered as core components of activity within ASPs.It is crucial for all HCWs to adhere to evidence-based measures of IPC to prevent the occurrence of HAIs. Effective IPC education and training significantly reduce HAIs –94, the Patients with HAIs require additional diagnostic and therapeutic procedures, have prolonged hospital stays, incur additional costs, and may have high morbidity and mortality. Moreover, many HAIs are caused by MDR bacteria , 97. In Five Moments for Hand Hygiene were promulgated by WHO to encourage HCW adherence to hand hygiene recommendations and minimize the risk of infection and transmission [Many HAIs are preventable. A reduction in HAI rates of 35–55% has been documented by implementing multimodal prevention and developing a safety-oriented approach, regardless of the countries’ income levels . Despitesmission  Fig. 8)Five MomeAlthough hand hygiene is accepted universally as a cost-effective IPC measure, compliance remains unacceptably low. In a systematic review , reporteSSIs remain the most common HAIs among surgical patients. They represent a major clinical problem in terms of morbidity, mortality, length of hospital stay, and overall direct and indirect costs worldwide. It is obviously important to improve patient safety by acting before, during, and after surgery to reduce the occurrence of SSIs –109.In 2016, WHO published evidence-based guidelines on the core components of effective IPC programs, to be implemented both at the national and hospital levels , 111. IPResults of a WHO global survey designed to assess implementation of these programs in healthcare facilities worldwide have been published. This survey provides an important overview of IPC program implementation in 4440 healthcare facilities (81 countries) across all six WHO regions and income levels. The findings identify strengths, gaps in IPC implementation, and key opportunities for improvement to inform ongoing global IPC improvement efforts, particularly in LMICs, which showed significantly lower IPC implementation .With the common goal of reducing AMR, IPC programs and ASPs should be partners in reducing HAIs. Support from institutional leadership is crucial for the success of each program and both together, including an effective microbiology laboratory  to enable rapid diagnosis, effective communication tools, and appropriate use of technology, including electronic health records. IPC and ASP programs are based on similar models of interdisciplinary work and activities such as education, monitoring, and feedback. Integrating these interventions may reduce redundancy and align forces for maximal influence on HCWs. ASPs, when implemented in concert with IPC interventions in hospitals, particularly hand hygiene, are significantly more effective in reducing the development and spread of MDR bacteria than ASPs alone .Enterobacterales (CRE), A. baumannii (CRAB), and P. aeruginosa (CRPA) are among the most difficult-to-treat bacteria due to a high prevalence of AMR. In 2017, the WHO published guidelines for the prevention and control of these bacteria in acute healthcare facilities [Containing the spread of antibiotic-resistant bacteria is challenging because of their propensity for human-to-human transmission . Carbapecilities . The supcilities . The mosP. aeruginosa [Haemophilus influenzae serotype B (HiB), influenza, and pneumococcal conjugate vaccines are examples demonstrating the effectiveness of vaccines in reducing antibiotic use and reducing AMR [S. pneumoniae (which is increasingly resistant to penicillin), HiB, and Neisseria meningitidis following splenectomy is effective in preventing overwhelming post-splenectomy infection that is usually caused by encapsulated organisms [Vaccination deserves mention as one of the most impactful and cost-effective prevention measures. Vaccines are mostly used prophylactically, including post-exposure prophylaxis, to decrease the number of infectious disease cases, and thus antibiotic use and the propagation of AMR. Vaccines are also being developed against resistant bacterial pathogens that cause a substantial disease burden  such as ruginosa , 121. Varuginosa . Haemophcing AMR –124. Sperganisms . Moreoverganisms . New vacrganisms .Clinicians prescribing antibiotics are faced with conflicting priorities. On the one hand, they must provide patients with the best possible treatment. On the other hand, they must preserve the efficacy of antibiotics, minimize opportunistic infections such as CDI, reduce the selection of resistant pathogens in individual patients, and prevent the continued global increase of AMR. These conflicts should be evaluated and balanced before prescribing antibiotics  Fig. 1010.Fig. 1colonization resistance. The indigenous bacteria of the microbiome provide an important host defense mechanism by inhibiting colonization by potentially pathogenic bacteria. However, in certain circumstances, a patient’s microbiota can be compromised, no longer protecting against colonization by opportunists.The intestinal microbiota has an important role in human health and can protect the patient against colonizing enteric bacteria , a phenoAntibiotics exert selection pressure on the human microbiome, predisposing to AMR. Antibiotic use can have unintended consequences on commensal intestinal microbiota. Whereas susceptible bacteria are destroyed, the resultant ecologic vacuum promotes the overgrowth of pathogenic bacteria that may already be antibiotic-resistant , 130. MoMany studies have evaluated the long‐term effect on gut microbiota following a course of antibiotics –137. To Candida difficile is rarely present in the gut of healthy adults (~ 3%) [C. difficile to proliferate 'and produce toxins [C. difficile [The commensal intestinal microbiota plays a pivotal role in protection against CDI . Candidas (~ 3%) . The cors (~ 3%) . Disrupte toxins . Animal ifficile . These aifficile , dependiifficile . Althougifficile .Surgical antibiotic prophylaxis (SAP) is a crucial component of perioperative infection prevention , 149, paAntibiotic therapy should be prescribed after a bacterial infection has been confirmed. Colonization by potential pathogens without associated signs of infection occurs frequently in certain patients . Appropriate evaluation requires obtaining a culture from these sites only when indicated, without contamination by the collection protocol itself  for that specific patient Fig. . The antThe most common antibiotics used for SAP have been first- and second-generation cephalosporins  , 149. CeThe administration is determined according to the antibiotic half-life. For most frequently used antibiotics, such as cefazolin or cefoxitin, intravenous administration 30–60 min before incision ensures effective tissue concentrations at the time of incision . RedosinRegarding empiric therapy before causative bacteria and susceptibilities are known, the optimal antibiotic choice should be based on the infection source, expected pathogens, the patient’s clinical condition, local epidemiology, and individual patient risk factors for MDR bacteria. Knowledge of patients’ risk factors for MDR bacteria is essential . TreatmeIn 2017, the WHO Expert Committee on Selection and Use of Essential Medicines established the AWaRe  classification of antibiotics to aid antibiotic stewardship efforts globally at all levels of care. This classification system groups antibiotics into the aforementioned three categories, based on treatment of common bacterial infections and their impact on AMR, focusing on the need for appropriate use. The AWaRe classification  was updaThe “Access” category refers to the antibiotic of choice for each of the 25 most common infections. These antibiotics should be available at all times and places and should be acceptable and affordable. The “Watch” category includes most of the “highest-priority critically important antibiotics”, which are recommended only for specific indications. The “Reserve” category includes antibiotics that should only be used as a last resort  and only when all other antibiotics have failed. WHO recommends reducing the use of antibiotics in the “Watch” and in the “Reserve” groups, and increasing the access and use of antibiotics in the “Access” group, expecting 60% of all antibiotic use in hospitals should come from this group . As a prAssessing the severity of infection is a crucial step in evaluating patients for antimicrobial therapy. Early implementation of appropriate empiric antibiotic therapy has a significant favorable impact on outcomes of septic shock, independent of infection site . WhereasDelayed antibiotic prescription is especially useful to help reduce antibiotic use, especially for community-acquired respiratory tract infections , many ofBy contrast, for patients (both adults and children) with sepsis-related shock and organ dysfunction, delay of appropriate empiric antibiotic therapy can be deleterious , 180; eaThe involvement of MDR pathogens in HAIs is a risk factor for inappropriate empiric therapy and, as such, for adverse outcomes. Prior knowledge of colonization caused by MDR bacteria via surveillance cultures improves the likelihood of appropriate initial antibiotic therapy for subsequent HAIs in critically ill patients with blood stream infections or VAP , 185. AdAdministering antibiotics in adequate doses should be based on the intrinsic pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of each antibiotic class and the specific agent, and on the specific pathophysiologic characteristics of the patient. Antibiotic PD refers to the relationship between the concentration of the drug and its ability to inhibit bacterial growth. The minimal inhibitory concentration (MIC) is the primary in vitro parameter used to assess the effectiveness of an antibiotic against its target bacteria. In order to obtain a therapeutic effect, the concentration at the site of infection should exceed the MIC against the target bacteria for at least 40% of the dosing interval, and ideally longer (if killing is time-dependent) or by > tenfold (if killing is concentration-dependent) . AntibioClinical- and antibiotic-related factors can contribute to a differential distribution of antibiotics at the target site . KnowledCritically ill patients are at high risk of infections, risking life-threatening sepsis and multiple organ dysfunction syndrome. The pathophysiology of sepsis and septic shock can have a major effect on PK parameters. Knowledge of pathophysiologic effects on PK/PD is essential for optimizing antibiotic treatment in critically ill patients with sepsis or septic shock , 197. HeThe dosing frequency of an antibiotic is determined by the concepts of time-dependent vs. concentration-dependent activity. For example, beta-lactam antibiotics exhibit time-dependent activity, whereby optimal bactericidal activity is achieved when antibiotic concentrations are maintained above the MIC over prolonged periods of time. For this reason, the serum concentration of the antibiotics should exceed the MIC for at least 40%  of the dosing interval . Higher VD) of hydrophilic agents  in septic shock patients may be increased due to increased microvascular endothelial permeability, expanding the extracellular fluid compartment. Loading doses of beta-lactams, aminoglycosides  or glycopeptides are recommended to maximize the therapeutic effect [In patients with septic shock, administering a first “loading” dose is probably as fundamental as the timing of administration, depending on the antimicrobial agent . The volc effect .D, especially for lipophilic antibiotics, which can lead to lower-than-expected plasma antibiotic concentrations. Augmented renal clearance is frequent. In addition, fatty infiltration of the liver may impair hepatic function. In general, regardless of body mass, the dosing of lipophilic antibiotics should be based on total body weight, or adjusted body weight for hydrophilic antibiotics. Individualized dosing, supported by laboratory testing, is essential owing to patient heterogeneity and clinical fluctuation.Once initiated, the antibiotic regimen should be reassessed at least daily, given that fluctuating organ function, common in critically ill patients, may substantially affect antibiotic exposure. For example, lower doses of antibiotics excreted in urine should be administered in the presence of impaired renal function, whereas higher than standard doses should be administered in patients with augmented renal clearance  . AntibioRecently, a revised consensus guideline and review on therapeutic monitoring of vancomycin for serious MRSA infections was published by the American Society of Health-System Pharmacists, the IDSA, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. This consensus revision evaluates the current scientific data and controversies associated with vancomycin dosing and serum concentration monitoring for serious MRSA infections  and provides new recommendations based on recent available evidence .Oral antibiotic administration has been shown to decrease the cost and length of hospitalization , 203. Thde-escalation. Antibiotic therapy reassessment based on microbiologic culture and susceptibility testing supports ASP and is associated with improved outcomes in severe infections [Microbiologic tests play a crucial role in selecting targeted antibiotic therapy. This testing allows clinicians to tailor the spectrum of the antibiotic, broadening if the initial choice was too narrow, but more commonly narrowing an empiric regimen spectrum that was too broad, known as fections .The de-escalation tactic involves transitioning from a broad-spectrum empiric antibiotic regimen to a narrower-spectrum regimen, or reducing the number of antibiotics used in combination therapy , or to mThe MIC, the lowest antimicrobial agent concentration that inhibits microbial growth, can be determined by different methods, such as broth or agar dilution, and disk or gradient diffusion. The MIC value, expressed as mcg/mL, is often translated by clinical microbiology laboratories as “susceptible,” “intermediate,” or “resistant” according to defined “breakpoints” established by the Clinical and Laboratory Standards Institute  or “susceptible,” “susceptible, increased exposure,” or “resistant” according to the criteria of the European Committee on Antimicrobial Susceptibility Testing  .Rapid diagnostics may contribute in furtherance by limiting unnecessary initiation of broad-spectrum therapy, thus decreasing the need for subsequent de-escalation , 212. MoThe greatest advantage of genotyping is undoubtedly speed, with turnaround times of 1–4 h. Employment of comparative genomics, probes, microarrays, nucleic acid amplification techniques, and deoxyribonucleic acid sequencing should allow for the detection of multiple resistance genes or variants simultaneously. However, a logistic challenge in practice is that when new antibiotics are marketed, there may be a lag before methods to measure in vitro susceptibility are validated for clinical use, which may limit the initial clinical use of new agents .Rapid diagnostic testing for possible pathogens is considered indispensable for ASPs. Coupled with prompt, appropriate therapy, antibiotic use is decreased, mortality is reduced, hospital stays are shortened, and cost is lowered –218. TheThe duration of antibiotic therapy prescribed in daily practice is often longer than recommended by guidelines . WHO 22 recommen. examined the effect of continued SAP on the rate of SSI [de Jonge et ale of SSI . Eighty-e of SSI , increas. showed that ASP advice to stop antibiotics or reduce their duration was accepted less often than advice to start or increase antibiotic exposure [A study of 34 urban and rural South African hospitals demonstrated that implementation of process improvement initiatives and principles targeted to institutional needs, utilizing pharmacists, effectively improved SAP guideline compliance and sustainable patient outcomes . Effortsexposure .Shortening the duration of antibiotic therapy is a crucial tactic for reducing unnecessary inpatient antibiotic use, where antibiotic pressure is intense . AlthougAntibiotic therapy of up to 21 days for VAP and hospital-acquired pneumonia (HAP) was used historically until several prospective studies demonstrated the effectiveness of shorter (7–8 days) therapy with no differences in mortality, intensive care unit (ICU) stay, mechanical ventilation-free days or organ failure-free days , 231. ThBacteremia caused by Enterobacterales has been treated traditionally with 2 weeks of antibiotics. Recent RCTs and meta-analyses investigating shorter (7–8 days) versus longer antibiotic courses (14–15 days) in patients with gram-negative bacteremia (mostly of urinary tract origin) demonstrate non-inferiority –239. RegGenerally, in critically ill patients, decisions about antibiotic therapy duration should be individualized, taking into account patient parameters such as severity of illness, the site and type of infection, whether source control has been achieved, whether PK has been optimized, and clinical response . ProcalcSource control aims to eliminate the source of infection, reduce the bacterial inoculum, and correct anatomic derangements to restore physiologic homeostasis. Additionally, it involves draining abscesses or infected fluid collections, debriding necrotic tissue, or removing contaminated medical devices, all being situations where antibiotics alone have limited efficacy.Source control is crucial in the management of surgical infections, particularly intra-abdominal and soft tissue infections. Adequate source control achieved by the index operation allows for a shorter course of antibiotic therapy, thereby improving patients’ outcomes, including lower risk of organ dysfunction , 246. InIn some circumstances, organizational determinants may influence the excessive use of antibiotics. For example, acute cholecystitis should be managed by early cholecystectomy . NeverthPseudomonas spp., S. aureus or fungal) constitutes source control. There is little reason to delay source control, even for a few hours, in patients with sepsis [The urgency  for source control is determined by the affected organ(s) and the rapidity at which underlying physiological stability deteriorates. Prompt source control may also be important for indolent infections . A challenging management problem is central venous catheters associated with catheter-related blood stream infections. In these cases, removal of the catheter  , coordinK. pneumoniae and vancomycin resistance in E. faecium increased during 2016–2020. Moreover, high rates of resistance to third-generation cephalosporins and high rates of carbapenem-resistant Acinetobacter spp. and P. aeruginosa in several European Region countries were identified.A recent joint publication by ECDC and the WHO Regional Office for Europe reported AMR rates in Europe, using data from invasive bacterial isolates . CarbapeAcinetobacter spp. and K. pneumoniae, resistance to third-generation cephalosporins in Enterobacterales, MDR and XDR tuberculosis, and MRSA will require ongoing close monitoring.In 2015, WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS), a collaborative effort to standardize AMR surveillance worldwide. Since its launch, GLASS has expanded its coverage and as of 2021, 109 countries and territories worldwide have contributed data to GLASS . High raInappropriate antibiotic use is a main driver of AMR . Data onOne of the goals of the WHO Global Action Plan on Antimicrobial Resistance  is to imThe ultimate goal of any stewardship program should be to stimulate a behavioral change in prescribing practices . It is iA cross-sectional study of perceptions and practices of physicians and pharmacists regarding antibiotic misuse at primary care centers in the Middle East reported a number of misconceptions and inappropriate practices relating to antibiotic use in Qatar by patients and healthcare providers .Interestingly, the study found that about a third (29.2%) of physicians felt they were often under pressure by patients to prescribe antibiotics. Physicians who are overworked, underinformed, or pressured tend to overprescribe antibiotics and thereby contribute to the spread of AMR. Patients often expect to be prescribed antibiotics, and this pressure can be difficult for physicians to ignore. However, physicians' communication with patients influences their satisfaction more than the actual receipt of antibiotics, especially when patients are asked by their physician to contact them if symptoms do not improve . TherefoThe promotion of ASPs is pivotal to ensure more standardized and responsible antibiotic use within a healthcare facility . ASPs prPromoting ASPs across clinical specialties is crucial to ensuring standardized, rational antibiotic use within a facility as well as a healthcare system . CollaboSurgeons are responsible for many of the processes that impact the risk for SSIs and play a key role in their prevention. Surgeons are also at the forefront in managing patients with infections, often providing prompt source control and appropriate antibiotic therapy, and are directly responsible for their outcomes. In this context, the direct involvement of surgeons is of utmost importance .Infections are the main factor contributing to ICU mortality. Intensivists have a crucial role in preventing and treating AMR in critically ill patients. Intensivists prescribe antimicrobial agents to challenging patients and thus are at the forefront of successful ASPs . EmergenSuccessful ASPs can reduce the incidence of infections and colonization with MDR bacteria, including CDI among inpatients . The bes. demonstrated the utility of computerized decision support of antibiotic usage and even in reduction of mortality in hospital settings [Due to the challenges posed by the development of new antibiotics, the emergence of MDR bacteria is likely to outpace the introduction of new drugs to combat them. Thus, it may be important to focus on alternative non-antibiotic measures to address AMR . Health settings .Whereas clinical research should work toward developing new management techniques and therapies to address AMR, physicians should continue to preserve the use of antibiotics as much as possible. Additionally, public health campaigns aimed at promoting awareness about the responsible use of antibiotics and IPC measures can also be crucial in reducing the spread of MDR bacteria.This document confirms the mission of the Global Alliance for Infections in Surgery, promoting standards of care in managing surgical infections through a cohesive and multidisciplinary approach. The axiom “if you want to go fast, go alone; if you want to go far, go together” reminds us that we need global solidarity not only to reduce health inequalities, but also to be united against all global health challenges, including AMR Fig. .Fig. 14SAppropriate use of antibiotics should be integral to good clinical practice and standards of care. Inappropriate antibiotic use as well as poor IPC practices are contributing to the development and spread of AMR. Antibiotics should be treated as a global public good on the verge of scarcity; there is a global collective responsibility to preserve them in order to avoid countless future victims of MDR infections. Infections, especially those with MDR bacteria, compromise the success of all medical practitioners, including surgeons. A technically proficient surgery will be unsuccessful if the patient succumbs to a HAI that cannot be treated. Through collaborative initiatives and a united front, a future of effective antimicrobial therapy can be envisioned for generations to come.


Inappropriate antibiotic prescribing upon hospital discharge has been identified as a significant problem. Despite high rates of antibiotic prescription errors, there is no widely accepted antimicrobial stewardship initiative to prevent such errors.The primary objective of this study was to determine the impact of hospital-based clinical pharmacist discharge prescription review on the appropriateness of antibiotic prescriptions.This was an observational study comparing the appropriateness of hospital discharge antibiotic prescriptions between two similar internal medicine services. One cohort of patients was admitted to medicine services where rounding clinical pharmacists performed routine antibiotic discharge assessment, and the comparator cohort was admitted to hospitalist services without routine pharmacist discharge antibiotic review.p = 0.025) and fewer cases of acute bacterial skin & skin structure infections (p = 0.001) in the hospitalist cohort. Antibiotic appropriateness was considerably greater in the medicine (pharmacist) group versus hospitalist group . The difference in appropriateness was mainly driven by pneumonia and urinary tract infection prescriptions.Our study included 150 cases per cohort. Baseline characteristics were similar between groups, except for increased age (Appropriateness of antibiotic prescriptions significantly improved in the setting of pharmacist discharge review. This initiative highlights the important role of clinical pharmacists in outpatient antimicrobial stewardship. Clinical pharmacists can perform meaningful discharge antibiotics assessment to ensure concordance with evidence-based medicine.The similarities of the two internal medicine cohort services allow for meaningful comparison of appropriate antibiotic prescribing.This study showed that non-infectious diseases clinical pharmacists can have a significant impact on discharge antibiotic prescribing.transitions of care, such as upon hospital discharge, many institutions lack effective monitoring of such practices . This difference was driven by increased appropriateness of antibiotic prescriptions for the treatment of UTI (p = 0.0019) and pneumonia (p = 0.0001) in the medicine cohort versus the hospitalist Cohort (Table p = 0.0017).Antibiotic appropriateness was significantly higher in the medicine (pharmacist-review) cohort versus the hospitalist cohort, [125/150 (83.3%) versus 81/150 (54.0%), respectively  cohort were similar to the findings of previous studies, in terms of rate of antibiotic prescription inappropriateness and the high rates of prescription errors due to duration of therapy –4. A recThis study has several limitations. First, this was a retrospective, single-center study. Therefore, we were unable to confirm that every antibiotic discharge prescription in the medicine cohort was reviewed by a pharmacist, even though this is a routine expectation. Thus, the results of the study may have been impacted by other variables, such as the differences in interdisciplinary rounding between the two cohorts. Second, this study identified patients for inclusion based on antibiotic discharge prescriptions. Therefore, this study did not include patients who were mistakenly discharged without antibiotic prescriptions. Additionally, there was a risk for bias, as the secondary adjudicating ID pharmacists were unblinded to the patient cohort when assessing appropriateness. Lastly, this study utilized a more recent study to support evidence-based guidance on Gram-negative bacteremia . While tAppropriateness of antibiotic prescriptions significantly improved in the setting of pharmacist discharge prescription review. This initiative emphasizes the importance of improved transitions of care and outpatient antimicrobial stewardship. Further prospective studies are needed to determine the full impact of pharmacist discharge prescription review on antibiotic prescriptions.


Mounting evidence in neoadjuvant immunotherapy has led to improvement in pathological tumour regression in patients with resectable oesophagal cancer. The latest results of the phase 1b trial (NATION‐1907) in the issue of 2Distant and locoregional relapses of locally advanced ESCC remain at 48% after standard‐of‐care neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) followed by surgery.p = .021) and 67% with nCT ; 2) neoadjuvant anti‐PD‐L1 blockade alone have non‐inferior OS compared with neoadjuvant chemoimmunotherapy followed surgery in some small phase II trials; Analysis of propensity score adjustment in patient baseline characteristics showed that the 2‐year OS was 93% in neoadjuvant anti‐PD‐L1 therapy, compared with 74%–87% with neoadjuvant anti‐PD‐1 blockade plus chemotherapy (p = .066); 3) neoadjuvant anti‐PD‐L1 blockade have significantly favorable safety profiles compared with standard‐of‐care or chemoimmunotherapy, which are friendly for patients over 70 years old or intolerant of chemotherapy or chemoradiotherapy. As a caveat, these conclusions are based on post‐doc comparative analysis after propensity score matching and should be further validated in randomized, controlled phase III trials.Preliminary evidence highlight three clinical opinions on the clinical efficacy and safety of neoadjuvant therapy in patients with locally advanced resectable ESCC, that is, 1) neoadjuvant anti‐PD‐L1 blockade alone followed surgery have superior OS compared with standard‐of‐care treatments; Post doc analysis demonstrated that the 2‐year OS was 94% in neoadjuvant anti‐PD‐L1 therapy, compared with 69% with nCRT ,p = .066; pCR, 8.0% versus 29.0%, p < .001).Traditionally, patients with pathological complete response (pCR) are expected to have longer OS than non‐pCR patients in resectable ESCCs. However, achievement of non‐pCR does not represent short‐term outcomes. Recent findings of two studies provide evidence challenging the validity of local tumour regression (pCR rate) as a surrogate for OS in the neoadjuvant setting. Although combined therapeutic strategies contribute to substantial improvement of pCR rates, they might not translate into OS benefits. This is based on the notion that there is no statistical difference in OS between nCRT and nCT in patients with stage cT3‐4aN0‐1M0 in the randomized, controlled phase III CMISG‐1701 trial  score’ signature and immune‐enriched tumour microenvironment phenotype to stratify for well responders who would benefit from neoadjuvant adebrelimab blockade, highlighting that anti‐PD‐L1 monotherapy may be sufficient in the immune “inflamed” patients. For patients with high infiltration of fibroblasts at baseline, immunotherapy combined with other drugs to shift the fibrotic tumour microenvironment may be a beneficial therapeutic strategy. PD‐L1 positive (combined positive score ≥10) shows superior clinical survival regardless of single‐agent immunotherapy or combined with other regimens.5Despite a flurry of encouraging discoveries and clinical benefits emerging from neoadjuvant immunotherapy with or without combinations of other agents, coupled with that translational research is still only scratching the surface of possibilities. The NATION‐1907 trial has confirmed a non‐inferior OS and favourable safety profiles of neoadjuvant immunotherapy compared to standard‐of‐care treatments. Whether the synergistic effects of immunotherapy and chemotherapy or chemoradiotherapy can overpower the side effects and bring survival benefits remains to be further investigated. With an elaborate design, impactful correlative studies can be fulfilled in a rather small‐sized clinical trial, which might eventually convey details surrounding the mechanism of response or resistance to immunotherapy.The authors declare no conflict of interest.This work was supported by the Guangdong Provincial Key Laboratory of Human Disease Genomics (2020B1212070028), The Science and Technology Commission of Shanghai Municipality (20ZR1411600), National Natural Science Foundation of China (82241013), Shanghai Hospital Development Center (SHDC2020CR4039).