Surgical site infections (SSIs) remain a significant concern in the field of surgery, contributing to patient morbidity, prolonged hospital stays, and increased healthcare costs. Antibiotic prophylaxis, the administration of antibiotics before surgery, has been a cornerstone in preventing SSIs for decades. This review explores the current state of antibiotic prophylaxis in surgery, offering insights into its effectiveness, challenges, and emerging trends. In this comprehensive analysis, we delve into the historical development of antibiotic prophylaxis, examining its evolution from early practices to modern guidelines. We explore the various classes of antibiotics commonly used, their dosing regimens, and the importance of timing in optimizing prophylactic interventions. Additionally, we investigate the role of patient-specific factors, such as comorbidities and allergies, in tailoring antibiotic prophylaxis to individual needs. While antibiotic prophylaxis has undeniably reduced the incidence of SSIs, concerns about antimicrobial resistance and adverse effects necessitate a reevaluation of current practices. This review presents a critical assessment of the challenges posed by the overuse and misuse of antibiotics in surgery and highlights the urgent need for judicious antibiotic stewardship. Moreover, the future of antibiotic prophylaxis holds promise with the emergence of innovative strategies such as antimicrobial coatings, probiotics, and immunomodulatory agents. We discuss these novel approaches and their potential to enhance SSI prevention while minimizing antibiotic-related risks. In conclusion, antibiotic prophylaxis in surgery has been instrumental in reducing SSIs, but its continued effectiveness requires a multifaceted approach. By addressing current challenges, promoting antibiotic stewardship, and embracing innovative strategies, we can advance the field of SSI prevention and improve patient outcomes in the years to come. This review provides valuable insights and direction for clinicians, researchers, and policymakers as they navigate the evolving landscape of surgical prophylaxis. Surgical site infections (SSIs) represent a significant and preventable complication in the field of surgery, posing substantial risks to patients and placing a substantial economic burden on healthcare systems. An SSI is a nosocomial infection at or near a surgical incision or operative site within 30 days following surgery or within 90 days if prosthetic material is implanted during surgery. SSIs can manifest as superficial infections involving the skin and subcutaneous tissue, deep infections affecting fascial and muscle layers, or organ/space infections involving any body part other than the incision site. These infections are characterized by localized signs and symptoms of inflammation, such as redness, swelling, warmth, and purulent discharge, and are often associated with systemic manifestations, including fever and leukocytosis -4.Firstly, SSIs can lead to substantial patient morbidity, prolong hospital stays, and, in severe cases, result in mortality. Moreover, SSIs may require additional surgical procedures, such as debridement or implant removal, to effectively manage the infection. Secondly, these infections place a considerable financial burden on healthcare systems due to increased hospitalization costs, prolonged antibiotic therapy, and potential legal liabilities. Consequently, mitigating SSIs improves patient outcomes and contributes to cost-effective healthcare delivery ,6. AntibSurgical site infections (SSIs)Types and Classifications of SSIsSuperficial SSIs: These infections are primarily localized to the outermost layers of the surgical site, namely the skin and subcutaneous tissue. They often manifest with visible signs of infection, such as redness, swelling, warmth, and purulent discharge. While superficial SSIs are generally less invasive than their deeper counterparts, they should be considered. If left untreated, they can progress, leading to more severe complications or even the development of deep or organ/space SSIs .Deep SSIs: In contrast to superficial SSIs, deep SSIs extend beyond the superficial layers of the surgical site, reaching the fascial and muscle layers beneath the incision. These infections are characterized by their invasiveness, potentially causing complications such as the formation of abscesses, tissue necrosis, or damage to vital structures. Deep SSIs are associated with a higher degree of morbidity, often requiring prolonged hospitalization, additional surgical procedures, and intensive medical management to address the deep-seated infection and prevent further harm to the patient .Organ/space SSIs: Organ/space SSIs encompass infections affecting any body part other than the incision site. These infections can be particularly challenging to diagnose and manage due to their potential involvement of vital organs or body cavities. Organ/space SSIs may require surgical intervention, such as drainage procedures or reoperation, and extended courses of antibiotic therapy to clear the infection effectively. Given their complexity and potential for severe consequences, these infections demand close monitoring and a multidisciplinary approach to treatment .Epidemiology and Prevalence of SSIsIncidence rates: SSIs are common healthcare-associated infections in surgical patients, with varying rates depending on factors such as the type of surgery, patient health, and adherence to infection prevention protocols. Invasive procedures and prosthetic implants pose higher SSI risks .Risk factors: Patient-specific and procedure-related factors increase SSI susceptibility. Immunosuppression from medical conditions or medications weakens the body's defenses. Conditions such as obesity and diabetes hinder wound healing and promote bacterial growth. Longer surgeries increase infection risk, especially for contaminated or dirty wounds. Foreign bodies such as surgical implants can also increase the risk, necessitating preventive measures .Economic impact: SSIs not only harm patient health but also strain healthcare systems economically. Treatment costs go beyond the hospital stay and include additional surgeries, diagnostic tests, and prolonged antimicrobial therapy. Legal battles can further escalate healthcare costs .Global variation: SSIs' prevalence varies globally due to healthcare resources, sanitation practices, and facility quality. Developing countries with limited resources and poor sanitation may have higher SSI rates. Overcrowded healthcare settings complicate understanding and managing SSIs in these regions .Impact on Patient Outcomes and Healthcare CostsPatient morbidity: SSIs cause significant suffering and reduced quality of life for patients. They affect emotional and psychological well-being, leading to extended healing processes, multiple healthcare facility visits, and continued reliance on healthcare resources .Prolonged hospitalization: SSIs result in longer hospital stays, which increase patient discomfort and strain healthcare resources. This strain can lead to delays in elective surgeries and affect the entire healthcare system .Mortality: While not always the direct cause of death, SSIs can contribute to mortality, especially in vulnerable populations. Complications from SSIs weaken patients and make them less able to handle other health challenges, making prevention crucial, especially in high-risk groups .Healthcare costs: SSIs impose a significant economic burden on healthcare systems. Direct costs include infection treatment expenses, additional surgeries, extended hospital stays, tests, and antimicrobial therapy. Indirect costs involve lost productivity due to extended hospitalization and potential legal issues in severe cases. Effective prevention strategies such as antibiotic prophylaxis are essential to redirect resources to other areas of patient care, research, and development .Historical perspectiveEvolution of Antibiotic Prophylaxis in SurgeryPre-antibiotic era: The pre-antibiotic era was characterized by surgical procedures fraught with a high risk of infection and dire patient consequences. Surgeons face formidable challenges in combating postoperative infections, primarily due to ineffective antimicrobial agents. Without antibiotics, the surgical arena was a battlefield against invisible adversaries, where even routine procedures carried a substantial risk of infection. Patients frequently succumbed to severe complications, and high morbidity and mortality rates marred the outcomes of surgeries. The lack of tools to control bacterial proliferation in surgical wounds cast a shadow over the field of surgery, highlighting the pressing need for a breakthrough .Discovery of antibiotics: The mid-20th century witnessed the groundbreaking discovery of antibiotics, a medical revolution that transformed surgical practice. The advent of penicillin and subsequent antibiotics provided hope for surgeons grappling with the scourge of SSIs. Antibiotics emerged as powerful weapons in the arsenal against infectious complications, ushering in a new era of proactive infection control. For the first time, surgeons had tools to combat bacteria directly, significantly reducing postoperative complications. This newfound ability to administer antibiotics prophylactically before surgical incisions marked a profound turning point, ultimately enhancing patient safety and reshaping the surgery landscape .Early Successes and ChallengesInitial successes: The initial application of antibiotics as prophylactic agents in surgical procedures yielded striking successes. These early triumphs were evident in the substantial reduction of SSIs, which had long plagued surgical practice. Surgeons and patients alike marveled at the tangible benefits as SSIs became less frequent and their associated morbidity and mortality rates plummeted. The introduction of antibiotics instilled newfound hope, transforming surgical interventions into safer and more reliable endeavors .Overuse and resistance: Despite the remarkable achievements, the euphoria surrounding antibiotics precipitated a darker issue. The widespread and indiscriminate administration of antibiotics, sometimes in situations where they confer minimal benefit, sowed the seeds of a formidable adversary: antibiotic resistance. The emergence of antibiotic-resistant strains of bacteria represents an enduring challenge in modern healthcare. The overreliance on these powerful drugs inadvertently fostered the survival of resistant organisms, diminishing the effectiveness of antibiotics over time. This challenge reverberates across various medical contexts, including surgical prophylaxis, reminding us of the importance of judicious antibiotic use .Challenges in selection: The selection of appropriate antibiotics for prophylaxis introduced yet another layer of complexity. Surgeons faced the daunting task of choosing antibiotics with an optimal spectrum of activity capable of targeting likely pathogens encountered during specific surgical procedures. This decision-making process necessitated a delicate balance between efficacy and minimizing the risk of adverse effects. Factors such as patient allergies, potential drug interactions, and evolving bacterial resistance patterns further compounded the challenge of antibiotic selection, underscoring the need for a nuanced and evidence-based approach .Development of Guidelines and ProtocolsEmergence of guidelines: As antibiotic prophylaxis became evident, healthcare organizations and professional societies stepped forward to provide much-needed guidance. These organizations, including the American College of Surgeons (ACS), the Centers for Disease Control and Prevention (CDC), and the World Health Organization (WHO), began issuing comprehensive guidelines. These guidelines were meticulously crafted, drawing upon a wealth of clinical evidence to offer evidence-based recommendations on various aspects of antibiotic prophylaxis .Protocol implementation: The adoption of guidelines by hospitals and surgical teams marked a significant shift in clinical practice. Protocols based on these guidelines became the standard of care for surgical procedures. They stipulated the precise timing of antibiotic administration, emphasizing the importance of giving antibiotics shortly before incision to ensure that therapeutic levels were present when the patient was most vulnerable to infection. Additionally, protocols underscored the discontinuation of antibiotics within 24 hours of surgery, a crucial step in minimizing the risk of antibiotic resistance [Quality improvement initiatives: Recognizing the need for ongoing monitoring and improvement, healthcare institutions established quality improvement programs. These initiatives were designed to systematically track guideline adherence and assess their real-world impact on SSI rates. By collecting and analyzing data, institutions could identify areas of improvement, implement corrective measures, and ensure that best practices are consistently applied throughout their surgical departments .Ongoing updates: The dynamic nature of medicine, including antimicrobial pharmacology and bacterial resistance patterns, necessitated regularly updating guidelines. To remain practical, guidelines needed to evolve in response to emerging scientific evidence and the ever-changing landscape of surgical practice. Regular updates ensure that practitioners stay aligned with the latest knowledge, allowing them to adapt their prophylactic approaches to new challenges and opportunities .Current practicesGuidelines for Antibiotic Prophylaxis in SurgeryProfessional societies: Leading professional organizations, including ACS, CDC, and WHO, are instrumental in providing comprehensive guidelines for antibiotic prophylaxis in surgical settings. These organizations leverage their expertise to synthesize the latest scientific evidence into practical recommendations that healthcare professionals can readily implement .Procedure-specific recommendations: Recognizing that not all surgical procedures carry the same risk of SSIs, these guidelines tailor their recommendations to specific types of surgeries. They consider the nuances of each procedure, such as the surgical site, patient characteristics, and surgical techniques employed. This individualized approach ensures that prophylactic antibiotic choices align closely with the unique infection risks of different surgeries .Selection of antibiotics: The guidelines are meticulous in selecting appropriate antibiotics for prophylaxis. They prioritize antibiotics with the optimal spectrum of activity against the likely pathogens encountered during specific surgical procedures. Furthermore, these guidelines consider local antibiotic resistance patterns, ensuring that the antibiotics chosen remain effective in the face of regional resistance trends. This strategic antibiotic selection enhances the prophylactic effect and contributes to antibiotic stewardship by minimizing unnecessary broad-spectrum use .Timing and Administration of AntibioticsTiming: Administering antibiotics at the right time is fundamental. Antibiotics should be given within a specific timeframe before surgical incision, ideally 30-60 minutes before the procedure commences. This timing is strategically chosen to ensure that therapeutic levels of the antibiotic are present in the patient's tissues precisely when potential bacterial exposure occurs, typically when the surgical incision is made [The rationale behind this precise timing is twofold. First, it allows antibiotics to reach the surgical site and adjacent tissues in concentrations that effectively combat any bacteria introduced during the procedure. Second, it aligns with the principle that antibiotic prophylaxis is most effective when the antibiotic's mechanism of action targets actively dividing bacteria, which are more vulnerable to antimicrobial agents. Administering antibiotics shortly before incision significantly increases the likelihood of eradicating these bacteria .Intraoperative dosing: The timing and duration of antibiotic administration during surgical procedures play a crucial role in infection prevention. While the initial preoperative dose is vital, it is important to consider that many surgical procedures may extend beyond the antibiotic's effective coverage window. In such cases, intraoperative dosing becomes a recommended practice, especially for surgeries lasting longer than 2-4 hours. Intraoperative dosing entails the administration of an additional dose of prophylactic antibiotics during the surgery, and it is employed to address the potential decline in antibiotic concentration over time. This supplementary dose is strategically administered to ensure that therapeutic levels of the antibiotic are maintained in the patient's tissues throughout the entire surgical procedure. Doing so guarantees continued protection against potential bacterial contamination and reduces the risk of SSIs . MoreoveSelection of Appropriate AntibioticsFirst-line agents: At the heart of antibiotic selection lies the preference for first-line agents, such as cefazolin. These antibiotics are favored for many surgical procedures due to their attributes, including a broad spectrum of activity against common pathogens encountered in surgery and a well-established safety profile. First-line antibiotics balance effectiveness and minimize the risk of adverse effects, making them the cornerstone of prophylaxis in various surgical settings. Their use reflects a conscious effort to provide patients with optimal protection against SSIs while ensuring safety .Allergies and sensitivities: The complexity of antibiotic prophylaxis deepens when patients present with allergies or sensitivities to certain antibiotics. In such cases, a critical aspect of antibiotic selection is to assess and document the patient's history of allergies meticulously. Identifying known allergies is imperative to avoid adverse reactions. When patient allergies are identified, healthcare providers must pivot to alternative antibiotics with a similar activity spectrum against likely pathogens. These alternative agents must be chosen judiciously, considering the patient's allergies and sensitivities. The goal remains unaltered: to protect against SSIs without compromising patient safety .Complex cases: Some surgical scenarios deviate from standard procedures, necessitating customized antibiotic regimens. These unique cases include surgeries involving the implantation of prosthetic materials or gastrointestinal procedures. The reason behind considering gastrointestinal surgery challenging in terms of SSI prophylaxis is primarily due to the distinct infection risks associated with these procedures. In such cases, guidelines offer precise recommendations for selecting and administering antibiotics to address this complexity. By providing tailored strategies for complex surgical procedures, these guidelines ensure that prophylactic antibiotics are aligned with the specific requirements of each surgery, thereby maximizing their effectiveness in preventing SSIs .Duration of Prophylactic TreatmentIn the majority of surgical procedures, a single prophylactic antibiotic dose administered shortly before the surgical incision is typically sufficient. This single-dose approach aligns with the principle of minimizing antibiotic exposure while ensuring that adequate antibiotic levels are present at the surgical site during the crucial initial stages of the procedure. This strategy aims to decrease the risk of selecting antibiotic-resistant bacterial strains in the patient's microbiome . ProphylAdherence to Guidelines in Clinical PracticeMultidisciplinary approach: The successful implementation of antibiotic prophylaxis guidelines necessitates a coordinated, multidisciplinary approach within the healthcare team. Collaboration among surgeons, anesthesiologists, nurses, and pharmacists is essential to optimize the administration of antibiotics. Surgeons and anesthesiologists must align surgical schedules with the timing of antibiotic administration, ensuring that antibiotics are given within the recommended timeframe before incision. Nurses are crucial in administering antibiotics and monitoring patients for adverse reactions or complications. Pharmacists contribute by ensuring the appropriate selection, dosing, and preparation of antibiotics and conducting medication reconciliation to avoid potential drug interactions. This collective effort ensures that antibiotic prophylaxis is seamlessly integrated into the surgical process, minimizing SSI risk .Monitoring and quality improvement: Healthcare institutions recognize the significance of guideline adherence and often establish robust monitoring and quality improvement programs. These initiatives serve as a vital feedback loop, allowing healthcare systems to assess compliance with antibiotic prophylaxis guidelines and track SSI rates. Continuous monitoring helps identify areas where adherence may be lacking or improvements can be made. By scrutinizing these data, healthcare institutions can implement targeted interventions and interventions to address compliance issues. This proactive approach contributes to refining practices, ensuring that adherence to guidelines becomes an ingrained part of the institutional culture. It also provides valuable insights into the impact of adherence on SSI rates, allowing for data-driven improvements in patient care .Education and training: Ongoing education and training programs for healthcare professionals are fundamental to successful adherence to antibiotic prophylaxis guidelines. These programs aim to raise awareness of the importance of guidelines and promote best practices among surgical teams. Healthcare professionals need regular updates on the latest guidelines, as recommendations may evolve based on new evidence and emerging trends in antibiotic resistance. Education also addresses common misconceptions and myths about antibiotic prophylaxis, ensuring that healthcare providers understand the guidelines' rationale. Training programs extend beyond just understanding guidelines; they also focus on practical aspects such as proper antibiotic administration techniques and recognizing potential adverse reactions. By investing in the education and training of healthcare professionals, institutions empower their teams to make informed decisions and deliver the highest standard of care, ultimately contributing to more effective SSI prevention through guideline adherence .Mechanisms of actionHow Antibiotics Prevent SSIsA key consideration in selecting antibiotics for surgical procedures is their pharmacokinetics, especially their distribution to the incision tissue. Antibiotics are chosen meticulously, taking into account their specific affinity for targeting particular groups of bacteria commonly encountered in surgical settings. These selected antibiotics are pivotal in disrupting critical bacterial processes, such as cell wall synthesis, protein production, DNA replication, and other vital functions. This deliberate targeting ensures that the antibiotics effectively eliminate or inhibit the bacteria responsible for SSIs while preserving the beneficial microorganisms . By consReducing bacterial load: A fundamental aspect of antibiotic prophylaxis involves substantially reducing bacterial populations at the surgical site. By decreasing the number of bacteria in the vicinity, antibiotics create a less favorable environment for establishing infections. This is particularly critical during the initial stages of wound healing when the surgical site is most vulnerable to bacterial invasion .Minimizing local spread: Antibiotics act as a formidable barrier against the local spread of bacteria beyond the confines of the surgical incision. They effectively curtail the migration of bacteria to deeper tissue layers or body cavities, where infections can become more severe and challenging to manage. Antibiotics help prevent the development of deep tissue and organ/space infections by containing bacteria at the incision site .Immune system support: Antibiotics indirectly support the patient's immune system in its battle against potential infections. Antibiotics afford the immune system a favorable environment by reducing the bacterial burden within the surgical area. This immune system support can enhance the body's natural defense mechanisms, allowing it to focus on clearing any remaining bacteria and expediting the healing process .Factors Influencing Antibiotic EfficacyTiming: The timing of antibiotic administration is of paramount importance. Antibiotics should be administered shortly before surgical incision, ideally within 30 to 60 minutes. This precise timing ensures that therapeutic antibiotic levels are present at the surgical site when the patient is most vulnerable to potential bacterial exposure. Early administration is crucial because delayed dosing can reduce antibiotic efficacy [Dosage and route of administration: Accurately administering antibiotics is crucial for optimal prophylaxis. It involves not only the correct dosage but also the appropriate route of administration. To ensure adequate tissue concentrations capable of inhibiting bacterial growth, the dosage should be meticulously calculated, considering factors such as body weight, renal function, and the volume of distribution. These factors collectively influence the selection of the most suitable route of administration, whether oral, intravenous, intramuscular, or another method. Under-dosing can render antibiotics ineffective, while excessive dosing may increase the risk of adverse effects without necessarily enhancing prophylactic benefits .Spectrum of activity: Antibiotics should possess a spectrum of activity broad enough to cover the likely pathogens associated with the specific surgical procedure. Tailoring antibiotic choice to the anticipated pathogens is crucial for efficacy. However, the selection of overly broad-spectrum antibiotics can be counterproductive, potentially contributing to the development of antibiotic resistance. Thus, a careful balance must be struck between targeted coverage and minimizing the risk of resistance .Patient factors: Patient-related variables, such as allergies, comorbidities, and immunosuppression, can significantly influence antibiotic prophylaxis efficacy. Knowledge of a patient's medical history and potential allergens is essential to selecting antibiotics that are both effective and safe. Patients with underlying health conditions may require antibiotic choice or dosage adjustments to ensure adequate prophylaxis .Surgical technique: The surgical technique can substantially impact antibiotic efficacy. Adequate tissue perfusion, proper wound closure, and meticulous aseptic practices are essential to maximizing antibiotic prophylaxis's effectiveness. Ensuring that the surgical environment is as free from contamination as possible and that wounds are well-approximated help prevent bacterial entry and subsequent infection .Role of Antibiotic ResistanceSelection pressure: The ubiquitous use of antibiotics, including their prophylactic administration, exerts relentless pressure on bacteria. This pressure encourages the survival and proliferation of bacterial strains that can withstand antibiotic exposure. Over time, these survivors develop genetic adaptations that confer resistance, rendering antibiotics less effective in subsequent encounters .Multidrug resistance: The most alarming manifestation of antibiotic resistance is the emergence of multidrug-resistant organisms (MDROs). These tenacious pathogens have evolved mechanisms to resist multiple classes of antibiotics, severely limiting treatment options. In surgical settings, encountering MDROs can lead to dire clinical challenges, heightening the risk of untreatable infections .Infection risk: Patients who harbor or are infected with antibiotic-resistant bacteria have an elevated risk of SSIs. Once stalwart defenders against infection, prophylactic antibiotics may prove less efficacious in the face of these resilient pathogens. Consequently, SSIs caused by antibiotic-resistant bacteria can be more challenging to manage and may lead to poorer patient outcomes .Balancing act: The crux lies in achieving a delicate balance. On the one hand, effective antibiotic prophylaxis remains pivotal in preventing SSIs and their associated complications. On the other hand, the overuse or misuse of antibiotics amplifies the peril of antibiotic resistance. Antibiotic stewardship programs, a linchpin of responsible antibiotic use, seek to harmonize these conflicting imperatives. By optimizing antibiotic use, these programs strive to curtail resistance while ensuring that antibiotic prophylaxis remains a potent safeguard against SSIs . Table 1Table Efficacy and effectivenessClinical Studies and Evidence Supporting Antibiotic ProphylaxisRandomized controlled trials (RCTs): Across a broad spectrum of surgical procedures, numerous RCTs have yielded consistent and compelling results. These studies demonstrate that antibiotic prophylaxis significantly reduces the incidence of SSIs. RCTs provide a robust foundation for the efficacy of prophylactic antibiotics, offering scientific rigor and minimizing biases that can influence outcomes. The rigorous design of RCTs ensures that the observed benefits can be confidently attributed to antibiotic prophylaxis .Procedure-specific evidence: Clinical trials often drill down to the nuances of specific surgical procedures, tailoring their investigations to colorectal surgery, orthopedic joint replacements, cesarean sections, and more. Procedure-specific evidence enhances our understanding of the effectiveness of antibiotic prophylaxis within distinct clinical contexts. This approach acknowledges that different surgeries may present with varying infection risks, patient populations, and bacterial flora, necessitating tailored prophylactic strategies. As a result, surgeons can make informed decisions about antibiotic selection and dosages to maximize the protective benefits for their patients .Meta-analyses: Beyond individual trials, meta-analyses offer a comprehensive synthesis of data from multiple RCTs. By pooling data across studies, meta-analyses provide a powerful overview of the overall benefit of antibiotic prophylaxis. These analyses help distill patterns and trends, lending further weight to the efficacy of prophylactic antibiotics. Importantly, meta-analyses accommodate the diversity of patient populations and surgical settings, offering a global perspective on the preventive impact of antibiotic prophylaxis .National and international guidelines: The recommendations from influential healthcare organizations, such CDC and WHO, are intricately informed by a thorough review of clinical evidence. These guidelines encapsulate a consensus view, aligning with the findings of clinical studies and RCTs. They serve as the cornerstone for best practices in antibiotic prophylaxis. The fact that these authoritative bodies unequivocally advocate for antibiotic prophylaxis underscores its critical role in safeguarding surgical patients from SSIs .Real-world observations: While RCTs and clinical trials provide controlled environments for evaluating interventions, real-world practice settings offer invaluable insights into the practical impact of antibiotic prophylaxis. Observational studies conducted in clinical practice settings have consistently corroborated the effectiveness of antibiotic prophylaxis. They demonstrate reductions in SSI rates when surgical teams adhere to established guidelines. These real-world observations underscore the translatable benefits of antibiotic prophylaxis, reflecting its pragmatic utility in diverse healthcare settings .Reduction in morbidity and mortality: Perhaps the most compelling evidence of antibiotic prophylaxis' efficacy emanates from its palpable impact on patient outcomes. Antibiotic prophylaxis significantly reduces patient morbidity, mortality, and healthcare costs linked to SSIs when appropriately administered. Beyond statistical significance, these tangible improvements in patient well-being are a poignant reminder of the profound value of antibiotic prophylaxis in surgical care. It reaffirms its status as an indispensable tool in the relentless pursuit of patient safety and surgical excellence .Risks and Side Effects of Antibiotic ProphylaxisAllergic reactions to antibiotics can range in severity, from mild skin rashes to life-threatening anaphylactic shock. The identification of patient allergies and the acquisition of a comprehensive medical history are crucial in managing this risk. In cases of known allergies, choosing alternative antibiotics with different chemical structures can help ensure patient safety while still effectively preventing SSIs . AntibioClostridium difficile infection (CDI). This potentially severe and recurrent gastrointestinal infection is caused by the overgrowth of C. difficile bacteria, often due to the disruption of the gut microbiome by antibiotics. CDI can lead to severe diarrhea, colitis, and even life-threatening complications [Prolonged or extensive use of antibiotics, even for prophylaxis, significantly increases the risk of developing ications . An overications .Certain antibiotics may interact with other medications that patients are taking concurrently. These interactions can alter the pharmacokinetics of both the antibiotic and the other drugs, potentially affecting their effectiveness or safety. Healthcare providers must remain vigilant in assessing potential drug interactions to prevent adverse outcomes . The indAreas of Improvement in Current PracticesAntibiotic stewardship: Implementing robust antibiotic stewardship programs within healthcare institutions is imperative. These programs aim to ensure the judicious and appropriate use of antibiotics for SSI prevention across all healthcare settings. By carefully monitoring and regulating antibiotic use, healthcare providers can reduce the risk of antibiotic resistance. Such programs involve continuous evaluation of prescribing practices, monitoring of resistance patterns, and the development of guidelines that emphasize the responsible use of antibiotics. They promote a delicate balance between preventing SSIs and safeguarding the long-term effectiveness of antibiotics .Tailored approaches: Recognizing that each patient is unique, conducting further research into patient-specific factors that can influence the efficacy and safety of antibiotic prophylaxis is essential. Age, comorbidities, immune status, and individual pharmacokinetics all play crucial roles in determining the optimal antibiotic regimen for a given patient. Tailoring antibiotic choices and dosages based on these factors can maximize the benefits of prophylaxis while minimizing the risks. This personalized medicine approach enhances SSI prevention and reduces potential adverse events and antibiotic resistance .Alternative strategies: Exploring and implementing alternative strategies for SSI prevention represents a promising avenue for reducing reliance on antibiotics. Antimicrobial-coated implants, for example, can help minimize the risk of infections associated with surgical devices. Immunomodulatory agents that enhance the patient's immune response may complement antibiotic prophylaxis, particularly in cases where infections are challenging to prevent solely with antibiotics. Additionally, enhanced perioperative infection control measures, such as strict adherence to aseptic techniques and advanced wound care practices, can reduce the risk of SSIs without additional antibiotics .Surveillance and feedback: Monitoring SSI rates and guideline adherence is essential for quality improvement in surgical practices. Healthcare institutions should establish comprehensive surveillance systems to track SSI occurrences and identify potential areas for improvement. Regular feedback loops with surgical teams can help address lapses in adherence to best practices. By analyzing data and sharing outcomes, institutions can drive change, reduce variation in practice, and ultimately enhance SSI prevention efforts. This approach fosters a culture of accountability and continuous improvement within the healthcare system .Education and training: Ensuring that healthcare professionals receive ongoing education and training on antibiotic prophylaxis guidelines and principles is paramount. Effective implementation of prophylactic measures relies on the knowledge and commitment of the healthcare workforce. Regular training programs can keep healthcare providers up-to-date with the latest guidelines, advances in pharmacology, and best practices for antibiotic prophylaxis. Furthermore, education can help raise awareness about the importance of adherence to guidelines and the responsible use of antibiotics, promoting a culture of patient safety and effective SSI prevention within healthcare institutions .Challenges and controversiesOveruse and Misuse of AntibioticsIn the context of low-risk surgical procedures, it is essential to consider the appropriateness of antibiotic prophylaxis and assess the risk of SSIs. Determining when to administer antibiotics in these cases is crucial, as the potential benefits must be weighed against the associated risks. Antibiotics are sometimes prescribed unnecessarily, depleting valuable medical resources and contributing to the emergence of antibiotic-resistant bacteria. Overusing antibiotics in low-risk procedures offers limited benefits and poses a substantial risk to public health . TherefoNon-compliance with guidelines: Another challenge lies in the practice variability among surgeons. Despite well-established guidelines outlining when and how antibiotic prophylaxis should be administered, deviations from these guidelines persist. Surgeons may need more awareness, clinical judgment, or personal preferences to diverge from established protocols. This inconsistency in guideline adherence can result in inappropriate antibiotic use, increasing the likelihood of antibiotic resistance and undermining the efficacy of prophylactic measures .Pressure for prophylactic use: A complex dimension of overuse is the pressure patients and their families exert for prophylactic antibiotic administration. Patients may seek antibiotics as reassurance, believing that antibiotics will guarantee protection against SSIs. This pressure can lead to the administration of antibiotics even in cases where guidelines advise against it. While patient satisfaction and peace of mind are valid concerns, succumbing to such pressures can perpetuate unnecessary antibiotic use, further fueling the problem of antibiotic resistance .Development of Antibiotic ResistanceSelection for resistant bacteria: The routine use of antibiotics as prophylactic measures in surgery has profound consequences for bacterial populations. It introduces a selective pressure favoring the survival and proliferation of bacteria with pre-existing resistance or those that acquire resistance mutations. The antibiotics act as a Darwinian filter, allowing resistant bacteria to thrive while susceptible ones are eliminated. This phenomenon is particularly concerning because it contributes significantly to the growing global problem of antibiotic resistance. The more antibiotics are used, especially when unnecessary, the more chances bacteria have to evolve mechanisms to evade these drugs .MDROs: The emergence of MDROs represents a critical juncture in the evolution of antibiotic resistance. MDROs are bacteria that exhibit resistance to multiple classes of antibiotics, including those considered as last-resort treatments. The widespread use of antibiotics, including prophylactic use, plays a pivotal role in developing MDROs. When repeatedly exposed to various antibiotics, bacteria can accumulate resistance mechanisms, rendering them impervious to conventional therapeutic options. This situation poses a dire challenge for clinicians, as it limits the arsenal of antibiotics available to combat infections caused by MDROs .Allergic Reactions and Other Adverse EventsAllergic reactions: Allergic reactions to antibiotics present a multifaceted challenge in SSI prevention. These reactions can manifest along a spectrum, ranging from mild skin rashes and itching to severe and life-threatening anaphylactic shock. The importance of identifying patient allergies cannot be overstated, as administering an antibiotic to which a patient is allergic can lead to dire consequences. To mitigate the risk, meticulous patient history-taking and allergy documentation are essential before any surgical antibiotic prophylaxis ,75.Clostridium difficile infection: The gut microbiome disruption due to prolonged antibiotic use, even when administered for prophylaxis, introduces another dimension of concern. This disruption can significantly increase the risk of CDI, a bacterial colon infection. CDI can manifest with severe diarrhea, abdominal pain, and, in some cases, life-threatening complications [ications . The relications .Economic considerations: The cost of antibiotics selected for prophylaxis can vary significantly, especially when considering newer or broader-spectrum agents. While these antibiotics may offer advantages in terms of their spectrum of activity, they often come with a substantial price tag. Healthcare providers face the challenge of balancing these antibiotics' clinical benefits against their economic costs. Striking this equilibrium is a continuous endeavor, requiring a nuanced assessment of the specific surgical context and patient population .Prophylactic antibiotics are primarily administered to prevent SSIs, and their efficacy can lead to substantial savings in healthcare expenses. Antibiotic prophylaxis can deliver significant economic benefits by avoiding the need for additional surgeries, prolonged hospital stays, and costly treatment of postoperative infections. However, this apparent economic gain must be weighed against the long-term costs of antibiotic resistance. The emergence of resistant bacterial strains can lead to challenging and costly treatment scenarios, negating the initial savings .Healthcare institutions often grapple with concerns related to legal liability in the context of SSIs. The prospect of litigation from patient infections acquired during surgery can be daunting. Some institutions may overreact to prophylactic antibiotics as legal protection in response to these legal worries. This practice can inadvertently contribute to antibiotic overuse and, in turn, fuel the problem of antibiotic resistance .In specific healthcare systems, reimbursement models can inadvertently incentivize the use of antibiotics for prophylaxis. Preventing complications, including SSIs, can lead to financial bonuses for healthcare providers. While the intention behind these incentives is to improve patient outcomes, there is a risk that they may encourage the indiscriminate use of prophylactic antibiotics. Striking a balance between incentivizing quality care and avoiding unnecessary antibiotic administration is an ongoing challenge within these reimbursement structures .Controversy Surrounding Antibiotic DurationThe controversy surrounding antibiotic duration is a subject of extensive discussion within the medical field, and it stems from the delicate equilibrium that must be established between effectively treating infections and curtailing the development of antibiotic resistance. The choice between short-term and long-term antibiotic regimens is at the heart of this controversy. Short-term treatment courses are often preferred due to their potential to minimize the risk of antibiotic resistance. The rationale here is that limiting bacteria's exposure to antibiotics diminishes the likelihood of them developing resistance. Consequently, shorter courses are commonly employed for routine infections where a swift and decisive response is highly effective ,36.However, the debate takes a more intricate turn when addressing severe or recurring infections. In these scenarios, the focus shifts toward longer antibiotic durations. Extended treatment courses are designed to ensure the thorough eradication of all infectious agents, reducing the risk of recurrent infections and the emergence of resistant strains. Striking the right balance between these two approaches becomes the central challenge in this debate. To bring clarity to this ongoing discussion, numerous reputable health organizations, including CDC, WHO, and the Infectious Diseases Society of America, have issued comprehensive guidelines and recommendations regarding antibiotic duration. These guidelines serve as invaluable references for healthcare practitioners, offering critical insights into the recommended treatment durations based on the type and severity of the infection. They guide navigating the complex terrain of antibiotic therapy duration, assisting healthcare providers in making well-informed decisions in various clinical scenarios ,37.Future directionsInnovations in Antibiotic ProphylaxisNanotechnology offers the potential to revolutionize antibiotic delivery in surgical prophylaxis with its precision and versatility. Nanoparticles can be designed to encapsulate antibiotics and release them slowly at the surgical site. This localized drug delivery minimizes systemic exposure, reducing the risk of adverse effects while maintaining therapeutic levels where they are most needed. This innovation enhances the efficacy of antibiotics and contributes to patient safety by minimizing the impact on the body's microbiome . CombiniThe era of personalized medicine extends its reach into antibiotic prophylaxis. Pharmacogenomics, which involves tailoring drug choices based on an individual's genetic profile, may soon become a standard practice in surgical settings. By analyzing a patient's genetic makeup, healthcare providers can identify genetic markers influencing how the body metabolizes and responds to antibiotics. This knowledge allows for selecting effective antibiotics against likely pathogens and optimized for the patient's unique physiology. Personalized prophylaxis ensures that patients receive the most appropriate antibiotic, minimizing the risk of adverse reactions and enhancing overall efficacy . To combPersonalized Medicine and Tailored ApproachesRecent research endeavors have delved into the intricate web of host factors that influence an individual's susceptibility to SSIs. These factors encompass many patient-specific characteristics, including genetics, immunological profiles, and microbiome composition. Genetic variations can predispose some individuals to a heightened risk of infections, while others may possess innate immunity that offers better protection. By identifying these host factors, clinicians can tailor prophylactic regimens to match a patient's unique vulnerabilities and strengths . The devAlternatives to Antibiotics for SSI PreventionAntimicrobial coatings: In surgical implants and medical devices, developing enhanced implant coatings with antimicrobial properties represents a promising avenue for reducing the risk of SSIs. These coatings are designed to release antimicrobial agents gradually, creating a protective barrier at the implant site. These coatings can significantly lower the likelihood of infections associated with implanted devices by inhibiting bacterial colonization and biofilm formation .Immunomodulatory therapies: Researchers are exploring immunomodulatory therapies as potential alternatives or adjuncts to antibiotic prophylaxis. These therapies aim to bolster the patient's immune response, empowering the body to fend off potential pathogens better. By optimizing the immune system's capacity to recognize and combat invading microorganisms, these treatments may offer a proactive defense against SSIs. While still in the experimental phase, immunomodulatory agents hold promise in reducing the need for antibiotics in preventing SSIs, particularly in cases where patient-specific factors make them susceptible to infections .Probiotics and prebiotics: The gut microbiome plays a pivotal role in overall health and immunity. Manipulating this microbial ecosystem with probiotics  and prebiotics (substances that promote their growth) is gaining attention as a strategy to reduce the risk of SSIs, particularly in gastrointestinal surgeries. Probiotics can enhance the balance of beneficial bacteria in the gut, strengthening the body's defenses against potential pathogens. Prebiotics provide nourishment for these helpful microbes, fostering a healthier gut environment. By fortifying the gut microbiome, probiotics and prebiotics may indirectly bolster the patient's overall immune response and, in turn, reduce the susceptibility to SSIs .Bacteriophages: Bacteriophages, viruses that infect and selectively kill bacteria, offer a targeted and precise approach to combat specific bacterial pathogens. They have gained attention as potential alternatives to antibiotics for SSI prevention. Bacteriophages can be tailored to target specific bacteria responsible for SSIs, leaving beneficial bacteria unharmed. By directly attacking the causative agents of infection, bacteriophages may provide an effective means of prevention while minimizing the disruption of the broader microbiome. Research into the use of bacteriophages in surgery holds promise for a future where antibiotic prophylaxis is complemented or even replaced by this particular and adaptable approach .Multidisciplinary Strategies for SSI PreventionMultidisciplinary teams are pivotal in enhancing infection control measures within healthcare settings. Collaboration among surgeons, nurses, infection control specialists, and environmental services staff allows for implementing stringent aseptic techniques. This includes maintaining sterile fields, using proper surgical attire, and adhering to rigorous hand hygiene protocols. Furthermore, teams work together to ensure meticulous surgical site preparation, reducing the microbial load at incision sites and minimizing the risk of contamination . ComprehAdvances in surgical techniques are continually reshaping the landscape of SSI prevention. Minimally invasive and robotic-assisted surgery techniques have gained recognition for their potential to minimize tissue trauma and reduce infection risk. These approaches often result in smaller incisions, decreased blood loss, and shorter hospital stays, all contributing to a reduced risk of SSIs . IntegraIn conclusion, the use of antibiotic prophylaxis in surgery represents a critical component of SSI prevention. This practice has evolved over the years, with current insights emphasizing the importance of selecting the right antibiotics, optimizing timing, and adhering to guidelines to minimize the risk of bacterial resistance. As we move forward, future directions in this field should focus on individualized approaches, incorporating advancements in diagnostics, and embracing innovative strategies such as immunomodulation to enhance SSI prevention. In an era of increasing antibiotic resistance, maintaining a delicate balance between effective prophylaxis and judicious antibiotic use is paramount. Surgeons, infection control specialists, and researchers should collaborate to refine existing protocols and explore novel methods to safeguard patient safety during surgical procedures. By doing so, we can look forward to a future where SSIs become a rarity rather than a risk, ultimately improving the overall quality of surgical care.


Saccharomyces boulardii CNCM I 745, to antibiotic prescription can serve as a potential option to mitigate this risk.This study aimed to review the existing literature to investigate the potential link between early-life antibiotic use and being overweight or obese in children. PubMed, Web of Science, Embase, Google Scholar, and Cochrane Library were searched to identify studies published until August 2021 that assessed the relationship between early-childhood antibiotic use and measures of body mass index. The studies included children aged 0-18 years. Only cohort studies were taken into consideration. Studies published in languages other than English were excluded. Antibiotic usage in early life may increase the risk of obesity in children and the addition of yeast probiotics, such as  Obesity is a complicated disease involving the interplay between biological, developmental, environmental, behavioral, and genetic variables, leading to an energy imbalance and the accumulation of extra adipose tissue ,2. The wIn many countries, obesity in children is rising faster than in adults . ApproxiIn India, stunting and underweight exist alongside overweight and obesity in children, creating a dietary conundrum. The prevalence of stunting, wasting, and being underweight in children aged five years was found to be 38%, 21%, and 36%, respectively, in the National Family Health Survey-4 2015-2016). According to the study, 2% of Indian children under the age of five years were overweight [-2016. AcIn addition to genetic and environmental variables, gut microbiota plays an essential role in the development of obesity. Gut microbiota dysbiosis, an imbalanced or disordered gut microbial ecology, impacts obesity etiology by affecting energy harvest, nutrition metabolism, inflammatory pathways, and the gut-brain axis -10.Antibiotics significantly contribute to altering the gut microbiota. They are regularly administered to infants and children, and up to 40% of infants are exposed to them either directly or indirectly through maternal intrapartum antibiotic prophylaxis . In the ObjectiveThe key objective of this review was to summarize the research investigating the potential link between antibiotic use and obesity/overweight in children. In addition, we aimed to review the role of probiotics in managing dysbiosis to avoid future adverse effects such as obesity.For this review, a data search was conducted on PubMed, Web of Science, Embase, Google Scholar, and the Cochrane Library to identify studies published until August 2021 that assess the relationship between early-childhood antibiotic use and the body mass of the child. Search terms such as “antibiotics,” “gut microbiota,” “overweight,” and “obesity” were used. The inclusion criteria included children aged between 0 and 18 years, and only cohort studies and English-language publications were considered. Studies on antibiotics of any kind, used for any duration, any method, or for any reason were recorded. Studies based on children who were extremely malnourished, affected by an underlying disease, born with low birth weight, or who were small for their gestational age were excluded  Antibiotic use early in life has been linked to a decrease in the quantity of beneficial gut flora, leading to reduced gut microbial diversity and lower rates of colonization of protective commensal bacteria. An increase in Enterobacteriaceae (phylum Proteobacteria) and a decrease in good bacteria, such as Bifidobacteria and butyrate markers, have been documented. Short-chain fatty acids (SCFA), which have beneficial effects on mammalian energy metabolism, are produced by Bifidobacteria (phylum Actinobacteria) and Lactobacilli (phylum Firmicutes) ,17.Bacteroides spp. may offer some protection against invasive pathogens; however, Bacteroides have also been linked to bloodstream infections and the development of abscesses [Antibiotic use has been linked to an increase in Bacteroidetes and Proteobacteria, with some species in these phyla associated with severe infections. bscesses ,18.Bifidobacteria protects against obesity and its metabolic consequences, partially by improving gut barrier function, which decreases metabolic endotoxemia, the abundance of bacterially generated lipopolysaccharides (LPS) in the blood. Once the ratio of Bifidobacteria to Bacteroides gets perturbed, the abundance of barrier function-improving microbes drops and the number of LPS-producing organisms increases ,20. LPS The synthesis of SCFA via colonic fermentation, which involves the anaerobic degradation of food fiber, protein, and peptides, helps the gut bacteria contribute to energy metabolism. SCFAs are bacterial waste products generated to maintain a healthy redox balance in the gut. Acetate, propionate, and butyrate are the most common SCFA species. The Bacteroidetes phylum produces acetate and propionate, whereas the Firmicutes phylum produces butyrate. Body weight, glucose homeostasis, and insulin sensitivity have all been found to benefit from them ,19-21.Is There Any Evidence That Antibiotics Have the Potential to Cause Obesity or Weight Gain?We found 20 observational studies encompassing a total of 1,412,275 participants that allowed us to assess the association between antibiotic exposure before the age of four years and later measurements of body mass or the risk of obesity/overweight in childhood  and showed that association with infection, but not with antibiotic usage, was linked to an increased risk of childhood obesity.The 17 studies comprising a total of 1,112,326 participants clearly highlighted that the use of antibiotics was linked to obesity. Antibiotic exposure in early infancy was related to a higher body mass index (BMI) and a higher prevalence of obesity in healthy children, according to these cohort studies.Aversa et al. demonstrated that antibiotic exposure during childhood was associated with an increased risk of childhood obesity, asthma, allergic rhinitis, atopic dermatitis, celiac disease, and attention-deficit hyperactivity disorder. The hazard ratios were 1.20-2.89, with a p-value <0.05 for all conditions. This study was conducted and published by the Mayo Clinic .Uzan-Yulzari et al. showed that antibiotic exposure during the neonatal phase was linked to a long-term disruption of the gut microbiota, which may cause stunted development in boys during the first six years of their life, whereas antibiotic usage later in childhood was linked to an increase in BMI. In most studies, antibiotic exposure occurred during the first two years of life and was significantly associated with weight gain/obesity .Another recent study by Aris et al. on 0-48-month-old children documented that antibiotic exposure was associated with statistically significant BMI trajectory milestones during infancy and early childhood. These associations were the strongest for children with at least four episodes of antibiotic exposure .Is There Any Treatment Option Available to Prevent the Consequences Associated With Dysbiosis?Probiotics seem to be a promising option to treat dysbiosis and are well-tolerated upon long-term usage. The World Health Organization defines probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” Probiotics are continually used to preserve human intestinal health by improving the equilibrium of internal microbiota. As a result, the number of harmful bacteria that cannot live in acidic environments decreases, whereas helpful bacteria that thrive in such environments multiply, thereby balancing the gut microbiota .Lactobacillus rhamnosus GG is a bacterial probiotic, whereas Saccharomyces boulardii CNCM I 745 is a yeast probiotic. Both have been extensively studied and are recommended as adjunct therapy while managing acute gastroenteritis and antibiotic-associated diarrhea (AAD) in children [Probiotics are available in various forms, the most common being bacterial and yeast probiotics. Only a few of the many available probiotics have scientific merit and global recommendations. children ,44.S. boulardii CNCM I 745 and L. rhamnosus GG can be used along with antibiotics for preventing it [AAD is characterized by the passage of loose, watery stools three or more times a day following the intake of antibiotics used to treat bacterial illnesses. It affects 5%-30% of patients, either early in the course of antibiotic medication or up to two months after the treatment is completed ,45. Althnting it ,47.L. rhamnosus GG and antibiotics faces the challenge that the antibiotic may potentially kill the bacterial probiotics. Hence, the two must be administered at least two to four hours apart. On the contrary, a time gap is not required while using S. boulardii CNCM I 745. Further, yeast probiotics are 10 times larger in size than bacteria and can adhere firmly to the epithelial layer of the intestine, precluding the adhesion of any pathogenic bacteria [S. boulardii CNCM I 745 neither shows resistance to antibiotics nor plays any role in genetic transfer [Probiotics should be administered along with antibiotics and should be continued for a few days after stopping antibiotics to obtain the desired results. However, the concurrent administration of bacteria ,46,47. Stransfer .S. boulardii CNCM I 745 has several established mechanisms of action [Clostridium difficile toxins A and B, cholera toxin, and Escherichia coli. It can interfere with gut infections either directly or indirectly. For example, it can directly suppress the growth of Salmonella typhimurium, Yersinia enterocolitica, and Aeromonas hemolysin. It can enhance the production of SCFAs, which are depleted during illness, suggesting altered intestinal fermentation. It can decrease mucositis, repair fluid transport routes, promote protein and energy synthesis, or serve as a trophic agent by producing spermine and spermidine, as well as other brush border enzymes that help enterocytes mature. Finally, it can modulate immune responses by acting as a stimulant or by decreasing pro-inflammatory responses. Intestinal secretory immunoglobulin A (IgA) levels may rise because of S. boulardii infection. It is also linked to elevated levels of blood IgG against C. difficile toxins A and B. It may disrupt nuclear factor-κB-mediated signaling pathways, which promote the generation of pro-inflammatory cytokines.f action ,47. It sS. boulardii CNCM I 745 along with antibiotics have shown that it helps prevent and manage dysbiosis. Additional details are presented in Table Some clinical studies that used A study of 60 women treated for bacterial vaginosis analyzed the effects of antibiotic therapy alone, concurrently with S. boulardii treatment, or followed by S. boulardii treatment. In the study, 60 women were given metronidazole (3 × 400 mg/day) and ciprofloxacin (2 × 500 mg/day) to treat bacterial vaginosis. Group I received antibiotics for the first and second weeks. Group II received 250 mg S. boulardii tid in addition to antibiotics for weeks one and two. Group III received antibiotics for weeks one and two, followed by 250 mg S. boulardii tid for weeks three and four. Fluorescence in situ hybridization analysis of Carnoy fixated stool cylinders was done from days -90, -60, -30, 7, 14, 28, 42, 56, and 70.S. boulardii  provided during antibiotic therapy can mitigate this loss by preserving the microbiome. If S. boulardii is given after antibiotic therapy , it can help the microbial community regenerate more quickly. As a result, a combination of both, with S. boulardii therapy during and after antibiotic treatment, would be ideal. The hypothetical black dotted line drawn from the other lines represents this. The worst-case situation is that no S. boulardii therapy is provided (blue line)  Figure .S. boulardii might reduce the suppression of these bacteria caused by the antibiotic. After receiving antibiotic therapy, S. boulardii dramatically accelerated the return of the natural microbiota. S. boulardii also decreased the number of pre- and post-mismatches in the microbial community. Contrary to what would have happened if S. boulardii had been provided, antibiotic therapy greatly increased population differences (compared to before treatment) [Although stable enterotypes were seen before treatment, the antibiotics led to the suppression of the habitual/essential  bacteria as well as other significant bacterial groups. If given concurrently with an antibiotic, eatment) .As this is an attempt to present a narrative review of the evidence, there are a few limitations to this review. We only considered cohort studies. Moreover, the age groups and study durations were different. Another important limitation is that we did not focus on any specific antibiotic while including studies in this review. Dosage regimens were different in all cohort studies. Finally, per the evidence, yeast probiotics are superior to bacterial probiotics, but head-to-head studies are very limited. Therefore, for establishing a strong correlation between antibiotics and obesity, we need further larger controlled studies.S. boulardii CNCM I 745 can be adjuvants to antibiotic therapy to modulate the gut microbiota.Antibiotics are very commonly used in the first few years of a child’s life, and there are many hypotheses linking early antibiotic exposure to childhood obesity. Antibiotics mainly impact the gut microbiota, and this altered gut microbiota increases BMI or obesity later in life. In this review, 17 studies showed an association between antibiotic usage in early life and obesity in later stages of life. Evidence-based yeast probiotics,


The penetrating repair material in this study has good infiltration performance, which can penetrate a certain depth in the surface pores and form a high-performance consolidation body, forming a “rooted type” filling.Concrete surface defects are very complex and diverse, which is a great test for repair materials. The efficiency and durability of the repair system depend on the bonding effect between the concrete and the repair material. However, the rapid increase in system viscosity during the reaction of repair materials is an important factor affecting the infiltration effect. In the present work, the infiltration consolidation repair material was prepared, and its basic properties  and mechanical properties were evaluated. Finally, the infiltration depth, film-forming thickness, and anti-spalling ability of concrete under a single-side freeze–thaw cycle are revealed. The results showed that using ethyl acetate could rapidly reduce the viscosity of the repair material, and the repair material could penetrate 20–30 mm into the concrete within 10 min. It was found by laser confocal microscopy that the thickness of the film formation after 3 days was only 29 µm. In the mortar fracture repair test to evaluate the bond strength, the bond strength of the repaired material reached 9.18 MPa in 28 days, and the new fracture surface was in the mortar itself. In addition, the freeze–thaw cycle test was carried out on the composite specimens under salt solution to verify the compatibility of the designed repair material with the concrete substrate. The data showed that the average amount of spalling was only 1704.4 g/m With the dramatic increase in traffic volume in recent years, concrete pavement bears more and more load. The long-term load and impact pressure, coupled with the destruction of the natural environment , concrete pavement withstands varying degrees of damage . Once thAt present, the materials used for concrete repair are mainly divided into three categories. The first category is inorganic repair materials which mainly include silica cement, fast-hardening Portland cement, magnesium phosphate cement, and so on ,11. The The research on concrete repair materials now focuses on good compatibility with concrete, good durability, and low viscosity for easy grouting and repair. Kim et al.  used a cAs surface defects contain many tiny cracks, it is difficult for high-viscosity organic repair materials to penetrate the surface layer to a certain depth. Moreover, the higher the viscosity, the poorer the wettability of repair materials, most of which remain on the concrete surface to form thick polymers ,19,20,21In view of this, tetrachloroethylene was selected as a shrinkage reducer , and anhThe design strength grade of an ordinary concrete specimen is C30, in which the cement is Conch brand P·O 42.5 ordinary Portland cement. The aggregate is a well-graded crushed stone with a particle size of less than 30 mm and a fineness modulus of 2.5 medium sand. See Methyl methacrylate (MMA) is the main raw material, dibenzoyl peroxide (BPO) is the initiator, dibutyl phthalate (DBP) is the plasticizer, tetrachloroethylene (PCE) is the shrinkage agent, N,N-dimethylaniline (DMA) is the curing agent, and the three diluents are absolute ethanol, ethyl acetate, and acetone. Preparation of the MMA-based repair materialsA certain amount of MMA was poured into a beaker, stirred at a speed of 300/min, and distilled in a water bath at 50 °C for 10 min.After distillation to remove the inhibitor, 1.5% BPO, 30% DBP, and 10% PCE was added and continuously stirred for 2 min.The curing agent DMA was added to the prepolymer and stirred evenly until the set time of the test was reached. The three-flask was quickly put into cold water to slow down the polymerization reaction, and the MMA-based repair material was obtained.MMA is used as the main raw material, BPO as the catalyst, DBP as the plasticizer, and PCE as the shrinkage agent to modify the repair material. The preparation process is as follows.2.Preparation of the MMA-based penetrating repair materialsThe configured prepolymer was added with a certain amount of DMA and stirred for 2 min at 300 r/min.After an average of 60 min, diluent was added and stirred at 300 r/min for 3 min to obtain permeable repair material.Infiltration-type repair materials penetrate a certain depth of concrete surface by self-weight. In order to ensure good infiltration performance of the repair materials, thinner is used to reduce the viscosity of the repair materials, and DMA is used to promote curing to prepare the penetrating repair materials. The preparation process is as follows.A number of 100 × 100 × 100 mm concrete specimens were prepared and placed in a laboratory with a temperature of (20 ± 2) °C and a relative humidity of (65 ± 5)% for 28 days. The cured specimens adopt the single-side freeze–thaw method according to the long-term performance and durability test method of ordinary concrete (GBT50082-2009) so that the infiltration surface of the repaired material is closer to the damaged concrete with surface defects. The specific specimen is shown in The initial viscosity of the repair material has a great influence on the infiltration performance. The smaller the viscosity of the repair material, the stronger its fluidity. In this study, the NDJ-1 rotary viscometer  was used to measure the viscosity of the repair material. The viscometer equipment is shown in The surface-drying time is determined according to the provisions of GB/T 1728-2020 method B (refers to trigger), and the surface of the coating film is considered dry when no paint adheres to the finger after touching the surface of the coating film. The through-drying time is determined according to the provisions of GB/T 1728-2020 in method C (blade method), and the coating film is considered dry by cutting and scraping the coating film on the template with a blade and observing that there is no adhesion phenomenon in the bottom layer and film.Film forming thickness is an important index to evaluate the surface properties of the tunnel. The thinner the film thickness is, the less influence it has on the original excellent friction property of the concrete surface. In this study, a laser confocal microscope  was used to observe a section of the concrete specimen after 6 h, 24 h, and 3 d of curing of the coated repair material at 25 °C. The equipment is shown in The infiltration performance of the repair material is evaluated by measuring the infiltration depth. A 100 × 100 × 100 mm concrete specimen is used, and the concrete surface is first cleaned of floating ash before applying the repair material. The repair material is applied three times with a 10-min interval between each application. The repaired specimen is then cured at room temperature for 3 d. The concrete block is cut, and the infiltration of the solidified repair material is observed from the cut surface. Three points with relatively uniform infiltration are selected, and the infiltration depth at each point is observed. The average of the infiltration depths at the three points is taken as the final infiltration depth of the repair material on the surface of the concrete.Using P·O 42.5 cement, mortar specimens with dimensions of 40 × 40 × 160 mm were prepared. The specimens were cured under standard conditions (temperature of (20 ± 2) °C and relative humidity of 95%) for 28 d. After curing, the specimens were placed in a drying oven at 105 °C for 6 h to serve as the dry interface specimens for bond strength testing. The specimens that had completed standard curing were used as the wet interface specimens for bond strength testing. The mortar flexural strength testing machine was used to break the specimens, and according to the Japanese standard JISA6024-1998, a gap of 3~5 mm was left between the two broken sections of the specimen and fixed in place. MMA prepolymer was then injected into the gap [The freeze–thaw cycle test after concrete repair can reflect the performance of the repaired material in an environment of large temperature difference . AccordiThe calculation and treatment of test results comply with the following provisions:The mass of crushed concrete debris on the surface of the specimen 2); After N freeze–thaw cycles, the total mass of detached particles per unit testing surface area of an individual specimen is calculated using Equation (2).The arithmetic mean value of the total spalling mass per unit area of each group of specimens was taken as the measurement value of the total spalling mass A JSM-IT200 scanning electron microscope  was used to observe the high-resolution microstructure of cement mortar. The equipment is shown in In this study, a curing agent was mainly added to accelerate the curing of repair materials. Therefore, the content of the curing agent has a great impact on the properties of the repair materials. In order to obtain the best preparation technology for infiltration consolidation repair materials, the average viscosity at 60 min, surface drying time, and tensile strength were used as evaluation indexes. The experiment investigated the addition of 0.3%, 0.5%, 0.7%, and 1% of the curing agent to the prepolymer with the proportion of MMA 60, BPO 1.5%, DBP 30%, and PCE 10%.The initial viscosity of the repair material is an important factor affecting the repair effect. Using the average viscosity after 60 min of adding the curing agent as the evaluation index, As shown in The drying time of the repair material directly affects the work performance and can also greatly shorten the construction period. The prepolymer is applied to the template and cured at 25 °C. The drying time and actual drying time of the repair material were discussed, and the effect of different curing agent dosages on the drying time and actual drying time of the material was analyzed, as shown in From After filling the cracks with prepolymers containing 0.3%, 0.5%, 0.7%, and 1% mass fraction of the curing agent using the bonding strength test method described in 2.4.7, the repaired specimens were cured for a certain period of time and then subjected to a flexural strength test. The location of the fracture surface was observed, and the average flexural strength of three specimens for each dosage was taken as the final result of the bonding strength of the repair material, which was compared with the strength of mortar when broken. The test results are shown in It can be seen from The comparison of the bond strength of the repair material on the dry and wet interfaces shows that the bond strength on the wet interface is reduced by 3.8 to 29.9% compared to that on the dry interface. This indicates that the surface moisture of concrete directly affects the repair effect of the MMA-based repair materials. The presence of surface moisture affects the degree of curing of the material at the interface and reduces the roughness of the concrete interface, resulting in a decrease in the adhesion of the repair material to the concrete and a decrease in the bond strength. In contrast, on the dry interface, the penetrating repair material can penetrate the concrete to a certain depth, and the acrylic resin molecules can wrap and anchor the concrete, thereby enhancing the mechanical strength of the concrete to a certain extent .Based on the optimal preparation process of MMA-based repair materials determined in To determine the trend of permeability of the MMA-based repair materials under different diluents, the effect of diluent type and content on the permeability of the repair materials was analyzed based on the determined optimal preparation process. The results are shown in As shown in In order to elucidate the effect of the three diluents on the film thickness of the repaired concrete surface, blank samples and infiltrated solidified repair materials with different proportions were prepared. The film thickness of the repair material on the concrete surface was measured using laser confocal microscopy at 6 h, 24 h, and 72 h after preparation. The samples that were not completely cured and those that were fully cured were compared. The results are shown in From The influence of the freeze–thaw cycles on the repaired concrete was investigated. By simulating temperature changes, the protective effect of the repair materials on the concrete was tested. The final results were converted into the amount of peeling per square meter as the evaluation standard for the concrete’s resistance to the freeze–thaw cycles. The results are shown in As shown in Samples W10, E10, and A10 were applied to the surface of the concrete and cured for 28 days under natural conditions. Samples were taken from the surface of the broken parts and observed under SEM to investigate the bonding between the repair materials and cement paste. The results are shown in In general, the optimum amount of curing agent is determined by adjusting the content of the curing agent. Then, by adding diluent, the repair material has good infiltration performance and can be consolidated in a certain depth of concrete surface, forming a “rooted type” filling so that the mechanical strength and durability of the concrete surface can be improved.It was found that the 60-min average viscosity of the repair material increased first and then decreased as the content of DMA added was 0.3%, 0.5%, 0.7%, and 1%. When the reaction time reached 40–60 min, the viscosity of the system increased significantly. The viscosity of the repair material with 1% DMA content reached 284 mPa·s at 60 min, which was 46.12% higher than that of 0.3% DMA on average. Considering the controllability of viscosity and the prevention of explosion, DMA content in the range of 0.3–0.5% is more suitable.After conducting surface-drying time, through-drying time, and bonding strength tests, it was found that the surface-drying time and through-drying time of the repair material with 1% DMA content were 0.8 h and 1.5 h, respectively, which were 60% and 67% shorter than those of the repair material with 0.3% DMA content. However, excessive addition of the curing agent can lead to a sharp increase in the reaction of the repair material, resulting in the formation of tiny bubbles. When the curing agent content was 0.5%, the bonding strength reached its peak, with values of 10.99 MPa and 9.24 MPa at the dry interface and wet interface, respectively. Therefore, the optimal curing agent content was determined to be 0.5%.A comparison study of three different diluents showed that sample E10 had a penetration depth of 24 mm and a film thickness of only 35 µm after 72 h. After the freeze–thaw cycling test, E10 showed the best protective performance for concrete, with an average peeling strength of only 1704.4 g/m². SEM showed that the polymer formed a tightly interwoven protective film on the surface of the cement paste, effectively preventing the ingress of corrosive substances.


The developing system was chloroform: methanol: formic acid: ammonia . Desnitometric analysis in UV absorbance mode was set at λ = 275 nm. While, fluorescence mode was performed with excitation at 260 nm for quantitative simultaneous determination of IVA and MET using optical filter K320. The retention factors values were 0.45 ± 0.05 and 0.89 ± 0.01 of IVA and MET, respectively. UV absorbance mode, linearity was 50.0–600.0 ng/band for IVA and 50.0–900.0 ng/band for MET. For fluorescence mode, the linearity ranges were 18.0–400.0 ng/band and 50.0–550.0 ng/band for IVA and MET; respectively. ICH guidelines were followed in respect to linearity and range, accuracy, precision and selectivity, limit of detection (LOD), limit of quantitation (LOQ) and robustness. The analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness metric tools were used to assess the suggested method. The quantitative proposed method results showed there was no statistically significant difference at 95% confidence when compared to the reported method of high performance liquid chromatography (HPLC).New, simple, accurate, sensitive and validated high performance thin layer chromatographic (HPTLC) method coupled with UV absorbance mode and fluorescence (FL) detectors which were used for simultaneous determination of ivabradine (IVA) and metoprolol (MET) in their bulk and pharmaceutical dosage form using TLC silica 60 F Moreover, the association between the log (1/retention factor) values, molecular polarizabilities of solvents and thermodynamic dependence were studied to analyze the effect of the electrostatic interaction to notice if there is influence on retention factor of ivabradine [Angina is described as chest pain or discomfort that frequently worsens with physical activity or stress and during an episode of angina the patient may experience shortness of breath, fatigue, nausea and dizziness. Myocardial oxygen demand and supply are typically imbalanced that happen in angina. The angina can caused by atherosclerosis, coronary heart disease (CHD), and microvascular dysfunction (MVD) . Ivabradabradine , 18. It ® tablets (Batch No.B08940622) labeled to contain 5 mg ivabradine were bought from local market. Seloken Zoc 25 mg® tablets (Batch No.200277) labeled to contain 25 mg metoprolol tartrate were obtained from local market. Seloken Zoc 50 mg® tablets (Batch No.200025) labeled to contain 50 mg metoprolol tartrate were bought from local market.Ivabradine hydrochloride (IVA) pure sample with 99.90% purity of raw material was donated from the national organization for drug control and research (NODCAR).Metoprolol tartrate (MET) standard was bought from Sigma Aldrich Co., Cairo, Egypt. The purity of MET was provided by company to be 99.90%.Bradipect 5 mgHPLC grade chloroform, methanol and formic acid from Fisher Scientific  were used. Ammonia solution was obtained from E. Merck .254 plates . Samples were applied by using CAMAG Linomat 5 auto-sampler with CAMAG microliter syringe (100.0 μL); . Samples were spotted in the form of bands 4 mm width, 10.0 mm from the bottom, 10.0 mm from the edge and 10.0 mm apart using a nitrogen aspirator. The plates were developed using a CAMAG twin trough glass chamber for 10.0 min. The migration distance was 80 mm. The chamber was saturated with mobile phase that consists of chloroform: methanol: formic acid: ammonia  at ambient temperature for 30.0 min. Furthermore, the plates were dried at room temperature. A CAMAG TLC scanner 3 with winCATS® software program was used for scanning and densitometric analysis of the development plates. The slit dimension was (3.0 × 0.45 mm) with reflectance measurement and scanning speed at 20.0 mm/s. Two detectors were used. The First one was for detecting the absorbance mode at 275 nm, deuterium lamp was used as a source of radiation for scanning TLC plates. The second one was for fluorescence detection, mercury (Hg) lamp was used for measuring the intensity of emitted light of IVA and MET after excitation at 260 nm using optical filter K320. For using fluorescence detector, the same instrument and conditions were applied except HPTLC plates were non-fluorescence plates by exposing to hydrochloric acid vapor. Elmasonic S 60 H water bath sonicator (Germany) was used for mixing the solutions in pharmaceutical preparation.The chromatographic separation has been achieved on HPTLC silica 60 FStock solutions of IVA and MET 1.0 mg/mL were prepared separately by weighing 100.0 mg powder of each cited drug, then transferred each one separately into 100.0 mL volumetric flasks. The final volumes were completed with methanol. 10.0 mL of IVA and MET stock solutions were transferred separately into 100.0 mL volumetric flasks. The volume was completed to the mark with methanol to prepare working solutions of IVA and MET with final concentrations of 100.0 μg/mL.254 plates were developed under prior chromatographic conditions that mentioned in Sect. “Various volumes from the working solutions of IVA and MET  of IVA and,  of MET were spotted on TLC plates using CAMAG Linomat 5 auto-sampler with CAMAG microliter syringe (100.0 μL) to give final concentrations  of IVA and  of MET. The HPTLC silica 60 FVarious mixtures including different ratios of IVA and MET were prepared from their working solutions 100.0 μg/mL. Mixtures were spotted on plates and developed under previously mentioned Sect. “® tablets labelled to contain 5 mg of IVA and Seloken Zoc 25 mg® tablets labelled to contain 25 mg of MET. Five tablets of Bradipect and Seloken Zoc were separately accurately weighed and grinded into fine powder. To simulate one tablet, an equivalent weight of 5 mg of IVA and 25 mg of MET were weighed separately from each tablet powder and transferred to 50.0 mL beaker where 50.0 mL of methanol was added. The solution was sonicated for 30.0 min and transferred to 100.0 mL volumetric flask. The volume was completed with methanol. The solution was filtered with 0.22 μm syringe filter. The final sample stock concentration was 50.0 μg/mL of IVA and 250.0 μg/mL of MET. Different volumes of sample stock of IVA and MET  were spotted on silica 60 F254 TLC plates to obtain concentrations  of IVA accompanied with  of MET. The plates were scanned using TLC scanner absorbance mode at 275 nm. For fluorescence detection, volumes of sample stock of IVA and MET  were spotted on TLC plates to obtain concentrations  of IVA accompanied with  of MET. The non-fluorescence plates development and scanning was carried out as mentioned under Sect. “® tablets labelled to contain 5 mg of IVA and Seloken Zoc 50 mg® tablets labelled to contain 50 mg of MET which recommended to be co-administrated for antianginal patients. The prepared sample stock concentration was 50.0 μg/mL of IVA and 500.0μg/mL of MET. Accurate volumes  were applied on TLC plates to obtain final concentrations  of IVA with their corresponding  of MET. The developed on silica 60 F254 TLC plates which UV absorbance mode were scanned at 275 nm. For fluorescence detection, volumes of sample stock of IVA and MET  were spotted on non-fluorescence TLC plates to obtain concentrations  of IVA accompanied with  of MET. The peak areas of the of corresponding concentrations were scanned using fluorescence detector of TLC scanner. The found concentrations were calculated from their regression equations, respectively. % Recoveries and standard deviation were calculated.IVA and MET (5/25 mg) combined dosage form was not available in the local market. So, synthetic tablets of mixture simulating through combining Bradipect 5 mg.The main advantage of HPTLC is the less consumption of the mobile phase and large sample capacity that can be applied on one TLC plate which leads to shorter time of analysis and cost-effectiveness . Moreove1The consecutive parameters need to be optimized in order to get good separation, symmetric sharp peaks, and acceptable retention factors for the cited drugs.v/v), toluene: ethyl acetate: methanol: trimethylamine , toluene: propanol: methanol: trimethylamine , ethyl acetate: methanol  and chloroform: methanol: ethyl acetate: formic acid . The optimum mobile phase system composition showing the best resolution and separation of two cited drugs was chloroform: methanol: formic acid: ammonia . Formic acid was used to reduce peak tailing of the drugs. The Rf values were 0.45 ± 0.05 and 0.89 ± 0.01 for IVA and MET, respectively as shown in Fig. 2.Several trials of mobile phases have been applied that composed of dichloromethane: methanol  and cut off filters (K320 and K400) were tested. But, all of them gave bad resolution and asymmetric peaks. The optimum excitation wavelength was 260 nm with using K320 cut off filter which gave sharp symmetric peaks and high fluorescence intensity for quantitative determination of IVA and MET.The optimum slit dimensions of scanning light beam of bands on TLC plates were (3.0 × 0.45 mm) which gave maximum sensitivity of the two cited drugs and good selectivity.The same degree of vapor saturation should be used each time where the plate is developed in order to get reproducible results . SeveralTo prevent the mobile phase evaporation from the plate edges and achieve a uniform movement of the analytes in the stationary phase , 80 mm w.The proposed method had been validated according to international conference on harmonization ICH guidelines regarding to linearity and range, accuracy, precision, selectivity, limit of detection (LOD) and limit of quantitation (LOQ) and robustness . The res2.A linear relationship was obtained between peak areas and their corresponding concentrations in range of (50.0–600.0 ng/band) and (50.0–900.0 ng/band) for IVA and MET, respectively. After the development of TLC silica gel plates 60 F254 under the previously mentioned chromatographic conditions and scanned using UV absorbance mode. The linearity was (18.0–400.0 ng/band) and (50.0–550.0 ng/band) for IVA and MET after using fluorescence mode, respectively, as presented in Table 2.For absorbance mode,  of IVA and  of MET were chosen to assess the accuracy of the proposed method. For fluorescence mode,  of IVA and  of MET were selected to test the accuracy of the proposed method. % Recoveries of three levels of chosen standard solutions of IVA and MET in triplicates were calculated. The results are represented in Table 3Intraday and interday precision were assessed. The intraday precision was tested through the determination of three concentrations level of the two cited drugs on the same day. The interday precision examined by analyzing three concentrations level on the three consecutive days. The calculated % RSD Values were less than 2 which indicate the proposed method has a good precision. As shown in Table , Figs. The peak purity of IVA and MET were tested. The developed plate was scanned through TLC scanner and absorption spectrum was recorded at different points throughout each peak. The correlation coefficient between the spectra recorded at peak start and peak maximum was 0.9998. The peak maximum and peak end spectra's correlation coefficient was 0.9997 which attained high values. The purity of peaks was obtained from the mathematic analysis of the software as shown in Fig. 5LOD is the lowest concentration can be detected. However, LOQ is the lowest concentration can be accurately quantified. They are computed according the following equations. LOD = 3.3 σ/S and LOQ = 10 σ /S. Where, σ is the calculated standard deviation of y-intercept and S is the slope from the attained calibration curves. The results are shown in Table Robustness was examined by exhibiting that the system is unaffected after deliberately variations of some chromatographic conditions. Some variations were applied as saturation time (± 5 min) and migration distance (± 5 mm). The peak under area of each experimental parameter was used in calculation of the percentage recoveries and relative standard deviations (%RSD). The % RSD values were less than 2 which indicates the good robustness of the proposed method. The results are reported in Table . The satisfactory percentage recoveries were proved that these method can be used for the routine analysis in determination of two studied drugs. As represented in Figs. 9.The method was applied for determination of IVA and MET in the simulated simulated combined dosage form. The results are shown in Table 7Table , sample collection and transport in the first pentagram have red color. As a result of distancing between production and quality control department in the pharmaceutical industry [The suggested methods were assessed by using three greenness tools. First one, the analytical eco-scale was used for determination the greenness of the method by calculating analytical eco-scale total score; more than 75% which corresponding to excellent green analysis, more than 50% representing acceptable green analysis and less than 50% that meaning inadequate green analysis, as displayed in Table 10industry .The suggindustry .Table 9TA new, rapid and sensitive suggested HPTLC method coupled with UV absorbance mode and fluorescence detectors were used for simultaneous estimation of IVA and MET in bulk and pharmaceutical preparations. The suggested method revealed advantage over the reported HPLC method as discussed in statistical analysis. The developed method has been validated as stated in ICH guidelines. The analytical Eco-scale, green analytical procedure index (GAPI) and analytical greenness metric were applied to evaluate our suggested method. The method is considered simple and do not need sophisticated sample treatment. The studied method could be routinely used for quantitative determination of the two cited drugs in quality control laboratories.