Gestão antimicrobiana, also known as antimicrobial stewardship, is a coordinated set of interventions designed to promote the rational and optimal use of antimicrobial agents such as antibiotics, antivirals, and antifungals. Its primary goal is to combat the growing global threat of antimicrobial resistance (AMR), which arises largely from the misuse and overuse of these drugs in human, animal, and environmental health sectors. This approach relies on a multidisciplinary team including infectious disease specialists, pharmacists, microbiologists, and nurses to ensure appropriate selection, dosing, duration, and route of administration. The strategy is supported by national and international frameworks such as the Pan American Health Organization (PAHO), the World Health Organization (WHO), and Brazil’s Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos (PAN-BR), which aligns with the One Health approach. Key components include the implementation of clinical protocols, continuous monitoring of antimicrobial consumption through indicators like Defined Daily Dose (DDD) and Days of Therapy (DOT), and integration with infection prevention and control (IPC) programs. Advanced diagnostic tools such as antimicrobial susceptibility testing and molecular diagnostics (e.g., PCR for carbapenemase genes) enable targeted therapy and reduce empirical broad-spectrum use. The success of these programs is evident in improved patient outcomes, reduced hospital stays, lower healthcare costs, and decreased incidence of multidrug-resistant infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE). Institutions like the Agência Nacional de Vigilância Sanitária (ANVISA) and the Fundação Oswaldo Cruz (Fiocruz) play pivotal roles in guiding policy, surveillance, and capacity-building across the Sistema Único de Saúde (SUS). [1] [2]

Definition and Objectives of Antimicrobial Stewardship

Antimicrobial stewardship, known in Portuguese as gestão antimicrobiana, refers to a coordinated set of actions aimed at ensuring the rational and efficient use of antimicrobial agents such as antibiotics, antivirals, and antifungals. Its primary goal is to combat the growing threat of antimicrobial resistance (AMR), a major global public health challenge driven largely by the misuse and overuse of these drugs across human, animal, and environmental health sectors. By promoting the appropriate selection, dosing, duration, and route of antimicrobial administration, stewardship programs enhance patient safety, improve clinical outcomes, and preserve the effectiveness of existing antimicrobial therapies [1].

Core Definition and Public Health Rationale

Antimicrobial stewardship is fundamentally defined as a systematic approach to optimizing antimicrobial therapy through evidence-based interventions. It involves ensuring that antimicrobials are used only when necessary, at the correct dose, via the appropriate route, and for the shortest effective duration. This practice is critical in reducing selective pressure on microbial populations, which otherwise accelerates the emergence and spread of resistant strains. The core rationale for antimicrobial stewardship in public health lies in its ability to curb the development of multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE), which are associated with higher mortality, prolonged hospital stays, and increased healthcare costs [1].

The inappropriate use of antimicrobials—such as unnecessary prescriptions, incorrect dosing, or excessively long treatment durations—fuels the selection of resistant microbes. Stewardship programs directly address these issues by implementing structured protocols and monitoring systems to guide clinical decision-making. In hospital settings, particularly in high-risk areas like intensive care units (ICUs), stewardship is essential due to the high frequency of antimicrobial use and the prevalence of severe infections [5].

Primary Objectives of Antimicrobial Stewardship

The principal objective of antimicrobial stewardship is the prevention and control of antimicrobial resistance. This overarching goal is supported by several specific aims designed to enhance patient care and public health outcomes:

  1. Improving Patient Outcomes: By ensuring that patients receive the most effective antimicrobial therapy based on clinical and microbiological data, stewardship reduces treatment failures, complications, and mortality. Targeted therapy also minimizes adverse drug reactions and the risk of secondary infections such as Clostridioides difficile [6].

  2. Promoting Patient Safety: Stewardship enhances safety by reducing exposure to unnecessary or inappropriate antimicrobials. This includes avoiding the use of broad-spectrum agents when narrow-spectrum alternatives are effective, thereby preserving the patient’s microbiome and reducing the risk of resistance development [7].

  3. Reducing Healthcare Costs: Inappropriate antimicrobial use increases hospitalization duration and the need for more expensive, last-resort drugs. Stewardship programs have been shown to lower antimicrobial consumption, shorten hospital stays, and decrease overall treatment costs [8].

  4. Supporting Infection Prevention and Control (IPC): Stewardship is intrinsically linked to IPC strategies. By minimizing the emergence and transmission of resistant organisms, it complements measures such as hand hygiene, isolation protocols, and environmental cleaning. This synergy is essential for effective containment of healthcare-associated infections (HAIs) [9].

  5. Preserving Antimicrobial Efficacy: A long-term objective is to extend the useful lifespan of existing antimicrobials. This requires a sustainable approach that balances immediate therapeutic needs with the future availability of effective treatments, ensuring access for future generations [10].

Integration with National and Global Frameworks

Antimicrobial stewardship is embedded within broader national and international public health strategies. In Brazil, the approach is aligned with the One Health model, which integrates human, animal, and environmental health to address AMR comprehensively. This intersectoral collaboration is formalized in the Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos no Âmbito da Saúde Única (PAN-BR), a national action plan that guides policy, surveillance, and intervention efforts across sectors [2].

The Brazilian Ministry of Health, in coordination with the Agência Nacional de Vigilância Sanitária (ANVISA), has issued key regulatory documents such as the Diretriz Nacional de Gerenciamento de Antimicrobianos, revised in 2023, which provides technical guidance for implementing stewardship programs in healthcare facilities. These frameworks emphasize the need for institutional leadership, multidisciplinary teamwork, and continuous monitoring of antimicrobial use and resistance patterns [12].

Globally, stewardship is supported by organizations such as the World Health Organization (WHO) and the Pan American Health Organization (PAHO), which advocate for standardized practices and capacity-building to combat AMR. These international efforts reinforce the importance of stewardship as a cornerstone of global health security and sustainable healthcare systems [10].

Core Components of Antimicrobial Stewardship Programs

Antimicrobial stewardship programs (ASPs) are structured initiatives designed to optimize the use of antimicrobial agents, minimize the development of antimicrobial resistance, and improve patient outcomes. These programs are essential in healthcare settings, particularly in high-risk areas such as intensive care units (ICUs), where antimicrobial use is frequent and complex. The effectiveness of an ASP relies on the integration of several core components, each contributing to a coordinated, evidence-based approach to antimicrobial management. These components are supported by national and international guidelines, including those from the World Health Organization (WHO) and the Agência Nacional de Vigilância Sanitária (ANVISA), and are aligned with the One Health framework that integrates human, animal, and environmental health [14].

Multidisciplinary Team Leadership and Institutional Commitment

A foundational element of any successful antimicrobial stewardship program is the establishment of a multidisciplinary team composed of key healthcare professionals. This team typically includes infectious disease specialists, pharmacists, microbiologists, nurses, and epidemiologists. The collaboration among these professionals ensures comprehensive oversight of antimicrobial use and facilitates timely interventions. The pharmacist, particularly the clinical pharmacist, plays a strategic role in reviewing prescriptions, adjusting dosages, and monitoring therapy [15]. The team is often coordinated through the Comissão de Controlo de Infecção Hospitalar (CCIH), which is mandated by Brazilian legislation and central to integrating infection control with antimicrobial use [16].

Institutional leadership and administrative support are equally critical. The success of an ASP depends on the commitment of hospital management to provide the necessary human, technological, and financial resources. This includes formalizing the program with clear objectives, integrating it into broader patient safety initiatives, and ensuring that policies are consistently implemented across departments [12].

Monitoring and Evaluation of Antimicrobial Use

Continuous monitoring of antimicrobial consumption is a cornerstone of stewardship. Programs must collect and analyze data on the types, doses, durations, and clinical indications of antimicrobial use. Key metrics include the Defined Daily Dose (DDD) and Days of Therapy (DOT), which allow for standardized comparisons across institutions and over time [18]. These indicators help identify patterns of inappropriate use, such as prolonged therapy or overuse of broad-spectrum agents, and guide corrective actions [19]. The analysis of such data is essential for evaluating the impact of stewardship interventions and for reporting to regulatory bodies like ANVISA [14].

Interventions to Optimize Antimicrobial Prescribing

Active interventions are implemented to ensure that antimicrobial therapy is appropriate and evidence-based. These include the review and adjustment of prescriptions, such as de-escalation from broad-spectrum to targeted therapy, discontinuation of unnecessary treatment, and optimization of dosing regimens. Prescribing should be guided by antimicrobial susceptibility testing and clinical guidelines, with empirical therapy adjusted as soon as microbiological results are available [21]. In critical care, principles of pharmacokinetics and pharmacodynamics (PK/PD) are applied to tailor therapy, especially in patients with organ dysfunction [22].

Education and Training of Healthcare Professionals

Ongoing education is vital to changing prescribing behaviors and promoting adherence to stewardship principles. Training programs for physicians, nurses, and pharmacists cover topics such as the appropriate use of antimicrobials, the mechanisms of resistance, and the interpretation of microbiological data. Institutions like the Fundação Oswaldo Cruz (Fiocruz) and the Instituto Racine offer specialized courses in antimicrobial stewardship and infectious disease management [23], [24]. Educational initiatives also target the broader healthcare team, reinforcing a culture of responsible antimicrobial use and patient safety [25].

Surveillance of Infections and Antimicrobial Resistance

Effective stewardship requires robust surveillance of both healthcare-associated infections and antimicrobial resistance patterns. This includes monitoring for multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and carbapenem-resistant Enterobacterales (CRE) [26]. Data from surveillance systems inform local treatment guidelines and help detect outbreaks early. The integration of laboratory data with clinical information enables rapid response and the adjustment of empirical therapy to reflect local resistance trends [14].

Performance Indicators and Program Evaluation

To measure the impact of stewardship efforts, programs must establish clear performance indicators. These include reductions in the use of broad-spectrum antimicrobials, decreases in the incidence of healthcare-associated infections, lower rates of antimicrobial resistance, and improvements in clinical outcomes such as mortality and length of hospital stay [28]. Regular evaluation using these metrics allows programs to demonstrate their value, secure ongoing support, and refine their strategies based on real-world data.

Integration with Infection Prevention and Control

Antimicrobial stewardship is inherently linked to infection prevention and control (IPC) strategies. While stewardship focuses on optimizing drug use, IPC measures such as hand hygiene, environmental cleaning, and patient isolation work to prevent the transmission of resistant organisms [9]. The synergy between these two domains is critical for reducing the overall burden of antimicrobial resistance. Joint efforts by the stewardship team and the CCIH ensure a comprehensive approach to patient safety and the preservation of antimicrobial efficacy [14].

Role of Multidisciplinary Teams in Antimicrobial Management

The success of antimicrobial stewardship programs hinges on the coordinated efforts of a multidisciplinary team, integrating diverse expertise to ensure the rational and effective use of antimicrobial agents. This collaborative approach is essential for reducing antimicrobial resistance (AMR), improving patient outcomes, and enhancing safety across healthcare settings. The team functions as the operational core of antimicrobial management, implementing evidence-based strategies and fostering a culture of accountability and continuous improvement.

Composition and Roles of Key Team Members

A well-structured antimicrobial stewardship team comprises professionals from various disciplines, each contributing specialized knowledge and skills. The primary members include:

  • infectious disease specialists: Often serving as leaders or key consultants, they provide expert guidance on the diagnosis and management of complex infections. They play a critical role in developing institutional clinical guidelines, interpreting microbiological data, and advising on the most appropriate antimicrobial selection based on clinical and epidemiological context [31]. Their involvement is crucial for the stewardship of high-risk antimicrobials and for managing infections caused by multidrug-resistant organisms (MDROs) such as carbapenem-resistant Enterobacterales (CRE).

  • pharmacists: Clinical pharmacists, particularly those specialized in infectious diseases, are pivotal in the day-to-day operations of stewardship programs. They conduct active reviews of antimicrobial prescriptions, identify and intervene on dosing errors, recommend adjustments for patients with organ dysfunction (e.g., insufficient renal function), and promote practices like therapeutic drug monitoring (TDM) for drugs with narrow therapeutic windows, such as vancomycin and aminoglycosides [15]. Their role in therapeutic de-escalation—switching from broad-spectrum to targeted therapy—is a key strategy for reducing selective pressure and preventing resistance.

  • microbiologists: These experts are central to the diagnostic process, performing and interpreting antimicrobial susceptibility testing (AST) to generate accurate antibiograms. They contribute to the standardization of testing methods through participation in committees like the Comitê Brasileiro de Testes de Sensibilidade (BrCAST), which aligns Brazilian practices with international standards [33]. The rapid identification of resistance mechanisms, such as carbapenemase genes (e.g., blaKPC), using molecular diagnostics like PCR, enables timely clinical decisions and outbreak control.

  • nurses: Nurses are essential for ensuring adherence to protocols at the bedside, including the correct administration of antimicrobials and adherence to infection prevention and control (IPC) measures. Their role has expanded with the authorization for nurse prescribing in certain clinical situations, allowing them to take a more active role in antimicrobial management and patient education [34].

  • Other professionals: The team may also include epidemiologists for data analysis, healthcare administrators to provide institutional support and resources, and infection control practitioners who bridge stewardship with IPC efforts. This broad representation ensures a comprehensive approach to combating AMR.

Core Functions and Collaborative Interventions

The multidisciplinary team executes a range of functions that are interdependent and synergistic. Their collaborative interventions are designed to optimize antimicrobial use at every stage of patient care.

  • Prescription Review and Intervention: A cornerstone of stewardship is the systematic review of antimicrobial prescriptions. The team, often led by a pharmacist or infectious disease specialist, audits patient records to assess the appropriateness of the agent, dose, duration, and indication. Interventions may include suggesting a switch to a more targeted agent, adjusting the dose based on pharmacokinetics and pharmacodynamics (PK/PD) principles, or discontinuing therapy when no longer indicated. This process, known as "audit and feedback," has been shown to reduce unnecessary antimicrobial use and improve patient safety [8].

  • Protocol Development and Implementation: The team develops and maintains institutional protocols for common infections, such as sepsis or urinary tract infections, which are based on local resistance patterns and national guidelines. These protocols standardize care, reduce practice variation, and support clinicians in making evidence-based decisions. For example, a protocol might guide the initial empirical therapy for a patient with suspected Gram-negative infection, which can then be de-escalated once microbiological results are available [36].

  • Education and Capacity Building: Continuous education is a vital function. The team organizes training sessions, workshops, and case discussions to update healthcare professionals on the latest evidence, resistance trends, and stewardship principles. This educational role is crucial for changing prescribing behaviors and fostering a culture of responsible antimicrobial use. Institutions like the Fundação Oswaldo Cruz (Fiocruz) offer specialized courses to support this ongoing learning [23].

  • Integration with Infection Control: The team works closely with the Comissão de Controle de Infecção Hospitalar (CCIH) to create a unified strategy against MDROs. While stewardship focuses on optimizing drug use, IPC focuses on preventing transmission through measures like hand hygiene and patient isolation. Together, these strategies form a comprehensive defense against the spread of resistant pathogens [9].

Leadership and Institutional Support

The effectiveness of a multidisciplinary team is contingent upon strong institutional leadership and commitment. The support of hospital administration is critical for allocating the necessary human, technological, and financial resources. The team must be formally recognized, with clear roles, responsibilities, and authority to implement its recommendations. This institutional backing is often formalized through policies and integrated into the hospital's quality and safety initiatives, ensuring that antimicrobial stewardship is a sustained priority rather than a temporary project [12].

Impact on Patient Outcomes and Healthcare Systems

The collaborative work of the multidisciplinary team translates into tangible benefits. Studies have consistently shown that stewardship programs lead to a reduction in the use of broad-spectrum antimicrobials, a decrease in the incidence of MDROs and Clostridioides difficile infections, shorter hospital stays, and lower healthcare costs [6]. By ensuring that the right patient receives the right drug at the right dose for the right duration, the team directly contributes to improved clinical outcomes and enhanced patient safety. This collective effort is a cornerstone of modern healthcare, essential for preserving the efficacy of antimicrobials for future generations.

Integration with Infection Prevention and Control Strategies

The integration of antimicrobial stewardship with infection prevention and control (IPC) strategies is a cornerstone of effective healthcare systems aiming to combat the growing threat of antimicrobial resistance (AMR). These two approaches are not standalone initiatives but complementary and interdependent components of a unified strategy to enhance patient safety, reduce healthcare-associated infections (HAIs), and preserve the efficacy of antimicrobial agents. In the Brazilian context, this synergy is formalized through national policies and institutional frameworks that align stewardship efforts with IPC practices under the broader umbrella of the One Health approach.

Synergistic Relationship Between Stewardship and IPC

Antimicrobial stewardship and infection prevention and control operate on different but convergent fronts in the fight against resistant pathogens. While stewardship focuses on optimizing the use of antimicrobials—ensuring the right drug, dose, duration, and indication—IPC emphasizes preventing the transmission of infectious agents through measures such as hand hygiene, environmental disinfection, and isolation protocols. When used in isolation, each strategy has limitations; however, their integration creates a powerful feedback loop. Effective IPC reduces the incidence of infections, thereby decreasing the need for antimicrobial use. Conversely, prudent antimicrobial use, guided by stewardship principles, reduces the selection pressure that drives the emergence and spread of resistant organisms, making IPC measures more effective.

This synergy is particularly evident in high-risk settings such as intensive care units (ICUs), where the convergence of critically ill patients, invasive devices, and high antimicrobial consumption increases the risk of multidrug-resistant organism (MDRO) transmission. In these environments, coordinated actions between the infection control team and the stewardship team are essential. For example, the early detection of a patient colonized with a carbapenem-resistant Enterobacterales (CRE) triggers both IPC measures (contact isolation, cohorting) and stewardship interventions (review of antimicrobial prescriptions, avoidance of unnecessary broad-spectrum agents). This dual response not only protects other patients but also prevents the overuse of last-resort antibiotics like carbapenems and colistin.

Role of Multidisciplinary Teams in Integrated Efforts

The success of integrating stewardship with IPC relies heavily on the collaboration of a multidisciplinary team that includes infectious disease specialists, pharmacists, microbiologists, nurses, and epidemiologists. The Comissão de Controle de Infecção Hospitalar (CCIH), mandated by Brazilian regulation (Portaria MS nº 2616/1998), plays a central role in this integration. The CCIH is responsible for implementing and monitoring IPC protocols, but its effectiveness is amplified when it includes stewardship activities such as antimicrobial use audits and feedback to prescribers.

The pharmacist, particularly the clinical pharmacist, is a key figure in bridging stewardship and IPC. By reviewing prescriptions, suggesting de-escalation, and ensuring appropriate dosing, pharmacists directly influence antimicrobial consumption patterns. Their participation in CCIH meetings ensures that antimicrobial use data are considered alongside infection surveillance data, enabling a more holistic approach to patient safety. Similarly, microbiologists provide critical data through antimicrobial susceptibility testing and the detection of resistance mechanisms such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases, which inform both IPC containment strategies and stewardship decisions on empirical therapy.

Surveillance and Data Integration as a Foundation

A robust system of epidemiological surveillance is the foundation for integrating stewardship and IPC. The monitoring of healthcare-associated infections (HAIs) and resistance patterns provides real-time data that guide both sets of interventions. In Brazil, the Agência Nacional de Vigilância Sanitária (ANVISA) has established guidelines for the surveillance of infections and antimicrobial use, including the mandatory reporting of data on pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and CRE. This data is used to generate local antibiograms, which in turn inform the empirical use of antimicrobials and the prioritization of IPC efforts.

The integration of data systems is crucial for this process. When electronic health records are linked with laboratory information systems and pharmacy databases, it becomes possible to track a patient’s infection status, antimicrobial exposure, and microbiological results in real time. This interoperability enables automated alerts for potential stewardship interventions—such as switching from broad-spectrum to targeted therapy when culture results are available—and triggers IPC actions like isolation when a resistant organism is identified. The Programa Nacional de Prevenção e Controle de Infecções em Serviços de Saúde (PNPCIRAS), approved by ANVISA in 2026, emphasizes the importance of such integrated surveillance systems in improving the quality of care and patient safety.

Impact on Clinical and Public Health Outcomes

The integration of antimicrobial stewardship with IPC has demonstrated significant positive impacts on both clinical and public health outcomes. Studies have shown that hospitals with coordinated stewardship and IPC programs experience reductions in the incidence of HAIs, lower rates of antimicrobial resistance, shorter hospital stays, and decreased mortality. For example, the implementation of bundled interventions—such as the central line bundle combined with daily antimicrobial review—has been associated with a marked decline in bloodstream infections and the use of broad-spectrum antibiotics.

At the national level, Brazil’s Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos (PAN-BR) explicitly promotes the integration of stewardship and IPC as a strategic objective. This plan, aligned with recommendations from the World Health Organization (WHO) and the Pan American Health Organization (PAHO), recognizes that sustainable progress against AMR requires a systems approach that unites clinical, laboratory, and public health efforts. By fostering collaboration between the Sistema Único de Saúde (SUS), research institutions like the Fundação Oswaldo Cruz (Fiocruz), and regulatory bodies such as ANVISA, Brazil is building a resilient infrastructure to combat the silent pandemic of antimicrobial resistance.

Use of Clinical Guidelines and Local Resistance Patterns

The integration of clinical guidelines with local resistance patterns is a cornerstone of effective antimicrobial stewardship, ensuring that antimicrobial use is both evidence-based and tailored to the specific epidemiological context of a healthcare facility or region. This approach prevents the inappropriate use of broad-spectrum agents, reduces the selection pressure that drives antimicrobial resistance (AMR), and improves patient outcomes by aligning empirical therapy with the most likely pathogens and their susceptibility profiles. In Brazil, this strategy is supported by national frameworks such as the Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos (PAN-BR), which emphasizes the need for localized, data-driven interventions across the Sistema Único de Saúde (SUS) [2].

Adaptation of Clinical Guidelines to Local Epidemiology

Clinical guidelines, whether national or international, must be adapted to reflect local resistance patterns to remain clinically relevant. The rigid application of global recommendations, such as those from the Infectious Diseases Society of America (IDSA), without considering regional data can lead to therapeutic failure and increased mortality, particularly in areas with high prevalence of multidrug-resistant organisms. In Brazil, the Sociedade Brasileira de Infectologia (SBI) plays a critical role by publishing updated national guidelines that incorporate local epidemiological data. For instance, the 2025 SBI guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacteria recommend combination therapies involving carbapenems, colistin, aztreonam, or newer beta-lactams, depending on the local resistance profile [36]. This adaptation is essential in a country where pathogens such as Klebsiella pneumoniae carbapenemase (KPC)-producing strains and carbapenem-resistant Acinetobacter baumannii have become endemic in many hospitals [43].

The process of adapting guidelines is facilitated by programs such as the Programa Nacional de Prevenção e Controle de Infecções em Serviços de Saúde (PNPIC-IRAS), approved by Agência Nacional de Vigilância Sanitária (ANVISA), which establishes strategic surveillance of healthcare-associated infections (HAIs) and resistance. This program enables healthcare facilities to generate and utilize local antibiograms—summaries of microbial susceptibility patterns—for the development of institution-specific protocols [44]. These locally adapted protocols are instrumental in guiding empirical therapy, especially in critical situations like sepsis, where timely and appropriate antimicrobial administration is life-saving.

Role of Local Resistance Data in Guiding Empirical Therapy

Local resistance data are fundamental for optimizing empirical antimicrobial therapy, which is often initiated before the causative pathogen is identified. The use of such data allows clinicians to select agents with the highest probability of covering the most prevalent resistant pathogens in their setting. For example, in hospitals with a high incidence of methicillin-resistant Staphylococcus aureus (MRSA), empirical coverage with agents like vancomycin may be warranted, whereas in facilities with lower MRSA rates, narrower-spectrum alternatives may be appropriate. Similarly, in regions with widespread extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, the empirical use of cephalosporins may be ineffective, necessitating the use of carbapenems or other agents with reliable activity.

The generation of local resistance data relies on robust microbiological surveillance. The Comitê Brasileiro de Testes de Sensibilidade (BrCAST) provides national standards for antimicrobial susceptibility testing (AST), ensuring that results are accurate, comparable, and clinically interpretable [45]. These standardized AST results are used to create hospital-specific antibiograms, which are regularly reviewed and updated by hospital committees, such as the antimicrobial management committee, to inform and revise empirical treatment protocols. This dynamic process ensures that clinical practices evolve in response to changing resistance trends, thereby maintaining the effectiveness of antimicrobial therapy.

Integration of Diagnostic Tools and Stewardship Interventions

Advanced diagnostic tools, including molecular methods like polymerase chain reaction (PCR) for the detection of resistance genes (e.g., blaKPC, blaNDM), significantly enhance the ability to tailor antimicrobial therapy. These rapid tests allow for the early identification of resistance mechanisms, enabling the de-escalation of therapy from broad-spectrum to targeted agents or the initiation of appropriate last-resort treatments when necessary. The integration of these diagnostics with stewardship interventions, such as the "antibiotic time-out" — a structured reassessment of antimicrobial therapy after 48–72 hours — ensures that treatment remains aligned with microbiological findings and clinical response [46].

Furthermore, the use of clinical decision support systems, such as institutional treatment guides and electronic prescribing alerts, helps embed local guidelines and resistance data into daily clinical workflows. These tools can prompt clinicians to consider local resistance patterns when selecting empirical therapy and provide real-time feedback on the appropriateness of antimicrobial choices. The success of these interventions is evident in hospitals that have implemented structured stewardship programs, where reductions in the use of broad-spectrum antimicrobials, shorter durations of therapy, and lower rates of resistance have been documented [6].

In conclusion, the effective use of clinical guidelines in conjunction with local resistance patterns is a dynamic and essential component of antimicrobial stewardship. By adapting national and international recommendations to reflect local epidemiology, leveraging data from susceptibility testing and molecular diagnostics, and integrating this information into clinical decision-making, healthcare institutions can ensure that antimicrobial use is both rational and effective. This approach not only improves individual patient outcomes but also contributes to the broader public health goal of preserving the efficacy of antimicrobial agents for future generations.

Pharmacokinetics and Pharmacodynamics in Critical Care

The application of pharmacokinetics (PK) and pharmacodynamics (PD) is fundamental to the optimization of antimicrobial therapy in critically ill patients, where complex and dynamic physiological alterations significantly impact drug disposition and response. In intensive care units (ICUs), the success of antimicrobial treatment depends not only on selecting the appropriate agent but also on tailoring dosing regimens to overcome the unique challenges posed by critical illness. These principles are integral to antimicrobial stewardship efforts, ensuring that therapy is both effective and safe, thereby reducing the risk of treatment failure and the emergence of antimicrobial resistance [48].

Physiological Alterations in Critical Illness Affecting Pharmacokinetics

Critically ill patients exhibit profound physiological changes that disrupt the standard assumptions of drug absorption, distribution, metabolism, and excretion (ADME). These alterations necessitate a departure from fixed dosing strategies and demand individualized approaches. A key challenge is the expanded volume of distribution (Vd), particularly for hydrophilic antimicrobials such as β-lactams, vancomycin, and aminoglycosides. This expansion is caused by systemic capillary leak, aggressive fluid resuscitation, and generalized edema, leading to lower than expected plasma concentrations when standard doses are administered [49].

Another critical factor is the alteration in renal and hepatic clearance. While organ failure reduces the elimination of many drugs, requiring dose reductions, a paradoxical condition known as augmented renal clearance (ARC) is common in younger, septic patients. ARC results in the rapid removal of renally excreted antibiotics like piperacilina/tazobactam and meropenem, leading to subtherapeutic drug exposure and a high risk of treatment failure [50]. Furthermore, life-support technologies such as continuous renal replacement therapy (CRRT), hemodiafiltration, and extracorporeal membrane oxygenation (ECMO) can significantly alter drug pharmacokinetics by removing antimicrobials or changing their distribution, necessitating complex dose adjustments [51].

Key Pharmacodynamic Parameters and Dosing Strategies by Drug Class

The efficacy of antimicrobial therapy is best predicted by PK/PD indices, which describe the relationship between drug exposure and its antimicrobial effect. The choice of the optimal dosing strategy depends on the specific PK/PD characteristics of each antimicrobial class.

For β-lactam antibiotics (e.g., meropenem, piperacilina/tazobactam), efficacy is primarily time-dependent. The critical parameter is the time that free drug concentrations remain above the minimum inhibitory concentration (T > MIC) of the pathogen. For severe infections, the target is often to maintain free drug concentrations above the MIC for 100% of the dosing interval. To achieve this in critically ill patients with an expanded Vd and potential for ARC, strategies such as administering higher loading doses, increasing the frequency of administration, or using prolonged (3–4 hours) or continuous infusions are essential [52].

In contrast, aminoglycosides (e.g., amikacin) exhibit concentration-dependent killing and a significant post-antibiotic effect. Their efficacy is best predicted by the ratio of the peak serum concentration to the MIC (Cmax/CIM), with a target of >8–10. This characteristic makes once-daily dosing the preferred strategy in critical care, as it maximizes bactericidal activity while minimizing the risk of nephrotoxicity [53].

For glycopeptides like vancomycin, the most predictive PK/PD parameter for both efficacy and safety is the ratio of the area under the concentration-time curve over 24 hours to the MIC (AUC24/CIM), with a target of ≥400. Achieving this target is challenging in critically ill patients due to variable Vd and clearance. Subtherapeutic levels increase the risk of treatment failure and the development of resistance, while supratherapeutic levels are strongly associated with nephrotoxicity, highlighting the need for careful monitoring [54].

Therapeutic Drug Monitoring and Individualized Dosing

To overcome the high inter-individual variability in drug exposure in the ICU, therapeutic drug monitoring (TDM) is an indispensable tool. TDM involves measuring serum concentrations of antimicrobials with a narrow therapeutic index, such as vancomycin, aminoglycosides, and increasingly, β-lactams in severe infections, to guide dose adjustments [55]. This practice allows for the individualization of therapy based on the patient's actual pharmacokinetic profile, rather than relying on population averages.

Advanced methods, such as Bayesian pharmacokinetic modeling, are being used to predict optimal dosing regimens by incorporating patient-specific factors (e.g., weight, renal function) and sparse drug concentration measurements. This approach has proven highly effective in optimizing therapy for vulnerable populations, including pediatric and critically ill patients, ensuring that PK/PD targets are met [56]. The integration of TDM into antimicrobial stewardship programs is a key strategy for improving clinical outcomes and combating resistance [57].

Integration with Clinical Guidelines and Stewardship

The principles of PK/PD are now central to modern clinical guidelines for managing severe infections. International societies such as the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) emphasize the need for empiric therapy to be rapidly followed by de-escalation based on culture results and the use of PK/PD principles to optimize dosing in critically ill patients [58]. In the context of sepsis and septic shock, the timely administration of appropriately dosed antimicrobials, often involving high-dose, prolonged infusions, is critical for improving survival [59]. This scientific foundation ensures that antimicrobial therapy in critical care is not only empiric but also rational and evidence-based, aligning perfectly with the goals of stewardship to preserve the efficacy of these vital drugs for future generations.

Monitoring and Evaluation Using Antimicrobial Use Indicators

The monitoring and evaluation of antimicrobial use through standardized indicators are critical components of antimicrobial stewardship programs, enabling healthcare institutions to assess the effectiveness of interventions, identify inappropriate prescribing patterns, and guide policy decisions. These indicators provide objective, quantifiable data that reflect both the volume and quality of antimicrobial consumption, allowing for comparisons across units, institutions, and over time. In Brazil, the integration of these metrics into national frameworks such as those developed by the Agência Nacional de Vigilância Sanitária (ANVISA) ensures alignment with public health goals and supports the broader fight against antimicrobial resistance (AMR) [14]. The use of such indicators is particularly vital in high-risk settings like intensive care units (ICUs), where antimicrobial use is most intense and the risk of selecting for resistant pathogens is greatest.

Key Antimicrobial Use Indicators and Their Application

Several standardized indicators are employed to monitor antimicrobial consumption, each offering distinct insights into prescribing practices. The most widely used metric is the Defined Daily Dose (DDD), a measurement established by the World Health Organization (WHO) to quantify drug utilization. The DDD represents the assumed average maintenance dose per day for a drug used for its primary indication in adults [18]. In clinical settings, antimicrobial consumption is typically expressed as DDDs per 1,000 patient-days or per 100 admissions, facilitating benchmarking between hospitals and tracking trends over time [62]. While the DDD is invaluable for aggregated analysis, it has limitations, particularly in pediatric and neonatal populations where actual dosing often differs significantly from the adult-based DDD, necessitating the use of complementary indicators [63].

To address these limitations and provide a more patient-centered view of antimicrobial use, the Days of Therapy (DOT) and Length of Therapy (LOT) are essential. DOT measures the number of days a patient receives a specific antimicrobial, regardless of dose or frequency, offering a more accurate reflection of actual patient exposure than DDD [64]. LOT, on the other hand, specifically measures the total duration of an antimicrobial course, serving as a direct clinical indicator of prescribing quality. Monitoring LOT is crucial for identifying and reducing unnecessarily prolonged treatments, which are a major driver of AMR and increase the risk of adverse events like Clostridioides difficile infection [8]. Another important indicator is the Prescribed Daily Dose (PDD), which reflects the actual average daily dose prescribed in clinical practice, allowing for a comparison with the standardized DDD to assess adherence to dosing guidelines [64]. The integration of these indicators—DDD, DOT, LOT, and PDD—provides a comprehensive picture of antimicrobial use, combining population-level consumption data with individual patient-level treatment patterns.

Role of Indicators in Evaluating Stewardship Program Effectiveness

The primary value of antimicrobial use indicators lies in their ability to evaluate the impact of antimicrobial stewardship interventions. By establishing baseline measurements, programs can track changes in consumption following the implementation of specific strategies, such as educational campaigns, protocol changes, or the introduction of pre-authorization requirements for restricted antimicrobials. For instance, a significant reduction in the DDD of broad-spectrum agents like carbapenems after an intervention signals a decrease in selective pressure, which is directly linked to a lower risk of emerging resistance [19]. Similarly, a downward trend in the average LOT for common infections like community-acquired pneumonia demonstrates improved adherence to evidence-based guidelines and more judicious prescribing practices [68].

The combination of DDD and LOT data is particularly powerful for a holistic evaluation. While DDD provides a broad, aggregated metric useful for institutional comparisons and longitudinal trend analysis, LOT offers granular, clinically relevant data that can drive direct patient care interventions. For example, a stewardship team might use high LOT values to trigger targeted audits and feedback sessions with prescribers, promoting timely de-escalation or discontinuation of therapy. Studies have consistently shown that hospitals with structured stewardship programs that actively monitor these indicators achieve significant reductions in both overall antimicrobial consumption and the duration of therapy, leading to improved patient outcomes, reduced healthcare costs, and lower rates of resistant infections [6]. These indicators are not only tools for internal quality improvement but are also increasingly required for national evaluations and accreditation processes, such as those conducted by ANVISA, which include specific antimicrobial use metrics for critical care units [14].

Integration with Clinical and Microbiological Data

For monitoring to be truly effective, antimicrobial use indicators must be integrated with clinical and microbiological data. This integration allows for the contextualization of consumption metrics and transforms raw data into actionable intelligence. For example, a rise in DDD for a particular agent is only meaningful when analyzed alongside local resistance patterns from the laboratory diagnostics department. If the increase in use of a specific antibiotic coincides with a rise in resistance to that agent, it provides compelling evidence for the need to revise empirical treatment protocols [71]. The work of the microbiologist and the Comitê Brasileiro de Testes de Sensibilidade (BrCAST) in providing accurate and timely susceptibility data is therefore fundamental to the stewardship process [45].

Furthermore, the analysis of antimicrobial use should be linked to patient outcomes. A successful stewardship program should demonstrate not only reduced consumption but also maintained or improved clinical outcomes, such as stable or decreasing mortality rates, shorter hospital stays, and lower rates of adverse drug events. This requires a multidisciplinary approach, with the pharmacist and infectious disease specialist working together to correlate prescribing data with patient-level outcomes. The use of electronic health records and clinical decision support systems can facilitate this integration, enabling real-time alerts for prolonged therapy or the use of high-risk agents, and supporting the practice of an "antibiotic time-out" to reassess the need for continued treatment based on culture results and clinical response [14]. This synergy between data monitoring and clinical expertise ensures that stewardship efforts are both data-driven and patient-centered, ultimately contributing to the sustainability of effective antimicrobial therapies within the Sistema Único de Saúde (SUS) and beyond.

Challenges and Implementation in the Brazilian Public Health System

The implementation of effective antimicrobial stewardship (AS) programs within the Sistema Único de Saúde (SUS) faces a complex array of structural and operational challenges, despite a robust national policy framework. While the Brazilian government, through agencies like the Agência Nacional de Vigilância Sanitária (ANVISA) and the Ministry of Health, has established comprehensive plans such as the Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos (PAN-BR), translating these directives into consistent, high-quality practice across the vast and diverse SUS network remains a significant hurdle. The success of these programs is critical to combat the escalating threat of antimicrobial resistance (AMR), which is associated with approximately 34,000 deaths annually in Brazil and contributes to around 138,000 fatalities [74].

Key Implementation Challenges

The primary challenges to implementing AS programs in the SUS are deeply rooted in systemic limitations. A major obstacle is the chronic underfunding and lack of adequate infrastructure, which results in a severe shortage of specialized personnel such as infectious disease specialists, pharmacists, and microbiologists in many public hospitals [75]. This human resource deficit is compounded by the absence of advanced technological support, such as electronic prescribing systems with clinical decision support, which are essential for real-time monitoring and intervention in antimicrobial use. Furthermore, a fragmented healthcare system creates discontinuity between primary, secondary, and tertiary care levels, hindering the tracking of antimicrobial use and the prevention of healthcare-associated infections (HAIs). This fragmentation makes it difficult to implement a cohesive, system-wide approach to AMR control [71].

Another critical challenge is the lack of consistent training and adherence to evidence-based practices among healthcare professionals. In the primary care setting, inappropriate prescribing is often driven by patient demand and a lack of up-to-date clinical knowledge, particularly for viral respiratory infections where antibiotics are ineffective. The absence of standardized, locally adapted clinical protocols further exacerbates this issue. Even when protocols exist, the lack of continuous education and a weak culture of patient safety can lead to poor adherence. The effectiveness of AS programs is also hampered by fragile surveillance systems. Although national plans exist, the monitoring of AMR and HAIs is often inconsistent, with issues of underreporting, delayed data analysis, and a lack of integration between clinical, laboratory, and public health information systems [77].

Synergies with Infection Prevention and Control

A powerful strategy to overcome these challenges is the synergistic integration of antimicrobial stewardship with infection prevention and control (IPC) programs. These two domains are fundamentally interconnected and form a cycle of mutual reinforcement. While IPC programs focus on physical and procedural barriers—such as hand hygiene, isolation precautions, and environmental cleaning—to prevent the transmission of pathogens, AS programs act as a "pharmacological barrier" by reducing the selective pressure that drives the emergence and spread of resistant organisms [6]. The success of one is intrinsically linked to the other; for example, the overuse of broad-spectrum antibiotics can increase the risk of infections like Clostridioides difficile, which are difficult to control. Conversely, robust IPC measures reduce the overall incidence of HAIs, thereby decreasing the need for antimicrobial therapy. This integrated approach is championed by national directives, which emphasize that effective IPC is a prerequisite for successful AS and vice versa, creating a comprehensive strategy to enhance patient safety.

The Strategic Role of Multidisciplinary Teams

Overcoming the challenges within the SUS requires a strong, multidisciplinary team approach. The pharmacist plays a central and strategic role in AS, conducting daily prescription reviews, identifying errors, suggesting dose adjustments, and advocating for therapeutic de-escalation or discontinuation [15]. Their presence in hospital Comissão de Controle de Infecção Hospitalar (CCIH) is mandated by the Federal Council of Pharmacy, underscoring their critical importance [80]. The infectious disease specialist provides leadership, develops institutional guidelines, and offers expert consultation on complex cases. The microbiologist is the cornerstone of the diagnostic process, providing rapid and accurate results from antimicrobial susceptibility testing and molecular diagnostics, which are essential for guiding targeted therapy and detecting resistance mechanisms like carbapenemases [45]. The integration of these professionals, along with nurses and epidemiologists, ensures a holistic and evidence-based approach to managing antimicrobial use.

Data-Driven Decision Making and Policy

The future of AS in the SUS hinges on robust, data-driven decision-making. The analysis of epidemiological data from both hospital and community settings is vital for informing effective public health policies. Systems for monitoring AMR, such as the national surveillance efforts, provide the evidence needed to prioritize pathogens, adapt clinical guidelines, and allocate resources strategically [74]. The use of key indicators like the Defined Daily Dose (DDD) and Days of Therapy (DOT) allows for the quantification of antimicrobial consumption and the evaluation of program effectiveness over time [64]. Furthermore, the emerging field of genomics, particularly microbial genomics, is transforming outbreak response by enabling high-resolution tracking of resistant clones and their transmission pathways [84]. The integration of these advanced data streams into a unified national platform, as envisioned by initiatives like the Genomas Brasil program, holds the promise of a more agile, precise, and effective national response to the growing crisis of antimicrobial resistance.

Role of Laboratory Diagnostics and Genomic Surveillance

Laboratory diagnostics and genomic surveillance are pivotal components in the effective implementation of antimicrobial stewardship programs, providing the scientific foundation for targeted therapy, outbreak control, and evidence-based policy development. These tools enable healthcare systems to move from empirical to precision medicine, significantly reducing the misuse of antimicrobials and mitigating the spread of antimicrobial resistance (AMR). By identifying pathogens and their resistance mechanisms with high accuracy and speed, laboratory and genomic technologies support clinical decision-making, infection prevention, and national surveillance strategies.

Diagnostic Microbiology and Antimicrobial Susceptibility Testing

The cornerstone of effective antimicrobial use lies in accurate and timely identification of infectious agents. Diagnostic microbiology laboratories perform essential functions such as culture, isolation, and identification of bacteria, fungi, and other pathogens from clinical specimens. These processes are critical for distinguishing between bacterial and viral infections, thereby preventing the inappropriate use of antibiotics in viral illnesses—a major contributor to AMR.

A key element of laboratory diagnostics is antimicrobial susceptibility testing (AST), which determines whether a microorganism is susceptible, intermediate, or resistant to specific antimicrobial agents. This information allows clinicians to transition from broad-spectrum empirical therapy to narrow-spectrum, targeted treatment, a practice known as de-escalation. In Brazil, the Comitê Brasileiro de Testes de Sensibilidade (BrCAST) plays a crucial role in standardizing AST methodologies and establishing breakpoints aligned with national epidemiological data, ensuring consistency and clinical relevance across laboratories [45]. The integration of AST results into clinical workflows enables the optimization of therapy, reduces toxicity, and minimizes the selection pressure that drives resistance.

Rapid Molecular Diagnostics and Detection of Resistance Genes

Beyond traditional phenotypic methods, molecular diagnostics have revolutionized the speed and precision of pathogen detection. Techniques such as polymerase chain reaction (PCR), including real-time PCR with high-resolution melting analysis, allow for the rapid identification of resistance genes—often within hours rather than days. This is particularly valuable for detecting genes encoding carbapenemases (e.g., blaKPC, blaNDM, blaOXA) and colistin resistance (e.g., mcr-1), which are associated with life-threatening infections caused by multidrug-resistant Enterobacterales [86].

The early detection of these resistance determinants enables prompt initiation of appropriate therapy, implementation of infection control measures such as patient isolation, and prevention of nosocomial outbreaks. For example, identifying a carbapenemase-producing Klebsiella pneumoniae strain allows for the immediate restriction of carbapenem use and activation of contact precautions. Molecular methods also support the development of rapid diagnostic assays (RAST) that are increasingly being adopted in clinical settings to guide stewardship interventions and reduce unnecessary antimicrobial exposure.

Genomic Surveillance and Pathogen Tracking

Genomic surveillance represents a transformative advancement in the monitoring and control of resistant pathogens. By sequencing the entire genome of bacterial isolates, researchers can identify not only resistance genes but also plasmids, transposons, and clonal lineages responsible for the spread of resistance. This high-resolution data allows for the differentiation between independent acquisitions of resistance and clonal outbreaks, enabling targeted public health responses.

In Brazil, initiatives such as the CABGen (Genômica Bacteriana Aplicada à Clínica) platform developed by the Fundação Oswaldo Cruz (Fiocruz) integrate genomic, phenotypic, and epidemiological data to support real-time surveillance [87]. Studies using whole-genome sequencing have revealed the nationwide dissemination of high-risk clones such as Acinetobacter baumannii ST79 and Pseudomonas aeruginosa ST277, often carrying OXA-type carbapenemases [88]. These insights are critical for understanding transmission dynamics and informing containment strategies.

Integration with National Surveillance and Policy Frameworks

The data generated through laboratory and genomic surveillance directly inform national policies and action plans. In Brazil, the Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos (PAN-BR) relies on surveillance data to prioritize interventions and allocate resources effectively [2]. The Agência Nacional de Vigilância Sanitária (ANVISA) has established technical guidelines and monitoring systems, such as the strategic surveillance of healthcare-associated infections (IRAS), to track resistance trends and evaluate the impact of stewardship programs [77].

The launch of the Rede Nacional de Vigilância Genômica Antimicrobiana (VigiRAM), coordinated by Fiocruz in collaboration with public and private laboratories, marks a significant step toward nationwide genomic surveillance [91]. This network aims to standardize sequencing protocols, build regional capacity, and create a centralized database to support rapid response to emerging threats.

Challenges and Future Directions

Despite these advances, challenges remain in scaling up diagnostic and genomic capabilities across the Sistema Único de Saúde (SUS). Disparities in infrastructure, funding, and technical expertise between regions hinder equitable access to advanced diagnostics. Additionally, the integration of genomic data into clinical and public health decision-making requires robust bioinformatics support and intersectoral collaboration.

Future efforts must focus on expanding access to rapid molecular tests, investing in sequencing infrastructure, and training a skilled workforce in genomic epidemiology. The success of initiatives like the Programa Nacional de Genômica e Saúde de Precisão – Genomas Brasil will be critical in positioning Brazil as a leader in antimicrobial resistance surveillance [92]. By strengthening the link between the laboratory, the clinic, and public health policy, Brazil can enhance its capacity to combat AMR and safeguard the effectiveness of antimicrobial therapies for future generations.

Policy Frameworks and National Action Plans

The development and implementation of comprehensive policy frameworks and national action plans are critical components in the global and national response to the escalating threat of antimicrobial resistance (AMR). In Brazil, a structured, multi-sectoral approach has been adopted, aligning with international guidelines from the World Health Organization (WHO) and the Pan American Health Organization (PAHO) to ensure coordinated action across human, animal, and environmental health sectors through the One Health paradigm [2].

National Strategic Framework: The PAN-BR

At the core of Brazil's national strategy is the Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos no Âmbito da Saúde Única (PAN-BR), launched by the Ministry of Health in 2019 and updated in 2024 [2]. This plan establishes a unified framework to combat AMR by integrating actions from the health, agriculture, and environmental sectors. The PAN-BR outlines strategic objectives such as reducing the incidence of resistant infections, promoting the rational use of antimicrobials, strengthening surveillance systems, and fostering innovation in diagnostics and therapeutics. It serves as a guiding document for public and private institutions, ensuring that efforts to implement antimicrobial stewardship are harmonized across the country [95].

Role of Regulatory Agencies and Technical Directives

The Agência Nacional de Vigilância Sanitária (Anvisa) plays a pivotal role in operationalizing the PAN-BR through the issuance of technical guidelines and regulatory measures. In 2023, Anvisa published a national plan specifically targeting the prevention and control of antimicrobial resistance for the period 2023–2027, providing detailed directives for healthcare services [5]. This includes the Diretriz Nacional de Gerenciamento de Antimicrobianos, revised in 2023, which mandates the establishment of structured antimicrobial stewardship programs (ASPs) in healthcare institutions, particularly those with intensive care units (ICUs) [12]. Furthermore, Anvisa has issued specialized guidelines, such as the 2025 Diretriz Nacional para Gerenciamento de Antimicrobianos em Serviços de Neonatologia, which addresses the unique challenges of managing antimicrobial use in vulnerable neonatal populations [98].

Integration with Infection Prevention and Control Programs

National policy frameworks emphasize the integration of antimicrobial stewardship with infection prevention and control (IPC) initiatives. Anvisa’s Programa Nacional de Prevenção e Controle de Infecções em Serviços de Saúde (PNPCIRAS), approved in 2026, establishes mandatory surveillance of healthcare-associated infections (HAIs) and antimicrobial resistance, setting standardized indicators and goals for healthcare facilities [44]. This program reinforces the role of hospital-based Comissões de Controle de Infecção Hospitalar (CCIH), which are legally required to coordinate IPC and stewardship activities. The integration of these programs ensures that efforts to reduce antimicrobial use are complemented by robust infection control practices, such as hand hygiene and environmental cleaning, to prevent the transmission of multidrug-resistant organisms like methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) [71].

Surveillance and Data-Driven Policy Making

Effective policy frameworks rely on robust surveillance systems to monitor trends in antimicrobial resistance and guide public health interventions. Brazil utilizes data from the Sistema de Informação de Resistência Microbiana (SIRAM) and other national databases to track the prevalence of resistant pathogens such as Klebsiella pneumoniae and Pseudomonas aeruginosa [74]. This data informs the development of local and national treatment protocols, ensuring they are based on current epidemiological patterns. The Nota Técnica ANVISA nº 01/2026 promotes a shift from regulatory surveillance to strategic, data-driven monitoring, empowering CCIHs to use local resistance profiles to adapt clinical guidelines and stewardship interventions [77]. This approach supports the creation of evidence-based policies that are responsive to regional variations in resistance.

National and Regional Implementation Challenges

Despite the existence of comprehensive national plans, their implementation across the vast and diverse network of the Sistema Único de Saúde (SUS) faces significant challenges. These include disparities in infrastructure, shortages of specialized personnel such as infectious disease specialists and pharmacists, and limited access to advanced diagnostic tools in primary care settings [8]. Regional differences in resistance patterns require the adaptation of national guidelines to local contexts, a process that demands strong leadership and continuous education. To address these issues, the Ministry of Health and Anvisa promote the use of simplified protocols for primary care, such as those developed by the state of Ceará and the city of Campinas, which provide practical algorithms for antimicrobial use based on clinical criteria [104]; [105].

Advancing Genomic Surveillance and Future Directions

Looking forward, Brazil is investing in advanced technologies to strengthen its policy response. The national Genomas Brasil program, established by the Ministry of Health, aims to create a comprehensive genomic database to enhance the monitoring of resistant pathogens [106]. The Rede Nacional de Vigilância Genômica Antimicrobiana (VigiRAM), coordinated by the Fundação Oswaldo Cruz (Fiocruz), integrates public and private laboratories to conduct real-time genomic surveillance of outbreaks [91]. This capability allows for the rapid identification of resistance genes (e.g., blaKPC, blaNDM) and the tracking of high-risk clones, providing critical intelligence for outbreak control and policy refinement. The integration of genomic data into national frameworks represents a transformative step toward a more agile and precise response to the evolving threat of antimicrobial resistance.

References