Unlocking the Power of Beta-lactamase Inhibitors: How These Agents Are Reshaping the Fight Against Drug-Resistant Bacteria. Discover Their Mechanisms, Innovations, and Future Impact. (2025)

• Introduction: The Urgency of Combating Antibiotic Resistance
• Beta-lactamase Enzymes: Mechanisms and Clinical Impact
• Classes and Types of Beta-lactamase Inhibitors
• Key Approved Beta-lactamase Inhibitors and Their Manufacturers
• Emerging Technologies and Novel Inhibitor Compounds
• Clinical Applications: Current Uses and Efficacy Data
• Regulatory Landscape and Guidelines (FDA, EMA, WHO)
• Market Trends and Growth Forecasts (2024–2030): Estimated 8–12% CAGR
• Challenges: Resistance Development and Unmet Needs
• Future Outlook: Innovations, Public Health Strategies, and Global Impact
• Sources & References

Introduction: The Urgency of Combating Antibiotic Resistance

Antibiotic resistance has emerged as one of the most pressing global health threats of the 21st century, undermining decades of progress in infectious disease management. The World Health Organization (WHO) has repeatedly warned that antimicrobial resistance (AMR) could lead to a post-antibiotic era, where common infections and minor injuries become potentially fatal due to the ineffectiveness of existing drugs. Among the various mechanisms by which bacteria evade antibiotics, the production of beta-lactamase enzymes is particularly significant. These enzymes hydrolyze the beta-lactam ring, a core structural component of penicillins, cephalosporins, carbapenems, and monobactams, rendering these antibiotics ineffective.

The widespread use and, at times, misuse of beta-lactam antibiotics in both human medicine and agriculture have accelerated the evolution and dissemination of beta-lactamase-producing bacteria. This has led to the emergence of multidrug-resistant organisms, including extended-spectrum beta-lactamase (ESBL) producers and carbapenemase-producing Enterobacteriaceae, which are now recognized as critical priority pathogens by the World Health Organization. The Centers for Disease Control and Prevention (CDC) also highlights the growing threat posed by these resistant bacteria, noting their association with increased morbidity, mortality, and healthcare costs.

In response to this escalating crisis, the development and deployment of beta-lactamase inhibitors have become a cornerstone strategy in preserving the efficacy of beta-lactam antibiotics. Beta-lactamase inhibitors are compounds designed to block the activity of beta-lactamase enzymes, thereby restoring the antibacterial activity of beta-lactam drugs against resistant strains. These inhibitors are often co-formulated with beta-lactam antibiotics, creating combination therapies that extend the spectrum of activity and improve clinical outcomes.

The urgency of combating antibiotic resistance in 2025 is underscored by the limited pipeline of new antibiotics and the rapid evolution of resistance mechanisms. International organizations such as the European Medicines Agency and the U.S. Food and Drug Administration are actively involved in facilitating the development and approval of novel beta-lactamase inhibitor combinations. Continued innovation, stewardship, and global collaboration are essential to ensure that beta-lactamase inhibitors remain effective tools in the fight against resistant bacterial infections.

Beta-lactamase Enzymes: Mechanisms and Clinical Impact

Beta-lactamase inhibitors are a critical class of compounds developed to counteract the growing threat of bacterial resistance to beta-lactam antibiotics. Beta-lactamases are enzymes produced by many Gram-negative and some Gram-positive bacteria, which hydrolyze the beta-lactam ring of antibiotics such as penicillins, cephalosporins, and carbapenems, rendering them ineffective. The clinical impact of beta-lactamase-mediated resistance has been profound, leading to increased morbidity, mortality, and healthcare costs worldwide.

To address this challenge, beta-lactamase inhibitors are co-administered with beta-lactam antibiotics to restore their efficacy. These inhibitors function by binding to the active site of beta-lactamase enzymes, thereby preventing the hydrolysis of the antibiotic. The first generation of inhibitors, including clavulanic acid, sulbactam, and tazobactam, primarily target class A beta-lactamases. These agents are often combined with antibiotics such as amoxicillin, ampicillin, or piperacillin, resulting in widely used formulations like amoxicillin-clavulanate and piperacillin-tazobactam.

However, the emergence of extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases, and carbapenemases has necessitated the development of newer inhibitors with broader activity. Recent advances have led to the approval of novel agents such as avibactam, relebactam, and vaborbactam. These next-generation inhibitors exhibit activity against a wider range of beta-lactamases, including class A, C, and some class D enzymes, and are used in combination with ceftazidime, imipenem, and meropenem, respectively. Their introduction has expanded therapeutic options for infections caused by multidrug-resistant organisms, particularly in hospital settings.

The clinical impact of beta-lactamase inhibitors is significant. They have enabled the continued use of beta-lactam antibiotics against resistant pathogens, reduced the need for more toxic or less effective alternatives, and contributed to improved patient outcomes. Nevertheless, resistance to inhibitor combinations is increasingly reported, often due to the production of metallo-beta-lactamases or mutations in target enzymes. This ongoing arms race underscores the importance of antimicrobial stewardship and the need for continued research and surveillance.

Global health authorities such as the World Health Organization and regulatory agencies like the U.S. Food and Drug Administration recognize the importance of beta-lactamase inhibitors in combating antimicrobial resistance. Pharmaceutical companies and research institutions continue to invest in the discovery and development of novel inhibitors, aiming to stay ahead of evolving resistance mechanisms and safeguard the efficacy of beta-lactam antibiotics for future generations.

Classes and Types of Beta-lactamase Inhibitors

Beta-lactamase inhibitors are a critical class of compounds used in combination with beta-lactam antibiotics to overcome bacterial resistance mechanisms. These inhibitors function by binding to and inactivating beta-lactamase enzymes, which are produced by many pathogenic bacteria to hydrolyze the beta-lactam ring of antibiotics, rendering them ineffective. The development and classification of beta-lactamase inhibitors have evolved significantly, with several distinct classes now recognized based on their chemical structure and mechanism of action.

The main classes of beta-lactamase inhibitors include:

• Clavulanic Acid Derivatives: Clavulanic acid, a naturally occurring beta-lactam compound, was the first clinically used beta-lactamase inhibitor. It is structurally similar to penicillins and acts as a “suicide inhibitor,” irreversibly binding to the active site of serine beta-lactamases. Clavulanic acid is commonly combined with amoxicillin or ticarcillin to enhance their spectrum of activity.
• Sulbactam and Tazobactam: These are semi-synthetic penicillanic acid sulfone derivatives. Like clavulanic acid, they inhibit serine beta-lactamases by forming a covalent bond with the enzyme. Sulbactam is often paired with ampicillin, while tazobactam is used with piperacillin. Both are effective against a broad range of class A beta-lactamases but have limited activity against class B (metallo-beta-lactamases) and some class D enzymes.
• Diazabicyclooctanes (DBOs): This newer class includes avibactam and relebactam. Unlike earlier inhibitors, DBOs are non-beta-lactam compounds and exhibit a broader spectrum of inhibition, including activity against class A, some class C (AmpC), and certain class D beta-lactamases. Avibactam, for example, is used in combination with ceftazidime, providing enhanced efficacy against multidrug-resistant Gram-negative bacteria.
• Boronic Acid Derivatives: Vaborbactam is a representative of this class, characterized by a boronic acid pharmacophore. It inhibits class A and C beta-lactamases, including the problematic Klebsiella pneumoniae carbapenemase (KPC). Vaborbactam is used in combination with meropenem for the treatment of complicated urinary tract infections and other serious infections caused by resistant bacteria.

Each class of beta-lactamase inhibitor has unique properties and spectrum of activity, influencing their clinical use and the choice of antibiotic partner. The ongoing development of novel inhibitors is driven by the emergence of new beta-lactamase variants and the global challenge of antimicrobial resistance. Regulatory agencies such as the European Medicines Agency and the U.S. Food and Drug Administration play a pivotal role in the evaluation and approval of these agents, ensuring their safety and efficacy for clinical use.

Key Approved Beta-lactamase Inhibitors and Their Manufacturers

Beta-lactamase inhibitors are a critical class of agents used in combination with beta-lactam antibiotics to overcome resistance mediated by beta-lactamase enzymes produced by various bacteria. These inhibitors function by binding to and inactivating the beta-lactamase enzymes, thereby restoring the efficacy of beta-lactam antibiotics such as penicillins and cephalosporins. Over the years, several beta-lactamase inhibitors have been approved for clinical use, often in fixed-dose combinations with specific antibiotics. The following are key approved beta-lactamase inhibitors as of 2025, along with their principal manufacturers:

• Clavulanic Acid: One of the earliest and most widely used beta-lactamase inhibitors, clavulanic acid is commonly combined with amoxicillin (as amoxicillin-clavulanate). The combination is marketed under various brand names, with GSK (formerly GlaxoSmithKline) being a primary manufacturer. Clavulanic acid is effective against a broad range of beta-lactamases, particularly those produced by Gram-negative and Gram-positive bacteria.
• Sulbactam: Sulbactam is another beta-lactamase inhibitor, often combined with ampicillin (ampicillin-sulbactam). Pfizer is a major producer of this combination, which is used to treat infections caused by beta-lactamase-producing organisms, especially in hospital settings.
• Tazobactam: Tazobactam is typically paired with piperacillin (piperacillin-tazobactam), a combination widely used for severe infections, including those caused by Pseudomonas aeruginosa. Pfizer is a leading manufacturer of this combination, which is marketed under the brand name Zosyn in several countries.
• Avibactam: Avibactam is a non-beta-lactam beta-lactamase inhibitor with activity against a broader spectrum of beta-lactamases, including some carbapenemases. It is co-formulated with ceftazidime (ceftazidime-avibactam) and marketed by Pfizer and Allergan (now part of AbbVie). This combination is reserved for complicated infections caused by multidrug-resistant Gram-negative bacteria.
• Vaborbactam: Vaborbactam is a boronic acid-based inhibitor, used in combination with meropenem (meropenem-vaborbactam). Merck & Co., Inc. (known as MSD outside the United States and Canada) manufactures this combination, which is indicated for complicated urinary tract infections and other serious infections caused by carbapenem-resistant Enterobacteriaceae.
• Relebactam: Relebactam is another novel beta-lactamase inhibitor, combined with imipenem and cilastatin (imipenem-cilastatin-relebactam). This combination is also produced by Merck & Co., Inc. and is used for the treatment of complicated infections due to multidrug-resistant Gram-negative pathogens.

These approved beta-lactamase inhibitors, developed and manufactured by leading pharmaceutical companies, play a vital role in combating antibiotic resistance and expanding the therapeutic options for treating serious bacterial infections. Ongoing research and development efforts continue to focus on next-generation inhibitors to address emerging resistance mechanisms.

Emerging Technologies and Novel Inhibitor Compounds

The ongoing evolution of bacterial resistance to beta-lactam antibiotics has driven significant innovation in the development of new beta-lactamase inhibitors (BLIs). Traditional BLIs, such as clavulanic acid, sulbactam, and tazobactam, have been effective against some beta-lactamase enzymes but are increasingly limited by the emergence of extended-spectrum beta-lactamases (ESBLs), AmpC enzymes, and carbapenemases. In response, research in 2025 is focused on next-generation inhibitors and novel technologies designed to overcome these advanced resistance mechanisms.

One of the most promising areas involves diazabicyclooctane (DBO) derivatives, such as avibactam and relebactam. These compounds exhibit a broader spectrum of activity, including inhibition of class A, C, and some class D beta-lactamases, and are less susceptible to hydrolysis by resistant enzymes. Avibactam, for example, is used in combination with ceftazidime and has demonstrated efficacy against multidrug-resistant Gram-negative pathogens. The development and clinical use of these agents are overseen by regulatory authorities such as the European Medicines Agency and the U.S. Food and Drug Administration, which ensure their safety and efficacy.

Another innovative approach is the design of boronic acid-based inhibitors, such as vaborbactam. Vaborbactam, when combined with meropenem, targets serine carbapenemases (notably KPC enzymes), providing a valuable option for treating infections caused by carbapenem-resistant Enterobacteriaceae. These advances are supported by ongoing research from academic institutions and pharmaceutical companies, often in collaboration with public health organizations like the Centers for Disease Control and Prevention, which monitor resistance trends and guide clinical use.

Emerging technologies also include the exploration of non-beta-lactam scaffolds and allosteric inhibitors, which aim to disrupt beta-lactamase activity through novel mechanisms. Structure-based drug design, enabled by advances in computational modeling and high-throughput screening, is accelerating the identification of new inhibitor candidates. Additionally, the use of combination therapies—pairing BLIs with both existing and novel antibiotics—remains a key strategy to extend the lifespan of current treatments and reduce the likelihood of resistance development.

Looking forward, the integration of genomics and rapid diagnostics is expected to further personalize and optimize the use of beta-lactamase inhibitors. By tailoring therapy to the specific resistance mechanisms present in a patient’s infection, clinicians can maximize efficacy and stewardship. The continued collaboration between regulatory agencies, research institutions, and industry stakeholders is essential to bring these emerging technologies and novel compounds from the laboratory to clinical practice.

Clinical Applications: Current Uses and Efficacy Data

Beta-lactamase inhibitors are a cornerstone in the management of bacterial infections, particularly those caused by organisms that produce beta-lactamase enzymes, which confer resistance to many beta-lactam antibiotics. These inhibitors are most commonly used in combination with beta-lactam antibiotics, such as penicillins and cephalosporins, to restore or enhance antibacterial efficacy. The clinical applications of beta-lactamase inhibitor combinations span a wide range of infections, including complicated urinary tract infections (cUTIs), intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP), and bloodstream infections.

The most established beta-lactamase inhibitor combinations include amoxicillin-clavulanate, piperacillin-tazobactam, and ampicillin-sulbactam. These combinations are widely used in both community and hospital settings due to their broad spectrum of activity against Gram-negative and some Gram-positive bacteria. More recently, novel inhibitors such as avibactam, relebactam, and vaborbactam have been developed to address resistance mediated by extended-spectrum beta-lactamases (ESBLs) and certain carbapenemases. These newer agents, when combined with ceftazidime, imipenem, or meropenem, have expanded the therapeutic options for multidrug-resistant (MDR) infections.

Clinical efficacy data support the use of beta-lactam/beta-lactamase inhibitor (BL/BLI) combinations in various settings. For example, randomized controlled trials have demonstrated that ceftazidime-avibactam is non-inferior to carbapenems for the treatment of cUTIs and cIAIs, with similar or improved safety profiles. Piperacillin-tazobactam remains a first-line agent for empiric therapy in severe infections, including sepsis, due to its broad coverage and favorable clinical outcomes. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved several BL/BLI combinations based on robust clinical trial data demonstrating efficacy and safety in diverse patient populations (U.S. Food and Drug Administration; European Medicines Agency).

Despite their effectiveness, the emergence of resistance to BL/BLI combinations is an ongoing concern, particularly among Enterobacterales and Pseudomonas aeruginosa. Surveillance data from organizations such as the Centers for Disease Control and Prevention and the World Health Organization highlight the importance of antimicrobial stewardship to preserve the utility of these agents. In summary, beta-lactamase inhibitors remain vital in clinical practice, offering effective treatment options for resistant bacterial infections, but their continued efficacy depends on judicious use and ongoing surveillance.

Regulatory Landscape and Guidelines (FDA, EMA, WHO)

The regulatory landscape for beta-lactamase inhibitors is shaped by stringent guidelines and oversight from major health authorities, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). These organizations play pivotal roles in ensuring the safety, efficacy, and quality of beta-lactamase inhibitor-containing products, which are critical in combating antimicrobial resistance.

The U.S. Food and Drug Administration (FDA) regulates beta-lactamase inhibitors as part of its broader mandate over antimicrobial agents. The FDA requires comprehensive preclinical and clinical data to demonstrate the efficacy of beta-lactamase inhibitors, particularly when combined with beta-lactam antibiotics. The agency has issued guidance documents outlining the design of clinical trials, endpoints for efficacy, and requirements for post-marketing surveillance. The FDA also emphasizes the importance of antimicrobial stewardship and the need to limit the use of these agents to cases where resistance is documented or highly suspected.

In the European Union, the European Medicines Agency (EMA) is responsible for the scientific evaluation, supervision, and safety monitoring of medicines, including beta-lactamase inhibitors. The EMA’s Committee for Medicinal Products for Human Use (CHMP) provides scientific advice and sets guidelines for the development and approval of new antibiotics and beta-lactamase inhibitor combinations. The EMA requires robust evidence of clinical benefit, particularly in infections caused by multidrug-resistant organisms. The agency also collaborates with national regulatory bodies to harmonize standards and facilitate the approval of innovative therapies.

The World Health Organization (WHO) plays a global role in setting standards and providing guidance on the use of beta-lactamase inhibitors. The WHO’s Model List of Essential Medicines includes several beta-lactam/beta-lactamase inhibitor combinations, reflecting their importance in treating serious bacterial infections. The WHO also issues technical reports and guidelines on antimicrobial resistance, advocating for the rational use of these agents to preserve their effectiveness. Furthermore, the WHO collaborates with international partners to monitor resistance trends and promote research and development of new inhibitors.

Overall, the regulatory framework for beta-lactamase inhibitors is characterized by rigorous evaluation processes, ongoing post-marketing surveillance, and a strong emphasis on antimicrobial stewardship. These measures are essential to ensure that beta-lactamase inhibitors remain effective tools in the fight against resistant bacterial pathogens.

Market Trends and Growth Forecasts (2024–2030): Estimated 8–12% CAGR

The global market for beta-lactamase inhibitors is projected to experience robust growth between 2024 and 2030, with an estimated compound annual growth rate (CAGR) ranging from 8% to 12%. This positive outlook is driven by several converging factors, including the rising prevalence of antimicrobial resistance (AMR), increased incidence of bacterial infections, and the ongoing need for effective combination therapies in both hospital and community settings. Beta-lactamase inhibitors, when co-administered with beta-lactam antibiotics, play a critical role in restoring the efficacy of these drugs against resistant bacterial strains, making them indispensable in modern antimicrobial stewardship programs.

Key drivers of market expansion include the growing burden of multidrug-resistant (MDR) Gram-negative pathogens, such as Escherichia coli and Klebsiella pneumoniae, which have rendered many traditional antibiotics less effective. The World Health Organization (World Health Organization) has repeatedly highlighted the urgent need for new and improved antimicrobial agents, including beta-lactamase inhibitor combinations, to address the global AMR crisis. In response, pharmaceutical companies and research institutions are intensifying their efforts to develop next-generation inhibitors with broader spectrums of activity, targeting both serine and metallo-beta-lactamases.

The market is also benefiting from increased regulatory support and expedited approval pathways for novel antimicrobial agents. Agencies such as the U.S. Food and Drug Administration and the European Medicines Agency have implemented programs to accelerate the development and review of critical anti-infective therapies, including those containing beta-lactamase inhibitors. This regulatory momentum is expected to facilitate the introduction of innovative products and expand treatment options for clinicians facing resistant infections.

Geographically, North America and Europe are anticipated to remain leading markets due to high healthcare expenditures, established surveillance systems for AMR, and the presence of major pharmaceutical manufacturers. However, the Asia-Pacific region is projected to witness the fastest growth, fueled by increasing healthcare investments, rising awareness of AMR, and expanding access to advanced antibiotics in populous countries such as China and India.

Looking ahead to 2030, the beta-lactamase inhibitor market is expected to be shaped by ongoing R&D investments, strategic collaborations between public and private sectors, and the integration of novel inhibitors into clinical practice guidelines. The continued emergence of resistant pathogens and the global prioritization of AMR mitigation will likely sustain strong demand and innovation in this critical therapeutic segment.

Challenges: Resistance Development and Unmet Needs

Beta-lactamase inhibitors (BLIs) have played a pivotal role in extending the clinical utility of beta-lactam antibiotics by neutralizing bacterial enzymes that confer resistance. However, the ongoing evolution of bacterial resistance mechanisms presents significant challenges to the long-term efficacy of these agents. One of the primary concerns is the emergence and dissemination of novel beta-lactamases, such as extended-spectrum beta-lactamases (ESBLs), AmpC enzymes, and carbapenemases, which can hydrolyze a broad range of beta-lactam antibiotics and, in some cases, evade inhibition by existing BLIs. Notably, metallo-beta-lactamases (MBLs) like NDM, VIM, and IMP types are not inhibited by currently approved BLIs, leaving a critical gap in therapeutic options for infections caused by these pathogens.

The rapid spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, has further complicated the clinical landscape. These organisms often harbor multiple resistance determinants, including both beta-lactamases and non-enzymatic mechanisms such as efflux pumps and porin mutations, which can diminish the effectiveness of even the most advanced beta-lactam/BLI combinations. The World Health Organization (World Health Organization) and the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention) have identified carbapenem-resistant Enterobacterales (CRE) and other MDR Gram-negative bacteria as urgent public health threats, underscoring the need for new therapeutic strategies.

Another challenge is the limited spectrum of activity of current BLIs. While agents such as clavulanic acid, tazobactam, and sulbactam are effective against many class A beta-lactamases, they are largely ineffective against class B (metallo-beta-lactamases) and class D (oxacillinases) enzymes. Newer BLIs like avibactam and relebactam have expanded coverage, but resistance has already been reported, often due to mutations in target enzymes or the acquisition of additional resistance genes. This highlights the dynamic nature of bacterial adaptation and the need for continuous surveillance and innovation.

Unmet needs in this field include the development of BLIs with broader inhibitory profiles, particularly against MBLs and class D enzymes, as well as agents that can overcome non-enzymatic resistance mechanisms. There is also a pressing requirement for rapid diagnostic tools to guide the appropriate use of beta-lactam/BLI combinations and to monitor emerging resistance patterns. Collaborative efforts by global health organizations, regulatory agencies, and pharmaceutical companies are essential to address these challenges and to ensure the continued effectiveness of beta-lactam antibiotics in the face of evolving resistance (European Medicines Agency).

Future Outlook: Innovations, Public Health Strategies, and Global Impact

The future outlook for beta-lactamase inhibitors is shaped by the urgent global need to combat antimicrobial resistance (AMR), particularly resistance to beta-lactam antibiotics. As resistance mechanisms evolve, the pharmaceutical and scientific communities are accelerating innovation in inhibitor design, public health strategies, and international collaboration to ensure effective treatment options remain available.

Innovations in beta-lactamase inhibitor development are increasingly focused on overcoming the limitations of earlier generations. Traditional inhibitors such as clavulanic acid, sulbactam, and tazobactam are effective primarily against class A beta-lactamases, but the emergence of extended-spectrum beta-lactamases (ESBLs) and carbapenemases has necessitated the development of novel agents. Newer inhibitors, including avibactam, relebactam, and vaborbactam, demonstrate broader activity against class A, C, and some class D enzymes, and are often paired with advanced cephalosporins or carbapenems to restore efficacy against multidrug-resistant Gram-negative bacteria. Research is also exploring non-beta-lactam scaffolds and allosteric inhibitors to target metallo-beta-lactamases, which remain a significant challenge due to their resistance to current therapies (U.S. Food and Drug Administration).

Public health strategies are increasingly integrating beta-lactamase inhibitors into stewardship programs to optimize antibiotic use and slow the spread of resistance. Organizations such as the Centers for Disease Control and Prevention and the World Health Organization emphasize the importance of surveillance, rapid diagnostics, and education to ensure these agents are used judiciously. The development and deployment of combination therapies are being guided by real-time resistance data, helping clinicians select the most effective regimens and reduce unnecessary exposure to broad-spectrum antibiotics.

Globally, the impact of beta-lactamase inhibitors extends beyond clinical outcomes to influence health policy and economic stability. The World Health Organization has identified AMR as one of the top ten global public health threats, and the preservation of beta-lactam efficacy is central to its action plans. International collaborations, such as the Global Antimicrobial Resistance Surveillance System (GLASS), are fostering data sharing and coordinated responses to resistance trends. Additionally, regulatory agencies like the European Medicines Agency are streamlining approval pathways for innovative inhibitors, encouraging investment and expediting access to new therapies.

Looking ahead to 2025 and beyond, the convergence of scientific innovation, robust public health strategies, and global cooperation is expected to drive significant advances in the fight against beta-lactamase-mediated resistance. Continued investment in research, surveillance, and stewardship will be essential to safeguard the effectiveness of beta-lactam antibiotics and protect public health worldwide.

Sources & References

• World Health Organization
• CDC
• European Medicines Agency
• European Medicines Agency
• GSK
• Merck & Co., Inc.
• Centers for Disease Control and Prevention
• World Health Organization