Bloodstream infections (BSIs) represent a critical healthcare issue in the United States, contributing significantly to morbidity, mortality, and healthcare costs. BSIs occur when bacteria or fungi enter the bloodstream, leading to severe systemic infections that can rapidly progress to sepsis, a life-threatening condition. The burden of BSIs is exacerbated by increasing rates of antimicrobial resistance, complicating treatment and management efforts. Staphylococcus aureus, particularly methicillin-resistant Staphylococcus aureus (MRSA), is a major pathogen associated with BSIs, posing significant challenges to healthcare providers.

BSIs are among the most common and severe healthcare-associated infections (HAIs). In the US, there are approximately 500,000 cases of BSIs annually. The incidence rate of BSIs is estimated to be 5-10 per 1,000 hospital admissions, with a higher prevalence in intensive care units (ICUs) and among patients with central venous catheters (CVCs) or other invasive devices.

BSIs are associated with significant morbidity, leading to prolonged hospital stays, increased need for intensive care, and severe complications, including sepsis and multi-organ failure. Patients with BSIs often experience longer recovery times, increased risk of readmission, and substantial declines in functional status and quality of life.

The mortality rate for BSIs is alarmingly high, with estimates ranging from 20% to 40%. The risk of death is particularly elevated in patients who develop sepsis or septic shock as a result of the infection. The presence of drug-resistant pathogens, such as MRSA, further increases the mortality risk due to the limited effectiveness of standard treatments.

The economic burden of BSIs on the US healthcare system is substantial. The cost of treating a single BSI case ranges from $30,000 to $70,000, depending on the severity and complications. The annual financial impact of BSIs is estimated to exceed $10 billion, driven by extended hospital stays, ICU admissions, and the need for complex and prolonged treatments.

The management of BSIs involves significant resource utilization, including the use of advanced diagnostic tests, prolonged antibiotic therapy, and intensive care support. The treatment of BSIs often requires a multidisciplinary approach, involving infectious disease specialists, critical care teams, and pharmacologists, to manage the infection and mitigate complications.

The increasing rates of antimicrobial resistance pose a major challenge in the treatment of BSIs. Multidrug-resistant organisms, including MRSA, vancomycin-resistant Enterococci (VRE), and extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria, are increasingly implicated in BSIs. The presence of these resistant pathogens complicates treatment, leading to higher mortality rates, longer hospital stays, and increased healthcare costs due to the need for more expensive and less effective alternative therapies.

Staphylococcus aureus is a leading cause of BSIs, responsible for approximately 20-30% of all cases. Among these, MRSA is a particularly problematic pathogen due to its resistance to multiple antibiotics, including methicillin and other beta-lactams. Infections caused by S. aureus are associated with severe outcomes, including high rates of sepsis, septic shock, and mortality.

The treatment of S. aureus BSIs, especially those caused by MRSA, requires the use of alternative antibiotics, such as vancomycin, linezolid, or daptomycin, which can be more toxic, less effective, and more expensive. The presence of MRSA in BSIs is associated with longer hospital stays, increased ICU admissions, and a higher risk of complications, further contributing to the overall burden of these infections on the healthcare system. BSIs represent a significant and growing challenge in the US healthcare system due to their high incidence, associated morbidity and mortality, and substantial economic burden. The increasing rates of antimicrobial resistance, particularly involving pathogens like Staphylococcus aureus and MRSA, complicate the management and treatment of BSIs. Addressing the burden of BSIs requires comprehensive strategies, including improved infection control practices, robust antimicrobial stewardship programs, and the development of new antimicrobial agents to effectively combat resistant pathogens, like LBP-SA01.

LBP-SA01 is a cocktail of engineered bacteriophages designed to precisely remove S. aureus in patients with BSIs. The rise of antibiotic resistance has led to a revival in the investigative and rescue use of bacteriophage (phage) therapy in patients with difficult-to-treat or life-threatening infections where there are frequently no alternative therapies. Locus has deployed a technology stack that provides a scale and capability set that has never been used in phage therapy, which is redefining the way engineered bacteriophages are used to treat disease.