Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent significant healthcare-associated infections (HAIs) that contribute to high morbidity, mortality, and healthcare costs in the United States. HAP is defined as pneumonia that occurs 48 hours or more after hospital admission, not present at the time of admission. VAP, a subset of HAP, occurs in patients who have been on mechanical ventilation for more than 48 hours. These infections are critical concerns due to their severe impact on patient outcomes and the healthcare system, further complicated by increasing rates of antimicrobial resistance.

HAP is one of the most common HAIs, with an estimated incidence of 5 to 10 cases per 1,000 hospital admissions in the US. VAP occurs in approximately 10-20% of patients who are mechanically ventilated, with an incidence rate ranging from 1 to 3 cases per 1,000 ventilator days.

Both HAP and VAP are associated with prolonged hospital stays, increased need for intensive care, and extensive use of healthcare resources. Patients with HAP have hospital stays extended by 7-9 days on average, while VAP can extend stays by an additional 7-13 days. These conditions lead to significant functional decline, increased dependency, and reduced quality of life for affected patients.

Mortality rates for HAP and VAP are substantial. HAP has a reported mortality rate of 20-30%, while VAP has an even higher mortality rate of 20-50%, depending on the patient population and comorbid conditions. VAP is recognized as the leading cause of death among HAIs, attributable to the severe complications and comorbidities it exacerbates.

The financial impact of HAP and VAP on the US healthcare system is considerable. The cost of treating HAP ranges from $28,000 to $40,000 per patient, while VAP can cost between $40,000 to $60,000 per patient. The annual economic burden of HAP and VAP in the US is estimated to be over $10 billion, driven by prolonged hospital stays, increased ICU admissions, and extensive use of antibiotics and other therapeutic interventions.

The treatment of HAP and VAP involves significant resource utilization, including increased use of diagnostic tests, extended ICU stays, prolonged mechanical ventilation, and the need for advanced therapeutic interventions. The management of these infections places a substantial burden on healthcare providers and systems, often requiring multidisciplinary approaches to care.

The rising rates of antimicrobial resistance (AMR) significantly complicate the treatment of HAP and VAP. Multidrug-resistant organisms (MDROs), such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and multidrug-resistant Gram-negative bacilli (e.g., P. aeruginosa), are increasingly implicated in these infections. The presence of MDROs is associated with higher mortality rates, longer hospital stays, and increased healthcare costs due to the limited effectiveness of standard antibiotic therapies and the need for more expensive and toxic alternatives.

Pseudomonas aeruginosa is a major pathogen in HAP and VAP, particularly in the ICU setting. It accounts for approximately 10-20% of all HAP and VAP cases. This pathogen is notorious for its intrinsic resistance mechanisms and ability to acquire new resistance traits, making it one of the most challenging bacteria to treat. Infections caused by P. aeruginosa are associated with high morbidity and mortality, with treatment often complicated by its resistance to multiple antibiotic classes, including beta-lactams, aminoglycosides, and fluoroquinolones.

The presence of P. aeruginosa in HAP and VAP cases necessitates the use of broad-spectrum antibiotics and combination therapies, further contributing to the overall burden of antimicrobial resistance. The management of infections caused by this pathogen requires careful selection of antibiotics based on susceptibility testing, often involving the use of more toxic or less effective drugs.

HAP and VAP pose significant challenges to 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 Pseudomonas aeruginosa, further complicate the management and treatment of these infections. Addressing the burden of HAP and VAP requires a multifaceted approach, including improved infection control practices, antimicrobial stewardship, and the development of new therapeutic strategies to combat resistant pathogens, like LBP-PA01.

LBP-PA01 is a cocktail of engineered bacteriophages designed to precisely remove P. aeruginosa in patients with HAP/VAP. 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.