Science

The rise of Antimicrobial Resistance

Antimicrobial Resistance (AMR) is predicted to be the #1 global cause of death by 2050. Nearly 100 years ago, antibiotics were among the first drugs ever to be developed, regulated, and commercialized. The “Golden Age” of antibiotic discovery soon followed but new drug development has dramatically slowed in recent years—despite the fact that AMR has increased creating an enormous healthcare void.

The lack of antimicrobial drug development, combined with the widespread use of existing antibiotics across medicine, agriculture, and other industries, has led to a surge of antimicrobial resistance throughout the world.

Process of Drug Discovery

The Dunman and Wozniak labs at the University of Rochester have taken a different approach to antibiotic drug discovery. Instead of synthesizing novel compounds, they search for novel combinations of existing antibiotics with synergistic effects—where the total impact is greater than the sum of the parts.

Advantages

Well Established Safety Data

Since these drugs have already passed regulation protocols and used in the clinic, safety concerns have been well established.

Broad-Spectrum

Most antibiotics are most effective against only certain types of pathogens. By combining Gram (+) and Gram (-) antimicrobial drugs together, the result can be high efficacy of pathogen killing across a broad-spectrum of bacteria.

Low-cost Production

Once a drug has gone off patent, it’s available for generic production and costs are reduced significantly. Since most novel antibiotics were developed over 40 years ago, their cost of production has greatly decreased.

Synergistic Efficacy

In both in vitro and in vivo studies of AV2019F2, the end product has a greater efficacy than the sum of each individual component.

Bacterial Keratitis is a vision-threatening disease impacting millions of patients around the world

What is Keratitis?

Keratitis is an infection of the cornea, the clear dome-shaped outer layer of the eye. Keratitis can be caused by bacterial, viral, or fungal infection. Our lead drug candidate, AV2019F2 Ophthalmic Solution, targets bacterial keratitis and we have antifungal products in development.

Why is Bacterial Keratitis so serious?

Bacterial Keratitis is a potentially blinding disease. If not treated effectively and efficiently, the cornea may rupture and patients may lose their vision—within days of the initial infection.

How do you treat Bacterial Keratitis?

Speed is of the essence when treating bacterial keratitis. American Academy of Ophthalmology (AAO) guidelines suggest treating empirically with broad spectrum antibiotics because there isn’t enough time to determine what kind of bacteria, Gram (-) or Gram (+), is the causative pathogen.

What’s wrong with current treatments?

There has not been a new antibiotic therapy approved for bacterial keratitis by the FDA in over 15 years. Existing treatments are used off label and bacteria are becoming more and more resistant to these agents every day.

Scientific Evidence

AV2019F2 rapidly kills a broad range of drug resistant bacteria that causes serious eye infections
Our combination is superior to current gold standards of treatment
AV2019F2 demonstrates complete eradication of infection in disease models

References

Chojnacki M, Philbrick A, Wucher B, Reed J, Tomaras A, Dunman PM, Wozniak RAF. Development of a Broad-Spectrum Antimicrobial Combination for the Treatment of Staphylococcus aureus and Pseudomonas aeruginosa Corneal Infections. Antimicrobial Agents and Chemotherapy. 2018; 63:e01929-18.

Chojnacki M, Philbrick A, Scherzi T, Pecora N, Dunman PM, Wozniak RAF. A Novel, Broad-Spectrum Antimicrobial Combination for the Treatment of Pseudomonas aeruginosa Corneal Infections. Antimicrobial Agents and Chemotherapy. 2019; 63:e00777-19

Laskey E, Chen Y, Gruber E, Chojnacki M, Wozniak RAF. Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Towards a Large Panel of Staphylococcus aureus Clinical Ocular Isolates from Around the World. Cornea. 2020; 39(10):1278-1284

Mei JA, Johnson W, Kinn B, Laskey E, Nolin L, Bhamare P, Stalker C, Dunman PD, Wozniak RAF. Antimicrobial Activity of a Triple Antibiotic Combination Towards Ocular Pseudomonas aeruginosa Clinical Isolates. Translational Vision Science & Technology. 2022; 11(5):26

Shah S, Wozniak RAF. Staphylococcus aureus and Pseudomonas aeruginosa Infectious Keratitis: Key Bacterial Mechanisms that Mediate Pathogenesis and Emerging Therapeutics. Frontiers Cellular and Infection Microbiology. 2023; doi:10.3389/fcimb/2023/1250257

Chen ER, Wozniak RAF. Reimagining the Past: A Future for Antimicrobial Drug Discovery in Ophthalmology. Cornea. 2024; doi:10.1097/ICO.3391

Lakshminarayanan G, Wozniak RAF, Dunman PM, Sheba E, Joseph J, Garg P. Efficacy of a Novel Antibiotic Drug Combination Towards Multi-Drug Resistant Ocular Pathogens. Cornea. 2024; doi:10/1097/ICO.3528

King, Anthony. Antibiotic Resistance Will Kill 300 Million People by 2050. Scientific American. 2014;