Abstract
ABSTRACTOphthalmia neonatorum, also called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life. Commonly caused by the bacterial pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring, perforation of the eye, and blindness. One approach that can be taken to prevent the disease is the use of an ophthalmic prophylaxis, which kills the bacteria on the surface of the eye shortly after birth. Current prophylaxes are based on antibiotic ointments. However, N. gonorrhoeae is resistant to many antibiotics and alternative treatments must be developed before the condition becomes untreatable. This study focused on developing a fatty acid-based prophylaxis. For this, 37 fatty acids or fatty acid derivatives were screened in vitro for fast antigonococcal activity. Seven candidates were identified as bactericidal at 1 mM. These seven were subjected to irritation testing using three separate methods: the bovine corneal opacity and permeability (BCOP) test; the hen’s egg test—chorioallantoic membrane (HET-CAM); and the red blood cell (RBC) lysis assay. The candidates were also tested in artificial tear fluid to determine whether they were effective in this environment. Four of the candidates remained effective. Among these, two lead candidates, monocaprin and myristoleic acid, displayed the best potential as active compounds in the development of a fatty acid-based prophylaxis for prevention of ophthalmia neonatorum.
Highlights
Ophthalmia neonatorum, called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life
Among thirty-seven potential candidates included in the initial screen, seven candidate organic acids were found to have potent antimicrobial properties against N. gonorrhoeae
Acid, linolenic acid, monocaprin, and sodium dodecanoate. These seven fatty acids were tested in three irritation assays, using two gold standards for ocular drug therapy development, i.e., the bovine corneal opacity and permeability (BCOP) assay and hen’s egg test— chorioallantoic membrane (HET-CAM) [19,20,21], and a more general red blood cell (RBC) lysis assay [22], which may be less informative for development of ocular therapies
Summary
Ophthalmia neonatorum, called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life. Caused by the bacterial pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring, perforation of the eye, and blindness. Two lead candidates, monocaprin and myristoleic acid, displayed the best potential as active compounds in the development of a fatty acid-based prophylaxis for prevention of ophthalmia neonatorum. A common cause is Neisseria gonorrhoeae, which has the potential to cause severe damage to the eye and blindness. This study was designed to identify new and unconventional drug candidates that could be used in an eye ointment to prevent the development of this disease. The potential candidates were screened for their ability to kill bacteria in tear fluid without causing damage to the eye. Further development and testing are required to formulate an eye treatment incorporating these drugs to prevent ophthalmia neonatorum. The disease can be controlled in three ways: selective treatment of expectant mothers via prenatal screening; blanket prenatal antimicrobial treatment of all expectant mothers; and postnatal application of prophylaxis to all neonates within the first few hours after birth
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