Abstract
BackgroundCorneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis.MethodsIn vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used.ResultsThe results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%.ConclusionOur results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.
Highlights
Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously
That is, when comparing kill rates between 60 min and 120 min at the same concentration. The reasons for this inconsistency is unclear, explanations include the possibility of polymerization effects occurring as a result of released free formaldehyde as well as possible reactions with the Formaldehyde releasers (FARs) products resulting in formation of either the starting material or additional reaction products
A summary of the results suggests that diazolidinyl urea (DAU), DMDM, and sodium hydroxymethylglycinate (SMG) all could be potentially used as Staphylococcus drugs (MRSA and methicillin-sensitive Staphylococcus aureus (MSSA))
Summary
Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The US Centers for Disease Control and Prevention estimates that over 2 million people are infected with drug-resistant microbes annually in the US [3, 4] This includes a soaring number of multi-resistant microorganisms affecting the human cornea (i.e. Pseudomonas aeruginosa (PA), methicillin- resistant Staphylococcus aureus (MRSA) and methicillin- susceptible Staphylococcus aureus (MSSA)) [5, 6]. The number of blind individuals as a result of corneal infections will rise as our ability to effectively treat infectious keratitis diminishes secondary to the increasing development of microbial pathogen resistance. This underlines a need to seek alternatives to available antibiotic treatment protocols [8]
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