Treatment of
P. aeruginosa keratitis involves intensive topical antimicrobial therapy using fluoroquinolones (e.g., moxifloxacin) or fortified Gram-negative antibiotics, including aminoglycosides (e.g., tobramycin), cephalosporins (e.g., ceftazidime), and synthetic penicillins (e.g., carbenicillin) and in severe cases, by their subconjunctival injection. Although antibiotics reduce bacterial burden, tissue damage occurs due to a poorly controlled host immune response
[34][35][34,35]. Additionally, antibiotic resistant bacteria are continuously emerging and pose serious challenges for the effective management of keratitis
[36]. Resistance to antimicrobials has been noted from the time the first antibiotics were discovered, and many genes that confer drug resistance upon some strains of bacteria pre-date antibiotics by millions of years
[37]. However, resistance has increasingly become problematic globally due to overuse of antimicrobials which has contributed to increasing the rate of resistance development and spread. The lack of new drugs to challenge these new “supermicrobes” exacerbates the problem. Besides treatment issues, there also is an economic impact of this growing problem, as more than 2 million infections a year are caused by bacteria that are resistant to first-line antibiotics,
[37] costing the US health system 20 billion dollars each year
[38].
P. aeruginosa, an opportunistic pathogen, that does not normally infect healthy individuals, but rather those who are hospitalized or immunocompromised in some way, causes 51,000 infections/year in the USA; 13 percent
[37] of these are multi-drug resistant (MDR) and increasingly difficult to treat. Other approaches, such as inhibition of HMGB1, provide novel alternatives to prevent and treat infections resulting from both resistant and non-resistant bacteria; it is both pressing and timely that we develop these alternative treatments.