Auriclosene

To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis.

Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694).

Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus.

Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression.

The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign.

Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age.

A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

Long-term use of indwelling urinary catheters can lead to urinary tract infections and loss of catheter patency due to encrustation and blockage. Encrustation of urinary catheters is due to formation of crystalline biofilms by urease-producing microorganisms such as Proteus mirabilis. An in vitro catheter biofilm model (CBM) was used to evaluate current methods for maintaining urinary catheter patency. We compared antimicrobial-coated urinary Foley catheters, with both available catheter irrigation solutions and investigational solutions containing NVC-422 (N,N-dichloro-2,2-dimethyltaurine; a novel broad-spectrum antimicrobial). Inoculation of the CBM reactor with 10(8) colony-forming units of P. mirabilis resulted in crystalline biofilm formation in catheters by 48 h and blockage of catheters within 5 days. Silver hydrogel or nitrofurazone-coated catheters did not extend the duration of catheter patency. Catheters irrigated daily with commercially available solutions such as 0.25 % acetic acid and isotonic saline blocked at the same rate as untreated catheters. Daily irrigations of catheters with 0.2 % NVC-422 in 10 mM acetate-buffered saline pH 4 or Renacidin maintained catheter patency throughout 10-day studies, but P. mirabilis colonization of the CBM remained. In contrast, 0.2 % NVC-422 in citrate buffer (6.6 % citric acid at pH 3.8) resulted in an irrigation solution that not only maintained catheter patency for 10 days but also completely eradicated the P. mirabilis biofilm within one treatment day. These data suggest that an irrigation solution containing the rapidly bactericidal antimicrobial NVC-422 in combination with citric acid to permeabilize crystalline biofilm may significantly enhance catheter patency versus other approved irrigation solutions and antimicrobial-coated catheters.