Abstract
Purpose: :
To evaluate the in vitro activity of a novel isothiazoquinolone, ACH-0139586, against common ocular pathogens (S. aureus, S. epidermidis, S. pneumonia, H. influenza, M. catarrhalis, and P. aeruginosa) compared with moxifloxacin and gatifloxacin. Isothiazoloquinolones are a new class of anti-infectives proven to inhibit bacterial DNA primase, in addition to DNA gyrase and topoisomerase IV, targeted by fluoroquinolones. Added inhibition of DNA primase increases antimicrobial efficacy and decreases chance for resistance compared to fluoroquinolones.
Methods: :
Non-duplicate, non-consecutive clinical isolates (including ocular) were selected from the Eurofins Medinet Bacterial Repository. Isolates with fluoroquinolone and methicillin resistance were preferentially selected to challenge ACH-0139586, which is reported to maintain potency against fluroquinolone resistant isolates. S. aureus with MRSA and FQ-R phenotypes, S. epidermidis with MRSE and FQ-R phenotypes, S. pneumoniae with MDR, Pen-R, and FQ-R phenotypes, H. influenzae with Beta-lactamase-positive and FQ-R phenotypes, M. catarrhalis with Beta-lactamase-positive phenotypes, and P. aeruginosa with Imipenem-R, FQ-R, and MDR phenotypes were included. Isolates were tested by broth microdilution in accordance with CLSI M7-A8 and Eurofins Medinet SOP as appropriate.
Conclusions: :
Against the evaluated isolates, ACH-0139586 was consistently more potent in vitro relative to gatifloxacin and moxifloxacin, regardless of methicillin and fluroquinolone resistance. The potency advantage was most apparent against evaluated gram-positive pathogens. ACH-0139586 proved to have increased potency against fluroquinolone resistant isolates, in particular S.aureus, where fluoroquinolone resistance is relatively common. These results show the ocular anti-infective therapeutic potential of ACH- 0139586.
Keywords: antibiotics/antifungals/antiparasitics