1588. Delafloxacin Activity Against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin, or Linezolid

Abstract

Background

Delafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by methicillin-resistant S. aureus. There is limited data available against methicillin-resistant S. aureus blood isolates (MRSABI), vancomycin intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin non-susceptible strains (DNSSA) and linezolid-resistant S. aureus (LRSA).

Methods

Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin, ceftaroline, and linezolid was determined against recent (2016–2018) MRSABI (110), VRSA (15), VISA (35), DNSSA (40), and LRSA (6). Broth microdilution testing using Mueller–Hinton broth was used to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics.

Results

Antimicrobial MIC₉₀ expressed in mg/L and (% susceptible)

	MRSABI	VISA	VRSA	DNSSA
Delafloxacin	1 (68)	1 (40)	4 (7)	1 (38)
Levofloxacin	>16 (38)	>16 (9)	> 16 (0)	>16 (15)
Vancomycin	1 (99)	8 (0)	>64 (0)	8 (35)
Daptomycin	1 (96)	4 (26)	1 (100)	4 (0)
Ceftaroline	1 (99)	1 (100)	1 (100)	1 (100)
Linezolid	2 (100)	2 (100)	2 (100)	2 (100)

None of the LRSA were susceptible to delafloxacin or levofloxacin. All strains that were susceptible to the antimicrobial agents above had an MBC that was the same as the MIC or one dilution greater except for linezolid which demonstrated an MBC that was more than eight-fold greater than the MIC. For MRSABI isolates with a levofloxacin MIC ≥ 8 mg/L (55/110) suggesting multiple mutations in the quinolone-resistant determining region, the delafloxacin MIC₉₀ was 1 mg/L with a 36.4% susceptibility rate.

Conclusion

Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA, and DNSSA.

Disclosures

All authors: No reported disclosures.

Session: 162. PK/PD and Susceptibility Testing

Friday, October 4, 2019: 12:15 PM