Activity of the Fluoroquinolone JNJ-Q2 Tested Against Contemporary (2012) Pathogens Isolated from the Global SENTRY Surveillance Platform

• JNJ-Q2 demonstrated excellent activity when tested against a global collection of 2012 CABP pathogens, including the most prevalent pathogen S. pneumoniae. Nearly all isolates (>99.9%) of pneumococci were inhibited at a MIC of ≤0.12 µg/mL. JNJ-Q2 also demonstrated excellent activity against H. influenzae and M. catarrhalis. • JNJ-Q2 exhibited good activity overall against this global collection of S. aureus, >98% of the isolates were inhibited at ≤0.5 µg/ mL. The potency of JNJ-Q2 was observed to be less in levofloxacin- resistant strains compared to levofloxacin-susceptible strains with a MIC 90 of 0.5 µg/mL for MRSA and 0.25 µg/mL for MSSA. JNJ-Q2 demonstrated excellent activity against β-haemolytic and viridans streptococci and good in vitro activity Enterococcus spp. • JNJ-Q2 showed good in vitro activity against Enterobacteriaceae but was less active against ESBL-phenotypes than non-ESBL- phenotypes which was directly related to the prevalence of ciprofloxacin resistance in the ESBL subpopulation. JNJ-Q2 also demonstrated good activity against Acinetobacter spp. being clearly more active than ciprofloxacin, moxifloxacin and levofloxacin and having similar activity to the two most active agents; tigecycline and colistin. Results: JNJ-Q2 was highly active against SPN, H. influenzae (HI), and M. catarrhalis (MC). All 2,162 SPN isolates were inhibited at ≤0.25 µg/mL (MIC 90 , 0.015 µg/mL). 17.5/1.3% of isolates were PEN-R (MIC, ≥2 µg/mL/ MIC, ≥8 µg/mL), 36.7% erythromycin (ERY)-R, 26.6% tetracycline (TET)-R and 1.2% levofloxacin (LEV)- R. The MIC 90 values for HI and MC were 0.015 µg/mL. The MIC 50/90 for JNJ-Q2 against 4,537 S. aureus (37.3% MRSA) was 0.008/0.25 µg/mL. LEV-R, ERY-R, and clindamycin-R were at 31.5, 43.0 and 16.4 respectively. The activity of JNJ-Q2 was lower in LEV-R strains; LEV- R MRSA and LEV-R methicillin-susceptible (MS) SA (MIC 50/90 , 0.25/0.5 and 0.12/0.25 µg/mL, respectively) compared to LEV-susceptible (S) strains (MIC 50/90 , 0.008/0.015 µg/mL). The JNJ-Q2 MIC 50/90 for Enterobacteriaceae (ENT) was (MIC 50/90 , 0.12/2 µg/mL) and for P. aeruginosa (PSA; MIC 50/90 , 1/>4 µg/mL). JNJ- - JNJ-Q2 demonstrated good activity overall (MIC 50/90 , 0.008/0.25 µg/mL) against 4,537 S. aureus (SA) with 99.7% all isolates inhibited at a MIC of ≤1 µg/mL (Table 1). There were 12 isolates (0.3% of 4,537) at 2 µg/mL and no isolates at >2 µg/mL. All 12 isolates were oxacillin- (methicillin-) resistant (MR), and were levofloxacin-, moxifloxacin-, and ciprofloxacin- resistant (MIC, >4 µg/mL). JNJ-Q2 (MIC 90 , 0.25 µg/mL) was 16-fold more potent than moxifloxacin (MIC 90 , 4 µg/mL) and at least 16-fold more potent than ciprofloxacin and levofloxacin (MIC 90 , both >4 µg/mL; Table 2). - Overall resistance rates were high for oxacillin (MRSA, 37.3%), erythromycin (43.0%), and clindamycin (16.4%). No resistance was observed when S. aureus were tested against tigecycline and susceptibilities to daptomycin, linezolid, and vancomycin were >99.9% (Table 2). • Activity of JNJ-Q2 against β-hemolytic streptococci (βHS) and viridans group streptococci (VGS). - JNJ-Q2 demonstrated excellent in vitro activity (MIC 50/90 , 0.015/0.015 µg/mL) against βHS (including 535 S. pyogenes) inhibiting all isolates at a MIC value of ≤0.25 µg/mL (Table 1). JNJ-Q2 (MIC 90 , 0.015 µg/mL) demonstrated a 16-fold greater potency than moxifloxacin (MIC 90 , 0.25 µg/mL), 64-fold greater potency than levofloxacin (MIC 90 , 1 µg/mL), and 64-fold greater potency than ciprofloxacin (MIC 90 , 1 µg/mL; Table 2). - JNJ-Q2 also demonstrated excellent in vitro activity (MIC 50/90 , 0.015/0.015 µg/mL) against 606 isolates of VGS inhibiting all isolates at a MIC value of ≤0.5 µg/mL (Table 1). JNJ-Q2 (MIC 90 , 0.015 µg/mL) demonstrated a 16-fold greater potency than moxifloxacin (MIC 90 , 0.25 µg/mL), 128-fold greater potency than levofloxacin (MIC 90 , 2 µg/mL), and 256-fold greater potency than ciprofloxacin (MIC 90 , 4 µg/mL; Table 2). • Activity of JNJ-Q2 against enterococci. - JNJ-Q2 showed good in vitro activity (MIC 50/90 , 0.25/2 µg/mL) against 853 isolates of Enterococcus spp. (E. faecalis 548 isolates, E. faecium 305 isolates) inhibiting 79.1% isolates at ≤1 µg/mL and 99.9% of isolates at a MIC value of ≤4 µg/mL (Table 1). Ampicillin and vancomycin resistance were 32.7 and 18.6%, respectively (Table 2). JNJ-Q2 was more active against vancomycin susceptible (MIC 50/90 , 0.06/1 µg/mL) than vancomycin non-susceptible (MIC 50/90 , 2/4 µg/mL; Table 1) strains. • Activity of JNJ-Q2 against Enterobacteriaceae. - Ciprofloxacin resistance was 23.2% overall against 3,543 Enterobacteriaceae (Table 2). JNJ-Q2 showed good in vitro activity (MIC 50/90 , 0.12/2 µg/mL) and based on the MIC 90 values demonstrated at least four- fold greater potency than moxifloxacin (MIC 50/90 , ≤0.12/>4 µg/mL). - JNJ-Q2 demonstrated similar activities against E. coli (MIC 50/90 , 0.03/2 µg/mL), Klebsiella spp. (MIC 50/90 , 0.06/4 µg/mL), Proteus mirabilis (MIC 50/90 , 0.12/4 µg/mL), Citrobacter spp. (MIC 50/90 , 0.06/2 µg/mL), Enterobacter spp. (MIC 50/90 , 0.06/2 µg/mL), indole-positive Proteus spp. (MIC 50/90 , 0.12/4 µg/mL), and Serratia spp. (MIC 50/90 , 0.5/1 µg/mL; Table 1). JNJ-Q2 was less active against ESBL-phenotypes of Enterobacteriaceae (MIC 50/90 , 2/>4 µg/mL) than non-ESBL-phenotypes (MIC 50/90 , 0.06/0.5 µg/mL; Table 1) which was directly related to the prevalence of ciprofloxacin resistance in the subpopulation (non-ESBL vs. ESBL). • Activity of JNJ-Q2 against P. aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. - Based on MIC 50 values, JNJ-Q2 (MIC 50/90 , 1/>4 µg/mL) demonstrated two-fold better activity than moxifloxacin (MIC 50/90 , 2/>4 µg/mL), two-fold less activity compared to levofloxacin (MIC 50/90 , 0.5/>4 µg/mL), and four-fold lower activity than ciprofloxacin (MIC 50/90 , 0.25/>4 µg/mL) against 954 P. aeruginosa