PATEL MV, GUPTE SV, AGARWAL SK, SREENIVAS K, NAIR SC, KHORAKIWALA HF, APPLEBAUM PC, JACOBS MR, DE SOUZA NJ; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. F-543.

Wockhardt Research Centre, Aurangabad, India

BACKGROUND: Incidence of FQ resistance in pneumococci is on the rise. Development of novel agents effective against such strains is needed. METHODS: Agar dilution MICs for 70 streptococci including FQ[R] (8 strains) and FQ[S] pneumococci, S. pyogenes, S. viridans and streptococci of C,G and F group (62 strains) were determined in Mueller Hinton agar (MHA) + 5% sheep blood. Six comparator FQs used were moxifloxacin (Moxi), levofloxacin (Levo), trovafloxacin (Trova), clinafloxacin (Clina), gatifloxacin (Gati) and sparfloxacin (Spar). Kill kinetics of FQ[S] and FQ[R] pneumococci upto 24 h were performed in MHB + 5% laked horse blood (inoculum 10[6] CFU/ml). Oral in vivo efficacy of WCK 919, Moxi and Levo was evaluated in systemic mouse infection (i. p.) model using SPN 6303 (type 3), SPN 731 (type 14), SPN 727 (type 19), SPN 733 (type 7B), SPN 706 (macrolide and penicillin resistant), SPN 745 (macrolide and FQ efflux positive), SPN 718 and SPN 5844 (FQ[R]). ED[50] s were determined on day 7. RESULTS: For FQ[S] streptococci, WCK 919 MICs were lowest (0.05 - 0.2 mcg/ml). MICs of WCK 919, Moxi, Levo, Trova, Clina, Spar and Gati for FQ[S]/FQ[R] pneumococci were 0.05/0.8, 0.2/3.12, 0.8/6.25, 0.1/6.25, 0.1/0.8, 0.8/6.25, 0.4/6.25 mcg/ml respectively. In kill kinetics against FQ[S] SPN strains, WCK 919, Trova and Moxi at 4X MIC caused 3 log reduction in 8 h. FQ[R] SPN 718 was killed by WCK 919 only (> 3 log kill by 24 h at 1X MIC). For FQ[S] SPN and other streptococci, ED[50] values of WCK 919 (2-10 mg/kg) were lowest compared to other quinolones. For FQ[R] SPN, ED[50] ranges for WCK 919, Moxi and Levo were 5 - 31, 50 - >100 and > 100 mg/kg respectively. CONCLUSION: WCK 919 is a potent respiratory FQ with excellent potential to treat both FQ[S] and FQ[R] pneumococcal infections by oral route.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Anti-Bacterial Agents
• Aza Compounds
• Fluoroquinolones
• In Vitro
• Mice
• Microbial Sensitivity Tests
• Naphthyridines
• Ofloxacin
• Penicillins
• Quinolines
• Quinolones
• Streptococcus
• Streptococcus pneumoniae
• clinafloxacin
• gatifloxacin
• moxifloxacin
• sparfloxacin
• trovafloxacin

Other ID:

• GWAIDS0030413

UI: 102270050

From Meeting Abstracts