A Comparative In Vitro Surveillance Study of Gemifloxacin Activities against 2,632 Recent Streptococcus pneumoniae Isolates from across Europe, North America, and South America

Abstract

From 1997 to 1999, 94 study centers in 15 European, 3 North American, and 2 South American countries contributed 2,632 isolates of Streptococcus pneumoniae to an international antimicrobial susceptibility testing study. Only 62.0% of isolates were susceptible to penicillin, while 22.3% were penicillin intermediate and 15.6% were penicillin resistant. Resistance to trimethoprim-sulfamethoxazole (24.4%), azithromycin (26.0%), and clarithromycin (27.1%) was also highly prevalent. For the penicillin-resistant isolates (n ‫؍‬ 411), the MICs at which 90% of isolates are inhibited (MIC 90 s) for gemifloxacin, levofloxacin, ofloxacin, clarithromycin, and azithromycin were 0.03, 1, 2, >16, and >64 g/ml, respectively. Similarly, for isolates resistant to both azithromycin and clarithromycin (n ‫؍‬ 649), gemifloxacin, levofloxacin, ofloxacin, and penicillin MIC 90 s were 0.03, 1, 2, and 4 g/ml, respectively. Overall rates of resistance to trovafloxacin (0.3%), levofloxacin (0.3%), grepafloxacin (0.6%), and ofloxacin (0.7%) were low. For ofloxacin-intermediate and -resistant isolates (n ‫؍‬ 142), gemifloxacin had the lowest MIC 90 (0.12 g/ml) compared to the MIC 90 s of trovafloxacin (0.5 g/ml), grepafloxacin (1 g/ml), and levofloxacin (2 g/ml). For all S. pneumoniae isolates tested, gemifloxacin MICs were <0.5 g/ml, suggesting that gemifloxacin has the potential to be used as a treatment for pneumococcal infections, including those arising from isolates resistant to ␤-lactams and macrolides.

Penetration of Topically Administered Ofloxacin and Trimethoprim Into Aqueous Humor

“…Relative penetration of antibiotics into the anterior chamber is generally chosen as a convenient indicator of permeation because aqueous humor samples may be obtained from patients undergoing cataract surgery. 21 8 (2632) 22 2 (703) 18 2 (2632) 22 Pseudomonas aeruginosa 2 (42) 5 3.2 (68) 16 4 (68) 15 .8 (1616) 18 12.5 (99) 19 Haemophilus influenzae 0.03 (32) 5 0.16 (32) 5 0.06 (256) 20 8 (256) 20 0.1 (72) 19 0.12 (668) 18 The mean concentration of ofloxacin measured in aqueous humor was 1.135 mg/ml, a value consistent with previously published measurements by HPLC following similar administration regimens (6,7,(9)(10)(11). The mean concentration of trimethoprim was 0.470 mg/ml, a value 2-fold greater than the only previously published measurement (4).…”

Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin

“…Such mutants may not be treatable with levofloxacin and exposure of these strains to this agent select second-step mutants [86]. Gemifloxacin has been shown to have the lowest MICs against a collection of these strains [83] and against ofloxacin-intermediate/resistant pneumococci [81,87], and while the proportion of levofloxacin resistant strains remains low, gemifloxacin should continue to be effective. This property of gemifloxacin makes it a realistic therapeutic option, particularly in regions of the world where multi-drug resistance is high, or in patients where there is concern that previous treatment with a quinolone may have generated first-step mutants that could become fully-resistant with another course of a similar quinolone agent.…”

“…Although still at a low level, what concerns clinicians is increasing resistance to earlier quinolones (ciprofloxacin, ofloxacin and levofloxacin) that has been reported, especially when this has emerged during therapy and has resulted in clinical failure [86]. Gemifloxacin has been shown to have lowest MIC 90 values of a range of quinolones to penicillin-and macrolide-resistant strains of S. pneumoniae (MIC 90 : gemifloxacin 0.03, ciprofloxacin 2, ofloxacin 2, levofloxacin 1, grepafloxacin 0.25, trovafloxacin 0.25 mg/l for both penicillin-resistant (n = 411) and macrolide-resistant (n = 649) isolates) [87]. Gemifloxacin has also been shown to possess potent activity against most pneumococcal strains that are intermediate and many that are resistant to ofloxacin and Table 5 presents the results found in a selection of studies.…”

Comparative in vitro and bactericidal activities of telithromycin against penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant Streptococcus pneumoniae by time-kill methodology

“…Outpatient treatment options for these infections have traditionally included ␤-lactams, macrolides, and fluoroquinolones [1][2][3]. However, pneumococcal isolates that are resistant to penicillin, oral cephalosporins, and macrolides have become common in the United States and worldwide, and many penicillin-resistant strains exhibit cross-resistance to other antimicrobial classes [4][5][6][7]. Fluoroquinolone resistance in S. pneumoniae is less prevalent, but increased fluoroquinolone use has been associated with reduced susceptibility [8].…”