Garenoxacin efficacy against multidrug-resistant Streptococcus pneumoniae: retrospective analysis of community-acquired pneumoniae isolates obtained from nine phase II and III clinical studies (19992003)
Abstract number: p1577
Black T., Waskin H., Hare R.
Garenoxacin (GRN) is a novel, des-F(6)-quinolone with excellent activity against S. pneumoniae, one of the most common pathogens causing community-acquired pneumoniae (CAP). The incidence of infections caused by antibiotic-resistant isolates of Streptococcus pneumoniae is on the increase, therefore information regarding the activity of new anti-infective drugs against populations of S. pneumoniae that are multi-drug resistant (MDR) is critical. MDR S. pneumoniae (MDRSP) includes isolates previously known as PRSP (penicillin-resistant S. pneumoniae), as well as strains resistant to two or more of the following antibiotics: second-generation cephalosporins, macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.
Pretreatment sputum and blood isolates collected worldwide during GRN phase 2/3 clinical CAP trials (19992003) were retrospectively analysed for the MDRSP phenotype. Of the 352 S. pneumoniae isolates originally identified, 208 from 180 subjects were subjected to secondary MDR susceptibility testing by central laboratories. Confirmed MDRSP isolates were matched to individual subjects to assess clinical and microbiological outcomes for MDRSP-infections treated with GRN.
Expanded susceptibility testing identified 53/208 MDRSP isolates from 44 unique subjects. The lowest MIC50 and MIC90 values for MDRSP isolates tested against a panel of representative drugs were observed for GRN (Table 1; 0.03 mg/ml and 0.06 mg/ml, respectively). The incidence of resistance to the five classes of drugs was 11%, 12%, 21%, 19% and 18% for penicillin, 2nd Generation Cep., macrolides, tetracycline and Tri/Sulf, respectively. No isolates were resistant to GRN using a proposed susceptibility breakpoint value of <=1 mg/ml. Thirty-five percent, 28%, 15%, 9% and 13% of isolates were resistant to 1, 2, 3, 4 and 5 drug classes, respectively. The worldwide incidence of MDRSP was 18% with an equivalent geographic distribution of 19%, 21% and 16% among North America, Europe and the Rest of World. Overall, GRN provided clinical and bacteriological success for 32/35 (91%) CAP evaluable subjects with MDR infection, which was similar to clinical success for evaluable subjects with non-MDRSP CAP infections 151/165 (92%).
These data demonstrate the ability of GRN to successfully eradicate MDRSP associated with CAP.
|Session name:||XXIst ISTH Congress|
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