Garenoxacin activity tested against S. pneumoniae, H. influenzae and M. catarrhalis with elevated or resistant fluoroquinolone MIC values
Abstract number: p1571
Jones R., Sader H., Fritsche T., Strabala P., Biedenbach D.
To assess the garenoxacin (GRN) potency against a vast number of international respiratory tract infection (RTI) pathogens, especially versus phenotypic (high MIC) or genotypic (sequence change) QRDR mutants. A total of 40,423 isolates from 6 continents were analysed (19992005).
S. pneumoniae (SPN; 18,887 strains), H. influenzae (HI; 15,555) and M. catarrhalis (MCAT; 5,981) were susceptibility (S) tested by CLSI both microdilution methods against GRN and 25 comparison agents. Phenotypic QRDR mutants (PQMs) were defined by a ciprofloxacin (CIPRO) or levofloxacin (LEVO) SPN MIC at >=4 mg/L; or CIPRO MIC of >=0.25 mg/L for HI and MCAT. 124 SPN strains in 3 S groups (1. CIPRO and LEVO MIC >=4 mg/L; 2. CIPRO >= 4 mg/L and LEVO <=2 mg/L; 3. CIPRO and LEVO <=2 mg/L) had QRDR sequences determined (gyr A,B; par C,E).
Penicillin, macrolides and ceftriaxone resistance (R) rates for SPN were 18.1, 28.4 and 0.8%, respectively. CIPRO (2.6% R) and LEVO (0.9% R) rates were low as were PQM occurrences among HI (19 strains, 0.1%) and MCAT (15 strains, 0.2%). GRN remained the most active fluoroquinolone (>90% S) against all mutant isolates, but HI isolates were 78.984.2% S (see table). QRDR sequencing demonstrated average numbers of mutations at 2.7, 1.5 and 1.1 for S groups 1, 2, and 3, respectively; GRN MIC 50/90 results are 0.5/2, 0.06/0.12 and 0.06/0.12 mg/L. Highest GRN MIC results (>=1 mg/L) were associated with >=3 QRDR mutations. (See Table)
GRN maintains clinically usable activity (MIC, <=1 mg/L) against important community-acquired RTI pathogens having R to presently marketed fluoroquinolones and against those isolates with documented QRDR mutations. Continued development of this novel des-F(6) quinolone agent appears desirable.
|Session name:||XXIst ISTH Congress|
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