Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci.
J Antimicrob Chemother
; 53(2): 305-10, 2004 Feb.
Article
en En
| MEDLINE
| ID: mdl-14729741
Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1x 125 mg/kg) was slightly less bactericidal (-0.30 Deltalog(10) cfu/mL(.)h) compared with levofloxacin (-0.45 Deltalog(10) cfu/mL(.)h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Deltalog(10) cfu/mL(.)h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strains.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Streptococcus pneumoniae
/
Ceftriaxona
/
Resistencia a las Penicilinas
/
Ofloxacino
/
Cefalosporinas
/
Levofloxacino
/
Meningitis Neumocócica
/
Antibacterianos
Límite:
Animals
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2004
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Reino Unido