Short-course therapy of gemifloxacin effective against pneumococcal pneumonia in mice.
Standard 7-14 day (d) courses of antimicrobial therapy for community-acquired pneumonia (CAP) are thought to have contributed to the emergence of resistant pneumoccoci. Consequently, short-course fluoroquinolone regimens have been proposed to minimize resistance. To test this, we examined 2-day versus 5-day regimens of gemifloxacin and levofloxacin for treatment of pneumonia in a murine model. In doing so, we also investigated whether the enhanced potency of gemifloxacin would influence outcomes. CD1 Swiss mice were infected intratracheally with 10(5)-CFU of a virulent Streptococcus pneumoniae strain. Drugs were administered every 8 h for 2 d and 5 d, starting at 24 h postinfection. Temperature was used to assess disease progression. Gemifloxacin remained effective for 2 d and 5 d, with survival rates of 100%-83% compared with 40%-58% for levofloxacin. Eighty-nine to 100% of gemifloxacin-treated mice were clear of pulmonary bacteria compared with only 0%-20% for levofloxacin. For levofloxacin-treated mice, 2 of 7 (29%) isolates with a levofloxacin minimum inhibitory concentration (MIC) 4 times that of the infecting parent strain had ParC mutations. By contrast, no isolates recovered from gemifloxacin-treated mice were reduced in susceptibility. Gemifloxacin could be effective in shortening duration of therapy for CAP treatment as well as minimize resistance development.
Bast
D J
DJ
Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Dresser
L
L
Duncan
C L
CL
Walker
S E
SE
Mandell
L A
LA
Low
D E
DE
de Azavedo
J C S
JC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects; D015169:Colony Count, Microbial; D027101:DNA Topoisomerase IV / Q000235:genetics; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077735:Gemifloxacin; D006801:Humans; D064704:Levofloxacin; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D000077735:Gemifloxacin