Efficacy of pulsatile amoxicillin and clarithromycin dosing alone and in combination in a murine pneumococcal pneumonia model.
OBJECTIVE
Amoxicillin and clarithromycin have been proven to be effective in the treatment of community-acquired pneumonia. This study investigated the in vivo bactericidal efficacy of a novel, pulsatile dosing strategy for amoxicillin and clarithromycin, when used as monotherapy and combination therapy.


METHODS
A neutropenic murine pneumonia model was used to assess the bactericidal activity of amoxicillin and clarithromycin, when the same total daily dose was administered as a traditional regimen (every 8 h and every 12 h, respectively) or as a pulsatile regimen (four doses of antibiotic given every 2 h over the first 6 h of the day) against three isolates of Streptococcus pneumoniae of varying resistance profiles. The three isolates consisted of SP21 (macrolide and penicillin susceptible), SP100 [mef(A) gene], and SP107 [mef(A) + erm(B) genes].


RESULTS
Pulsatile dosing showed similar reductions in bacterial density for amoxicillin and clarithromycin when either drug was given alone compared with traditional dosing regimens against all three bacterial isolates. When amoxicillin and clarithromycin were combined, improved activity was found compared with monotherapy. Overall, when comparing the different combination regimens, the pulsatile regimens provided similar activity compared with the traditional regimens. For one isolate, SP107, pulsatile amoxicillin combination regimens were less effective compared with traditionally dosed amoxicillin combination regimens.


CONCLUSIONS
Pulsatile dosing resulted in comparable bactericidal activity against the three isolates tested and may represent an alternative dosing strategy, which may help to alleviate problems with patient adherence to drug therapy.
Sun
Heather K
HK
Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
Lee
Su Young
SY
Banevicius
Mary Anne
MA
Du
Xiaoli
X
Maglio
Dana
D
Nicolau
David P
DP
D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D017291:Clarithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D008565:Membrane Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D020551:Pulse Therapy, Drug; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D001426:Bacterial Proteins; D004338:Drug Combinations; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D000658:Amoxicillin; D008780:Methyltransferases; C431709:ErmA protein, Bacteria; D017291:Clarithromycin