A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections.
We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sulbactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 microg/ml, respectively), as well as against a beta-lactamase-positive Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 microg/ml) and a beta-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.
Bantar
C
C
Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina. cbantar@armet.com.ar
Nicola
F
F
Fernandez Canigia
L
L
Arenoso
H J
HJ
Soutric
J
J
Montoto
M
M
Blanco
M
M
Smayevsky
J
J
Jasovich
A
A
D000284:Administration, Oral; D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D017714:Community-Acquired Infections / Q000097:blood / Q000188:drug therapy / Q000382:microbiology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006192:Haemophilus Infections / Q000097:blood / Q000188:drug therapy / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008954:Models, Biological; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000302:isolation & purification; D016870:Neisseriaceae Infections / Q000097:blood / Q000188:drug therapy / Q000382:microbiology; D010406:Penicillins / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000097:blood / Q000188:drug therapy / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D013407:Sulbactam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D010406:Penicillins; D000658:Amoxicillin; D013407:Sulbactam