Rationale for treating community-acquired lower respiratory tract infections with amoxicillin/sulbactam combination through pharmacodynamic analysis in the setting of aminopenicillin-resistant organisms.
In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxicillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 microg/ml) and a beta-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by beta-lactamase-positive H. influenzae or penicillin-resistant (MIC > or =2 microg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations.
Bantar
C
C
Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina. cbantar@arnet.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 / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000302:isolation & purification; D010403:Penicillin Resistance; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D013407:Sulbactam / Q000494:pharmacology
D000658:Amoxicillin; D013407:Sulbactam