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 res piratory tract infections, we assess here the pharmacodynamics of amoxicill in/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 a nd currently available in 17 countries, against the major pathogens, in com parison with that of a novel formulation (875mg/125mg, see J Chemother 2000 ; 12: 223-227). In time-kill studies, both bactericidal and inhibitory acti vity 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 -intermedi ate Streptococcus pneumoniae strain, as well as against Moraxella catarrhal is 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 mug/ml) and a beta -lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a su itable option for treating community-acquired lower respiratory tract infec tions, allowing a b.i.d. dosing schedule. Caution should be taken with pneu monia caused by beta -lactamase-positive H. influenzae or penicillin-resist ant (MIC greater than or equal to2 mug/ml) S. pneumoniae isolates. Either s horter dosing intervals (t.i.d.) or a higher amoxicillin content in the for mulation (i.e. 875 mg) may be required in these situations.