The efficacy of a new pharmacokinetically enhanced formulation of
amoxycillin/
clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of
amoxycillin over the 12-h dosing interval to eradicate
penicillin-resistant Streptococcus pneumoniae (PRSP) with
amoxycillin (+/-clavulanic acid) MICs of </=4 mg/l, was evaluated in patients with
respiratory infections caused by S. pneumoniae, including PRSP (
penicillin MICs 2-16 mg/l). Data from nine clinical studies were combined (total intent-to-treat N=
5531). Six randomized, double-blind studies used
levofloxacin 500 mg od in acute bacterial
sinusitis (ABS),
levofloxacin 500 mg od in acute exacerbations of
chronic bronchitis (AECB),
clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired
pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators. The three remaining studies (two in ABS and one in CAP) were non-comparative. In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S. pneumoniae
infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA MICs of >/=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae
infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of
respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae
infection as this formulation covers many PRSP that are non-susceptible to
amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common
beta-lactamase-producing respiratory pathogens.