Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate

Int J Antimicrob Agents. 2002 Oct;20(4):235-47. doi: 10.1016/s0924-8579(02)00130-9.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amoxicillin / adverse effects
  • Amoxicillin / therapeutic use
  • Amoxicillin-Potassium Clavulanate Combination / administration & dosage
  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics*
  • Amoxicillin-Potassium Clavulanate Combination / pharmacology
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Bronchitis / drug therapy
  • Bronchitis / microbiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Multicenter Studies as Topic
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / immunology
  • Respiratory Tract Infections / drug therapy*
  • Respiratory Tract Infections / metabolism
  • Respiratory Tract Infections / microbiology
  • Streptococcal Infections / drug therapy*
  • Streptococcal Infections / metabolism
  • Streptococcal Infections / microbiology
  • Streptococcus pneumoniae / drug effects*
  • Treatment Outcome*


  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin