title: Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate.
abstract: 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.
authors.affiliation: Summa Health System, Northeastern Ohio Universities College of Medicine, 75 Arch Street, Suite 105, Akron, OH 44304, USA. filet@summa-health.org
authors.forename: Thomas M
authors.initials: TM
authors.lastname: File
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: Michael D
authors.initials: MD
authors.lastname: Poole
authors.forename: Brian
authors.initials: B
authors.lastname: Wynne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D001991:Bronchitis / Q000188:drug therapy / Q000382:microbiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000276:immunology; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin