Efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg (PKE AMX/CA) in patients with community-acquired pneumonia, including cases caused by penicillin-resistant S. pneumoniae

Abstract number: 1134_02_88

Bhatt K., Kalia V., Berkowitz E., Twynholm M., Abraham-van Parijs B., Hodge R.

Objectives:

To evaluate the efficacy and safety of PKE AMX/CA against CAP, a common, costly respiratory illness, particularly cases caused by Streptococcus pneumoniae, including penicillin-resistant (PRSP, penicillin MICs >=2 mg/L) strains.

Methods:

An open-label, non-comparative, multicentre study. Patients with a diagnosis of CAP received oral PKE AMX/CA, 2x 1000/62.5 mg tablets twice daily, for 7 days. Patients were required to provide a sputum sample or, if clinically indicated, an invasive respiratory sample for bacteriological evaluation. Positive pneumococcal urine antigen test and/or the presence of Gram+ diplococci by direct examination of a sample smear was added to inclusion criteria via protocol amendment. Patients were to attend clinic at screening (Day 0), on therapy (Day 3–5), end of therapy (EOT, Day 9–11) and follow-up (FU, Day 28–35).

Results:

A total of 1903 patients were enrolled, 1888 of whom (including 984 post-protocol amendment) received study medication and had verifiable efficacy results (intent-to-treat [ITT] population). Of these, 665 had >=1 typical pathogen identified at screening (bacteriology ITT population). The majority of patients (58.7%) were male and the mean age was 46.5 years. Bacteriological success (eradication or presumed eradication of screening pathogen) in the bacteriology ITT population at FU (primary efficacy endpoint) was 79.7% (530/665; 95% CI 76.4, 82.7) and at EOT was 87.4% (581/665; 95% CI 84.5, 89.7). Bacteriological success at FU against S. pneumoniae was 84.0% (331/394) in the bacteriology ITT population, including 81.4% (35/43) of patients with PRSP, and against Haemophilus influenzae was 79.0% (128/162). Clinical success (resolution of signs/symptoms of CAP such that no further antibacterial therapy was needed) and radiological success (improvement/resolution of radiological signs of CAP) were achieved in >77% of patients at FU and >80% of patients at EOT. In the safety population (N = 1900), diarrhoea was the most frequently reported adverse event (AE), occurring in 14.3% of patients. Headache (4.6%, 87/1900) and nausea (3.3%, 62/1900) were the only other AEs to occur in >=3% of patients. The majority of AEs were mild to moderate in severity. Only 4.9% (93/1900) of patients in the ITT population withdrew from the study due to AEs.

Conclusions:

PKE AMX/CA was effective in treating CAP, including cases caused by PRSP, and was well tolerated, with few patients withdrawing from the study due to AEs.