Safety and efficacy of different drug forms of amoxicillin / clavulanic acid in treatment of lower respiratory tract infections in adults: an open prospective randomized trial

Abstract

Amoxicillin/clavulanic acid (ACA) is one of the drugs of choice for treatment of lower respiratory tract infections (LRTI) in adults. One of the serious disadvantages of ACA is relatively high rate of gastrointestinal adverse events (AE). A new form of ACA, which is dispersable tablets Solutab, could potentially reduce the rate of AE because of more rapid and predictable absorption of clavulanic acid from intestine and improve clinical outcomes due to higher adherence to treatment. This trial was aimed to compare AE rate and clinical efficacy of the new dispersable ACA form Solutab with those of traditional ACA tabs in adult patients with non-severe LRTI. The treatment regimen comprised 500/125 mg t.i.d. during 5 to12 days. This was an open, prospective randomized trial performed at 4 clinical centres. Adults with clinically and radiologically detected non-severe community-acquired pneumonia or I or II types COPD exacerbations with purulent sputum received dispersable ACA tablets (the 1st group) or traditional coated tabs of ACA (the 2nd group) in a random proportion of 1 : 1. Clinical efficacy was evaluated with clinical signs, physical symptoms, additional laboratory and instrumental testing. The safety was assessed based on the patient's complaints and results of physical and laboratory examination in visits 2 (Day 3 or 4), 3 (Day 5 to 12), and 4 (Day 30 to 40 after taking the first dose of the drug). The trial involved 200 patients, the mean age, 32.7 ± 18.7 and 33.3 ± 18.6 yrs in the 1st and the 2nd groups, respectively. The groups were similar for history, severity, and clinical course of the disease. Clinical efficacy was 96.9 % in both groups in visit 3, 95.9 % and 96.9 % in the 1st and the 2nd group, respectively, in visit 4. The mean duration of antibacterial therapy was 7.1 ± 1.5 days in the 1st group and 7.2 ± 1.4 days in the 2nd group. AE were reported in 15 % and 31 % of the patients, respectively (p = 0.01). Gastrointestinal AE predominated in both the groups but the rate of diarrhea was lower in patients receiving dispersable ACA: 6 % vs. 17 % in the 2nd group (p = 0.027). Therefore, the new dispersable drug form of ACA has better safety profile in adult patients with non-severe LRTI compared to traditional ACA that was demonstrated by reduction in the AE, mainly diarrhea, rate. Both drug forms showed equally high clinical efficacy.