ABSTRACT
Ipsat P1A is a recombinant beta-lactamase which degrades antibiotic residue in the gastrointestinal tract. In an open-label, single-center controlled trial, 36 healthy subjects were randomized to receive (i) ampicillin (1 g intravenously [i.v.] every 6 h [q6h]), (ii) oral P1A recombinant beta-lactamase (8.2 mg q6h), or (iii) ampicillin (1 g i.v. q6h) in combination with oral P1A recombinant beta-lactamase (8.2 mg q6h) for 5 days. Fecal samples were collected before treatment, during treatment (days 3 to 5), and at follow-up (day 12). The primary end points were (i) changes in gastrointestinal microflora (determined by temperature gradient gel electrophoresis [TGGE]) and (ii) emergence of bacterial resistance (determined by conventional microbiology and PCR of TEM beta-lactamase genes). Thirty-five subjects completed the study. The mean similarity percentages of TGGE profiles between baseline and each treatment day sample were significantly lower for the ampicillin group than for the group receiving ampicillin plus P1A recombinant beta-lactamase on days 3, 4, and 5 (P < 0.001). Compared with the ampicillin group, subjects receiving ampicillin plus P1A recombinant beta-lactamase had significantly fewer ampicillin-resistant coliforms on days 3, 4, and 5 and at follow-up (P < or = 0.001) and fewer TEM beta-lactamase genes on days 3, 4, and 5 (P < 0.02). P1A recombinant beta-lactamase was safe and well tolerated. In healthy subjects, P1A recombinant beta-lactamase prevents ampicillin-induced alterations in intestinal microflora, emergence of resistance, and the number of TEM genes.
