Amdinocillin is a novel
penicillin whose antibacterial activity is derived from its ability to bind specifically and avidly to
Penicillin Binding Protein-2 (PBP 2). Other
beta-lactams bind almost exclusively to PBPs 1 and 3. This unique feature has prompted many investigators to predict that
amdinocillin would aggressively synergize with other antimicrobials, particularly other
beta-lactams. Certain features of these predictions have been realized.
Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant.
Amdinocillin, in combination with many
beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species.
Amdinocillin is not
beta-lactamase stable. Organisms which produce high levels of plasma-mediated
beta-lactamase are resistant to the
drug.
Amdinocillin is widely distributed to most tissues of the body. It is removed by renal tubular secretion which results in prodigious levels of the
drug in the urine. Co-administration of
probenecid results in markedly elevated plasma levels of
amdinocillin and delays its excretion.
Amdinocillin has a plasma half-life of about one hour in patients with grossly normal renal function. Its half-life increases to 3 to 6 hours in anephric patients. The spectrum of adverse reactions observed with
amdinocillin is similar to that of other
penicillins.
Amdinocillin, as a single agent, is effective in the treatment of
urinary tract infections caused by susceptible strains of E. coli and klebsiella and enterobacter species. When
amdinocillin is used in concert with other antimicrobials, synergy can frequently be demonstrated but it is essentially limited to gram-negative aerobic organisms. At present, insufficient data are available to precisely profile the utility of
amdinocillin, either alone or in combination, in the treatment of systemic
infections.