Laboratory and clinical studies on lenampicillin (kbt-1585) A new penicillin antibiotic

Laboratory and clinical studies on lenampicillin (KBT-1585), a newly developed ampicillin prodrug, were carried out with following results. 1) Antibacterial activity: The in vitro antibacterial activity of KBT-1585 was tested by the serial microbroth dilution method using MIC 2000 system (Dynatek Co.). The minimum inhibitory concentrations (MICs) of ABPC against total 433 strains consisting of 26 standard strains and 407 clinical isolates including Staphylococcus aureus 48, Staphylococcus epidermidis 42, Streptococcus pneumoniae 48, Streptococcus faecalis 44, Escherichia coli 52, Klebsiella aerogenes 49, Proteus mirabilis 47, Haemophilus influenzae 63 were compared with those of amoxicillin (AMPC), mecillinam (MPC) and piperacillin (PIPC). Antibacterial activities of ABPC against S. aureus, S. epidermidis and 5. faecalis were almost equal to those of AMPC, and more potent than those of PIPC and MPC. AMPC and PIPC were two times more active than ABPC against S. pneumoniae. On the other hand, antibacterial activities of ABPC and AMPC against Enterobacteriaceae such as K. aerogenes, E. coli and P. mirabilis were less potent than those of PIPC and MPC. PIPC was most active against H. influenzae and followed by ABPC and AMPC. 2) Serum and sputum levels in patients with chronic respiratory tract infection: Two patients with chronic respiratory tract infections were objected in this study. After a dose of 500 mg of KBT-1585 was given to them orally, their levels in sera and sputa were measured by bioassay method. As a result, peak serum levels were obtained at one hour after administration showing values of 6.39 to 10.64 μg/ml. On the other hand, concentrations of sputum reached its peak at 4 to 6 hours after administration in one case with purulent sputum and the value was 0.38 μg/ml. But in one case, the value was under the limit of measurement. 3) Clinical evaluation and adverse reaction: Forty patients with respiratory infections (pneumonia 16, chronic bronchitis 15, bronchiectasis 8, organizing pneumonia 1) were treated with 0.75 to 1.0 g of KBT-1585 daily for 3 to 21 days by oral administration. Twenty-nine of 39 patients responded satisfactorily to the treatment and the efficacy rate was 74.4% (excellent 9, good 20, fair 5, poor 5, unknown 1). Subjective and objective symptoms, hematological and biochemical data and renal functions were checked up before and after administration of KBT-1585. Abnormal laboratory findings were observed in 3 cases: elevation of S-GOT in 1, BUN in 1 and Al-Pase in 1.