Fundamental and clinical studies on hbk, a new aminoglycoside antibiotic

Fundamental and clinical studies on HBK, a novel aminoglycoside antibiotic, were carried out with following results. 1) Antibacterial activity : The in vitro antibacterial activity of HBK was tested by the serial microbroth dilution method using MIC 2000 system (Dynatek Co.). The minimum inhibitory concentrations (MICs) of HBK against total 336 strains consisting of 26 standard strains and 310 clinical isolates were compared with those of gentamicin (GM), tobramycin (TOB), dibekacin (DKB) and amikacin (AMK). The activity of HBK was higher than that of AMK, although it was 50 to 100% of SISO and GM. However, HBK showed the highest activity among these antibiotics against the resistant strains. 2) Absorption and Excretion : The pharmacokinetic study was made in four patients by the bioassay method. Serum levels of HBK were measured in two patients given by intramuscular injection of 50 mg and one patient intravenous drip infusion of 100 mg. The peak concentration in serum was 5. 2 μg/ml and 8.8μg/ml at 30 min. and one hour after administration by intramuscular injection, respectively, and 4. 24 μg/ml at one hour after the beginning of intravenous drip infusion. In the case of sputum, the peak concentration was 0. 32 μg/ml at 3 to 4 hours and 1.76 μg/ml at 2 to 3 hours after intramuscular injection, and 1. 32 μg/ml at 3 to 4 hours after the beginning of intravenous drip infusion. The urinary recovery rate of HBK until 6 hours after intramuscular administration of 50 mg was 51.2%. 3) Transition of bacteria in sputum : S. aureus in the sputum of a patient with chronic bronchitis began to decrease from the initial 10⁷cfu/ml to 10⁵ cfu/ml for the first 6 hours after intramuscular injection, and was completely eliminated on the third day of treatment. However, H. influenzae in two patients and P. aeruginosa in one patient were not eliminated from the sputa in spite of 7 days treatment, and S. pneumoniae was isolated from the sputum on the third day of treatment in one case. 4) Clinical evaluation and adverse reaction : Twenty four and 10 out of 34 patients with respiratory infections (pneumonia in 15, lung abscess in 1, chronic bronchitis in 8, bronchiectasis in 5, diffuse panbronchiolitis(D. P. B.) in 2, bronchial asthma with infection in 2 and pulmonary tuberculosis in 1) were treated by intramuscular injection and intravenous drip infusion, respectively. The efficacy rate was 60.6% in total (That of the former was 65.2% and the latter was 50.0%). Four out of total patients showed the following adverse reactions : eruption, slight elevation of BUN, slight elevation of S-GOT and S-GPT, and slight decreasernent of creatinine-clearance in each patient.