A clinical phase III study of pazufloxacin in patients with bacterial pneumonia

The clinical efficacy and safety of pazufloxacin(PZFX), an injectable fluoroquinolone antimicrobial, administered at a dose of 1,000 mg twice daily, were evaluated for 99 subjects with bacterial pneumonia, including severe or intractable pneumonia or that caused by Streptococcus pneumoniae in an open uncontrolled clinical study. The relationship between pharmacokinetics and the clinical efficacy or safety of PZFX was also investigated. Clinical efficacy rate at the end of treatment was 81.8% (81/99 subjects) in all pneumonia, 76.9% (20/26 subjects) in pneumonia caused by S. pneumoniae, and 81.3% (13/16 subjects) in severe or intractable pneumonia including 4 caused by S. pneumoniae. Eradication rate at the end of treatment was 96.8% (60/62 strains) in all pneumonia, 100% (25/25 strains) in pneumonia caused by S. pneumoniae, and 100% (9/9 strains) in severe or intractable pneumonia including 4 caused by S. pneumoniae. Main causative organisms were 26 S. pneumoniae, 17 Haemophilus influenzae, 8 Moraxella (Branhamella) catarrhalis, and 7 Klebsiella pneumoniae. PZFX MICs against S. pneumoniae were 0.78-3.13 μg/mL, and MIC₉₀ was 1.56 μg/mL. PK parameters by 1,000 mg dose were 137.0 μg·hr/mL for AUC and 32.0 μg/mL for Cmax. Clinical efficacy rate were 77.3% (34/44 subjects) and 78.0% (32/41 subjects) in those whose fAUC/MIC and Cmax/MIC exceeded the target. Eradication rate were 98.1% (51/52 strains) and 98.0% (48/49 strains) in those whose fAUC/MIC and Cmax/MIC exceeded the target. Adverse events were observed in 114 of 140 subjects (81.4%), and adverse drug reactions in 93 (66.4%). Severe adverse drug reactions were one each of asthma and interstitial pneumonia Adverse drug reactions exceeding 5% were injection site in 36.4% (51/140 subjects), increased ALT in 12.1% (17/143 subjects), increased AST in 12.1% (17/140 subjects). Most adverse drug reactions were mild or moderate and similar to those previously known for PZFX. A relationship was seen between the incidence of moderate or severe adverse events and AUC and/or Cmax. To ensure safety, it is vital to adequately observe and consider the interval of drug-administration or dosage adjustment in low Ccr subjects. We concluded that 1,000 mg dose twice daily is useful in those with bacterial pneumonia, including pneumonia severe or intractable or caused by S. pneumoniae.