BASIC AND CLINICAL STUDIES ON TAZOBACTAM/PIPERACILLIN IN PEDIATRIC FIELD

Abstract

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed β-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1: 4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows:
1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and theothers were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 106 CFU/ml.
The MIC₉₀ values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05μg/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39μg/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC₉₀ of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10μg/ml and similar to those of PIPC. The MIC₉₀ of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05μg/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non β-lactamase producing strain and a low-β-lactamaseproducing strain, were 0.78μg/ml and 3.1μg/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05μg/ml, and the others at 1.56μg/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce β-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against β-lactamase nonproducing strains were≤0.025μg/ml in 5 strains and 0.39μg/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high β-lactamase producing strain was 0.78μg/ml; similar to that of SBT/CPZ and smaller than that of PIPC.
2. The results of clinical effects on 7 diseases in 33 cases were as follows:
TAZ/PIPC was clinically judged “gexcellent” in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of “excellent” and “good” was 93.9%.
3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated.
4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%).
5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.