[Antibacterial activity of quinolones against various clinically isolated strains and evaluation of efficacy based on the pharmacokinetics/pharmacodynamics theory].
We compared the antimicrobial activities of oral quinolones, ciprofloxacin (CPFX), gatifloxacin (GFLX), garenoxacin (GRNX), levofloxacin (LVFX), moxifloxacin (MFLX), norfloxacin (NFLX), prulifloxacin (PUFX), and tosufloxacin (TFLX) using Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus agalactiae, Streptococcus pyogenes, extended spectrum beta-lactamase(ESBL) producing Klebsiella pneumoniae, and methicillin-susceptible Staphylococcus aureus (MSSA) isolated from clinical materials. Based on the pharmacokinetics-pharmacodynamics theory, the target attainment rate at the area under the curve (AUC)/MIC of 120 or more for Gram-negative and 30 or more for Gram-positive bacteria was calculated using Monte Carlo simulation (MCS), and was assessed as the efficacy. GRNX showed the lowest MIC50 and MIC90 values (0.03 and 0.06 microg/ml, respectively) against S. pneumoniae, suggesting its potent antimicrobial activity. GRNX also exhibited the most potent antimicrobial activity against Gram-positive bacteria (S. agalactiae, S. pyogenes, MSSA) other than S. pneumoniae. The antimicrobial activity of CPFX against H. influenzae was most potent. The MIC50 and MIC90 values were 0.016 microg/ml each. However, the MIC50 and MIC90 values of the other agents were also favorable. PUFX showed the most potent antimicrobial activity against ESBL-producing K. pneumoniae. Both of MIC50 and MIC90 values were 0.06 and 1 microg/ml, respectively. On efficacy assessment using MCS, GRNX, GFLX, and MFLX showed a probability of 90% or more against S. pneumoniae and S. pyogenes. Against S. agalactiae, GRNX, MFLX, and GFLX showed a probability of approximately 60%. All agents showed a low probability against ESBL-producing K. pneumoniae; PUFX showed a maximum (43.63%). GRNX, MFLX, GFLX, and LVFX showed a probability of 90% or more against MSSA. Furthermore, we investigated the probability that the target value of resistance inhibition, an AUC/MIC of more than 200 against S. pneumoniae, is achieved. GRNX showed the highest probability (95.05%). It also exhibited a similar probability even when the target value was established as 250. Recently, the widespread use of quinolones has increased the number of quinolone-resistant bacteria. In the future, antimicrobial agents should be selected with respect to more potent therapeutic effects and resistance inhibition, and an appropriate dose and administration method must be employed.
Nakamura
Tatsuya
T
Department of Clinical Laboratory, Kansai Medical University Hirakata Hospital.
Shimizu
Chihiro
C
Hirakawa
Kaname
K
Inui
Sachiko
S
Okuda
Kazuyuki
K
Nakata
Chiyo
C
Fujimoto
Hiroko
H
Okura
Hiroe
H
Uemura
Yoshiko
Y
Takahashi
Hakuo
H
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007564:Japan; D009010:Monte Carlo Method; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D015363:Quinolones