[Optimization of antibiotics in combination].
OBJECTIVE
To evaluate the antibacterial activity of Ciprofloxacin, Amikacin in combination with beta-lactams against Pseudomonas aeruginosa strains in vitro, to optimize treatment regime for antibiotics on the basis of pharmacokinetics (PK)/pharmacodynamics (PD) and drug sensitivity tests. Methods With checkerboard titration method, the minimal inhibitory concentrations (MIC) of a combination of antibiotics in different concentrations for 33 clinically isolated Pseudomonas aeruginosa strains were determined by broth dilution. Fractional inhibitory concentrations (FIC) were calculated for judging synergic effect of antibiotics.


RESULTS
The combination of Amikacin and Ceftazidime showed synergic effects (accounting for 57.6%). The combinations of Ciprofloxacin with Ceftazidime, Cefepime, Imipenem/Cilastatin, Meropenem showed synergic or additive effect. In the study with PK/PD, C(max)/MIC was the principal parameters for evaluation of aminoglycoside and fluoroquinolone antibiotics, while T > MIC was the principal parameter to be used to evaluate beta-lactams antibiotics.


CONCLUSIONS
When antibiotics are used in combination, MICs can be reduced significantly and antibacterial activities are enhanced remarkably. The combination of antibiotics results mainly in synergic or additive effect, and no inhibitory effect is observed. PK/PD analysis plays an important role in planning optimal combination regime to raise clinical efficacy.
Zhang
Li-Hua
LH
Department of Pharmacy, Third Affiliated Hospital of Inner Mongolia Medical College, Baotou 014010, PR China.
Wang
Ling-Feng
LF
Meng
Zhao-Yan
ZY
Yu
Qing-Ping
QP
Gao
Bai-Qing
BQ
Ba
Te
T
Wang
Xiao-Dong
XD
Ma
Wen-Hui
WH
Li
Yao-Yu
YY
Zhang
Jun
J
D000583:Amikacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002053:Burn Units; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D047090:beta-Lactams / Q000493:pharmacokinetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002939:Ciprofloxacin; D000583:Amikacin