In Vitro Antibacterial Activity Of Combined Used Fosfomycin,Minocycline, And Polymyxin B On Pan-drug Resistant Acinetobacter Baumanii

Objective:The study is to determine the effect of combined use of fosfomycin, minocycline and polymyxin B for the treatment of the Pan-drugresistant Acinetobacterbaumanii (PDR-Ab).Method:The in vitro antibacterial activities of the drugs were examined by determination of the minimum inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI). Twenty-five strains of Pan-drug resistant Acinetobacter baumanii were selected by using the VITEK32microbial analysis instrument and the Kirby-Bauer (K-B) method. Broth microdilution method was used to determine MIC for the three drugs, and the checkerboard method was simultaneously used to determine the MIC for the combined use of drugs. FICI values were also calculated.FICI values are<0.5,0.5-1.0,1.0-4.0, or>4.0, they were considered to indicate a synergistic effect, additive effect, independent effect, or antagonistic effect respectively.Results:While fosfomycin alone is ineffective for the treatment of Pan-drug resistant Acinetobacter baumanii, its MIC value is significantly reduced when used in combination with minocycline or polymyxin. The combined use of minocycline and polymyxin B also significantly reduces the MIC values of each other. The FICI values also show a synergistic or additive effect of combined use of drugs.Conclusions:The determination of MIC and FICI values for combined use of drugs demonstrate that there is synergistic or additive effect upon the combined uses of fosfomycin and minocycline or polymyxin. The combined use of minocycline and polymyxin B also results in a significant reduction in the MIC values. These experimental results provide a basis for future clinical treatment of Acinetobacter baumanii.Significance:At present, the drugs used for treatment of pan-drug resistant Acinetobacter baumannii(PDR-Ab) is few in category and species, not highly sensitive and PDR-Ab infection is difficult to cure. Currently there are enzyme inhibitors, tetracycline class and polymyxin class for clinical relative effective drugs. For the treatment of systemic infection caused by PDR-Ab, a single drug is generally ineffective, so it is preferred to advocate the drug combination clinically. Although fosfomycin is invalid for multiple drug-resistant bacteria, it synergies effectively with other antibiotics, without inducing cross resistance.The combined use of Minocycline and polymyxin B can obviously increase the antibacterial activity of each other, while the combination of fosfomycin and one of the former two can also decrease the bacteriostatic concentration and reduce the chances of side effects occurrence. In vitro experiment can provide evidence for the clinical therapy of severe Acinetobacter baumannii infections and drug-resistant bacteria infection and guide the application of clinical antibacterial drugs. The best treatment effect can be achieved by reasonable choice of antibiotics in the limited drugs, reasonable drug combination and appropriate drug dosage. It can improve the curative effect, shorten treatment period, reduce or delay the produce of drug-resistant bacteria, reduce combined drug dosage and also reduce the adverse reaction of antibiotics. At the same time, it can cut down medical consumption for the patients and society and bring considerable social benefits.