Bacteriostatic Effect Of Fluoroquinolones Combined With Doxycycline Against E.coli From Cattle In Vitro

The discovery and application of antibiotics has brought new hope for the prevention and treatment of bacterial disease. Now antimicrobial drugs are widely used in clinical treatment, and they are used in livestock production as growth promoting agents added to the feed.Because of the abuse of antibiotics, a significant bacteria resistance to antibiotics was caused, which make it more difficult to prevent and treatbacterial diseases. Escherichia coli(E. coli)is the body’s natural flora,it can exist in environment. Once the immunity of body declined,it wouldbecome pathogenic bacteria, thus, great attention has been paid to its drug resistance status both in people and livestock production.In recent years, as the cow colibacillosis have brought farmers a huge economic loss,prevention and therapyof colibacillosishas become an important issue concerned by researcherand workers in the fieldof livestock.At present, antibiotics dosage are based on the minimum bacteriostas for E. coli treatment in cattle, With the development of the research, from which drug resistance aggravation was observed. Then Zhao et al put forward a new regimen that reduce the mutant prevention concentration of antibiotics or close and narrow mutant selection windows.Based on the theory, effect of fluoroquinolone drugs combined doxycycline on the drug-resistant mutant selection window were demonstrated.In the study, sensitivity of 40 E.coli strains from cattle to 14 antimicrobial agents were tested using K- B test. The results showed that condition of E.coli strains drug resistance was terrible.drug resistant rate of fluoroquinolones, cephalosporin and ceftazidime is between 20% and 32.5%,under 50%, and only 2.5% respectively. However, the resistant rate of TMP reached up to 85%,followed by over 60% of AM, AMX. Florfenicol and doxycycline was 7.5% and 35%. Further,quantitative and qualitative double broth dilution methodand combined sensitivity test were adopted to determine MIC of ofloxacin, ciprofloxacin and doxycycline on 40 E. coli strains, The MIC of doxycycline combined with toofloxacin and ciprofloxacin respectively on 4 E. coli strainswas tested then the FIC index was calculated. The results showed the MIC of combination of the two drugs on 2 strains were reduced in different degree compared with two drug used individually, FIC≤1 indicated that the combination was additive effec against 4 strains.The MPC 、MSW and SI of ofloxacin, ciprofloxacin and doxycycline used individually and doxycycline combined with ofloxacin and ciprofloxacin respectively were measured against E. coli1、E1、E2、E3by the agar plate dilution method, then, the MPC of the ofloxacin, ciprofloxacin,andoxycycline were respectively 12.8μg·m L-1、6.4μg·m L-1、2.56μg·m L-1、81.6μg·m L-1;16μg·m L-1、10.24μg·m L-1 、 16μg·m L-1 、 10.24μg·m L-1;102.4μg·m L-1 、 65.64μg·m L-1 、 52.43μg·m L-1 、256μg·m L-1;SI was respectively 6.4/12.8/10.24/10.2;16/20.48 6.4/12.9;12.8/16.4/13.11/16. the MSW of comninationgroup on 4 strains was respectively decreased by 4.6, 2.4, 3.4, 2.4 times;8.7,4.2, 2, 5.4 times;5.7, 2.6, 2.7, 2.6 times. These results showed that combination of the fluoroquinolones and doxycycline could reduce the MPC and narrow the MSW of the two drugs used individually.From growth curve of drug-resistant mutant strains treated with different drug concentrations,it was concluded that the growth platform stage of drug combinations were shorter than drugs used individually and the curves moved leftwards, which indicated that combination of fluoroquinolones and tetracyclines could narrow mutant selection window compared with them used respectively.