RESUMO
Objective: To investigate the antibacterial impact of daptomycin and azithromycin in vitro on methicillin-resistant Staphylococcus aureus (MRSA) biofilm. Methods: (1) Measure the strain growth curve and the biofilm formation curve. (2) Determine the minimum inhibitory concentrations (MICs) of daptomycin and azithromycin. (3) Investigate the antibacterial impact of the combination of daptomycin and azithromycin. (4) Perform the evaluation of the intervention impact of antimicrobial agents on MRSA biofilm. (5) Observe the biofilm after intervention with the antibacterial agent. Results: (1) MRSA exhibited three phases: lag phase (0-4 h), logarithmic growth (4-8 h) and stationary phase after 18 h; its biofilm began to form at 6 h, semi-matured at 24 h, and reached maturity after 48 h. (2) The MICs of daptomycin and azithromycin were 8 µg/mL and greater than 256 µg/mL, respectively. (3) The combination of daptomycin and azithromycin has an additive effect on MRSA (Fractional Inhibitory Concentration Index [FICI] 0.625) (FICI = MIC of drug A in combination/MIC of drug A alone + MIC of drug B in combination/MIC of drug B alone). Evaluation criteria: Synergistic effect is considered when FICI ≤ 0.5; additive effect is considered when 0.5 < FICI ≤ 1; irrelevant effect is considered when 1 < FICI ≤ 2; antagonistic effect is considered when FICI > 2). (4) Daptomycin or azithromycin at MICs inhibited not only the growth of planktonic bacteria but also the formation of biofilm. (5) The combination of both, in which group the ratio of live/dead bacteria is low and the biofilm morphology was incomplete, was more productive than monotherapy in against biofilm. Conclusion: Both daptomycin and azithromycin have anti-MRSA biofilm activity, and daptomycin is dominant. The fact that the combination of both can significantly inhibit the further maturation of MRSA biofilm and destroy already formed biofilm demonstrates the superiority of the combination over the monotherapy.
RESUMO
OBJECTIVE: To investigate the protection mechanism of reduced glutathione (GSH) in acute lung injury in rats with sepsis. METHODS: Sepsis in Sprague-Dawley (SD) rats were reproduced by cecal ligation and puncture (CLP). They were randomly divided into four groups, sham-operated group, model group, GSH treatment group and levofloxacin (LEV) treatment group. Heart blood of 7 rats in all groups was collected at 3, 6, 12, 24 hours after operation. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. The lung ultrastructure changes were observed with electron microscope at 24 hours in all groups. RESULTS: Compared with the sham-operated group, the plasma level of TNF-alpha increased more obviously at 6 hours of the model group [(227+/-28) microg/L vs. (132+/-9) microg/L, P<0.01]. Compared with the model group, the plasma level of TNF-alpha in the GSH treatment group decreased obviously [(144+/-28) microg/L], and it was obviously lower than that of LEV treatment group [(214+/-48) microg/L , both P<0.01] . No obvious difference of plasma level of TNF-alpha was found at 3, 12, 24 hours among all the groups. Compared with the sham-operated group, the plasma level of IL-6 of the model group raised obviously at 3 hours [(267.65+/-72.87) microg/L vs. (135.43+/-40.08) microg/L, P<0.01]. In the GSH treatment group, the plasma level of IL-6 [(191.97+/-62.98) microg/L] was lower than that of the model group and the LEV treatment group [(268.75+/-74.67) microg/L, both P<0.05]. The plasma level of IL-6 was not obviously different among all groups at 6, 12, 24 hours. In the model group, the injury of pulmonary ultrastructure was obvious, especially in the mitochondria of the pulmonary cells. In the GSH treatment group, the change in ultrastructure of the lung was slight. CONCLUSION: TNF-alpha and IL-6 play significant role in the development of pulmonary ultrastructure injury in acute lung injury of septic rats. Treatment with GSH was effective in preventing such injury.