Effect Of Macrolide (Azithromycin) Against Streptococcus Pneumoniae In A Murine Lung Infection Model

[Background and Objective]Macrolidehave been already used as the first-line therapy against Streptococcus pneumoniae (SP)since 1993. However, drug resistance rate among respiratory pathogens has been increased rapidly in recent years, notably SP which has shown high resistant levels of penicillin and macrolide. Although there were some reports of treatment failure with macrolides used as first-line therapy for SP infection, other observational data suggested that in vitro susceptibility might not correlate with clinical efficacy. However, there are some ethic issues that have limited our further studies on human, a larger study is necessary to prove the efficacy against macrolide-resistant S. Pneumoniae. The murine lung infection model was used to evaluate the efficacy of Macrolide (Azithromycin) against Streptococcus pneumoniae.[Material and Methods]SPF BALB/c mice (female,6-8 week) were used in this lung infection model. Mice were randomly divided to 4 groups and were infected with PBS and different strains of Streptococcus Pneumoniae (susceptible strain, ermB strain and mefA strain).24 hours after infection, mice were treated with Azithromycin (AZM) and/or Ceftriaxone (CEF). Survival rate were examined on the 10 dpi (days post-infection).The bacterial counts and azithromycin in lung were detected at 3 and 5 dpi as well. The inflammatory factors (IL-6, IL-10 and TNF-a) in BALF and serum were assayed by ELISA. Changes in lung tissue histopathology were observed with HE staining through light microscope.[Results]AZM were extremely efficacious for susceptible isolate. Survival rate of mice treated AZM alone in susceptible group reached 100%. Mortality of mice treated with AZM alone in ermB and mefA groups reached 80% and 60%. The concentration of AZM remained a high level in lung tissues on both 3 and 5 dpi. In susceptible group, AZM reduced significantly bacteria counts in the lungs on both 3 and 5 dpi (P<0.01, vs. mice treated with PBS). In ermB and mefA group, AZM reduced bacteria counts significantly (P<0.05, vs. mice treated with PBS). We also determined pro-inflammatory factors (IL-6, TNF-a) and anti-inflammatory factor (IL-10) in mice B ALF and serum. The results showed that AZM reduced differently levels of theses pro-inflammatory factors and enhanced the level of IL-10 in susceptible, ermB and mefA groups (P<0.05, vs. mice treated with PBS).In ermB and mefA groups, compared with CEF, AZM showed lower bacteria clearance capacity, but reduced significantly the levels of IL-6 and TNF-a and enhanced the level of IL-10 (P<0.05, vs. mice treated with CEF). AZM improved the phagocytic function of macrophages.[Conclusions]AZM showed more efficacious for susceptible isolate. Although mice were infected by streptococcus pneumoniae with low level of macrolide resistance, AZM could increase survival of SP-infected mice by decreasing bacteria counts, reducing levels of inflammatory cytokines, remaining high concentration levels in lung and improving the phagocytic function of macrophages. If streptococcus pneumoniae was detected high level of macrolide resistance, according to our research, AZM shouldn’t be the first choice.