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Background:Neisseria gonorrhoeae(NG) infection is a serious public health problem.The third-generation extended-spectrum cephalosporins (ESCs) have been used as the first-line treatment for NG infection for almost three decades.However,in recent years,treatment failures withthe oral third-generation ESCs have been reported worldwide.This study aimed to estimate worldwide susceptibilityrates of NG to cefixime and cefpodoximeby analyzingdata from all relevant published studies.Methodology/principal findings:Two researchersindependently searched five databases to identify studies on susceptibilities of NG to cefixime and cefpodoximepublished between January 1,1984 and October 15,2012.A fixed-effect model was used to perform group analysis,and a χ2 test was employed to make subgroup comparison.Publication bias was assessed withthe Begg rank correlation test.The pooled susceptibility rate of NG isolates to cefixime was 99.8% (95% CI:99.7%-99.8%).Thecefixime susceptibility rate of NG isolates from men was significantly lower than that from patients without information of gender or from men and women;the susceptibility rate of NG isolates from Asia was significantly lower than that from other continents;and the susceptibility rate of NG isolates collected before or during 2003 was significantly higher than that after 2003.The pooled susceptibility rate of NG isolates to cefpodoxime was 92.8% (95% CI:89.0%-95.3%),which was lower than that to cefixime (92.8% vs.99.8%,χ2=951.809,P <0.01).Conclusions:The susceptibility rate of NG isolates to cefixime varied with the gender of patients and geographical location from which NG isolates were collected,and declined with time.The reported lower susceptibility rate of NG isolates to cefixime and associated treatment failures,as well as the emergence of NG strains with cephalosporin resistance call for the more effective control of NG infection and the development of new antibiotics.