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The Susceptibility Of Neisseria Gonorrhoeae To Cephalosporins And Other Antibiotics And MLVA Analysis, And In Vitro Synergy Testing Of Azithromycin And Ceftriaxone Combination Therapies Against Neisseria Gonorrhoeae In China

Posted on:2016-02-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:R X YuFull Text:PDF
GTID:1224330461476733Subject:Dermatology and Venereology
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Section 1. A Meta-analysis on cefixime and azithromycin susceptibility of Neisseria gonorrhoeaeObjective to estimate wordwide susceptibility rates of Neisseria gonorrhoeae (NG) to cefixime and cefposoxime by analyzing data from all relevant published studies; to get information on azithromycin susceptibility rates of NG isolates in China. Methods Two researchers independently searched PubMed, Embase, Web of Science, CNKI, and Wanfang to identify studies on susceptibilities of NG to cefixime and cefpodoxime. A total of 21 studies on susceptibilities of NG to cefixime and 5 studies on cefpodoxime were included in this study. A total of 8 studies on susceptibility of NG to azithromycin were included in another Meta-analysis. Results The pooled susceptibility rate of NG isolates to cefixime was 99.8% (95% CI:99.7%-99.8%). The cefixime susceptibility rate of NG isolates from men was significantly lower than that from patients without information of gender (96.5% vs.99.9%, x2=1341.499, P<0.001) or from men and women (96.5% vs.99.8%, x2=6776.778, P<0.001); the susceptibility rate of NG isolates from Asia was significantly lower than that from Europe (97.4% vs.99.0%, x2=669.637, P<0.001), North America (97.4% vs.99.9%, x2=183.740, p<0.001), and Africa (97.4% vs.99.5%, x2=3.987, P=0.046); and the susceptibility rate of NG isolates collected before or during 2003 was significantly higher than that after 2003 (99.8% vs.99.0%, χ2=198.597, P<0.001). 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%, x2=951.809, P<0.01). The pooled resistant rate of NG to azithromycin was 6.3% (95%CI:3.3%-11.6%). The resistant rate of NG isolates collected before 2008 to azithromycin was 2.0% (95%CI 0.9-4.4%), and in and after 2008 was 12.5%(95%CI: 7.1%-20.3%). This parameter between two subgroup was statistical difference (χ2=27.650, P<0.001). The azithromycin resistant rate of NG isolates collected from Guangdong, Nanjing and Chongqing, and Shandong and Heibei was statistical difference (x2=22.321,P<0.001). Conclusion In general, the NG isolates were susceptible to cefixime worldwide. But 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. Azithromycin was not fit for the first line drug for NG infection in China, especially in Guangdong province.Section 2. Cefixime and other antibiotics susceptibility evaluation and multiple-locus variable number tandem repeat analysis of Neisseria gonorrhoeae isolates in China,2012Objective to gain information on cefixime and other antibiotics susceptibility and molecular epidemiological typing of NG isolates in Guangzhou, Nanjing, and Tianjin in China in 2012. Methods A total of 244 NG isolates were collected from Guangzhou, Nanjing, and Tianjin in 2012. NG susceptibilities to penicillin and tetracycline were examined by detecting penicillinase-producing NG (PPNG) and high-level tetracycline-resistant NG (TRNG); and NG susceptibilities to ciprofloxacin, spectinomycin, and ceftriaxone were determined using agar dilution method, and cefixime using Kirby Bauer test. NG isolates were typed by multiple-locus variable number tandem repeat analysis (MLVA). χ2 tests, and univariate and multivariable analyses were also conducted. Results NG isolates gathered from the three cities differed significantly in the prevalence of TRNG (x2=26.418, P< 0.001), NG with decreased ceftriaxone susceptibility (χ2=4.417, P=0.093), and NG with decreased ceftriaxone susceptibility and non-susceptible cefixime (χ2=2.768, P=0.096). NG with decreased ceftriaxone susceptibility was significantly associated with Guangzhou (odds ratio 14.428,95%CI 3.194-65.169, P=0.001), Nanjing (odds ratio 6.959,95%CI 1.532-31.616, P=0.012), and NG non-susceptible to cefixime (odds ratio 2.378,95%CI 1.103-5.310, P=0.027). NG with non-susceptible to cefixime was significantly associated with PPNG (odds ratio 0.537,95%CI 0.267-1.080, P=0.081), TRNG (odds ratio 0.472,95%CI 0.232-0.964, P=0.039), and NG decreased susceptible to ceftriaxone (odds ratio 2.017, 95%CI 0.957-4.249, P=0.065). The analysis of the combination of the seven variable number of tandem repeats loci for all of the 244 isolates yielded 110 MLVA types falling into five clusters. Cluster Ⅲ was associated with PPNG (P=0.008), while cluster Ⅱ was associated with non-PPNG (P=0.008) and NG with decreased ceftriaxone susceptibility (P=0.024). Conclusion In Guangzhou, Nanjing, and Tianjin, Antimicrobials that can be used with confidence to treat NG infection currently include ceftriaxone and spectinomycin; but not penicillin, tetracycline, ciprofloxacin, and cefixime. Moreover, the MLVA scheme applied to this study was effective in typing NG isolates, and some of the resulting clusters were associated with NG isolates susceptibility to antibiotics.Section 3. In vitro synergy testing of ceftriaxone and azithromycin combination against Neisseria gonorrhoeaeObjective to investigate in vitro synergy testing of ceftriaxone and azithromycin combination against NG Methods A total of 25 NG isolates were collected from Dalian in 2012, using Etest method to test the synergy of ceftriaxone and azithromycin combination therapies against NG Results The FICI range was 0.724-2.696, and the combinations of ceftriaxone and azithromycin produeced FICIs of indifference.Conclusion At last, the ceftriaxone with azithromycin would be a future treatment option in China.
Keywords/Search Tags:Neisseria gonorrheoae, Meta analysis, cefixime, ceftriaxone, azithromycin, MLVA type
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