| Chapter ?The Clinical Efficacy of Moxifloxacin in Treating Mycoplasma Genitalium Infection and the Mutation Rate of Macrolide Resistance Genes in Mycoplasma genitalium:systematic reviews and meta-analysesObjective:These meta-analyses aim to estimate the treatment efficacy of moxifloxacin in treating Mycoplasma genitalium infection and the mutation rate of macrolide resistance genes in Mycoplasma genitalium worldwide.Methods:A comprehensive search was conducted by researchers in PubMed,Embase,Cochrane and Google Scholar with relevant keywords.The data of those documents meeting the inclusion criteria for meta-analysis were extracted and analyzed in STATA 14.0 software.Result 1:A total of 17 articles studying the effective rates of moxifloxacin for Mycoplasma genitalium met the inclusion criteria and a total of 252 patients were included.The random effect model analysis showed the pooled microbial cure rate was 96%(95%confidence interval[CI],90%-99%;I2=28.59%,P=0.13).The subset analysis revealed that the the pooled elimination rate of moxifloxacin for Mycoplasma genitalium infection had declined from 100%(95%CI,99%-100%;I2-0.00%,P =1.00)in 2010 to 89%(95%CI,82%-94%;I2=0.00%,P=0.59)after 2010.Result 2:A total of 28 studies detecting macrolide resistance-associated mutations in Mycoplasma genitalium fulfilled the inclusion criteria.The overall mutation rate was 39%(95%Cl,30%-48%;I2 = 98.2%,P = 0.000).The subset analysis suggested that the rate of macrolide resistance-associated mutations had increased from 31%(95%Cl,22%-40%;I2 = 93.6%,P = 0.000)in 2013 to 44%(95%CI,29%-59%;I2 = 98.2%,P = 0.000).The meta regression analysis showed that the rate of macrolide resistance-associated mutations was on the rise year by year in Europe and Australia.Conclusion:Moxifloxacin still has a relatively high clearance rate of Mycoplasma genitalium.However,its failure rate has been increasing obviously,which should be given enough attention from the academic world.Generally,the rate of macrolide resistance-associated mutations is increasing obviously.The guidelines that recommend azithromycin as first-line therapy for the treatment of Mycoplasma genitalium infection need to be re-evaluated.Sentinel sites should be established to monitoring antimicrobial resistance in Mycoplasma genitalium.Chapter ?The prevalence of Mycoplasma genitalium infection among male patients with urethritis and Detection of Macrolide and Quinolone Resistance-Associated Mutations in Mycoplasma genitalium in NanjingObjective:To determine the prevalence of Mycoplasma genitalium infection in male patients with urethritis attending STD Clinic of our Hospital,and to detect macrolides and quinolones resistance-associated mutations in Mycoplasma genitalium.Methods:Male patients presented with symptomatic urethritis who visited STD Clinic of our hospital from April 2011 to August 2015 were consecutively enrolled and the Urine samples were collected.Urine samples were tested for Mycoplasma genitalium by in-house nested PCR targeting mgpA gene and sequencing.Macrolide resistance-mediating mutations in the 23S rRNA gene and quinolone resistance-mediating mutations in the gyrA and parC genes were determined by sequencing.Results:A total of 1,816 urine samples were collected from male patients with urethritis.The overall prevalence of Mycoplasma genitalium infection was 19.7%(358/1816).The rate of Neisseria gonorrhoeae infection was 46.6%(847/1816).Among 973 patients with non-gonococcal urethritis,the infection rates of Chlamydia trachomatis,Mycoplasma genitalium,Ureaplasma urealyticum,Trichomonas vaginalis and Mycoplasma hominis were 42.1%(410/973),28.19%(273/973),21.2%(182/859),3.6%(35/973)and 0.7%(6/859),respectively.For a total of 358 patients with Mycoplasma genitalium infection,the phylogenetic tree constructed based on mgpA genes showed that 358 Mg-positive samples could be divided into five major subgroups.Among 358 Mg positive samples,successful sequencing of 23S rRNA gene was accomplished in 341 samples,and parC gene and gyrA gene were successfully amplified and sequenced in 344 and 339 samples,respectively.The mutation rates of 23S rRNA,parC and gyrA genes were 88.9%(303/341),89.5%(308/344)and 12.4%(42/339),respectively.The most common mutation patterns of 23S rRNA genes were A2059G(211/303;69.6%),A2058G(60/303;19.8%)and A2059T(30/303;9.9%),respectively.The most common mutation pattern of parC genes was G248T(289/344;84%),while that of gyrA gene was G285A(22/339,6.5%).Conclusion:M genitalium is associated with non-gonococcal urethritis in men with clinical symptoms.The high rate of mutations in 23S rRNA and parC genes has been found in Mycoplasma genitalium in Nanjing.Clinical studies on the treatment efficacy of different drugs for Mycoplasma genitalium infection need to be carried out in the region.Also,surveillence network monitoring antimicrobial resistance in Mycoplasma genitalium is to be established.Chapter ?Clinical observation on the treatment efficacy of antibiotics for Mycoplasma genitalium infectionObjectives:To understand the efficacy of azithromycin,doxycycline and moxifloxacin in the treatment of Mycoplasma genitalium infection and the relationship between treatment failure and mutation of drug-resistant genes.To observe the clinical efficacy of spectinomycin for refractory Mycoplasma genitalium infection in 3 cases.Methods:This study was a single-center,randomized,clinical observation on two parallel medicines.Patients with non-gonococcal urethritis were randomly treated with either doxycycline or azithromycin.Those who suffered from treatment failure were treated with moxifloxacin again.Also,the urine samples were collected,and mutations associated with macrolide and fluoroquinolone resistance were detected by sequencing.In addition,three patients with refractory Mycoplasma genitalium infection were treated with spectinomycin 2g intramuscularly once dailly for 7 days.Drug efficiency was examinated after drug withdrawal at least 2 weeks,to understand the treatment effect of the drug.Results:A total of 22 patients with Mycoplasma genitalium infection were enrolled,and 8 patients(36.4%.)lost to follow-up.Among the 14 patients completing the clinical treatment and follow-up,8 was treated with doxycycline and had a Mycoplasma genitalium clearance rate of 62.5%(5/8),and 6 received azithromycin treatment with a clearance rate of 33.3%2/6).5 of 7 patients failing in the treatment of doxycycline or azithromycin received moxifloxacin,and Mycoplasma genitalium clearance rate was 80.0%(4/5).Among the 4 patients failing in azithromycin treatment,the mutations at 2058 and 2059 sites of 23S rRNA gene were detected,and no mutation was detected in 23S rRNA gene in patients with successful azithromycin treatment.Mutations in both parC and gyrA genes were detected in the patient failing in moxifloxacin treatment,while among the 4 patients with successful moxifloxacin treatment,parC mutations were found in three patients.Three patients with refractory Mycoplasma genitalium infection were successfully treated with a 7-day regimen of spectinomycin.The NAAT tests of Mycoplasma genitalium were negative and the symptoms disappeared.Conclusions:The small sample clinical observation shows that azithromycin is less effective than doxycycline.As a second-line medicine,moxifloxacin still delivers a high clearance rate of Mycoplasma genitalium.The failure of azithromycin treatment is associated with mutations at sites 2058 and 2059 in 23S rRNA gene,while the failure of moxifloxacin treatment may correlate with the simultaneous mutations in both parC and gyrA genes.Spectinomycin successfully treated three cases of refractory Mycoplasma genitalium infection and might be used as an alternative treatment option for patients with refractory Mycoplasma genitalium infection. |
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