In vitro Activities of Nemonoxacin and Other Antimicrobial Agents Against Human Mycoplasma and Ureaplasmas Isolates and Their Defined Resistance Mechanisms

Wang, Na; Liu, Wan cheng; Zhou, Yun Heng; Liu, Yang

doi:10.3389/fmicb.2019.01890

Cited by 11 publications

(11 citation statements)

References 61 publications

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“…Valentine-King and Brown found U. parvum to have low resistance to azithromycin (MIC of �0.5-2 μg/ml) for 60 isolates from the United States and only slightly higher MICs for U. urealyticum (MIC of �0.5-4 μg/ml) [45]. A similar trend towards higher MIC for U. urealyticum was reported from China [46], and a study analyzing ureaplasmas from neonates from the UK found no resistance to macrolides and no different activity of azithromycin, but a significantly higher erythromycin MIC for U. urealyticum [47]. However, these in vitro studies may not reflect the in vivo activity, where factors like biofilm or pH may influence the activity of antibiotics.…”

Section: Plos Onesupporting

confidence: 60%

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Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

et al. 2020

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The human vagina harbor a rich microbiota. The optimal state is dominated by lactobacilli that help to maintain health and prevent various diseases. However, the microbiota may rapidly change to a polymicrobial state that has been linked to a number of diseases. In the present study, the temporal changes of the vaginal microbiota in patients treated for sexually transmitted diseases or bacterial vaginosis (BV) and in untreated controls were studied for 26 days. The patients included 52 women treated with azithromycin, tetracyclines or moxifloxacin for present or suspected infection with Chlamydia trachomatis or Mycoplasma genitalium. Women with concurrent BV were also treated with metronidazole. The controls were 10 healthy women of matching age. The microbiota was analyzed by 16S rRNA gene deep sequencing, specific qPCRs and microscopy. There was generally good correlation between Nugent score and community state type (CST) and qPCR confirmed the sequencing results. By sequencing, more than 600 different taxa were found, but only 33 constituted more than 1 ‰ of the sequences. In both patients and controls the microbiota could be divided into three different community state types, CST-I, CST-III and CST-IV. Without metronidazole, the microbiota remained relatively stable regarding CST although changes were seen during menstrual periods. Administration of metronidazole changed the microbiota from CST-IV to CST-III in approximately 50% of the treated patients. In contrast, the CST was generally unaffected by azithromycin or tetracyclines. In 30% of the BV patients, Gardnerella vaginalis was not eradicated by metronidazole. The majority of women colonized with Ureaplasma parvum remained positive after azithromycin while U. urealyticum was eradicated.

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Section: Plos Onesupporting

confidence: 60%

“…A similar trend towards higher MIC for U . urealyticum was reported from China [ 46 ], and a study analyzing ureaplasmas from neonates from the UK found no resistance to macrolides and no different activity of azithromycin, but a significantly higher erythromycin MIC for U . urealyticum [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

et al. 2020

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“…The mechanism of quinolone resistance involves mutations in the gyrA and gyrB subunits of DNA gyrase and parC and parE subunits of topoisomerase IV that probably arise because of antimicrobial selective pressure [ 17 , 21 ]. Wang et al reported that nemonoxacin, a novel nonfluorinated quinolone, may have increased antibacterial activity and decreased adverse effects on account of its C-8-methoxy structure on the quinolone ring [ 22 ]. The resistance rates for tetracyclines including tetracycline, doxycycline, and minocycline remained below 3%, and the resistance rates for macrolides including josamycin, roxithromycin, clarithromycin, and azithromycin were approximately 20%.…”

Section: Discussionmentioning

confidence: 99%

Infection Prevalence and Antibiotic Resistance Levels in Ureaplasma urealyticum and Mycoplasma hominis in Gynecological Outpatients of a Tertiary Hospital in China from 2015 to 2018

Zhang

et al. 2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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The aim of this study was to estimate the Ureaplasma urealyticum and Mycoplasma hominis infection prevalence and antibiotic resistance levels in gynecological outpatients. Clinical characteristics and laboratory data of gynecological outpatients of the Fourth People’s Hospital of Chongqing from 2015 to 2018 were retrospectively analyzed. Antibiotic resistance levels in U. urealyticum and M. hominis were defined by a commercial Mycoplasma kit for antibiotic susceptibility testing. Univariate analysis and multivariate logistic regression analysis were performed to evaluate risk factors associated with Mycoplasma isolation. Comparisons of yearly distributions and resistance rates were assessed by chi-square tests. Fifty-six percent of gynecological outpatients were positive for U. urealyticum, and 11.02% were positive for M. hominis. In the univariate analysis, women aged 30–39 years or with a history of pregnancy or gynecological diseases had an increased risk for Mycoplasma isolation, while women who were postmenopausal or had an education level of undergraduate degree or above had a decreased risk of Mycoplasma isolation. In the multivariate logistic regression model, an independent risk factor for Mycoplasma isolation was a history of gynecological diseases, while a bachelor’s degree, master’s degree, or above were protective factors against Mycoplasma isolation. There were distinctly gradual increases in the positivity rates of U. urealyticum and M. hominis from 2015 to 2018 and an overall increasing trend of resistance to ten antibiotics among U. urealyticum and M. hominis. The top three antibiotics associated with resistance were ofloxacin, sparfloxacin, and levofloxacin. Doxycycline, josamycin, and minocycline were preferred because they had the lowest levels of resistance. Increases in the prevalence of infection and antibiotic resistance in U. urealyticum and M. hominis were observed from 2015 to 2018, clearly confirming the necessity to monitor the standardized administration of antibiotics.

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“…The resistance mechanisms of MRMP have been demonstrated by in vitro selection that involves point mutations in the peptidyl transferase loop of 23S rRNA and point mutations, insertions, or deletions in ribosomal proteins L4 and L22 ( Lucier et al., 1995 ; Pereyre et al., 2004 ; Ou et al., 2015 ; Waites et al., 2017 ). Some of these changes were observed in clinical MRMP isolates ( Morozumi et al., 2005 ; Xin et al., 2009 ; Wang et al., 2019 ), while some were not ( Pereyre et al., 2004 ; Ou et al., 2015 ), probably because these MRMP strains were induced by subminimum inhibitory concentrations of macrolide antibiotics. The investigation of macrolide resistance mechanisms in M. pneumoniae has mainly been focused on the single 23S RNA gene and ribosomal protein genes, and so further analysis on other potential resistance mechanisms is required.…”

Section: Introductionmentioning

confidence: 99%

Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae

Wang

Xiao

et al. 2023

Front. Cell. Infect. Microbiol.

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Mycoplasma pneumoniae is an important pathogen causing upper and lower respiratory tract infections in children and other age groups. Macrolides are the recommended treatments of choice for M. pneumoniae infections. However, macrolide resistance in M. pneumoniae is increasing worldwide, which complicates the treatment strategies. The mechanisms of macrolide resistance have been extensively studied focusing on the mutations in 23S rRNA and ribosomal proteins. Since the secondary treatment choice for pediatric patients is very limited, we decided to look for potential new treatment strategies in macrolide drugs and investigate possible new mechanisms of resistance. We performed an in vitro selection of mutants resistant to five macrolides (erythromycin, roxithromycin, azithromycin, josamycin, and midecamycin) by inducing the parent M. pneumoniae strain M129 with increasing concentrations of the drugs. The evolving cultures in every passage were tested for their antimicrobial susceptibilities to eight drugs and mutations known to be associated with macrolide resistance by PCR and sequencing. The final selected mutants were also analyzed by whole-genome sequencing. Results showed that roxithromycin is the drug that most easily induces resistance (at 0.25 mg/L, with two passages, 23 days), while with midecamycin it is most difficult (at 5.12 mg/L, with seven passages, 87 days). Point mutations C2617A/T, A2063G, or A2064C in domain V of 23S rRNA were detected in mutants resistant to the 14- and 15-membered macrolides, while A2067G/C was selected for the 16-membered macrolides. Single amino acid changes (G72R, G72V) in ribosomal protein L4 emerged during the induction by midecamycin. Genome sequencing identified sequence variations in dnaK, rpoC, glpK, MPN449, and in one of the hsdS (MPN365) genes in the mutants. Mutants induced by the 14- or 15-membered macrolides were resistant to all macrolides, while those induced by the 16-membered macrolides (midecamycin and josamycin) remained susceptible to the 14- and 15-membered macrolides. In summary, these data demonstrated that midecamycin is less potent in inducing resistance than other macrolides, and the induced resistance is restrained to the 16-membered macrolides, suggesting a potential benefit of using midecamycin as a first treatment choice if the strain is susceptible.

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In vitro Activities of Nemonoxacin and Other Antimicrobial Agents Against Human Mycoplasma and Ureaplasmas Isolates and Their Defined Resistance Mechanisms

Cited by 11 publications

References 61 publications

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

Infection Prevalence and Antibiotic Resistance Levels in Ureaplasma urealyticum and Mycoplasma hominis in Gynecological Outpatients of a Tertiary Hospital in China from 2015 to 2018

Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae

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