Induced Macrolide Resistance in Mycoplasma genitalium Isolates from Patients with Recurrent Nongonococcal Urethritis

Yew, Haur Sen; Anderson, Trevor P.; Coughlan, Edward; Werno, Anja M.

doi:10.1128/jcm.02475-10

Cited by 37 publications

(34 citation statements)

References 8 publications

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“…Several recent studies have highlighted that azithromycin (AZM)-resistant M. genitalium strains are emerging worldwide (35)(36)(37)(38)(39)(40)(41)(42), two of which provide molecular evidence that resistance can be induced with 1 g of STAT dosing (38,42). Using conventional PCR and Sanger sequencing, analysis of the M. genitalium-positive subjects in this study showed that none of their infecting strains possessed mutations that confer macrolide resistance (data not shown).…”

Section: Resultsmentioning

confidence: 72%

“…AZM treatment failures using the 1-g dose have ranged from 15 to 60% (47)(48)(49). Other studies have highlighted the hazard of STAT 1-g AZM therapy by describing the molecular mechanisms of induced resistance and subsequent treatment failure (35,38,42). Since AZM is commonly used to treat male NGU and is also included in the current CDC treatment guidelines for gonorrheae, it remains imperative to monitor resistance patterns for M. genitalium and other bacterial STIs since virtually all men with urethritis receive AZM.…”

Section: Discussionmentioning

confidence: 99%

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Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

Dehon¹,

McGowin²

2014

J Clin Microbiol

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Cervicitis is a common clinical finding often attributed to sexually transmitted infections (STIs), but no etiologic agent is identified in the majority of cases. In this study, we comparatively assessed inflammation among the common infectious etiologies of cervicitis and assessed the potential value of liquid cytology specimens for predicting STIs. Among 473 Louisiana women at low risk for acquiring STIs, the prevalences of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in liquid-based cytology specimens were 1.5, 2.1, 0.6, and 4.4%, respectively. N. gonorrhoeae and human papillomavirus 18 (HPV18) infections were significantly more common among subjects infected with M. genitalium. Using direct microscopy, we observed significant increases in leukocyte infiltrates among subjects with monoinfections with M. genitalium or C. trachomatis compared to women with no detectable STIs. Inflammation was highest among subjects with M. genitalium. Using a threshold of >2 leukocytes per epithelial cell per high-powered field, the positive predictive values for M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were 100, 70, 67, and 20%, respectively. Several novel M. genitalium genotypes were identified, all of which were predicted to be susceptible to macrolide antibiotics, suggesting that different strains may circulate among low-risk women and that macrolide resistance is substantially lower than in high-risk populations. This study highlights the capacity of M. genitalium to elicit cervical inflammation and, considering the strong epidemiologic associations between M. genitalium and human immunodeficiency virus (HIV), provides a potential mechanism for acquisition and shedding of HIV via chronic leukocyte recruitment to the cervical mucosa.

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Section: Resultsmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

Dehon¹,

McGowin²

2014

J Clin Microbiol

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“…Identification of mutations in the 23S rRNA gene at nucleotides 2058 and 2059, positions known to be linked to high-level AZM resistance (25,26), allowed for the first estimate of the prevalence of AZM resistance in M. genitalium in Sydney, Australia. The overall prevalence was 43%, with a lower prevalence in 2011 (36%) than High levels of resistance may be the result of frequent selection of resistant strains by a 1-g AZM dose (30), as several studies have shown that selection of resistant strains commonly occurs over the course of 1-g AZM treatment (25,27,29). Alarmingly, a very recent study reported that selection over the course of treatment accounted for 55% of AZM treatment failure cases (30).…”

Section: Discussionmentioning

confidence: 99%

“…Alarmingly, studies investigating the effectiveness of either 1 g or 1.5 g AZM treatment have reported microbiological treatment failure in 16% to 33% of patients (19,(21)(22)(23)(24). Point mutations at positions 2058 and 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene (25,26) are consistently identified in M. genitalium strains taken from patients in whom AZM treatment has failed; these strains exhibit high levels of AZM resistance in vitro (25,(27)(28)(29).Moxifloxacin (MXF) is used as a second-line treatment for M. genitalium-associated NGU and cervicitis (21,30) and is consistently found to be among the most active drugs against M. genitalium in vitro (31, 32). Clinical resistance to MXF has not yet been formally reported in M. genitalium infections.…”

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confidence: 99%

Fluoroquinolone and Macrolide Resistance-Associated Mutations in Mycoplasma genitalium

et al. 2013

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dMycoplasma genitalium is a significant sexually transmitted pathogen, causing up to 25% of cases of nongonococcal urethritis in men, and it is strongly associated with cervicitis and pelvic inflammatory disease in women. Currently, the usual first-line treatment is the macrolide antibiotic azithromycin, but an increasing incidence of treatment failure over the last 5 years suggests the emergence of antibiotic resistance. The mutations responsible for macrolide resistance have been found in the 23S rRNA gene in numerous M. genitalium populations. A second-line antibiotic, the fluoroquinolone moxifloxacin, was thought to be a reliable alternative when azithromycin began to fail, but recent studies have identified mutations that may confer fluoroquinolone resistance in the genes parC and gyrA. The aim of this study was to determine the prevalence of antibiotic resistance in M. genitalium in Sydney, Australia, by detecting relevant mutations in the 23S rRNA gene, parC, and gyrA. M. genitalium-positive DNA extracts of specimens, collected from patients attending sexual health clinics in Sydney, were tested by PCR amplification and DNA sequence alignment. The 186 specimens tested included 143 initial patient specimens and 43 second, or subsequent, specimens from 24 patients. We identified known macrolide resistance-associated mutations in the 23S rRNA gene in 43% of the initial patient samples and mutations potentially associated with fluoroquinolone resistance in parC or gyrA sequences in 15% of the initial patient samples. These findings support anecdotal clinical reports of azithromycin and moxifloxacin treatment failures in Sydney. Our results indicate that further surveillance is needed, and testing and treatment protocols for M. genitalium infections may need to be reviewed. Mycoplasma genitalium, one of the smallest known self-replicating organisms (1), is an obligate parasite, preferring the human genital tract as its host environment (2-4). In men, M. genitalium is a significant cause of both acute and chronic nongonococcal urethritis (NGU) (5-7) and is estimated to account for 15% to 25% of cases of NGU in some populations (2). In women, M. genitalium has been significantly associated with both cervicitis (2, 8-10) and pelvic inflammatory disease (2,(11)(12)(13)(14), and it has been identified in up to 7.3% of women in high-risk populations (15). In Australia, M. genitalium has been reported to account for between 4.5% and 9% of cases of NGU (16, 17), while it was identified in 4% of women attending a Sydney sexual health clinic and was the second most common cause of cervicitis (9).The usual treatment regime for clinically diagnosed NGU and cervicitis is a single dose of 1 g azithromycin (AZM) (18). An extended regime (1.5 g over 5 days) is often prescribed if singledose AZM is unsuccessful, but there is contention regarding the effectiveness of this extended treatment (19,20). Alarmingly, studies investigating the effectiveness of either 1 g or 1.5 g AZM treatment have reported microbiological treatment f...

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“…Macrolide-resistant M. genitalium isolates have been detected in patients from Australia, Sweden, Norway, and the United States, and mutations in domain V of the 23S rRNA gene have been detected in specimens from Greenland, Japan, France, and an increasing number of other countries (8,9,(12)(13)(14). The resistance mutations consist mainly of adenine-to-guanine mutations in the 23S rRNA gene at position 2058 or 2059 (Escherichia coli numbering) (9,12,15,16).…”

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confidence: 99%

Direct Detection of Macrolide Resistance in Mycoplasma genitalium Isolates from Clinical Specimens from France by Use of Real-Time PCR and Melting Curve Analysis

et al. 2014

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Induced Macrolide Resistance in Mycoplasma genitalium Isolates from Patients with Recurrent Nongonococcal Urethritis

Cited by 37 publications

References 8 publications

Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

Mycoplasma genitalium Infection Is Associated with Microscopic Signs of Cervical Inflammation in Liquid Cytology Specimens

Fluoroquinolone and Macrolide Resistance-Associated Mutations in Mycoplasma genitalium

Direct Detection of Macrolide Resistance in Mycoplasma genitalium Isolates from Clinical Specimens from France by Use of Real-Time PCR and Melting Curve Analysis

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