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1.
Lancet Infect Dis ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32622378

RESUMO

BACKGROUND: Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370. RESULTS: Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8-42·5); prevalence increased from 10·0% (95% CI 2·6-20·1%) before 2010, to 51·4% (40·3-62·4%) in 2016-17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5-11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3-4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region. INTERPRETATION: Global surveillance and measures to optimise the efficacy of treatments-including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches-are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains. FUNDING: Australian National Health and Medical Research Council.

2.
Sex Transm Dis ; 47(5): 321-325, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32304528

RESUMO

BACKGROUND: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are increasingly recognized as common infections among women. Little is known about the prevalence of rectal Mycoplasma genitalium (MG), rectal MG/CT/GC coinfection, or MG antimicrobial resistance patterns among women. METHODS: In 2017 to 2018, we recruited women at high risk for CT from Seattle's municipal sexually transmitted disease clinic. Participants self-collected vaginal and rectal specimens for CT/GC nucleic acid amplification testing. We retrospectively tested samples for vaginal and rectal MG using nucleic acid amplification testing and tested MG-positive specimens for macrolide resistance-mediating mutations (MRM) and ParC quinolone resistance-associated mutations (QRAMs). RESULTS: Of 50 enrolled women, 13 (26%) tested positive for MG, including 10 (20%) with vaginal MG and 11 (22%) with rectal MG; 8 (62%) had concurrent vaginal/rectal MG. Five (38%) were coinfected with CT, none with GC. Only 2 of 11 women with rectal MG reported anal sex in the prior year. Of MG-positive specimens, 100% of rectal and 89% of vaginal specimens had an MRM. There were no vaginal or rectal MG-positive specimens with ParC QRAMs previously associated with quinolone failure. Five MG-infected women received azithromycin for vaginal CT, 4 of whom had a MG MRM detected in their vaginal and/or rectal specimens. CONCLUSIONS: We observed a high prevalence of macrolide-resistant vaginal and rectal MG among a population of women at high risk for CT. This study highlights how the use of antimicrobials designed to treat an identified infection-in this case, CT-could influence treatment outcomes and antimicrobial susceptibility in other unidentified infections.

3.
J Infect Dis ; 221(6): 1017-1024, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031634

RESUMO

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

4.
BMC Genomics ; 21(1): 116, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013864

RESUMO

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.

6.
Sex Transm Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32073547

RESUMO

BACKGROUND: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are increasingly recognized as common infections among women. Little is known about the prevalence of rectal Mycoplasma genitalium (MG), rectal MG/CT/GC co-infection, or MG antimicrobial resistance patterns among women. METHODS: In 2017-2018 we recruited women at high risk for CT from Seattle's municipal STD clinic. Participants self-collected vaginal and rectal specimens for CT/GC nucleic acid amplification testing (NAAT). We retrospectively tested samples for vaginal and rectal MG using NAAT, and tested MG-positive specimens for macrolide resistance-mediating mutations (MRM) and ParC quinolone resistance-associated mutations (QRAMs). RESULTS: Of 50 enrolled women, 13 (26%) tested positive for MG, including 10 (20%) with vaginal MG and 11 (22%) with rectal MG; 8 (62%) had concurrent vaginal/rectal MG. Five (38%) were co-infected with CT; none with GC. Only 2 of 11 women with rectal MG reported anal sex in the prior year. Of MG-positive specimens, 100% of rectal and 89% of vaginal specimens had a MRM. There were no vaginal or rectal MG-positive specimens with ParC QRAMs previously associated with quinolone failure. Five MG-infected women received azithromycin for vaginal CT, four of whom had a MG MRM detected in their vaginal and/or rectal specimens. CONCLUSIONS: We observed a high prevalence of macrolide-resistant vaginal and rectal MG among a population of women at high risk for CT. This study highlights how the use of antimicrobials designed to treat an identified infection - in this case CT - could influence treatment outcomes and antimicrobial susceptibility in other unidentified infections.

7.
J Clin Microbiol ; 58(4)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31941694

RESUMO

Sexually transmitted infections (STIs) by Mycoplasma genitalium are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of M. genitalium and the epidemiology of antimicrobial resistance. This mgpB-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively. This well-defined structuration suggests the presence of two independent sexual networks with little connectivity between them. On the other hand, the study demonstrates the multiclonal feature of the emergence of antibiotic resistance in M. genitalium to both macrolides and fluoroquinolones. The high prevalence of macrolide resistance in M. genitalium among MSM, influenced by dense network connectivity and strong antibiotic selective pressure, may correspond to allodemics affecting other STIs such as gonorrhea, syphilis and enteric pathogens. Collaterally, the structural and functional impact of mutations in the mgpB gene, encoding the major adhesin P140 (MgpB), may require further investigation.

8.
BMC Infect Dis ; 19(1): 827, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547805

RESUMO

BACKGROUND: The worldwide expansion of macrolide-resistant Mycoplasma genitalium (MG) in cases of genital infections has led to an increased recurrence rate of these infections after first-line azithromycin treatment. By detecting the presence of azithromycin-resistant MG, the patient's antibiotic treatment can be targeted and the spread of resistance prevented. With this aim in mind, macrolide-resistance detection kits are helpful tools for the physician. METHODS: Azithromycin resistance mutations in MG are targeted using a four-color multiplex real-time RT-PCR assay. Tested targets include plasmid DNA (as positive controls) as well as macrolide-sensitive and macrolide-resistant genomic DNA from characterized cell lines and clinical samples. RESULTS: The analytical data presented here were generated from plasmid DNA and genomic RNA/DNA and include adaptation to an internal control, specificity between targets, specificity vs non-MG species, limit of detection (LoD) and interference studies (co-infection and endogenous substances). The clinical data were based on the application of the assay to clinical samples characterized by sequencing. CONCLUSIONS: A new NAAT (nucleic acid amplification test) prototype has been developed in collaboration with the Diagenode s.a. company, this prototype targets MG and azithromycin-resistance mutations in that pathogen.


Assuntos
Azitromicina/farmacologia , Farmacorresistência Bacteriana/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Mutação , Mycoplasma genitalium/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Antibacterianos/farmacologia , Humanos , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Especificidade por Substrato
9.
J Clin Microbiol ; 57(11)2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31434719

RESUMO

Mycoplasma genitalium causes a common sexually transmitted infection with a marked propensity to develop antimicrobial resistance. As few treatment options exist, this poses significant challenges to clinicians. Recent diagnostic advances have resulted in tests that report the simultaneous detection of M. genitalium and any resistance to macrolides, the first-line treatment. This allows for therapy to be tailored to the individual, thereby optimizing treatment outcomes. However, resistance to fluoroquinolones, the second-line treatment, is increasing in M. genitalium In this study, we describe a new assay, MG+parC (beta), which simultaneously reports the detection of M. genitalium and five parC mutations that have been associated with resistance to fluoroquinolones. These mutations affect the amino acid sequence of ParC at residues S83R (A247C), S83I (G248T), D87N (G259A), D87Y (G259T), and D87H (G259C). The study tested the MG+parC (beta) assay with 202 M. genitalium-positive clinical samples from Australia (n = 141) and Spain (n = 61). Compared to Sanger sequencing, the assay performed with a kappa value of 0.985 (95% confidence interval [CI], 0.955 to 1.000), with a mutation detection sensitivity of 97.6% (95% CI, 87.4 to 99.9), and specificity of 100.0% (95% CI, 97.7 to 100.0). Fluoroquinolone resistance-associated mutations in parC targeted by the assay were more prevalent among the Australian cohort (23.4% [95% CI,16.3 to 31.8]) compared to the Spanish population (8.8% [95% CI, 2.9% to 19.3%]) (P = 0.019). The MG+parC (beta) kit is a simple and reliable method for simultaneous detection of M. genitalium and fluoroquinolone resistance-associated mutations in clinical settings. This novel diagnostic tool may extend the utility of the second line of antimicrobial therapies in M. genitalium infection.

11.
Sex Transm Dis ; 46(10): 676-682, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31356530

RESUMO

BACKGROUND: Standard counseling at nongonococcal urethritis (NGU) diagnosis includes advice to abstain from sex for at least 7 days and until symptoms resolve. METHODS: From December 2014 to July 2018, we enrolled men who have sex with men and received azithromycin (1 g) for NGU at the Public Health-Seattle and King County STD Clinic. Over 12 weeks of follow-up, participants reported daily urethral symptoms and sexual activity on web-based diaries. Nongonococcal urethritis was defined as urethral symptoms or visible urethral discharge plus 5 or greater polymorphonuclear leukocytes per high-power field. Time of symptom resolution was defined as the first of 5 consecutive asymptomatic days. RESULTS: Of 100 participants with NGU and no Chlamydia trachomatis (CT)/Mycoplasma genitalium (MG) coinfection, 36 (36%), 22 (22%), and 42 (42%) had CT-NGU, MG-NGU, and non-CT/non-MG NGU, respectively. Among men with MG-NGU, 94% had a macrolide resistance mutation. For all etiologies, median time to symptom resolution after azithromycin was 7 days (95% confidence interval [CI], 5-9); 37% had symptoms lasting longer than 7 days. For men with CT-NGU, MG-NGU, and non-CT/non-MG NGU, median time to symptom resolution was 4 days (95% CI, 2-6; 16% >7 days), undefined days (95% CI, 7 to undefined; 60% >7 days), and 7 days (95% CI, 5-11; 46% >7 days), respectively. Median time to first sexual activity (any type) was 12 days (95% CI, 11-17); it was 16 days (95% CI, 12-18) to first urethral sexual exposure. Twenty-seven percent did not avoid urethral exposure for the recommended period. CONCLUSIONS: Counseling at NGU diagnosis should educate patients that symptoms may persist more than 7 days, particularly for non-CT NGU, and emphasize the rationale for the 7-day abstinence period.

12.
Sex Transm Dis ; 46(12): 805-809, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31259853

RESUMO

From February 2015 to October 2017, among 20 men who have sex with men with Mycoplasma genitalium-associated nongonococcal urethritis, 15% had macrolide resistance and S83I ParC mutations. Azithromycin followed by moxifloxacin cleared Mycoplasma genitalium in 2 of 2 with and 11 of 13 without S83I mutations. Dual failures were cleared after doxycycline. S83I mutations were not associated with moxifloxacin failure.

13.
Clin Infect Dis ; 68(4): 554-560, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29873691

RESUMO

Background: Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay. Methods: In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14-90 days after the second antibiotic. Results: Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%-74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%-98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%-95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%-9.2%]) macrolide-susceptible infections. Conclusions: In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.


Assuntos
Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos , Farmacorresistência Bacteriana , Macrolídeos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Adulto , Antibacterianos/farmacologia , Feminino , Humanos , Macrolídeos/farmacologia , Masculino , Infecções por Mycoplasma/microbiologia , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
Clin Infect Dis ; 69(1): 113-120, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30281079

RESUMO

BACKGROUND: Although Mycoplasma genitalium (MG) is an acknowledged cause of nongonococcal urethritis (NGU), access to diagnostic testing is limited. Syndromic management is common, yet little is known about natural history. METHODS: Between August 2014 and April 2016, 13 heterosexual men aged ≥16 years with MG were identified within a cohort study of men with and without NGU attending an urban sexually transmitted diseases clinic. Men had 6-7 monthly visits. NGU was defined as ≥5 polymorphonuclear leukocytes per high-power field on urethral Gram stain plus either visible urethral discharge or urethral symptoms. Men with NGU received 1 g of azithromycin. Men with persistent NGU received moxifloxacin 400 mg for 14 days. First-void urine was retrospectively tested for MG using transcription-mediated amplification. Resistance-associated mutations were detected by polymerase chain reaction (PCR) and sequencing. Organism load was determined by quantitative PCR. RESULTS: Sixty-two percent of MG-positive men had macrolide resistance-mediating mutations (MRMM) at enrollment; 31% had parC mutations (all outside the quinolone resistance-determining region). MG persisted after azithromycin in 7 men, 6 of whom had MRMM. The median duration of persistence in the absence of curative therapy was 143 days (range, 21-228). Five men experienced symptom resolution after azithromycin, but MG persisted for another 89-186 days before moxifloxacin. Organism load was somewhat lower in MRMM than wild-type infections (P = .16). CONCLUSIONS: The high prevalence of macrolide resistance and long duration of infection after symptom resolution highlights the need for diagnostic MG testing of men with NGU to direct therapy.

15.
Int J STD AIDS ; 29(13): 1258-1272, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30049258

RESUMO

Four common pathological conditions are associated with vaginal discharge: bacterial vaginosis, aerobic vaginitis, candidosis, and the sexually transmitted infection, trichomoniasis. Chlamydial or gonococcal cervical infection may result in vaginal discharge. Vaginal discharge may be caused by a range of other physiological and pathological conditions including atrophic vaginitis, desquamative inflammatory vaginitis, cervicitis, and mucoid ectopy. Psychosexual problems may present with recurrent episodes of vaginal discharge and vulval burning. These need to be considered if tests for specific infections are negative. Many of the symptoms and signs are non-specific and a number of women may have other conditions such as vulval dermatoses or allergic and irritant reactions.


Assuntos
Guias como Assunto , Doenças Sexualmente Transmissíveis , Tricomoníase/diagnóstico , Descarga Vaginal/etiologia , Vaginite/etiologia , Vaginose Bacteriana/microbiologia , Europa (Continente) , Feminino , Humanos , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Tricomoníase/tratamento farmacológico , Descarga Vaginal/diagnóstico , Descarga Vaginal/tratamento farmacológico , Vaginite/diagnóstico , Vaginite/tratamento farmacológico , Vaginose Bacteriana/tratamento farmacológico , Organização Mundial da Saúde
16.
Int J STD AIDS ; 29(10): 994-998, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29742999

RESUMO

Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women. The prevalence of M. genitalium infections in Cuban patients with urogenital syndromes is unknown. The aim of this study was to analyse the prevalence of M. genitalium infection in sexually-active Cuban men and women with urogenital syndromes as a part of aetiological surveillance of urogenital syndromes in Cuba. Samples from men and women with urogenital syndromes submitted to the Mycoplasma Reference Laboratory for mycoplasma diagnosis from 1 January 2014 to 1 June 2015 were analysed by polymerase chain reaction (PCR) for detection of M. genitalium. A total of 971 samples were received and processed. Of the patients tested, 5.7% (47/824) of women and 27.9% (41/147) of men were positive for M. genitalium. This paper presents the largest study of M. genitalium infections among Cuban patients with urogenital syndromes and is Cuba's first M. genitalium survey. We suggest that M. genitalium should be considered in the Cuban sexually transmitted infection management protocols as an important pathogen, particularly in men.


Assuntos
Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/isolamento & purificação , Mycoplasma genitalium/patogenicidade , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Uretrite/microbiologia , Adulto , Cuba/epidemiologia , Feminino , Humanos , Masculino , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/genética , Doença Inflamatória Pélvica/epidemiologia , Doença Inflamatória Pélvica/microbiologia , Reação em Cadeia da Polimerase , Vigilância da População , Prevalência , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Uretrite/diagnóstico
17.
Sex Transm Dis ; 45(8): 514-521, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29465649

RESUMO

BACKGROUND: Little is known about the natural history of Mycoplasma genitalium (MG) infection in women. We retrospectively tested archived vaginal fluid samples to assess MG prevalence, incidence, persistence, recurrence and antimicrobial resistance markers among women participating in the Preventing Vaginal Infections trial, a randomized trial of monthly presumptive treatment to reduce vaginal infections. METHODS: High-risk, nonpregnant, HIV-negative women aged 18 to 45 years from Kenya and the United States were randomized to receive metronidazole 750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5 consecutive nights each month for 12 months. Clinician-collected swabs containing cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification testing at enrollment and every other month thereafter. Specimens that were MG+ underwent additional testing for macrolide resistance-mediating mutations by DNA sequencing. RESULTS: Of 234 women enrolled, 221 had available specimens and 25 (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking was independently associated with incident MG infection (adjusted hazard ratio, 3.02; 95% confidence interval, 1.32-6.93), and age less than 25 years trended toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95-3.06). Median time to clearance of incident MG infections was 1.5 months (interquartile range, 1.4-3.0 months). Of the 120 MG+ specimens, 16 specimens from 15 different women were macrolide resistance-mediating mutation positive (13.3%), with no difference by country. CONCLUSIONS: M. genitalium infection is common among sexually active women in Kenya and the Southern United States. Given associations between MG and adverse reproductive health outcomes, this high burden of MG in reproductive-aged women could contribute to substantial morbidity.


Assuntos
Antibacterianos/farmacologia , Macrolídeos/farmacologia , Metronidazol/farmacologia , Miconazol/farmacologia , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/isolamento & purificação , Administração Intravaginal , Adolescente , Adulto , Farmacorresistência Bacteriana , Feminino , Humanos , Incidência , Quênia/epidemiologia , Pessoa de Meia-Idade , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/genética , Prevalência , Estudos Retrospectivos , Comportamento Sexual , Estados Unidos/epidemiologia , Vagina/microbiologia , Adulto Jovem
19.
Emerg Infect Dis ; 24(2): 328-335, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29350154

RESUMO

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.


Assuntos
Antibacterianos/farmacologia , Macrolídeos/farmacologia , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Pristinamicina/uso terapêutico , Adulto , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/genética
20.
APMIS ; 126(2): 123-127, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29235145

RESUMO

Mycoplasma genitalium, causing non-gonococcal non-chlamydial urethritis and associated with cervicitis, has developed antimicrobial resistance (AMR) to both the macrolide azithromycin (first-line treatment) and the fluoroquinolone moxifloxacin (second-line treatment). Our aim was to estimate the prevalence of resistance, based on genetic AMR determinants, to these antimicrobials in the M. genitalium population in two Swedish counties, Örebro and Halland, 2011-2015. In total, 672 M. genitalium positive urogenital samples were sequenced for 23S rRNA and parC gene mutations associated with macrolide and fluoroquinolone resistance, respectively. Of the samples, 18.6% and 3.2% in Örebro and 15.2% and 2.7% in Halland contained mutations associated with macrolide and fluoroquinolone resistance, respectively. The predominating resistance-associated mutations in the 23S rRNA gene was A2059G (n = 39) in Örebro and A2058G (n = 13) and A2059G (n = 13) in Halland. The most prevalent possible resistance-associated ParC amino acid alterations were S83I (n = 4) in Örebro and S83N (n = 2) in Halland. Resistance-associated mutations to both macrolides and fluoroquinolones were found in 0.7% of samples. Our findings emphasize the need for routine AMR testing, at a minimum for macrolide resistance, of all M. genitalium-positive samples and regular national and international surveillance of AMR in M. genitalium, to ensure effective patient management and rational antimicrobial use.


Assuntos
Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Macrolídeos/farmacologia , Mycoplasma genitalium/efeitos dos fármacos , Farmacorresistência Bacteriana , RNA Ribossômico 23S/genética , Fatores de Tempo
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