scholarly journals An alarming high prevalence of resistance-associated mutations to macrolides and fluoroquinolones in Mycoplasma genitalium in Belgium: results from samples collected between 2015 and 2018

2020 ◽  
pp. sextrans-2020-054511
Author(s):  
Irith De Baetselier ◽  
Chris Kenyon ◽  
Wim Vanden Berghe ◽  
Hilde Smet ◽  
Kristien Wouters ◽  
...  

ObjectivesThe number of reported cases of multiresistant Mycoplasma genitalium (MG) is increasing globally. The aim of this study was to estimate the prevalence of macrolide and possible fluoroquinolone resistance-associated mutations (RAMs) of MG in Belgium.MethodsThe study was performed retrospectively on two sets of MG-positive samples collected in Belgium between 2015 and 2018. The first set of samples originated from routine surveillance activities and the second set came from a cohort of men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV transmission. Detection of RAMs to macrolides and fluoroquinolones was performed on all samples using DNA sequencing of the 23S ribosomal RNA gene, the gyrA gene and the parC gene.ResultsSeventy-one per cent of the MG samples contained a mutation conferring resistance to macrolides or fluoroquinolones (ParC position 83/87). RAMs were more frequently found among men compared with women for fluoroquinolones (23.9% vs 9.1%) and macrolides (78.4% vs 27.3%). Almost 90% of the MG infections among MSM possessed a RAM to macrolides (88.4%). In addition, 18.0% of the samples harboured both macrolides and fluoroquinolone RAMs; 3.0% in women and 24.2% in MSM. Being MSM was associated with macrolide RAMs (OR 15.3), fluoroquinolone RAMs (OR 3.8) and having a possible multiresistant MG infection (OR 7.2).ConclusionThe study shows an alarmingly high prevalence of MG with RAMs to macrolides and fluoroquinolones in Belgium. These results highlight the need to improve antimicrobial stewardship in Belgium in order to avoid the emergence of untreatable MG.

Author(s):  
I. De Baetselier ◽  
C. Kenyon ◽  
W. Vanden Berghe ◽  
H. Smet ◽  
K. Wouters ◽  
...  

ABSTRACTObjectivesThe number of reported cases of multi-resistant Mycoplasma genitalium (Mg) is increasing globally. The aim of this study was to estimate the prevalence of macrolide and possible fluoroquinolone resistance associated mutations (RAMs) of Mg in Belgium.MethodsThe study was performed retrospectively on two sets of Mg positive samples collected in Belgium between 2015-2018. The first set of samples originated from routine surveillance activities and the second set came from a cohort of men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV transmission. Detection of RAMs to macrolides and fluoroquinolones was performed on all samples using DNA sequencing of the 23S ribosomal RNA gene, the gyrA gene and the parC gene.ResultsSeventy-six percent of the Mg samples contained a mutation conferring resistance to macrolides or fluoroquinolones (parC position 83/87). RAMs were more frequently found among men compared to women for fluoroquinolones (28.7% vs 9.1%) and macrolides (82.9% vs 27.3%). More than 90% of the Mg infections among MSM possessed a RAM to macrolides (90.7%). In addition, 23.4% of the samples harboured both macrolides and fluoroquinolone RAMs; 3.0% in women and 30.7% in MSM. Being MSM was associated with macrolide RAMs (Odds ratio: 15.1), fluoroquinolone RAMs (Odds ratio: 3.4) and having a possible multi-resistant Mg infection (Odds ratio: 8.2).ConclusionThe study shows an alarmingly high prevalence of Mg with RAMs to macrolides and fluoroquinolones in Belgium. These results highlight the need to improve antimicrobial stewardship in Belgium in order to avoid the emergence of untreatable Mg.KEY MESSAGESOur study reports an alarmingly high prevalence of Mycoplasma genitalium antimicrobial resistance to either macrolides or fluoroquinolones in Belgium (76.6%).Multi-resistant Mg was found in almost 25% of cases, however, the prevalence of multi-resistant Mg was remarkably higher in men (27.1% vs 3.0%).The number of Mg resistant cases was much higher in men who have sex with men compared to heterosexual men and women.These results highlight the need to improve antimicrobial stewardship in Belgium.


2019 ◽  
Vol 70 (5) ◽  
pp. 805-810 ◽  
Author(s):  
Yang Li ◽  
Xiaohong Su ◽  
Wenjing Le ◽  
Sai Li ◽  
Zhaoyan Yang ◽  
...  

Abstract Background Mycoplasma genitalium (MG) causes symptomatic urethritis in men, and can infect alone or together with other sexually transmitted infection (STI) agents. Methods The prevalence of MG and other STIs was determined in 1816 men with symptomatic urethritis. Resistance of MG to macrolides and fluoroquinolones was determined by sequencing; the impact of recent antimicrobial usage on the distribution of MG single or mixed infections was determined. Results Overall, prevalence of MG infection was 19.7% (358/1816). Fifty-four percent (166/307) of MG infections occurred alone in the absence of other STI agents. Men with single MG infection self-administered or were prescribed antibiotics more often in the 30 days prior to enrollment than subjects with urethritis caused by MG coinfection (P < .0001). Higher rates (96.7%) of infection with macrolide resistance in MG were identified in men who had taken macrolides prior to enrollment (P < .03). Overall, 88.9% (303/341) of 23S ribosomal RNA (rRNA) genes contained mutations responsible for macrolide resistance; 89.5% (308/344) of parC and 12.4% (42/339) of gyrA genes had mutations responsible for fluoroquinolone resistance. Approximately 88% (270/308) of MG had combined mutations in 23S rRNA and parC genes; 10.4% (32/308) had mutations in all 3 genes. Conclusions MG was the single pathogen identified in 11% of men with symptomatic urethritis. Overall, nearly 90% of MG infections were resistant to macrolides and fluoroquinolones. Men who took macrolides in the 30 days prior to enrollment had higher rates (97%) of macrolide-resistant MG. Resistance was associated with numerous mutations in 23SrRNA, parC, and gyrA genes.


2018 ◽  
Vol 94 (6) ◽  
pp. 406-410 ◽  
Author(s):  
Deborah L Couldwell ◽  
Dean Jalocon ◽  
Melissa Power ◽  
Neisha J Jeoffreys ◽  
Sharon C-A Chen ◽  
...  

ObjectivesWe aimed to estimate the prevalence of Mycoplasma genitalium infection and of mutations linked to macrolide resistance using the ResistancePlus MG assay (SpeeDx, Sydney, New South Wales, Australia) in first-void urine (FVU), anorectal and oropharyngeal samples from men who have sex with men (MSM) attending Western Sydney Sexual Health Centre (WSSHC).MethodsConsecutive symptomatic and asymptomatic MSM attending for STI testing were prospectively enrolled. M. genitalium testing using the ResistancePlus MG assay was performed on FVU, anorectal and oropharyngeal samples routinely collected for Chlamydia trachomatis and Neisseria gonorrhoeae assays.ResultsOverall, the prevalence of M. genitalium infection in the study group was 13.4% (68/508). Most (79.4%, 54/68) M. genitalium harboured macrolide resistance mutations (87.5% of urethral and 75.6% of anorectal infections). The anorectum was the most commonly infected site (45/505, 8.9%), followed by the urethra (24/508, 4.7%). No oropharyngeal M. genitalium infections were detected (0/508). Most of the anorectal (93.3%) and urethral (79.2%) infections were asymptomatic.MSM who were taking HIV pre-exposure prophylaxis (PrEP) were twice as likely to be infected with M. genitalium compared with MSM who were not on PrEP (OR 2.1, 95% CI 1.3 to 3.6; P=0.0041). Always using condoms for anal sex in the last 3 months was protective of infection (OR 0.8, 95% CI 0.6 to 1.0; P=0.0186).ConclusionsWe demonstrated a high prevalence of M. genitalium and very high levels of macrolide resistance among MSM attending WSSHC. Our findings support the routine use of an assay to detect macrolide resistance mutations in M. genitalium infections. This will ensure, in regions or populations with high rates of macrolide resistance among M. genitalium strains, that first-line treatment with azithromycin will only be used if a macrolide-sensitive strain is identified.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S833-S833
Author(s):  
Alyson L Singleton ◽  
Brandon D Marshall ◽  
Xiao Zang ◽  
Amy S Nunn ◽  
William C Goedel

Abstract Background Although there is ongoing debate over the need for substantial increases in PrEP use when antiretroviral treatment confers the dual benefits of reducing HIV-related morbidity and mortality and the risk of HIV transmission, no studies to date have quantified the potential added benefits of PrEP use in settings with high treatment engagement across variable sub-epidemics in the United States. Methods We used a previously published agent-based network model to simulate HIV transmission in a dynamic network of 17,440 Black/African American and White MSM in Atlanta, Georgia from 2015 to 2024 to understand how the magnitude of reductions in HIV incidence attributable to varying levels of PrEP use (0–90%) changes in potential futures where high levels of treatment engagement (i.e. the UNAIDS ‘90-90-90’ goals and eventual ‘95-95-95’ goals) are achieved and maintained, as compared to current levels of treatment engagement in Atlanta (Figure 1). Model inputs related to HIV treatment engagement among Black/African American and White men who have sex with men in Atlanta. A comparison of current levels of treatment engagement (Panel A) to treatment engagement at ‘90-90-90’ (Panel B) and ‘95-95-95’ goals (Panel C). Results Even at achievement and maintenance of ‘90-90-90’ goals, 75% PrEP coverage reduced incidence rates by an additional 67.9% and 74.2% to 1.53 (SI: 1.39, 1.70) and 0.355 (SI: 0.316, 0.391) per 100 person-years for Black/African American and White MSM, respectively (Figure 2), compared to the same scenario with no PrEP use. Additionally, an increase from 15% PrEP coverage to 75% under ‘90-90-90’ goals only increased person-years of PrEP use per HIV infection averted, a measure of efficiency of PrEP, by 8.1% and 10.5% to 26.7 (SI: 25.6, 28.0) and 73.3 (SI: 70.6, 75.7) among Black/African American MSM and White MSM, respectively (Figure 3). Overall (Panel A) and race-stratified (Panel B and Panel C) marginal changes in HIV incidence over ten years among Black/African American and White men who have sex with men in Atlanta across scenarios of varied levels of treatment engagement among agents living with HIV infection and levels of pre-exposure prophylaxis use among HIV-uninfected agents. Note: All changes are calculated within each set of treatment scenarios relative to a scenario where no agents use pre-exposure prophylaxis. Person-years of pre-exposure prophylaxis use per HIV infection averted among Black/African American (Panel A) and White (Panel B) men who have sex with men in Atlanta across scenarios of varied levels of treatment engagement among agents living with HIV infection and levels of pre-exposure prophylaxis use among HIV-uninfected agents. Note: The number of HIV infections averted is calculated within each set of treatment scenarios relative to a scenario where no agents use pre-exposure prophylaxis. Conclusion Even in the context of high treatment engagement, substantial expansion of PrEP use still contributes to meaningful decreases in HIV incidence among MSM with minimal changes in person-years of PrEP use per HIV infection averted, particularly for Black/African American MSM. Disclosures All Authors: No reported disclosures


Epidemics ◽  
2019 ◽  
Vol 28 ◽  
pp. 100337 ◽  
Author(s):  
Ganna Rozhnova ◽  
Janneke C.M. Heijne ◽  
Maartje Basten ◽  
Chantal den Daas ◽  
Amy Matser ◽  
...  

2020 ◽  
Author(s):  
Linwei Wang ◽  
Nasheed Moqueet ◽  
Anna Simkin ◽  
Jesse Knight ◽  
Huiting Ma ◽  
...  

ABSTRACTBackgroundHIV pre-exposure prophylaxis (PrEP) may change serosorting patterns. We examined the influence of serosorting on the population-level HIV transmission impact of PrEP, and how impact could change if PrEP users stopped serosorting.MethodsWe developed a compartmental HIV transmission model parameterized with bio-behavioural and HIV surveillance data among men who have sex with men in Canada. We separately fit the model with serosorting and without serosorting (random partner-selection proportional to availability by HIV-status (sero-proportionate)), and reproduced stable HIV epidemics (2013-2018) with HIV-prevalence 10.3%-24.8%, undiagnosed fraction 4.9%-15.8%, and treatment coverage 82.5%-88.4%. We simulated PrEP-intervention reaching stable coverage by year-1 and compared absolute difference in relative HIV-incidence reduction 10-year post-intervention (PrEP-impact) between: models with serosorting vs. sero-proportionate mixing; and scenarios in which PrEP users stopped vs. continued serosorting. We examined sensitivity of results to PrEP-effectiveness (44%-99%) and coverage (10%-50%).FindingsModels with serosorting predicted a larger PrEP-impact compared with models with sero-proportionate mixing under all PrEP-effectiveness and coverage assumptions (median (inter-quartile-range): 8.1%(5.5%-11.6%)). PrEP users” stopping serosorting reduced PrEP-impact compared with when PrEP users continued serosorting: reductions in PrEP-impact were minimal (2.1%(1.4%-3.4%)) under high PrEP-effectiveness (86%-99%); however, could be considerable (10.9%(8.2%-14.1%)) under low PrEP effectiveness (44%) and high coverage (30%-50%).InterpretationModels assuming sero-proportionate mixing may underestimate population-level HIV-incidence reductions due to PrEP. PrEP-mediated changes in serosorting could lead to programmatically-important reductions in PrEP-impact under low PrEP-effectiveness (e.g. poor adherence/retention). Our findings suggest the need to monitor sexual mixing patterns to inform PrEP implementation and evaluation.FundingCanadian Institutes of Health ResearchRESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for full-text journal articles published between Jan 1, 2010, and Dec 31, 2017, using the MeSH terms “pre-exposure prophylaxis (PrEP)” and “homosexuality, male” and using key words (“pre-exposure prophylaxis” or “preexposure prophylaxis” or “PrEP”) and (“men who have sex with men” or “MSM”) in titles and abstracts. Search results (520 records) were reviewed to identify publications which examined the population-level HIV transmission impact or population-level cost-effectiveness of PrEP in high-income settings. We identified a total of 18 modelling studies of PrEP impact among men who have sex with men (MSM) and four studies were based on the same model with minor variations (thus only the most recent one was included). Among the 15 unique models of PrEP impact, three included serosorting. A total of nine models have assessed the individual-level behaviour change among those on PrEP and its influence on the transmission impact of PrEP. Specifically, the models examined increases in number of partners and reductions in condom use. Most models predicted that realistic increases in partner number or decreases in condom use would not fully offset, but could weaken, PrEP”s impact on reducing HIV transmission. We did not identify any study that examined the influence of serosorting patterns on the estimated transmission impact of PrEP at the population-level, or what could happen to HIV incidence if the use of PrEP changes serosorting patterns.Added value of this studyWe used a mathematical model of HIV transmission to estimate the influence of serosorting and PrEP-mediated changes in serosorting on the transmission impact of PrEP at the population-level among MSM. We found the impact of PrEP was higher under epidemics with serosorting, compared with comparable epidemics simulated assuming sero-proportionate mixing. Under epidemics with serosorting, when PrEP users stopped serosorting (while other men continue to serosort among themselves) we found a reduced PrEP impact compared with scenarios when PrEP users continued to serosort. The magnitude of reduction in PrEP impact was minimal if PrEP-effectiveness was high; however, could be programmatically-meaningful in the context of low PrEP-effectiveness (e.g., poor adherence or retention) and high PrEP coverage. To our knowledge, our study is the first to directly examine the influence of serosorting and PrEP-mediated changes in serosorting on the transmission impact of PrEP and its underlying mechanism.Implications of all the available evidenceOur findings suggest that models which do not consider baseline patterns of serosorting among MSM could potentially underestimate PrEP impact. In addition to monitoring individual-level behavioural change such as condom use, our findings highlight the need to monitor population-level sexual mixing patterns and their changes over time among MSM in the design and evaluation of PrEP implementation.


2021 ◽  
Vol 70 (9) ◽  
Author(s):  
Teck-Phui Chua ◽  
Kaveesha Bodiyabadu ◽  
Dorothy A. Machalek ◽  
Suzanne M. Garland ◽  
Catriona S. Bradshaw ◽  
...  

Introduction. Failure of fluoroquinolones, the principal treatment option for macrolide-resistant Mycoplasma genitalium infections, has recently emerged. This is of particular concern for men who have sex with men (MSM), who have high proportions of macrolide-resistant M. genitalium infections. Treatment failure with moxifloxacin is likely the result of single nucleotide polymorphisms (SNPs) in parC, whilst concurrent gyrA mutations may play a role. Gap Statement. The levels of fluoroquinolone resistance and dual-class (i.e. macrolide and fluoroquinolone) resistance in M. genitalium among asymptomatic MSM is unknown. Aim. To (i) determine the proportion of fluoroquinolone resistance and dual-class resistance in M. genitalium infections among asymptomatic MSM, (ii) explore any clinical and behavioural associations with fluoroquinolone resistance, and (iii) determine the distribution of antibiotic resistance among M. genitalium mgpB sequence types (STs). Methodology. M. genitalium positive samples (N=94) were obtained from 1001 asymptomatic MSM enrolled in a study at Melbourne Sexual Health Centre (Carlton, Australia) between August 2016 and September 2017. Sanger sequencing was performed to determine the proportion of M. genitalium infections with SNPs in parC that have previously been associated with failure of moxifloxacin (corresponding to amino changes S83I, D83R, D87Y and D87N) and in gyrA (corresponding to amino acid changes M95I, D99N, D99Y and D99G). Associations between clinical/behavioural factors and parC SNPs were examined. Strain typing was performed by sequencing a portion of the mgpB gene. Results. The proportion of MSM with infections harbouring parC and gyrA SNPs was 13.0 % [95 % confidence interval (CI): 6.8–23.2 %] and 4.7 % (95 % CI: 1.1–13.4 %), respectively; dual-class resistance was 13.0 %. No significant clinical/behavioural associations were found. Antibiotic resistance was not restricted to specific mgpB STs. Conclusion. One in eight (13 %) of asymptomatic MSM with M. genitalium had an infection with dual-class-resistance mutations. Typing by mgpB sequence suggested fluoroquinolone resistance is arising from independent mutation events. This study illustrates that asymptomatic MSM may act as a reservoir for antibiotic-resistant M. genitalium .


Author(s):  
Liping Wang ◽  
Anwarud Din ◽  
Peng Wu

In this paper, to investigate the synthetic effect of PrEP (pre-exposure prophylaxis) and ART (antiretrovial therapy) on HIV transmission among MSM (men who have sex with men) in heterogenous environment, an realistic HIV epidemic model with spatial diffusion is established. Here, HIV infectious people are divided into three immunity based compartments, i.e., CD4+ T cell count less than 350, between 350 and 500, and more than 500, respectively. The basic reproduction number $R_0$ is established and proved as a threshold parameter: The global asymptotic stability of the disease-free steady state holds for $R_0<1$, and the disease will be present if $R_0>1$. Considering the substantial advantages of PrEP and ART in controlling HIV transmissions among MSM, the optimal control problem is presented for the case of positive constant diffusion coefficients, which minimize the total population of susceptible individual and HIV infected individual, the cost of PrEP and ART thearpy. As an illustration of our theoretical results, we conduct numerical simulations. We also conduct an optimal control case study where model parameters are estimated from the demographic and epidemiological data from China. This work suggests: (1) Spatial factors cannot be ignored during the HIV intervention; (2)Taking the PrEP intervention measure for HIV transmissions among MSM as early as possible will help to improve the control efficiency and reduces its cost; (3) Reducing the PrEP drug costs will promote the efficiency of PrEP treatment in preventing the spread of HIV among MSM.


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