High Prevalence and High Rate of Antibiotic Resistance of Mycoplasma genitalium Infections in Men who Have Sex with Men. A Sub-Study of the ANRS Ipergay PrEP Trial

2020 ◽  
Author(s):  
Béatrice Berçot ◽  
Isabelle Charreau ◽  
Rousseau Clotilde ◽  
Constance Delaugerre ◽  
Christian Chidiac ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycoplasma Genitalium ◽  
Urine Samples ◽  
High Rate ◽  
Post Exposure Prophylaxis ◽  
Open Label ◽  
Sex With Men ◽  
Incident Cases ◽  
The Impact

Abstract Background Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. In this study, we assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on demand TDF/FTC for HIV prevention and the impact of doxycycline post-exposure prophylaxis (PEP). Methods 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples, oro-pharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQ) and to doxycycline were investigated in the French National Reference Centre of bacterial STI. Results The all-site prevalence of MG at baseline was 10.5% [6.3% in urine samples, 4.3% in anal swabs and 0.5% in throat swabs] and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP and 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQ was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA which could be associated with tetracycline resistance was observed in 12.5% of specimens tested. Conclusions The prevalence of MG infection among MSM on PrEP was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM- and FQ-resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.

Effects of Ofloxacin Administration on the Reliability of Urine Glucose Testing

1996 ◽  
Vol 30 (5) ◽  
pp. 469-472
Author(s):  
Tsong-Mei Tsai ◽  
Brian F Shea ◽  
Paul F Souney ◽  
Fred G Volinsky ◽  
Joseph M Scavone ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Tertiary Care ◽  
Urine Samples ◽  
Care Hospital ◽  
Open Label ◽  
Urine Glucose ◽  
Glucose Testing

OBJECTIVE: TO study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0–4 hours postdose, and (3) pooled 4–8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0,25,50, 100, 200,400, and 800 μg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. Supported by a grant from the RW Johnson Pharmaceutical Research Institute. Presented in abstract form at the American College of Clinical Pharmacy 1994 Winter Practice and Research Forum, February 6–9, 1994, San Diego. CA.

scholarly journals Lipophilicity and Click Reactivity Determine the Performance of Bioorthogonal Tetrazine Tools in Pretargeted in Vivo Chemistry

2020 ◽  
Author(s):  
Johanna Stéen ◽  
Jesper Tranekjær Jørgensen ◽  
Denk Christoph ◽  
Umberto Maria Battisti ◽  
Kamilla Nørregaard ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Rational Design ◽  
Structural Parameters ◽  
Early Time ◽  
High Rate ◽  
Drug Conjugates ◽  
Compound Libraries ◽  
Drug Concentrations ◽  
The Impact

<p>The development of highly selective and fast biocompatible reactions for ligation and cleavage has paved the way for new diagnostic and therapeutic applications of <i>in vivo</i> chemistry. The concept of bioorthogonal pretargeting has attracted considerable interest, in particular for the targeted delivery of radionuclides and drugs. In nuclear medicine, pretargeting can provide increased target-to-background ratios at early time-points compared to traditional approaches. This reduces the radiation burden to healthy tissue and, depending on the selected radionuclide, enables better imaging contrast or higher therapeutic efficiency. Moreover, bioorthogonally triggered cleavage of pretargeted antibody-drug conjugates represents an emerging strategy to achieve controlled release and locally increased drug concentrations. The toolbox of bioorthogonal reactions has significantly expanded in the past decade, with the tetrazine ligation being the fastest and one of the most versatile <i>in vivo</i> chemistries. Progress in the field, however, relies heavily on the development and evaluation of (radio)labeled compounds, preventing the use of compound libraries for systematic studies. The rational design of tetrazine probes and triggers has thus been impeded by the limited understanding of the impact of structural parameters on the <i>in vivo</i> ligation performance. In this work, we describe the development of a pretargeted blocking assay that allows for the investigation of the <i>in vivo</i> fate of a structurally diverse library of 45 unlabeled tetrazines and their capability to reach and react with pretargeted <i>trans</i>-cyclooctene (TCO)-tagged antibodies in tumor-bearing mice. This study enabled us to assess the correlation of click reactivity and lipophilicity of tetrazines with their <i>in vivo</i> performance. In particular, high rate constants (>50,000 M<sup>-1</sup>s<sup>-1</sup>) for the reaction with TCO and low calculated log<i>D</i><sub>7.4</sub> values (below -3) of the tetrazine were identified as strong indicators for successful pretargeted <i>in vivo</i> click chemistry. Click-radiolabeling gave access to a set of selected <sup>18</sup>F-labeled tetrazines, including highly reactive scaffolds, which were used in pretargeted PET imaging studies to confirm the results from the blocking study. These insights thus enable the rational design of tetrazine probes for <i>in vivo</i> application and will thereby assist the clinical translation of bioorthogonal pretargeting.</p>

scholarly journals Prevalence of Mycoplasma genitalium fluoroquinolone-resistance markers, and dual-class-resistance markers, in asymptomatic men who have sex with men

2021 ◽  
Vol 70 (9) ◽  
Author(s):  
Teck-Phui Chua ◽  
Kaveesha Bodiyabadu ◽  
Dorothy A. Machalek ◽  
Suzanne M. Garland ◽  
Catriona S. Bradshaw ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Type Species ◽  
Health Centre ◽  
Mycoplasma Genitalium ◽  
Fluoroquinolone Resistance ◽  
Content Type ◽  
Link Type ◽  
Resistance Markers ◽  
Sex With Men ◽  
Dual Class

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 .

scholarly journals Enterococcus faecalisCRISPR-Cas is a robust barrier to conjugative antibiotic resistance dissemination in the murine intestine

2018 ◽  
Author(s):  
Valerie J. Price ◽  
Sara W. McBride ◽  
Karthik Hullahalli ◽  
Anushila Chatterjee ◽  
Breck A. Duerkop ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Conjugative Plasmids ◽  
Resistance Plasmids ◽  
The Impact ◽  
Mammalian Intestine

AbstractCRISPR-Cas systems are barriers to horizontal gene transfer (HGT) in bacteria. Little is known about CRISPR-Cas interactions with conjugative plasmids, and studies investigating CRISPR-Cas/plasmid interactions inin vivomodels relevant to infectious disease are lacking. These are significant gaps in knowledge because conjugative plasmids disseminate antibiotic resistance genes among pathogensin vivo, and it is essential to identify strategies to reduce the spread of these elements. We use enterococci as models to understand the interactions of CRISPR-Cas with conjugative plasmids.Enterococcus faecalisis a native colonizer of the mammalian intestine and harbors pheromone-responsive plasmids (PRPs). PRPs mediate inter- and intraspecies transfer of antibiotic resistance genes. We assessedE. faecalisCRISPR-Cas anti-PRP activity in the mouse intestine and under varyingin vitroconditions. We observed striking differences in CRISPR-Cas efficiencyin vitroversusin vivo. With few exceptions, CRISPR-Cas blocked intestinal PRP dissemination, whilein vitro, the PRP frequently escaped CRISPR-Cas defense. Our results further the understanding of CRISPR-Cas biology by demonstrating that standardin vitroexperiments do not adequately model thein vivoanti-plasmid activity of CRISPR-Cas. Additionally, our work identifies several variables that impact the apparentin vitroanti-plasmid activity of CRISPR-Cas, including planktonic versus biofilm settings, different donor/recipient ratios, production of a plasmid-encoded bacteriocin, and the time point at which matings are sampled. Our results are clinically significant because they demonstrate that barriers to HGT encoded by normal human microbiota can have significant impacts onin vivoantibiotic resistance dissemination.ImportanceCRISPR-Cas is a type of immune system encoded by bacteria that is hypothesized to be a natural impediment to the spread of antibiotic resistance genes. In this study, we directly assessed the impact of CRISPR-Cas on antibiotic resistance dissemination in the mammalian intestine and under varyingin vitroconditions. We observed a robust effect of CRISPR-Cas onin vivobut notin vitrodissemination of antibiotic resistance plasmids in the native mammalian intestinal colonizerEnterococcus faecalis. We conclude that standard laboratory experiments currently do not appropriately model thein vivoconditions where antibiotic resistance dissemination occurs betweenE. faecalisstrains. Moreover, our results demonstrate that CRISPR-Cas encoded by native members of the mammalian intestinal microbiota can block the spread of antibiotic resistance plasmids.

scholarly journals Mycoplasma genitalium in Singapore is Associated with Chlamydia trachomatis Infection and Displays High Macrolide and Fluoroquinolone Resistance Rates

2020 ◽  
Author(s):  
Tim Hart ◽  
Wen Ying Tang ◽  
Siti Aminah Mansoor ◽  
Martin Tze-Wei Chio ◽  
Timothy Sebastian Barkham
Keyword(s):  
Antibiotic Resistance ◽  
Sexual Health ◽  
Mycoplasma Genitalium ◽  
Routine Screening ◽  
High Rate ◽  
Fluoroquinolone Resistance ◽  
Health Clinic ◽  
Resistance Mutations ◽  
Transmitted Infection ◽  
Sexually Transmitted

Abstract Background: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates. Methods : Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium . Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance. Results : We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection. Conclusions : Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

scholarly journals Study Protocol for a Pilot, Open-Label, Prospective, and Observational Study to Evaluate the Pharmacokinetics of Drugs Administered to Patients during Extracorporeal Circulation; Potential of In Vivo Cytochrome P450 Phenotyping to Optimise Pharmacotherapy

2019 ◽  
Vol 2 (2) ◽  
pp. 38
Author(s):  
Santosh Kumar Sreevatsav Adiraju ◽  
Kiran Shekar ◽  
Peter Tesar ◽  
Rishendran Naidoo ◽  
Ivan Rapchuk ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Laparoscopic Cholecystectomy ◽  
Observational Study ◽  
Extracorporeal Circulation ◽  
Control Group ◽  
Open Label ◽  
Cyp Enzymes ◽  
Post Surgery ◽  
The Impact

Pharmacokinetic alterations of medications administered during surgeries involving cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) have been reported. The impact of CPB on the cytochrome P450 (CYP) enzymes’ activity is the key factor. The metabolic rates of caffeine, dextromethorphan, midazolam, omeprazole, and Losartan to the CYP-specific metabolites are validated measures of in vivo CYP 1A2, 2D6, 3A4, 2C19, and 2C9 activities, respectively. The study aim is to assess the activities of major CYPs in patients on extracorporeal circulation (EC). This is a pilot, prospective, open-label, observational study in patients undergoing surgery using EC and patients undergoing laparoscopic cholecystectomy as a control group. CYP activities will be measured on the day, and 1–2 days pre-surgery/3–4 days post-surgery (cardiac surgery and Laparoscopic cholecystectomy) and 1–2 days after starting ECMO, 1–2 weeks after starting ECMO, and 1–2 days after discontinuation from ECMO. Aforementioned CYP substrates will be administered to the patient and blood samples will be collected at 0, 1, 2, 4, and 6 h post-dose. Major CYP enzymes’ activities will be compared in each participant on the day, and before/after surgery. The CYP activities will be compared in three study groups to investigate the impact of CYPs on EC.

The clinical view of antibiotic resistance: Unexpected treatment failures and the impact of pharmacokinetic-pharmacodynamic interactions in vivo.

2002 ◽  
Vol 59 (1) ◽  
pp. 11-19 ◽  
Author(s):  
M. Rossi ◽  
A. U. Gerber
Keyword(s):  
Antibiotic Resistance ◽  
Klinische Studien ◽  
Pharmacodynamic Interactions ◽  
Kontrollierte Klinische Studien ◽  
The Impact

Die Wirksamkeit eines Antibiotikums in vivo wird nicht nur durch dessen in vitro-Wirksamkeit bestimmt. Zusätzliche Faktoren sind für die in vivo-Wirksamkeit relevant, Phänomene, welche wir bis heute nur unvollständig verstehen. Neben physikalischen und biochemischen Faktoren am Herd der Infektion sind in unterschiedlichem Ausmaß pharmakokinetisch/pharmakodynamische Parameter einer Antibiotika/Mikroorganismus Konstellation von Bedeutung: (i) Das Verhältnis zwischen Spitzenkonzentration eines Antibiotikums und dessen antimikrobieller Potenz (gemessen an der MHK), (ii) das Verhältnis zwischen AUC des Antibiotikums und der MHK des Ziel-Mikroorganismus und schließlich (iii) die Zeitdauer supra-inhibiotischer Konzentrationen (Zeit über MHK) am Herd der Infektion. Die Zeit über der MHK ist der entscheidende Faktor für die antibakterielle Aktivität von Beta-Laktamantibiotika, Makroliden, Clindamycin und Linezolid. Andererseits sind das Peak/MIC Verhätnis und das AUC/MIC Verhältnis die wichtigen Parameter für eine optimale Wirkung von Aminoglykosiden und Fluorochinolonen. Für das Entstehen und die epidemiologische Ausbreitung mikrobieller Resistenz scheint schließlich eine bislang noch schlecht definierte «Mutations-Präventions-Konzentration» von Bedeutung. Um die Relevanz der besprochenen Phänomene für den klinischen Alltag besser zu verstehen, fehlen uns bis heute prospektive kontrollierte klinische Studien.

scholarly journals Antibiotic resistance detection is essential for gonorrhoea point-of-care testing: A mathematical modelling study

2017 ◽  
Author(s):  
Stephanie M. Fingerhuth ◽  
Nicola Low ◽  
Sebastian Bonhoeffer ◽  
Christian L. Althaus
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Pathways ◽  
Point Of Care ◽  
High Sensitivity ◽  
Nucleic Acid Amplification ◽  
Transmission Model ◽  
Antibiotic Resistant ◽  
Sex With Men ◽  
The Impact ◽  
Resistance Detection

AbstractAntibiotic resistance is threatening to make gonorrhoea untreatable. Point-of-care (POC) tests that detect resistance promise individually tailored treatment, but might lead to more treatment and higher levels of resistance. We investigate the impact of POC tests on antibiotic-resistant gonorrhoea. We used data about the prevalence and incidence of gonorrhoea in men who have sex with men (MSM) and heterosexual men and women (HMW) to calibrate a mathematical gonorrhoea transmission model. With this model, we simulated four clinical pathways for the diagnosis and treatment of gonorrhoea: POC test with (POC + R) and without (POC − R) resistance detection, culture, and nucleic acid amplification tests (NAATs). We calculated the proportion of resistant infections, cases averted after 5 years, and compared how fast resistant infections spread in the populations. The proportion of resistant infections after 30 years is lowest for POC + R (median MSM: 0.18%, HMW: 0.12%), and increases for culture (MSM: 1.19%, HWM: 0.13%), NAAT (MSM: 100%, HMW: 99.27%), and POC − R (MSM: 100%, HMW: 99.73%). NAAT leads to 36 366 (median MSM) and 1 228 (median HMW) observed cases after 5 years. When compared with NAAT, POC + R results in most cases averted after 5 years (median MSM: 3 353, HMW: 118 per 100 000 persons). POC tests that detect resistance with intermediate sensitivity slow down resistance spread more than NAAT. POC tests with very high sensitivity for the detection of resistance are needed to slow down resistance spread more than using culture. POC with high sensitivity to detect antibiotic resistance can keep gonorrhoea treatable longer than culture or NAAT. POC tests without reliable resistance detection should not be introduced because they can accelerate the spread of antibiotic-resistant gonorrhoea.

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