Dual Azithromycin/Ceftriaxone Therapy for Gonorrhea in PrEP Cohorts Results in Levels of Macrolide Consumption That Exceed Resistance Thresholds by up to 7-Fold

Kenyon, Chris

doi:10.1093/infdis/jiab178

Cited by 15 publications

(14 citation statements)

References 5 publications

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“…The prevalence of N. gonorrhoeae in this population typically exceeds 10%, where it mostly circulates asymptomatically [ 31 ]. This population is exposed to high volumes of antimicrobials [ 31 , 32 ]. As a result, when strains of N. gonorrhoeae spread within this sexual network, they become repeatedly subjected to high doses of CRO and other microbials, which could potentially lead to the development of tolerance [ 30 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

et al. 2022

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In addition to antimicrobial resistance, bacteria contain other mechanisms to survive antibiotic exposure such as tolerance, defined as the ability to slow metabolism by the extension of the lag phase without altering antimicrobial susceptibility. In a number of bacterial species, tolerance has been associated with treatment failure and infection chronicity and is found to precede and facilitate antimicrobial resistance. It is unknown if tolerance can be induced in Neisseria gonorrhoeae. In this study, we determined if tolerance to ceftriaxone (CRO) can be induced in N. gonorrhoeae and detected in clinical isolates. To induce tolerance, WHO P N. gonorrhoeae reference strain samples were grown under daily 3 h intermittent CRO exposure (10× the MIC), partitioned by overnight growth in GC broth. This cyclic exposure was performed for 7 consecutive days in sextuplicate, with two control cultures to which GC medium without antibiotics was added. To detect tolerance and assess CRO susceptibility, modified Tolerance Disc (TD) and Epsilometer tests were performed on isolates after each CRO exposure cycle. Additionally, this experiment was carried out on 18 clinical N. gonorrhoeae isolates. Tolerance was first detected after two CRO exposure cycles in five out of six samples. The phenotype differed per cycle with no clear pattern. No tolerance was found in control samples but was detected in 10 out of 18 clinical isolates. The present study is the first to demonstrate the induction of tolerance to CRO in N. gonorrhoeae through antibiotic exposure. In addition, tolerance to CRO was found in clinical samples.

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Section: Discussionmentioning

confidence: 99%

Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

et al. 2022

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“… 1 – 3 Proponents of monotherapy have noted that dual therapy results in extremely high levels of macrolide consumption in core groups such as men who have sex with men taking pre-exposure prophylaxis. 2 , 3 These high levels of macrolide exposure may directly induce macrolide resistance in not only N. gonorrhoeae but also in other bacteria. Recent studies have suggested that azithromycin may promote antimicrobial resistance to other classes of antimicrobials via inducing mutations that act as stepping–stones to antimicrobial resistance.…”

Section: Introductionmentioning

confidence: 99%

Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study

González

Laumen²,

Abdellati³

et al. 2023

F1000Res

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Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO–F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO–F WT and WHO–F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions: We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.

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“…12 The increased testing for STIs in MSM driven by PrEP use is associated with increased macrolide use and risk of increasing rates of antimicrobial resistance. 13 A delayed diagnoses of syphilis due to a reduction in STI screening in MSM using PrEP could result in serious sequelae. There are several limitations to our study including being a single centre clinic-based study which included patients attending for PrEP during the COVID-19 pandemic which may have affected access to services.…”

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confidence: 99%

Sexually transmitted infection testing and prevalence among MSM using event-based dosing HIV pre-exposure prophylaxis

Simmons¹,

Fitzpatrick

Richardson

2023

Sex. Health

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Dual Azithromycin/Ceftriaxone Therapy for Gonorrhea in PrEP Cohorts Results in Levels of Macrolide Consumption That Exceed Resistance Thresholds by up to 7-Fold

Cited by 15 publications

References 5 publications

Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

Tolerance to Ceftriaxone in Neisseria gonorrhoeae: Rapid Induction in WHO P Reference Strain and Detection in Clinical Isolates

Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study

Sexually transmitted infection testing and prevalence among MSM using event-based dosing HIV pre-exposure prophylaxis

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