Failure of Azithromycin 2.0 g in the Treatment of Gonococcal Urethritis Caused by High-Level Resistance in California

Gose, Severin; Soge, Olusegun O.; Beebe, James L.; Nguyen, Duylinh; Stoltey, Juliet; Bauer, Heidi M.

doi:10.1097/olq.0000000000000265

Cited by 23 publications

(11 citation statements)

References 16 publications

(18 reference statements)

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“…These findings indicate that the susceptibility of N. gonorrhoeae isolates to AZM is decreasing; therefore, there is concern that treatment failures will increase. Taken together with the findings described in previous reports (22,23), our results suggest that adequate therapeutic effects cannot be obtained, even upon AZM-SR administration. Although descriptions of the effectiveness of AZM for the treatment of gonococcal urethritis have been added to the guidelines revised in 2016 (4), the decreasing susceptibility of N. gonorrhoeae to AZM has been reported in Japan (22,24).…”

Section: Discussionsupporting

confidence: 68%

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis

Soda

Ito

Matsumaru

et al. 2018

Antimicrob Agents Chemother

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The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain.

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Section: Discussionsupporting

confidence: 68%

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis

Soda

Ito

Matsumaru

et al. 2018

Antimicrob Agents Chemother

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“…After a brief decline in 2013, the proportion of gonococcal isolates that had an elevated ceftriaxone minimal inhibitory concentration (MIC) (>0.125 µg/ml) in the Gonococcal Isolate Surveillance Project increased in 2014 [ 37 ]. There have also been reported cases of isolates with even higher ceftriaxone MICs (>0.5 µg/ml) and high-level azithromycin resistance [ 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Sexually transmitted infections and pre-exposure prophylaxis: challenges and opportunities among men who have sex with men in the US

Scott

Klausner

2016

AIDS Res Ther

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Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in “real world” reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.

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“…High-level resistance to azithromycin (HLAzi-R) was first verified from an isolate from Argentina in 2001 34 and since then, cases have been reported in the UK, Ireland, Sweden, USA, China and Australia. [35][36][37][38][39][40][41] Initial cases were sporadic or occurred in small clusters, suggesting that resistance may be associated with a reduction in fitness and reversion to full sensitivity can occur. 32 However, more recently, there is evidence for sustained transmission of these HLAzi-R strains, both within and between heterosexual and MSM networks, 42,43 and an adaptive increase in biological fitness in animal and cellular models has been described.…”

Section: Azithromycin Resistance Patternsmentioning

confidence: 99%

Should we still use azithromycin for gonorrhoea treatment?

Mensforth

Ross

2019

Sex. Health

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This review presents the evidence for azithromycin in the treatment of gonorrhoea, both as monotherapy and as a component of dual therapy. Uncertainties are explored regarding the efficacy of a dual treatment strategy, combining ceftriaxone and azithromycin, in the context of resistance trends and extra-genital infections. The association between microbiological testing and clinical outcome for the individual patient, and the effect of azithromycin use on other sexually transmissible infections, are considered. Finally, in the absence of imminent new antimicrobials, optimising the dose of azithromycin while maintaining tolerability is discussed.

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Failure of Azithromycin 2.0 g in the Treatment of Gonococcal Urethritis Caused by High-Level Resistance in California

Cited by 23 publications

References 16 publications

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis

Sexually transmitted infections and pre-exposure prophylaxis: challenges and opportunities among men who have sex with men in the US

Should we still use azithromycin for gonorrhoea treatment?

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