3 years ago

Evaluation of the microbiological efficacy of a single 2-g dose of an extended-release azithromycin by population pharmacokinetics and simulation in Japanese patients with gonococcal urethritis.

Miho Yamamoto, Takashi Deguchi, Kiyoyuki Kitaichi, Hikari Takahashi, Yuta Ohno, Shin Ito, Izumi Nagase, Sakiko Nakamura, Naoki Matsumaru, Midori Soda, Yoshinori Itoh, Mitsuru Yasuda, Katsura Tsukamoto
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 on gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, AZM minimum inhibitory concentration (MIC) values for Neisseria gonorrhoeae isolates were determined, and microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/L. The mean value of the area under the concentration-time curve (AUC), estimated using a two-compartment model by population PK analysis, was 20.8 mg⋅h/L. Logistic regression analysis showed that the PK/PD target value to predict N. gonorrhoeae eradication rate ≥95% was calculated as AUC/MIC ≥ 59.5. The AUC/MIC value was significantly higher in microbiologically cured patients than in microbiologically failed patients. Monte Carlo simulation using this MIC distribution revealed the probability of AZM-SR monotherapy exceeding the AUC/MIC target (59.5) was 47%. Furthermore, the MIC distribution associated with strains isolated in this study was mostly consistent with that for current strains in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, either a single use of 2 g AZM-SR with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or diagnosed to possess AZM-sensitive strain.

Publisher URL: http://doi.org/10.1128/AAC.01409-17

DOI: 10.1128/AAC.01409-17

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