Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
International Centre for Diarrhoeal Diseases and Research, Dhaka, Bangladesh.
Clin Infect Dis. 2021 May 18;72(10):1793-1798. doi: 10.1093/cid/ciaa363.
Azithromycin is frequently used to treat shigellosis; however, clinical outcomes are uncertain.
We performed an observational cohort study in Bangladesh of patients with invasive diarrhea treated empirically with azithromycin. Susceptibility testing was performed by broth microdilution and disk diffusion post hoc on all Shigella isolates and clinical response was correlated with in vitro susceptibility.
There were 149 Shigella culture-positive patients in the primary analysis. Infection with Shigella with decreased susceptibility to azithromycin was significantly associated with persistence of diarrhea at day 5 (31% vs 12%; relative risk [RR], 2.66; 95% confidence interval [CI], 1.34-5.28), culture positivity at day 5 or 6 (35% vs 5%; RR, 5.26; 95% CI, 1.84-14.85), and a higher rate of overnight hospitalization (58% vs 39%; RR, 1.49; 95% CI, 1.06-2.09). Shigella flexneri was more common than Shigella sonnei (58% vs 36%); however, S. sonnei constituted most of the isolates with decreased susceptibility to azithromycin (67%) and most of the multidrug-resistant strains (54%); thus, poor clinical outcomes were associated with S. sonnei. The current epidemiological cutoff for S. flexneri of ≥16 µg/mL to define decreased susceptibility to azithromycin was clinically predictive of poor outcome. Patients with S. sonnei and a low MIC (4 µg/mL) still had elevated rates of persistent diarrhea and culture positivity.
This study documents worse clinical outcomes for S. flexneri with decreased susceptibility to azithromycin, as well as S. sonnei, and supports the utility of susceptibility testing and clinical breakpoints for azithromycin. S. sonnei is an emerging drug-resistant threat.
NCT03778125.
阿奇霉素常用于治疗志贺氏菌病；然而，临床疗效尚不确定。
我们在孟加拉国进行了一项观察性队列研究，对接受经验性阿奇霉素治疗的侵袭性腹泻患者进行研究。在所有志贺菌分离株中进行了肉汤微量稀释法和纸片扩散法的药敏试验，然后将临床反应与体外药敏试验相关联。
在主要分析中，有 149 例志贺菌培养阳性患者。对阿奇霉素敏感性降低的志贺菌感染与第 5 天腹泻持续存在（31%比 12%；相对风险 [RR]，2.66；95%置信区间 [CI]，1.34-5.28）、第 5 或 6 天培养阳性（35%比 5%；RR，5.26；95% CI，1.84-14.85）和更高的住院过夜率（58%比 39%；RR，1.49；95% CI，1.06-2.09）显著相关。福氏志贺菌比宋内志贺菌更常见（58%比 36%）；然而，对阿奇霉素敏感性降低的志贺菌分离株中，宋内志贺菌占大多数（67%），且大多数为多重耐药菌株（54%）；因此，不良临床结局与宋内志贺菌有关。目前，将 16µg/mL 定义为福氏志贺菌对阿奇霉素敏感性降低的流行病学折点（EC），可预测不良结局。MIC 值较低（4µg/mL）的宋内志贺菌患者腹泻持续和培养阳性的发生率仍较高。
本研究表明，对阿奇霉素敏感性降低的福氏志贺菌以及宋内志贺菌的临床结局更差，支持阿奇霉素药敏试验和临床折点的应用。宋内志贺菌是一种新兴的耐药威胁。
NCT03778125。
