致死的スーパーバグC. difの治療が弱まる可能性(Treatment for Deadly Superbug C. diff May Be Weakening)

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2024-04-25 ヒューストン大学(UH)

致死的スーパーバグC. difの治療が弱まる可能性(Treatment for Deadly Superbug C. diff May Be Weakening)
Clostridium difficile bacterium, 3D illustration Courtesy: GETTY Images

ヒューストン大学薬学部の新しい研究によると、致死的なスーパーバグC. difficile(C. diff)による感染症の初期治療として推奨される抗生物質バンコマイシンの効果が低下している可能性があります。2018年の臨床ガイドラインに基づき、過去6年間でバンコマイシンの使用は54%増加しましたが、治療成功率は2000年代初頭のほぼ100%から現在の臨床試験で約70%に低下しています。アン・J・ゴンザレス=ルナ教授は、C. diffに対するバンコマイシンの効果が低下しているデータが増えているにもかかわらず、これが臨床結果にどのように影響するかについての理解が不足していると報告しています。

<関連情報>

Clostridioides difficileにおけるバンコマイシン感受性低下は、初回治癒率および臨床効果持続率の低下と関連する Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response

Taryn A Eubank, Chetna Dureja, Kevin W Garey, Julian G Hurdle, Anne J Gonzales-Luna
Clinical Infectious Diseases  Published:21 February 2024
DOI:https://doi.org/10.1093/cid/ciae087

Abstract

Background
Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR).

Methods
This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes.

Results
A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5–16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28–.97]; P = .04).

Conclusions
Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.

有機化学・薬学
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