常听讲“以毒攻毒”，科学家尝试使用致病艰难梭菌(Clostridium difficile)的近源无毒菌种来治疗致病艰难梭菌所致腹泻，并取得明显疗效，该项研究发表在Journal of the American Medical Association上。

艰难梭菌产生毒素，感染后引起腹泻和发热等症状。艰难梭菌感染是全球范围的常见病，仅在美国，每年因艰难梭菌感染所致死亡病例就约29000人。艰难梭菌常在抗生素杀死肠道正常菌群后趁机占领肠道阵地。对付艰难梭菌感染，当前多是使用更多的抗菌素，使原本已经脆弱、失调的肠道菌群环境更趋恶化，从而导致恶性循环。

艰难梭菌所致腹泻和发热症状为其所产生的毒素所致。基于此，美国Loyola大学的研究团队尝试使用非产毒的艰难梭菌芽孢来应对致病艰难梭菌。

结果显示这种策略十分有效。非产毒艰难梭菌占领原本由产毒致病菌所拥有的生存环境，从而阻止了致病艰难梭菌卷土重来。在非产毒艰难梭菌成功定居的肠道后，致病艰难梭菌难于再次感染，引发症状。

非致病菌通过与致病菌竞争而夺回阵地是一个非常有价值的思路。如果这种疗法能最终成功（已面临三期试验），不但可以用于处理致病艰难梭菌所致肠炎，还可以用于保护面临抗生素治疗的病人免于艰难梭菌趁虚而入。

另外一种对付致肠炎艰难梭菌的疗法是粪便移植法（faecal transplant），将健康亲属的肠道菌群移过来，让其在患者体内定居。上文所述非致病艰难梭菌疗法可以看做是粪便移植的精简版本，或说修正版本，总之都属“以菌制菌”的范例。

原文链接如下：http://jama.jamanetwork.com/article.aspx?articleid=2281703

Administration of Spores of NontoxigenicClostridiumdifficileStrain M3 for Prevention of RecurrentC difficileInfectionA RandomizedClinical Trial

ImportanceClostridium difficileis the most common cause ofhealth care–associated infection in US hospitals. Recurrence occurs in 25% to30% of patients.

ObjectiveTo determine the safety, fecal colonization, recurrence rate, andoptimal dosing schedule of nontoxigenicCdifficilestrain M3 (VP20621;NTCD-M3) for prevention of recurrentCdifficileinfection (CDI).

Design, Setting, and ParticipantsPhase 2, randomized, double-blind, placebo-controlled,dose-ranging study conducted from June 2011 to June 2013 among 173 patientsaged 18 years or older who were diagnosed as having CDI (first episode or firstrecurrence) and had successfully completed treatment with metronidazole, oralvancomycin, or both at 44 study centers in the United States, Canada, andEurope.

InterventionsPatients were randomly assigned to receive 1 of 4 treatments: oralliquid formulation of NTCD-M3, 10⁴spores/d for 7 days (n=43), 10⁷spores/d for 7 days (n=44), or 10⁷spores/d for 14 days (n=42), or placebo for 14 days (n=44).

Main Outcomes and MeasuresThe primary outcome was safety and tolerability of NTCD-M3 within7 days of treatment. Exploratory secondary outcomes included fecal colonizationwith NTCD-M3 from end of study drug through week 6 and CDI recurrence from day1 through week 6.

ResultsAmong 168 patients who started treatment, 157 completed treatment.One or more treatment-emergent adverse events were reported in 78% of patientsreceiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominalpain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33%of placebo patients, respectively. Serious treatment-emergent adverse eventswere reported in 7% of patients receiving placebo and 3% of all patients whoreceived NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3patients: 71% with 10⁷spores/d and 63% with 10⁴ spores/d. Recurrence of CDI occurredin 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (oddsratio [OR], 0.28; 95% CI, 0.11-0.69;P=.006); the lowest recurrence was in 2 (5%) of 43 patientsreceiving 10⁷spores/dfor 7 days (OR, 0.1; 95% CI, 0.0-0.6;P=.01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients whowere colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were notcolonized (OR, 0.01; 95% CI, 0.00-0.05;P<.001).

Conclusions and RelevanceAmong patients with CDI who clinically recovered followingtreatment with metronidazole or vancomycin, oral administration of spores ofNTCD-M3 was well tolerated and appeared to be safe. NontoxigenicC difficilestrain M3 colonized the gastrointestinaltract and significantly reduced CDI recurrence.

群晓科苑

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