Why does it return? Recurrent CDI

If this is not the first time you are battling C. difficile, it is not your fault. You understand why the infection returns so stubbornly, and why it is precisely the restoration of the flora that breaks this spiral.

The numbers behind which you, too, stand

Many patients believe that once they are "over it", that's the end of it. The reality is that C. difficile infection often returns. After the first episode, the infection flares up again in roughly 20–30 per cent of patients. That is already a high rate on its own — but the situation is even more telling if someone has relapsed more than once.

This is because every relapse further increases the chance of the next. In someone in whom the infection has already recurred several times, the probability of the next recurrence can exceed 60 per cent. So it is no accident that you feel it getting harder and harder: the infection falls into a self-feeding pattern, and after each round it returns ever more easily.

So if you, too, are at your umpteenth episode, that does not mean you did something wrong, or that you are "weaker". The return stems from the nature of the disease — and it is precisely this nature that the DiffBiome course targets, attacking not only the pathogen but also the underlying problem that feeds the return.

The vicious cycle — why does it spiral?

The mechanism of recurrence is logical if we think it through step by step. The typical initial treatment of C. difficile infection is an antibiotic, which does indeed push the pathogen back — the complaints ease temporarily. The catch is that this same antibiotic further thins out the protective flora, so colonisation resistance^[G] — the natural shield discussed in the previous chapter — cannot recover.

Meanwhile the tough spores of C. difficile survive in the bowel. As soon as the antibiotic course ends, and the flora is still weak and thinned out, the surviving spores germinate, the bacterium multiplies again, and the complaints return. Another antibiotic follows — which again further weakens the flora. This is the vicious cycle: after each round the protection is weaker, the return easier.

The solution, therefore, cannot be to try to overcome the pathogen with ever-stronger antibiotics — that only deepens the problem. The spiral can be broken where it arises: at the rebuilding of the flora^[G]. If the diverse, protective gut flora is restored, colonisation resistance returns, the surviving spores cannot germinate, and the cycle is broken. This is exactly the goal of DiffBiome FMT^[G].

What can happen, and what is not your fault

Many patients live for months or years with the diarrhoea returning again and again, with the constant uncertainty of "when the next attack will come". This is exhausting, and often leaves its mark on mood, work and social life too. It needs to be said plainly: this burden is not your fault, and it is not because you "weren't careful enough".

The good news is that it is precisely in recurrent cases that the benefit of flora restoration is most striking. The more relapses you have been through, the greater the chance that the pathogen-targeting antibiotic on its own would no longer be enough — and the more you gain with the DiffBiome course, namely that you are not only suppressing the symptoms but treating the root of the return. In your diary, over the coming weeks, you will be able to see for yourself how the symptom trend turns steadily in the right direction.

🍽️ Eating during these days

During these three days you understand why the infection returns so stubbornly, and why it is the restoration of the flora that breaks the recurrence spiral — and your eating now supports your bowel settling while this flora rebuilds. Since the danger of diarrhoea and dehydration still remains, the goal is a gentle, firming diet: plenty of fluids, easily digestible foods and soluble fibre. Soluble fibre forms a gel in water, which slows the passage of bowel contents and supports a firmer stool, while plenty of fluids replace the amount lost with the looser stool. Your concrete tasks: on all three days take the daily dose according to the usual routine, drink an extra glass of water after every looser stool, and do not start a further antibiotic or probiotic course on your own that would again disturb the flora that is now rebuilding.

In this early phase there is not yet a daily plant — the Plant Calendar only starts from day 15. For now stay with easily digestible, boiled or steamed foods, and avoid raw, coarse, strongly gas-forming foods; building up a varied, diverse diet comes later, as the symptoms settle.

References

[7] van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013. Link

Open-label RCT in patients with recurrent C. difficile infection comparing duodenal donor faeces infusion (after short vancomycin + bowel lavage) with standard 14-day vancomycin, with or without bowel lavage. The primary endpoint was diarrhoea resolution without relapse at 10 weeks. The trial was stopped early at interim analysis: 13/16 patients (81\%) in the FMT arm achieved resolution after a single infusion, substantially exceeding both vancomycin arms. Establishes FMT as superior to antibiotic monotherapy for recurrent CDI and provides the landmark evidence base for FMT clinical translation.

[36] Cammarota G, Ianiro G, Tilg H et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017. Link

European consensus conference developing evidence-based recommendations on FMT for clinical practice, with 28 experts from 10 countries collaborating in working groups. Statements were generated through evidence-based review, evaluated electronically via a Delphi process, and finalized in a plenary consensus session. Recommendations cover FMT indications, donor selection, faecal material preparation, clinical management, faecal delivery, and minimum requirements for establishing an FMT centre. Provides the European standardization framework for safe and governed FMT delivery.

[346] Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015. Link

In an active 2011 population- and laboratory-based surveillance across ten US areas, 15,461 incident C. difficile infection cases were identified. 65.8% were health-care associated, but only 24.2% had hospital-onset disease, indicating that most health-care-associated cases were diagnosed after discharge or in non-acute settings. National estimates derived from regression modeling indicated approximately 453,000 incident CDI cases, 83,000 first recurrences and 29,300 deaths within 30 days of diagnosis annually. NAP1 strains predominated among health-care-associated isolates. The study established CDI as a leading cause of US healthcare-associated infection and a growing community burden.

[347] Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, Beldavs ZG, Kainer MA, Karlsson M, Gerding DN, McDonald LC; Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med. 2020. Link

Building on the Emerging Infections Program surveillance in ten US sites, the authors estimated the national burden of C. difficile infection from 2011 to 2017, adjusting for the higher sensitivity of NAAT-based diagnostics. The estimated total burden decreased over the period, driven largely by a reduction in health-care-associated CDI, while community-associated CDI remained stable. First-recurrence rates and in-hospital deaths also declined modestly. Trends were modeled with weighted random-intercept negative-binomial and logistic regression. The findings indicate that US-wide infection-prevention efforts have measurably reduced the health-care-associated CDI burden without comparable progress on community-associated disease.

[349] Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021. Link

This 2021 IDSA/SHEA focused-update guideline addresses fidaxomicin and bezlotoxumab in adult C. difficile infection (CDI) management. Recommendations were derived from systematic literature review and graded using GRADE. The panel recommends fidaxomicin over vancomycin for initial CDI episode and for first recurrence (conditional, moderate certainty), citing reduced recurrence risk. Bezlotoxumab is suggested as adjunct to standard antibiotic therapy for patients at high risk of CDI recurrence (conditional, very low certainty). The update reflects accumulating RCT evidence and refines positioning of newer agents within the CDI treatment algorithm.