Effective Treatments For Recurrent Clostridium Difficile Infection: A Systematic Review

Analysis of Key Elements of the Article

Questions:

1. Analysis of key elements of the article?

2. Potential impact of the article on clinical practice?

Many instances of infection at the health care settings due to Clostridium difficle is evident through researches. This research highlights the hypervirulent strain of C. difficile BI/NAP/27 and its association with the incurrence of Clostridium difficle infection (CDI) and its recurrence. It also points to the incidence of adverse health outcomes as increased toxin production and diarrhea. This study identifies the high cost of over $13,000/relapse of RCDI (recurrence CDI) in hospital patients. As per the declaration of the IDSA (Infectious Diseases Society of America), a major emphasis is put on recognizing an effective treatment for RCDI immediately. Through an extensive study of the various eminent treatments prevailing in this context, the current article intends to present a clear and in-depth idea of the most effective treatment to be used for RCDI among all.

Treatment approaches and their effectiveness-

The 8 methods of treatment approaches identified in this article are extensively evaluated for their efficacy in preventing any further Clostridium difficile infection. Around 1/3rd of the patient reveals the recurrence of a Clostridium difficile infection (CDI). A highly considerable recurrence CDI (RCDI) shows close association with high rate of morbidity, expense and mortality (Gough, Shaikh & Manges, 2011). However, through the systematic review conducted on the 64 selected articles it is evident that the lack of extensive examination regarding the treatment of RCDI. The drugs identified in this article that proves effective for treating CDI include Metronidazole, rifampin, vancomycin, probiotics, fidaxomicin, fecal bacteriotherapy, immunoglobins and nitazoxanide. The article highlights the efficacy of Vancomycin and metronidazole are similar for treating RCDI. However, the efficacy of Fidaxomicin is found to be more effective than the earlier two medicines. A high level of efficacy is revealed by the Fecal bacteriotherapy (FBT) as well.

Search strategy-

Electronic databases such as CINAHL, Cochrane Review Database, EMBASE and MEDLINE are searched to select the most appropriate research articles on the topic of RCDI treatment. As opined by Wenisch et al. (2012), the adoption of a suitable inclusion and exclusion criteria enable the correct selection of materials to study. This systematic review depicts inclusion criteria of human trials and reports identifying results for a particular intervention application. Relevance of the criteria with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement increases the efficacy and reliability of the search strategy. The specific data considered to select the articles for the review are of vital significance to ensure that the review covers a wide range of information related to the topic.

Treatment interventions-

Vancomycin: This drug depicted efficiency in treating RCDI with pulsing or tapered doses in small studies or subgroups. Moderate evidence supporting its efficacy is present in the study. With considerable variability in dose and duration of the RCDI, vancomycin stands as the standard of care for treatment of RCDI currently. However, its comparative study with metronidazole shows the latter’s efficacy slightly higher than vancomycin (O’Horo et al. 2014).

Potential Impact of the Article on Clinical Practice

Metronidazole: The study of large RCTs with metronidazole treatment revealed high efficacy in initial response. However, it fails with the new strain of BI/NAPI/027 C. difficile thus restricting its use after a first recurrence. As conveyed by Lo Vecchio & Zacur (2012), it risks the accumulation of neurotoxic metabolites.

Immunoglobulins: Monoclonal immunoglobulin treatments reveal high (80%) initial response to RCDI prevention. Oral immunoglobulin treatment is more effective with promising outcome potential. However, its expense is still higher than vancomycin thus giving the latter a higher preference (Drekonja et al. 2011).

Probiotics: These seem to be highly effective in recolonization of colon preventing pathogenic invasion from C. difficile. It works in preventive manner and proves beneficial in treating RCDI in many cases. The study identifies species providing probiotic formulations. They include Enterococcus faecium, Saccharomyces boulardii, Lactobacillus spp. and Bifidobacteria spp. The S. boulardii is the only one showing moderate evidence of its efficacy in treating RCDI. The others lack sufficient support data.

Fecal bacteriotherapy (FBT): It is a highly efficient treatment option for RCDI since a long time. Studies reveal its efficacy over vancomycin use. With an initial response rate of 81% and subsequent rate of 94%, the FBT provides sufficient evidence to support its effectiveness in treating RCDI. However, this intervention bears the concerning risk of gastrointestinal bleeding from the nasogastric tube placement (Jorup-Ro¨nstro¨m et al. 2012).

Other antibiotics: Other antibiotics as nitazoxanide, an anti-parasitic agent depicted safe and well-tolerated initial response as metronidazole. Rifaximin also shows similar response rate. Fidaxomicin showed very high response rate at 93% initially overcoming the efficiency of vancomycin. However, its higher expensiveness puts vancomycin on a more preferable option.

This study highlights the limitations in the number of treatment approaches to avail for RCDI prevention and cure. It however, asserts the effect of the RCDI on patients due to the health concerns and the high expense of the available treatment methods. With a moderate amount of support evidence for the treatment options for RCDI the study identifies the immense need of researches to be conducted on the treatments to derive higher evidential support for their efficacy and risks. As put forward by Ghantoji et al. (2010), the clinical practice regarding any treatment option for a disease needs to have a sound evidence and information regarding the significant aspects as its doses, concerns, methods to deal with any complications and effectiveness criteria. This study highlights the relevant dosing regimen present for the interventions with identified medicines, concerns associated and the areas that need research for improvement. By identifying the weak and strong areas of the interventions for RCDI this article seems to drive the clinical practice towards a better, relevant and more effective standard.

Going through the study of the article, a limited range of available treatments for RCDI is recognized. The treatment approaches of RCDI with oral metronidazole and oral vancomycin showed consistent efficiency to cure the infection clinically. As asserted by Mezoff et al. (2011), the evidence for proper dosing regimen of a drug is highly essential for its application towards an effective treatment outcome. However, the identification of the lack of proper evidence for the optimal dosing regimens for these drugs is a major issue in RCDI treatment. It drives the clinical practice sector of the healthcare system to put higher emphasis on identifying the optimal dosing regimen for the drugs to treat RCDI.

Systematic Review of Treatments for RCDI

This review points out a lack of research regarding the intravenous metronidazole therapy for treating RCDI. The clinical professionals can opt for this technique to identify its effectiveness in the clinical practice. The study identifies the maximal use of fidaxomycin in primary RCDI treatments. However, a lack of parameters to ensure appropriate use is identified. This study exerts a higher focus on examining the effect of nitazoxanide and deriving better quality evidence for its use in RCDI treatment. A lesser research on the application of non-antimicrobial treatment options is evident thus, driving the clinical professionals to put stress on evaluating its efficacy for RCDI treatment (Rohlke et al. 2010).

The study is efficient in identifying one treatment intervention with high quality evidence for its effectiveness. It is the use of S. boulardii as an adjunctive therapy in combination with high dose of Vancomycin. A scope for future research in the identification of efficacy of monoclonal and oral immunoglobulin for treating RCDI is evidence in this study. It encourages the clinical practice professionals to work towards identifying the effectiveness of this immunoglobulin (Abougergi & Kwon, 2011). The study is able to identify the high (89%) success rate of FBT in treating RCDI. The clinical practice can be highly improved with these information and enable a more effective treatment of RCDI patients.

The current study identifies the most effective clinical approach to apply for treating RCDI as initially removing the infection triggering antibiotics, followed by drugs as vancomycin or metronidazole in combination with adjuvant probiotics. Fidaxomicin can also be used considering the expense factors. Finally, a FBT is effective. Although not examined but this study mentions two more interventions as colonic irrigation and tigecycline with success reports but inadequacy of sufficient support data. The clinical practice system can employ to examine these interventions more precisely to identify their efficacy. The study also highlights the Antimicrobial stewardship programs to prevent CDI. It thus presents the ways to improve the treatment and healthcare services’ efficacy regarding treating patients with CDI and RCDI. The study provides eminent and effective steps to adopt for the clinical practice to improve its efficiency in the context of RCDI treatment.

Conclusion:

The current study thus highlights efficient treatment options available for RCDI patients with identification of vancomycin, metronidazole and FBT as the most effective ones to use. It recognizes the lack of sufficient data regarding efficacy of other drugs and treatment options as nitazoxanide, non-antimicrobial treatment options and intravenous metronidazole therapy. It also points out the potential treatment interventions as monoclonal and oral immunoglobulin’s’ use with high success rate and adopting antimicrobial stewardship programs to prevent RCDI. It thus efficiently provides adequate scopes of future research and improvement in the clinical practice for treating RCDI with effective interventions.

Reference

Abougergi, M. S., & Kwon, J. H. (2011). Intravenous immunoglobulin for the treatment of Clostridium difficile infection: a review. Digestive diseases and sciences, 56(1), 19-26.

Drekonja DM, Butler M, MacDonald R, Bliss D, Filice GA, Rector TS, et al. (2011) Comparative effectiveness of Clostridium difficile treatments: a systematic review. Ann Intern Med, 155:839–47

Ghantoji SS, Sail K, Lairson DR, DuPont HL, & Garey KW (2010) Economic healthcare costs of Clostridium difficile infection: a systematic review. J Hosp Infect. 74, pp.309–18

Gough, E., Shaikh, H., & Manges, A. R. (2011). Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clinical infectious diseases, 53(10), 994-1002

Jorup-Ro¨nstro¨m C, Ha°kanson A, Sandell S, Edvinsson O, Midtvedt T, & Persson AK, et al. (2012) Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 47, pp. 548–52. doi:10.3109/00365521.2012. 672587.

Lo Vecchio A & Zacur GM. (2012) Clostridium difficile infection: an update on epidemiology, risk factors, and therapeutic options. Curr Opin Gastroenterol. 28, pp.1–9

Mezoff E, Mann EA, Hart KW, Lindsell CJ, & Cohen MB. (2011) Clostridium difficile infection and treatment in the pediatric inflammatory bowel disease population. J Pediatr Gastroenterol Nutr. 52, pp.437–41.

O’Horo , J. C. Jindai, K. Kunzer B.& Safdar, N.  (2014) Treatment of recurrent Clostridium difficile infection: a systematic review, Infection (2014) 42:43–59, DOI 10.1007/s15010-013-0496-x

Rohlke F, Surawicz CM, Stollman N. (2010) Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J Clin Gastroenterol. 44, pp. 567–70.

Wenisch JM, Schmid D, Tucek G, Kuo HW, Allerberger F, Michl V, et al. (2012) A prospective cohort study on hospital mortality due to Clostridium difficile infection. Infection. 40, pp. 479–84. doi:10.1007/s15010-012-0258-1.