Antibiotic therapy and Clostridium difficile infection – primum non nocere – first do no harm

Figures & data

Table 1 Therapeutic regimens for CDI

First-line option	Second-line option
Nonsevere CDI
Metronidazole (500 mg TID 10 days)*	Vancomycin (125 mg QID 10 days)**
	Fidaxomicin (200 mg BID 10 days)**
Severe CDI
Vancomycin (125 mg QID 10 days)*	Fidaxomicin (200 mg BID 10 days)**
First recurrence
Vancomycin (125 mg QID 10 days)**	Metronidazole (500 mg TID 10 days)***
Fidaxomicin (200 mg BID 10 days)**

Notes: For information on rates of recurrence for each therapeutic regimen, please refer ESCMID guidelines.

* Indicates strong support for recommendation of use;

** Indicates moderate support for recommendation of use;

*** Indicates marginal support for recommendation of use. Data from Debast et al.³⁰

Abbreviations: CDI, Clostridium difficile infection; TID, three times daily; QID, four times a day; BID, twice daily.

Table 2 Alternative Clostridium difficile infection preventative and therapeutic approaches

Approach	Product	Development stage
Microbiological	• Microbiota supplementation (fecal microbiota transplant)	n/a
	• RBX2660 (Rebiotix; an oral preparation of live microbes)	Phase II
	• SER109 (SeresHealth; an orally delivered combination of spores)	Phase I/II
	• VP20621 (Shire [formerly ViroPharma]; spores of NTCD strain M3)	Phase II
Nonmicrobial biological	• Passive immunization (MK3415A [Merck])	Phase III
	• Vaccines:
	C. diffense (Sanofi Pasteur)	Phase III
	PF-06425090 (Pfizer)	Phase II
	IC84 (Valneva)	Phase I
Antibiotic inactivation	• S YN-004 (Synthetic Biologics; a synthetic Class A β-lactamase enzyme for use with IV cephalosporins [including ceftriaxone] and penicillins)	Phase II
	• DAV132 (DaVolterra; a medical device consisting of an activated-charcoal- based product in an enteric- coated pill)	Phase I

Note: Adapted from Drug Discovery Today, Volume 20, Ivarsson ME, Leroux J, Castagner B, Investigational new treatments for Clostridium difficile infection, Pages 602–608, Copyright 2015, with permission from Elsevier.³⁹

Abbreviations: n/a, not available; NTCD, nontoxigenic Clostridium difficile.

DebastSBBauerMPKuijperEJEuropean Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infectionClin Microbiol Infect201420Suppl 212624118601

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IvarssonMELerouxJCastagnerBInvestigational new treatments for Clostridium difficile infectionDrug Discov Today20152060260825499664

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