Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole

• Published in: PloS one 2013-10, Vol.8 (10), p.e76269-e76269
• Main Authors: Abujamel, Turki, Cadnum, Jennifer L, Jury, Lucy A, Sunkesula, Venkata C K, Kundrapu, Sirisha, Jump, Robin L, Stintzi, Alain C, Donskey, Curtis J
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Antibiotics; Bacteria; Biochemistry; Bioinformatics; Catabacter hongkongensis; Clostridium difficile; Clostridium difficile - classification; Clostridium difficile - drug effects; Clostridium difficile - genetics; Clostridium infections; Clostridium Infections - drug therapy; Clostridium Infections - microbiology; Colonization; Complications and side effects; Data recovery; Developed countries; Diagnosis; Diarrhea; Diarrhea - drug therapy; Diarrhea - microbiology; Dosage and administration; Drug Resistance, Bacterial; Drug therapy; Education; Feces - microbiology; Female; Genomes; Geriatrics; Health aspects; Health care; Humans; Immunology; Infections; Infectious diseases; Laboratories; Male; Medicine; Metronidazole; Metronidazole - administration & dosage; Metronidazole - pharmacology; Metronidazole - therapeutic use; Microbiota; Microbiota - drug effects; Middle Aged; Patients; Prospective Studies; rRNA 16S; Therapy; Vancomycin; Vancomycin - administration & dosage; Vancomycin - pharmacology; Vancomycin - therapeutic use; Veterans
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076269

Clostridium difficile is an anaerobic, spore-forming bacterium that is the most common cause of healthcare-associated diarrhea in developed countries. A significant proportion of patients receiving oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined. In a prospective study of CDI patients, we demonstrated that most vancomycin-treated patients maintained inhibitory concentrations of vancomycin in stool for 4 to 5 days after therapy, whereas metronidazole was only detectable during therapy. From the time of elimination of the antibiotics to 14 to 21 days after therapy, a majority of stool suspensions supported growth of C. difficile and deep 16S rRNA sequencing demonstrated persistent marked alteration of the indigenous microbiota. By 21 to 28 days after completion of CDI treatment, a majority of stool suspensions inhibited growth of C. difficile and there was evidence of some recovery of the microbiota. These data demonstrate that there is a vulnerable period for re-establishment of C. difficile colonization after CDI treatment that begins within a few days after discontinuation of treatment and extends for about 3 weeks in most patients.