Clostridium difficile infection natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.
Overview
Following ingestion of C. difficile spores, patients are colonized with the organism. Typically, young healthy individuals with adequate immune responses are able to clear the organism without development of any clinical manifestations. But patients with risk factors, such as recent antibiotic use, recent hospitalization, advanced age, or immunodeficiency, are at an increased risk of developing persistent colonization and/or developing signs and symptoms of the infection. The onset of clinical manifestations may occur within 2 hours up to several months following antibiotic administration. Patients typically develop mild/moderate watery diarrhea (possibly bloody) associated with colicky diffuse abdominal pain, nausea, malaise, and fever. If left untreated, patients may develop colitis (with or without pseudomembrane formation). Approximately 3% of patients develop complications, which might be colonic (fulminant colitis) or extracolonic (small intestine involvement, bacteremia, skin infections, reactive arthritis, abscess formation, empyema, or death). The majority of patients with C. difficile infection recover without sequelae and are responsive to antimicrobial therapy. Nonetheless, C. difficile is associated with a high lifetime recurrence rate that ranges between 20% to 60%, most of which occur a few weeks following the successful completion of antimicrobial therapy.
Natural History
1. Carrier Stage
- Following ingestion of C. difficile spores, patients are colonized with the organism.
- Typically, young healthy individuals with adequate immune responses are able to clear the organism without development of any clinical manifestations.
- In contrast, patients with risk factors, such as recent antibiotic use, recent hospitalization, advanced age, or immunodeficiency, are more predisposed to persistent colonization and/or develop signs and symptoms of the infection.
- The carrier stage may be as short as 2 hours following antibiotic administration to several months.[1][2]
2. Clinical Manifestations
- The onset of clinical manifestations may occur within 2 hours up to several months following antibiotic administration.[2]
- Patients typically develop mild/moderate watery diarrhea (possibly bloody) associated with colicky diffuse abdominal pain, nausea, malaise, and low-grade fever.[2]
- Diarrhea typically persists for more than 2 days, and patients commonly develop colitis with or without pseudomembrane formation.
- A minority of patients do not develop diarrhea. Instead, stool analysis demonstrating increased stool leukocytes may be the only clinical manifestation.[3]
3. Pseudomembranous Colitis
- If left untreated, patients may develop pseudomembranous colitis, which is characterized by the development of yellowish plaques in the colorectal mucosa.
- Clinical manifestations include abdominal pain, watery diarrhea, and fever with worsening symptoms, dehydration, and further elevation in the concentration of inflammatory markers.[3]
4. Development of Complications
- In the minority of patients (approximately 3%), clinical manifestations may persist, and C. difficile infection may have a complicated course.
- Fulminant colitis, extracolonic manifestations, and death have been more frequently reported since the emergence of the hypervirulent C. difficile strain.[3]
5. Recurrence/Reinfection
- Approximately one-fourth of patients adequately treated with antimicrobial therapy develop recurrence within 4 weeks of therapy completion.[4]
- Approximately 20-60% of patients experience a lifetime recurrence of C. difficile infection with a new strain following successul completion of antimicrobial therapy.[4][5]
Complications
Colonic Complications
- Fulminant colitis: A relatively rare, but fatal, complication of C. difficile infection. Manifestations typically include worsening abdominal pain, prolonged ileus, megacolon, and high-grade fever.
Extracolonic Complications
If left untreated, C. difficile infection may progress, and patients may develop extracolonic complications[6][3][7]:
- Pseudomembrane formation in small intestine
- Ulcer formation in the small intestine
- Ileal-pouch anal anastomosis
- Dehydration
- Acute kidney injury
- Bacteremia
- Reactive arthritis
- Tenosynuvitis
- Visceral (e.g. splenic abscess) or intraabdominal abscess
- Appendicitis
- Cellulitis
- Necrotizing fasciitis
- Prosthetic device infection
- Osteomyelitis
- Empyema
- Death
Prognosis
- The majority of patients with C. difficile infection recover without sequelae and are responsive to antimicrobial therapy.
- Patients with comorbidities and risk factors, such as immunodeficiency or inflammatory bowel disease, are at an increased risk of developing complications.
- C. difficile is associated with a high lifetime recurrence rate that ranges between 20% to 60%. Patients are not necessarily reinfected with the same strain.
- The majority of recurrent cases occur within a few weeks of successful completion of antimicrobial therapy.
References
- ↑ Wenisch JM, Schmid D, Kuo HW, Simons E, Allerberger F, Michl V; et al. (2012). "Hospital-acquired Clostridium difficile infection: determinants for severe disease". Eur J Clin Microbiol Infect Dis. 31 (8): 1923–30. doi:10.1007/s10096-011-1522-5. PMID 22210266.
- ↑ 2.0 2.1 2.2 Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RL, Donskey CJ (2007). "Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents". Clin Infect Dis. 45 (8): 992–8. doi:10.1086/521854. PMID 17879913.
- ↑ 3.0 3.1 3.2 3.3 Vaishnavi C (2010). "Clinical spectrum & pathogenesis of Clostridium difficile associated diseases". Indian J Med Res. 131: 487–99. PMID 20424299.
- ↑ 4.0 4.1 Barbut F, Jones G, Eckert C (2011). "Epidemiology and control of Clostridium difficile infections in healthcare settings: an update". Curr Opin Infect Dis. 24 (4): 370–6. doi:10.1097/QCO.0b013e32834748e5. PMID 21505332.
- ↑ Johnson S (2009). "Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes". J Infect. 58 (6): 403–10. doi:10.1016/j.jinf.2009.03.010. PMID 19394704.
- ↑ Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muto CA (2008). "Antimicrobial-associated risk factors for Clostridium difficile infection". Clin Infect Dis. 46 Suppl 1: S19–31. doi:10.1086/521859. PMID 18177218.
- ↑ Jacobs A, Barnard K, Fishel R, Gradon JD (2001). "Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature". Medicine (Baltimore). 80 (2): 88–101. PMID 11307591.