vancocin

Presentation and Clinical Manifestations of Clostridium Difficle Associated Disease (CDAD)

Clostridium difficile is a spore-forming, gram-positive anaerobic bacillus that was first recognized as a major cause of antibiotic-associated diarrhea in 1977.1 Some strains of the bacterium (so called "toxigenic strains") produce two toxins, toxin A, an enterotoxin, and toxin B, a cytotoxin. Infection with toxin-producing C. difficile may result in a wide spectrum of clinical illness ranging in severity from diarrhea to inflammation of the colon and pseudomembranous colitis, to toxic megacolon, and death.2 Symptoms can occur within a few days of starting antibiotic therapy or a few months following a course of antibiotic therapy.

C. difficile is shed in feces as a highly contagious and easily spread spore.3 The organism thrives on any surface, device, or material (e.g., commodes, bathing tubs, and electronic rectal thermometers) that becomes contaminated with feces. These surfaces may serve as a reservoir for the C. difficile spores and spores can be spread from patient to patient, patient to health-care worker to patient, or patient to inanimate object to patient.4

Diagnosis of CDAD can be confirmed by a number of different tests including culture of C. difficile, a cytotoxicity assay or detection of one of the toxins.5 Diagnosis can also be made by endoscopy and biopsy.5

Toxigenic C. difficile is now recognized as a frequent cause of antibiotic-associated diarrhea and colitis. It is implicated in 20% to 30% of patients with antibiotic-associated diarrhea, in 50% to 75% of those with antibiotic-associated colitis, and in more than 90% of those with antibiotic-associatedpseudomembranous colitis.6 Vancocin® HCl Capsules (vancomycin hydrochloride capsules, USP) can be used to treat antibiotic-associated pseudomembranous colitis caused by C. difficile.

CDAD occurs most commonly in hospitalized patients. Most patients have been exposed to an antimicrobial agent (the most commonly implicated agents include third-generation cephalosporins, ampicillin or amoxicillin, and clindamycin).7 Other non-antimicrobial agents (such as doxorubicin, cisplatin, cyclophosphamide, and proton-pump inhibitors) have also been implicated as potential triggers for C. difficile disease.8,9 The exposure to an antimicrobial agent alters the microecology of the gut,4 making patients more susceptible to C. difficile acquisition and overgrowth. This, in addition to other risk factors, are likely to determine whether or not a patient develops C. difficile infection and what severity of disease ultimately presents.

The incidence of CDAD is generally higher in the winter months, probably associated with the increased incidence of infections such as community-acquired pneumonia requiring hospitalization and the use of broad-spectrum antibiotics. The overall incidence of CDAD is increasing,10 as the major risk factors for development of CDAD, namely increased age, antimicrobial use, increased severity of underlying illness, and surgical manipulation of the gastrointestinal tract, are more prevalent in hospitalized patients.


Rising Incidence of CDAD

The severity of disease may also be increasing related to changes in susceptibility to antimicrobials (clindamycin-resistance11 and fluoroquinolone-resistance), the expression of a "binary toxin," or variations in a gene that down regulates toxin production.12,13

As of January 2007, this strain has been reported in 27 states in the United States (Figure 2).

ref.http://www.cdc.gov/ncidod/dhqp/id_Cdiff_data.html


Treatment

Although the majority of patients will require specific drug therapy, discontinuation of antimicrobial therapy may be the only intervention necessary in 15% to 23% of patients.5,14,15 A number of antibiotics have been shown to have some activity against C. difficile, but the most effective and most widely used are oral vancomycin (the only FDA-approved treatment) and metronidazole.5

In addition to the increased severity of disease, a review of US death certificates for the period 1999-2002 indicates an increase in the annual number of deaths attributed to C. difficile that is most pronounced in those >60 years of age (Figure 3).13

Identification of the Epidemic Strain

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VANCOCIN HCl Capsules may be administered orally for treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains) and antibiotic-associated pseudomembranous colitis caused by Clostridium difficile. Parenteral administration of vancomycin is not effective for the above indications; therefore, VANCOCIN HCl Capsules must be given orally for these indications. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vancocin Capsules and other antibacterial drugs, Vancocin Capsules should only be used to treat or prevent infections that are proven or strongly suspected to be caused by a susceptible bacteria. When culture and sensitivity are available, they should be considered in selecting or modifying antibacterial therapy.

Adverse events include nephrotoxicity, ototoxicity, reversible neutropenia, thrombocytopenia, and “Red Man’s Syndrome”. In patients with renal dysfunction or those receiving concomitant therapy with an aminoglycoside, serial renal function testing should be performed. In patients receiving concomitant therapy with another ototoxic agent, serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity. Infrequently allergic reation, including anaphylaxis, and exfoliative dermatitis have been reported.

Clinically significant serum concentrations of vancomycin have been reported in some patients treated with Vancocin capsules for pseudomembranous colitis caused by Clostridium difficile. It is noteworthy that total systemic and renal clearance of vancomcyin are reduced in the elderly. Monitoring of serum concentrations may be appropriate in patients with renal insufficiency and/or colitis.

Vancocin capsules are contraindicated in patients with a known hypersensitivity to vancomycin.

References

  1. Bartlett JG et al. JID 1977;136:701-705.
  2. Bartlett JG. NEJM 2002;346:334-339.
  3. Poutamen SM and Simor AE. CMAJ 2004;171:51-58.
  4. Johnson S and Gerding DN. Clin Infec Dis 1998;26:1027-1036
  5. Fekety R. Amer J Gastro 1997;92:739-750.
  6. Kelly CP et al. Clostridium difficile colitis. N Engl J Med 1994;330:257-262
  7. Gorbach SL. N Engl J Med 1999;341:1690-1691.
  8. Dial S et al. C Med Assoc J 2004;171:33-38
  9. Anand A et al. Clin Infec Dis 1993;17:109-113
  10. McDonald LC, et al. Emerg. Infect Dis. 2006; 12:409-415
  11. Johnsons et al. NEJM 1999; 341:1645-1651
  12. McDonald LC, et al. NEJM 2005; 353:2433-41.
  13. Spigaglia P et al. J Clin Microbiol 2002;40:3470-3475
  14. Olson MM, Shanholtzer CJ, Lee JT, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994; 15: 371-81
  15. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile-associated diarrhoea and colitis. Lancet 1983;2:1043-6.
  16. Wysowski DK. Increase in deaths related to enterocolitis due to Clostridium difficile in the United States 1999-2002. Public Health Reports 2006; 121: 361-2.