Clostridium difficile

Clostridium difficileOverviewCase reportHistoryOrganism and propertiesEpidemiology

DiseaseDiagnosisTreatmentInfection controlCase60 yo male admitted to hospital for community acquired pneumonia, treated with levofloxacin and discharged7 days later, seen at another hospital because of 12-15 pound weight gain over last few days (my abdomen has never been so big) and hypertension (213/106)Afebrile, WBC of 8.5, albumin 3.1, creatinine 0.9, no diarrhea notedAdmitted, treated for hypertension and ciprofloxacin given to complete treatment for CAP; discharged 3 days later

Case study 1 Day 1Presents to ER 3 days after dischargeFever (101), diarrhea, generally feeling ill, no abdominal painWBC 27.8K, albumin 2.9, creatinine 1.2Admitted with C. difficile colitis listed as a possible dx, but not treated (except for levofloxacin)Day 210 stools/day, altered mental statusC. difficile EIA positive; put on metronidazole 500 mg TID

Case study 1Day 3Transferred to SICU, anuric, abdominal pain, distension, developed cardiac complications, ventilated, renal failure. Poor prognosis and colectomy ruled out following surgical consultOral and rectal vancomycin addedWBC > 30K, albumin 2.3, creatinine 3.1Day 4WBC 59.6K, toxic megacolonDay 5WBC 88K, made DNI/DNR, died

Clostridium difficileGram-positive, anaerobic, spore-forming bacillusVegetative cells die quickly in an aerobic environmentSpores are a survival form and live for a very long time in the environmentGrows on selective media in 2 days and smells like horse manure (p-cresol)

SporesResistant to heat, drying, pressure, and many disinfectantsResistant to all antibiotics because antibiotics only kill or inhibit actively growing bacteriaSpores survive well in hospital environmentSpores are not a reproductive form, they represent a survival strategy

Sources of InfectionSpores in hospital, nursing home, or long-term care environment associated with ill patientsLarge numbers of spores on beds, bed-rails, chairs, curtains, medical instruments, ceiling, etc.Asymptomatic carriers in those same environmentsLow risk compared to patients with active diseaseFalse negative lab tests (low sensitivity)Unknown in community based infections, but food has been implicatedRisk Factors for InfectionHospitalization or long-term care facilityAntibiotics (some more than others)Increasing age (>65, >>80)Co-morbiditySurgery? Proton-pump inhibitorsCommunity-associated casesPeri-partumClose contact of CDI (C. difficile infection) caseFood

Role of AntibioticsAll antibiotics (including metronidazole and vancomycin) are associated with CDIHigh-risk groupClindamycinCephalosporins/penicillins/beta-lactamsFluoroquinolonesAlteration of normal colonic flora thought to favor growth of C. difficileAntibiotics do not know they are suppose to kill/inhibit only the bad guys

IncidenceUnited StatesCDI is not a reportable disease so exact number of cases and deaths remain unknownBased on discharge diagnoses, CDI cases have tripled over last 5 yearsUnited KingdomDeaths in UK ~ 9,000/year

PathogenesisToxigenic strains produce 2 large protein exotoxins that are associated with virulenceToxins A and BMutants strains that do not make toxins A and B are not virulentSome strains make a third toxin known as Binary ToxinBy itself, not pathogenicMay act synergistically with toxins A and B in severe colitisMore common in animal strains

Symptoms of CDIAsymptomatic colonizationDiarrheamild moderate severeAbdominal pain and distensionFeverPseudomembranous colitisToxic megacolonPerforated colon sepsis death

Markers of Severe DiseaseLeukocytosisProminent feature of severe diseaseRapidly elevating WBCUp to >100 K>10 BM/dayAlbumin < 2.5Creatinine 2x baselineHypertensionPseudomembranous colitisToxic megacolonSevere distension and abdominal pain

Pseudomembranous colitis & Toxic Megacolon

http://www.nejm.org/doi/full/10.1056/NEJMicm050923#t=article15TestingToxin testingQuick same dayStool cultureTakes 46-96 hoursTesting for C. diff should be done on unformed (liquid) stool unless ileus is suspected

Treatment ofMild to Moderate DiseaseStop antibiotic(s) if medically reasonableMetronidazoleOral or IV, 500 mg TID for 10-14 days is standard therapy520% failure rate20% relapse rateCan use a full 2nd course for failure/relapse but beyond 2 courses, switch to vancomycinFailures not due to metronidazole resistance

Initial Treatment Options for CDI Metronidazole250 mg QID or 500 mg TID

Vancomycin125 mg QID

May be administered PO or IVDevelopment of resistance rareHistorical first-line agent

Effective in enteral (oral or rectal) form only Typically reserved for severe disease, those failing to respond to metronidazole, or cases in which metronidazole is contraindicatedIV=intravenously; PO=orally.Fekety R. Am J Gastroenterol. 1997;92:739-750.Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.American Society of Health-System Pharmacists. Am J Health-Syst Pharm. 1998;55:1407-141118Recurrence CDIRates of recurrence 20% after 1st episode45% after 2nd episode65% after two or more recurrencesThis was from the video but I need to source it. 19