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current as of March 4, 2009.Online article and related content http://jama.ama-assn.org/cgi/content/full/301/9/954. 2009;301(9):954-962 (doi:10.1001/jama.2009.171)
JAMA
Ciarán P. Kelly
InfectionC difficileAssociated Diarrhea: Review ofClostridium difficileA 76-Year-Old Man With Recurrent
Correction
Citations
Topic collections
DiseasesDrug Therapy, Other; Gastroenterology; Gastrointestinal Diseases; InfectiousAging/ Geriatrics; Bacterial Infections; Infectious Diseases, Other; Drug Therapy;
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CLINICIAN’S CORNER
CLINICAL CROSSROADS
CONFERENCES WITH PATIENTS AND DOCTORS
A 76-Year-Old Man With Recurrent
Clostridium difficile–
Associated Diarrhea
Review of
C difficile
Infection
Ciara´n P. Kelly, MD, Discussant
D
R
R
EYNOLDS
:
Mr S is a 76-year-old man with hyperten-sion,hypertensiverenaldiseasewithcadavericrenaltrans-plantation in 1988 and again in 1998, spinal stenosis, uri-nary retention due to the spinal stenosis and to benignprostatichypertrophy(treatedwithanindwellingFoleycath-eter), and recurrent
Clostridium difficile
infection (CDI).MrS’scurrentillnessbeganwhenhewasadmittedtothehospital with a urinary tract infection. He received ceftri-axone and ciprofloxacin; after discharge, he developed di-arrhea. After several weeks of diarrhea, his nephrologisttreatedhimempiricallyforCDIwitha10-daycourseofmet-ronidazole; he improved and his stools initially becameformed.However,aboutamonthafterdischarge,hewasstillhaving 4 to 5 loose stools daily along with poor appetite,weightloss,fever,chills,andweakness.Hewasreadmittedto the hospital and a stool sample was found to be positivefor
C difficile
toxin. He was placed on contact precautionsand treated with oral vancomycin and again improved, butagainrelapsedandwastreatedwithalong(6-8weeks)courseof oral vancomycin followed by a tapering dose. Four daysafter stopping the oral vancomycin, Mr S again began ex-periencingdiarrhea.Intheensuingmonths,hehadseveralhospitalizations for diarrhea; he also had another urinarytract infection and was treated first with cefpodoxime andthenwithciprofloxacin.Hewasprescribedstandingoralvan-comycin and rifaximin together. This combination con-trolled his diarrhea at the time of his interview. He is cur-rently having semiformed, soft stools once or twice a day.He is not experiencing any bleeding. His appetite is good.Mr S has had a 10- to 15-lb (4.5- to 6.75-kg) weight lossover the past 6 months and attributes this to his diarrhea.MrSalsohasarthritisofhisleftshoulderwithsevereshoul-der pain, and he is mostly confined to a wheelchair be-
Clostridium difficile
infection (CDI) is a common andincreasingly severe nosocomial infectious disease. Thecase of Mr S, a 76-year-old man with multiple recur-rences of CDI, illustrates the difficulties in treatingrecurrent disease and the way it complicates the man-agement of other medical conditions. Risk factors for CDI include antimicrobial use, hospital admission,advancing age, and severe underlying disease. A clini-cal diagnosis of CDI is usually confirmed by identify-ing
C difficile
toxins in a stool sample. Evidence sup-ports metronidazole, 500 mg every 6 hours for 10 to14 days, as the treatment of choice for mild to moder-ately severe CDI. Oral vancomycin, 125 mg every 6hours for 10 to 14 days, is recommended for severeCDI, for which it is more effective than metronidazole.Recurrent CDI occurs in more than 20% of patientswhen metronidazole or vancomycin treatment is dis-continued. Few studies have evaluated treatmentoptions for recurrent CDI, but a prolonged, tapering,and pulse-dosed regimen of oral vancomycin is com-monly used. Careful attention to antimicrobial stew-ardship and infection control practices is essential tocurb this nosocomial, iatrogenic disease.
JAMA. 2009;301(9):954-962
www.jama.com
See also Patient Page.
CME available online at www.jamaarchivescme.comand questions on p 979.
This conference took place at
the Medicine Grand Rounds at Beth Israel Deacon-ess Medical Center, Boston, Massachusetts, on November 15, 2007.
Author Affiliation:
Dr Kelly is Associate Professor of Medicine, Harvard MedicalSchool,MedicalDirector,CeliacCenter,Chief,HerrmanL.BlumgartInternalMedi-cine Firm, and Director, Gastroenterology Fellowship Training, Beth Israel Dea-coness Medical Center, Boston, Massachusetts.
Corresponding Author:
Ciara´n P. Kelly, MD, Beth Israel Deaconess MedicalCenter, 330 Brookline Ave, East/DA-601, Boston, MA 02215 (ckelly2@bidmc.harvard.edu).
ClinicalCrossroadsatBethIsraelDeaconessMedicalCenter
isproducedanded-itedbyRisaB.Burns,MD,serieseditor;TomDelbanco,MD,HowardLibman,MD,Eileen E. Reynolds, MD, Amy N. Ship, MD, and Anjala V. Tess, MD.
Clinical Crossroads Section Editor:
Margaret A. Winker, MD, Deputy Editor.
954
JAMA,
March 4, 2009—Vol 301, No. 9
(Reprinted)
©2009 American Medical Association. All rights reserved.
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cause of his spinal stenosis and resultant weakness in hislegs, although he can walk short distances with a walker.Further evaluation of his urinary problems during his re-centhospitalizationrevealedaneurogenicbladderthoughtto be due to his spinal stenosis; the Foley catheter was re-moved and he has learned to use straight catheters. He hadbeenscheduledforsurgeryforthespinalstenosisbutitwaspostponed when he developed CDI.Mr S’s medications include prednisone, 4 mg daily; cy-closporine, 50 mg daily; and diltiazem, trazodone, ateno-lol, minoxidil, furosemide, long-acting nitrates, finaste-ride,anderythropoietin,alongwiththestandingvancomycinand rifaximin.Mr S is retired and lives with his wife and adult son. Hedoesnotsmokeandhedrinksonly1alcoholicbeveragepermonth.On physical examination, Mr S is thin, weighing 135 lb(61kg),andis69in(175cm)tall(bodymassindex,19.9).His blood pressure is 150/70 mm Hg and his heart rate is68/min. No neurological or spinal examination was per-formedforthediscussion,buthisphysicalexaminationwasotherwiseremarkableonlyforhisleftlowerquadrantrenalallograft, which was tender and without bruits, and for 1
pitting edema in his lower extremities.MrS’slaboratorytestresultsshowabaselinecreatininelevelof 1.8 mg/dL and a serum urea nitrogen level of 68 mg/dL.Hisstoolstudieswerepositivefor
C difficile
toxinAdur-inghisinitialhospitalizationfordiarrhea;subsequentsamplesobtained when symptoms have recurred have been nega-tive. Mr S’s most recent urine culture showed resolution of a previous
Pseudomonas
infection.
MR S: HIS VIEW
Iwouldtaketheregimenofmedicinesprescribedbythedoc-tor. Three or four days after finishing the regimen, I wouldgetbetter.ThenIwouldturnrightaround;I’dgetthechillsandstartshaking,sometimesuncontrollably.I’dhavetoputthe covers on, even in the summertime. I would take [acet-aminophen/paracetamol], and it would bring the tempera-ture down and the medicine would control the
C difficile
.This illness has been very distressing. Sometimes I wouldbe on the toilet and would think I’m done. I get about half-waybacktothebedroom,thenIhavetogobackagain.Some-timesthiswouldhappen3timesina15-minuteperiod.Rightnow, it seems the pills are curing me, and I’m getting better.I’m not going as frequently, but I’m still going 4 or 5 times aday. I might wake up in the evening and go once or twice.My back is giving me a lot of problems. I get a lot of painwhen I try to move. I can’t walk as well, and I have to usemy walker. I’m really slow. I had a procedure done on myneck in November. And I was supposed to have the secondprocedure done on my spine, but we had to cancel that be-cause of the
C difficile
.I’d be kind of frightened if somebody told me I had to goback on antibiotics after this. I wouldn’t wish this illnessonanybody.
Cdifficile
isoneofthemostterriblethingsthatI’ve been dealing with in my whole life, and I’ve dealt witha lot of things since my kidney transplant. I hope that thislatest regimen of pills will cure me—because I’m going outof my mind.
ATTHECROSSROADS:QUESTIONSFORDRKELLY
How common is
C difficile
after an initial episode of anti-biotic treatment and how are rates affected by age or im-munestatus?Howshouldthediagnosisbemadeandisem-pirical treatment an acceptable strategy? How common isrecurrentinfectionandaretheseusuallyrelapseorreinfec-tion? What is the evidence for the most effective treatmentforfirstandrecurrentepisodes?Whatshouldphysiciansdoto prevent
C difficile
in terms of prescribing and infectioncontrol practices? What do you recommend for Mr S?
D
R
K
ELLY
:
Mr S is a 76-year-old retiree with a function-ingrenaltransplant,benignprostatichypertrophy,andspi-nalstenosiswhosecaseillustratesthechallengingproblemofCDI.Hereceivedbothceftriaxoneandciprofloxacindur-ing inpatient treatment for a urinary tract infection, devel-oped diarrhea, and was treated with oral metronidazole forpossible CDI. He subsequently experienced multiple epi-sodes of recurrent CDI leading to hospital admissions andrequiringrepeatedandprolongedtreatmentswithoralvan-comycin.
Disease Pathogenesis
Clostridium difficile
is a gram-positive, spore-forming, an-aerobic bacillus first isolated in 1935 from the stool of ahealthy neonate.
1
The finding that
C difficile
is an opportu-nisticpathogenwasnotmadeuntilthelate1970s,whentheclinical entity of antibiotic-associated,
C difficile
–induceddiarrheaandcolitiswasfirstcharacterized.
Clostridium dif- ficile
infectionisnowbyfarthemostcommonknowncauseofinfectiousdiarrheainhospitalpatientsinNorthAmericaand Europe, where both the incidence and severity of dis-ease have increased alarmingly since 2000.
2
Although
C difficile
is common in the general environ-ment, only 1% to 4% of healthy adults carry this organism.A normal colonic microflora confers “colonization resis-tance” against CDI.
2
Neonates, lacking an established in-testinal microflora, frequently have
C difficile
colonizationbut, interestingly, seldom experience
C difficile
toxin–induceddiarrheaorcolitis,possiblybecauseofalackoftoxinreceptor expression in the immature gut.
1
In adults, loss of colonizationresistancetoCDIismostoftentheresultofan-timicrobial therapy. All antimicrobials are not equal in thisregard, and the risk of CDI associated with different anti-microbials results from a complex combination of their lu-minalconcentrations,theireffectsonthenormalintestinalmicroflora, and their activity against
C difficile
.
2-5
The abil-ityofclindamycintoimpaircolonizationresistanceandin-duceCDIiswellknown.
3
However,incurrentmedicalprac-tice, second- and third-generation cephalosporins and
CLINICAL CROSSROADS
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(Reprinted) JAMA,
March 4, 2009—Vol 301, No. 9
955
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