Patient Safety Advisory Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Produced by ECRI & ISMP under contract to the Pennsylvania Patient Safety Authority Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use “C. diff”: What Is It? antibiotic upon discharge and finished T echnically, Clostridium difficile (C. diff) is a bacte- ria in the Clostridia family, which also includes C. perfringens (gas gangrene), C. tetani (tetanus), and the full course of medication at home. The patient also complained of diarrhea, nausea, and abdominal discomfort over C. botulinum (botulism). The Clostridia bacteria are the previous week. The patient arrived, spore-forming anaerobic gram positive bacilli which in fact, in septic shock. Fecal testing are particularly virulent because of the toxins they was positive for C. diff. Despite aggres- produce. sive intervention, the patient died of C. diff sepsis within 16 hours of returning to Clinically, “C. diff” refers to an overgrowth of C. diffi- the ED. cile in the colon which can manifest as diarrhea, sometimes profound, colitis, or toxic megacolon, An 87-year-old patient was discharged sometimes complicated by dehydration, colonic perfo- to a rehabilitation facility after repair of a ration, and/or death. The overgrowth of C. diff in the hip fracture and receipt of antibiotic ther- colon usually results from alterations in the normal apy. Eighteen days later, the patient re- colonic flora associated with use of antibiotics. turned to the hospital in septic shock associated with C. diff. The patient died A Serious Problem Reported to PA-PSRS the day she returned to the hospital de- C. diff is documented in almost half the reports sub- spite aggressive intervention. mitted to PA-PSRS under the Event Type code “Nosocomial infection: antibiotic-associated diarrhea.” The Bottom Line However, of greatest concern is the number of reports The message for the healthcare community is to involving patient deaths in which C. diff is mentioned avoid complacency about the risk of C. diff infection as a major contributing factor. PA-PSRS has received and to help patients to understand when they need to 15 such reports to date. Diagnoses include sepsis/ return to the healthcare system for additional treat- septic shock, toxic megacolon, colitis, diarrhea, and ment, especially for diarrhea complicating antibiotic abdominal pain. Most patients in these reports (86%) use. The risks of surgical complications may over- were age 70 or older. shadow the risks of prophylactic antibiotics not only in the minds of patients and their families but also Several reports indicate that patients treated with anti- among healthcare workers. biotics prophylactically for an elective surgical proce- dure developed symptoms of C. diff infection in the C. Diff Infections community after discharge. They failed to return to While much attention has been focused on such hos- the healthcare system until their disease had pro- pital-acquired infections as MRSA (Methicillin- gressed significantly. From the patient’s perspective, resistant Staphylococcus aureus) and VRE the relatively routine nature of the surgery in several (Vancomycin-resistant enterococcus), C. diff has be- cases (e.g., knee replacement, repair of a hip or ankle come a growing concern. C. diff-associated diseases fracture, hysterectomy) may have obscured the con- cause significant morbidity and mortality. Patients nection between the gastrointestinal symptoms of C. diff infection and their recent treatment. This article is reprinted from the PA-PSRS Patient Safety Advisory, Vol. 2, No. The following reports submitted to PA-PSRS illustrate 2—June 2005. The Advisory is a publication of the Pennsylvania Patient Safety Authority, produced by ECRI & ISMP under contract to the Authority as this point. part of the Pennsylvania Patient Safety Reporting System (PA-PSRS). A 72-year-old patient came to the ED Copyright 2005 by the Patient Safety Authority. This publication may be re- complaining of a near syncopal episode. printed and distributed without restriction, provided it is printed or distributed in its entirety and without alteration. Individual articles may be reprinted in their He had been discharged two weeks be- entirety and without alteration provided the source is clearly attributed. fore, after being treated for community- acquired pneumonia. He was taking an To see other articles or issues of the Advisory, visit our web site at www.psa.state.pa.us. Click on “Advisories” in the left-hand menu bar. ©2005 Pennsylvania Patient Safety Authority Page 1 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) with C. diff-associated diarrhea (CDAD) have hospital Approximately 1-3% of patients with C. diff infection stays that are, on average, 3.6 days longer, and each develop fulminant colitis.11 Symptoms include severe patient results in additional hospital costs of an aver- diarrhea, marked leukocytosis, high fever, chills, and age of $3,669.1 A conservative estimate of the cost of severe lower quadrant or diffuse abdominal pain.11 this disease in the US is over $1 billion annually.1 The colon may become so compromised that a para- lytic ileus may develop,2 in which case diarrhea is ab- In its spore form, C.diff can withstand drying and heat, sent,2,11 and constipation may be apparent.12,13 Ab- and is resistant to many disinfectants. The spores can dominal distension may develop.11 survive up to five months in the environment.2,3 It can be transmitted from person-to-person, as well as by Toxic megacolon may ensue;11 this is a life- persons touching objects contaminated with the or- threatening complication of colitis with an acute dilata- ganism.3 In the healthcare environment, C. diff has tion of all or a substantial portion of the colon to a di- been cultured in rooms of infected individuals up to 40 ameter larger than 6 cm. It is associated with sys- days post discharge. Objects from which C. diff has temic toxicity.14 Surgery is required in 65-71% of been cultured include: scales, call buttons, tele- these cases.14The literature indicates that subtotal phones, floors, bedpans, toilets/commodes, bed colectomy is the procedure of choice to reduce mor- frames, bathing tubs, and electronic thermometers.2- tality.14 Colonic perforation can occur,6,11 and the pro- 4 It has also been cultured from healthcare workers’ tein-losing enteropathy can lead to hypoalbuminemia shoes, fingernails and fingertips, as well as the under- and ascites.2,11 side of rings.2,3 Death is also a reported complication of C. diff infec- For the organism to cause disease, C. diff must be in tion.3,6 Mortality associated with active C. diff infec- the gastrointestinal system. Then, there must be a tions is 0.6% for those with pseudomembranous coli- change in the normal colonic flora to allow the organ- tis and 57% in patients requiring colectomy for toxic ism to grow and flourish. Finally, the C. diff must pro- megacolon. The mortality rate for fulminant C. diff duce toxins.2 The organism produces two toxins. colitis is also high. This may be due to a failure to di- Toxin A is an enterotoxin that causes excretion of agnose this disease in its early, more subtle stages, large amounts of fluid from the bowel. Toxin B is cyto- particularly if diarrhea is not present and abdominal toxic, attacking and disintegrating cells of the intes- findings are unclear.11 Overall, studies have reported tines. In addition, C. diff produces tissue- degradative mortality rates associated with CDAD ranging from enzymes.3,5 These processes elicit a profound inflam- 0.6%9 to 3%.1 matory response within the colon that can result in a spectrum of diseases. Concern The incidence and severity of C. diff infection and Spectrum of Disease related diseases appears to be increasing in devel- At one end of the spectrum, C. diff can reside in the oped countries, such as the US, UK, and Canada, gut asymptomatically.2,3 Many patients colonized with probably due to increased use of broad-spectrum an- C. diff do not develop clinical signs of the disease.6,7 tibiotics, such as third-generation cephalosporins, This organism can be isolated in up to 3% of healthy during the past 20 years.6 adults in the general population and from 50% to 80% of healthy newborns and infants.2,3 A Canadian study describing cases of CDAD in one institution over a 13-year period found that incidence C. diff also causes simple antibiotic-associated diar- increased from 35.6 per 100,000 population in 1991 rhea.2,3 C. diff is a leading cause of nosocomial diar- to 156.3 per 100,000 in 2003. In the patients aged 65 rhea in the US,8 accounting for nearly 20% of antibi- years or older, the rate increased from 102.0 to 866.5 otic-associated diarrhea.9,10 While there is evidence of during the same period. Complicated cases of C. diff community-acquired C.diff-related diarrhea, it is rare;2 infection increased from 7.1% to 18.2%. The propor- only about 20,000 cases are diagnosed in the outpa- tion of patients who died within 30 days after diagno- tient setting annually.3 The diarrhea is watery and sis of C. diff infection increased from 4.7% to 13.8%.15 may contain mucus. A study in the US Pacific Northwest describing a sin- More serious manifestations of infection are colitis gle institution’s 20-year experience with C. diff colitis and pseudomembranous colitis.2,3,6 In addition to diar- found that the number of cases rose by more than rhea, there may be loss of appetite, nausea, and ab- 30% when comparing the first and last 10-year peri- dominal tenderness or pain.3,7 C. diff is responsible for ods. The mortality rate increased from 3.5% to 50-70% of antibiotic-related colitis.10 15.3%.16 Page 2 ©2005 Pennsylvania Patient Safety Authority Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) Hospitalization is a risk factor. Studies indicate that A study conducted in Pennsylvania indicated that inci- from 13-31% of inpatients are colonized with C. diff if dence of fulminant C. diff colitis increased from 0% in hospitalized more than one week, and 56% of these 1990 to 3.2% in 2000.17 Another study in a Pennsyl- develop CDAD.1,3 Those hospitalized more than four vania teaching hospital18 found an increase in the weeks may have a rate of acquisition of 50%.3 incidence of nosocomial C. diff from 2.7 to 6.8 cases per 1,000 discharges from 1999 to 2000-01. Further, Gastrointestinal surgery is associated with increased 0.15 cases per 1,000 discharges of severe C. diff- risk of C. diff-associated disease. Procedures include: related disease in 1999 rose to 0.60 in 2000-01. recent gastrointestinal (GI)/bowel surgery or manipu- Some severe cases resulted in colectomy and death. lation of the GI tract;7 non-surgical GI procedures;19 presence of nasogastric tube/tube feedings.2,19 Recent case studies and anecdotal reports indicate that the course of C. diff-related disease may be Patients with C. diff colitis and a markedly elevated changing. There appears to be a trend of more debili- leukocyte could have a poor prognosis and higher tating disease from this infection, higher mortality mortality rate than those without a leukemoid reac- rates, and an increased need for operative treat- tion.20 ment16—from an organism that has previously been considered relatively innocuous and responsive to In the northern hemisphere during winter, CDAD out- treatment.17 breaks are more likely. Risk Factors Treatment Once C. diff becomes resident in the gastrointestinal The following interventions can be implemented once tract, the predominant risk factor for developing dis- a C. diff-associated disease is diagnosed: ease is treatment with antibiotics, particularly broad- spectrum antibiotics.2,6-8,10,16,19 Though disease may • Discontinuing the offending antibiotic.2-4 occur in the absence of a history of antibiotic ther- apy,2 the use of the following antibiotics are most fre- • Administering another antibiotic only if contin- ued antimicrobial therapy is needed and using quently associated with the development of C. diff- antimicrobics that are less frequently associ- associated disease: cephalosporins, penicillins ated with the C.diff-associated disease.3 (ampicillin and amoxicillin), and clindamycin.3,7,16 More recently, there have been reports of fluoroquinolone- • Providing supportive measures to correct fluid associated CDAD,6,8,18 including ciprofloxacin8 and loss and electrolyte imbalances.3 levofloxacin.18 Antibiotic use, whether for prophylaxis • Implementing enteric isolation precautions for or treatment, is a more important risk factor for C. diff- infected patients.3 related disease and potentially poor outcomes than • Treating the infection with vancomycin, met- horizontal transmission via exposure to contaminated ronidazole, or bacitracin as first line therapy.1-3 surfaces.16 Treatment is more likely to be successful if administered orally for 10 days.4 However, use Other general factors that determine whether C. diff- of vancomycin continues to be restricted be- related disease develops include the type and timing cause of the risk of developing vancomycin- of antibiotic exposure, the virulence of the strain of C. resistant enterococcus. Ordinarily, oral vanco- diff, and susceptibility or immune status of the pa- mycin is reserved for patients with metronida- tient.3 zole intolerance. Metronidazole continues to be the drug of choice for CDAD.3 A multitude of patient factors may place patients at higher risk for C. diff-associated disease, increased • If a patient receiving metronidazole therapy mortality and morbidity, and recurrent infection. These develops a white blood cell count greater than include: advanced age;2,6-8,19 severity of co-morbid 20,000 cells/mm3 and/or an elevated conditions;2,19 renal disease;2,6,12,13 cancer;2 diabetes creatinine level, it may be an indication of mellitus;16 diseases that compromise the immune sys- more severe C. diff-related outcomes. Based tem;7,16 patients in intensive care units;2,19 and pa- on limited observational data, vancomycin tients with a low serum albumin.19 In these situations, treatment may be indicated in such patients’ ability to mount an immune response against cases.15,21,22 Large, prospective, randomized the bacteria is compromised.8 controlled trials are needed, however, to con- firm the effectiveness of such a change in ther- ©2005 Pennsylvania Patient Safety Authority Page 3 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) apy. (CDC) guidelines for hand hygiene in healthcare set- • In patients with refractory or recurrent C. diff tings21 contains information concerning: handwashing colitis, a recently published uncontrolled study and hand antisepsis, hand hygiene technique, surgi- of 103 patients indicated that the rate of suc- cal hand antisepsis, selection of hand hygiene cessful treatment was about the same whether agents, and skin care. These guidelines include infor- prolonged metronidazole therapy or vancomy- mation that can be applied to preventing transmission cin was used.23 of C. diff by healthcare workers. C. diff spores have been shown to be present on clinicians’ hands, which • Avoiding peristaltic agents3 and antidiarrheal/ may become contaminated through contact with in- antiperistaltic agents. Antidiarrheal agents fected fixtures, equipment, and patients and may then such as loperamide may delay clearance of C. be instruments of contamination themselves.2 diff toxins from the patient’s colon and may predispose the patient to toxic megacolon.4,7 No agent used in antiseptic handwash or antiseptic hand-rub preparations is reliably sporicidal against C. Healthcare workers can provide supportive care; ob- diff (chlorhexidine, hexachlorophene, iodophors, alco- serve and document bowel habits and changes; hols, PCMX, triclosan). Spores may be physically re- document the characteristics of bowel movements; moved from contaminated hand surfaces by washing and educate patients/relatives about infection control hands vigorously with either non-antimicrobial or an- procedures, such as handwashing and wearing of timicrobial soap and water.21 gloves and gowns if directly involved with the patient’s incontinence care or toileting needs.2 Several other While gloves are worn when caring for patients with approaches to the management and prevention of C. C. diff diarrhea, after glove removal, hands are diff are being studied, as well, such as drugs washed with a non-antimicrobial or an antimicrobial (tinidazole or nitazoxanide), immunotherapy, vaccine, soap and water, or are disinfected with an alcohol- and probiotics (Lactobacillus species or Saccharomy- based hand rub. During outbreaks of C. diff-related ces boulardii).1,4,23 infections, washing with soap and water after remov- ing gloves is prudent, as frequent use of alcohol- Prevention based hand rubs may dry the skin, making it more Several interventions can help prevent C. diff trans- vulnerable to breakdown.21 mission in the healthcare environment. Handwashing also reduces contamination by the Handwashing vegetative state of C. diff. Technique is important, The Centers for Disease Control and Prevention however, if this decontamination process is to be ef- Emerging Strain of Clostridium Difficile On April 11, 2005, at the annual meeting of the Society for In May 2005, a Pennsylvania facility submitted a report to PA- Healthcare Epidemiology of America, infectious disease ex- PSRS indicating that the CDC had confirmed a genetically perts presented information concerning a new, highly toxic, altered virulent strain of C. diff in a patient’s specimen. A 30- strain of Clostridium difficile. This emerging strain is associ- year-old patient with multiple trauma received antibiotics, then ated not only with severe diarrhea and colitis, but also colec- developed a C. diff infection, which was treated with Flagyl. However, the patient developed pseudomembranous colitis tomy and death. and required an emergent total colectomy. Fortunately, the The strain contains a mutation on a gene that regulates pro- patient survived. duction of toxins A and B and which also may produce an Sources additional toxin. The strain produces a higher level of toxin Canadian Press. Quebec C. difficile strain has high toxin levels. [online]. 2005 than most other strains, and it is also resistant to fluoroquinolones. Apr 11 [cited 2005 May 16]. Available from Internet: http://www.ctv.ca/servlet/ ArticleNews/story/CTVnews/1113222804128_6/?hub-Health Since 2001, this strain has been identified in outbreaks in at Acambis. Emerging strain of common bacteria Clostridium difficile is highly toxic. [online]. 2005 Apr 11 [cited 2005 May 16]. Available from Internet: http:// least seven US hospitals in six states, as well as in Sher- www.acambis.com/documents/sites/1/News_releases/SHEA_release.pdf brooke and Montreal in Quebec, Canada. International Society for Infectious Diseases. Researchers report emergence of epidemic strain of C. difficile. Archive number 20041004.2735. [online]. 2004 The hospital in Sherbrooke has substantially reduced the use Oct 3 [cited 2005 May 16]. Available from Internet: http://www.promedmail.org/ of antibiotics known to be associated with C. diff infection. pls/askus/f?p=2400:1001:491458::NO::F2400_P1001 This was followed by a 33-50% reduction in C. diff-associated _BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,26867 disease. Page 4 ©2005 Pennsylvania Patient Safety Authority Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) fective in preventing transmission. Such techniques are described in Figure 1.2,3,7,21 When using soap and water: • First, wet the hands with water The Veterans Administration’s National Center for • Apply the manufacturer-recommended amount of the Patient Safety has recently recommended that when product to the hands C. diff is suspected, caregivers’ hands hygiene in- • Rub hands together vigorously at least 15 seconds cludes increasing glove use to protect hands from • Cover all fingers and surfaces of the hands contamination and handwashing with soap and water • Rinse hands thoroughly with water for decontamination.25 • Dry completely with a disposable towel • Turn off the faucet with the towel Isolation • Avoid using hot water because repeated exposure to • Instituting contact and enteric precautions3,26 hot water may increase the risk of dermatitis until the patient has formed stools—ideally for 48 hours after diarrhea ceases.2 When decontaminating with an alcohol-based hand rub: • Placing the patient in a private room with pri- • Apply the product to the palm of one hand vate toilet6,24 or placing patients with C. diff- • Rub hands together associated disease in the same room • Cover all hand and finger surfaces until the hands (cohorting).26 are dry • Using disposable equipment and dedicating • Follow the manufacturer’s recommendations regard- reusable equipment solely for that patient.7,26 ing the volume of the product to use Personal Protective Equipment • Wearing gloves when entering patients’ Figure 1. Handwashing Techniques rooms and when providing care to a patient with C. diff-associated disease.3,26 frequently touched.7,26 • Wearing gowns when there is a possibility • Following manufacturer instructions for disin- that the clinician’s clothing might become fection of endoscopes and other devices.26 soiled while caring for the patient.7,26 • Alcohol-based disinfectants are not effective • If the patient is experiencing explosive CDAD, against C. diff and are therefore inappropriate using goggles might be prudent during incon- for disinfection of environmental surfaces.26 tinence care. Prudent Antibiotic Use Cleaning/Disinfection Some healthcare facilities have changed antibiotic Thorough cleaning of surfaces, equipment, reusable policies to limit use of broad spectrum antibiotics as- devices, and the hospital environment prevents C. diff sociated with C. diff infection.2 The restriction of transmission, acquisition, infection, and reinfection.7,26 fluoroquinolone use among inpatients has been For example: shown to decrease CDAD rates.8 In one study, a for- mulary restriction of clindamycin was associated with • After cleaning surfaces and reusable devices a decrease in the incidence of CDAD.27 Restricting according to label instructions, using an EPA- the use of fluoroquinolones, however, needs to be registered hypochlorite-based disinfec- balanced with the drug’s advantages such as efficacy tant,3,6,24 alkaline gluteraldehyde, or ethylene of oral administration and convenient dosing.8 oxide.3 • Generic sources of hypochlorite, such as Several hospitals in the UK have implemented antibi- household chlorine bleach, may be diluted otic policies in which later-generation cephalosporins and used as labeled.26 have been replaced with narrow-spectrum penicillins, • Cleaning with a hypochlorite disinfectant has fluoroquinolones, clarithromycin, pipericillin- been found to be more effective than using a tazobactam, metronidazole, trimethoprim, and/or ami- neutral detergent to decrease the incidence noglycosides. Diseases treated were pneumonias, of C. diff contamination.6 severe sepsis/septic shock, urinary tract infections, H. influenzae. The number of CDAD cases decreased • Carefully cleaning/disinfecting environmental significantly after the implementation of such poli- surfaces and items that are likely to be con- cies.6,28,29 taminated with fecal material and/or that are ©2005 Pennsylvania Patient Safety Authority Page 5 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) Education An important factor in encouraging the prevention of Notes C. diff transmission is education.8 Healthcare workers 1. Kyne L, Hamel MB, Polavaram R, et al. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium can receive information about the disease, its epide- difficile. CID 2002 Feb 1;34:346-53. miology, methods of preventing transmission, hand- 2. Jenkins L. The prevention of Clostridium difficile associated diar- washing techniques, personal protective equipment, rhea in hospital. Nurs Times 2004 Jun 29-Jul 6;100(26):56-7,59. cleaning/disinfection, as well as the potential for se- 3. Hurley BW, Nguyen CC. The spectrum of pseudomembranous vere sequelae from C. diff infection. enterocolitis and antibiotic-associated diarrhea. Arch Intern Med 2002 Oct 28;162(19):2177-84. Healthcare workers can also teach patients, family 4. Gerding DN, Johnson S, Peterson LR, et al. Clostridium difficile- members, and visitors about effective handwashing associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459-77. techniques, as well as use of personal protective equipment if family is to become involved in inconti- 5. Naaber P, Mikelsaar M. Interactions between Lactobacilli and antibiotic-associated diarrhea. Advances in Applied Microbiology nence care/toileting of an infected patient.2,7 The 2004;54:231-60. CDC has fact sheets for healthcare providers and the 6. Riley TV. Nosocomial diarrhea due to Clostridium difficile. Curr general public that describe the disease and how to Opin Infect Dis 2004 Aug;17(4):323-7. prevent transmission.24,30 7. McConnell EA. Prevent the spread of Clostridium difficile. Nurs- ing 2002;32(8):24-5. Both patients and healthcare workers also can de- 8. McCuster ME, Harris AD, Perencevich E, et al. Fluoroquinolone velop awareness that if a patient with current or re- use and Clostridium difficile-associated diarrhea. Emerging Infec- cent antibiotic use develops diarrhea or abdominal tious Diseases [online]. 2003 Jun [cited 2004 Dec 15]. Available from Internet: http://www.cdc.gov/ncidod/EID/vol9no6/02- symptoms, it may be indicative of C. diff-associated 0385.htm. disease with the potential for serious, life-threatening 9. Miller MA, Hyland M, Ofner-Agostini M, et al. Morbidity, mortality, ramifications.11 and healthcare burden of nosocomial Clostridium difficile- associated diarrhea in Canadian hospitals. Infect Control Hosp While antibiotic use precedes almost all cases of C. Epidemiol 2002 Mar;23(3):137-40. diff-associated disease, 11 the onset of such diseases 10. Koehler R, Mone M, Kimball E, et al. Clostridium difficile peri- carditis complicating pseudomembranous colitis in a trauma pa- may occur during or several weeks after therapy.3 C. tient. J Trauma 2003 Oct;55(4):771-3. diff-associated diseases are no longer exclusively 11. Longo WE, Mazuski JE, Virgo KS, et al. Outcome after colec- hospital-acquired infections,2 and symptoms do not tomy for Clostridium difficile colitis. Dis Colon Rectum 2004 Oct;47 necessarily begin during a hospital stay. Inpatient (10:1620-6. hospital stays continue to grow shorter, pre- and post- 12. Kovithavongs T. Clostridium difficile colitis associated with operative/procedure antibiotic therapy is conducted chronic renal failure. Nephrol Dial Transplant 1999;14:2256-7. outside of the healthcare facility. The number of pro- 13. Cunney RJ, Magee C, McNamara E, et al. Clostridium difficile cedures conducted in ambulatory surgery centers colitis associated with chronic renal failure. Nephrol Dial Transplant continues to rise. Fluoroquinolones are prescribed for 1998;13:2842-6. [Abstract] patients in the community because they can be taken 14. Dobson G, Hickey C, Trinder J. Clostridium difficile colitis caus- orally. ing toxic megacolon, severe sepsis and multiple organ dysfunction syndrome. Intensive Care Med 2003;29:1030. All of these factors contribute to the likelihood of pa- 15. Pepin J, Valiquette L, Alary ME, et al. Clostridium difficile- associated diarrhea in a region of Quebec from 1991 to 2003: a tients experiencing initial symptoms of C. diff- changing pattern of disease severity. CMAJ 2004 Aug 31;171 associated disease in a community setting. At least (5):466-72. half of the C. diff-associated deaths reported to PA- 16. Morris AM, Jobe BA, Stoney M, et al. Clostridium difficile colitis. PSRS indicated that the onset of diarrhea occurred Arch Surg 2002 Oct;137:1096-100. outside the acute hospital setting. 17. Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant Clos- tridium difficile: an underappreciated and increasing cause of death Patients, family members, referring physicians, and and complications. Ann Surg 2002 Mar; 235(3):363-72. healthcare workers in all settings can benefit from 18. Muto CA, Pokrywka M, Shutt K, et als. A large outbreak of recognition that antibiotic use has the potential of Clostridium difficile-associated disease with an unexpected propor- tion of deaths and colectomies at a teaching hospital following causing substantial morbidity and even mortality. If increase fluoroquinolone use. Infection Control and Hospital Epide- the index of suspicion is raised about this link, medi- miology 2005 Mar;26(3):273-80. cal intervention for evaluation and early treatment of 19. Eckel F, Huber W, Weiss W, et al. Recurrent pseudomembra- C. diff-associated diseases may be sought in a more nous colitis as a cause of recurrent severe sepsis. Z Gastroenterol timely manner, thus helping to prevent serious nega- 2002 Apr;40(4):255-8. tive outcomes. 20. Marinella MA, Burdette SD, Bedimo R, et al. Leukemoid reactions complicating colitis due to Clostridium difficile. South Med Page 6 ©2005 Pennsylvania Patient Safety Authority Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) Clostridium Difficile: A Sometimes Fatal Complication of Antibiotic Use (Continued) J 2004 Oct;97(10):959-63. cile: information for health care providers [online]. 2004 Sep 23 [cited 2005 Feb 3]. Available from Internet: http://www.cdc.gov/ 21. Gerding DN. Metronidazole for Clostridium difficle-associated disease: is it ok for mom? Clin Infect Dis 2005 Jun 1;40:1598-1600. ncdod/hip/gastro/ClostridiumDifficileHCP.htm. 27. Climo MW, Israel DS, Wong ES, et al. Hospital-wide restriction 22. Pepin J, Alary M-E, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficle colitis in Quebec, of clindamycin: effect on the incidence of Clostridium difficile- associated diarrhea and cost. Ann Int Med 1998;128:989-95. Canada. Clin Infect Dis 2005 Jun 1;40:1591-7. 23. Musher DM, Aslam S, Logan S, et al. Relatively poor outcome 28. McNulty C, Logan M, Donald IP, et al. Successful control of Clostridium difficile infection in an elderly care unit through use of a after treatment of Clostridium difficile colitis with metronidazole. restrictive antibiotic policy. J Antimicrob Chemother 1997 Nov;40 Clin Infect Dis 2005 Jun 1;40:1586-90. (5):707-11. 24. Centers for Disease Control and Prevention (CDC). Guideline 29. O’Connor KA, Kingston M, O’Donovan M, et al. Antibiotic for hand hygiene in health-care settings. MMWR 2002 Oct 25;51 (RR-16):1-48. prescribing policy and Clostridium difficile diarrhea. QJM 2004 Jul;97(7):423-9. 25. Eldridge N, Danko L. Hand hygiene and diarrheal diseases in 30. Centers for Disease Control and Prevention. Clostridium diffi- healthcare settings. Topics in Patient Safety 2005 May/Jun;5(3):2. cile: general information [online]. 2004 Aug 10 [cited 2005 Feb 3]. 26. Centers for Disease Control and Prevention. Clostridium diffi- Available from Internet: http://www.cdc.gov/ncidod/hip/gastro/ ClostridiumDificileGEN.htm. ©2005 Pennsylvania Patient Safety Authority Page 7 Reprinted from the PA-PSRS Patient Safety Advisory—Vol. 2, No. 2 (June 2005) An Independent Agency of the Commonwealth of Pennsylvania The Patient Safety Authority is an independent state agency created by Act 13 of 2002, the Medical Care Availability and Reduction of Error (“Mcare”) Act. Consistent with Act 13, ECRI, as contractor for the PA-PSRS program, is issuing this newsletter to advise medical facilities of immediate changes that can be instituted to reduce serious events and incidents. For more information about the PA- PSRS program or the Patient Safety Authority, see the Authority’s website at www.psa.state.pa.us. ECRI is an independent, nonprofit health services research agency dedicated to improving the safety, efficacy and cost-effectiveness of healthcare. ECRI’s focus is healthcare technology, healthcare risk and quality management and healthcare environmental management. ECRI provides information services and technical assistance to more than 5,000 hospitals, healthcare organizations, ministries of health, government and planning agencies, and other organizations worldwide. The Institute for Safe Medication Practices (ISMP) is an independent, nonprofit organization dedicated solely to medication error prevention and safe medication use. ISMP provides recommendations for the safe use of medications to the healthcare community including healthcare professionals, government agencies, accrediting organizations, and consumers. ISMP's efforts are built on a non-punitive approach and systems-based solutions. Page 8 ©2005 Pennsylvania Patient Safety Authority