How to Treat PULL-OUT SECTION www.australiandoctor.com.au Complete How to Treat quizzes online (www.australiandoctor.com.au/cpd) to earn CPD or PDP points. inside Epidemiology Risk factors Presentation Diagnostic tests Management Recurrent episodes The authors Dr Nemes Sandanayake consultant physician and gastroenterologist, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, and the Mater Hospital, Crows Nest, NSW. Clostridium difficileassociated Dr Katie Ellard gastronenterologist in private practice, St Leonards, NSW. Introduction TWENTY-five years ago, Clostridium difficile-associated was a footnote in medical textbooks as a very rare cause of infective. It was known to occur after exposure to antibiotics, particularly clindamycin. However, over the past decade there has been a very worrying increase in both the frequency and the severity of C. difficile, coupled with a significant number of deaths. This has been the case for both hospital- and communityacquired infections. There are several reasons for this, including the appearance of hypervirulent strains that have been identified in Australia in recent years, and the widespread and inappropriate use of antibiotics in hospitals and the community. Proton-pump inhibitors may also be a risk factor and the US Food A D E _ 2 6 0 6 _ I M _ b a n n e r 2. p d f P a g e 1 1 6 / 0 8 / 1 2, 1 2 : 1 8 P M and Drug Administration has issued a specific warning highlighting a possible connection between acid suppression from PPI drugs and C. difficile-associated, particularly in the elderly. could well be a canary in the mine a warning of the possible implications of indiscriminate use of potent antibiotics and PPIs. cont d next page SEMINAR FOR GPs 2012 Authoritative, independent and relevant one day seminar INTERNAL MEDICINE Earn CPD points www.australiandoctor.com.au/seminars SYDNEY 13 October 2012 University of Sydney, Camperdown Campus www.australiandoctor.com.au 28 September 2012 Australian Doctor 23
How To TREAT Clostridium difficile-associated Epidemiology CLOSTRIDIUM difficile is a gram-positive toxin-producing anaerobic bacterium. It was first isolated, with difficulty, from healthy neonates in 1935 and was originally named Bacillius difficilis. In the 1970s it was recognised as a cause of antibiotic-associated colitis. C. difficile can be carried in the colon without developing symptoms and about 2% of healthy adults and 70% of healthy neonates have C. difficile in their stools. The percentage of people who carry C. difficile but do not have increases markedly once people have been admitted to hospital and, in many hospitals in the US and UK, 20% of inpatients carry C. difficile in their stools. Transmission occurs via the faecal oral route. In some nursing homes, the carrier rate approaches 50%, and carriers act as a reservoir of infection in these institutions. Treatment of carriers is not recommended in this setting because eradication is difficult. There has been a dramatic increase in the incidence of C. difficile-associated in the past couple of decades and it is now the most common cause of in the healthcare context. It is estimated there are three million cases in the US each year, making C. difficile the most common cause of bacterial in that country. The reasons for the increase in are multifactorial, but it has been suggested that important factors include increased pathogenicity of new strains, food and water contamination, more frequent carrier state in humans, the ageing of the population, and the widespread use of antibiotics and proton pump inhibitors. Outside the colon, C. difficile C. difficile spores are easily spread as a result of the challenges associated with tolieting elderly, infirm residents. takes the form of an extremely robust spore that is routinely found on all types of surfaces in hospitals and is difficult to eradicate with commonly used surface cleaners, particularly alcoholbased agents. In some NHS hospitals in the UK that have experienced significant mortality owing to C. difficile, wards have had to be closed for long periods in order to eradicate the spores. If a patient suspected of carrying the infection requires a colonoscopy, infection control guidelines state that the procedure should be done at the end of the list, so that the room can be thoroughly cleaned afterwards. As a result of the widespread presence of spores, infection can be spread easily from person to person in hospitals, regardless of the use of antibiotics. It is interesting to note that patients who enter a hospital colonised with C. difficile are less likely to develop, indicating that previous colonisation may offer some immunity. Data from the US Centers for Disease Control and Prevention note that while more than 90% of people who presented with had attended a healthcare facility before the onset of their illness, fewer than 25% were hospitalised at the time they became unwell. A significant proportion of those who acquired the infection in hospital had been discharged before symptoms began. This emphasises the fact that GPs need to be aware of the possibility of C. difficile as a cause of in the community and the importance of a history of the patient s recent antibiotic use. Community-acquired C. difficile infection At present, community-acquired accounts for about 20% of infectious. If a person develops associated with C. difficile within 48 hours of admission to a healthcare facility or 12 weeks after discharge, the infection is classified as having been acquired within the community. The incidence appears to be increasing and infection is not always associated with antibiotics, with fewer than 50% of affected patients having received any antibiotics within the three months before onset of symptoms. Patients who have community-acquired C. difficile-associated tend to be younger than the patients of hospital-acquired cases. The association between C. difficile-associated and PPI use is also less clear in people with community-acquired infection. Community-acquired C. difficile is usually less severe than that acquired in hospital. However, in a large study from Olmsted County in the US, 40% of people with communityacquired C. difficile infection required admission to hospital for treatment. Nursing home residents are particularly vulnerable to C. difficile-associated. This is because the carrier rate of C. difficile is often high in these communities, the elderly are frequently treated with antibiotics for other infections and C. difficile spores are easily spread as a result of the challenges associated with toileting elderly, infirm residents. During any outbreak of in an aged-care facility, stool samples should be tested specifically for C. difficile. Residents diagnosed with C. difficile-associated should be nursed in a single room, and sharing of bathrooms and commodes with other residents should be avoided. The importance of regular hand washing with soap and water should be stressed to staff as spores are resistant to alcohol sanitisers. Hypervirulent strains of C. difficile The most significant hypervirulent strain of C. difficile is NAP1/ BI/027, which produces more spores and appears to be more toxic due to a single gene deletion, resulting in the loss of an inhibitory protein signal. This leads to significantly larger production of toxins. A further mechanism is via production of a binary toxin which is an extra toxin not found in the less virulent strains. These factors are associated with an increased rate of septic shock and toxic megacolon. The increasing use of fluoroquinolones worldwide may be associated with the emergence of this particular strain, which has also been identified in Australia. Risk factors Risk factors Antibiotics Age Immunosuppression Gastric acid suppression Antibiotics most commonly associated with C. difficileassociated Cephalosporins Ampicillin/amoxycillin Clindamycin Antibiotics CLINDAMYCIN was the first antibiotic associated with C. difficile-associated. However, any antibiotic can be the precipitant. The classes of antibiotics that most frequently induce C. difficile-associated include broad-spectrum penicillins, broadspectrum cephalosporins and fluoroquinolones. Sulfonamides, trimethoprim and macrolides are also implicated. Even metronidazole and vancomycin, which are the mainstay of treatment for C. difficile-associated, have been reported to cause the condition. It is reasonable to suspect that any patient taking an antibiotic who presents with, particularly if it does not resolve after stopping the antibiotic, could have and should be investigated with a stool sample. Patients who receive long-term antibiotics, for example, for an infected joint replacement or subacute bacterial endocarditis, should be warned that they need to report a change in bowel habit due to their increased risk of C. difficile-associated. Patients presenting with should be asked about recent antibiotic use, including treatment for Helicobacter pylori infection and dental work. It is also important to remember that the doesn t necessarily start during the course of antibiotics there are reports of the developing up to 12 weeks after antibiotics have stopped so causality may not be obvious. Even brief exposure to antibiotics for example, a couple of doses may cause C. difficileassociated. Proton-pump inhibitors There is some controversy about whether or not PPIs increase the risk of acquiring C. difficile infection. However, the evidence is sufficient to have prompted the US Food and Drug Administration to issue a Drug Safety Communication in February 2012 advising that, particularly in elderly people, a diagnosis of should be considered for patients taking PPIs who develop that does not improve. The possibility that H2 receptor antagonists are also a potential risk factor was mentioned. Some experts have suggested that the association is spurious, because PPI prescriptions are more common in elderly people, who are also more likely to be or have been hospitalised and are more likely to have comorbidities. However, studies have shown that patients who develop C. difficile-associated in hospital are often on PPI therapy for no specific indication for example, no history of peptic ulcer, GORD or medications that increase the risk of peptic ulceration. The possibility that PPIs are contributing to the increase in C. difficile-associated is a good reason to assess the appropriateness of therapy, both in the community and hospital. Age The risk of C. difficile-associated increases over the age of 65, however age is not a clear risk factor in community-acquired. Inflammatory bowel disease Patients with ulcerative colitis and Crohn s disease are at increased risk of acquiring C. difficile-associated. These patients are also likely to be receiving immunosuppressive drugs as part of their treatment, including prednisone, azathioprine and anti-tumour necrosis factor antibodies. Antibiotics such as metronidazole and ciprofloxacin are used in the treatment of Crohn s disease in particular. However, patients with inflammatory bowel disease may present with C. difficile-associated without having been exposed to antibiotics. Sometimes the symptoms will be very similar to those caused by an exacerbation of inflammatory bowel disease. It is important to have a high index of suspicion for in this group of patients and stool testing should be performed when there is a poor response to their usual therapy. Immunosuppression Immunosuppression is an important risk factor and can be iatrogenic or associated with underlying disease. Hospital patients receiving chemotherapy are particularly vulnerable to C. difficile-associated. 24 Australian Doctor 28 September 2012 www.australiandoctor.com.au
Presentation THE classic presentation of C. difficile-associated is watery, up to 10-15 times a day, during or after a course of antibiotics. This can be associated with fever, crampy abdominal pain and/or severe abdominal pain as a result of toxic megacolon. Spontaneous perforation of the colon can occur. There are less severe forms of illness, where the stool is more formed and less frequent. Patients with inflammatory bowel disease may appear to have an exacerbation of their usual symptoms. Very occasionally, C. difficileassociated can present with ileus, fever, abdominal pain and distension, and no, which can present a real diagnostic challenge. Diagnostic tests Stool sample IT is appropriate to arrange for a stool sample to be examined for C. difficile if a patient has significant while taking antibiotics or after completion of a course of antibiotics in the past 12 weeks. The stool test is only useful in the proper clinical setting where a patient has watery. For instance, it would not be appropriate to test a young person with typical IBS symptoms of alternating constipation and for. There are several different types of stool tests available and GPs don t have to specify the type of C. difficile test. Each pathology provider has its preferred testing methods, from those described below. The pathogenic strains of C. difficile produce a toxin that causes the inflammation and some tests focus on the presence or absence of toxin. However, as the tests require a certain threshold of toxin to be present to give a positive result, there is a risk of a falsenegative result. The toxin can also be assessed in a test that measures cytotoxicity, but this test is difficult to perform and relatively slow. An alternative is to test for the presence of C. difficile glutamate dehydrogenase, which is produced by all C. difficile strains and then, if it is present, test for the toxin. Several Australian laboratories use a PCR test, which is directed at the gene that confers pathogenicity and allows toxin production by C. difficile. The PCR test, also called the gene test, is both sensitive and specific. Culture is difficult, slow and not usually performed. Colonoscopy Colonoscopy is not mandatory in all cases of C. difficile-associated. If the diagnosis is confirmed via a positive stool test, treatment should begin without Figure 1: Histology: Pseuodomembrane consisting of a dense inflammatory infiltrate on the surface of the colonic mucosa (H&E 10). Tests for C. difficileassociated C. difficile toxin assay C. difficile glutamate dehydrogenase PCR (gene test) for pathogenic loci in the C. difficile Cell culture with cytotoxic assay Colonoscopy with biopsy for pseudomembrane waiting to visualise the colon or take biopsies to confirm the presence of a pseudomembrane (figure 1). However, colonoscopy can be helpful, particularly in people with inflammatory bowel disease, where there might be some doubt about whether symptoms are from the underlying inflammation or a superimposed infection. A percentage of patients with IBD may be carriers of C. difficile that is not causing their. Some patients will also have a colonoscopy arranged to investigate where C. difficile is clinically less risky, particularly those who haven t had antibiotics. A normal sigmoidoscopy is not sufficient to rule out C. difficile A normal sigmoidoscopy is not sufficient to rule out the possibility of C. difficile infection, as occasionally the infection is apparent only in the right colon. infection as occasionally the infection is apparent only in the right colon. The classic appearance of C. difficile infection at colonoscopy is a yellowish pseudomembrane that can be washed off the inflamed mucosa (figure 2B). About 20% of patients will have a visible pseudomembrane. Figure 2: A: Normal colonic mucosa. B: Mucosa showing yellow pseudomembrane. A B As with all pathological processes, there is a progression in the severity of the findings. Occasionally the colon will appear mildly inflamed rather than showing a distinct pseudomembrane. Biopsies should be taken and the resulting pathology should show the typical changes. It is not always possible for the endoscopist or the pathologist to distinguish between inflammatory bowel disease and, so stool testing is still essential. Imaging If there is any suspicion of toxic megacolon, colonoscopy is contraindicated because of the risk of bowel perforation. Toxic megacolon can be diagnosed on a plain abdominal X-ray, while a CT scan of the abdomen and pelvis with IV contrast patient renal function permitting can be useful to assess the extent and severity of disease and exclude microperforation. Management SOME patients with C. difficileassociated recover without treatment, or indeed diagnosis. However, there is substantial mortality in frail elderly and immunosuppressed patients. In some studies this has reached 25% in this group. The high mortality is multifactorial but probably relates in part to the greater pathogenicity of new strains of C. difficile, as well an increase in elderly population numbers. Once the diagnosis of C. difficile-associated has been confirmed, there are some general treatment measures and some specific therapies. Antibiotics should be withdrawn if at all possible and, if not, there is some benefit in avoiding broad-spectrum antibiotics. It is also advisable to avoid drugs that will reduce colonic peristalsis; for example, narcotics and loperamide. Medical treatment Treatment should target the colon. It is important to consider how unwell the patient is as a result of the C. difficile-associated. If they are mildly or moderately unwell, first-line therapy is oral metronidazole. Australian guidelines recommend initial treatment of metronidazole 400mg orally tds for 10 days. If the patient can t tolerate oral metronidazole, it can be administered IV, 500mg hourly for 10 days. If treatment with metronidazole is ineffective clinically, it is appropriate to switch to oral vancomycin. Patients who are very unwell should be treated initially with oral vancomycin, 125mg qid for 10 days. IV vancomycin is not effective. Vancomycin is usually well tolerated; however, there are cases of a rare but severe side effect called the Red Man Syndrome caused by a direct effect of vancomycin on mast cells. This hypersensitivity reaction causes an itchy, erythematous rash that invloves the face, neck and upper torso. In rare cases, the flushing can be generalised and the patient can drop their blood pressure. The syndrome is more likely to be associated with the administration of IV vancomycin. Vancomycin is generally not absorbed from the gut, but theoretically a patient with significant gut inflammation (increasing absorption) and renal impairment (limiting cont d page 28 www.australiandoctor.com.au 28 September 2012 Australian Doctor 25
How To TREAT Clostridium difficile-associated from page 25 excretion) could develop blood levels of vancomycin sufficient to cause Red Man Syndrome. If the patient has difficulty swallowing or has an ileus, vancomycin can be administered through a nasogastric tube or as an enema. A pharmacist can make up a retention enema as vancomycin 500mg in 100mL of normal saline per rectum, to be administered 2-3 times daily. As vancomycin is not well absorbed from the GI tract, monitoring serum levels is not required except in patients initially diagnosed with acute severe colitis who may have increased absorption of the drug due to profound mucosal inflammation. In Australia, vancomycin requires an authority script, stating that the patient has antibiotic-associated pseudomembranous colitis due to C. difficile that is either unresponsive or intolerant to metronidazole. This is aimed at limiting inappropriate use of vancomycin because of its important role in treating enterococci. Generally, vancomycin is well tolerated. It is not appropriate to do a stool sample for C. difficile on completion of therapy in a patient who has clinically responded to treatment, or prescribe additional treatment on the basis of a positive test, as C. difficile may still be present in the stool sample. Further treatment is not required in these cases and has not been shown to be helpful in decreasing the relapse rate. The situation is different in a sick patient with ongoing. Surgical treatment C. difficile infection can cause toxic megacolon with a high risk of perforation and death. Therefore if there is evidence of increasing abdominal pain and distension of the colon on imaging, it is appropriate to obtain surgical opinion where colectomy may be indicated. This is more likely in the elderly and the immunosuppressed. Alternative and emerging treatment The balance and alterations in colonic flora are suspected to be of great importance in a variety of gastrointestinal diseases from IBS to IBD, and there is no doubt it plays a significant role in C. difficile-associated. The difficulty has been to discover the most effective way to alter the colonic flora, as it appears to be an ecosystem that not only varies from person to person as individual Antibiotic treatment of Metronidazole 400mg tds for 10 days If unsuccessful or not tolerated: Vancomycin 125mg orally qid for 10 days as a fingerprint but also tends to return to its original equilibrium when left alone. Changing diet can bring about lasting modifications in the profile of colonic flora. The evidence that probiotics can do this is variable. Probiotics The idea of probiotics to treat is attractive; however, the science of using probiotics is complicated by the fact that there are so many different strains of probiotic bacteria available, which may have Changing diet can bring about lasting modifications in the profile of flora. The evidence that probiotics can do this is variable. a variable effect on the colonic flora of different individuals. This is a problem encountered in trials using probiotics to treat IBS, IBD and recurrent C. difficile-associated. Studies using the probiotic Saccharomyces boulardii have been encouraging. Patients on long-term antibiotics will often spontaneously take probiotics or eat yoghurt, but there is no evidence this reduces the risk of. Immunotherapy Studies have been conducted using IV immunoglobulin and monoclonal antibodies to neutralise the toxin produced by the C. difficile and vaccines have been proposed as a potential therapy in recurrent disease. Faecal microbiota transplant One area of great interest to the medical profession and the tabloid press is faecal microbiota transplant. Faecal microbiota transplant has been used in a number of studies of recurrent C. difficile-associated. It was initially proposed as a means of providing the patient with healthy flora that could suppress the pathogenic C. difficile. A donor is identified who is well, has no gastrointestinal disease, and has been screened for infections, including HIV, and hepatitis B and C. They donate, after having taken a laxative the night before, and a liquid mixture is prepared and then infused into the recipient s caecum at colonoscopy. The recipient takes loperamide to slow colonic emptying after receiving the donation. At this time there are about 275 cases in the medical literature and it will be of great interest to see the results of randomised trials. Recurrent episodes UP to 35% of patients will relapse with a further episode of significant C. difficile and, unfortunately, recurrent episodes are associated with less effective responses to the antibiotic that was initially successful. Recurrences will usually, but not always, occur about a week after antibiotic treatment is stopped. This, after the increased incidence and virulence of infection, is the next big problem with. Management The first recurrence should be treated as for the initial episode, with either metronidazole or vancomycin. Unfortunately, this treatment is less likely to be effective with recurrence. There are several possible approaches following a second relapse. It would be inappropriate to retrial metronidazole; however, vancomycin can be used again. The dose of vancomycin is either tapered from the initial dose and/or used as a pulse therapy every two days at the end of the course. The dosing pattern of vancomycin is changed to 125mg qid for 14 days, followed by 125mg bd for a week, then 125mg bd every second day for a week. Novel antibiotics Several new antibiotics have been studied for recurrent C. difficileassociated. They are not available on the PBS, although nitazoxanide and rifaximin can be obtained in Australia after application to the Therapeutic Goods Administration. Consultation with a microbiologist regarding treatment is recommended before contemplating prescription of these drugs. However, it is worthwhile mentioning these drugs as a watch this space message. Nitazoxanide has been shown to be equal to both vancomycin and metronidazole in efficacy. Rifaximin, which is enjoying popularity in the US as a therapy for IBS, has been shown to be effective in C. difficile-associated without having a negative effect on the colonic flora. Fidaxomicin is the most promising new antibiotic as it appears to have quite specific activity against C. difficile without altering the colonic flora significantly. There is also optimism that this drug might reduce the risk of relapse. 28 Australian Doctor 28 September 2012 www.australiandoctor.com.au
Conclusion THE incidence of C. difficile- associated is increasing and it is an important cause to consider when assessing community-acquired. Doctors need to remain mindful to prescribe antibiotics and PPIs Case studies judiciously, as there is a definite association with antibiotics and research is indicating that PPIs may be implicated in the increase in. Hand washing in hospitals and residential facilities needs to be emphasised as an important strategy in reducing the spread of C. difficile and there are encouraging results from research into novel antibiotics and treatments in treating this frequently recurrent disease. Further reading Hamilton M et al. Standardised frozen preparation for transplantation of Fecal Microbiota for Recurrent Clostridium Difficile Infection. American Journal of Gastroenterology 2012; 107:761-67. Cheng A et al. Australasian Society for Infectious Diseases Guidelines for the diagnosis and treatment of Clostridium difficile infection. Medical Journal of Australia 2011; 194:353-58. Case 1 A 65-YEAR-old man presents with explosive, painless 5-6 times a day over the past six weeks. He has lost a little weight as a result of not eating in order to reduce the frequency of the. He hasn t changed medication, travelled or started any supplements recently. He reports that he had three courses of ampicillin and metronidazole for a rootcanal infection. He was well for six weeks after the final course. In the past his bowel habit has been normal. He had a normal colonoscopy three years ago because of a family history of colorectal cancer in a first-degree relative. He presents on this occasion to arrange a repeat colonoscopy as he is worried that these symptoms represent a change in bowel habit that could indicate malignancy. Physical examination is normal and the patient looks perfectly well. His FBC is normal, TSH is within normal limits and coeliac serology, consisting of tissue transglutaminase antibody and endomysial antibody, is normal. A stool sample is examined for red and white blood cells, ova, cysts and parasites, bacterial culture and C. difficile toxin. The toxin is present and the patient is initially treated with metronidazole (even though one of the antibiotics he received for treatment of his dental infection was metronidazole). There is no response to treatment after a 10-day course, so he is treated with oral vancomycin for 10 days. There is an immediate improvement in his bowel habit in terms of consistency and frequency of motion. After completion of the course of vancomycin, there is still a mild change in his bowel habit compared with his usual pattern of one formed motion every morning, consisting of a less-well-formed motion twice a day, with a marked gastrocolic reflex, resulting in an urge to defecate after meals. C. difficile testing is not repeated at this stage because it may still be positive despite adequate treatment. He is reassured that his continuing symptoms are most likely a form of post-infectious IBS that is very likely to resolve with time. There is gradual improvement over the next couple of months. He is advised that he should mention this episode if he is prescribed antibiotics in the future to reduce the risk of further C. difficile infection. In particular, an effort should be made to avoid broad-spectrum antibiotics. Case 2 A 25-year-old woman has had ulcerative colitis for eight years. It is prudent to have a very low threshold for testing the faeces of patients with ulcerative colitis or Crohn s disease for C. difficile. Colonoscopy has demonstrated a left-sided colitis that has been severe enough to require admission to hospital for intravenous steroids in the past. She has been well for the past three years on oral mesalazine 3g nocte and azathioprine 125mg daily. Her LFTs and FBC are tested every six weeks because of the association between azathioprine and drug-induced hepatitis and bone marrow suppression, but her blood tests have been satisfactory. She presents with an exacerbation of, consisting of 6-7 motions per day, which are unformed and mixed with blood and mucus. She has crampy, lower-abdominal pain and thinks she may have had a fever. She had a recent episode of sinusitis and was prescribed cephalexin for a week. As she has been documented as having a left-sided colitis in the past, she is started on mesalazine enemas 4gm/60mL nocte in addition to her usual medications, but there is no improvement in her symptoms. After a two-week period she commences 40mg of prednisolone mane, but there is still no improvement after two weeks. She then attends for a flexible sigmoidoscopy under sedation, without receiving any bowel prep other than 24 hours of a diet limited to clear fluids. The mucosa in the rectum and left colon shows inflammation, with a typical pseudomembrane. Biopsies are consistent with C. difficile infection, as well as showing chronic changes consistent with ulcerative colitis. A stool sample taken at the time of the flexible sigmoidoscopy demonstrated C. difficile toxin. The young woman was started on oral vancomycin and her resolved within three days. The dose of prednisolone was quickly tapered and ceased, and the mesalazine enemas were ceased immediately. The patient had stated on a number of occasions that this particular exacerbation felt different to the episodes of she had suffered with inflammatory bowel disease in the past. It is prudent to have a very low threshold for testing the faeces of patients with ulcerative colitis or Crohn s disease for C. difficile, as they are in a high-risk group. Case 3 An independent 84-year-old woman presented to hospital after two weeks of profuse watery, nausea and vomiting. She had received amoxycillin for a week, followed by amoxycillin and clavulanic acid for five days for an cont d next page www.australiandoctor.com.au 28 September 2012 Australian Doctor 29
How To TREAT Clostridium difficile-associated from previous page upper respiratory chest infection three weeks before the onset of the. She was admitted to hospital and given IV fluids. A stool sample was positive for C. difficile glutamate dehydrogenase antigen and she was treated with oral metronidazole 400mg tds for five days, without improvement. She was changed to oral vancomycin 125mg qid for a week. There was sufficient improvement for her to leave hospital, but she was readmitted a couple of weeks later with the same symptoms, a CRP of 150 (<5mg/L), serum albumin of 21 (36-45g/ L). She was treated with both oral vancomycin, IV metronidazole and IV tigecycline and also required total parenteral nutrition. The frequency of her decreased and her CRP fell, but she had persistent loose stools and abdominal pain. On the basis of recurrent, severe and PCR detection of the hypervirulent strain, the decision was made to perform a faecal microbiota A stool sample was positive for C. difficile glutamate dehydrogenase antigen and she was treated with oral metronidazole 400mg tds for five days, without improvement. transplant, which was performed two days after the antibiotics and the total parenteral nutrition were ceased. There was a good clinical response over several days and there has been no recurrence of nine months later. How to Treat Quiz Clostridium difficile-associated 28 September 2012 Instructions Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes by post or fax. The mark required to obtain points is 80%. Please note that some questions have more than one correct answer. Online ONLY www.australiandoctor.com.au/cpd/ for immediate feedback 1. Which THREE statements regarding epidemiology of C. difficile-associated are correct? a) About 30% of healthy adults are carriers of C. difficile b) About 70% of healthy neonates have C. difficile in their stools c) In many UK and US hospitals, up to 20% of inpatients carry C. difficile d) In some nursing homes the carrier rate of C. difficile approaches 50% 2. Several reasons have been suggested for the increased incidence of C. difficileassociated. Which THREE of the following reasons are correct? a) The decreased pathogenicity of new strains of C. difficile b) Development of more frequent carrier status of C. difficile in humans c) The ageing of the population d) The widespread use of antibiotics 3. Which THREE statements are correct? a) C. difficile is spread via the faecal oral route b) C. difficile is difficult to eradicate with commonly used surface cleaners, particularly alcohol-based agents, since C. difficile spores are resistant to killing by alcohol c) Patients who enter hospital colonised with C. difficile are more likely to develop d) A significant proportion of patients who acquire the infection in hospital are discharged before symptoms begin 4. Which THREE statements regarding community-acquired C. difficileassociated are correct? a) Community-acquired C. difficile-associated accounts for about 20% of cases of infectious b) diagnosed within 48 hours of admission to a health care facility is classified as community acquired c) diagnosed three weeks after discharge from a health facility is classified as community acquired d) Patients who have community-acquired tend to be younger than the patients with hospitalacquired infection 5. Which THREE statements are correct regarding nursing home residents and? a) The carrier rate of C. difficile is often high in nursing home residents b) All nursing home residents should have testing and treatment to eradicate C. difficile c) C. difficile spores are easily spread due to challenges associated with toileting elderly, infirm residents d) The importance of regular hand washing with soap and water should be stressed to staff in nursing homes, as C. difficile spores are resistant to alcohol sanitisers 6. Which TWO statements are correct? a) The increasing use of fluoroquinolones worldwide may be associated with the emergence of the most significant hypervirulent strain of C. difficile that has been identified in Australia, NAP1/BI/027 b) The classes of antibiotics that most frequently induce C. difficile-associated include broad-spectrum penicillins, broad-spectrum cephalosporins and fluoroquinolones c) Metronidazole and vancomycin never induce d) There is definite evidence that proton-pump inhibitors increase the risk of acquiring C. difficile infection 7. Which TWO statements are correct? a) Age over 65 is a clear risk factor for community-acquired C. difficile-associated b) Patients with ulcerative colitis and Crohn s disease have a decreased risk of acquiring c) In patients with ulcerative colitis and Crohn s disease, stool testing for C. difficile should be performed when there is a poor response to their usual therapy d) Hospital patients receiving chemotherapy are particularly vulnerable to C. difficileassociated 8. Which TWO statements regarding C. difficile investigations are correct? a) Stool culture provides the fastest result for the presence of C. difficile b) Testing for the presence of glutamate dehydrogenase, which is produced by all C. difficile strains, is often used in combination with a test for toxin c) The C. difficile PCR test, also called the gene test, is both sensitive and specific d) Colonoscopy is mandatory in all cases of 9. Which TWO statements regarding treatment of C. difficile-associated are correct? a) First-line therapy for mild-to-moderate is oral metronidazole b) IV vancomycin is very successful in the treatment of c) Assessment of treatment with probiotics is complicated by the fact that there are so many different strains of probiotic bacteria available, which may have a variable effect on the colonic flora of different individuals d) Faecal microbiota transplant is a wellestablished treatment for recurrent 10. Which THREE statements regarding recurrent C. difficile-associated are correct? a) Fewer than 5% of patients will relapse with a further episode of significant C. difficile b) A first recurrence of C. difficile-associated should be treated with the same antibiotic regime as the initial episode; however, the response is less likely to be effective c) Following a second recurrence of C. difficileassociated, vancomycin can be used as a tapering dose or as a pulse therapy d) Fidaxomicin is the most promising new antibiotic for treatment of C. difficileassociated, as it appears to have quite specific activity against C. difficile without significant alteration of the colonic flora CPD QUIZ UPDATE The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online. how to treat Editor: Dr Barbara Tink Email: barbara.tink@reedbusiness.com.au Next week More than three million Australians are obese. Finding a solution to this massive health problem is difficult, however, bariatric surgery is one solution. Next week s How To Treat examines bariatric surgery options, their safety and effectiveness. The author is Emeritus Professor Paul O Brien, head of the Centre for Bariatric Surgery and Emeritus Professor of Surgery at Monash University, Melbourne, Victoria. 30 Australian Doctor 28 September 2012 www.australiandoctor.com.au