Microbiology only test those stools that adhere to the definition, otherwise we would have lots of asymptomatic patients with c.diff positive results which has implications for infection control i.e. not enough side rooms, treatment costs would increase.
Varying degrees of severity therefore all signs and symptoms may not be present.
Range of symptoms from mild diarrhoea to bloody diarrhoea, PMC which may require surgical intervention, perforation and bacteraemia from toxic megacolon. Serum lactate ≥5 mmol/l is associated with 100% mortality
Greater risk in > 65 years, and with an ageing population this is only set to get worse. There is in vitro evidence that their faecal flora are less inhibitory to the growth of C. diff. They also have higher rates of asymptomatic carriage about 1/3. It is not well understood why some people develop mild disease, some fatal PMC, others remain asymptomatic despite toxins being present. Approximately 70% of the population have antibodies against toxin a and/or b. There is some evidence that the ability to neutralise toxin decreases with age. Studies have shown that asymptomatic carriers had significantly greater levels of igG antitoxin A than those whose had CDAD. A separate study showed that significantly higher levels of anti-toxin IgG in those with one as opposed to multiple episodes. Higher prevalence of antibiotic exposure especially long durations and combinations on elderly wards. Also Elderly have reduced antibody production, greater underlying disease, longer hospital stays and NG tubes. Spores can survive for months. Chlorine only agent to eradicate spores. Hand should be washed thoroughly with soap and water, alcohol gel does not remove spores. Explosive diarrhoea, spores everywhere, inadequate cleaning or hygiene, transmission by contact with contaminated surfaces. Typing is not routinely done unless there is an outbreak. But we should be alert to changes in clinical presentation and/or the local epidemiology of CDI, particularly noting any increases in number or severity of cases and higher mortality than expected, as we could have a more virulent strain present. Type 027 is thought to be a hyper-producer of toxin and sporulates more frequently. Has been known to have caused outbreaks in several European countries and in US. Has been identified in UK.
Unfortunately it is not as simple as it seems, all antibiotics have the potential to cause CDAD. In order to colonise the gut of a normal individual the resident gut flora which usually inhibit C. diff must be reduced. Typically diarrhoea starts within a few days of commencing antibiotics, although can occur up to 12 weeks after taking antibiotics. Very occasionally no antibiotics have been consumed.
15% of patients respond to stopping antibiotic alone. In practice it is a difficult decision to not start treatment as it is not possible to predict who will spontaneously improve and who will have protracted and worsening symptoms. PPIs also increase risk of CDAD so should be stopped. Agents affecting gut motility should also be stopped to allow c. diff. to be cleared from the GI tract.
No statistically significant difference in the response or relapse rate between metronidazole or vancomycin, But metronidazole may be less effective in more virulent strains ie 027. also it has been found that the mean duration of symptoms is shorter with vancomycin than metronidazole by 1-2 days but the considerable cost difference means that it is not cost-effective, except for severe cases. Vancomycin reserved for more severe cases because of the risk of VRE also. Injection is cheaper but may not be accepted orally by patients because of its taste, but no reason not to give it NG. Once reconstituted can be kept in the fridge for 24 hours. Using 500mg vial. No evidence of a benefit of using either agents to prevent CDAD in patients receiving other antibiotics. No reports of resistance to either agents in the UK, although reports of resistance to metronidazole in Spain.
Antimicrobial resistance is increasing. Antibiotic use is necessary to treat disease but we can use them more wisely to protect individual patients and society as a whole.
A summary of pharmaceutical microbiology part 3 - c difficile infection
Part 3 <ul><li>CDAD </li></ul>
Clostridium difficile associated disease <ul><li>Definition of CDAD </li></ul><ul><li>“ One episode of loose stool enough to take the shape of the container, not attributable to any other cause and occurring at the same time as a positive toxin assay and/or endoscopic evidence of pseudomembranous colitis” </li></ul>
Signs and Symptoms <ul><li>Diarrhoea with characteristic foul odour </li></ul><ul><li>Abdominal pain </li></ul><ul><li>Pyrexia </li></ul><ul><li>Raised WCC </li></ul><ul><li>Raised serum creatinine </li></ul>
Risk factors <ul><li>Patient </li></ul><ul><li>> 65 years of age </li></ul><ul><li>Immunosuppressed </li></ul><ul><li>Antibiotic exposure </li></ul><ul><li>Asymptomatic carriage by patients and staff </li></ul><ul><li>Prolonged hospital stay </li></ul><ul><li>? Other drugs e.g. PPIs </li></ul><ul><li>NG tube </li></ul><ul><li>Environmental </li></ul><ul><li>Inadequate isolation facilities </li></ul><ul><li>Inadequate cleaning of ward facilities and equipment </li></ul><ul><li>Poor Hand Hygiene by patients and staff </li></ul><ul><li>Increased movement of patients in hospitals </li></ul><ul><li>More virulent strains emerging e.g. type 027 </li></ul>
Antibiotics and risk of C. difficile infection Trimethoprim Vancomycin Rifampicin Tetracyclines Tazocin Macrolides Fluoroquinolones Co-amoxiclav Metronidazole Co-trimoxazole Cephalosporins Aminoglycosides Ampicillin/Amoxicillin Clindamycin Low Risk Medium Risk High Risk
Treatment <ul><li>Stop precipitating antibiotic if possible. </li></ul><ul><li>If not switch to an antibiotic with a lower risk of inducing CDAD. </li></ul><ul><li>Review other medicines – PPIs, anti-motility agents, laxatives. </li></ul>
Treatment (contd) <ul><li>Usual treatment is: </li></ul><ul><li>- 1 st line (no severity factors) – metronidazole 400mg tds po for 10-14 days, can also be given iv </li></ul><ul><li>2 nd line (1 or more severity factors) – vancomycin 125mg qds po for 10-14 days, not iv. </li></ul><ul><li>Vancomycin injection is now licensed to be given orally. After reconstitution, the selected dose may be diluted in 30ml of water and drunk or via NG tube </li></ul><ul><li>For 14 days treatment: metronidazole = £0.57, vancomycin caps = £97.36, vancomycin inj = £26.74 </li></ul>
Which antibiotic is most appropriate for society? <ul><li>Minimise resistance potential (4 ways) </li></ul><ul><ul><li>Prescribe antibiotics ONLY if indicated </li></ul></ul><ul><ul><li>Three RIGHTS: </li></ul></ul><ul><ul><ul><li>RIGHT drug at RIGHT dose for RIGHT duration </li></ul></ul></ul><ul><ul><li>Use combination therapy when required </li></ul></ul><ul><ul><li>Narrow spectrum antibiotics where possible </li></ul></ul><ul><ul><li>Balance against risk of missing pathogen </li></ul></ul><ul><li>Maximise cost-effectiveness </li></ul><ul><ul><li>Resources are limited in UK healthcare system </li></ul></ul>