Infectious diarrhoea & C. difficile infections.
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Transcript of Infectious diarrhoea & C. difficile infections.
Infectious diarrhoea & C. difficile infections
Objectives
Different types of infectious diarrhoeaRisks and complicationsWhen and how to treat
Healthcare associated diarrhoeaGovernment legislationImpact on prescribing practice
Infectious diarrhoea
Bacterial, viral or parasitic causesDefinition:
3 or loose stools a dayor
increase in frequency from normal and change in consistency
ClassificationWHO – symptomology:
acute diarrhoea – several hours/ days acute bloody diarrhoea (“dysentery”) persistent diarrhoea – duration > 14 days
• e.g. chronic infection, malabsorption
Microbiological – gut reaction type I – non-inflammatory – watery diarrhoea type II – inflammatory – white cell infiltration type III – penetrating – patient become bacteraemic e.g. typhoid
World-wide impactSecond leading cause of death in children under 5
1.5 million children per year
Preventable and treatable2 billion cases per year globallyMainly affects children <2 yearsLeading cause of malnutrition in children <5 yearsMortality due to dehydration
Global incidence
DehydrationEarly
no signs or symptoms
Moderate thirst, restless/irritable, decreased skin elasticity, sunken eyes
Severe shock – decreased consciousness, low urine output, cool moist extremeties, rapid pulse, low blood pressure, pale skin
Causes of diarrhoea
Infectious causesBacteria
e.g. Escherichia coliViral
e.g. rotavirusParasitic
Worse disease in children, the elderly or those who are immunosuppressed
Bacterial gastroenteritisEscherichia coliSalmonellaShigellaCampylobacterVibrio choleraeYersinia enterocoliticaPreformed toxins
Bacillus cereus, Clostridium perfringens, Staphylococcus aureus, Botulism
Others Treponema whipplei, Listeria monocytogenes
E. coliAbout 5% of the normal gut floraUseful as it aids digestionQuick to acquire pathogenicity via plasmidsInfectious dose is about 108 organismsReservoir of pathogenic bacteria in animal guts
associated with poorly prepared meatVarious pathogenic types
Enterotoxigenic E. coli
Produces a cholera-like toxinCommonest cause of bad traveller’s diarrhoea & diarrhoea in developing world childrenGenerally self-limiting
Enterohaemorrhagic E. coliAssociated with sporadic outbreaks
e.g. petting zoos (carried in animal gut), pates, Scottish butcher
Produces a shigella-like toxin binds to gut, cleaves human RNA turning off protein synthesis and shedding of cells systemic absorption of toxin causing haemolytic-uraemic syndrome (HUS)
Identified as only sorbitol non-fermenter E. coli then serotyped (O157 being significant)
Enteropathogenic E. coli
Adhere to vili and destroy the brush border disrupting intestinal functionCauses a prolonged diarrhoea responsible for malnutrition
Management of E. coli diarrhoea
Antibiotics not usually neededContraindicated in O157 infection
antibiotic exposure (especially fluoroquinolones) can increase toxin production worsens risk of HUS
Salmonella4 types
S. enteritidis & S. typhimurium – commest causes of bacterial food poisoning in the UK (poorly cooked chicken or eggs from unvaccinated hens) S. typhi & S. paratyphi – cause typhoid (enteric fever)
Transmitted via contaminated food and waterCan be transmitted person-to-person (106 organisms)Prolonged excretion occurs for years (ensuring clearance is important) in about 2% of patientsCan settle in bone (sickle cell) and the aorta (elderly)
Typhoid
Most UK cases are importedIncubation period is 7-14 daysSymptoms include fever, chills, malaise, abdominal pain & can be diarrhoea or constipationComplications include GI perforation, pneumonia & meningitis
Management of Salmonella
Simple diarrhoea – usually self-limitingSevere diarrhoea, signs of bacteraemia or typhoid – iv ceftriaxone or oral ciprofloxacin for 14 daysAlternatives – azithromycin, chloramphenicolDexamethasone may help if shocked
Shigella
S. sonnei, S. flexneri, S. boydii, S. dysenteriaeGenerally mild and self-limitingUsually sensitive to ciprofloxacinSmall infective dose (10-100 organisms)
Invasion of Shigella
CampylobacterC. jejuni is the most common cause of bacterial diarrhoea in the UKGenerally acquired from poorly cooked meat but reservoir in wild birds (via delivered milk)Typically causes a watery diarrhoea with cramping painIncubation period is up to a week (compared to ≈ 72 hours for Salmonella/ Shigella)Rarely invasiveErythromycin generally preferred treatment if needed
Vibrio choleraeEpidemics and pandemicsVaccination possible for people going to at risk areasDisease is due to toxin productionDeath is due to dehydration (50% if untreated)Treat empirically with co-trimoxazole or tetracyclines and rehydrationCarriage for 2-3 weeks which is why outbreaks can last so long
Toxin
Enters intestinal cell activates continuous cAMP production activates CFTR dramatic efflux of ions and water
Yersinia enterocolitica
Causes inflammatory colitis and can invade and cause abscesses and reactive arthritisDifficult to identify in the laboratory
Viral diarrhoeas
RotavirusNorovirusAdenovirus – self-limitingHepatitis A/E – present with diarrhoea as well as jaundice & liver dysfunctionCytomegalovirus – particularly in immunosuppressed patients
RotavirusMost common cause of diarrhoea, particularly in infantsIncubation is 1-2 daysAcute onset vomiting followed by 4-7 days of diarrhoeaInfected intestinal cells destroyed, causing malabsorption and diarrhoeaSymptomatic treatment only
Norovirus
Commonest cause of diarrhoea in adultsPattern similar to rotavirus; cramping Readily spread from person-to-person and therefore around institutionsTreatment of dehydration is the priority
Parasitic diarrhoeasGiardia lambiaEntamoeba histolyticaCryptosporidium Ascaris lumbricoidesIsosporaCyclosporaMicrosporaStrongyloides
similar to Cryptosporidium
Giardia
Very common3 week cycles of intermittent diarrhoea (parasite life-cycle involves germination and re-infection) and abdominal crampsOocytes easily seen in stoolTreat with metronidazole or tinidazole
AmoebiasisTypically causes dysenteryCysts survive in the environment and are ingestedDamage mucosa and cause GI ulcerationPossible perforation, bloodstream invasion and abscesses (particularly liver)Treatment with tissue (e.g. metronidazole) and luminal (e.g. paromomycin, diloxanide) amebicides
Cryptosporidium
Outbreaks in drinking water suppliesGenerally self-limiting in immunocompetent patientsMain treatment is reversing immunosuppression as appropriateDrug treatment: nitazoxanide, spiramycin
General diarrhoea adviceLoperamide should be avoided – prolongs gut carriage and increases crampsOral rehydration solution
½ teaspoon salt 6 teaspoons sugar 1 litre boiled and cooled water
Zinc supplements reduce diarrhoea duration by 25% and severity; reduces malnutrition and deaths due to diarrhoeaEarly visit to HCP if moderate/ severe dehydration
Prevention of diarrhoea
Safe drinking waterGood sanitationBreastfeeding for the first 6 months of lifeGood personal and food hygieneHealth educationVaccination
Clostridium difficile
Spore-forming Gram positive bacteria Spores are transmissible, contaminate environment, persist for long periods Germinate in the gut once ingested
Incidence significantly higher in the elderly more frequent & severe infections, more antibiotic exposure & prosthetic material
Clostridium difficile Ribotyping Network (CDRN)
Receive samples and genotype to gather information about C. difficile
Factors associated with CDI mortalityAge > 60 years, severe CDI and ribotype 027 significantly associated with mortality027 genotype metronidazole MIC highest and 94% of isolates with a metronidazole MIC > 4mg/L were the 027 genotype
Antibiotic exposure and CDIDifferent risks of CDAD
luminal concentration effect on gut flora activity against C. difficile
Can occur months after antibiotic exposureLoss of colonisation resistance
bowel prep., chemotherapy, colitisIncreasing reports of disease without antibiotic exposure
Antibiotic exposure and CDI
CDI treatment
Shift towards prescribing of vancomycin: 2007/8 – 27% 2008/9 – 64%
Vancomycin MIC shows little variability between genotypes
CDI infection in UHS
Non-severe – po metronidazoleSevere – po vancomycin (clear RCT evidence of efficacy)
WCC > 15 x 109, Cr > 50% over baseline, temperature > 38.5ºC, signs of colitis
Severe CDI treatment
po vancomycin + iv metronidazole consider rifampicin 300mg bd consider iv immunoglobulin 400mg/kg stat consider colectomy