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