an approach to infective diarrhoea in the community and rational antibiotic therapy dr. tahir iqbal...
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An Approach to Infective Diarrhoea in the Community and
Rational Antibiotic TherapyDr. Tahir Iqbal
Senior Registrar MedicineMcps, fcps
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Introduction
• Major public health problem in Pakistan under 5 years. 1/3 of admission and 17% of death)
• Definition “passage of loose, liquid or watery stool”.• Acute diarrhoea (GE)- sudden onset which usually last 3-
7 days, may 10-14 days. • Non inflammatory e.g. V. cholerae (no abnormal
histology)• Inflammatory- with blood and mucus e.g. Shigella
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0
10
20
30
40
DiarrhoeaOthersARIVPDNeonatal
Diarrhoea 32 16
Others 34 31
ARI 13 13
VPD 15 25
Neonatal 4 13
Admission Death
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Chronic Diarrhoea (>14 days)
• Inflammatory- ulcerative colitis, Crohn’s disease, radiation colitis
• Osmotic- Whipple’s disease, Celiac sprue, Pancreatic insufficiency
• Secretory- Carcinoid syndrome, ZE syndrome, VIP adenomas etc.
• Altered motility- IBS, neurologic disease, fecal impaction
• Factitious- laxative abuse
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Cause of Acute diarrhoea (<14 days)
• Infectious diarrhoea• Medications• Ischemic colitis• Sup. Mesenteric arterial or venous thrombosis• Acute diverticulitis
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Infectious diarrhoea- Mechanisms & causes
Mechanism Examples
Toxin Production
Preformed ToxinEnterotoxinCytotoxin
B. cereus, C. perfringens, S. aureusAeromonas, ETEC, V. choleraeC. difficile, E. coli O157:H7
Enteroadherence Cryptosporidium, cyclospora, EPEC, EAEC, Giardia
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Infectious diarrhoea- Mechanisms & causes
Mechanism Examples
Mucosal Invasion
MinimalVariable
Severe
Norwalk, Rota, Adeno, Calici, Corona, CMVAeromonas, Campylobacter, Salmonella, V. parahaemoliticusE. histolytica, EIEC, Shigella
Systemic Infection Legionella, Listeria, Measles, Psittacosis
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Diarrhoea in HIV/AIDS patient
Bacteria Virus ParasiteC. jejunii CMV CryptosporidiumShigella sp Enteric adeno Isospora belliSalmonella Calici virus CyclosporaC. difficle HIV MicrosporidiaEAECMycobacterium avium complex
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Diagnostic approach to Infective Diarrhoea
• History Dietary details, travel history, source of drinking water, sexual preferences
• Physical examinationBP, pulse rate, pulse volume, Abd. Exam,
hepatosplenomegaly, lymphadenopathy
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Lab Diagnosis- Sample collection
-collected in acute stage-before the start of the treatment-before the radiological examination-no contamination with urine water or any other infective
material -In wide mouthed leak proof screw capped container (25 ml)
with a spoon (do not soil the rim of the container)-amount 5 ml of liquid stool/pea size of formed stool-Number – max. 3 samples (2 after normal movement and 1
after cathartic)
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Lab Diagnosis- Sample Transport
• Cary blair transport media (pH 8.4)- Campy., Vibrio• Buffered glycerol transport media (pH 7.0)- Shigella• V.R media (pH 8.6)- V. cholerae• Hank’s balanced salt solution- Virus• Stuart and Amies- general purpose transport media
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MicroscopyWet mount- Ova and trophozoites of parasites
WBCs indicate invasive pathogensPhase contrast microsciopy- CampylobacterImmune electron microscopy- Viruses Staining methods -
Oocyst Acis-fast stains- Cold/hot Kinyoun modified stain, Giemsa stain, PAS stain, Direct fluorescence stain,E. histolytica- Trichrome stainMicrosporidium- ModifiedTrichromeGram stain
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Lab Diagnosis- Enrichment medium
Medium Incubation timeFor Salmonella and ShigellaGram negative broth 4-6 hrSelenite F-broth 12 hrTetra thionate broth 12 hrFor V. choleraeAlkaline peptone water 6-8 hrMonsur’s taurocholate telllurite peptone water
6-8 hr
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Formed/semiformed stool (1:10 dilution in 2-3 ml PBS or 0.1% peptone water)
Liquid stool
(Cholera suspected by characteristic Motility and immobilisation by specific sera)
Grams stain if required MacConkey Selenite F broth XLD/DCA GN broth
Typical morphology DSRA Further processing Subculture on of DCA/MAC Pure LF cononies within 6 hourAll NLF col(oxidase negative) on MacConkey, should be S/c on DCA All black centered colony on DCA All non sorbitol fermenter colony (EHEC)
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Classification of Enteropathogenic E. coliPathotype Clin Features Epidem. Features Virulence factors
EPEC Watery diarr., vomiting
Infants, Developing countries
Bundle forming pilus, attaching-effacing
EHEC Watery diarr., Hg. colitis
Food & water borne Shiga toxins, attaching-effacing
ETEC Watery diarr Childhood diarr., Traveler's diarr.
Pili, ST & LT entero toxins
EAEC Diarr with mucus
Childhood diarr. Pili, cytotoxins
EIEC Dysentery/ watery diarr
Food borne Cellular invasion, intra cellular motility
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Antibiotic Associated Diarrhea
Most common cause of diarrhea among hospitalized patients (Range-1 in 10 to 1 in 10000)
3-5 billion annual infection annually, 3 million deaths/ year.
1.5 episodes per person/ year > 50% death: elderly Self limiting, ~ 50% within 3 days.
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Antibiotics implicated in AAD
• Frequently: Ampicillin, Amoxicillin-clavulenate, 2nd & 3rd generation Cephalosporin, Clindamycin
• Uncommon: Tetracycline, sulfonamides, Quinalone, Erythromycin, Chloramphenicol, TMP,
• Antineoplastic agents > Methotrexate, Other agents (Anon, 1993)- Dexorubin, cyclophosphamide
• Tube feeding- Nosocomial CD collitis.
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Lab Diagnosis of AAD
• Specimen- Stool (fresh sample), colonic biopsy• Non specific- leucocytes in stool in AAD & PMC• Colonoscopy/ sigmoidoscopy (erythema, edema,
friability, adhered yellow plaques) in PMC. Endoscopy ? Normal in mild cases
• Radiographic imaging• Surveillance of nosocomial infection-
– Swab from inanimate surroundings & hospital personnel
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Stool Tests for C. difficile Infection
Test Detects Advantages Disadvantages
Cytotoxin Tox B Gold standard sen. & specific
Tissue culture ,24-48 hr
ELISA Tox A or B Fast (2-6 hr), Easy, high specificity
Not as sensitive as cytotoxin assay
LAgg Bacterial enzyme (glutamat dehydrogenase)
Fast, InexpensiveEasy to perform
Poor sensitivity & specificity
Culture Tox and Nontox C. difficile
SensitiveAllows strain tytping in epidemics
Requires O2, 2-5 days
Not specific for tox producing bacteria
PCR Tox A or B gene in isolates or directly in feces
High sensitivity & specificity
Requires expertise
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Viruses causing Acute Gastroenteritis
Virus(IP)
Family EM shape Nucleic acid
Charecterization
Rota Reoviridae Wheel shaped dsRNA Gp A, B, C, multiple serotypes, classified according to outer capsid proteins (P, G)
Calici(24-48 hr)
Caliciviridae Small round ss (+)RNA Genogroups- Norwalk like viruses and Sapporo like viruses
Astro Astroviridae Star shaped ss (+)RNA 8 serotypes
Adeno(3-10 days)
Adenoviridae Icosahedral dsDNA 40,41,31, 42-48
Other viruses- Torovirus [ss(+)RNA], Picovirna virus [dsRNA], Enterovirus 22 [ss(+)RNA],Aichi virus [ss(+)RNA
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Diagnosis of Viral diarrhoea
Non Rota- – Direct and immune Em– Antigen detection- EIA with hyper immune sera , EIA with
monoclonal antibody– Antibody detection– Culture– Hybridization probes- for adeno viruses– RT-PCR for HuCV
Rota- EIA, membrane EIA, LA, EM, culture, RT-PCR
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Rational Antibiotic Therapy
Most cases are self limiting and subside with supportive therapyIndication of antibiotic therapy • Cholera• Febrile bloody diarrhoea• Travelers diarrhoea • extremes of age• Food handlers • Immunocompromised• Day care attendee• Residents of institutional facility• Epidemic outbreaks
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Rational Antibiotic Therapy
Problems of empiric therapy-• Not effective in EHEC, salmonella enterocolitis• In children- most cases are viral• Emerging drug resistance• Side effects • Alteration of gut flora• Induction of disease producing phage e.g; Shigatoxin
phage induced by quinolones
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Therapeutic recomendations
• Shigella- TMP-SMZ, Cipro, Norflox• Salmonella-Quinolones, Ceftrixone• V.cholerae - Doxycycline, Tetracycline, Erythromycin• E. coli-Cipro, norflox• C. difficile-Metronidazole, Vanco• Cryptosporidium- Paromomycin• Isospora- TMP-SMZ, • Cyclospora-TMP-SMZ
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Control measures
WHO, UNICEF- oral rehydration therapy.Short-term:(a) ORT – 1978 started in 85-86 (National program), 92-93
(included in maternal and child health program)(b) normal food intake, breast fed (c)Chemotherapy- Infective; Cholera
Toxins; Shigella, E. coli, Campylobacter
Invasive; Salmonella
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Control measures
Long-term: • Nutrition• Sanitation- to stop the transmission
Oro-FaecalWater supplyFood
• Health education- environment, clean drinking water• Immunization • Fly control
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Vibrio cholerae on TCBS
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Salmonella on XLD
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Cryptosporidium parvum in stool(Modified acid fast)
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Isospora belli-Direct smear(Kinyoun stain)
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Cyclospora cayetanensis-oocyst (modified acid fast)
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Microsporidian spores(Modified Trichrome blue stain)
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Clostridium difficile growth under UV light