Pharmacotherapy of enteric fever pp.pptx

Enteric fever,pharmacotherapy of eneteric fever

1. Pharmacotherapy of Enteric Fever Drug Interaction: Nitrates + Beta blockers in Angina Presenter: Dr Anoop Kumar (JR2) Moderator: Dr Shoebul Haque (SR) Peer Support: Dr Hasan Abbas (JR2) Department of Pharmacology & Therapeutics King George’s Medical University Lucknow, Uttar Pradesh, India-226003 Email : [email protected]

2. Contents Introduction Cause and transmission pathophysiology Clinical features-stages Treatment Prevention Drug interaction – Nitrate and Beta blocker Summary

3. Specific learning objectives At the end of the teaching-learning session, the audience will be able to Explain the pathophysiology and transmission of Salmonella typhi in enteric fever Identify the key clinical manifestations and complications of typhoid fever Understand diagnosis and discuss the appropriate antibiotic treatment strategies, challenges related to drug resistance Analyze drug interactions in typhoid fever management, including the effects of combining antibiotics with other medications .

4. Introduction Enteric fever is also known as typhoid fever Acute illness caused by Salmonella typhi/Salmonella paratyphi (less severe) Major cause of morbidity and mortality Food & water borne disease

5. Cause Caused by Bacteria - Salmonella t yphi Family - Enterobacteriacea Gram negative bacilli Best grows at 37° C

6. Transmission Faeco-oral route Close contact with patients or carriers Contaminated water and food Flies and cockroaches

7. Pathophysiology Ingestion of contaminated food Ingested bacilli invade small intestinal mucosa Taken up by macrophage & transported to regional lymph node S.typhi multiply in the intestinal lymphoid tissue Interact with enterocytes & M cells( ileal Peyer's patches ) during the 1-3 week of incubation period End of incubation period, bacilli enter bloodstream ( Bacteremia phase) Bacteria invade the gallbladder, biliary system & lymphatic tissue of the bowel & multiply Then pass into the intestinal tract (stool) (Diarrhoea) (onset of typhoid fever)

8. Clinical features Stage 1 ( 1 st week) Slowly rising (stepladder fashion) of temperature for 4-5 days Headache Relative bradycardia

9. End of 1 st week Rose spots may appear on the upper abdomen & back Splenomegaly Abdominal distension & tenderness Diarrhoea

10. Stage 2 (2 nd week) Signs and symptoms of 1st week progress End of 2 nd week Delirium, complications, then coma & death (if untreated)

11. Stage 3 ( 3rd week) Febrile become toxic & anorexic Significant weight loss Typhoid state (Apathy, confusion & psychosis) High risk hemorrhage and perforation may cause death

12. Stage 4 (4 th w eek) : R ecovery period Fever, mental state, and abdominal distension slowly improve over a few days Intestinal and neurologic complications may occur in untreated individuals Weight loss and debilitating weakness last months May become asymptomatic S typhi carriers

13. Complications Bowel Perforation Hemorrhage Septicaemic Foci Bone and joint infection Meningitis Cholecystitis

14. Diagnosis and Investigation Blood culture Specific serologic test Identify Salmonella antibodies/antigens [ Fluorescent antibody study to look for substances that are specific to Typhoid bacteria] Widal Test and ELISA Urine and Stool Culture (2nd & 3rd week)

15. Marrow Culture 90% sensitive unless until after 5 days commencement of antibiotic Punch-biopsy samples of rose spots Culture - 63 % sensitive

16. Specimens collection based on different phases of enteric fever Duration of disease Specimen examination % positivity 1 st Week Blood culture 90 2 nd Week Blood culture Faeces culture Widal test 75 50 Low Titre 3 rd Week Widal test Blood culture Faeces culture 80-100 60 80

17. Treatment Activity Rest is helpful Medical care Antibiotic Therapy Corticosteroids (for severe typhoid fever) Antipyretics

18. Diet Fluid and electrolytes should be monitored Soft digestible diet is preferable in absence of abdominal distension and ileus Surgical care In cases of intestinal perforation

19. Antibiotic Therapy Fluoroquinolone - Ciprofloxacin (500mg bd ) or Ofloxacin (400 mg bd ) 3rd generation cephalosporin - Ceftriaxone , C efotaxime Azithromycin ( 1 g once daily) alternative when fluoroquinolone resistant is present

20. Treatment of complicated typhoid fever CNS –Seizures, Altered sensorium Ceftriaxone 60mg/kg/day for 2 weeks or Cefotaxime 80mg/kg/day for 2 weeks

21. Advantages of ceftriaxone in treating typhoid fever Quick defervescence, usually in 2-3 days Early abetment of symptoms Low risk of relapse and complications Prevention of carrier state due to bacterio cidal action on the bacilli Can be used to treat typhoid carriers

22. Role of Steroids Severe typhoid fever = shock Dexamethasone 3mg/kg stat Dexamethasone 1mg/kg every 6 hrs for 8 doses

23. XDR (extensive drug resistance) Meropenem 1g tds for 14 days

24. Treatment should be continued for 14 days Chronic carriers were formerly treated for 4 weeks with ciprofloxacin but may require an alternative agent and duration Cholecystectomy in severe cases

25. Typhoid fever prevention Wash Hands Drink Boiled Water Clean fruits and vegetables Get vaccinated

26. Drug interaction : Nitrates + Beta Blockers in angina Nitrates and beta blockers are commonly used together in the management of angina to Improve oxygen delivery to the heart Reduce myocardial oxygen demand

27. Mechanism of action Nitrates Cause vasodilation by increasing nitric oxide Reduce preload and afterload, lowering myocardial oxygen demand Beta Blockers Decrease heart rate, contractility, and blood pressure Reduce myocardial oxygen demand by blocking sympathetic activity

28. Benefits of Combination Synergistic Effect Nitrates : decrease preload and afterload Beta blockers : Reduce heart rate and contractility This combination is effective in reducing the frequency and severity of angina attacks

29. Adverse effects of interaction Hypotension: Both lower blood pressure. May cause excessive hypotension, which can lead to dizziness, fainting, or syncope Bradycardia Fatigue and Weakness: Fatigue, weakness and reduced exercise tolerance

30. Clinical considerations Monitoring: Blood pressure and heart rate Patient Education: Patients should be advised on signs of hypotension (dizziness, fainting) and bradycardia (fatigue, palpitations )

31. L earning objectives covered At the end of the teaching-learning session, the audience will be able to Explain the pathophysiology and transmission of Salmonella typhi in enteric fever Identify the key clinical manifestations and complications of typhoid fever Understand diagnosis and discuss the appropriate antibiotic treatment strategies, challenges related to drug resistance Analyze drug interactions in typhoid fever management, including the effects of combining antibiotics with other medications .

32. Summary Enteric fever, also called typhoid fever, is caused by Salmonella typhi/ paratyphi and spreads through contaminated food and water The bacteria invade the intestines , spread through the bloodstream Diagnosis involves cultures and serological tests Treatment involves antibiotics such as fluoroquinolones and ceftriaxone , but rising resistance, especially in South Asia, poses challenges Nitrates and beta blockers used together for angina treatment improve outcomes but require monitoring to prevent hypotension & bradycardia

33. References Davidson’s Principle and Practice of Medicine. 22nd ed. Hutchison’s Clinical Methods: An Integrated Approach to Clinical Practice. 23rd ed. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002 Nov 28;347(22):1770–82. Noorul N, Shakrin N, Noor S, Adnan A, Hani A, Wahab A, et al. Molecular detection of Salmonella enterica serovar Typhi by Vi-qPCR. Malays J Microbiol. 2018 Jan 1;14:483–9. Nuhu Ja’afar J, Goay Y, Mohd Zaidi NF, Low HC, Hussin H, Hamzah W, et al. Epidemiological analysis of typhoid fever in Kelantan from a retrieved registry. Malays J Microbiol. 2013 Jun 1;9:147–51

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