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 : dranoopkumarkgmu@gmail.com

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 typhi
• 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

8. 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)

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

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

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

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

13. Stage 4 (4th
week) : Recovery 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

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

15. 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)

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

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

18. Treatment
• Activity
Rest is helpful
• Medical care
1. Antibiotic Therapy
2. Corticosteroids (for severe typhoid fever)
3. Antipyretics

19. • 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

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

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

22. 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 bacteriocidal action on the bacilli
• Can be used to treat typhoid carriers

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

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

25. • 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

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

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

28. 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

29. 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

30. 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

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

32. Learning 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
.

33. 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

34. 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

35. THANK YOU