Rational Chemoprophylaxis presentation.pptx

Rational Chemoprophylaxsis

1. Rational Chemoprophylaxis Major Kajri Bhargava Resident Pharmacology

2. Overview Definition Types Principles Classification Demerits

3. Definition Chemoprophylaxis is the practice of administering an antimicrobial agent for preventing an infection or for avoiding development of a potentially dangerous disease in those who already have evidence of infection

4. Types Primary prophylaxis Aims to prevent initial infection or disease (e.g. to cover a surgical procedure) Secondary prophylaxis Aims to prevent recurrent disease (e.g. giving penicillin to a patient who has had rheumatic fever).

5. Principles The antimicrobial drug used must have activity against the infectious agent or must disrupt pathogenesis The host should have a well-defined increased risk of disease eg high likelihood of development of infection following exposure, the severity of infection, and communicability to others Complications due to drug administration should not outweigh the risks of infection (an acceptable risk-to-benefit ratio).

6. Principles.. Adequate tissue concentrations must be present at the time of exposure to the infectious agent A narrow-spectrum antibiotics shld be considered to target the most important infectious organisms and do not target all possible bacteria Limit the duration of prophylaxis to be as short as the time in which maximum contamination is expected Apply PK/PD knowledge

7. Classification Surgical chemoprophylaxis Non surgical chemoprophylaxis 1.Chemoprophylaxis for specific diseases 2.Chemoprophylaxis in immunocompromised patients 3.Postexposure prophylaxis

8. Surgical chemoprophylaxis Rationale Wound infection results when a critical number of bacteria are present in the wound at the time of closure Chemoprophylactic antimicrobial agents directed against the invading microorganisms may reduce the number of viable bacteria below the critical level and thus prevent infection.

9. Surgical chemoprophylaxis Right drug A bactericidal agent should be used which is active against the probable infecting organism Penetrates the likely site of infection has a favorable safety profile Right dose The drug concentration should be maintained above the target MIC throughout the operative period Doses depends on the length of procedure and likely blood loss

10. Surgical chemoprophylaxis Right route This depends on the nature of the procedure and the pharmacokinetics of the drug Right time of administration Antimicrobial prophylaxis should be administered 0–2h before the surgical incision Right Duration Prophylactic antibiotics should not usually be given for >24h

11. Non surgical prophylaxis Chemoprophylaxis for specific diseases ( given to close contacts/patient itself ) Tuberculosis(close contact)- INH for 1 year + Ethambutol for 9 months Pertussis (close contact) - Erythromycin or Ampicillin for 10 days Swine flu (H1N1) (close contact)- Oseltamivir 75 mg once daily for 10 days

12. Non surgical prophylaxis Cholera(close contact) – Tetracycline 500 mg twice daily for 3 days Doxycycline300 mg single dose Malaria (Traveler who travels to malaria endemic area)- Mefloquine 250 mg once a week for 1-3 weeks before exposure and should be stopped after 4 weeks postexposure Doxycycline 100 mg daily started 1-2 days before and stopped after 3-7 days post exposure

13. Non surgical prophylaxis Meningococcal meningitis(close contacts) – 2-day regimen of Rifampicin (600 mg every 12 h for 2 days in adults) Alternatives: Ciprofloxacin ,Ceftriaxone Group B streptococcal infection (intrapartum chemoprophylaxis for at risk pregnant women) – loading dose of 5 million units of Penicillin G followed by 2.5 million units every 4 h until delivery

14. Non surgical prophylaxis Leptospirosis (person exposed to risk factors eg flood) – Doxycycline 200 mg PO once a week Rheumatic fever(patient) – Benzathine penicillin G 12 lakh units IM once a month HIV (close contact)- Raltegravir 400mg BD plus Tenofovir disoproxil fumarate 300mg OD for 4 weeks Dolutegravir 50mg OD plus Tenofovir disoproxil fumarate 300mg OD for 4 weeks

15. Non surgical prophylaxis Chemoprophylaxis in immunocompromised patients Includes HIV patients, post transplantation and on immunosupression medications Rationale : Immunocompromised patients are at high risk for opportunistic infections specific antimicrobial therapy is administered based on well defined pattern of pathogens that are major causes of morbidity due to immunosuppression

16. Non surgical prophylaxis Infections targeted : Pneumocystis jiroveci , MAC, Toxoplasma gondii, Candida species, Aspergillus species a.HIV patients : Risk benefit analysis determines choice and duration of prophylaxis Prophylaxis for opportunistic infections started when CD4 count is below 200 cells/mm 3 and discontinued above 200 cells/mm 3 (CDC guidelines)

17. Non surgical prophylaxis Pathogen Drug Pneumocystis Pneumonia Cotrimoxazole Dapsone daily MAC Rifabutin TB ( montoux test induration >5mm in HIV patients is considered positive) Isoniazid daily for 9 months to 1 year

18. Non surgical prophylaxis b. Post transplantation patients and on immunosuppression : Time since transplant determines the duration of prophylaxis Prophylactic treatment stopped after a predetermined cut off time like 1year

19. Postexposure prophylaxis Rationale : Antimicrobial therapy after exposure to certain infections like HIV has been found effective in preventing the infection in the exposed person Eg : HIV infection – All those who are exposed are recommended to start PEP Raltegravir 400 mg twice daily or Dolutegravir 50mg once daily + FDC of Tenofovir 300 mg +Emtricitabine 200 mg once daily preferred for adults Duration :4 weeks

20. Demerits of chemoprophylaxis: • Adverse effects associated with specific drug (e.g. penicillin anaphylaxis) • Emergence of antibiotic-resistant organisms • Alteration of normal flora

21. References Goodman and Gillman 14 th edition Park’s textbook of preventive and social medicine 27th edition https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395692/ Harrison’s principles of internal medicine 21st edition Oxford handbook of infectious diseases and microbiology https://www.sciencedirect.com/book/9781437727029/principles-and-practice-of-pediatric-infectio us-diseases https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm#tab1