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Ama for BPH 2017
1. Principles of Antimicrobial Therapy
and Public Health Implication of
Antimicrobial Resistance - I
For BPH 1st Year
Dr. Pravin Prasad
Resident 2nd Year, MD Clinical
Pharmacology
Maharajgunj Medical Campus
6th April, 2017 (Chaitra 24, 2073) Thursday
2. Antimicrobial Agents: Introduction
• Antibiotics:
• Substances produced by microorganisms, which
selectively supress the growth or kill the microorganisms
at very low concentrations
• What does it excludes?
3. Antimicrobial Agents: Introduction
• Chemotherapeutic agents and antimicrobial agents:
• Synthetic compounds used to selectively supress the
growth or kill the microorganisms at very low
concentrations
• Synthetic as well as naturally obtained drug that attenuate
microorganisms
4. Antimicrobial Agents: Introduction
•Chemotherapy:
• Treatment of systemic infections with specific drugs that
selectively supress the infecting micro-organism without
significantly affecting the host.
• Why is this term used for cancer therapy?
5. Choice of an Antimicrobial Agent
Organism
related
Drug
related
Patient
related
6. • Age
• Renal or Hepatic Function
• Local factors
• Drug Allergy
• Impaired Host Defence
• Pregnancy
• Genetic Factors
Choice of an Antimicrobial Agent: Patient
Related Factors
7. • Clinical Diagnosis itself directs the choice of the AMA
• A good guess can be made
• Choice based on bacteriological examination
• Bacterial services are not available
• Bacterial services are available but treatment cannot be
delayed
• Bacterial services are available and treatment can be
delayed
Choice of an Antimicrobial Agent: Organism
Related Considerations
8. • Spectrum of activity
• Type of activity
• Sensitivity of organism
• Relative toxicity
• Pharmacokinetic profile
• Route of administration
• Evidence of clinical efficacy
Choice of an Antimicrobial Agent: Drug
Related Factors
9. Combined Use of Antimicrobial Agents
• To achieve synergism
• To reduce severity of adverse effects
• To prevent emergence of resistance
• To broaden the spectrum of antimicrobial action
• Disadvantages??
Static Cidal
Static Additive ?
Cidal ? Additive
10. Prophylactic Use of Antimicrobials
• Prophylaxis against specific organisms
• Prevention of infection in high risk situations
• Prevention of infection in general
11. Adverse Effects of AMA
• Toxicity
• Hypersensitivity reaction
• Drug Resistance
• Superinfection
• Nutritional Deficiencies
• Masking of an infection
12. Principles of Antimicrobial Therapy
and Public Health Implication of
Antimicrobial Resistance- II
For BPH 1st Year
Dr. Pravin Prasad
Resident 2nd Year, MD Clinical
Pharmacology
Maharajgunj Medical Campus
13th April, 2017 (Chaitra 31, 2073) Thursday
13. Antimicrobial Resistance (AMR)
AMR is resistance of a microorganism to an
antimicrobial drug that was originally effective for
treatment of infections caused by it.
-WHO
14. AMR: Global Status
•Present in all parts of the world
•2012: Gradual increase in resistance to HIV drugs (WHO)
•2013: Multidrug-resistant tuberculosis (MDR-TB) and
Extensively drug-resistant tuberculosis (XDR-TB)
•Greater Mekong sub-region, resistance to the artemisinin-
based combination therapies (ACTs) for falciparum malaria
15. AMR: Global Status
•High proportions of antibiotic resistance in bacteria
•Major number of Hospital-acquired infections: drug
resistant organisms
•Treatment failures for Gonorrhea
•Infections caused by drug-resistant bacteria
• At increased risk of worse clinical outcomes, death
• Consumes more health-care resources
16. AMR: Why a Global Concern?
•AMR kills
•Hampers the control of infectious disease
•Increases the costs of health care
•Jeopardizes health care gains to society
17. Deaths Attributable to AMR every year
Ref: Antimicrobial Resistance:Tackling a crisis for the health and wealth of nations; The Review on Antimicrobial Resistance
Chaired by Jim O’Neill December 2014
18. AMR: Status in South East Asian Region
Ref: Regional Report on Antimicrobial Resistance, Bangkok, Thailand 6-10 August, 2012, WHO Regional Office for South East Asia
Tuberculosis
Kala-azar
Typhoid Fever
ARI
S. aureus
A. baumannii
19. AMR: Status in Nepal
• Started in Nepal in 1999 with technical assistance from ICDDR,
Bangladesh.
• National Public Health Laboratory (NPHL) is the focal point
• Now supported by WHO.
• Has conducted surveillance of 7 microorganisms:
• Salmonella, Shigella, V. cholerae, S. pneumoniae, H. influenzae, N.
gonorrhoeae and ESBL E.coli.
20. National Public Health Laboratory (NPHL)
• Working in close coordination with 18 governmental hospitals,
mission hospitals and private medical college hospitals
• Receives, examines, stores local isolates from the participating
laboratories
• Sends the isolates for EQAS every three months
• Participating laboratories send the testing reports to NPHL and the
NPHL sends the feedback
• Conducts quality assurance training, refresher training, workshop to
enhance the diagnostic capacity of the participating laboratories.
21. AMR Resistance Patterns in Nepal
•A total of 1346 isolates were reported in 2011.
•Salmonella is the highest (1018).
• Salmonella resistance against Nalidixic acid (S. paratyphi A
98%; S. typhi 91%).
•Shigella, 75% were resistant to Cotrimoxazole, 70%
resistant to amoxicillin and 44% to nalidixic acid.
22. AMR Resistance Patterns in Nepal
•S. pneumoniae: 22% resistant to multiple drugs.
•H. influenza: 53% resistant to co-trimoxazole (53%)
• Included in the treatment guideline for ARI
•ESBL E. coli: 100% resistance to the quinolones, 99% to
ciprofloxacin and ceftriaxone.
• Increasing resistance for combination of third generation
cephalosporin (cefotaxime, ceftazidime) with clavulanic acid
23. • The Drug Act, 1978 and the rules thereunder: poor implementation
• National Antibiotic Treatment Guidelines: drafted
• Treatment Protocol for TB, leprosy, ARI, HIV/AIDS, malaria and
childhood illness are available.
• The National Health Laboratory Policy 2069 existent
• Little importance to community empowerment for AMR
• posters, pamphlets, publication of bulletin
• No programme for school children for AMR awareness exists.
AMR: Status in Nepal
24. AMR:
Future
Plans
(GoN)
National Steering
Committee
Drug Act, 1978
National Medicine
Policy, 2007
Health Laboratory
Act and Regulation
Strengthening
existing labs
Strengthening
existing labs
National Antibiotic
Policy
Standard Treatment
Guidelines
Public AwarenessRestricted Use
Greatest contribution of 20th century to therapeutics
Are one of the few drugs which can cure
Most frequently used and misused drugs
Other natural substance that inhibit microorganisms but are produced by higher forms (eg. Antibodies) or even those produced by microorganisms but are needed in high concentration (ethanol, lactic acid, H2O2)
Designed to inhibit/kill the infecting organism and to have no/minimal effect on the recipient
Is it necessary?
Considerations:
Patient factors
Organism-related considerations
Drug Factors
Age:
kinetics of AMA varies, age-related toxicity of AMA
Chloramphenicol conjugation and excretion limited in newborn- gray baby syndrome
Sulfonamides displaces bilirubin from proteins- kernicterus in babies
Aminoglycoside T ½ prolonged in elderly, more prone to develop VIII nerve toxicity
Tetracycline deposit in developing bones and teeth- weak and discoloured parts if given before 6 yrs
Drug allergy: penicillin allergic syphilis pt- tetracycline. Lactams, sulphonamides, FQ, nitrofurantoin
Host defence: neutropenic pts, AIDS
Pregnancy safety: penicillins, many cephalosporins and erythromycin
Tetracycline: acute yellow atrophy of liver, pancreatitis & KIDNEY DAMAGE to mother
Aminoglycoside fetal ear damage
FQ, CO-tri, Chloramphenicol, sulfonamides., nitrofurantoin showed fetal damage in animal studies.
Highly sensitive to cidal drugs- response equal to static drug given alone (apparent antagonism)
Low sensitive to cidal drugs – synergism may be seen
To broaden the spectrum of antimicrobial action
Treatment of mixed infection
Initial treatment of severe infections
Topically
Disadvantages??
Acquired resistance: mutation or gene transfer
Natural resistance: cell wall arrangement of gram negative bacteria
Drug tolerant
Drug destroying
Drug impermeable
Greatest contribution of 20th century to therapeutics
Are one of the few drugs which can cure
Most frequently used and misused drugs
2013: about 480 000 new cases of multidrug-resistant tuberculosis (MDR-TB). Extensively drug-resistant tuberculosis (XDR-TB) has been identified in 100 countries.
High proportions of antibiotic resistance in bacteria that cause common infections in all regions of the world.
Major number of Hospital-acquired infections: methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Gram-negative bacteria.
Treatment failures for gonorrhea have been reported from 10 countries.
Infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and death, and consume more health-care resources than patients infected with the same bacteria that are not resistant.
International Centre for Diarrhoeal Disease Research, Bangladesh