1. Antimicrobial resistance
Beena Jimmy
Department of Pharmacy Practice
School of Pharmacy
University of Nizwa

2. Antimicrobial agents substantially reduced the threat posed by infectious diseases.
Increased life expectancy
Seriously jeopardized by another recent development, ‘anti-microbial resistance’
Antibiotic resistant bacteria- are bacteria that mutate and are able to resist the antibiotics that are meant to kill them.

3. Causes
Mechanisms of acquired resistance result from changes in the cellular physiology and structure of a microorganism due to alterations in its usual genetic makeup.
3 main mechanisms
1. prevention of intracellular drug accumulation
2. alterations in the drug target
3. production of a drug inactivating enzyme

4. Mechanisms of Antibiotic Resistance
Enzymatic destruction-
of drug
Prevention of penetration-
Alteration of drug's target-
site
Rapid ejection of the drug

5. Prevention of intracellular drug accumulation
By alterations in the bacterial outer membrane, such that the drug no longer binds to the exterior of the microorganism
Active transport of the drug across the cytoplasmic membrane in the cell ceases, or
Active efflux (pumping) of the drug out of the cell before it can damage the micro-organism

6. Alteration in the drug target
Alteration in the drug target (the part of the micro-organism where damage is done) which leads to ineffective levels of drug binding to or near the target site;

7. Production of drug inactivating enzyme
Production by the microorganism of a drug-inactivating enzyme that destroys or greatly diminishes the drug’s ability to kill the micro-organism
Many of these mechanisms result from genetic mutations, the acquisition of resistance genes from other microorganisms via gene transfer, and combinations of these two types of events.

8. How did it happen?
When anti-microbials are used incorrectly - for too short a time, at too low a dose, at inadequate potency; or for the wrong disease - the chances that bacteria and other microbes will adapt and replicate rather than be killed is greatly enhanced.
Underuse through lack of access, inadequate dosing, poor adherence, and substandard anti-microbials may play as important a role as overuse.

9. Consequences Consequences are severe
Infections caused by resistant microbes fail to respond to treatment
Resulting in
- prolonged illness,
- greater risk of death,
more expensive alternatives sometimes more toxic as well,
longer periods of infectivity, thereby exposing the general population to the risk of contracting a resistant strain of infection

10. Key Prevention Strategies
Prevent infection
Diagnose and treat infection effectively
Use antimicrobials wisely
Prevent transmission

11. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
General health communication strategy
Goals:
inform clinicians, patients, and other health care providers
raise awareness about the escalating problem of antimicrobial resistance in healthcare settings
motivate interest and acceptance of interventional programs to prevent resistance

12. Methods to Improve Antimicrobial Use
Passive prescriber education
Standardized antimicrobial order forms
Formulary restrictions
Prior approval to start/continue
Pharmacy substitution or switch
Multidisciplinary drug utilization evaluation (DUE)
Interactive prescriber education
Provider/unit performance feedback
Computerized decision support/on-line ordering

13. Gram positive organisms
Gram positive cocci-
Enterococci faecalis- Ampicillin+ genta/streptomycin
Staphylococcus aureus- TMP + sulphamethoxazole, clindamycin, ampi +sulbactum
Streptococcus pneumoniae- penicillin, erythromycin
Gram positive bacilli-
- Clostridium perfringens- Penicillin G+ clindamycin/doxycycline

14. Gram negative organisms
Gram negative cocci-
Morexella catarrhalis- Amox- clav, ampi-sulbactum
Neisseria gonorrhoea-
Ceftriaxone or cefotaxime; oral follow up cefpodoxime, ciprofloxacin
Gram –ve bacilli
Acinetobacter spp- imipenem, meropenem+ aminoglycosides
E.coli- TGC, meropenem
Pseudomonas aeruginosa- TGC, amino, piperacillin
Improving use is a priority if the emergence and spread of resistance are to be controlled.