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

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.

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

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

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

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;

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.

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.

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

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

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

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

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

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.