About antimicrobial drug resistance -2021

Mechanism of Antibiotics resistance 

Principle and definition 

1.Clinical resistance

Clinical resistance to an antimicrobial agent occurs when the MIC of the drug for a particular strain of bacteria exceeds that which death is capable of being achieved with safety in vivo. Resistance to an antimicrobial can arise:

i) By mutation in the gene and determines sensitivity/resistance to the agent

ii) By acquisition of extrachromosomal DNA carrying a resistance gene.

Resistance that appears after introduction of an inter microbial agent into the environment usually results from a selective process, i.e the antibiotics selects  for survival of those strains processing a resistance gene. Resistance can be developed in a single step or it can result from the accumulation of multiple mutation. 

2.Cross resistance 

Cross resistance implies that a single mechanism confers resistance to multiple antimicrobial agents while  multiple resistances imply that multiple mechanisms are involved.Cross resistance is commonly seen with closely related antimicrobial agents while multiple resistance are seen with unrelated antimicrobial agents.

B.Mechanism of resistance 

1.Altered  permeability of the antimicrobial agent

Altered permeability may be due to the inability of antimicrobial agent to entire the bacterial cell or alternatively to the active export of the agent from the cell. 

2.Inactivation of the antimicrobial agent 

Resistance is often the result of production of an enzyme that is capable of inactivating the antimicrobial agent.

3.Altered target site

Resistance can arise due to alteration of the target site for the antimicrobial agent.

4.Replacement of a sensitive pathway 

Resistance can result from the acquisition of a new enzyme to replace the sensitive one.

Fig: Mechanism of antimicrobial resistance 

Effects of antimicrobial resistance 

The effects -------------------------------Examples 

Morbidity and mortality	All-cause
	Attributable to infection
	Increased length of hospital stay
	Increased length of mechanical ventilation
	Increased need for intensive care and invasive devices
	Excess surgery
	Functional decline and need for post-acute care
	Need for contact isolation
	Loss of work.
Increased resource utilization and cost	-Hospital, intensive-care unit and post-acute care beds
	-Additional nursing care, support services, diagnostic tests and imaging
	-Additional use of isolation rooms and consumables (gloves, gowns)
	-Cost of targeted infection control programmes including screening and isolation
Guideline alterations	-Loss of narrow-spectrum antibiotic classes
	-Altered empiric therapy regimens
	-Use of agents with reduced efficacy
	-Use of agents with increased toxicity
Reduced hospital activity	-Unit closures
	-Cancellation of surgery