Q&A: Concerning Antimicrobial and Antibiotic Resistance

Antimicrobial stewardship consists of systematic measurement and coordinated interventions designed to promote the optimal use of antimicrobial agents, including their choice, dosing, route, and duration of administration. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use. Additional benefits include improving susceptibility rates to targeted antimicrobials and optimizing resource utilization.

This article is for Medical Students & Professionals

This is a Question & Answer revision article designed for medical students and professionals preparing for the PLAB, MRCP or USMLE examinations. They are based on actual questions from these examinations. You may find the Antimicrobial (Antibiotic) Resistance article more useful, or one of our many articles on Diseases & Conditions, Medical Syndromes, Health & Wellness or Home Remedies.

In this article:
Basic concepts of antimicrobial resistance
MCQ: clinical scenario
MCQ: answer
MCQ: explanation

Basic concepts of antimicrobial resistance

Intrinsic versus acquired resistance — Bacteria can have either intrinsic or acquired resistance to antimicrobials.

Intrinsic resistance is inherent resistance to an antimicrobial that all or almost all members of a species display, rendering susceptibility testing unnecessary. As an example, Klebsiella pneumoniae is intrinsically resistant to the antimicrobial ampicillin.

In contrast, acquired resistance is the development of resistance to an antimicrobial to which members of the wild-type bacterial population are susceptible. Bacteria can acquire resistance through chromosomal mutations; through the horizontal transfer of genes via plasmids, integrons, transposons, or transformation; or through a combination of these mechanisms. Unlike intrinsic resistance, acquired resistance in a specific bacterial isolate is not reliably predictable. The goal of antimicrobial susceptibility testing is to determine the degree of acquired resistance to antibiotics that might be employed therapeutically.

Constitutive versus inducible resistance mechanisms — The expression of some bacterial resistance mechanisms is variable, potentially complicating their detection in the microbiology laboratory and requiring special consideration.

Constitutively expressed resistance mechanisms are expressed continuously, while inducible expression occurs following exposure to a particular inciting agent. For example, use of third generation cephalosporins for infections caused by certain Enterobacteriaceae can induce production of a chromosomally encoded AmpC beta-lactamase, which results in resistance to this subgroup of beta-lactam antimicrobials.

Heteroresistance — The phenotypic expression of an antimicrobial resistance mechanism within a bacterial population can be homogeneous or heterogeneous.

Heterogeneous expression, or heteroresistance, can lead to bacterial subpopulations within a microbiological sample that have varying degrees of phenotypic resistance, making the in vitro identification of resistance more difficult. Some conventional antimicrobial susceptibility testing methods can be insufficiently sensitive for the identification of heteroresistance, leading to the misclassification of certain bacterial strains as susceptible. Antimicrobial susceptibility testing methods that use higher inocula can overcome this barrier, facilitating the detection of small subpopulations with intermediate or resistant minimum inhibitory concentrations. Heteroresistant vancomycin-intermediate Staphylococcus aureus is an example of an organism with the capability of heterogenous expression.

MCQ: clinical scenario

Salmonella bacteria are more resistant than Streptococci to penicillin G.

Which of the following factors is most closely associated with this difference?

a) cytoplasmic membrane
b) cytoplasm
c) plasmids
d) peptidoglycan
e) outer membrane

MCQ: answer

The correct answer is E

MCQ: explanation

Gram-negative bacteria are inherently resistant to penicillin because their vulnerable cell wall is protected by an outer membrane that prevents permeation of the penicillin molecule. In gram-negative bacteria, the cell envelope is composed of the outer membrane, peptidoglycan and the cytoplasmic membrane. The outer membrane acts as a sieve to restrict the entry of molecules into the gram-negative cell.

Although bacterial cells have only one main chromosome, they may have other pieces of genetic material. These smaller pieces of DNA are known as plasmids and are defined as extrachromosomal pieces of DNA which are capable of autonomous (or regulated) replication. Some plasmids code for proteins that degrade antibiotics but this is not the most correct answer in this case.

Reference(s)
1). UpToDate: Overview of antibacterial susceptibility testing. Available online: https://www.uptodate.com/contents/overview-of-antibacterial-susceptibility-testing