Antibiotic Resistance Quiz

Pharmaceutical Microbiology PM 502, Lecture 5

• Bacterial resistance is a significant concern in the field of pharmaceutical microbiology.
• Antimicrobial resistance is defined as the ability of a microorganism to survive and multiply in the presence of an antimicrobial agent that was intended to inhibit or kill it.
• Resistance leads to treatment failure and increased mortality.
• Resistant bacteria, including Pseudomonas, Streptococci, Staphylococci, Enterococci, and Klebsiella pneumoniae can spread in communities and healthcare facilities (nosocomial infections).

Lecture Outline

• What is antimicrobial resistance?
• Why is antimicrobial resistance a concern?
• Factors that promote antimicrobial resistance
• Strategies to contain or overcome bacterial resistance
• Genetic basis of bacterial resistance (intrinsic and acquired)
• Mechanisms of resistance to antimicrobials
• What is a secondary infection (superinfection)?

Introduction

• Throughout history, humans have battled microorganisms causing infections and diseases.
• Antimicrobial resistance is a significant issue.

Evolution of Bacterial Resistance

• The observation of Staphylococcus spp. growing in the presence of penicillin marked the beginning of the antimicrobial resistance era.
• The timeline shows the development of antibiotic resistance observed over time.

What is Antimicrobial Resistance?

• Antimicrobial resistance is the ability of a microorganism to survive and multiply in the presence of an antimicrobial agent designed to inhibit or kill it.
• Resistant organisms result in treatment failure and heightened mortality rates.
• Resistant bacteria such as Pseudomonas, streptococci, staphylococci, enterococci, and Klebsiella pneumoniae can spread in the community and healthcare settings (nosocomial infections).

Factors Promoting Antimicrobial Resistance

• Antibiotics sold without proper medical supervision.
• Failure to take prescribed antibiotics correctly.
• Exposure to suboptimal levels of antimicrobial agents.
• Taking antibiotics for viral infections.
• Use of antibiotics in animal feed and agriculture to prevent infection and promote growth.

Strategies to Overcome Bacterial Resistance

• Educational programs for healthcare workers.
• Requiring justification for prescribing antibiotics.
• Physicians taking responsibility for accurate diagnoses and correct therapies.
• Ensuring patients take the correct dosage of antibiotics by the appropriate route and for the correct duration.
• Restricting the use of valuable antimicrobials to only one or two types of infections.
• Reducing the addition of antimicrobials to animal feeds globally.

Bacterial Resistance to Antibiotics

• Resistance can be intrinsic (innate) or acquired.
• Intrinsic resistance occurs in organisms that have never been susceptible to a particular drug. It's usually due to inherent properties of the organism.
• Acquired resistance occurs when a microorganism becomes resistant after exposure to an antibiotic. This can be due to mutations or horizontal gene transfer.

Examples of Intrinsic Resistance

• Obligate anaerobes lack the electron transport system, making them resistant to aminoglycosides because this system is required for drug uptake.
• Mycoplasma lacks a cell wall, making them inherently resistant to beta-lactams and other cell wall-targeting antibiotics.
• Gram-negative bacteria are resistant to vancomycin due to its size; it cannot pass through the porin channels in their outer membrane.
• Many Gram-negative organisms are resistant to macrolides and certain beta-lactams because of their hydrophobic nature.

Acquired Resistance

• Acquired resistance is the ability of a microorganism to resist the activity of a particular antimicrobial agent after being previously susceptible..
• Unlike intrinsic resistance, the traits associated with acquired resistance only appear in some strains or subpopulations within a bacterial species.

Mechanisms of Acquired Resistance (a) Chromosomal Mutations

• Changes in a single base pair can alter the amino acid sequence of an enzyme or cellular structure.
• This, in turn, changes the affinity of the microorganism for the antibiotic, affecting its activity.

Mechanisms of Acquired Resistance (b) Horizontal Gene Transfer

• Resistance genes can be acquired from plasmids or transposons transferred through conjugation, transformation, or transduction.
• Plasmids are extra-chromosomal DNA elements that replicate independently in the cytoplasm.
• R-plasmids carry resistance genes.
• Transposons are "jumping" genes capable of moving between different DNA molecules (chromosomes or plasmids).

Biochemical Mechanisms of Antibiotic Resistance

• Decreased membrane permeability: Alteration in membrane structure decreases antibiotic uptake.
• Efflux pumps: Proteins actively pump antibiotics out of the cell.
• Enzyme inactivation: Enzymes (e.g., beta-lactamases) modify or inactivate antibiotics.
• Target site alteration: Modification of target sites (e.g., ribosomes, DNA gyrase) reduces the efficacy of antibiotics.
• Alternative metabolic pathways: Microorganisms use alternative pathways to satisfy metabolic requirements, unaffected by the antibiotic.

Superinfections

• Broad-spectrum antimicrobials can destroy beneficial microbes, allowing resistant microbes to overgrow and cause a secondary infection.
• Certain infections (e.g., pseudomembranous colitis, vaginal candidiasis, oral candidiasis) are examples of superinfections that may occur after antibiotic use.

Clinical Situations with Prophylactic Antibiotics

• Pretreatment for preventing streptococcal infections in patients with a history of rheumatic heart disease.
• Pretreatment for patients undergoing dental extractions or having implanted prosthetic devices.
• Pretreatment before most surgical procedures can reduce post-operative infections.