MICROPARA LEC - Lecture 4 and 5: Intro to AMR and Bacterial Infections Pt1

Antimicrobial Resistance (AMR)

The ability of microorganisms to resist drugs that once killed or inhibited them.

Why is AMR a major health concern?

It makes infections harder to treat, increases mortality, recovery time, and healthcare costs, and threatens humans, animals, and the environment.

How many global and Philippine deaths were linked to AMR in 2019?

- Worldwide 4.95 million (1.27 million direct)

- Philippines 15,700 attributable / 56,700 associated

What drives the development of resistance?

Natural selection and misuse/overuse of antibiotics.

Why is immune-drug synergy important?

Drugs lower pathogen load so the immune system can finish clearing infection.

This happens if synergy or dosing is suboptimal

Resistant microbes survive and multiply.

Minimum Inhibitory Concentration (MIC)

Lowest concentration preventing growth

Minimum Bactericidal Concentration (MBC)

Lowest concentration that kills

4Rs of Proper Therapy

- Right drug

- Right dose

- Right duration

- Right route

Bacteriostatic Agents

Agents that halt growth (preferred if immune intact)

Bactericidal Agents

Agents that kill (preferred if immune weak)

Example of Synergism

Co-trimoxazole (SMX + TMP)

Example of Antagonism

Tetracycline + Penicillin in pneumococcal meningitis

5 Main Mechanisms of Resistance

- Drug inactivation

- Altered target

- Reduced permeability/efflux

- Resistant pathway

- Biofilm shield

Example of Drug Inactivation

β-lactamase destroying penicillin

Example of Altered Target Site

MRSA (altered PBP gene mecA)

Example of Drug Inaccessibility

Efflux pumps in Pseudomonas aeruginosa

Intrinsic Resistance

Resistance (natural trait)

- e.g., Mycoplasma no cell wall

Acquired Resistance

Resistance (mutation or gene transfer)

Horizontal Gene Transfer

Movement of resistance genes via plasmids, transposons, or phages.

ESKAPE

- Enterococcus faecium

- Staphylococcus aureus

- Klebsiella pneumoniae

- Acinetobacter baumannii

- Pseudomonas aeruginosa

- Enterobacter spp.

Antimicrobial Stewardship (AMS)

Coordinated strategies to use antibiotics wisely and slow resistance.

AMS Core Principles

- 4Rs + use narrow spectrum

- Review/stop when not needed

- Use culture results

Antimicrobial Resistance Surveillance Program (ARSP)

A DOH program (1988) monitoring AMR through sentinel labs and WHONET

Purpose of an Antibiogram

Provides annual summary of local susceptibility data to guide empiric therapy

Main Function of the Nose

Its function is to filter air via cilia

Main Function of the Lungs

Its function is for gas exchange in alveoli

Common Upper Respiratory Tract Infections

- Pharyngitis

- Scarlet Fever

- Diphtheria

- Otitis Media

Causes of Strep Throat

Streptococcus pyogenes (Group A)

Key Feature of Scarlet Fever

"Strawberry tongue" rash from erythrogenic toxin

What makes Corynebacterium diphtheriae pathogenic?

β-phage carrying the toxin gene (tox⁺ strain)

Common Cause of Otitis Media

Streptococcus pneumoniae ± H. influenzae, M. catarrhalis

Pertussis (Cause & Mechanism)

Bordetella pertussis - tracheal cytotoxin & pertussis toxin damage cilia → whooping cough

Tuberculosis Causative Agent and Key Trait

- Mycobacterium tuberculosis

- Acid-fast waxy cell wall (mycolic acid)

How does TB survive inside macrophages?

Blocks phagolysosome fusion

Ghon Complex

Primary lesion + infected hilar lymph node

Ranke Complex

Calcified, healed TB granuloma visible on X-ray

Drugs for Active TB

- Isoniazid

- Rifampin

- Ethambutol

- Pyrazinamide

MDR-TB vs XDR-TB

Multi-Drug Resistant vs Extremely Drug Resistant

- Treated with Pretomanid, Bedaquiline, Linezolid.

Pneumonia

Infection of lung tissue causing inflammation and fluid in alveoli.

Main Bacterial Causes of Pneumonia

- S. pneumoniae

- H. influenzae

- S. aureus

- M. pneumoniae

Stages of Pneumonia

1. Congestion - fluid in alveoli

2. Red hepatization - solid liver-like lung

3. Gray hepatization - RBC breakdown

4. Resolution - recovery

Types of Pneumonia

- CAP (Community)

- HAP (Hospital)

- VAP (Ventilator)

- Aspiration

- Atypical

- Lobar

- Bronchopneumonia

DTaP Vaccine

Vaccine that prevents Pertussis

Mycobacterium Tuberculosis

A pathogen that is acid-fast

Mycoplasma Pneumoniae

A pneumonia that is "walking"

β-lactamase

Enzyme that destroys penicillin