PHARMACOTHERAPY OF INFECTIOUS
DISEASES
Summary
1. General principles of anti-infective pharmacology
2. Therapeutic strategy for infections
3. Main pharmacological groups used in clinical practice
4. Bacterial resistance and solutions
Bibliography
Goodman & Gilman’s The Pharmacological Basis of Therapeutics
Human Pharmacology, Jesús Flórez, 6th edition
Harrison’s Principles of Internal Medicine, 18th edition
1. Introduction
Modern anti-infective pharmacotherapy originates from the work of Pasteur, Koch,
and Ehrlich. The era of modern antimicrobial therapy began with the synthesis of
sulfonamides (1936); until then, metal ions were used, which were as harmful to the
host as to the pathogen. The appearance of penicillin (1941) triggered an
unstoppable expansion of effective anti-infective agents.
Infectious diseases remain one of the greatest therapeutic challenges in medicine.
Approximately 34% of deaths worldwide are due to infections, with acute
respiratory infections, tuberculosis, and diarrheal diseases topping the list.
Infection is a clinical term that implies contamination, an immune response, and
structural damage of the host caused by a pathogenic microorganism – that is,
tissue invasion by the germs themselves, their products (toxins), or both.
Symptoms result from the effects of the microorganisms on the affected organs
and from the host’s own defence mechanisms. They can be classified as
non-specific or specific.
, 2. General Principles of Anti-infective Pharmacology
The goal of antimicrobial therapy is to exploit the biochemical differences between
the infectious agent and the host. Fortunately, these differences are sufficient to
allow selective toxicity – the foundation of anti-infective pharmacology.
New anti-infective agents have been developed in two ways:
a) Chemical modification of the core structures of original antibiotics (e.g., the
many penicillin and cephalosporin derivatives). Therefore, the term “antibiotic” –
originally reserved for substances produced by a microorganism – has lost its
restrictive meaning.
b) Synthesis of entirely new molecules capable of acting against bacteria, fungi,
viruses, and parasites (e.g., isoniazid, ethambutol, imidazole antifungals, and
antivirals).
Antimicrobial activity is defined by the spectrum – the range of microorganisms
susceptible to the drug. Ideally, the drug should reach effective concentrations at
the site of infection without causing toxicity. Most antibiotics act on several species,
and many pathogens are susceptible to multiple antibiotics, so an individualised
choice must be made.
Classification by mechanism of action
(Commonly used classification based on chemical structure and target)
Mechanism of action Antibiotic families
Inhibition of cell wall synthesis β-lactams, fosfomycin, cyclosporine,
vancomycin, bacitracin
Disruption of cytoplasmic Polymyxins, amphotericin B, nystatin
membrane
Inhibition of protein synthesis – Tetracyclines, aminoglycosides (also
30S subunit bactericidal)
Inhibition of protein synthesis – Chloramphenicol, erythromycin, lincosamides
50S subunit
Interference with nucleic acid Rifampicin (DNA-dependent RNA polymerase),
synthesis/metabolism quinolones (DNA gyrase), metronidazole,
antivirals
Blockade of folic acid synthesis Sulfonamides, pyrimethamine, trimethoprim
Bactericidal vs. bacteriostatic
DISEASES
Summary
1. General principles of anti-infective pharmacology
2. Therapeutic strategy for infections
3. Main pharmacological groups used in clinical practice
4. Bacterial resistance and solutions
Bibliography
Goodman & Gilman’s The Pharmacological Basis of Therapeutics
Human Pharmacology, Jesús Flórez, 6th edition
Harrison’s Principles of Internal Medicine, 18th edition
1. Introduction
Modern anti-infective pharmacotherapy originates from the work of Pasteur, Koch,
and Ehrlich. The era of modern antimicrobial therapy began with the synthesis of
sulfonamides (1936); until then, metal ions were used, which were as harmful to the
host as to the pathogen. The appearance of penicillin (1941) triggered an
unstoppable expansion of effective anti-infective agents.
Infectious diseases remain one of the greatest therapeutic challenges in medicine.
Approximately 34% of deaths worldwide are due to infections, with acute
respiratory infections, tuberculosis, and diarrheal diseases topping the list.
Infection is a clinical term that implies contamination, an immune response, and
structural damage of the host caused by a pathogenic microorganism – that is,
tissue invasion by the germs themselves, their products (toxins), or both.
Symptoms result from the effects of the microorganisms on the affected organs
and from the host’s own defence mechanisms. They can be classified as
non-specific or specific.
, 2. General Principles of Anti-infective Pharmacology
The goal of antimicrobial therapy is to exploit the biochemical differences between
the infectious agent and the host. Fortunately, these differences are sufficient to
allow selective toxicity – the foundation of anti-infective pharmacology.
New anti-infective agents have been developed in two ways:
a) Chemical modification of the core structures of original antibiotics (e.g., the
many penicillin and cephalosporin derivatives). Therefore, the term “antibiotic” –
originally reserved for substances produced by a microorganism – has lost its
restrictive meaning.
b) Synthesis of entirely new molecules capable of acting against bacteria, fungi,
viruses, and parasites (e.g., isoniazid, ethambutol, imidazole antifungals, and
antivirals).
Antimicrobial activity is defined by the spectrum – the range of microorganisms
susceptible to the drug. Ideally, the drug should reach effective concentrations at
the site of infection without causing toxicity. Most antibiotics act on several species,
and many pathogens are susceptible to multiple antibiotics, so an individualised
choice must be made.
Classification by mechanism of action
(Commonly used classification based on chemical structure and target)
Mechanism of action Antibiotic families
Inhibition of cell wall synthesis β-lactams, fosfomycin, cyclosporine,
vancomycin, bacitracin
Disruption of cytoplasmic Polymyxins, amphotericin B, nystatin
membrane
Inhibition of protein synthesis – Tetracyclines, aminoglycosides (also
30S subunit bactericidal)
Inhibition of protein synthesis – Chloramphenicol, erythromycin, lincosamides
50S subunit
Interference with nucleic acid Rifampicin (DNA-dependent RNA polymerase),
synthesis/metabolism quinolones (DNA gyrase), metronidazole,
antivirals
Blockade of folic acid synthesis Sulfonamides, pyrimethamine, trimethoprim
Bactericidal vs. bacteriostatic
