All About Bacteria and Antibiotics

Antibiotics

• Antibiotics are drugs produced by a living being or a synthetic derivative of it
• They kill or stop the growth of another microorganism at low concentrations

Bacteria Characteristics

• Bacteria can be classified based on several characteristics
• Some bacteria have flagella, while others do not
• Bacteria can be motile or non-motile
• Bacteria can be saprophytes and are symbiotic
• Nutrition is a key aspect of bacteria
• Some bacteria are gram-negative
• Other bacteria are gram-positive according to the Gram stain test
• Reproduction is asexual
• Some are aerobes
• Some are anaerobes
• Bacteria shapes include cocci, bacilli, and spirilla

Bacterial Diseases

• Tetanus (Clostridium tetani), cholera (Vibrio Cholerae), and syphilis (Treponema pallidum) are bacterial diseases
• Other bacterial diseases: throat infection (Streptococcus pneumoniae), botulism (Clostridium botulinum), anthrax (Bacillus anthracis), pneumonia, and ear infections (Staphylococcus aureus)
• The plague is caused by Yersinia enterocolitica

Antibiotic Requirements

• Antibiotics should have specificity. This refers to the spectrum of antimicrobial activity
• It is defined by its ability to bind to a specific site on the bacteria
• Antibiotics needing "in vivo" efficacy: it must be bacteriostatic or bactericidal in vivo, meaning its action should not be reversed in the body
• Antibiotics need selective toxicity or be toxic to the microorganism but harmless to the host in clinical settings

Historical Background

• Paul Ehrlich created the first synthetic chemical compound (Salvarsan) in 1908
• Salvarsan could cure the infection syphilis (Treponema pallidum)

Origin of Antibiotics

• The discovery of the first antibiotic, penicillin, was a game-changer for infectious diseases. This included tuberculosis, syphilis, cholera, and pneumonia

Further on the Origin of Antibiotics

• The Penicillium notatum fungus inhibits the growth of Staphylococcus aureus

Classification of Antibiotics

• Antibiotics are classified by: Reversibility of effect, mechanism of action, toxicity, spectrum of action, and chemical structure

Reversibility of Effect

• Bacteriostatic antibiotics are reversible or primarily so, including beta-lactams (penicillins and cephalosporins) and aminoglycosides (streptomycin)
• Bactericidal antibiotics are irreversible or primarily so, including tetracyclines and chloramphenicol

Spectrum of Action

• Broad-spectrum antibiotics: Active against G+ and G- bacteria, including chloramphenicol and tetracyclines, as well as broad-spectrum penicillins
• Intermediate spectrum antibiotics: Active against G+ bacteria, including Penicillin G and Oxacillin
• Narrow-spectrum antibiotics: Active against Cocci G+ and bacilli G-, including Vancomycin and Polymyxin

Mechanism of Action

• Antibiotics work by: inhibiting cell wall synthesis, inhibiting nucleic acid synthesis, and inhibiting protein synthesis

Synthesis of Proteins

• Subunit 30S: Aminoglycosides (streptomycin) and tetracyclines
• Subunit 50S: Chloramphenicol and macrolides (erythromycin)

Type of Resistance

• Antibiotic resistance is the ability of a strain to resist the action of a given concentration of an antibiotic in a culture medium
• This is caused by PBP modifications

Antibiogram by Diffusion (Kirby-Bauer Technique)

• It is the most widely used method, and is practical and easy to implement
• A large number of antibiotics can be analyzed at the same time and under the same conditions
• It delivers a qualitative result; it determines if the bacteria are considered sensitive or resistant

Outcome

• Resistant bacteria: there is no halo of inhibition around the antibiotic disc
• Sensitive bacteria: there is a halo of inhibition around the antibiotic disc

Chemical Structure

• Antibiotics that have a chemical structure: tetracyclines, aminoglycosides, chloramphenicol macrolides, quinolones, and beta-lactams

Penicillins

• Includes: a side chain, a thiazolidine ring, and a β-lactam ring
• Types: PNC G potassium and Amoxicillin

Quinolones

• Characteristics: a double ring with N in position 1, a carbonyl in 4, and a carboxyl attached to carbon in the 3 position of the first ring

Aminoglycosides

• Dr. Selman Waksman studied Streptomyces griseus in 1944
• With this fungus, he created the first aminoglycoside in history, Streptomycin
• Streptidine: central core of Streptomycin

Chloramphenicol

• Contains a nitrobenzene portion derived from dichloroacetic acid
• Use: Antibiotic ophthalmic, to be used externally to affected area
• IV, adults: 500mg of a solution at 10-20% every 6 hours, until the fever disappears

Macrolides

• Macrolides are named because they contain a lactone ring of many members, to which one or more deoxy sugars are attached
• Erythromycin MK - MK: Bottle for 60ml of powder for suspension of 200mg/5ml
• Box for 36 tablets of 600mg
• Children: 50mg/kg/day divided into 3 doses, adults: 1.5 to 2g divided into 3 doses

Antibiotic Classes

• Natural Penicillins: Penicillin G, Procaine PCN G, and Penicillin Benzathine
• Aminopenicillins: Ampicillin, Amoxicillin, Amoxicillin-clavulanate, and Sulbactam-ampicillin
• Penicillinase-resistant Penicillins: Oxacillin, Nafcillin, and Cloxacillin/dicloxacillin
• Carboxi/ureido Penicillins: Ticarcillin-clavulanate and Piperacillin-Tazobactam

Mechanism of Action pt 2

• Penicillins bind to and inhibit penicillin-binding proteins.
• A strong bond with a PBP-1 causes rapid bacterial eradication in gram-positives and anaerobes
• Penicillins require bacterial growth for bactericidal action and are antagonized by bacteriostatic antibiotics

Coverage

• Penicillins have different ranges of species coverage
• Susceptible: S. pyogenes; S. pneumoniae sensitive penicillin, oral flora
• Broad Coverage: E. Coli, Salmonella Spp, Enterococci sensitives, H Influenzae
• MSSA is indicated for: Cellulitis caused by S. aureus o pyogenes, completion of cellulitis therapy
• Combinations against P. aeruginosa, MSSA: Infections, intra-abdominal infections, prostatitis
• Amoxicillin is good for otitis media and sinusitis

Other Information

• Probenecid delays penicillin excretion and it penetrates cavities but with inflamation
• Some penicillins are excreted by the liver and aren't effective against bacteremia S. Aureus
• Resistance most effective against B-lactamase Gram-negatives

Composition of Viruses

• Viruses do not possess organelles
• Contain: enzymes, genome, capsomeres, capsid, envelope, and peplos or peplomeres
• The union of the capsid with the nucleus generates the nucleocapsid

Classification of Viruses

• Viruses are classified by: symmetry, envelope (enveloped or naked), genome, and tropism

Antiviral Therapy

• The goal is to inhibit or eliminate the activity of a virus
• Accomplish the goal while also having minimal effects on the host
• This has a low therapeutic index or significant toxicity for humans

More Notes on Antiviral Therapy

• Antivirals inhibit specific steps of replication
• They are not effective against latent viruses
• They have a restricted spectrum and are virostatic

Mechanism of Action pt 3

• Antivirals work by: interfering with the virus's attachment to the cell membrane and its entry inside
• Antivirals also block uncoating, inhibit nucleic acid synthesis, or block viral assembly and release
• Antivirals can target herpesvirus, papillomavirus, human immunodeficiency virus, and influenza A and B
• Target diseases like the (flu)

Mechanism of Resistance

• The development of nucleotide mutations can lead to resistance, and the strains can develop cross-resistance

Viral Class

• Can be: Double stranded DNA viruses(HSV-1 and 2, and CMV), Single stranded RNA viruses (hepatitis C, VIH)
• Con envoltura has HIV-1 and 2 while Desnudo has Papovaviridae and Adenoviridae

Classification

• Can be class III to VI
• Icosahedral vs Helical
• Naked vs Enveloped

Classification of antivirals

• Inhibitors of RNA and DNA synthesis:
  • PURINE analogs: ACYCLOVIR, GANCICLOVIR, VALACICLOVIR, PENCYCLOVIR, and KAMCICLOVIR
    • RIBAVIRINA
  • PIRIMIDINE analogs
    • IDOXURIDINE, TRIFLURIDINE
• Inhibitors of reverse transcriptase (antiretroviral)
  • ZIDOVUDINE, DIDANOSINE, and ZALCITABINE
• Other drugs
  • INDINAVIR, AMANTADINA, and RIMANTADINE
    • INTERFERON