Understanding antibiotics

Antibiotics are drugs that kill or slow the growth of certain types of bacteria, and are considered broadly as antimicrobials. Antimicrobials also include antivirals, antifungals, and antiparasitic drugs. We derive antibiotics from microorganisms, like bacteria or fungi.

We use antibiotics to treat bacterial infections. Single-cell organisms are normal and natural, but can overgrow, causing infections, with unpleasant signs and symptoms in humans.

A microbe that can cause infection, and actively tries to do so at every opportunity, is called a pathogen. Many bacteria are harmless, but different strains of the same species can prove more virulent and troublesome than others. Strain is everything. 

Ways in which antibiotics work

  • Bactericidal (kills)
  • Bacteriostatic (stops multiplying)

Antibiotics may interrupt the life process of a bacteria, like disrupting its ability to use glucose for energy or to build its cell wall. If this process is interrupted, it kills the bacteria and is bactericidal. Broad-spectrum antibiotics work against a wide range of bacteria, while narrow-spectrum antibiotics only work on a few.

Antibiotic resistance

Antibiotic resistance occurs when a bacteria modifies itself over time to avoid being killed by certain antibiotics. The genetic code for this resistance gets passed around, and thus a microbe can be ‘born’ naturally resistant to some bacteria.

Antibiotic resistance is occurring at a rapid pace with overuse of antibiotics by the population, driven by doctor prescribing. This is a very serious problem, since once we’ve used up all of our antibiotic options, we can’t kill the bacteria and can get very sick or have ongoing infections.

Classes of antibiotics

There are several major classes of antibiotics based on their chemical structure.

  • Beta-Lactams (includes sub-classes of penicillins and cephalosporins)
  • Macrolides
  • Fluoroquinolones
  • Tetracyclines
  • Aminoglycosides

Penicillins

  • Oldest antibiotics
  • Bicyclic penam compounds, share chemical structure with cephalosporins
  • Usually bactericidal (kills) – inhibit formation of bacterial cell wall
  • Treats skin infections, dental infections, ear infections, respiratory tract infections, urinary tract infectionsgonorrhoea
  • Side-effects include diarrhoea, nausea, vomiting, upset digestion
  • Generally considered very safe with minimal toxicity
  • Rarely may cause immediate or delayed allergic reaction with skin rash, fever, anaphylaxis, severe hypersensitivity
  • Pregnancy category B

There are four types of penicillins:

  1. Natural penicillins – active against gram-positive streptococci, staphylococci, some gram-negative bacteria like meningococcus
  2. Penicillinse-resistant penicillins (methicillin, oxacillin) – active against beta-lactamase-producing bacteria, inactivates most penicillin antibiotics
  3. Aminopenicillins (ampicillin, amoxicillin) – active agaisnt a wider range of bacteria, better oral absorption than other penicillins
  4. Extended-spectrum penicillins (mezlocillin, piperacillin, ticarcillin)
Cephalosporins
  • Identical mechanism of action to penicillins, but chemical structure differs
  • Has beta-lactam ring that inhibits synthesis of bacterial cell wall, so bactericidal (kills)
  • Derived from cephalosporin C, produced by Cephalosporium acremonium
  • Treats pneumonia, strep throat, staph infections, tonsillitis, bronchitis, ear infections, skin infections, gonorrhoea, UTIs, bone infections
  • May be used as surgical prophylaxis to prevent infections
  • Very safe
  • Few side-effects, but may include diarrhoea, nausea, stomach cramps, digestive upset
  • Those allergic to penicillins may also have reactivity with cephalosporins and are therefore contraindicated in those with allergic reactions to penicillins
  • Pregnancy category B

Cephalosporins are classified by the generation they are in, with each newer generation being broader spectrum than the previous one. There are currently four generations.

#1 First generation cephalosporins

Similar to each other in spectrum, good gram-positive coverage but poor gram-negative coverage.
+ Cepahlothin
+ Cefazolin
+ Cephapirin
+ Cephalexin
+ Cefadroxil

#2 Second generation cephalosporins

Extended gram-negative spectrum plus gram-positive coverage of the first generation.
+ Cefaclor
+ Cefamandole
+ Cefonicid
+ Ceforanide
+ Cefuroxime

#3 Third generation cephalosporins

Greater gram-negative activity, but some members have lowered action against gram-positive bacteria. Can be expensive.
+ Cefcapene
+ Cefditoren
+ Cefetamet
+ Cefixime
+ Cefmenoxime
+ Cefodizime
+ Cefoperazone
+ Cefotaxime
+ Cefpimizole
+ Cefpodoxime
+ Ceftibuten
+ Ceftriaxone

#4 Fourth generation cephalosporins

Extended spectrum antibiotics with gram-positive action more like the first generation, with greater resistance to beta-lactamases. May cross blood-brain barrier, may work in meningitis.
+ Cefclidine
+ Cefepime
+ Cefluprenam
+ Cefozopran
+ Cefpirome
+ Cefquinome

Fluoroquinolones

  • Newest class of antibiotics
  • Generic name often includes ‘floxacin’
  • Synthetic (not bacterially derived)
  • Early forms named quinolones, but poorly absorbed so often used for UTIs
  • New forms of fluroquinolones very well absorbed orally, can be used intravenously and orally
  • Used to treat UTIs, skin infections, respiratory tract infections (sinusitis, pneumonia, bronchitis), lung infections like in cystic fibrosis
  • Bactericidal (kils) by inhibiting an enzyme DNA gyrase
  • Generally well tolerated and safe
  • Side-effects include nausea, vomiting, diarrhoea, abdominal pain
  • Uncommonly may cause headache, confusion, dizziness, tremor, phototoxicity, tendon rupture, convulsions

Types of fluoroquinolones include:

+ Clinafloxacin
+ Ciprofloxacin
+ Gatifloxacin
+ Levofloxacin
+ Lomefloxacin
+ Ofloxacin
+ Sparfloxacin
+ Trovafloxacin

Tetracyclines

  • Old class of antibiotics
  • Derived from Streptomyces bacteria
  • Bacteriostatic (hinders multiplying) agents that inhibit bacterial protein synthesis via interaction with the 30S subunit of bacterial ribosome
  • Broad action – works on spirochetes, atypical bacteria, rickettsia, amebic parasites
  • Often used to treat acne and rosacea, peptic ulcer disease, cholera, respiratory tract infections, Rocky Mountain spotted fever, Lyme disease, typhus
  • Common side-effects include stomach cramps, diarrhoea, nausea, vomiting, oesophageal ulcers, sore mouth, sore tongue, skin photosensitivity
  • May cause allergy
  • Do not use in children under eight, and specifically during periods of tooth development, may cause grey/yellow discolouration of actively forming teeth and deposition in growing bones
  • Pregnancy catergory D

Tetracyclines include:

+ Doxycycline
+ Minocycline
+ Oxytetracycline
+ Tetracycline

Macrolides

  • Derived from Streptomyces bacteria
  • Mainly bacteriostatic (hinders multiplying), targets ribosomes and prevents protein production
  • Newer members good for lung penetration
  • Treats respiratory tract infections, pharyngitis, sinusitis, bronchitis, genital infections, digestive tract infections, skin infections
  • Side-effects may include nausea, vomiting, abdominal discomfort and diarrhoea
  • Allergic reaction possible
  • Adverse effects possible including stomach irritation and thrombophlebitis, and in liver dysfunction
  • Pregnancy category B for azithromycin, erythromycin
  • Pregnancy category C for clarithromycin, dirithromycin, troleandomycin

Macrolide antibiotics include:

+ Azithromycin
+ Clarithromycin
+ Dirithromycin
+ Erythromycin
+ Roxithromycin
+ Troleandomycin

Aminoglycosides

  • Derived from species of Streptomyces
  • Bactericidal (kills) by binding to the 30S subunit of the bacterial ribosome, blocks protein synthesis
  • Treats infections by gram-negative bacteria
  • May be used in conjunction with penicillins or cephalosporins for better coverage
  • Bacteria may become resistant
  • Broken down quickly in stomach so must be injected
  • Short treatment periods
  • Side-effects may include damage to hearing and ear (permanent), kidney damage

Aminoglycosides include:

+ Amikacin
+ Gentamicin
+ Kanamycin
+ Neomycin
+ Streptomycin
+ Tobramycin



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