Introduction

 

The field of microbiology and antbiotics can appear vast, complex and unattainable to the average undergraduate (well it does to me anyway!). As a friend said to me the other day after an antibiotics lecture, "it's like the lecturer was name-dropping famous people...only they were anitibiotics!".

 

There are a variety of ways to break down and learn the topic, so what follows is not prescriptive (if you'll excuse the pun!) but just what I find helpful. This article focuses on the antibiotic stuff that tends to get tested in exams; selecting an appropriate antibiotic for a specified infection, knowing the mode of action of an antibiotic and knowing special circumstances about certain antibiotics such as in pregnancy and interactions.

 

It is highly recommended that in addition to this article you consult the BNF before choosing an antibiotic.  The most recent editions include a section at the beginning of the 'Infections' chapter to guide you in prescribing antibiotics in various different situations.

 

The top ten rules!

 

Before we consider each antibiotic class in more detail, below are the top ten rules to remember:

 

1.    All cell wall inhibitors are Beta-lactams (penicllins, cephalosporins etc) (except vancomycin).

2.    All penicllins are water soluble (except nafcillin).

3.    All protein synthesis inhibitors are bacteriostatic, (except for the aminoglycosides)

4.    All cocci are gram positive, (except Neisseria spp.)

5.    All bacilli are gram negative, (except anthrax, tetanus, botulism and diphtheria bugs)

6.    All spirochaetes are gram negative

7.    Tetracylcines and macrolides are used for intracellular bacteria

8.    Beware pregnant women, or potentially pregnant women, and tetracylcines, aminoglycosides, fluoroquinolones and sulfonamides.

9.    Antibitoics beginning with 'C' are particularly associated with pseudomembranous colitis (aka antibiotic associated diarrhoea, C. dif overgrowth) i.e. Cephalosporins, Clindamycin and Ciprofloxacin.

10.    While the penicillins are the most famous for causing allergies, a significant proportion of people with penicillin allergies may also react to cephalosporins.  These should therefore also be avoided.

 

Classifying Antibiotics

 

There are a variety of ways to classify antibiotics:

 

  • What is its mode of action? 

              BACTERICIDAL (kills the bug)

              BACTERIOSTATIC (stops the bug multiplying)

 

    • What is its spectrum of activity? 

                  BROAD (e.g. effective a variety of gram negative and gram positive bacteria)

                  NARROW (e.g. effective only against gram negative or gram positive)?

     

      • How does it work? Inhibition of; 

                    CELL WALL synthesis

                    Bacterial PROTEIN synthesis

                    NUCLEIC ACID sythnesis

                    CELL MEMBRANE synthesis)

         

        It might seem a bit irrelevant but making sure you know which category an antibiotic falls into will be useful both for exams (as past papers show questions testing this exact topic) and for being a real doctor (as an antibiotic acting against a cell wall won't be of much use for the non-walled mycoplasma bacteria).

         

        For those of you who like mnemonics, here's a way to remember which are bacteriostatic and which are bactericidal:

                      We're ECSTaTiC about bacteriostatic

                  (Erythromycin, Clindamycin, Sulphonamides, Tetratcyclines, Trimethoprim, Chloramphenicol)

         

                      Very Finely Proficient At Cell Murder

                  (Vancomycin, fluoroquinolones, penicillins, aminoglycosides, cephalosporins, metronidazole)

         

        Antibiotic Action

        Bog standard BETA-LACTAMS

         

        Examples: Benzylpenicillin/Benpen/Penicillin G, Flucloxacillin, Amoxicillin

        Mode of Action: Bactericidal - inteferes with cell wall synthesis.

        Key side effect: hypersensitivity in 10% of the population, ranging from a rash to full blown anaphylaxis (0.5% of those classified as hypersensitive).

        Good to know: Some bacteria secrete an enzyme called beta lactamase which destroys the beta lactam ring, rendering beta-lactam antibiotics ineffective. The solution is to add clavulanic acid (a beta-lactamase inhibitor) i.e. co-amoxiclav (aka Augmentin).  Another example is the combination of piperacillin and tazobactam (aka Tazocin).

        Nice to know: Benpen is not well absorbed from the gut so it's usually given i.m. but others, such as fluclox or amoxicillin, are well absorbed and so can be given orally.

         

        Amoxicillin used for: streptococcal infections (middle ear, throat, pneumonia)

        Fluclox used for: staphylococcal infections (endocarditis, cellulitis)

        Benpen used for: meningitis, syphilis

        Tazocin: pseudomonas infections.

         

        Cool CEPHALOSPORINS

         

        Examples:

              1st generation=cephalexin

              2nd generation=cefuroxime

              3rd generation=ceftriaxone

        Mechanism of action: bactericidal, inhibit cell wall synthesis. Cephalosporins are also beta-lactams so can be degraded by beta-lactamase secreting bacteria.

        Key side effect: risk of antibiotic associated colitis.

        Good to know: The 'generation' classfication system used for cephalosporins refers to the spectrum of activity; the higher the generation, the broader the spectrum. E.g. ceftriaxone (3rd generation) is effective against more gram negative bacteria than cephalexin (1st generation).

         

        Cephalexin used for: Strep and staph infections (skin, respiratory).

        Cefuroxime used for: Bronchitis, UTI, gonorrhoea, Lyme disease.

        Ceftriaxone used for: Septicaemia, pneumonia, meningitis, surgical prophylaxis.

         

        Magical MACROLIDES

         

        Examples: Erythromycin, Clarithromycin, Azithromycin

        Mode of action: Bacteriostatic - inhibits protein synthesis

        Key side effect: GI upset

        Good to know: Take on an empty stomach

         

        Erythromycin used for: penicillin alternative, strep throat, listeria, whooping cough (bordetella).

        Clarithromycin used for: part of H. pylori treatment, strep infections.

        Azithromycin used for: STI's, respiratory tract infections.

         

        Terrific TETRACYCLINES

         

        Examples: Oxytetracycline, doxycycline

        Mode of action: Bacteriostatic - inhibits protein synthesis.

        Key side effect: Increased skin photosensitivity.

        Good to know: Contraindicated in children (it stains their teeth yellow), and in pregnancy and breast feeding (it affects bone and teeth development).

         

        Oxytetracycline: used for acne vulgaris.

        Doxycycline: used for malaria prophlyaxis and treatment, chlamydia.

         

        Quirky QUINOLONES

         

        Examples: Ciprofloxacin, Moxifloxacin

        Mode of action: Bactericidal - inhibits nucleic acid synthesis.

        Key side effects: Tendon rupture, CNS toxicity

        Good to know: Not recommended for children 

         

        Ciprofloxacin used for: anthrax, gram negative infections such as pseudomonas infection, campylobacter, neisseria

        Moxifloxacin used for: gram positive infections such as pneumococcus

         

        Amazing AMINOGLYCOSIDES

         

        Example: Gentamicin

        Mode of action; Bactericidal - inhibits protein synthesis

        Key side effect: ototoxicity, nephrotoxicity

        Good to know: Only available IV as not absorbed by gut

        Nice to know: Gentamicin is also available in topical form for ear infections and provided the eardrum is intact they are NOT ototoxic

         

        Gentamicin used for: Serious infections - septicaemia, meningitis, endocarditis

         

        Mysterious MISCELLANEOUS

         

        TRIMETHOPRIM

        Mode of action: Bacteriostatic - inhibits protein synthesis.

        Good to know: Contraindicated in pregnancy and breast feeding.  Many areas of the country now have trimethoprim-resistant UTI's.

        Used for: UTI, and with sulfamethoxazole to treat and prevent PCP in HIV positive patients (generic name = co-trimazole, brand name = Septrin)

         

        NITROFURANTOIN

        Mode of action: Bactericidal - complex mechanism including damage to DNA and vital intracellular enzymes.

        Key side effect: Stains urine dark orange/brown.

        Good to know: Can be used in pregnancy before 38 weeks, as may cause neonatal haemolysis.  Do not use in combination with quinolones as they are mutually antagonistic.

        Used for: UTI treatment and prophylaxis.

         

        CLINDAMYCIN

        Mode of action:Bacteriostatic - inhibits protein synthesis.

        Key side effect: Antibiotic associated colitis. 

        Used for: Osteomyelitis, intrabdominal sepsis, cellulitis, acne vulgaris (in combination with benzoyl peroxide).

         

        METRONIDAZOLE

        Mode of action: Bactericidal - inhibits nucleic acid synthesis.

        Key side effect: Metallic taste in mouth, avoid in pregnancy. 

        Good to know: narrow spectrum - active only against anaerobes and protozoa. 

        Used for: C. difficile, Trichomonas vaginalis, Giardia lambia, surgical prophylaxis, aspiration pneumonia.

         

        VANCOMYCIN

        Mode of action: Bactericidal - inhibits cell wall synthesis, only effective against gram positive infections

        Key side effect: Ototoxic, nephrotoxic 

        Used for: C. difficile, treatment & prophylaxis of endocarditis and other serious strep infections, MRSA infection.

         

        CHLORAMPHENICOL

        Mode of action: Bacteriostatic - inhibits nucleic acid synthesis.

        Key side effects: Myelosupression therefore rarely used systemically, contraindicated in pregnancy and breast feeding. 

        Used for:  Topically - conjunctivitis, ear infections; IV - serious systemic infections (such as typhoid and H. influenzae).   

         

        Antibiotics Summary

        References:

        1. Antibiotics Lecture.  Google Docs: unknown contributor.  Available from http://docs.google.com/present/view?id=dd87tgxw_30d6rvgtg6 [Accessed 18th February 2011].
        2. Fishman J, Fishman L. MCQs in Applied Basic Sciences for Medical Students Volume 2.  Pastest; 2006.
        3. Longmore M, Wilkinson I, Turmezei T, Cheung CK.  Oxford Handbook of Clinical Medicine.  7th ed.  Oxford University Press; 2007.
        4. Clinical Antibiotic Tutorial Site.  Molson Informatics Project; 1999.  Available from http://sprojects.mmi.mcgill.ca/antibiotic/ [Accessed 18th February 2011].
        5. British Medical Association and the Royal Pharmaceutical Society of Great Britain.  British National Formulary.  60th Ed.  UK: BMJ Publishing Group; 2010.  (Can also be accessed via free registration here).
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