Antibiotics Study Guide

Introduction

Bacterial Structure

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 Bacteria Outer Layers

Gram Positive Cell Gram Negative

Surface Cell Surface

Cell Wall

Cell Wall

• Cell wall classification by gram-stain

• Gram positive-thicker cell wall
• Gram negative-thinner cell wall
• Classification by shape
– Spherical-Cocci
– Cylindrical-Rods/bacilli
• Combined Classification
– Gram positive cocci/rod
– Gram negative rod/cocci
Gram Positive Cocci Gram Negative Rod/Bacteria

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 Gram-Positives Gram Stain Gram-negatives

Gram-positive cocci in clusters (Staphylococci) Gram-negative rods

Gram-positive rods

Gram-positive Cocci in
chains (Streptococci) Gram-negative cocci

Antibiotics

What are Antibiotics?

These are molecules that kill or inhibit the growth of bacteria

How do we classify antibiotics?

This is based on the relatedness of the molecules and fortunately this also
predicts how each member of a class of antibiotics will work on bacteria as well
as how the body handles such an antibiotic.

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Classification of Antibiotics

Cell Wall Active Antibiotics

1 Beta Lactams
o All antibiotics in this group are based on addition a beta lactam ring hence
the name

o Mode of Action: All beta lactams destroy bacteria cell wall leading to
bacterial death. Hence the term bactericidal.

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 Antibiotics Against Bacterial Cell Wall

Cell wall

Osmotic
Pressure

Cell Membrane

Antibiotic against cell wall

Osmotic
Pressure
Cell membrane
Rapture

o Beta lactams can be further be subdivided into;

o Penicillins
§ Penicillin V (Pen V)
§ Benzylpenicillin
§ Amoxicillin (Also co-amoxiclav/Augmentin)
§ Piperacillin ( piperacillin with tazobactam/ Tazocin)
§ Flucloxacillin

o Cephalosporins
§ Cefalexin
§ Cefuroxime
§ Cefotaxime
§ Ceftriaxone
§ Ceftazidime

Narrow spectrum
These beta lactams destroy the least group of bacteria for example streptococci
only or staphylococcus only. Penicillin V, Benzylpenicillin and Flucloxacillin
have the narrowest spectrum of activity. They are less destructive to the innocent
and protective bacteria.

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Broad Spectrum
These beta lactams apart from destroying the infecting bacteria also destroy to
varying extent innocent and protective bacteria. Pathological bacteria such as
Clostridium difficile (Cdiff) can then take over and cause disease. Bacteria with
resistance will survive and outgrow the good bacteria. In this way bacterial
resistance is promoted.
Amoxicillin is the least broad spectrum but this in markedly increased when it is
in the form of co-amoxiclav.
The rest of the beta lactams have broad spectrum of activity with the highest
activity demonstrated by carbapenems.

Beta lactams are most commonly used group of antibiotics

Beta Lactam Spectrum of Activity Table

Antibiotic Streptococci Staphylococcus Gram Pseudomonas

aureus negatives
(eg E.
Penicillins coli)
Penicillin V √ x x x
Benzylpenicillin √ X X X
Amoxicillin √ X x/√ X
Co-amoxiclav √ √ √ X
Flucloxacillin √ √ X
Cephalosporins

Ceftriaxone √ √ √ X

√ Active
X Not active
X/√ Limited activity

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 Penicillin
Clostridium Streptococcus

Bacteroides Enterococcus

Staphylococcus
Pseudomonas

Haemophilus E.coli

Neisseria Other coliforms

Amoxicillin
Clostridium Streptococcus

Bacteroides Enterococcus

Staphylococcus
Pseudomonas

Haemophilus E.coli

Neisseria Other coliforms

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 Amoxicillin-clavulanate (Co-amoxiclav)
Clostridium Streptococcus

Bacteroides Enterococcus

Staphylococcus
Pseudomonas

Haemophilus E.coli

Neisseria Other coliforms

Ceftriaxone
Clostridium Streptococcus

Bacteroides Enterococcus

Staphylococcus
Pseudomonas

Haemophilus E.coli

Neisseria Other coliforms

Common Problems
• Allergy. There is cross reaction among the subgroups
o ~10-15% of patients who react to penicillin will react to
cephalosporins
o Patients who have simple skin reaction to penicillin can be tried on
a cephalosporin or a carbapenem

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 o Patients who have complicated reaction to penicillin such as
anaphylaxis should NEVER be given another beta lactam
antibiotic (e.g. cephalosporins)

Resistance to Beta Lactams

• Mainly due to enzymes produced by bacteria that destroy the beta lactam
ring. The enzymes are called beta lactamases.
• Simple beta lactamases only destroy limited number of antibiotics such as
benzylpenicillin, amoxicillin and flucloxacillin.
• As beta lactamases are modified they become more active against a wider
range of beta lactams including cephalosporins.
• Extended spectrum beta lactamases (ESBLs) are beta lactamases
which are so active that they destroy most beta lactam antibiotics

Macrolides
o All antibiotics in this group are based on a common molecular
structure
o Mode of Action: Protein synthesis prevention leading to failure to
multiply but not death of the bacteria. They are thus bacteriostatic.
The host immune system is required to kill off the bacteria.

o Examples
• Erythromycin
• Clarithromycin
• Azithromycin

Macrolides are especially useful in atypical infections as well as alternatives in

penicillin allergy for less severe infections caused by streptococci

Macrolides Spectrum of Activity Table

Antibiotic Streptococci Staphylococcus Gram Legionella Chlamydia,

aureus negatives Mycoplasma
(eg E.
coli)
Erythromycin √ x/√ x √ √
Clarithromycin √ X/√ X √ √
Azithromycin √ X/√ x √ √
√ Active

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 X Not active
X/√ Limited activity

Common problem
• Gastric irritation leading to diarrhoea especially for erythromycin

Tetracyclines

o Mode of Action: Protein synthesis prevention leading to failure

to multiply but not death of the bacteria. They are thus
bacteriostatic. The host immune system is required to kill off
and clear the bacteria.

Key examples:

• Tetracycline
• Doxycycline

Tetracyclines are especially useful in atypical infections as well as alternatives in

penicillin allergy for less severe infections caused by streptococci

Tetracyclines Spectrum of Activity Table

Antibiotic Streptococci Staphylococcus Gram Legionella Chlamydia,

aureus negatives Mycoplasma
(eg E.
coli)
Tetracycline √ x/√ x √ √
Doxycycline √ X/√ X √ √
√ Active
X Not active
X/√ Limited activity

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Quinolones/Fluoroquinolones

Fluoroquinolones Spectrum of Activity Table

Antibiotic Streptococci Staphylococcus Gram Pseudomonas
aureus negatives
(eg E.
coli)

Ciprofloxacin X √ √ √

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OTHER IMPORTANT ANTIBIOTICS

Antibiotic Class/Action Clinical Use

Trimethoprim Dihyrofolate reductase inhibitor. Urinary tract infection
Folic acid formation inhibition,
bactericidal
Metronidazole A nitroimidazole. Cytotoxic by Anaerobic infections
production of free radicals in the and some protozoa
bacterial cell. Bactericidal.
Nitrofurantoin Nitrofuran. Mechanism not clear UTI caused by both
but does cause DNA damage and Gram negative and
inhibit other bacterial functions positive bacteria

First line for UTI

Common Clinical Syndromes and Appropriate Antibiotics

Clinical Common Causes Possible Appropriate

Syndrome Antibiotics. For UHCW adult
antibiotic guidelines go to
http://webapps/elibrary/
Community Streptococcus Benzylpenicillin/amoxicillin
Acquired pneumoniae, Legionella Clarithromycin/erythromycin/
Pneumonia (CAP) pneumophila, doxycycline
Mycoplasma pneumoniae,
Chlamydia
Infective Streptococcal Co-amoxiclav, doxycycline (No
exacerbation of pneumoniae, cover against Pseudomonas)
COPD Haemophilus influenzae,
Moraxella catarrhalis For Pseudomonas, ciprofloxacin is
Pseudomonas appropriate
Meningitis Streptococcus Benzylpenicillin, Ceftriaxone
pneumoniae, Neisseria
meningitidis (in neonates
Group B streptococcus is
important.
Skin and soft Staphylococcus aureus, Flucloxacillin/Clindamycin
tissue infections beta haemolytic
streptococci
UTI Gram negative bacilli – Trimethoprim, Nitrofurantoin
especially Escherichia coli
Urosepsis/Pyelone Gram negative bacilli Co-amoxiclav

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phritis (coliforms), Gram positive
cocci
Intra-abdominal Gram negative bacilli, Co-amoxiclav
sepsis anaerobes, Gram positive
cocci
Bone and native Staphylococcus aureus, Flucloxacillin, Co-amoxiclav
joint infection beta haemolytic
streptococci

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