3. ANTIBIOTICS
OVERVIEW
ā£ Without functioningĀ antibiotics,Ā common infections such
as cellulitis, chest infections and ear infections have the
potential to be much more serious
ā£ Learning Goal
ā£ To cover the main classes of antibiotics, giving
common examples of drugs within each class, and their
indications, mechanisms, common side effects,
interactions and cautions for use
4. ANTIBIOTICS
PENICILLINS
ā£ Mechanism
ā£ Penicillins competitively inhibit penicillin-binding proteins such as the
enzymeĀ DD-transpeptidase
ā£ Which catalyses the cross-linking of peptidoglycans in bacterial cell
walls
ā£ Inhibition of this process weakens the cell walls, allowing an influx of
water into the cell, which leads to cell swelling and thenĀ cell lysis
ā£ These antibiotics have aĀ Ć-lactamĀ ring in their chemical structure
ā£ Some bacteria can produce theĀ Ć-lactamaseĀ enzyme, which breaks down the
Ć-lactam ring in the penicillin,Ā resulting in resistance
8. ANTIBIOTICS
PENICILLINS
ā£ Common Side Effects
ā£ GI upset, including antibiotic-associatedĀ C. difficile
infection
ā£ A degree ofĀ allergyĀ to penicillin is very common,
affecting up to 10% of the population
9. ANTIBIOTICS
CEPHALOSPORINS AND CARBAPENEMS
ā£ These antibiotics are grouped together due to their similar structural
properties and mechanisms of action
ā£ Mechanism
ā£ Like penicillins, these antibiotics get their antimicrobial effect from
the presence of aĀ Ć-lactamĀ ring in their structure; they inhibit the
cross-linking of peptidoglycans in bacterial cell walls
ā£ Examples
ā£ Cephalosporins ā Cefotaxime, Cetriaxone, Cefuroxime
ā£ Carbapenems ā Meropenem is the major example
10. ANTIBIOTICS
CEPHALOSPORINS AND CARBAPENEMS
ā£ Coverage
ā£ Cephalosporins and Carbapenems are broad-
spectrum, but as they have evolved, cephalosporins
have become more suited for use againstĀ Gram-
negativeĀ bacteria
ā£ As both these types of antibiotic have a high chance of
leading toĀ bacterial resistance,Ā they are usually
reserved for very serious infections
11. ANTIBIOTICS
CEPHALOSPORINS AND CARBAPENEMS
ā£ Common Side Effects
ā£ Simple GI upset
ā£ Antibiotic-associatedĀ colitis
ā£ Hypersensitivity reactions
ā£ As their structure and mechanism is similar to penicillin, there may beĀ cross-
reactivityĀ in penicillin-allergic patients, and so caution should be taken
ā£ Cautions/Contraindications
ā£ Use with extreme caution in those with penicillin allergy
ā£ Use with caution in those at high risk ofĀ C. difficile
ā£ Use with caution in renal impairment
12. ANTIBIOTICS
GLYCOPEPTIDES
ā£ Mechanism
ā£ Similar to but distinct from penicillins, glycopeptides prevent
the formation of cross links in the peptidoglycan cell wall
ā£ While penicillinsĀ irreversibly and competitively inhibit DD-
transpeptidase, glycopeptides bind to theĀ proteins in the cell
wallĀ themselves to prevent DD-transpeptidase from binding
ā£ Resistance can occur when the last amino acid residue on the
cross link changes from alanine toĀ D-lactate
14. ANTIBIOTICS
GLYCOPEPTIDES
ā£ Examples and coverage
ā£ Vancomycin
ā£ orally forĀ severeĀ C. difficileĀ infections
ā£ intravenously for severe soft tissue/bone/joint infections as
gram-positive cover (MRSA)
ā£ Teicoplanin
ā£ used IV for gram-positive cover, either as treatment or
commonly as surgicalĀ prophylaxisĀ in penicillin allergic patients
15. ANTIBIOTICS
GLYCOPEPTIDES
ā£ Cautions
ā£ Vancomycin is an antibiotic that accumulates in renal
disease, and so dosing is done according to the
patientās weight andĀ creatinine clearanceĀ (not eGFR)
ā£ Monitoring
ā£ Pre-doseĀ (trough)Ā levelsĀ are taken before the third or
fourth dose, and the dosing regimen is adjusted
accordingly depending on the serum level
16. ANTIBIOTICS
AMINOGLYCOSIDES
ā£ Mechanism
ā£ Inhibit bacterial protein synthesis by binding to theĀ 30S
subunitĀ of the ribosome
ā£ Examples
ā£ GentamicinĀ is the most commonly used example, but
others include neomycin and tobramycin
17. ANTIBIOTICS
AMINOGLYCOSIDES
ā£ Coverage
ā£ Aminoglycosides tend to be used for severe infections, especially those caused
byĀ Pseudomonas
ā£ They are also often combined with penicillins or metronidazole where the causative
organism of severe infection is unknown
ā£ Common Side Effects
ā£ Nephrotoxicity
ā£ especially if combined with other nephrotoxic drugs
ā£ Ototoxicity
ā£ usually only if used long-term - symptoms can include tinnitus, hearing loss or
vertigo, and these may be irreversible
18. ANTIBIOTICS
AMINOGLYCOSIDES
ā£ Interactions
ā£ Loop diuretics such as Furosemide ā high risk of ototoxicity
ā£ Vancomycin ā risk of nephrotoxicity and ototoxicity
ā£ Monitoring
ā£ AĀ plasma drug concentrationĀ level must be taken 18 ā 24
hours after the first dose
ā£ Itās also important to monitor the renal function regularly
19. ANTIBIOTICS
MACROLIDES
ā£ Mechanism
ā£ Inhibit bacterial protein synthesis by binding to theĀ 50S
subunitĀ of the ribosome, preventing ribosomal
translocation and therefore protein elongation
ā£ Examples
ā£ Clarithromycin,Ā Erythromycin, Azithromycin
20. ANTIBIOTICS
MACROLIDES
ā£ Coverage
ā£ Macrolides are usually used for respiratory, skin and soft tissue infections in those
with a penicillin allergy
ā£ They are also used inĀ H. pyloriĀ eradication (along with a PPI + amoxicillin or
metronidazole ā this is known as ātriple therapyā)
ā£ Common Side Effects
ā£ GI irritation/upset common if given orally
ā£ Macrolides are pro-kinetic and can be used therapeutically inĀ gastroparesis
ā£ Prolonged QT interval
ā£ Ototoxicity
21. ANTIBIOTICS
MACROLIDES
ā£ Interactions
ā£ Macrolides areĀ CYP450 inhibitorsĀ (except Azithromycin) so increase the
concentration of drugs metabolized by CYP450 enzymes
ā£ eg. this increases the bleeding risk with warfarin
ā£ CYP450 inhibitors in turn decrease the efficacy of macrolides
ā£ Macrolides should also not be given with other drugs that prolong the
QT interval
ā£ Cautions/Contraindications
ā£ Use with caution in severe renal or hepatic impairment
22. ANTIBIOTICS
QUINOLONES
ā£ Mechanism
ā£ Inhibit bacterial DNA duplication through inhibition
ofĀ topoisomerases,Ā which interfere with DNA
unwinding and therefore transcription and translation
ā£ Examples
ā£ CiprofloxacinĀ is the most commonly used quinolone,
but others include levofloxacin and ofloxacin
23. ANTIBIOTICS
QUINOLONES
ā£ Coverage
ā£ The quinolone group of antibiotics are used mainly for
Gram-negative infections
ā£ They should be reserved for 2ndĀ or 3rd-line treatment
only as there is increasingĀ resistanceĀ to these antibiotics,
and they also commonly causeĀ C. difficile
ā£ NOTE: Ciprofloxacin is the only antibiotic available in oral
form which is active againstĀ Pseudomonas aeruginosa
24. ANTIBIOTICS
QUINOLONES
ā£ Key Side Effects
ā£ GI upset
ā£ Prolonged QT interval
ā£ High risk ofĀ C. difficile
ā£ Interactions
ā£ Should not be used with other drugs that prolong the QT interval
ā£ Administration
ā£ Equal bioavailability oral and IV, so only needed intravenously in those
who cannot swallow or are NPO
25. ANTIBIOTICS
METRONIDAZOLE
ā£ Mechanism
ā£ Once in itsĀ reducedĀ form, metronidazole inhibits bacterialĀ DNA synthesis
ā£ As metronidazole is only reduced in this way in anaerobic bacteria, it is a
specific antibiotic for anaerobic infections
ā£ Coverage
ā£ Used against anaerobic bacteria includingĀ C. difficile, oral infections and
intra-abdominal or pelvic infections
ā£ It is also active againstĀ protozoalĀ infections e.g. giardiasis, dysentery
andĀ trichomonas vaginalis
26. ANTIBIOTICS
METRONIDAZOLE
ā£ Common Side Effects
ā£ GI upset
ā£ Hypersensitivity reactions
ā£ Peripheral and opticĀ neuropathyĀ (high dose/long term use only)
ā£ Seizures andĀ encephalopathyĀ (high dose/long term use only)
ā£ Interactions
ā£ Inhibits CYP450Ā so increases the effect of drugs metabolized by these
enzymes, and in turn these drugs will decrease the efficacy of metronidazole
ā£ Lithium ā metronidazole increases the risk of lithium toxicity
27. ANTIBIOTICS
METRONIDAZOLE
ā£ Cautions/Contraindications
ā£ Alcohol must not be drunk while on metronidazole and
for ~48 hours after the end of the course
ā£ Metronidazole interferes withĀ alcohol metabolismĀ and
gives severe side effects as a result
ā£ Use with caution in severe liver disease
28. ANTIBIOTICS
NITROFURANTOIN
ā£ Mechanism
ā£ Damages bacterial DNA causing cell death
ā£ Coverage
ā£ Used to treat UTIs caused by both Gram-positive and Gram-
negative bacteria
ā£ Common Side Effects
ā£ GI upset
ā£ Hypersensitivity reactions
29. ANTIBIOTICS
NITROFURANTOIN
ā£ Cautions/Contraindications
ā£ Contraindicated inĀ pregnant womenĀ towards term and babies in
the first 3 months of life
ā£ Contraindicated in renal impairment
ā£ Caution if using as long-term prevention as higher risk of side
effects
ā£ Monitoring
ā£ If using as long-term prophylaxis for UTIs, monitor the patient for
side effects such as breathlessness and pins and needles
30. ANTIBIOTICS
TRIMETHOPRIM
ā£ Mechanism
ā£ Inhibits bacterialĀ folate synthesisĀ through inhibition of dihydrofolate
reductase
ā£ Coverage
ā£ Similar to Nitrofurantoin ā used to treat UTIs caused by both Gram-positive
and Gram-negative bacteria, although resistance is increasing and
therefore it is less commonly used now as the first-line treatment forĀ UTI
ā£ Also used as treatment or prophyalxis forĀ Pneumocystis pneumoniaĀ asĀ Co-
TrimoxazoleĀ (Trimethoprim combined with Sulfamethoxazole, a
sulfonamide antibiotic)
31. ANTIBIOTICS
TRIMETHOPRIM
ā£ Common Side Effects
ā£ Commonly causes a skin rash
ā£ GI upset
ā£ Hypersensitivity is common and can be severe
ā£ Hyperkalaemia
ā£ Cautions and Contraindications
ā£ Contraindicated inĀ 1stĀ trimesterĀ of pregnancy
ā£ Caution in folate deficiency and renal impairment
32. ANTIBIOTICS
TRIMETHOPRIM
ā£ Interactions
ā£ Drugs which also cause hyperkalaemia e.g. ACE
inhibitors, spironolactone, angiotensin II receptor
blockers
ā£ Folate antagonists or drugs that increase folate
metabolism e.g. methotrexate and phenytoin
ā£ Enhances effect of Warfarin due to gut flora death
33. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following describes the mechanism of action
of penicillins?
ā£ Inhibit bacterial protein synthesis
ā£ Inhibit bacterial DNA synthesis
ā£ Inhibit cross-linking of peptidoglycan in bacterial cell
walls
ā£ Inhibit bacterial folate synthesis
34. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following describes the mechanism of action
of penicillins?
ā£ Inhibit bacterial protein synthesis
ā£ Inhibit bacterial DNA synthesis
ā£ Inhibit cross-linking of peptidoglycan in bacterial
cell walls
ā£ Inhibit bacterial folate synthesis
40. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Vancomycin:
ā£ Is well absorbed orally
ā£ Can be used IV to treat C diff
ā£ Requires monitoring to ensure correct serum levels
ā£ Is a carbapenem
ā£ Vancomycin requires serum levels before the third or
fourth dose to inform future dosing
41. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following describes the antimicrobial
mechanism of aminoglycoside antibiotics?
ā£ Inhibit bacterial protein synthesis
ā£ Inhibit bacterial DNA synthesis
ā£ Inhibit cross-linking of peptidoglycan in bacterial cell
walls
ā£ Inhibit bacterial folate synthesis
42. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following describes the antimicrobial
mechanism of aminoglycoside antibiotics?
ā£ Inhibit bacterial protein synthesis
ā£ Inhibit bacterial DNA synthesis
ā£ Inhibit cross-linking of peptidoglycan in bacterial cell walls
ā£ Inhibit bacterial folate synthesis
ā£ Through binding to the 30S subunit of the ribosome
43. ANTIBIOTICS
REVIEW QUESTIONS
ā£ It is extremely important to avoid alcohol while taking
which of the following antibiotics?
ā£ Metronidazole
ā£ Co-amoxiclav
ā£ Ciprofloxacin
ā£ Nitrofurantoin
44. ANTIBIOTICS
REVIEW QUESTIONS
ā£ It is extremely important to avoid alcohol while taking which of
the following antibiotics?
ā£ Metronidazole
ā£ Co-amoxiclav
ā£ Ciprofloxacin
ā£ Nitrofurantoin
ā£ Metronidazole inhibits alcohol metabolism leading to
acetaldehyde accumulation
45. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following antibiotics has equal bioavailability
orally and IV?
ā£ Metronidazole
ā£ Co-amoxiclav
ā£ Ciprofloxacin
ā£ Nitrofurantoin
46. ANTIBIOTICS
REVIEW QUESTIONS
ā£ Which of the following antibiotics has equal bioavailability
orally and IV?
ā£ Metronidazole
ā£ Co-amoxiclav
ā£ Ciprofloxacin
ā£ Nitrofurantoin
48. PATHOGENS
OVERVIEW
ā£ PathogensĀ are ādisease causing micro-organismsā
ā£ They are categorized into four broad groups:
ā£ bacteria, viruses, fungi and parasites
ā£ Understanding pathogens allows us to understand how they cause
disease, and also helps us understand howĀ antimicrobial agentsĀ work
to prevent and treat infections caused by them
ā£ Learning Goal
ā£ To look at the different pathogens, how they can be classified and
consider some examples of how they cause disease
49. PATHOGENS
BACTERIA
ā£ Bacteria areĀ prokaryoticĀ micro-organisms/pathogens and along with viruses, account
for the majority of infectious diseases in humans
ā£ Bacteria can be classified simply by their shape and the key groups are as follows:
ā£ Bacilli:Ā Also known as rods, these are long and thin
ā£ Cocci:Ā These spherical micro-organisms are found grouped together, as
staphylococci (clusters), streptococci (lines) or diplococci (paired)
ā£ Spirilla:Ā Spiral-shaped bacteria, although these are less common
ā£ Vibrios:Ā Flagellated (tailed) organisms, a notable example of which
isĀ VibrioĀ cholerae,Ā the causative organism of cholera
ā£ Spirochaete:Ā These are tightly coiled. An example of isĀ Treponema pallidum, the
causative organism of syphilis
50. PATHOGENS
GRAM-STAINING
ā£ The second way of classifying bacteria is according toĀ Gram-staining
ā£ Gram-staining separates bacteria into Gram-positive and Gram-
negative organisms, depending on the thickness ofĀ peptidoglycan
present in the cell wall
ā£ Gram-positive bacteria have a thick layer of peptidoglycan,
whereas Gram-negative have a thin layer
ā£ Not all bacteria can be gram-stained
ā£ Mycobacterium tuberculosisĀ is the causative organism of
tuberculosis and is considered gram-indeterminate
52. PATHOGENS
GRAM-STAINING TECHNIQUE
ā£ By understanding the technique used during Gram-staining, it can help you to remember
which colours represent gram-positive and gram-negative organisms respectively
ā£ Initially, positively chargedĀ crystal violetĀ is added to the cells, which binds to
negatively charged cell components
ā£ IodineĀ is then added, which forms large molecular complexes with crystal violet and
this stains the cell blue/purple
ā£ A decolouriser such as acetone or methanol is then added to attempt to remove
these large complexes from the cell
ā£ If the cell wall has a thin layer ofĀ peptidoglycan,Ā these complexes pass out through
the cell wall, removing the blue colouration
ā£ The cells are then stained red withĀ safranin
53. PATHOGENS
GRAM-STAINING TECHNIQUE
ā£ Gram-positive organisms have a thick cell wall of peptidoglycan and so retain
the crystal violet stain when washed with acetone/methanol
ā£ When safranin is added, it is retained but obscured by the crystal violet so that
these cells stainĀ purple
ā£ In contrast, gram-negative organisms have an outer lipopolysaccharide layer
ā£ When acetone is added these lipids dissolve, exposing the relatively thin
peptidoglycan membrane
ā£ Crystal violent/iodine complexes are able to exit which decolourises the cell
ā£ Therefore when the red counterstain is added, gram-negative bacteria
stainĀ red
54. PATHOGENS
AEROBIC VS ANAEROBIC
ā£ The final way of classifying bacteria is into aerobic and
anaerobic, depending on their ability to survive with or
without oxygen
ā£ Aerobic bacteria can survive in the presence of oxygen,
and obligateĀ aerobesĀ absolutely require oxygen to
survive
ā£ Anaerobic bacteria can survive without oxygen, and
obligateĀ anaerobesĀ can only survive in an environment
without oxygen
57. PATHOGENS
VIRUSES
ā£ When considering viruses, it is key to note that they are unable to self-replicate, and need to hijack
the replication abilities of their host in order to multiply
ā£ Viral Structure
ā£ Viruses are extremely small pathogens and can only be visualized with an electron microscope
ā£ In general terms, viral particles consist of aĀ nucleic acid core,Ā either DNA or RNA, which is either
single or double stranded
ā£ The RNA can be eitherĀ āpositive senseāĀ or ānegative senseā depending on the polarity of the
nucleic acid
ā£ Positive sense (5ā²-3ā²) RNA is directly translatable into viral proteins, whileĀ negative senseĀ (3ā² to
5ā²) is not
ā£ The virus is covered by a protein coat known as theĀ ācapsidā
ā£ Some viruses also have an outer envelope
59. PATHOGENS
VIRUSES
ā£ The cell capsid, or outer envelope if present,
hasĀ glycoproteinsĀ attached to it
ā£ These bind to appropriate receptors on certain host cells,
for example, glycoprotein 120 on the HIV virus binds to
CD4 receptors on host T cells
ā£ This allows the virus to replicate and establish a viral
infection
61. PATHOGENS
VIRAL REPLICATION
ā£ The virus is adsorbed onto the host cell membrane
ā£ Through the process of pinocytosis, the virus enters the cell in a vacuole
ā£ Un-coating occurs, where the outer protein coat is stripped to expose the genomic material
ā£ If an RNA virus, mRNA is generated directly
ā£ If a DNA virus or a negative sense RNA virus, transcription occurs to create mRNA
ā£ Viral mRNA hijacks host machinery to generate viral proteins
ā£ Viral nucleic acid is generated to facilitate further replication
ā£ The virion is assembled, which is an immature, inactive version of the virus
ā£ This contains the newly synthesized viral proteins and viral genomic material
ā£ The virion exits to infected another host cell, and the cycle repeats
63. PATHOGENS
FUNGI
ā£ Fungi can be sub-divided intoĀ yeasts,Ā which are single-
celled, andĀ moulds,Ā which are multicellular
ā£ Examples of yeasts includeĀ Candida albicans, which causes
thrush infections, andĀ Pneumocystis jirovecii, which is a
cause of pneumonia inĀ immunocompromisedĀ individuals
ā£ Examples of moulds include theĀ AspergillusĀ species, which
can cause respiratory infections in susceptible individuals
64. PATHOGENS
PARASITES
ā£ Parasites are less clinically relevant in the UK, but parasitic infections
do sometimes occur and are an important cause of infection
worldwide
ā£ Parasites can be subdivided intoĀ Protozoa,Ā which are single-celled,
andĀ Helminths,Ā which are worms
ā£ Protozoa include Giardia lamblia, which causesĀ giardiasis,
characterized by diarrhoea following foreign travel
ā£ Examples of Helminths includeĀ roundwormsĀ and tapeworms, both of
which can live in the gut and cause symptoms such as nausea and
diarrhoea
65. PATHOGENS
REVIEW QUESTIONS
ā£ Which of the following statements is true?
ā£ Gram negative bacteria have a thick layer of peptidoglycan in
their cells walls and stain red
ā£ Gram positive bacteria have a thick layer of peptidoglycan in
their cells walls and stain red
ā£ Gram negative bacteria have a thin layer of peptidoglycan in
their cell walls and stain blue
ā£ Gram positive bacteria have a thick layer of peptidoglycan in
their cell walls and stain blue
66. PATHOGENS
REVIEW QUESTIONS
ā£ Which of the following statements is true?
ā£ Gram negative bacteria have a thick layer of peptidoglycan in
their cells walls and stain red
ā£ Gram positive bacteria have a thick layer of peptidoglycan in
their cells walls and stain red
ā£ Gram negative bacteria have a thin layer of peptidoglycan in
their cell walls and stain blue
ā£ Gram positive bacteria have a thick layer of peptidoglycan in
their cell walls and stain blue
67. PATHOGENS
REVIEW QUESTIONS
ā£ Escherichia coli, a bacterium which is a common cause of
food poisoning, is an example of a
ā£ Gram positive cocci
ā£ Gram negative cocci
ā£ Gram positive bacilli
ā£ Gram negative bacilli
68. PATHOGENS
REVIEW QUESTIONS
ā£ Escherichia coli, a bacterium which is a common cause of
food poisoning, is an example of a
ā£ Gram positive cocci
ā£ Gram negative cocci
ā£ Gram positive bacilli
ā£ Gram negative bacilli
69. PATHOGENS
REVIEW QUESTIONS
ā£ Neisseria meningitidis is an example of:
ā£ Gram positive cocci
ā£ Gram negative cocci
ā£ Gram positive bacilli
ā£ Gram negative bacilli
70. PATHOGENS
REVIEW QUESTIONS
ā£ Neisseria meningitidis is an example of:
ā£ Gram positive cocci
ā£ Gram negative cocci
ā£ Gram positive bacilli
ā£ Gram negative bacilli
71. PATHOGENS
REVIEW QUESTIONS
ā£ The nucleic acid of viruses is:
ā£ DNA or RNA, but always single-stranded
ā£ Always in the form of double stranded DNA
ā£ May be DNA or RNA, and may be double or single-
stranded
ā£ Always DNA, may be double or single stranded
72. PATHOGENS
REVIEW QUESTIONS
ā£ The nucleic acid of viruses is:
ā£ DNA or RNA, but always single-stranded
ā£ Always in the form of double stranded DNA
ā£ May be DNA or RNA, and may be double or single-
stranded
ā£ Always DNA, may be double or single stranded
75. References
These slide reflect a summary of the contents of
TeachMePhysiology.com and are to be used for
educational purposes only in compliance with the terms of
use policy.
Specific portions referenced in this summary are as follows:
ā£ https://teachmephysiology.com/immune-system/infections/antibiotics/
ā£ https://teachmephysiology.com/immune-system/infections/pathogens/
ā£ https://teachmephysiology.com/immune-system/infections/viral-infection/
Additional sources are referenced on the slide containing
that specific content.
