Microbiology Flashcards
Pathogen
Organism that causes or is capable of causing disease
Commensal
Organism which colonises the host but causes no disease in normal circumstances
Opportunist Pathogen
Microbe that only causes disease if host defences are compromised
Virulence/Pathogenicity
The degree to which a given organism is pathogenic
Asymptomatic carriage
When a pathogen is carried harmlessly at a tissue site where it causes no disease
What is the genus of Staphylococcus aureus
Staphylococcus
What is the Species of Staphylococcus aureus
Aureus
Coccus
bacterial cell that has the shape of a sphere
Rods (bacilli)
bacterial cell that has the shape of a rod
Coccus vs Rod
Bacteria may be either round (cocci) or rod-shaped (bacilli). Either shape may be gram-positive or gram-negative. A mixture of gram-positive and gram-negative bacteria can occur in the same field.
Cocci morphology
Diplococcus- pair of coci
Chain of cocci
Cluster cocci
Rod morphology
Chain of rods
Filamentous/branching bacteria
Vibrio- curved rod
Spirochaete- spiral rod
Organelle of bacteria
Cell wall, outer membrane, inner membrane, pili, chromosome of circular double stranded DNA, Capsule (not all bacteria)
Gram +ive cell envelope, outermost to innermost
Capsule, peptidoglycan, lipoteichoic acid, cytoplasmic membrane
Gram -ive cell envelope, outermost to innermost
Capsule, LPS (endotoxin), outer membrane, lipoprotein, peptidoglycan, inner membrane
Lipopolysaccharide (LPS/ENDOTOXIN)
Made up of Lipid A, O antigen and terminal sugars, toxin
Gram staining process
Crystal violet (both purple), iodine, (both purple), decolourisation (+ive purple, -ive colourless), counter stain (+ive purple, -ive pink)
Gram staining results
Positive= purple
Negative= pink
Remember: Positive stain purPle, Negative stain piNk
Bacterial environment for growth
Temperature: <-800C to + 80C (1200C for spores)
pH: <4-9
Water/dessication: 2 hours – 3 months (>50 years for spores)
Light: UV
Average bacteria growth rate
double every 20 minutes
ENDOTOXIN
Component of the outer membrane of bacteria, eg lipopolysaccharide in Gram negative bacteria
EXOTOXIN
Secreted proteins of Gram positive and Gram negative bacteria
Endotoxin vs Exotoxin- Composition
Composition: Exo=protein Endo=LPS
Endotoxin vs Exotoxin- Action
Action: Exo=specific Endo=non-specific
Endotoxin vs Exotoxin- Effect of heat
Effect of heat: Exo=labile Endo=stable
Endotoxin vs Exotoxin- Antigenicity
Antigenicity (ability of an antigen to induce an immunological response when it is encountered by the human body) Exo=strong Endo=weak
Endotoxin vs Exotoxin- Produced by
Produced by: Exo= gram +ive/-ive Endo=LPS- gram -ive
Endotoxin vs Exotoxin- Convertibility
Convertibility to toxoid (a toxin treated (usually with formaldehyde) so that it loses its toxicity but retains its antigenicity) Exo= Yes Endo= no
Bacterial genetics - enzyme responsible of transcription
RNA polymerase to produce mRNA
Bacterial genetics - translation
mRNA translated in to protein by 30s/50s ribosome
Bacterial genetic variation- mutations
-base substitutions, deletion, interion
2 types DNA present in bacteria
Bacterial chromosome, Plasmid DNA
Bacterial genetic variation- Gene transfer
Transformation eg via plasmid
Transduction eg via phage
Conjugation eg via sex pilus
Genetic variation in bacteria
Mutation or gene transfer
Initial classification of bacteria
Obligate intracellular bacteria or bacteria that may be cultured on artificial media
Example of Obligate intracellular bacteria gensus
Rickettsia, Chlamydia, Coxiella
Division of bacteria that may be cultured on artificial media
With a cell wall or no cell wall
Example gensus of bacteria that may be cultured on artificial media with no cell wall
Mollicutes
Division of bacteria that may be cultured on artificial media with a cell wall
Growing as single cells or growing as filaments
Example genus of bacteria that may be cultured on artificial media with a cell wall growing as filaments
Actinomyces, nocardia, streptomyces
Division of bacteria that may be cultured on artificial media with a cell wall growing as single cells
Rods, cocci, spirochaetes
Example genus of spirochaetes
Leptospira, treponema, borrelia
Spirochaetes
long and tightly coiled bacteria
Division of cocci
Gram positive or negative
Division of gram -ive cocci
Anaerobic or aerobic
Example genus of aerobic gram -ive
Neisseria
Example genus of anaerobic gram -ive
Veillonella
Division of gram +ive cocci
Gram positive or negative
Division of aerobic gram +ive cocci
Staphylococcus or Streptococcus
Sub-division of Streptococcus
Beta-haemolytic, alpha-haemolytic, non-haemolytic, enterococcus
Example genus of anaerobic gram +ive
Peptostreptococcus
Staphylococcus
Aerobic, gram positive cocci, forms clumps, positive catalase test
Streptococcus
Aerobic, gram positive cocci, forms grows in chains, negative catalase test
Streptococcus vs Staphylococcus
Both aerobic gram positive cocci. Staphylococci form clumps, whereas Streptococci grow in chains. They can be discriminated by catalase test because Staphylococci have the capability to produce catalase
Division of aerobic gram +ive cocci test
Catalsae test, +ive=Staphylococcus -ive=Streptococcus
Division of Rods
Ziehl-Neelsen positive stain, gram +ive or gram -ive
Example genus of Ziehl-Neelsen positive stain
Mycobacteria
Division of gram positive/gram negative Rods
Anaerobic or aerobic
Example genus of anaerobic gram +ive rods
Clostridium, Propionibacterium
Example genus of aerobic gram +ive rods
Corynebacterium, listeria, bacillus
Example genus of anaerobic gram -ive rods
Bacteroides
Example genus of aerobic gram -ive rods
Coliforms, vibrio, pseudomonads, parvobacteria
gram positive
Gram-positive bacteria lack an outer membrane but are surrounded by layers of peptidoglycan many times thicker than is found in the Gram-negatives
Staphylococci
Currently at least 40 species
Coagulase +ve or – ve
S.aureus most important (coag. +ve)
Coagulase -ve species, e.g. S epidermidis important in opportunistic infections
Normal habitat- nose and skin
Coagulase
Enzyme produced by bacteria that clots blood plasma. Fibrin clot formation around bacteria may protect from phagocytosis
Staphylococcus aureus spread
Spread by aerosol and touch- carriers & shedders
Staphylococcus aureus
Virulence factors
Pore-forming toxins (some strains)- a - haemolysin & Panton-Valentine Leucocidin
Proteases - Exfoliatin
Toxic Shock Syndrome toxin (stimulates cytokine release)
Protein A (surface protein which binds Ig’s in wrong orientation)
MRSA (Methicillin-resistant Staphylococcus aureus)
resistant to: beta-lactams, gentamicin, erythromycin, tetracycline
Staphylococcus aureus symptoms
Pyogenic- wound infection, abscesses, impetigo, septicaemia, osteomyelitis, pneumonia, endocarditis
Toxin mediated- scaled skin syndrome, toxic shock syndrome, food poisoning
Coagulase-negative Staphylococci examples
S.epidermidis: -Infections in debilitated, prostheses (opportunistic)
-Main virulence factor - ability to form persistent biofilms
S.saprophyticus- Acute cystitis (haemagglutinin for adhesion, urease)
Haemolysis
used to describe the destruction of red blood cells
Beta-Haemolysis
complete lysis e.g. S.pyogenes
Haemolysins O & S
Alpha- Haemolysis
partial, greening e.g. S.intermedius
Non (gamma)- Haemolysis
no lysis e.g. some S.mutans
Sero-grouping
Grouping by Carbohydrate cell surface antigens
Lancefield A-H and K-V
Antiserum to each group added to a suspension of bacteria
-clumping indicates recognition
Lancefield Group A+B
Group A - S.pyogenes; important pathogen
Group B - S.agalactiae neonatal infections
S.pyogenes virulence exported factors
Enzymes
Hyaluronidase - spreading
Streptokinase - breaks down clots
C5a peptidase - reduces chemotaxis
Toxins
Streptolysins O&S - binds cholesterol
Erythrogenic toxin - SPeA – exaggerated response
S.pyogenes virulence surface factors
Capsule - hyaluronic acid
M protein – surface protein (encourages complement degradation)
Infections caused by S.pyogenes
Wound infections»_space; cellulitis, puerperal fever
Tonsillitis & pharyngitis
Otitis media
Impetigo
Scarlet fever
Complications -rheumatic fever
-glomerulonephritis
Virulence (factors)
ability of an organism to infect the host and cause a disease. Virulence factors are the molecules that assist the bacterium colonize the host at the cellular level
Gram positive bacilli
Listeria monocytogenes, Bacillus anthracis, Corynebacterium diphtheriae
Gram positive bacilli- Clostridia
Spore forming , Survive in environment, Produce toxins
C. tetani- Tetanus
C. botulinum - Botulism
C. difficile- antibiotic associated diarrhea
-pseudomembranous colitis
Gram positive vs Gram negative stain
+ive- crystal-violet
-ive- fuchsin or safranin counterstain
Pathogenicity determinants
Any product or strategy that contributes to pathogenicity/virulence
Colonisation factors: adhesins, invasins, nutrient acquisition, defence against the host
Toxins (effectors): usually secreted proteins -Damage
-Subversion
Types of aerobic gram -ive rodes
Coliforms, Vibrio, parvobacteria, pseudomonads
Coliforms
Enterobacteriaceae or Enterobacteria
Rod-shaped
Motile (most)
Peritrichous flagella
Facultatively anaerobic
Colonise the intestinal tract- Advantageously or disadvantageously
MacConkey-lactose agar
Lactose fermenters – red (pink)
Acid produced by fermentation turns neutral red dye in plate red
Xylose Lysine Deoxycholate (XLD)
Lactose fermenters turn phenol red in media yellow
Isolates Salmonella and Shigella
Shigella cannot ferment lactose remains red
Salmonella cannot ferment lactose but reduce thiosulphate to produce hydrogen sulphide (black)
Cell surface antigens of Gram negative bacteria
Amino acid or carbohydrate variation in cell surface structures gives rise to antigenic variation among species AND between isolates (strains) of the same species
Capsule – polysaccharide
LPS – polysaccharide
Flagellum - protein
Serovars
groups within a single species of microorganisms, such as bacteria or viruses, which share distinctive surface structures
gram negative bacteria
Gram-negative bacteria are surrounded by a thin peptidoglycan cell wall, which itself is surrounded by an outer membrane containing lipopolysaccharide.
Bacteroides
Non-motile rods
Commensal flora (large intestine) - most abundant (30-40% of the total)
Opportunistic - tissue injury (surgery, perforated appendix or ulcer)
Spirochaetes
Long, slender, helical, highly flexible
Most are free-living and non-pathogenic
Pathogenic varieties difficult to culture
Modified outer membrane (“outer sheath”)
Propels bacterium in a corkscrew motion
Obligate intracellular bacteria
organisms that absolutely require an eukaryotic host to survive and replicate
Examples of mycobacterium species
M. tuberculosis-TB
M. avium complex (MAC)- disseminated infection in AIDS, chronic lung infection
M. Kansaii- Chronic lung infection
Mycobacteria
-Slightly curved, beaded bacilli
-High lipid content with mycolic acids in cell wall makes Mycobacteria resistant to Gram stain
-Identified by Ziehl-Neelsen stain
Mycobacteria Microbiology
Aerobic, simple rod shapes (bacillus), thick cell wall, high molecular weight lipids
Slow growing
Challenges from mycobacteria microbiology
Thick lipid rich cell makes immune cell killing and penetration of drug challenging
Slow grow- gradual onset of disease, takes much longer to diagnose/treat
How does TB infect us?
Transmission via air
Primary TB in lung
Latent TB can remain for decades
Can spread beyond lungs
Primary Tuberculosis
Initial ‘contact’ made by alveolar macrophages
Bacilli taken in lymphatics to hilar lymph nodes
Latent Tuberculosis
-no clinical disease
-detectable CMI to TB on tuberculin skin test
-Cell mediated immune (CMI) response from T-cells
-Primary infection contained but CMI persists
Pulmonary Tuberculosis
Could occur immediately following primary infection (post-primary) or month later after reactivation
Granulomas forms around bacilli that have settled in apex
In apex of lung there
Is more air and less
blood supply (fewer defending
white cells to fight)
TB may spread in lung causing other lesions
Primary complex- TB
=Granuloma + Lymphatics + Lymph nodes
Where does TB spreads beyond lungs
Bacilli in lungs apex and lymph nodes
TB meningitis, miliary TB, Pleural TB, bone and joint TB, Genito urinary TB,
TB: Hallmark granuloma formation
If the granuloma works: Mycobacteria shut down metabolically in order to survive – dormancy
But if fails, e.g. in the lung, this can result in the formation of a cavity full of live mycobacteria and eventual disseminated disease (consumption)
What does our body do to protect us from TB?
Primarily controlled by macrophages
Requires a CD4 T cell response to be controlled
Involves many cells of immunity- formation of granulomas
Granuloma stability controls reactivation of TB
Clinical diagnostic methods- TB
Slow growth is challenging for diagnosis using microbiology
Nucleic acid detection is more rapid
Can use immune response as a diagnosis test- tuberculin skin test (TST)
Tuberculin skin test (Mantoux)
The highly immunogenic nature of mycobacterial lipids stimulates T-cell responses in 3-9 weeks after exposure to M. tuberculosis
This reactivity is measured in the tuberculin skin test (TST) an intradermal injection of purified protein derivatives.
Available therapies and resistance
Long treatment regimes
Multiple avenues to drug resistance
XDR TB problematic to treat
A pressing need for new therapies
Resistance mechanisms
Drug inactivation, drug titration, alteration of drug target, altered cell envelope
How do we study TB?
-Animal models a way to understand complex immunology
-Mouse not a natural host of TB
-Fish have their own mycobacterial species that can be used to help investigate host-directed therapies
What is a virus
An infectious, obligate intracellular parasite
Comprising genetic material
(DNA or RNA) surrounded by aprotein coat and/or a membrane
Virus vs bacteria- Cell wall
V=no B=yes
Virus vs bacteria- Organelles
V=no B=yes
Virus vs bacteria- DNA and RNA
V=no B=yes
Virus vs bacteria- Dependent of host cell
V=yes B=no
Virus vs bacteria- Alive
V=no B=yes
Different Shapes of viruses
Helical, icosahedral, comples
Different Structures of viruses
Non-enveloped or enveloped
Envelope of virus
envelope= lipid coat derived from plasma membrane of the host cell
Can viruses replicate independently?
No, Viruses require a host cell and it’s machinery in order to replicate
How do viruses replicate?
- ATTACHMENT to specific receptor
- CELL ENTRY
- HOST CELL INTERACTION + REPLICATION
- ASSEMBLY OF VIRION
- RELEASE OF NEW VIRUS PARTICLES
HOST CELL INTERACTION + REPLICATION of viruses
-Migration of genome to cell nucleus
-Transcription to mRNA using host materials
Translation of viral mRNA to produce: -structural proteins
-viral geniome
-non-structural proteins
Location of assembly of virion
Occurs in different locations depending on virus
-Nucleus (e.g. herpes viruses)
-Cytoplasm (e.g. poliovirus)
-At cell membrane (e.g. influenza virus)
Release of new virus
-bursts out > cell death e.g. rhinovirus
-budding/exocytosis
e.g. HIV, influenza
True or false: Viruses are large, and consist of genetic material surrounded by a lipid coat
False, Viruses are very small, and consist of genetic material surrounded by a protein coat
How do viruses cause disease?
a) Direct destruction of host cells
b) Modification of host cell
c) “Over-reactivity” of immune system
d) Damage through cell proliferation
e) Evasion of host defences
Viruses causing disease example: Direct destruction of host cells
e.g. poliovirus- host cell lysis and death after a viral replication period of 4 hours
Viruses causing disease example: Modification of host cell
e.g. rotavirus- atrophies villi and flattens epithelial cells
Viruses causing disease example: “Over-reactivity” of immune system
e.g. hepatitis B, Sars-CoV-2
Viruses causing disease example: Damage through cell proliferation
e.g human papillomavirus > cervical cancer
Viruses causing disease example: Evasion of host defences- Cellular level
Cellular level- Latency: e.g. herpesviridae
-Cell-cell spread: e.g. measles, HIV
Viruses causing disease example: Evasion of host defences- Molecular level
Molecular level- Antigenic variability e.g. influenza, HIV, rhinovirus
-Prevention of host cell apoptosis e.g. herpesviridae
-Downregulation of interferon and other intracellular host defence proteins e.g. many
-Interference with host cell antigen processing pathways e.g. herpesviridae, measles, HIV
Recognising how viruses cause disease allows us to?
-Understand transmission and natural history
-Know who is most at risk
-Develop treatments and “preventative” drugs
Do all viruses cause the same clinical symptoms
Viruses vary wildly in therange of clinical syndromes they can cause, due to:
-Different host cells and tissues that they can infect
-Different methods of interaction with the host cell
What is meningitis?
Meningitis describes inflammation of the meninges (membranes) which cover the brain and spinal cord
three layers of meninges
dura mater
arachnoid mater
pia mater
Causes of meningitis: infection
Bacteria e.g. meningococcus, pneumococcus
Viruses e.g. coxsackievirus, echovirus, herpes virus, mumps virus, influenza, HIV etc
Less common infective causes include fungi, protozoa, and other parasites.
Causes of meningitis: non-infectious
Medications e.g. antibiotics (amoxicillin, trimethoprim/sulfamethoxazole), carbamazepine, lamotrigine, NSAIDs, ranitidine
Cancers e.g. melanoma, lung cancer, breast cancer, lymphoma, leukaemia
Autoimmune disease e.g. Systemic lupus erythematosus (SLE), Behçet’s syndrome.
Invasive meningococcal disease
Infection with Neisseria meningitidis
Gram-negative diplococci
Carried by 10-24% of the population
Humans are only known reservoir
Transmission by respiratory droplets/ naso-pharyngeal secretions
Incubation period 2-10 days, usually 3-4 days
Two main manifestations of invasive meningococcal disease
Meningitis: a localised infection of the meninges, with “local” symptoms
Septicaemia : a systemic infection with widespread signs, and generalised organ damage
Risk factors for meningitis
Extremes of age
Immunocompromised (e.g. HIV) or immunosuppressed (e.g. chemotherapy)
Asplenia/hyposplenia
Cancer – people with leukaemia and lymphoma
Sickle cell disease
Organ dysfunction – e.g. liver or kidney disease
Smokers
Contiguous infection
Living in overcrowded households, college dormitories or military barracks
People who have had contact with a case
Travellers abroad to high risk area - increased risk of encountering the pathogen
Meningococcal meningitis symptoms
Fever, stiff neck, headache, confusion, increased sensitivity to light, nausea and vomiting
Meningococcal meningitis symptoms- Do babies always present with classic symptoms
They may be: -slow or inactive
-irritable
-vomiting
-feeding poorly
-or have a bulging anterior fontanelle (the soft spot of the skull)
Brudzinski’s neck sign
keeps one hand behind the patient’s head and the other on chest in order to prevent the patient from rising. Reflex flexion of the patient’s hips and knees after passive flexion of the neck constitutes a positive Brudzinski sign
+ive sign of meningitis
Meningococcal septicaemia symptoms
Fever and chills
Fatigue
Vomiting
Cold hands and feet
Severe aches or pain in the muscles, joints, chest, or abdomen
Rapid breathing
Diarrhoea
Non blanching rash (petechiae)
In the later stages, a dark purple rash (purpura)
Disseminated Intravascular Coagulation (DIC)
Caused by sepsis
the activation of coagulation pathways that results in formation of intravascular thrombi (clots) and depletion of platelets and coagulation factors.
These clots can cause arterial occlusions leading to gangrene of extremities & auto-amputations
Auto-amputation
spontaneous detachment of an appendage from the body as a result of arterial occlusions
Close contacts are identified by;
- People living in the same household as the case
- Anyone who slept overnight in the same household as the case in previous 7 days
- Other household members if case stayed overnight elsewhere in previous 7 days
- Intimate kissing contacts in last 7 days
Chemoprophylaxis
Antibiotics given to eradicate throat carriage- stops transmission, doesn’t stop infection
What are fungi
Eukaryotic
Chitinous cell wall
Heterotrophic
“Move” by means of growth or through the generation of spores (conidia), which are carried through air or water
Yeast
small single celled organisms that divide by budding
Mould
Moulds form multicellular hyphae and spores
Options for selective fungi toxicity
DNA/RNA synthesis,
protein synthesis- Similar to mammalian
Cell wall- doesn’t exist in humans
Plasma membrane- human cell membrane contains cholesterol not ergosterol
Why does fungi have limited options for selective toxicity?
They are eukaryotes and have several similarities to human cells
Is ringworm caused by a worms?
No, its caused by a fungus
Dermatophytes
Fungal organisms that require keratin for growth. These fungi can cause superficial infections. Human-human or animal-human transmission
Sampling presumed dermatophyte infections
-plucked hair
-scalp scraping
-scarping of scaled edge of lesion
-nail clippings
Dimorphic fungi
Fungi that have a yeast phase (at 37C in organism) and a mould phase (ambient temp).
Dimorphic fungi transmission
Infection via inhalation of conidia from soil or implantation
Coccidioides geography
warm, arid conditions in SW USA
Coccidioides disease
-Asymptomatic/subclinical infection common (2/3)
-Most of rest – community acquired pneumonia 1-3 weeks post-exposure (1/3 of CAP in Ariziona)
-Severe disease > respiratory failure or septic shock in context of high inoculum or cell-mediated immune defect – e.g. HIV
-Late disease – does not correlate with the severity of initial symptoms
Invasive candidiasis
A serious Infection caused by a yeast called Candida, can affect the blood, heart, brain, eyes, bones, or other parts of the body.
Main causes of invasive candidiasis
mostly due to infection of prosthetic devices or intra-abdominal disease
Cryptococcus causes
Acute or chronic meningitis in patients with reduced cell mediated immunity
Differential diagnosis of sub-acute/chronic meningitis- Infective
-Tuberculosis
-Cryptococcus
-Dimorphic fungi –Histoplasma, Coccidioides, Blastomyces
-Lyme
-Brucella
-Syphilis
Differential diagnosis of sub-acute/chronic meningitis- Non-infective
-Sarcoidosis
-Behçets’s
-SLE
-Malignant
-Drug induced
Cryptococcus
Association with rotting wood and bird guano
Vast majority of human disease caused by C. neoformans (only causes disease in immunocompromised) and C. gattii (more likely in immunocompetent)
Invasive aspergillosis
associated with profound immunocompromise but is increasingly recognised in patients with severe viral infection
Mucoraceous moulds (zygomyctes)
-Rare but cause devastatingly rapidly progressive infections that cross tissue planes
-need aggressive antifungal therapy and surgery for optimal outcomes
Pneumocystis jirovecii
Pneumocystis jirovecii causes a pneumonitis with severe hypoxia in the immunocompromised
Antibiotic
Antibiotics are molecules that work by binding a target site on a bacteria- the crucial binding site will vary with the antibiotic class
Beta lactam antibiotics
-disrupt peptidoglycan production
-by binding covalently and irreversibly to the Penicillin Binding Proteins
Beta lactam antibiotics- gram +ive or -ive
gram-positive usually more susceptible to β-lactams than gram-negative bacteria
What causes differences in β-lactam antibiotics
Differences in the spectrum and activity of β-lactam antibiotics are due to their relative affinity for different PBPs.
Why are beta-lactam antibiotics ineffective in the treatment of intracellular pathogens?
Because the penicillins poorly penetrate mammalian cells
Beta Lactams- examples
Penicillins, Cephalosporins, Carbapenems, Monobactams
Beta Lactams-Penicillins
Penicillin V
Penicillin G (Benzyl penicillin)
Flucloxacillin
Amoxicillin/Ampicillin
Pipericillin
Beta Lactams-Cephalosporins
Cefuroxime
Cefotaxime Ceftriaxone
Beta Lactams-Carbapenems
Meropenem
Nucleic acid synthesis
group of antibiotics that interfere with DNA synthesis by inhibiting n enzymes involved in DNA replication
Metronidazole action
Rifampicin- inhibits protein synthesis by interacting with DNA, and causes a loss of helical DNA structure and strand breakage
Ciprofloxacin action
Quinolones- target by inhibiting the DNA gyrase (catalyses the super-coiling of double-stranded closed-circular DNA)
Gentamicin action
Aminoglycosides- action involves inhibition of bacterial protein synthesis by binding to 30S ribosomes
Doxycycline action
Tetracyclines- reversibly binds to the 30S ribosomal subunits, blocking the binding of aminoacyl tRNA to the mRNA and inhibiting bacterial protein synthesis
Clindamycin action
Lincosamides- binding to the 50s ribosomal subunit of bacteria. This agent disrupts protein synthesis by interfering with the transpeptidation (transfer of AA) reaction, which thereby inhibits peptide chain elongation
TURNS OFF NASTY TOXINS MADE BY Gram positive bugs
Clarithromycin action
Macrolides- inhibits bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit, interferes with amino acid translocation during the translation and protein assembly process
Trimethoprim action
Trimethoprim- inhibits folate synthesis- blocks the reduction of dihydrofolate to tetrahydrofolate (active form of folic acid)
Co-trimoxazole
co-trimoxazole blocks two consecutive steps in folate synthesis process
Fungal cell properties vs mammalian cell
DNA/RNA synthesis,
protein synthesis- Similar to mammalian
Cell wall- doesn’t exist in humans
Plasma membrane contains ergosterol whereas human cell membranes contain cholesterol
Bactericidal Antibiotics
The agent kills the bacteria, inhibits cell wall synthesis
Bacteriostatic Antibiotics
inhibitory to growth- antibiotics that Inhibit protein synthesis, DNA replication or metabolism
Minimum inhibitory Concentration (MIC)
the lowest concentration of an antibiotic that inhibits the growth of a given strain of bacteria
Does the lowest MIC=best antibiotic?
No, drug must not only attach to its binding target but also must occupy an adequate number of binding sites for a sufficient period of time
Two major determinants of anti bacterial effects
Concentration and the Time that the antibiotic remains on these binding sites
Time dependent killing
t>MIC- time that serum concentrations remain above the MIC during the dosing interval
Concentration -Dependent Killing
peak concentration/MIC ratio- how high the concentration is above MIC
Pharmacokinetic processes for antibiotics
-release from dose form
-absorption into blood
-distribution in body
-rate of elimination via metabolism (liver) or excretion (kidney)
Target sites of antibiotics
Cell wall/membrane synthesis, nucleic acid synthesis (folate synthesis/DNA gyrase/RNA polymerase), protein synthesis (50s/30S subunit)
Antibiotic resistant- Change in antibiotic target- Flucloxacillin and MRSA
Flucloxacillin (or methicillin) is no longer able to bind penicillin binding protein of Staphylococci – MRSA (methicillin resistant S. aureus)
Antibiotic resistant- Change in antibiotic target- vancomycin and VRE
Wall components change in enterococci and reduce vancomycin binding – VRE (Vanocmicin resistant Enterococci)
Antibiotic resistant- Change in antibiotic target- Rifampicin and MDR-TB
Rifampicin activity reduced by changes to RNA polymerase in MTB – MDR-TB (Multi drug resistant TB)
Antibiotic resistant- destroy antibiotic- penicillin
Beta lactam ring of Penicillin and cephalosporins hydrolysed by bacterial enzyme ‘Beta lactamase’
Methods of antibiotic resistance
Change in antibiotic target, destroy antibiotic, prevent antibiotic access, remove antibiotic from bacteria
Intrinsic resistance
All subpopulations of a species will be equally resistant
Intrinsic resistance- example
-Aerobic bacteria are unable to reduce metronidazole to its active form
-Vancomycin cannot penetrate outer membrane of gram negative bacteria
Acquired resistance
-A bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic
-Only certain strains or subpopulations of a species will be resistant
MRSA (Methicillin resistant Staphylococcus aureus)
Resistance to all β-lactam antibiotics in addition to methicillin (= flucloxacillin)
Bacteriophage mediated acquisition of Staphylococcal cassette chromosome mec (SCCmec)
contains resistance gene mecA encodes penicillin-binding protein 2a
VRE (vancomycin-resistant enterococci)
-Plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding
-Promoted by cephalosporin use
ESBL (extended spectrum beta lactamase)
Extended spectrum beta lactamase (ESBL) inhibition
These hydrolyse oxyimino side chains of cephalosporins: cefotaxime,ceftriaxone, andceftazidime and monobactams: aztreonam
Carbapenems- Meropenem
-in contrast to other b-lactams, are highly resistant to degradation by b-lactamases or cephalosporinases
-often the antimicrobials of last resort to treat infections due to ESBL
CRE (Carbapenem Resistant Enterobacteriaceae)
Produce carbapenemases so are resistant to carbapenem so treatment options are very few
and very toxic
factors to consider when deciding if an antibiotic is safe to prescribe
Intolerance, allergy and anaphylaxis
Side effects
Age
Renal and Liver function
Pregnancy and breast feeding
Drug interactions
Risk of Clostridium difficile
Benifts of using cephalosporins instead of penicillin’s
Good for people with penicillin allergy
Work against some resistant bacteria
Get into different parts of the body e.g. meningitis
Gram positive antibiotic choice
Thick cell wall therefore need a simple cell wall weapon- think beta-lactams
Gram negative antibiotic choice
Thin cell wall, therefore need a different weapon
