1: Microbial Infection and Antimicrobial Therapies Flashcards
5 main types of infectious agents
Viruses
Bacteria
Fungi
Protozoa
Helminths
Viruses
obligate intracellular parasites
contain RNA/DNA
Replicate using host cell machinery : Budding, Cytolysis
specific to host cell
e.g HIV retrovirus
4 routes of viral infection
Faecal-oral
Airborne
Insect vectors
Blood borne
Bacteria
prokaryotes - no internal cell surface membrane
single circular chromosome - haploid
poorly defined cytoskeleton
cell wall - peptidoglycan
Binary fission
Examples of Bacteria
Shigella - GI tract , faecal-oral transmission
Neisseria Meningitidis - Commensal > pathogen, community acquired, can cause septicaemia, meningitis and septic shock
C.Difficile & MRSA - hospital acquired infection
mycobacterium tuberculosis - TB= top infectious killer
Helicobacter pylori - peptic ulcer, Gastric cancer
Pathogenic e.coli - faecal-oral route
Why do bacteria have high mutation rates?
smaller generation times - quick replication
haploid, so only one gene needs to be mutated to have a phenotypic effect
Fungi
eukaryotic - unicellular or multicellular
exist as yeasts, filaments or both
yeast spread by budding
filaments have hyphae which have cross walls/septa
causes mycoses:
cutaneous - skin
mucosal - inner lining
systemic - whole body
Protozoa
unicellular eukaryotic
intestinal, blood or tissue parasites
Binary fission or formation of trophozoites
often two hosts - infection acquired by ingestion or through vector
Protozoa examples
malaria
leshmania species e.g leshmaniasis
Malaria
Plasmodium species e.g malaria
- blood and tissue parasites
- acquired via mosquito vector
- spread by forming trophoziotes inside cell
Leshmaniasis
leshmania species
- blood and tissue parasites
- acquired via sandfly vector
- spreads by forming trophoziotes inside cell
- causes cutaneous and visceral diseases
Helminths
macroscopic multi-cellular eukaryotes
life cycle outside human host
replicate sexually - eggs: some hermaphroditic
e.g roundworms, flatworms, tapeworms
faecal-oral transmission
Antibiotic
antimicrobial agent produced by microorganism that kills or inhibits other microorganisms
Antimicrobial
chemical that selectively kills or inhibits microbes
Bactericidal
kills bacteria
Bacteriostatic
stops bacterial growth
Antiseptic
chemical that kills/inhibits microbes, often used topically
Minimum inhibitory concentration (MIC)
lowest [AB] needed to inhibit growth of bacteria
Protonsil
first sulphonamide antibiotic
acts only on Gram +ve bacteria
Bacteriostatic and synthetic
Treats ; UTIs, RTIs, bacteraemia & given as prophylaxis for HIV
some toxicity, but used due to resistance to other ABs
Gram positive bacteria
peptidoglycan wall
one membrane
Gram negative bacteria
two membranes
thin peptidoglycan wall
(class) Beta-Lactams
Penicillin, methicillin
Binds to PBPs; inhibit peptidoglycan wall synthesis
inhibit gram +ve bacteria
(class) Aminoglycosides
Gentamycin, Streptomycin
Bactericidal, target 30s ribosome subunit, prevent PS; damage cell membrane
Host toxicity but used more due to other AB resistance, inhibit both gram +/- bacteria
(class) Macrolides
Erythromycin, azithromycin
Targets 50s ribosomal subunit preventing amino-acyl transfer and truncation of polypeptides
Gram +ve and some gram -ve
(class) Quinolones
Bactericidal; synthetic, broad spectrum; targets DNA gyrase in Gram -ve and topoisomerase in Gram +ve
Rifampicin
Bactericidal, target RpoB subunit of RNA polymerase
spontaneous resistance common; red excretions, inhibits both gram +/-
(class) Sulphonamides
prontosil, trimethoprim, sulpha-methoxazole
Bacteriostatic, synthetic
host toxicity but used more due to other AB resistance
Vancomycin
Bactericidal; inhibits cell wall biosynthesis and prevents cross-linking between peptidoglycan units
used more due to other AB resistance (MRSA), Inhibits gram +, administered by IV
Linezolid
Bacteriostatic, inhibits protein synth. by binding to 50s rRNA subunit
gram +ve
given orally
Daptomycin
Bactericidal; targets bacterial cell membrane
gram +ve only
toxicity so low dose
Ab target sites
Inhibition of cell wall synthesis
Inhibition of nucleic acid replication and trasncription
Injury to plasma membrane
Inhibition of synthesis of essential metabolites
Inhibition of protein synthesis
Examples of Gram-negative bacteria
Pseudomonas aeruginosa - CF, burn wound infections, survives on abiotic surfaces
E. Coli (ESBL) - Gi infections, neonatal meningitis, septicaemia, UTI
E. Coli, Klebisiella spp (Carbapenase producing)
Salmonella spp. (MDR) - GI infection, typhoid fever
Acinetobacter baumannii (MDRAB) - opportunistic, wounds, UTI, pneumonia (VAP)
Neisseria gonorrhoeae - Gonorrhoea
Haemophilus influenzae - fever and malaise
Examples of gram positive bacteria
Staphylococcus aureus (MRSA, VISA)- wound and skin infect. pneumonia, septicaemia, infective endocarditis
Streptococcus pneumoniae - pneumonia, septicaemia
Clostridium difficile - pseudomembranous colitis, antibiotic-associated diarrhoea
Enterococcus spp (VRE) - UTI, bacteraemia, infective endocarditis
Mycobacterium tuberculosis (MDRTB, XDRTB) - TB
How has Antibiotic resistance evolved through natural selection
Diverse bacterial population with some Ab resistance due to DNA mutations
Selective pressure –> resistant strains survive and multiply
No selection pressure –> low prevalence of Ab resistance
Ab resistance genes are found in
Plasmids
Transposons
Naked DNA - DNA from dead bacteria released into environment
resistance genes in plasmids
extra-chromosomal circular DNA, often multiple copy
Often carry multiple AB resistance genes- selection for one maintains resistance to all
resistance genes in transposons
integrate into chromosomal DNA
Allow transfer of genes from plasmid to chromosome and vice versa
Which 3 ways can bacteria transfer Ab resistance genes?
Transformation - uptake from extracellular DNA
Conjugation - DNA transfer
Transduction -phage-mediated DNA transfer
4 mechanisms of antibiotic resistance
Altered target site: alternative gene which codes for different/modified Ab target site (MRSA, Strep pneumoni)
Inactivaton of Ab- gene that degrades Ab e.g Beta-lactamase
Altered metabolism - bacteria switch to other metabolic pathways to synthesis a certain substance
Decreased drug accumulation - reduced penetration of Ab into bacteria, increased efflux of Ab
How does Ab resistance lead to increased mortality, morbidity and cost?
STATE (the effects)
Second choice- use of less effective Abs
Time - increased time to effective therapy
Additional approaches - e.g surgery
Toxic drug use - more toxic drugs used
Expensive- newer drugs = costly
Why might treatment with antibiotics fail?
inappropriate choice for organism
poor penetration of AB into target site
inappropriate dosage (issues with half-life)
inappropriate administration
commensal flora are Ab resistant
Common Hospital Acquired Infections
MRSA - methicillin resistant S. aureus
VISA - Vancomycin-insensitive S. aureus
Clostridium difficle
E. Coli
Why do HAIs arise
many ill people with high AB dosage
crowded wards
different pathogens
broken skin
staff transmission
intubation
Commensal flora
Harmless bacteria already present within the body
can be impaired by Ab therapy
How can Abs affect commensal flora
broad spectrum ABs attack commensal flora
AB resistant pathogen now has no competition
pathogen produces toxins and damages host
How can we prevent the emergence of drug resistant bacteria?
BE SICK
Broad spectrum reduction
Existing medication alteration
Strategies of prescription
Identifying resistant strains quickly
Combination of Abs and inhibitors
Knowledge of local strains/patterns
Streptococcus pyogenes is
species of Gram-positive extracellular bacteria that spreads through airborne droplets, shared food and drinks, and direct contact with infected carriers. A Streptococcus pyogenes infection manifests as:
Rheumatic fever
Scarlet fever
Streptococcal pharyngitis
Rheumatic fever
inflammatory disease involving the heart, joints, and skin, typically developing a few weeks after a streptococcal throat infection. This occurs due to cross reactive antibodies being produced by the host towards the bacterial antigens that mimic host antigens. Antibodies produced may target cardiac tissue, such as heart valves, resulting in rheumatic heart disease.
Scarlet fever
characterised by a red rash on the tongue, as well as a sore throat, fever, and swollen lymph nodes. The bacteria produce pyrogenic exotoxin which causes the disease in patients without antitoxin antibodies
Streptococcal pharyngitis
symptoms include fever, sore throat, enlarged and red tonsils and lymph nodes. This is caused by group A streptococcus.
Staphylococcus aureus
gram +ve bacteria
releases superantigens that interfere with T-cell function = massive cytokine release (cytokine storm), causes high fever, nausea, fatigue and can lead to coma
Aureus also releases leukocidins which directly lead to neutrophil cell death
