Path - Micro - Exam 3 Flashcards
- Outline the types of beta-lactam antibiotics and describe their common structural feature.
- penicillins
- cephalosporins
- carbapenems
- monobactams
They all contain a beta lactam ring.
- Describe the final stage in the production of the bacterial cell wall with emphasis on the role of the transpeptidase enzyme.
The peptidoglycan meshwork is assembled in several staged, the final one being the cross linking of the backbone molecules via peptide links. This is done by the enzyme TRANPEPTIDASE.
- Describe the mechanism of action of beta-lactam antibiotics and demonstrate understanding of why transpeptidase enzymes are also known as penicillin binding proteins.
Cell wall = peptidoglycan surrounding cytoplasmic membrane.
Transpeptidase enzymes are also known as penicillin binding proteins as beta lactam antibiotics bind to them and prevent them from working.
. Outline the main ways in which bacteria produce resistance to antibiotics.
a) inhibition of ingress of antibiotic
b) enhanced egress of antibiotic
c) enzymatic destruction of antibiotic
d) alteration of antibiotic target
Explain the mechanism of action of beta-lactamases.
- Beta lactamases are enzymes that destroy beta lactam antibiotics.
- There are many different types produced by gram positive and negative bacteria.
- I.e. penicillinases, cephalosporinases, carbapenemases
- I.e. S. aureus – about 80% resistant to penicillin due to penicillinases
Name the penicillinase resistant beta-lactams and explain what the term implies.
- methicillin
- flucloxacillin
- dicloxacillin
- cephalexin
Penicillinase resistant beta lactamases.
What are two common beta lactamase inhibitors? How do they work? What are some fo the antibiotic names?
- clavulanic acid
- tazobactam
The inhibtors are combined with antibiotics, and will inhibit the function of beta lactamase.
Clavulanic acid + amoxicillin = augmentin
Clavulanic acid + ticarcillin = Timentin
Tazobactam + piperacillin = Tazocin
Explain the meaning of MRSA and the underlying mechanism.
MRSA = methicillin resistant staph aureus.
Mechanism = PBP2a transpeptidase
Instead of producing beta lactamases, it changes the drug target (transpeptidase) so none of the B-lactams can work on it. A genetic alteration makes a new transpeptidase – PBP2a, which the B-lactams have reduced binding for.
Flucloxacillin is what we use now instead of methicillin, but it is still called MRSA. If it is resistant to Flucloxacillin, IT IS MRSA.
Name both an oral and an intravenously administered antibiotic that may be used to treat infections with MRSA.
Oral – clindamycin
IV - vancomycin
Define the meaning of MIC.
MIC = minimum inhibitory concentration
The minimum concentration of an antibiotic that inhibits visible growth of bacteria in an in vitro test system.
Demonstrate an understanding that strains of a given bacterial species may exhibit a range of MICs to an antibiotic, resulting in degrees of susceptibility or resistance.
Routine susceptibility tests are done in simplified form. If the susceptibility measurement is above a chosen MIC called the breakpoint (i.e. the MIC of that bacteria is above the breakpoint), it is RESISTANT, if below the breakpoint, it is SUSCEPTIBLE.
Testing lots of different isolates of bacterial species against a given antibiotic may produce a scatter of different MIC values, with some intermediate degrees of resistance around the break point – i.e you may get a continuum.
Use bacterial endocarditis caused by viridans streptococci to illustrate how the range of MICs is clinically relevant.
Viridans streptococci, such as S. mitis, exhibit varying degrees of susceptibility to penicillin.
Highly and relatively susceptible, resistant, highly resistant to penicillin.
Explain the meaning of antibiotic synergy and describe how this is exploited in the treatment of bacterial endocarditis.
Antibiotic synergy occurs when multiple antibiotics are used to treat an infection and their response is stronger or faster than what use of a single antibiotic is. It is opposed to antibiotic antagonism.
Bacterial Endocarditis - could treat highly susceptible viridans strep with:
a) IV penicillin for 4 weeks, OR
b) IV penicillin + IV gentamicin for 2 weeks
Demonstrate understanding that there are alternative antibiotics to the beta-lactams and name some of those used to treat a community acquired UTI.
For an E. coli UTI…
First line – amoxycillin – a penicillin beta lactam
BUT many are resistant, therefore use augmentin = amoxyxillin + clavulanic acid
If no beta lactamases – nitrofurantoin, trimethoprim, norfloxacin which is exclusively used for UTIs.
Demonstrate appreciation that Pseudomonas aeruginosa is inherently resistant to antibiotics and name two antibiotics from each of the following classes to which it may be susceptible: penicillins, cephalosporins, carbapenems, aminoglycosides and quinolones.
Pseudomonas aeruginosa has a number of resistance mechanisms.
Penicillins:
Ticarcillin
Piperacillin
Cephalosporins:
Ceftazidime
Cefepime
Carbapenems:
Imipenem
Meropenem
Aminoglycosides:
Gentamicin
Tobramicin
Quinolones:
Norfloxacin
Ciprofloxacin (Moxifloxacin)
Name the four generations of cephalosporins and name an antibiotic from each.
*1st generation:
cephalexin
2nd generation
*3rd generation:
ceftriaxone
4th generation:
cefepime
Advanced:
ceftaroline
Explain in general terms how the spectra of activity of cephalosporins differ between the generations.
*1st generation:
S. aureus
Strep
Some Entero
2nd generation
1 + *H. influenzae
*3rd generation: Strep Entero H. influenzae *P. aeruginosa
4th generation: S. aureus Strep Entero H. influenzae *P. aeruginosa
Advanced:
All of the above + MRSA S. aureus
Name the two most significant mechanisms of Gram negative resistance to beta-lactam antibiotics.
a) ampC enzyme production (Class I beta lactamase production)
- cephalosporinases
- gene is turned on if exposed to antibiotic
b) ESBL production (Extended Spectrum Beta Lactamase)
- Mutant gene – lactamaseses are capable of destroying 3rd gen
- some active against 4th gen
Appreciate the mechanisms of ampC enzyme production and ESBL production confer resistance to 3rd and 4th generation cephalosporins.
a) ampC enzyme production – gene if repressed until induced by antibiotic, but mutations in the gene may result in ‘stably de-repressed’ mutant which is a hyperproducer of cephalosporinase. They setroy 3rd generation cephalosporins. Therefore use of 3rd gen selects out these mutants within hospitals.
b) ESBL production – active against 3rd gen and some active against 4th
Name the main antibiotic class used to treat gram negative rods with ampC enzyme or ESBL production.
Carbapenems
Explain why empirical antibiotics must be used against life-threatening infections such as bacterial meningitis. Explain why ceftriaxone is used for this purpose.
Don’t have time to test for pathogen and need to cover potential pathogens:
Neisseria meningitides
Streptococcus pneumonia
Haemophilus influenzae
Ceftriaxone covers all of these
Describe the epidemiology of N. meningitidis infection, explaining the potential evolution of carriage to invasive disease.
Bacteria is in nasopharynx of about 10% of population – carriers. In a small portion of carriers, the bacteria invades the blood or meninges leading to an invasive disease.
Discuss the difference between antibiotic eradication of carriage and treatment of invasive infection; list the antibiotics used for each.
If people have been exposed to certain infections, prophylaxis is used for eradication of possible carriage.
Treatment of invasive infection: ceftriaxone until antibiotic resistance can be determined. Then switch to best option, i.e. may be IV penicillin for N meningitides.
Prophylaxis:
Adult – ciprofloxacin
Children – rifampicin
Pregnant women – ceftriaxone injection
Describe the range of microorganisms causing urethritis.
STD: • Chlamydia trachomatis • Neisseria gonorrhoeae • Ureaplasma urealyticum • Mycoplasma genitalium
Discuss why empirical treatment of urethritis is often necessary
Culture results may not be available for 24-28 hours but treatment may be needed earlier. People with suspected STDs may be less likely to show up for follow up appointments.
Discuss the implications for treatment of detecting N. gonorrhoeae in culture as opposed to PCR.
Resistant to anti-g antibiotics is widespread and increasing, therefore may need to change empiric treatment to one guided by lab susceptibility testing. Culture will tell you what to use.
Gonno:
Empiric choice in rural/remote areas – amoxicillin and probenicid.
Multi resistance is not common here.
Empiric choice metro areas – IMI ceftriaxone (used to be ciprofloxacin)
Overseas strains are more prevalent.
State the antibiotic regimen used for the empirical treatment of urethritis and explain why each drug is used.
Empiric choice in rural/remote areas – amoxicillin and probenicid.
Multi resistance is not common here.
Empiric choice metro areas – IMI ceftriaxone (used to be ciprofloxacin)
Overseas strains are more prevalent.
In general:
Gonno – ceftriaxone – can be used for overseas strains as well
Chlamydia – azithromycin - only single dose
Explain the term “atypical pneumonia”.
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
- Influenza, depending on season
- Legionella pneumophila
- Legionella longbeachae
- Chlamydophila psitacci
Describe a recommended regimen for the treatment of mild community pneumonia and explain why each antibiotic is used.
If not atypical: Oral amoxicillin: - Strep. Pneumonia - H. influenzae If atypical: - doxocycline po (oral) - clarithromycin po - azithromycin po
Demonstrate appreciation of the grading schemes for pneumonia and describe where information about pneumonia treatment can be found.
Pneumonia Severity Scores, i.e. CURB, SMART-COP and PSI (pneumonia severity index).
Tells you about severity, i.e. risk of death, and treatment advice.
Explain what is meant by a polymicrobial infection.
More than one species of microorganism present.
In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease.
Explain why diabetic foot ulcers are polymicrobial.
They are chronic infections – lots of different microbes will find its way there. Can house aerobic bacteria, anaerobic bacteria and even fungi.
List the types of bacteria you would expect to find causing a diabetic foot ulcer.
Gram neg:
- Enterobacteriaceae
- Pseudomonas aeruginosa
Gram positive:
- Staphylococcus aureus
- β-haemolytic streps
- α-haemolytic streps
Anaerobes:
- Bacteroides & others
- Peptococcus spp.
- Peptostreptococcus spp.
List the antibiotics with clinically useful activity against anaerobic bacteria.
- augmentin
- clindamycin
- metronidazole
- Timentin IV
- Tazocin IV
Describe a typical antibiotic regimen for early diabetic foot infections and explain why each antibiotic is included.
- If early:
Augmentin po:
- gram +
- entero (not P. aeruginosa)
- anaerobes
Clindamycin po + ciprofloxacin po:
- gram +
- anaerobes
- gram –
- Inclues P. aeruginosa
Cephalexin po + metronidazole po
- gram +
- some entero (not P. aeruginosa or enterococci)
- anaerobes (metro)
- If deep or bone infection:
Timentin IV, or
Tazocin IV:
- Entero
- P. aeruginosa
- Gram +
- Anaerobes
Meropenem IV:
- very broad
- gram +
- gram –
- P. aeruginosa
- Anaerobes
- NOT MRSA or entero
Describe the different types of respiratory tract infections according to anatomical location
- Bronchitis – bronchial tubes
- Pharyngitis - pharynx
- Rhinopharyngitis – nose and pharynx
- Laryngotracheitis – larynx and trachea
- Pneumonia – lung inflammation
- Sinusitis
- Otitis media – middle ear
Which viruses cause (most of) the common cold?
- rhinovirus
- coronavirus
- adenovirus
Describe the range of symptoms caused by influenza virus
- fever
- headache
- myalgia
- sore throat
- rhinitis
- non productive cough
- otitis media, nausea and vomiting in children
- can lead to pneumonia
In relation to influenza, what is an antigenic shift and antigenic drift?
Antigenic drift
- results from mutations in the gene coding for the NA (less frequently the HA)
- despite the altered NA, the viral subtype remains the same (eg. H3N2 remains H3N2) but the population is less immune
- immunological selection of the new strain takes place in the population and yearly outbreaks of influenza occur
Antigenic shift
- major antigenic changes in HA or NA
- result from genetic reassortment – exchange of genetic material between a human influenza virus and an animal influenza virus
- the result is a new HA or NA; eg. H2N2 becomes H3N2
- lack of immunity in the population to the new subtype results in the major epidemics or pandemics of influenza (1918, H1N1; 1957, H2N2; 1968, H3N2; 1977, H1N1)
Why does the influenza have sometimes become epidemic?
1) A novel (new) virus which humans have no immunity
2) The virus causes significant human illness and death
3) The virus can spread easily from person to person (Avian flu does not have this)
In what way do influenza viruses represent emerging pathogens?
- avian flu
- swine flu
Antigenic shift – genetic reassortment between a human flu and animal flu
Explain briefly why outcomes to the fetus may be different when maternal infection occurs at different stages of pregnancy
Fertilization – week 8 = embryogenesis and organogenesis. Early malformations are usually gross deformities or lethal. Errors in organogenesis often results in errors in developmental processes. More sensitive and greater possibility of maldevelopment.
Name the viral infections which may have deleterious effects on the developing fetus
- parvovirus
- CMV
- VZV
- Rubella
- HHV6
- Mumps and measles – increased fetal loss
Describe the main features of infection with Rubella in the non-pregnant host
- erythematous maculopapular rash with lymphadenopathy
- arthritis/arthralgia
Describe briefly the potential outcomes to the fetus if infected with rubella.
- intellectual disabilities
- cataracts, glaucoma
- deafness
- cardiac defects
- intrauterine growth retardation
- may be born with haemorrhagic rash
- microcephaly
- inflammatory lesions
Describe the main features of infection with Parvovirus B19 in the non-pregnant host
- fever
- headache
- malaise
- erythematous rash of the cheeks
- rash of the trunk and arthritis may occur
Describe briefly the potential outcomes to the fetus if infected with parvovirus B19.
- excess fetal loss
- ascites (causing abdominal swelling)
- pleural effusion
- pericardial effusion
- skin edema
- polyhydramnios (excess amniotic fluid in amniotic sac)
Describe the main features of infection with VZV in the non-pregnant host
- chickenpox – rash which progresses from small fluid filled vesicles through to pustules and crusty scabs.
- risk of varicella pneumonitis in adults
- risk of varicella encephalitis in adults
- Zoster – virus in one dermatome
Describe briefly the potential outcomes to the fetus if infected with VZV.
- early foetal loss
- foetal varicella syndrome:
- limb atrophy
- skin scarring
- ocular abnormalities
- neurological abnormalities
- shingles early in life
- in utero chickenpox/shingles
Describe the main features of infection with CMV in the non-pregnant host
- fatigue
- fever
- mildly enlarged liver and spleen
- hepatitis
- raised lymphocyte count in blood
Describe briefly the potential outcomes to the fetus if infected with CMV.
- fetal death
- jaundice
- microcephaly
- intellectual disability
- hepatitis
- thrombocytopaenia
- **deafness
List the most clinically important types of blood-borne viral infection.
- HIV,
- HCV (Hep C),
- HBV
What are the most clinically important types of Herpesvirus infection?
- VZV
- HSV
- EBV
- CMV
What are two types of HIV virus and describe the differences in their geographical distribution
- HIV 1 - most common cause of HIV
- found throughout the world - HIV 2 - it is less transmissible and causes a less severe infection
- much less common than HIV 1
- largley confined to West Africa
In general, over 2/3 of people living with hIV are in Sub-Saharan Africa
Outline the lifecycle of the HIV virus in the human host
Lifecycle:
- HIV binds to the CD4 receptor on hosts T helper cell surfaces
- it transcribed its genomic RNA to DNA with reverse transcriptase
- the viral DNA is then integrated into human DNA
- The viral genes encode (transcribe) a variety of proteins, and new virions are produced.
- host cell dies
Demonstrate why it is important to understand the HIV lifecycle to appreciate antiretroviral action
- The aim of HIV treatment is to suppress virological replication and allow recovery of the CD4 cell population.
- Antiviral meds include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and fusion inhibitors
Describe the routes of transmission of HIV
Fluids that can transmit HIV:
- blood
- semen
- vaginal secretions
- breast milk
These must come in contact with a mucous membrane or damaged tissue, or be directly injected into the blood-stream for transmission to occur.
Most common methods of transmission:
- sexual
- mother to child
- sharing needles
Less common:
- oral sex
- exposure to infected vlood
- transfusion
- organ transplant
Describe briefly the time course of HIV infection and the development of AIDS
- Acute infection
- 0-9 weeks
- peak of HIV RNA copies in plasma, then sudden decrease before latency
- CD4 lymphocyte count decreases and then starts to increase before latency - Clinical Latency
- 9wks - 7 years
- HIV RNA copies in plasma increases slowly over time
- CD4 lymphocyte count increases for a bit and then decreases slowly over time - Symptomatic Infection
- 7 years +
- HIV RNA copies in plasma increases quicker
- CD4 lymphocyte count continues to decrease
Median period for progression to AIDS is 10 years if not treated
Most infectious in early and late infection
Name the main infectious and neoplastic conditions associated with AIDS
- Opportunistic infections:
- Pneumocystis pneumonia
- tuberculosis
- Progressive Multifocal Leukoencephalopathy
- Cerebral toxoplasmosis
- Cryptococcal infection
- Cryptosporidiosis
- Cytomegalovirus retinitis
- Disseminated MAC (Mycobacterium avid complex) - Neoplasia:
- Kaposi’s Sarcoma (proliferation of vascular structures within the skin, mucous membranes, and rarely organs.)
- non-Hodgkin’s lymphoma
- multiple myeloma
- melanoma
- solid organ cancers
