Flashcards in antimicrobials Deck (47):
What are the MINDME guidelines for antimicrobial therapy?
M: microbiology guidelines used whenever possible
I: indications should be evidence based
N: narrowest spectrum required
D: dosage appropriate to the site and type of infection
M: minimise duration of therapy
E: ensure mono therapy in most situations
What is directed therapy vs. empirical therapy?
directed therapy - base choice of therapy on culture or susceptibility test results
empirical therapy - known common pathogens and resistance patterns (seasonality)
duration should be as short as possible, should not exceed 7 days unless there is proof this length of time is inadequate
Targets of antibacterials?
cell wall synthesis
DNA- inhibit cell division
other metabolic processes
Factors affecting choice of antibacterial
bacterial factors: what type of organism, how resistant
host factors: site of infection, allergies, renal/hepatic function, concomitant drugs, age
drug factors: spectrum of activity, pharmacokinetics, adverse effects profile, cost
Antibacterial families targeting cell wall bio synthesis
beta-lactams, glycopeptides, cephalosporins
Antibacterial families targeting protein biosynthesis
macrolides, tetracyclines, aminoglycosides, oxazolidinones
Antibacterial family targeting DNA replication and repair
antibacterial families targeting folate synthesis?
antibacterial family targeting cell membrane?
antibacterial families targeting protein synthesis?
linezolid, tetracyclines, macrolides, aminoglycosides
size of virus particles
size range 10-400nm in diameter, most need to be viewed with EM
Can visions exist extracellularly?
Yes, rotavirus exists extracellularly for a few hours in the air
What is a nucleocapsid?
composed of DNA or RNA or a capsid, some viruses may also have an envelope
structural elements of a virus?
1. nucleic acid: DNA or RNA, genome can be segmented or circular
2. capsid: capsomeres
what is the ending for virus order, family, subfamily and genus
what are the two main systems for classifying viruses
ICTV: international committee on taxonomy of viruses
- main body
Baltimore system complements ICTV, focusses on viral genome and the methods used to synthesise mRNA
How would you classify viruses based on the genome? (5)
dsDNA, ssDNA, dsRNA, ssRNA
- in ssRNA, + strand RNA is identical to mRNA sequence produced by the virus (positive strand)
- strand RNA is complementary to mRNA sequence (negative strand)
common target of antiviral drugs? problems that can occur?
viral polymerase; toxicity can arise when viral polymerase is similar to host cell polymerase
most agents are virustatic - often by the time a viral infection is diagnosed, the virus spread and replication is complete
What does aciclovir target?
viral DNA/RNA synthesis
What does zidovudine target?
viral DNA/RNA synthesis
What do interferons target?
viral protein synthesis
Mechanism of acyclovir?
(prodrug, activated by viral kinases)
= chain terminating agent; added to chain by viral polymerase but lacks 3'OH required for chain extension
Mechanism of zidovudine?
(prodrug, activated by viral kinases)
= NRTI (nucleoside reverse transcriptase inhibitor)
= chain terminator, inhibits viral reverse transcriptase
- has some toxicity: bone marrow suppression, nausea, vomiting, malaise
- resistance is well recognised
- combination/alternating therapy slows development of resistance and minimised toxicity to a particular tissue
ways to monitor antiviral therapy
- measure viral load e.g. by real time PCR
- monitoring mutation rates e.g. by RFLP (restriction fragment length polymorphism) and sequencing
mechanism of ritonovir?
prevent processing of viral polyproteins, inhibit viral maturation
used in combination with NRTIs
mechanism of oseltamivir
- competitive, reversible inhibitors of neuraminidase
- active against influenza A and B
- resistance minimal to date
- reduce viral shedding and disease duration if given early
what disease is ritonavir used to treat?
types of drugs used to treat HIV?
non-NRTIs and protease inhibitors
types of drugs to treat influenza?
ion channel blockers and neuraminidase inhibitors
types of drugs used to treat HBV?
NRTIs and NNRTIs
drug used to treat HCV?
interferon, half-life can be extended by PEG-ylation; used in combination with ribavirin with effectiveness depending on HCV genotype
side effects of interferon used to treat hepatitis?
flu-like symptoms: fever, myalgia, headache
What is amphotericin - B used to treat?
- candidiasis = systemic mycoses (fungal infections)
- caused most frequently by candida albicans (causing cutaneous lesions of nails and skin, mucosal lesions of mouth and vagina, systemic lesions of immunocompromised patients)
- used for superficial and systemic fungal infections
- severe side effects: damage to kidney and blood forming tissues, cardiac arrest
Targets for antifungals?
- azoles: inhibit enzyme for sterol synthesis (inhibit fungal cell membrane biosynthesis)
- polyenes: bind to membranes causing cell leakage and death
- inhibit nucleic acid synthesis
metronidazole may target two types of antimicrobials, which ones?
bacteria and protozoa
Ivermectin: what microbe is it used to treat, what is its target?
nematodes, unique neurotransmitters
3 features of Kingdom Protista?
most are unicellular
lack level of tissue organisation present in higher eukaryotes
What is Trichomonas vaginalis?
= pathogenic trichomonad. Anaerobic, flagellated protozoan parasite
Trichomoniasis is a sexually transmitted infection in humans
cause of African sleeping sickness?
pathogenic Euglenozoa: trypanosomes
specifically T. brucei gambiense and T. brucei rhodesiense
Tsetse fly is a Trypanosoma vector
What does entamoeba histolytica cause?
causes amoebic dysentery
3rd leading cause of parasitic death worldwide
acquired by consuming E. histolytica cysts
may migrate to lungs, brain, liver or skin
What is the effect of toxic algal blooms?
- brevetoxins produced by dinoflagellates are toxic by inhalation or ingestion
- oxygen depletion of the water column
Example of an apicomplexan?
Plasmodium, causing malaria
clonal and sexual stages are haploid except for zygotes
sporozoite is the motile, infective stage
Structures making up the apical complex of anti-protozoal
polar ring, conoid, subpellicular microtubules, micronemes, rhoptry, micropore
4 main human species of plasmodium
P. falciparum, vivid, malariae, ovale
What mosquito transmits plasmodium?
anopheles (~40 species transmit plasmodium)
Drugs to treat malaria?
quinine - serious side effects
chloroquinone - used in prophylaxis and treatment; P. falciparum resistant and P. vivax is developing resistance
antifolate compounds: mefloquine, widespread resistance