Antimicrobial Chemotherapy Flashcards
What are antibiotics effective against?
Bacteria?
What does bactericidal mean?
Antimicrobial that kills bacteria.
What does bacteriostatic mean?
Antimicrobial that inhibits the growth of bacteria.
What is the MBC?
Minimum bactericidal concentration- minimum concentration required to kill the bacteria.
What is the MIC?
Minimum inhibitory concentration- minimum concentration required to inhibit the growth of the bacteria.
What are the routes of antimicrobial administration?
Topical
Systemic
Parenteral
How are topical antimicrobials administered?
Applied to a surface (skin/mucous membranes)
How are systemic antimicrobials administered?
Taken internally (oral/parenteral)
How are parenteral antimicrobials administered?
Intravenously.
What are the 3 areas of metabolic activity that antimicrobials use to kill/inhibit bacteria?
Inhibition of the cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
What drugs inhibit cell wall synthesis?
Beta-lactams (Penicillin and Cephalosporins)
Glycopeptides
What are beta-lactams and what are they effective against?
Bactericidal
Effective against gram positive bacteria
How do beta-lactams work?
They disrupt peptidoglycan synthesis by inhibiting the enzymes (PBPs) which are responsible for cross-linking the carbohydrate chains.
Why are many gram-negative bacteria resistant to beta-lactams?
Inability to penetrate the gram-negative cell wall.
What are glycopeptides and what are they effective against?
Bactericidal
Effective against gram-positive bacteria
How do glycopeptides work?
They act on cell wall synthesis at a prior cell to B-lactams; inhibiting the assembly of a peptidoglycan precursor.
How are glycopeptides administered and why?
Parenterally- not absorbed in the GI tract.
Give an example of a toxic glycopeptide.
Vancomycin
What drugs inhibit protein synthesis?
Aminoglycosides Macrolides Tetracyclines Oxazilidinones Cyclic lipopeptide
What are aminoglycosides used for?
Bactericidal (concentration-dependent)
Treat gram-negative infections
What is the most common aminoglycoside?
Gentamycin- toxic.
What are macrolides used for?
Bactericidal / bacteriostatic
Treat gram-positive infection
What category of patients are macrolides particularly useful in?
Patients who are allergic to penicillin.
What are tetracyclines used for?
Bacteriostatic
Treat gram-positive infection
What is a disadvantage of macrolides and tetracyclines?
Increasing antibiotic resistance (S.aureus/S.pyogenes/Strep)
What are oxazolidinones used for?
Bacteriostatic/bactericidal
Gram-positive infection
Give an example of an oxalidinone.
Linezolid- reserved for serious infection (MRSA).
What are cyclic lipopeptides used for?
Bactericidal (strong)
Gram-positive infection
Give an example of a cyclic lipopeptide .
Daptomycin
What drugs inhibit nucleic acid synthesis?
Purine synthesis inhibition drugs
Fluoroquinolones
How do drugs work in purine synthesis inhibition?
Bacteriostatic but can kill when combined.
Combined form is co-trimoxazole.
How do fluoroquinolones work?
Bactericidal
Gram-negative including pseudomonas.
Why can fluoroquinolones not be used in children?
Adverse effect on cartilage development.
Give an example of a fluoroquinolone.
Ciprofloxacin / levofloxacin.
What is the clinical definition of antibiotic resistance?
An antibiotic is considered to be resistant when it is unable to respond to attainable levels of that drug in tissues.
How is antibiotic resistance measured for clinical practice?
Sensitivity is measured in laboratory.
What are the two types of antibiotic resistance?
Inherent (due to mutation/changes etc)
Intrinsic (natural resistance through binding etc)
How does the widespread use of antibiotics lead to resistance?
Creates a selective pressure and encourages new resistant organisms to outgrow sensitive strains.
What are B-lactamases?
B-lactamases are bacterial enzymes which cleave the B-lactam ring of the antibiotic and thus render it ineffective.
What bacteria produce B-lactamases?
Most strains of staphylococcus aureus
Many gram-negative bacteria
How is B-lactamase combatted?
Modification of the antibiotic side chain, producing a new antibiotic resistant to the effects of B-lactamse
(Co-trimoxaclav- Amoxycillin + Clavulanic acid).
To produce a second component (B-lactamase inhibitor) to the antibiotic- preventing enzyme degradation.
(Flucloaxcillin- modified form of penicillin).
What drugs are resistant to B-lactamases?
Co-trimoxaclav
Flucloaxicillin
What are ESBL’s?
Extended spectrum B-lactamases:
Problem in hospitals with some gram-negative organisms- ESBL carrying patients have selective infection control measures in addition to usual regulations.
What are carbapenems?
Very strong antibiotic agents which are used for the treatment of moderate/high-risk infections.
What are carbapenems reserved for?
Multi-drug resistant (MDR) bacterial infection.
What class of antibiotics are carbapenems in?
B-lactam.
What are CPE/CRE?
Carbapenemase producing enterobacteriae
Carbopenem resistant enterobacteriae
What are the major issues with CPE/CRE?
Carbopenem resistance is mainly an issue in gram-negative organisms and is becoming a huge problem in terms of clinical infection control and the fact that there are often no antimicrobial therapies available for it.
How does alteration of PBP target sites allow resistance?
Altering the target sites for penicillin binding proteins can allow resistance as the structure changes and penicillin is thus unable to bind.
How do alterations in the PBP target sites develop?
Mutations in the PBP gene conferring structural change.
What is the best known example of PBP target site alterations causing antibiotic resistance?
MRSA.
What is MRSA?
MRSA refers to any staphylacoccus aureus which has, through horizontal gene transfer/mutations, developed multiple drug resistance to B-lactams.
How are bacteria resistant to B-lactams treated?
Flucoaxicillin not MRSA
Vancomycin
Linezolid
Is glycopeptide resistance common?
Gram-positive resistance to vancomycin has been uncommon but is now developing.
What are glycopeptide resistant bacteria called?
VRE (Vancomycin resistant enterococci)
How does resistance to glycopeptides work?
Vancomycin acts by inhibiting the production of a peptidoglycan precursor in cell wall formation. In VRE, the peptidoglycan precursor to which vancomycin usually binds has an altered structure.
Why is VRE a problem?
Could potentially spread into S.aureus.
What is benzyl penicillin used to treat?
Gram-positive infection
Intravenous administration
Best choice of IV for serious streptococcus pneumonia.
What is amoxycillin used to treat?
Gram-negative infection
Better oral absorption
20-30% coliforms resistant.
What is ampicillin used to treat?
Gram-negative infection
Better oral
What is co-amaxiclav used to treat?
Gram-negative
Combines amoxycillin with clauvanic acid to inhibit B-lactamase.
What is flucoaxicillin used to treat?
Staphylococci
Modified form of penicillin resistant to B-lactamase
What is piperacillin used to treat?
Broad spectrum, extensive gram-negative cover, pseudomonas
What is imipenem used to treat?
Most bacterium including anaerobes. (widest range)
What is meropenem used to treat?
Carbopenem- wide range of most bacterium including anaerobes.
What do cephalosporins treat?
Gram positive/negative infection
Described in generations.
How does cephalosporin activity relate with generations?
Gram negative activity increase from first to subsequent generations.
Activity against gram positive activity decreases from first to subsequent generations.
What are the glycopeptides called and how are they administered?
Gram positive only
Vancomycin
Teicoplanin
Describe an example of an aminoglycoside.
Gentamycin- toxic
Parenteral administration
How do tetracyclines act?
Broad spectrum
Useful in chlamydia/resp. tract infections
Give examples of macrolides and their use.
Allergy to penicillin:
Erythromycin
Clarithromycin
Azithromycin (chlamydia)
Give an example of an oxazolidinone and its use.
Linezolid- MRSA use
Give an example of a cyclic lipopeptide and its use.
Daptomycin- Gram positive and MRSA use
What agents are used only in the treatment of UTIs?
Nalidixic acid
Nitrofurantoin
What are quinolones used to treat?
Gram-negative, pseudomonas
What are the Fluoroquinolones?
Ciprofloxacin / Levofloxacin
Why are Fluoroquinolones not used in paediatrics?
Disruption to cartilage development.
What is the incidence of ADR’s dependent on?
Dosage and drug.
What happens in immediate hypersensitivity to an antibiotic?
Anaphylactic shock (parenteral administration of the antibiotic)- IgE mediated response occurs within minutes of administration. Can include itching, nausea, urticaria, vomiting, wheezing and shock. Laryngeal oedema can prove fatal unless the airway is cleared.
What happens in delayed hypersensitivity to an antibiotic?
Takes hours or days to develop, immune complex or cell-mediated mechanism. Can include rashes, fever, serum sickness.
What are the gastrointestinal side effects of antibiotics?
Vomiting / nausea / diarrhoea
Why is thrush a common side effect?
Suppression of normal flora, resulting in growth of resistant organisms.
What body systems often experience side effects?
Liver and renal (nephrotoxicity of excretion)
How can antibiotics affect haematology?
There can be a toxic effect on the bone marrow resulting in the selective depression of one cell line or unselective depression of all bone marrow elements.
When should antibiotics be prescribed?
When absolutely necessary.
When is antimicrobial prophylaxis used?
Patients in close contact with contagious others.
Following surgery with high post-op infection rates.
What is the simplest type of therapy?
Monotherapy
What are the 3 outcomes of antimicrobials being used in combination?
Additive
Antagonistic- combined effect less than individual
Synergistic- combined effect greater than individual
What antibiotics should be monitored even more closely?
Those with a low therapeutic index.
Why would the laboratory monitor the serum levels of antibiotic?
- To ensure that the therapeutic levels have been achieved
2. To ensure that the levels are not high enough to reach toxicity
Do antibiotics affect fungal infection?
No.
What are the 4 types of fungal drug?
Polyenes
Azoles
Allylamines
Echinocandins
What do polyenes do?
Active against yeast and moulds
What do azoles do?
Inhibit ergosterol synthesis.
What do allylamines do?
Suppress ergosterol synthesis at various points
Terbinafine
What do echinocandins do?
Inhibit synthesis of gluten polysaccharide.
Do antibiotics affect viruses?
No.
What is aciclovar used to treat?
Herpes
What therapy is usually given for HIV?
Combination triple-drug therapy.
What are Interferon-A and ribavirin used for?
Chronic hepatitis B/C.
What are ribavirin and zanamivir used for?
Viral respiratory infection.
What must still be monitored in viral therapy?
Balance of therapeutic index/toxicity and links to resistance.
