Antimicrobial Chemotherapy Flashcards
Benzyl penicillin’s
Inhibit cell wall synthesis
Beta lactam
Bactericidal
Mainly effective against gram positive bacteria
Gram negatives are widely resistant
Cephalosporins
Inhibit cell wall synthesis
Bactericidal
Second large group of beta lactams
What is the mechanism of beta lactams?
They inhibit peptidoglycan synthesis by inhibiting the enzymes (penicillin binding proteins) that cross link the carbohydrate chains of the peptidoglycan cell wall.
Glycopeptides
Group of antibiotics that inhibit cell wall synthesis
Bactericidal
Only act on gram positive organisms
Act on cell wall synthesis a stage prior to beta lactams
Inhibit assembly of a peptidoglycan precursor
Only given parenterally
Vancomycin
Glycopeptide
Toxicity is common
I.V. infused and carefully monitored
Teicoplanin
Glycopeptide
Less toxic than vancomycin
Aminoglycosides
Inhibit protein synthesis
Concentration dependant bactericidal antibiotics
Useful in treating serious gram-negative infection
Mechanism of aminoglycosides
Inhibit protein synthesis
Acts only on bacterial protein synthesis due to differences in bacterial and mammalian ribosomes.
Binding impairs the proofreading of translation leading to mistranslation of the RNA message and inaccuracy of the translated protein product.
Gentamicin
Aminoglycoside
Toxic and requires a careful dosing regime and close monitoring.
Macrolides
Inhibit protein synthesis
Bactericidal or bacteriostatic
Useful in treating gram positive infections when patient has a penicillin allergy
Macrolide mechanism
Inhibit protein synthesis
Prevent peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid
Also inhibits ribosomal translation
Erythromycin
Example of a macrolide
Tetracyclines
Inhibit protein synthesis
Batceriostatic antibiotics
Treats gram positive infections
A significant percentage of staph. and strep. strains are resistant
Mechanism of tetracyclines
Tetracyclines prevent the introduction of new amino acids to the nascent peptide chain
Oxazolidinones
Inhibit protein synthesis
Bacteriostatic or bactericidal dependant on the bacteria being treated
Usually treat gram positive infections
Linezolid
Oxadolidinone
Only antibiotic in this class in common use
Generally reserved for serious infections
Cyclic lipopeptides
Inhibit protein synthesis
Strong bactericidal agents
Treat gram positive infections
Daptomycin
Cyclic lipopeptide
Acts against gram positives and MRSA in particular
Alters the curvature of the membrane, causing holes that leak ions, deplarization and bacterial cell death
Purine synthesis inhibitors
Inhibit nucleic acid synthesis
Bacteriostatic and bactericidal when combined
Inhibit DNA synthesis directly or by interrupting precursors for DNA synthesis
Trimethoprin and sulphamethoxazole
Often used in combination as co-trimoxazole
Does not predispose C.difficle
Fluroquinolones
Bactericidal
Inhibit nucleic acid synthesis
Particularly effective against gram negative organisms
Inhibit DNA synthesis more directly
Ciprofloxacin and levofloxacin
Fluroquinolones
What are the two types on antibiotic resistance
Inherent and acquired
Inherent resistance
When all strains of a given species are resistant to an antibiotic
Streptococci are always resistant to aminoglycosides
Gram negative organisms are always resistant to vancomycin
Acquired resistance
May be present in certain strains but not others
Laboratory sensitivity testing is required to establish the sensitivity of the patients bacterial isolate
What is antibiotic resistance a good example of?
Natural selection
Two ways that resistance is acquired
1) Spontaneous mutation
2) Genes that code for resistance can be spread from organism to organism or species to species
Genes can be carried on plasmids or transposons
Conjugation
DNA transfer between bacterial cells
Transformation
Naked DNA uptake by bacteria
Transduction
Bacterial viruses transferred by viruses
Beta lactamases
Enzymes produced that cleave the beta lactam ring of an antibiotic and thus render it inactive
Where are beta lactamases most often seen?
In most hospital strains of staph. aureus and also in many gram-negative bacilli
Two ways of combatting beta lactamase
1) Modify the antibiotic side chain to include a beta lactamase inhibitor
2) Introduce a second compartment to the antibiotic (beta lactamase inhibitor) protecting the antibiotic from enzymatic degradation
Co-amoxiclav
Amoxicillin plus beta lactamase inhibitor clavulanic acid
Flucoxaicillin
Modified form of penicillin that resists beta lactamase
Extended spectrum beta lactamases
Enzymes that mediate resistance to extended spectrum cephalosporins
Antibiotic resistance transferred by conjugation
Carbapenemase-producing enterobacteriaceae
Bacteria resistant to carbapenem family of antibiotics by producing carbapenemase
Carbapenem Resistant Enterobacteriaceae
Bacteria resistant to carbapenem family of antibiotics by any mechanism
Serious problem as this sometimes leaves no options for antimicrobial therapy.
What mechanism has MRSA developed to become multi-drug resistant?
It has developed resistance to beta lactams by changing the shape of its penicillin protein binding sites. The PBP changes shape causing a modified binding site that beta lactams can’t bind to.
What can MRSA be treated with?
Vancomycin or Linezolid
Glycopeptide resistance
Before gram positive resistance to glycopeptides was virtually unknown.
Recently vancomycin resistant enterococci have been emerging
The peptidoglycan precursor that vancomycin usually binds to has an altered structure.
Agents used only in UTI’s
Nalidixic acid and nitrofurantoin
What can cause thrush (overgrowth of candida albicans)
Therapy with penicillin’s or cephalosporins
Polyenes
Anti-fungal drug
Binds to ergosterol, present in the fungal cell wall
Active against yeasts and filamentous fungi
Amphotericin B
Polyene
Only available for IV use and used in serious fungal infections
Extremely toxic
Nystatin
Polyene
Available for topical use
Azoles
Anti-fungal drug
Inhibits ergosterol synthesis
Fluconazole
Azole
Oral and parenteral treatment of yeast infections
No serious toxicity
Some yeasts are resistant
Itraconazole
Active against yeasts and filamentous fungi
Allylamines
Suppress ergosterol synthesis
Anti-fungal
Only allylamine used is terbinafine which is active against dermatophyte infections of the skin
Echinocandins
Anti-fungal
Inhibit the synthesis of glucan polysaccharide in several types of fungi
Only used in serious candida and aspergillus infections
Nucleoside analogues
Most anti viral drugs
Interfere with nucleic acid synthesis
Aciclovir
Nucleoside analogue
Anti-herpes virus drugs
Specific for virus infected cells
Active against herpes simplex and varicella zoster
Valaciclovir, famciclovir, valganciclovir
Anti-herpes virus drugs
Herpes viruses
Herpes simplex, CMV, varicella-zoster, epstein-barr virus
Zidovudine
First anti-HIV drug
How do we usually treat HIV now?
Combination therapy with at least 3 drugs
Drugs active on at least 2 different stages of HIV replication
2 nucleoside analogue reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor or a viral protease inhibitor
Interferon-A, ribavirin, adevofir dipivoxil
Drugs for chronic hepatitis B and C
Drugs for viral respiratory infections
Zanamivir, oseltamivir, ribavirin
