7. Introduction To Antibiotics And Resistance Flashcards
What are the types of antimicrobials?
Antibacterial
Antifungal
Antiviral
Antiprotozoal
How can antimicrobial agents be classified?
Bactericidal or bacteriostatic Spectrum - broad vs narrow Target site (mechanism of action) Chemical structure (antibacterial class)
How do you choose an antibiotic?
Is it active against target organism?
Does it reach site of infection? (Cross blood-brain barrier)
Is it available in right formulation? (IV or oral)
What is the half life? (Decides dosing frequency)
Does it interact with other drugs?
Is there toxicity issues?
Does it require therapeutic drug monitoring?
How can you measure antibiotic activity?
Disc sensitivity testing - measure zone of clearance for each antibiotic
Disc diffusion testing
Broth microdilution - minimum inhibitory concentration (MIC)
E test - strip of varying gradients of antibiotics, MIC
What are the classes of antibacterial and their mechanism of action?
Cell wall synthesis: beta-lactams (penicillin, cephalosporins), glycopeptides
Cell membrane function: polymixins (colistin)
Protein synthesis: tetracyclines, aminoglycosides, macrolides
Nucleic acid synthesis: quinolones, trimethoprim, rifampicin
How does penicillin work?
Prevents penicillin binding protein from binding cell wall of bacteria together
How does vancomycin work?
Prevents cell wall cross-linking enzyme working by blocking it
What are the types of resistance?
Intrinsic - no target or access for drug, permanent
Acquired - acquires new genetic material or mutates, permanent
Adaptive - organism responds to a stress, can go back to being sensitive
What are the mechanisms of resistance?
Enzymatic modification or destruction of antibiotics
Enzymatic alteration of antibiotic targets
Mutations of bacterial target sites
What is horizontal gene transfer?
Donor with plasmid with resistant gene can give the gene to a different protein, so more bacteria are resistant
Are penicillins active against gram-positive or gram-negative?
Gram-positive
Amoxicillin has some activity against gram-negatives
What is penicillin active against?
Mainly streptococci
What is flucloxacillin active against?
Staphylococci and streptococci
What are the B-lactamase inhibitor combinations and what are they active against?
Co-amoxiclav - streptococci, staphylococci, anaerobes, more gram negative
Piperacillin/tazobactam - streptococci, staphylococci, lots more gram negative including pseudomonas), effective in sepsis
What are cephalosporins active against?
Generations with increased Gneg and decreased Gpos
Broad spectrum but not anaerobe activity
Ceftriaxone has good activity in CSF
Concern over association with C. difficile
What are the carbapenems?
Meropenem
Ertapenem
Imipenem
What are carbapenems?
Very broad spectrum
Active against most gram negs
Generally safe in penicillin allergy
Often considered reserve antibiotic for gram neg infections
What are the two types of glycopeptides?
Vancomycin
Teicoplanin
What is vancomycin?
Active against most gram pos
Some enterococci resistant (VRE) - hospital associated
Resistance in straphs rare
Not absorbed (oral for C. difficile only)
Therapeutic drug monitoring required
What is teicoplanin?
Similar activity to vancomycin
Easier to administer (given once a day, monitor less)
What are tetracycline and doxycycline?
Similar spectrum, both oral only
Broad spectrum but specific use in penicillin allergy, usually gram pos
Active in atypical pathogens in pneumonia
Active against chlamydia and some Protozoa
Not given to under 12 years, pregnant and breast feeding women (causes staining of developing teeth)
What is aminoglycosides?
Most common agent is gentamicin Profound activity against gram negs Good activity in blood/urine Potentially nephrotoxic/ototoxic Therapeutic drug monitoring required Generally reserved for severe gram neg sepsis
What are macolides?
Erythromycin and clarithromycin
Well distributed including intracellular penetration
Alternative to penicillin for mild gram pos infections
Active against atypical respiratory pathogens
What are quinolones?
Ciprofloxacin
Inhibit DNA gyrase
Very active agains gram negs and atypical pathogens
Increasing resistance and risk of C. difficile
Association with tendinitis and rupture, aortic dissection and CNS effects
What is trimethoprim and sulphonamides?
Inhibitors of folic acid synthesis
Trimethoprim used alone in UK for UTI
When combined with sulphamethoxazole: co-trimoxazole, used for pneumocystis jirovecii, has activity against MRSA, can cause severe skin reactions
What are the 2 types of antifungals?
Azoles
Polyenes
What are azoles?
Active against yeasts and molds
Inhibit cell-membrane synthesis
Fluconazole used to treat candida
Itra/vori/poaconazole also active against aspergillus
What are polyenes?
Nystatin and amphotericin
Inhibit cell membrane function
Nystatin for topical treatment of candida
Amphotericin for IV treatment of systemic fungal infections
What are the 2 types of antivirals?
Aciclovir
Oseltamivir
What is aciclovir?
When phosphorylated inhibits viral DNApolymerase
Herpes simplex - genital herpes, encephalitis
Varicella zoster - chickenpox, singles
What is oseltamivir (tamiflu)?
Inhibits viral neuraaminidase
Influenza A and B
What is metronidazole?
Antibacterial and antiprotozoal agent
Active against anaerobic bacteria and protozoa
Amoebae, giardia, trichomonas, C. diff
