Resistance Mechanisms and Side Effects Flashcards
Intrinsic resistance
Natural resistance
Usually due to inability of drug to permeate bacterial cell
All Gram(-) bacteria are resistant to vancomycin
All streptococci are resistant to aminoglycosides
Laboratory sensitivity testing irrelevant
Acquired resistance
Spontaneous mutation alters drug target
Gene transfer via plasmids/transposons
Laboratory sensitivity testing necessary for treatment
Darwinian evolution in action - AB is selective pressure
Beta lactam resistance
Beta lactamase production (cleaves beta lactam ring)
- common in Gram(-) bacilli
- present in most nosocomial S. aureus strains
- use beta lactamse inhibitor e.g. clavulanic acid
- modify beta lactam R1 chain e.g. flucloxacillin
Alteration of PBPs
ESBLs (Extended Spectrum Beta Lactamases)
Can break down third generation cephalosporins
Organism is resistant to all beta lactams
CPEs (Carbamenemase Producing Enterobacteriaceae)
Extremely resistant Gram(-) organisms
Resistant to carbapenems
PBP mutations
Beta lactam resistance
Modified target
Addition of beta lactamse makes no difference
Present in MRSA, S. pneumonia
VRE (Vancomycin Resistant Enterococci)
Resistant to glycopeptides
Altered target site mechanism
Occurs in Gram(+) organisms
Common side effects
Allergic reactions Liver toxicity Renal toxicity Neurological Toxicity Heamatological Toxicity Thrush
Allergic Reactions
Most commonly associated with beta lactams
Immediate hypersensitivity
Delayed hypersensitivity
GI side effects
Immediate hypersensitivity
Anaphylactic shock
Within minutes of administration
Usually follows parenteral administration
IgE mediated
Delayed hypersensitivity
Hours to days Immune complex/cell mediated Maculopapular skin rash Drug fever Serum sickness Erythema nodosum Stevens-Johnson syndrome - associated with sulphonamides; involvement of skin and mucous membranes
GI side effects
Nausea
Vomiting
Diarrhoea due to C. diff overgrowth
- diminished normal flora
- carried asymptomatically in very
young and very old
- produces toxins - EIA detection from
stool sample
- CDAD - CDI - pseudomembr colitis
- CDI barrier nursed unti asymp for 48h
- oral metronidazole/vancomycin
- stop precipitating ABs
- spore forming - not killed by alcohol
Thrush
Candidiasis
Result of broad spectrum antibiotics suppressing normal flora and allowing overgrowth of resistant organisms
Liver toxicity
More common in patients with pre-existing liver disease and pregnant women
Can lead to severe hepatitis
E.g. tetracycline, isoniazid, flucloxacillin, rifampicin
Renal toxicity
More common in patients with pre-existing renal disease
Dose related
Usually associated with vancomycin and aminoglycosides
