PoD - Antimicrobial Chemotherapy Flashcards
define bactericidal
- antimicrobial that kills bacteria
define bacteriostatic
- antimicrobial that inhibits growth of bacteria
what does it mean if an organism is ‘sensitive’ to an antimicrobial?
- organism is sensitive if it is inhibited or killed by the antimicrobial available
what does it mean if an organism is ‘resistant’ to an antimicrobial?
- organism is resistant if it is not inhibited or killed by the antimicrobial
what does minimal bactericidal concentration mean?
- MBC is the minimum concentration of antimicrobial needed to kill a given organism
what does minimal inhibitory concentration mean?
- MIC is the minimum concentration of antimicrobial needed to inhibit growth of a given organism
list the main routes of administration
- topical
- systemic
- parenteral (injection)
what are the 3 methods antibiotics use to inhibit/kill bacteria?
- inhibition of cell wall synthesis
- inhibition of protein synthesis
- inhibition nucleic acid synthesis
what are the main differences between gram +/-ve bacteria?
- gram positive = thick peptidoglycan layer = PURPLE
- gram negative = thin peptidoglycan layer = PINK
what antibiotics inhibit cell wall synthesis?
Penicillins & cephalosporins (beta-lactams)
- bactericidal antibiotics
- effective against most gram-positive bacteria
- disrupt peptidoglycan synthesis by inhibiting the enzymes (penicillin binding proteins) responsible for cross-linking the carb chains needed to create cell wall
Glycopeptides
- bactericidal antibiotics
- only act on gram-positive bacteria
- inhibit assembly of peptidoglycan precursor. Prevent the binding of proteins to PBPs
- need to be given parenterally, can’t absorbed from GI tract (vancomycin - toxicity is common)
what antibiotics are given to inhibit protein synthesis?
Aminoglycosides - bactericidal antibiotics
- used in treatment of serious gram negative
- binding impairs translation ‘proof-reading’ so leads to RNA being mis-read, premature termination or inaccuracy of product
(gentamicin - toxicity is common)
Macrolides - bactericidal or static depending on conc
- useful alternative to penicillin
Tetracyclines - bacteriostatic
- gram positive infections
- a significant percentage of staph.aureus/strep.pyogenes/strep.pneumoniae are resistant
Oxazolidones - bacteriostatic or cidal
- treatment of gram positive infection
- prevents formation of complex required for bacterial reproduction
(linezolid - new class, given orally, serious infection)
what antibiotics inhibit nucleic acid synthesis?
co-trimoxazole - bacteriostatic
- inhibit purine synthesis
- inhibit DNA synthesis directly or indirectly
fluroquinolones - bactericidal
- gram-negative organisms
- direct inhibition of DNA synthesis
- used orally/parenterally can’t be used with children
define bacterial resistance
- an organism is considered resistant to a given drug when it is unlikely to respond to attainable levels of that drug in tissue
what is intrinsic resistance? give examples
- all strains of a given species are naturally resistant to an antibiotic
- streptococci resistant to aminoglycosides
- gram-negative organisms always resistant to vancomycin
what is acquired resistance?
- an example of ‘natural’ selection that may or may not be present in strains
- can occur by spontaneous mutation (change in structure or function which prevents the antibiotic from acting) or spread of resistance (resistant gene spread via plasmids or transposons)
how does b-lactamase cause antibiotic resistance?
- bacterial enzyme cleaves the B-lactam ring of the antibiotic (penicillin/cephalosporin), rendering it inactive
- staph.aureus produces B-lactamase (also g -ve)
how do we combat b-lactamase in bacteria?
- modify the antibiotic side chain, producing new antibiotic resistant to actions of B-lactamase
(co-amoxiclav - amoxicillin (b-lactam) plus b-lactamase inhibitor clavulanic acid) - introduce second component to the antibiotic protecting it from enzymatic degradation (flucloxacillin - modified form of penicillin)
- extended spectrum B-lactamases (ESBLs) - problem in hospitals by some g -ve bacteria)
what is carbapenemase producing enterobacteriaceae (CPE) or Carbapenem-resistant-E (CRE)?
- carbapenems are highly effective antibiotic agents used for treatment of severe/high-risk or suspected multi-drug resistant bacterial infections
- carbapenems = B-lactam ring
- carbapenemase = enzyme
how does altering the PBP site cause resistance?
- mutations in PBP genes result in a modified target site to which B-lactams can no longer bind
- methicillin resistant staph.aureus (MRSA) - multiple drug resistance to B-lactam antibiotics
- combated with vancomycin (inhibit cw synthesis) or linezolid (inhibit p synthesis)
what does vancomycin resistant enterococci (VRE) mean?
- in VRE (faecalis/faecium), the peptidoglycan precursor to PBP which vancomycin normally binds to has altered structure
- major problem with infection control…potential to spread to staph.aureus
can antimicrobials cause adverse reactions?
- most have potential
- incidence dependent on dose and duration of therapy
- most adverse reactions are trivial and reversible upon withdrawal of antimicrobial
- some cases can be severe or fatal
what antibiotics are likely to develop adverse reactions?
- commonly associated with B-lactams
- true penicillin hypersensitivity is rare
what is immediate hypersensitivity?
- anaphylactic shock
- IgE mediated reaction occurs within minutes administration
- itching, nausea, wheezing, shock
what is delayed hypersensitivity?
- immune response takes hours or days to develop
- immune complex or cell mediated mechanism
- rashes, fever, serum sickness
what are common GI/abdo side effects?
- nausea and vomiting
- diarrhoea associated with toxic production by clostridium difficile
- thrush
- liver toxicity
- renal toxicity
what are common neurological toxic side effects?
- ototoxicity (ear)
- optic neuropathy
- peripheral neuropathy
- encephalopathy/convulsions
what are common haematological toxic side effects?
- toxic effect on the bone marrow resulting in selective depression of one cell line or unselective depression of all bone marrow elements
when should antimicrobials be prescribed?
- prophylaxis
- preventative against future infections
- patient exposed to other patients with highly communicable disease
- patients about to be subjected to surgical procedures
- most abdominal operations
- when the organism(s) causing infection is not known - empirical antimicrobial therapy commenced if urgent
