antimicrobial chemotherapy - 1st yr - optional Flashcards
<p>define bactericidal</p>
<p>antimicrobial that kills bacteria
| e.g. penicillin</p>
<p>define bacteriostatic</p>
<p>antimicrobial that inhibits the growth of bacteria
| e.g. erythromycin</p>
<p>define sensitive</p>
<p>an organism is considered sensitive if it is inhibited or killed by levels of the antimicrobial that are available at the site of infection</p>
<p>define resistant</p>
<p>an organism is considered resistant if it isn't killed or inhibited by levels of the antimicrobial that are available at the site of the infection</p>
<p>define MIC</p>
<p>minimal inhibitory concentration
| the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism</p>
<p>define MBC</p>
<p>Minimum bactericidal concentration
| the minimum concentration of the antimicrobial needed to kill a given organism</p>
<p>what are the 3 routes of administration</p>
<p>topical
systemic
parenteral (IV/IM)</p>
<p>3 sites of antibiotic action</p>
<p>inhibition of cell wall synthesis
inhibition of protein synthesis
inhibition of nucleic acid synthesis</p>
<p>antibiotics that inhibit cell wall synthesis</p>
<p>- penicillins and cephalosporins (beta lactams)
| - glycopeptides</p>
<p>penicillins and cephalosporins</p>
<p>- beta lactam antibiotics
- disrupt peptidoglycan synthesis by inhibiting the enzymes (PBPs) responsible for cross-linking the carbohydrate chains</p>
<p>benzyl penicillin resistance</p>
<p>many gram -ve are resistant to benzyl penicillin due to the relative impermeability of the gram -ve cell wall</p>
<p>beta lactamas are effective against mostly gram</p>
<p>+ve bacteria</p>
<p>glycopeptides</p>
<p>work on gram +ve only
vancomycin and teicoplanin
inhibit assembly of a peptidoglycan precursor
can't penetrate the gram -ve cell wall
vancomycin and teicoplanin arent absorbed from the GI tract so are only given parenterally</p>
<p>vancomycin toxicity</p>
<p>local tissue damage can occur if it leaks from the veins
side effects: ototoxicity, nephrotoxicity, skin rashes
important to measure levels
teicoplanin appears to be less toxic</p>
<p>antibiotics that inhibit protein synthesis</p>
<p>aminoglycosides
macrolides and tetracyclines
oxazolidinones
cyclic lipopeptide</p>
<p>Aminoglycosides</p>
<p>e.g. gentamicin
concentration dependent bactericidal
gram -ve resistance is unusual - main use is to treat gram -ve infections
most staphylococci are sensitive, streptococci aren't
gentamicin is toxic and requires careful dosing regime</p>
<p>macrolides and tetracyclines</p>
<p>macrolides are useful alternatives to penicillin when treating gram +ve infections in patients who are allergic to penicillin
>10% of Staph aureus, strep pyogenes and strep pneumonia strains are resistant</p>
<p>oxazolidinones</p>
<p>bacteriostatic/bactericidal depending on the bacteria
linezolid - good activity against MRSA, orally</p>
<p>cyclic lipopeptide</p>
<p>strong bactericidal
daptomycin - activity against gram +ve, particularly MRSA
last resource</p>
<p>antibiotics that inhibit nucleic acid synthesis</p>
<p>trimethoprim and sulphamethoxazole
| fluoroquinolones</p>
<p>trimethoprim and sulphamethoxazole</p>
<p>both inhibit different steps in purine synthesis
used in a combined form - co-trimoxazole
less likely than other broad spectrum agents to cause C. diff infections</p>
<p>fluoroquinolones</p>
<p>e.g. ciproflaxin inhibit DNA synth more directly given orally and parenterally effective against gram -ve can't be used in children - interference with cartilage growth
levofloxacin has more activity against gram +ve</p>
<p>what are the 2 types of antibiotic resistance</p>
<p>inherit/intrinsic resistance
| acquired resistance</p>
<p>inherit/intrinsic resistance</p>
<p>- all strains of a given species are naturally resistant to an antibiotic
- usually due to the inability of the drug to penetrate the bacterial cell wall to exert its action
e. g. streptococci resistance to amino-glycosides, gram -ve resistance to vancomycin</p>
<p>acquired resistance</p>
resistance may be present in some strains of the species but not others
lab sensitivity testing is essential to establish the likely sensitivity of any individual isolate from a patient
mechanisms of acquired resistance
- spontaneous mutation during multiplication of the bacterial DNA, can result in change in structure/function
- genes that code for resistance can spread from organism to organism or from species to species (commonest method)
widespread use of antibiotics causes …
selective pressure and encourages new resistant organisms to outgrow sensitive strains (natural selection)
mechanisms of resistance to beta lactams
- beta lactamase production
- alteration of PBP target site
beta lactamase production
- bacterial enzymes that cleave the beta lactam ring of the antibiotic and make it inactive
- common is hospital strains of S aureus and most gram -ve bacteria
- extended spectrum beta lactamases (ESBLs) are produced by some gram -ve organisms can break down 3rd generation cephalosporins as well as penicillin and render the organism resistant to all beta lactam antibiotics
combating beta lactamase production
- introduce a 2nd component to the antibiotic (beta lactamase inhibitor) - protects the antibiotic from enzymatic degradation e.g. co-amoxiclav
- modify the antibiotic side chain to produce an antibiotic that is resistant to beta lactamase action e.g. flucoxacillin
carbapenemase producing enterobacteriaciae
group of extremely resistant gram -ve organisms
resistant to carbapenems
usually also resistant to multiple other classes of antibiotics - often leaves no antimicrobial options for therapy
carbapanems
highly effective antibiotics
used for severe/high risk bacterial infections
member of beta lactam class
reserved for multi-drug resistant infections
alteration of PBP target site
- results in a modified target site to which all beta lactams will no longer bind
these organisms are resistant to all beta lactam agents
addition of beta lactamase inhibitor makes no difference
e.g. MRSA - resistant to all penicillins and cephalosporins
treatment of MRSA
- flucloxacillin: beta lactamase resistant, treats beta lactamase producing s aureus (NOT MRSA)
- vancomycin and linezolid - MRSA treatment
glycopeptide resistance
- vancomycin resistant enterococci - peptidoglycan precursor to which vancomycin normally binds has an altered target site
these types of bacteria have appeared very recently
vancomycin resistance is unusual in gram +ve organisms
penicillins (examples of drugs)
benzyl penicillin (penicillin G) amoxicillin, ampicillin co-amoxiclav flucloxacillin piperacillin imipenem, meropenem
spectrum of benzyl penicillin
largely acts against gram +ve organisms
best choice for IV treatment of serious pneumococcla, meningococcla and S pyogenes infection
phenoxymethylpenicillin has slightly better absorption when taken orally
amoxicillin, ampicillin spectrum
better oral absorption that benzylpenicillin
originally better gram -ve activity
20-30% of coliform organisms are now resistant due to beta lactamase production
covers streptococci, enterococci and some coliforms
co-amoxiclav spectrum
amoxicillin + beta lactamase inhibitor clavulanic acid
extends the spectrum to cover beta lactamase producing coliforms