antimicrobial therapy week 5 Flashcards
what is bactericidal
antimicrobial that kills bacteria
what is bacteriostatic
antimicrobial that inhibits growth of bacteria
what is M.B.C
minimal bactericidal concentration: minimum concentration of antimicrobial needed to kill a given organism
what is M.I.C
minimal inhibitory concentration: minimum concentration of antimicrobial needed to inhibit growth of a given organism
what is topical administration
applied to surface e.g. skin or mucuos membrane
what is systemic administration
taken internally, (orally or parenterally)
what is parenteral administration
administered intra-venously or intra-muscularly or occasionally subcutaneously
what are the mechanisms of action of antibiotics
3 ways:
- inhibition of cell wall synthesis
- inhibition of protein synthesis
- inhibition of nucleic acid synthesis
what antibiotics use inhibition of cell wall mechanism
- penicillins
- cephalosporins
(beta lactams) - penicillin and cephalosporins contain b lactam rings - effective mostly against gram positive bacteria
- glycopeptides (bactericidal) e.g. vancomycin and teicoplanin
why is the inhibition of cell wall synthesis only effective in gram positive organisms
there is an inability to penetrate the gram negative cell wall
what antibiotics use the inhibition of protein synthesis mechanism
- aminoglycosides (concentration dependent bactericidal antibiotics) = useful in the treatment of serious gram negative infection e.g. coliform
- gentamicin - macrolides (depending on conc. and species bactericidal or bacteriostatic) = useful alternatives to penicillin for gram positive in those allergic
- erythromycin - tetracyclines (bacteriostatic) = treatment of gram positive
- tetracyclines - oxazolidinones (bacteriostatic or bactericidal depending on bacteria being treated) = treatment of gram positive
- linezolid - cyclic lipopeptide (strong bactericidal) = treatment of gram positive
- daptomycin
what antibiotics use inhibitors of nucleic acid synthesis mechanism
- inhibition in purine synthesis (bacteriostatic, when combined bactericidal)
- trimethoprim
- sulphamethoxazole
(these two are used in combination in the drug co-trimoxazole) - fluroquinolones (bactericidal) = particularly effective against gram negative
- ciprofloxacin
- levofloxacin
what are the two types of antibiotic resistance
- inherent or intrinsic resistance
- acquired resistance
what is inherent or intrinsic resistance
- strains are given a natural resistance to an antibiotic
e. g. streptococci always resistant to aminoglycosides
e. g. gram negative organisms always resistant to vancomycin
how do you get acquired resistance
can occur in two ways:
- spontaneous mutation
- spread of resistance - gene that codes for resistance spread via plasmids or transposons from organism to organism
what are the types of horizontal gene transfer in bacteria
- conjugation - DNA transfer via plasmids or transposons
- transformation - naked DNA exchanged
- transduction - bacterial DNA transferred by viruses
what is the issue with beta lactase production in antibiotic resistance
- b lactamases are bacterial enzymes which cleave the b lactam ring of the antibiotic and thus render it inactive (most hospital strains of staphylococcus aureus produce b lactamase ) (b lactamase also common in gram negative bacilli)
what are the two ways to combat b lactamase
- modify the antibiotic side chain, this produces new antibiotic resistance to the actions of b lactamase
- co-amoxiclav = amoxicillin plus the b lactamase inhibitor clavulanic acid - introduce a second component to the antibiotic (b lactamase inhibitor) protecting the antibiotic from enzyme degradation
- flucloxacillin (antistaphylococcal) = a modified form of penicillin
what are extended spectrum b lactamases (ESBLs)
enzymes that mediate resistance to extended spectrum cephalosporins (an antibiotic)
- problem in hospitals by some gram negative organisms
what are carbapenemase producing enterobacteriaceae (CPE)
a bacterium that is a member of the enterobacteriaceae family, resistant to the carbapenem class of antibiotics through the production of carbapenemase
what are carbapenem resistant enterobacteriaceae (CRE)
a bacterium that is a member of the enterobacteriaceae family, resistant to the carbapenem class of antibiotics by any means
- there are some extremely resistant gram negative organisms
- in some cases NO antimicrobial options available!!!!
what is alteration of penicillin binding protein (PBP) target site
- develop resistance to b lactams by changing the structure of their PBPs
- mutations in PBP genes result in a modified target site to which b lactams will no longer bind
- MRSA is any strain of s. aureus that has developed resistance to b lactam antibiotics
- can be treated with flucloxacilin, linezolid and vancomycin
- ALTHOUGH.. there are now vancomycin resistant enterococci
what are some commonly used penicillins
benzyl penicillin - gram positive organisms
amoxicillin, ampicillin - gram negative activity
co-amoxiclav - b lactamase producing coliforms
flucloxacillin - staphylococcal infections (resistant to b lactamase)
what are some common b lactams: cephalosporins
first gen. = cepharadiine
second gen. = cefuroxime
third gen. = ceftriaxone and cerftazidime
( gram negative activity increases through generations and gram positive decreases)
what is a common aminoglycosides
- gentamicin
- gram negative organisms
- parenteral use only
- serum levels must be monitored because of potential toxicity
- cheap and common
what are some common glycopeptides
- vancomycin (levels must be monitored due to toxicity)
- gram positive
what are some common macrolides
- clarithromycin (atypical pneumonia)
- erythromycin (atypical pneumonia)
- azithromycin (chlamydia)
- gram positive
- alternative to penicillin
what are some common quinolones
third gen = levofloxacin
- nearly all gram negative
- this group is only possibility for oral therapy for pseudomonas infections
miscellaneous common agents
trimethoprim - treatment of urinary infections
co-trimoxazole = trimethoprim + sulphamethoxazole (chest infections)
fusidic acid - anti-staphylococcal (should always be used in combination)
clindamycin - gram positive
what are some newer agents
linezolid - treats MRSA
daptomycin - gram positive (can be used in serious MRSA infections)
common urinary tract agents
- nalidixic acid
- nitrofurantoin
what are some side effects of antibiotics
- allergic reactions (associated with b lactams)
- immediate hypersensitivity (IgE mediated due to parenteral administration)
- delayed hypersensitivity (immune complex or cell mediated)
- gastrointestinal side effects (nausea and vomiting common)
- thrush (normal flora suppressed so less competition for yeast)
what are some toxicity effects
- liver toxicity
- renal toxicity
- neurological toxicity (ototoxicity - hearing, optic toxicity, peripheral neurpathy - numbness, encephalopathy and convulsion - brain)
- haematological toxicity e.g. linezolid causes bone marrow suppression
what are some polyene anti-fungal drugs
amphotericin B (extremely toxic) - only drug for IV use nystatin - topical use only
how do polyenes (anti-fungal) work
bind to ergosterol (present in fungal wall but not bacteria) and this results in increased permeability of the cell wall
what are some anti-fungal azoles
fluconazole - oral and parenteral treatment of yeast infections
itraconazole - active against both yeasts and filamentous fungi
voriconazole - treats aspergillosis
how do azoles (anti-fungals) work
inhibition of ergosterol synthesis (component of fungal cell wall)
what is a allylamines anti-fungal drug
terbinafine - acts against dermatophyte infections
- suppresses ergosterol synthesis
what are some anti-fungal echinocandins
- caspofungin
- micafungin
- andulafungin
used for serious candida and aspergillum infections
they inhibit the synthesis of gluten polysaccharide in fungi
what type of drugs are all anti-viral drugs
they are all virustatic (inhibit growth/replication)
what are some anti-herpes virus drugs
- aciclovir (low toxicity) (extremely active!)
- valganciclovir (bone marrow toxicity)
- gangciclovir (toxic)(IV)
- foscarnet (highly nephrotoxic)
anti-HIV drugs
- zidovudine (nucleoside analogue)
- nevirapine (non-nucleoside reverse transcriptase inhibitor)
- saquinavir (viral protease inhibitor)
- combination therapy is normal
- usually zidovudine + nevirapine or saquinavir
drugs for chronic hepatitis B and C
- interferon-a (protein that forms part of the host immune response)
- ribavirin
- lamivudine + adefovir dipivoxil
drugs for viral respiratory infections
- zanamivir
- oseltamivir
both for influenza - ribavirin (occasionally for respiratory syncytial virus - RSV)
- remdesivir (covid 19)
what is prophylaxis
the administration of antimicrobials to prevent the future occurrence of infection
- e.g. in most abdominal operations
what is empirical antimicrobial therapy
when the organism causing infection is not known empirical antimicrobial therapy may have to be commenced if urgent treatment is required
e. g adult with local pneumonia is likely to be infected with pneumococci and thus an agent such a benzylpenicillin or amoxicillin should be included
- intra-abdominal infection would require an agent of combination of agents that are likely to cover coliform and anaerobic organisms
what is additive effect of combined antibiotics
additive 1+1=2
synergistic 1+1=5 (combined effect much greater)
what is the simplest way to measure M.I.C
(minimum inhibitory concentration)
using an E-test
- paper strip
how do labs test for susceptibility of bacteria to antibiotics
automated methodology
