Clinical Uses of Antibiotics Flashcards
how are most penicillins administered
IM or IV
not very soluble or stable in stomach acid
what does the R-group of a penicillin determine
selectivity, solubility, stability, bioavailability, beta-lactamase resistance
what penicillins are beta-lactamase sensitive
benzylpenicillin, phenoxymethylpenicillin
what penicillins are beta-lactamase resistant
flucloxacillin, temocillin
what are some broad spectrum penicillins
ampicillin, amoxicillin, co-amoxiclav
what penicillins are anti-pseudomonal
piperacillin
what are the pharmacokinetics of benzylpenicillin
IM or IV slow infusion, high blood conc achieved rapidly, non-toxic, good diffusion into body and tissues, low CSF levels, long post-antibiotic effect, rapid excretion in urine
how to maintain benzylpenicillin blood levels
administer large doses
frequent dosing
what is benzylpenicillin used for
mild to moderate throat infections, otitis media, cellulitis, pneumonia, endocarditis, meningitis
what causes meningitis
neisseria meningitis, stapholococcus pneumoniae, haemophilus influenzae
what are the pharmacokinetics of amoxicillin
70-90% absorption, peak blood conc after 90 min, good CSF levels in meningitis, mainly excreted in urine
what are the clinical uses of amoxicillin
RTIs, oral infections, otitis media, sinusitis, UTIs, GI, listerial meningitis
what are the side effects of amoxicillin
hypersensitivity, neurotoxicity, renal failure, diarrhoes and pseudomembranous colitis (c. diff)
what is the origin of cephalosporins
isolated from cephalosporium acremonium
what are the properties of cephalosporins
resistant to beta lactamases, originally active against gram positive bacteria, risk of c.diff
what is the cephalosporin activity aainst gram positive bacteria
affinity for PBPs, resistant to beta lactamases
what is the cephalosporin activity against gram negative bacteria
penetration through outer membrane
what are second generation cephalosporins
active against gram positive and some gram negatives
more resistance to beta lactams
used for severe infections
what are third generation cephalosporins
broad spectrum, increased activity and increased resistance to beta lactamases
active against pseudonomas
what are carbapenems
inhibitors of cell wall synthesis
highly resistant to beta lactamases, broad spectrum activity
what are glycopeptides
inhibitors of cell wall synthesis
only active against gram positive (too large to pass through membrane of gram negative)
what are some examples of glycopeptides
vancomycin, teicoplanin
what is vancomycin used for
systemic infections (IV) orally (c.diff)
what is teicoplanin used for
IM or IV injection for systemic infections
also for infection from b-lactam resistant organisms (MRSA)
what are some features of vancomycin and teicoplanin
penetrate CSF, excreted by kidney, cannot be absorbed through the gut, can be used orally for c.diff
what are the side effects of vancomycin and teicoplanin
pain at injection site, renal toxicity, ototoxicity, blood disorders, anaphylactoid reactions
what antimicrobials affect bacterial membranes
polymyxin (colistin) - active on gram negative bacteria (disrupt membrane and cause leakage of cytoplasm)
what are polymyxins used for
IV for resistant gram negative infections, nebulised or DPI for p.aeruginosa in GF patients
what are the side effects of polymyxins
highly neurotoxic and nephrotxic
what antimicrobials affect bacterial membranes
lipopeptides like daptomycin
how does daptomycin (lipopeptide) work
active on gram positive bacteria
rapid depolarisation of cytoplasmic membrane resulting in loss of function due to leakage of ions and depolarisation of cell
what are the uses of lipopeptides
IV for skin and soft tissue infections, endocarditis caused by resistant gram positives (MRSA)
what are some side effects of lipopeptides
nephrotoxicity, myopathy, peripheral neuropathy, colitis
what are examples of metabolic inhibitors of nucleic acid synthesis
sulphonamides, trimethoprim
sulfonamides more selective than trimethoprim
where do sulphonamides act
on para-amino benzoic acid conversion to dihydropteroic acid in nucleic acid synthesis
where does trimethoprim work
on dihydrofolic acid in nucleic acid synthesis
what are the uses of sulphonamides
limited uses
what are the uses for trimethoprim
UTI and acne
what are the side effects of trimethoprim
(rare) GI tract, allergy, myelosuppression
avoid in 1st trimester pregnancy
what are examples of fluoroquinolones
ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin
what is ciprofloxacin
flouroquinolone
synthetic, broad spectrum, bacterialcidal, inhibit DNA gyrase and IV topisomerase
what are the uses of ciprofloxacin
active against gram negative bacteria and intracellular pathogens like chlamydia, myobacteria
limited use with streptococci and enterococci
what are the side effects of ciprofloxacin
GI, CNS, tendon damage, photosensitiviy, renal impairment
interacts with a lot of CYP enzymes
what is a dietary caution with ciprofloxacin
avoid dairy as they contain a lot of cations
avoid iron tablets as they can affect absorption
what is an example of a RNA polymerase inhibitor
rifamycin
e.g.rifampicin
what is rifampicin
semi-synthetic bactericidal antibiotic
penetrates deep into bone
what are the uses for rifampicin
TB, meningitis prophylaxis, infections of joints, endocarditis
what are dietary cautions for rifampicin
avoid dairy or taking iron tablets at the same time
can turn urine red
what are the side effects of rifampicin
hepatotoxicity, fever/rash, GI, orange-red colour to secretions
can increase metabolism of other drugs
what is an example of a DNA inhibitor
nitromidazoles
e.g. metronidazole
what are the uses of metronidazole
anaerobic infections, genital tract infections, SSTIs where anaerobes are suspected, abdominal and dental infections
what are the side effects of metronidazole
GIT, candida infections, CNS, hypersensitivity, red/brown urine
how does nitrofurantoin work
its active metabolites target DNA synthesis, RNA synthesis, protein synthesis, aerobic energyy metabolism, cell wall synthesis
it accumulates in the bladder and cannot be used on patients with a catheter
what are the uses for nitrofurantoin
treating non-catheterised UTI caused by gram positive and gram negative aerobic bacteria
summary of agents for cell wall synthesis
glycopeptides
summary for agents for cell membrane
polymyxin
daptomycin
summary of agents for nucleic acids
sulphonamides/trimethorpim, fluoroquinolones, rifamycin, metronidazole, nitrofurantoin
what are some examples of aminoglycosides
gentamicin, amikacin, tobramycin, streptomycin
what is gentamicin used for
serious infections caused by aerobic bacteria
active against gram negatives like pseudonomas
active against gram positives like staphylococci
what are the pharmacokinetics of aminoglycosides
Iv, IM or topically for wounds, oral for gut contamination as it is not absorbed, short half life, crosses placenta, prro penetration, renal excretion
what are the side effects of aminoglycosides
nephrotoxicity (reversible, caused by the drug accumulating in proximal tubule)
ototoxicity (irriversible, drug accumulates in fluid-filled inner ear and damages hair cells)
what are examples of tetracyclines
coxycycline, minocycline, oxytetracycline
what are tetracyclines used for
acne, RTIs, chlamydia, SSTIs
what are the pharmacokinetics of tetracyclines
high absorption but decreased by cations, well distributed (inclusing foetus), accumulation and excretion in bile
what are the side effects of tetracyclines
GI, deposition in forming bone/teeth, lover damage, vertigo, photosensitivity
what are the side effects of doxycycline
incorporation into tissues that are calcifying at time of administration (staining of teeth)
photosensitivity from aromatic rings absorbing light energy, producing reactive O2 intermediates which can damage cell membranes
what are macrolides
alternatives to penicillin for trating infections caused by streptococci
what are examples of macrolides
erythromycin, azithromycin, clarithromycin
what is the mode of action of erythromycin
bind 23S rNA in 50S subunit, decreasing translocation and release of tRNA
what are the pharmacokinetics of erythromycin
oral or IV, acid labile, rapidly absorbed and well distributed, metabolised in liver and excreted in bile
what are the side effects of erythromycin
GI, cholestatic jaundice, reversible ototoxicity, allergic reactions, cardiac arrhythmia
what is am example of a lincosamide
clindamycin
what is clindamycin used for
staphylococcal bone and joint infections, RTs, peritonitis, scepticaemia
what is an example of oxazolidinones
linezolid
how is linezolid used
infection cause by resistant gram positive bacteria (MRSA) and vancomycin resistant enterococci
no major side effects - rarely used
what is fusidic acid
narrow spectrum for staphylococcal infections
how does fusidic acid work
affects EF-G which supplies energy for translocation stage of protein synthesis
what is fusidic acid used for
topical for skin and eye infections
oral or IV for osteomyelitis and endocarditis
what is the mode of action for chloramphenicol
binds to 50s subunit and prevents peptide bond formation
what are the pharmacokinetics of chloramphenicol
topical/oral/IV, penetrates all tissues including the brain, metabolised in the liver and renally excreted
what are the side effects of chloramphenicol
bone marrow suppression, GI, peripheral or optic neuritis, aplastic anaemia
what is aplastic anaemia
bone marrow stem cells die - normal haemopoietic cells are absent and the space is filled by adipose tissue
rare but fatal
caused by chloramphenicol
summary of antibacterials which inhibit protein synthesis
aminoglycosides/oxazolidinones, tetracyclines, macrolides/lincosamides, fusidic acid, chloramphenicol
what is the definition of surgical site infection (superficial)
occurs 30 days postoperatively and involves skin or subcutaneous tissue of the the incision and drainage/symptom of infection/culture
what is the definition of surgical site infection (deep)
30 days postoperatively or within one year if an implant is left in place, infection involves deep soft tissues and pt has drainage/fever/localised pain and tenderness/abcess
what is the definition of surgical site infection (organ)
part of the body opened during operative procedure, pt has drainage/infective organisms/abcess
what are the meausres that can prevent surgical site infection
theatre airflow and workflow, skin prep, bowel prep, implants/foreign meterials containing antimicrobials, screening, prophylaxis
what is a clean degree of contamination
no inflammation, respiratory/GI tract not entered
what is clean-contaminated degree of contamination
respiratory/GI tracts entered without spillage
what is contaminated degree of contamination
accute inflammation without pus, visible wound contamination
what is dirty degree of contamination
presence of pus, compound/open injuries more than four hours old
what is the duration of antibiotic prophylaxis recommended for a clean-contaminated proceedure
one dose
what is the duration of antibiotic prophylaxis recommended for a contaminated proceedure
5-7 days of treatment
when is non-surgical prophylaxis given
recurrent infections, endocarditis, high risk contacts (HIV, meningitis, influenza), immunosuppressed (chemotherapy)
what is asplenia
removal of spleen after it ruptures
spleen stores white blood cells so pts now have higher risk of infection
prophylaxis recommended
