Antimicrobials 2 Flashcards
What are examples of adverse events in 5% of hospitalised patients?
GI upset Fever and rash Renal dysfunction Acute anaphylaxis Hepatitis
What does the the choice of abx depend on?
Host characteristics- pregnant, young, elderly, renal failure
Antimicrobial susceptibilities of the-often unknown, most empiric
Organism itself
Site of infection
What influences choice of drug?
Pharmacokinetics eg clindamycin good for abcesses but doesn’t get into CNS
Route of admin
Dosage
What should the choice of drug ideally be?
Narrow spectrum Bactericidal- bacteraeima eg lactam or glycosides Based upon bacterial diagnosis Local sensitivity patterns Cost
What is the minimum inhibitory concentration?
Least amount of drug required to inhibit the organism in vitro
At this breakpoint, if mic is less than that it’s sensitive, above its resistance
Resistance is a continuum
How does the agar diffusion method work?
Abx impregnated disc absorbs moisture from the agar, abx diffuses into the agar medium
Distance from disc increases, there is a logarithmic reduction in abx
Diffused abx at interface of growing and inhibited bacteria is MIC
What do you do if you need to treat on an empirical basis?
Use broad spectrum- especially septic patients, then de-escalate, shift from initially using narrow.
No tx equals efficacy of abx but no other tx affects society at large
Collect specimen for culture
Then change empirical cover to narrow
What does identification of infecting organism involve?
Gram stain
Rapid antigen detection. Use IF for organisms that are hard to grow eg PCP.
Don’t use PCR so widely- doesn’t give sensitivities
What affects site of infection and thus local conc of abx?
pH at infection site eg low ph deactivate aminiglycosides. tigecytin good for tissue bad for blood
Clinda for strep but not urinary excretion so bad for group b UTI. poor choice
Lipid solubility of drug
Ability to penetrate BBB
Endocarditis, bactercidal is impt
What is evidence of a systemic response?
Fever
Raised CRP
increased WBC or decreased
Duration of symptoms, underlying risk factors, likely source of infection
What are issues with route of admin?
Cephalosporin- poor oral absorption
IM- not for long term, avoid if bleeding tendency
Topical don’t have systemic side fx
Recommend switch to po after iv
What pharmacokinetic factor effects glycosides?
Gentamicin has rapid bacericidal effect which is influenced by peak above MIC, greater clinical outcome. Aminiglycosides have post abc effect, so when curve goes under mic, it still has effect. Peak is important, once daily dosing
What pharmacokinetic factor effects pencillin?
The time above the MIC ie exposure. Amount isn’t impt, need frequent doses. Infusion would be good
What pharmacokinetic factor effects vancomycin?
Conc and time above is impt eg area under curve
What abx needs maximum concentration?
Amino
Daptomycin
Fluoroquinonlones
Jet oldies
Which abx need maximum duration?
Carbapenems Cephalosporin Erythomycin Linezolid Pencillin
Which abx need maximum amount of drug?
Azithromycin Clindamycin Oxazolidinones Tetracycline Vancomycin
What are a few of the recommended tx courses for particular infections?
N meningitis- 7 days Acute osteomyelitis- 6 weeks Bacterial endocarditis- 4-6 weeks Gp A strep pharyngitis-10 days Simple cystitis- 3 days
What should you use for skin infections eg impetigo, cellulitis, wound infections?
Flucloxacillin, unless MRSA/allergic use clarithromycin or clindamycin
What is used in severe skin infections?
Aggressive and early debridement- group a strep
Adjunctive use of protein synthesis inhibitors esp clindamycin, bacteria in stationary cycle of division.
Use of IVig
What is the eagle effect?
Originally referred to reduced antibacterial effect of pencillin at high doses, recently refers to lack of efficacy of beta lactam antibacterial drugs on infections having large number of bacteria
What is the mechanism of the eagle effect?
In cases of high bacterial burden, bacteria may be in stationary phase of growth, due to nutrient restriction.
So pencillin has no activity, only works on rapidly dividing cells.
Which bacteria are covered by pencillin in resp tract infection?
Haemophilus and pneumococci
What is given in severe pneumonia?
Co amox - lots of haemophilus produce b lactamase
What is given for atypical pneumonia?
Clar- mycoplasma, legionella
What cause HAI pneumonia?
Gram neg
Give cephalosporin, ciprofloxacin or tazocin
If MRSA colonised, consider adding vanco
What do you give in bacterial meningitis?
Strep pneumo or n meningitis
Ceft +/- amox if listeria likely
What do you use in baby under 3 months for meningitis?
Cefotaxime plus amox
Don’t give ceftriaxone, displaced bilirubin from albumin and can cause biliary sludging
NM- benzypencillin or ceft
How is resistance caused in nm pencillin?
Production of altered PBPA
Treatment may still be affected with higher dose of pencillin
How do you treat c diff?
Treat with metro oral
If fails, use vanco oral
How is misuse of antimicrobial agents common?
No infection present Selection of incorrect drug Inadequate or excessive dose Inappropriate duration of therapy Expensive agent used when cheaper is available
