antimicrobials Flashcards
Why would a bacteriostatic agent be used?
if you can stop growth, immune system can take over
-not a good option in immunosuppressed patients
post antibiotic effect
inhibition does cont fairly long time after a drug is d/c’d
- persistent suppression of microbial growth after antimicrobial agent has been cleared
- Long PAE with intracellular bacteriostatic agents, short or no PAE with beta-lactams
- might make length of dosing interval versus the the drug half life less of a concern
MBC vs MIC
MBC = minimal bactericidal concentration MIC = minimal inhibitory concentration
antibiotic in the blood should exceed the MIC by 2-8x to offset tissue barriers to infection site (pus, CNS, tissue)
Which mechanisms of action are bacteriostatic
folic acid metabolism inhibition, PRO synthesis inhibition
concentration dependent antibiotics
antibiotic effectiveness is dependent on achieving peak concentration periodically in multiple dosing regiment Peak/MIC or AUC/MIC
-common for bactericidal agents to show concentration dependent technology
time dependent antibiotics
effectiveness dependent on time (%) that concentration remains above MIC (time > MIC)
- common for drugs like cell wall synthesis inhibitors, slow killing req maintained concentrations
- ex: PCN
- requires minimization of dosing interval relative to drug t1/2 or IV infusion
narrow spectrum antibiotics
- effectively mainly against either Gm+ or Gm-
- optimal against specific organisms
- lower risk of superinfections
extended spectrum antibiotics
-affects a variety of Gm+ and Gm-
broad spectrum
affects both Gm+ and Gm - bacterial, plus other micororg as well (rickettsia
clinical effectiveness of antibiotics
dependent on drug’s maximal efficacy (limit of the dose-response relation), not its potency
what contributes to antimicrobial drug resistance
- misdiagnosis
- inherent microbial resistance (certain strains)
- acquired drug resistance
Forms of acquired microbial resistance
- drug fails to reach target (transporters)
- drug is inactivated (enzymes, pumped out of cells by efflux pump)
- drug target is altered (rapid multiplication leads to rapid mutation)
-occurs as a result of antibiotic use
how is drug resistance acquired genetically?
- chromosomal resistance (mutant genes and PRO, drug target is altered)
- sex, plasmid, and transposon mediated resistance
- conjugation (imp for gram neg)
- transduction (imp)
- transformation (not imp)
non-genetic drug resistance
- growth latency, anaerobic conditions
- protoplasts (no cell wall)
definitive antimicrobial therapy
- identificaiton of specific pathogen prior to rx
- presumptive dx of infection, severity/need for immediate rx, and probable pathogens
- formulate a microbial dx
- direct examination, gram stain, etc.; growht & sensitivity tests
- select most appropriate antibiotic therapy
- evaulate effectiveness (72h) and reassess
empiric antimicrobial rx
-rx without formal id of specific pathogen
-used in critical conditions or when dx is likely to be unneccessary or cost prohibitive
-presumptive dx of infection, severity/need for rx, and probable pathogens
-rx with antimicrobial agents likely to be effective
(consider local bacterial resistance patterns, generally involves broader spetrum agents, isolation of cultures prior to antimicrobial rx, eval effectiveness and reassess)
adverse effects of antimicrobial therapy
- allergy
- superinfection (appearance of a secondary infection during antimicrobial rx of a primary infection)
- organ tox
- selection of resistant microbes
valid indications for combination antimicrobial therapy
- empirical therapy of severe infection of unknown cause
- rx of polymicrobial infections
- enhancement of antibacterial activity in the treatment of specific infections
- preventing the emergence of resistant microbes
disadvantages of combination antimicrobial therapy
- synergistic toxicity (one agent enhances toxicity of the other)
- cost
- antagonism
- selection for drug resistant bugs
prophylaxis of antimicrobial therapy
- pre-surgery patients with indwelling medical devices
- prevent wound infection following surgery (oral, GU, bowel)
- sexual contacts of patients with STDs
- dental procedures in patients with indwelling medical devices, heart defects (recommendations have changed)
