Rational Antimicrobials 2 Flashcards
Designation Codes “S, I, R”
> what do they mean?
§ “S”; sensitive; high likelihood of success at label dose
§ “R”; resistant; poor likelihood of success at label dose
§ “I”; intermediate; buffer zone to prevent errors
what are the cut-off values for S, I, R values based on? what are clinical break-point MIC’s / zones of inhibition influenced by?
- Cut-off value for codes based on break-point MICs/zones
clinical break-point MIC’s/zones of inhibition are influenced by:
§ historic susceptibility patterns for the organism (s)
§ pharmacokinetics (Cmax) of the drug tested
§ clinical responses to the drug at label doses
definition of Clinical break-point values
Clinical break-point values are the approximate blood levels of a drug safely achieved at label doses, that can result in a clinical cure against the organism”
Pitfalls of C/S testing (5)
- Assumes causative bug is isolated and being tested
§ sample error
§ normal flora versus infecting flora
§ C/S testing limited to non-fastidious bugs usually - Very stringent testing criteria required (pH, temp. etc)
- MIC’s may not reflect level of drug achieved at the infection site
§ host factors or local factors (penetration) can affect drug levels achieved - In vitro findings do not mimic the host target site
§ hostile microenvironment factors
§ absence of local host immunity factors in vitro - Interpretive criteria may be based on:
§ human pathogens
§ total plasma drug levels and not tissue drug levels
drug classification as cidal vs static is based on
-in vitro term
cidal vs static efefcts of a drug is influenced by what factors
§ affected by mechanism of action
§ drug concentration achieved at infection site
what do bacteriocidal agents do? general considerations of their MBC/MIC?
Bacteriocidal agents kill susceptible organisms
§ do not rely on host defenses
§ MBC/MIC ratio is low; 1-2 tubes; bugs killed § MBC usually safely attainable in the host
what do bacteriostatic agents do? general considerations of their MBC/MIC?
Bacteriostatic agents inhibit growth of organism
§ rely on host defenses for help with infection
§ MBC/MIC ratio is large; several tubes away; bugs inhibited at MIC
§ MBC often not safely attainable in host
Situations where bacteriocidal agents are recommended
Chronic infections
§ Endocarditis, UTIs
Immunocompromised or neutropenic patients
§ eg. viral infections, neonates, concurrent steroids
Life threatening or serious infections
§ Osteomyelitis, Bacterial Meningitis, Septicemia, Peritonitis
Compromised blood supply
Surgical prophylaxis
what characteristics of a mixed infection suggest we should use combination therapy
§ knowledge of likely pathogens is high
§ organisms not susceptible to same drug
classes
Situations where combination therapy is recommended? what should combination therapy be based on?
§ ideally combination therapy should be based on the target organism and mechanism of drug action
Mixed bacterial infections
Initial therapy of life (organ)-threatening condition to extend antibacterial spectrum
Known favorable drug interactions: synergism
Prevent or reduce bacterial resistance
in a life or organ threatening situation, what factors suggest that we should use combination therapy?
§ pathogen (s) unknown
§ pathogens susceptibility profile unpredictable
§ location of infection questionable
§ consequences of failure are high
§ eg sepsis, pneumonia,
peritonitis, meningitis
what is the four-quadrant approach to combinational therapy? what combos are good?
gram +, gram -, aerobes, anaerobes
>target all
§ aminoglycoside + penicillin (parenteral)
§ fluoroquinolone + potentiated-penicillin (oral)
§ imipenem-cilastin
what does synergism mean for combination therapy? what does it take advantage of?
§ efficacy of both is greater than either alone; 1+1 > 2
§ decreased toxicity possible from lower doses of each
§ takes advantage of different mechanisms of action:
§ amoxicillin + clavulinic acid
§ aminoglycoside + b-lactam
§ trimethoprim + sulfonamide
what combinations of drugs are good for preventing or reducing bacterial resistance?
§ erythromycin + rifampin
§ aminopenicillins + clavulinic acid
§ trimethoprim + sulfonamide
