Principles of Antimicrobial Therapy

what are the 4 primary goals of antimicrobal therapy?

• kill bacteria or stop growth to allow the patient’s immune system to eradicate the bacteria

• Optimal therapy should exhibit selective therapy

• target difference between bacteria & patient

• target processes that are critical to survive replication of bacteria

Define Selective toxicity

dose that is toxic to the bacteria & not the host

Define Therapeutic index

indication of safety (larger the ratio/difference the safer the drug)

• TD50/ ED50

Define Spectrum of activity

range of microorganisms it can kill or inhibit

• broad: kills multiple bacteria

• narrow: kills specific bacteria

define bactericidal

disrupts the bacterial cell & kills it

• acts on the cell well, cell membrane, DNA synthesis

• used in serious infections & when the immune system is depressed

define bacteriostatic

inhibits bacterial replication & growth

• acts through inhibition of protein synthesis

• works w/ host defenses to clear infectious organisms

Define post-antibiotic effect

antimicrobial still works after drug levels have fallen below MIC

• Slow bacteria recovery after damage to cell structure

• bacteria needs to build more proteins before growth continues

• persistence of drug at target

• microorganism more susceptible to the patient’s immune system

Define MIC

Lowest concentration of drug required to inhibit visible growth

breakpoint concentration

highest concentration of antibiotic that can be safely achieved in a patient

what are consequences of antibiotic use?

• allergy/ hypersensitivity (IgE mediated or delayed)

• Adverse reactions/toxicities

• Alterations in normal microbial populations:

  • GI (Diarrhea) & Vaginal (yeast infections)

  • more common w/ broad spectrum drugs

  • patients can develop C.diff

• Antibacterial resistance

How are antimicrobial suscepibility test interpreted ?

Compares MIC to Breakpoint

• Susceptible(S): MIC < breakpoint

• Intermediate(I): MIC is close to or at the breakpoint

• Resistant(R): MIC>Breakpoint

What is the difference between concentration-dependent & time-dependent drugs?

bactericidal drugs

• Concentration-depending killing: increase the rate of killing as you increase concentration

  • Concentration to MIC ratio

  • Cmax/AUC>MIC

• Time-depending killing: maximum killing depends on how long the concentration is above MIC

  • achieved by continuous infusion or frequent dosing

  • increased concentration doesn’t increase killing

When should bactericidal agent be indicated to use ?

• serious infections

• patient immunocompromised

• prevents resistance (less time alive, less chances of resistance)

What is prophylaxis, Empiric, and definitive antimicrobial therapy?

• Prophylaxis: trying to prevent an infection before it happens by taking antibiotics

• Empiric: treating an assumed infection based off the patient’s s/sx before getting labs back

• Definitive: switching treatment once the labs have confirmed the pathogen

Microorganism: influence success of antimicrobial therapy

• which organism is it?

  • Gram Stain

  • Serology/culture

  • biochemical tests

  • bacteriologic statistics (Usual suspects)

• What is the organism sensitive to?

  • MIC: susceptible vs. resistance

  • local resistance pattern

Drug: influence success of antimicrobial therapy

• PD

  • what is the drugs target

  • static vs. cidal

  • time or concentration-dependent

  • PAE

• PK

  • access to infection site?

  • Does it reach effective levels?

  • Administration route?

  • Metabolism (drug interactions)

  • dose adjustments

  • AEs profile

  • hydrophilic/lipophilic drugs

Patient: influence success of antimicrobial therapy

• previous use of antibiotics

• age (renal/hepatic/drug related AEs)

• pregnancy/lactation

• travel

• allergy/hypersensitivity

• concomitant disease states ( other meds the pt is taking)

• Genetics (HLA-B* 5701 or G6PD deficiency)

• Cost

Explain why patients may not be responding to antimicrobial therapy

• wrong drug dose, administration route, or inadequate penetration( not getting to the bug/infections site)

• PT is immunosuppressed, presence of abscess(low pH/oxgen; degrades antibiotic), necrotic tissue (low oxygen), biofilm (covers the bacteria & block antibiotic from working)

• lack of information related to organism

• patient not adherent

What are the types of mechanism for antimicrobial resistance?

• Target Modification/Mutation

• Permeability Reduction

• Efflux Pumps

• Inactivating Enzymes

• Target Protective Proteins