Antimicrobial Therapies (Intro) Flashcards
Principles of
Antimicrobial Therapy
Overview
Antimicrobials [also called antibiotics]—injure or kill an invading pathogen without harming the cells of the host
Selection requires knowledge of:
-The identity of the pathogen
-Susceptibility of the pathogen
-Site of infection
-Patient factors
-Safety and efficacy of the agent
-Cost
Most patient will require empiric therapy prior to bacterial identification
Identification of the Pathogen
Most of the time, we have to do a culture to know the culprit pathogen we are treating and determine susceptibility, so we went
to ensure all cultures are done before empiric therapy is started
If culture nonconfirmatory, or not an option—other avenues may be helpful—detection of antigens, DNA or RNA; detection of an
inflammatory response
Newest techniques PCR and matrix assisted laser desorption/ionization time of flight [MALDI-TOF] mass spectrometry to obtain accurate, rapid identification of the organism
Empiric Therapy
Timing
• Acutely ill patient with FUO
• Neutropenic patient
• Patient with meningitis
• Others that require immediate therapy
Selecting a Drug
• Choosing a drug without susceptibility is influenced by site, patient history, local
susceptibility patterns
• Broad spectrum indicated initially when pathogen unknown or polymicrobes are suspected
• Choice may also be guided by known association of particular organisms in a given clinical setting
Bacteriostatic vs. Bactericidal
Bacteriostatic
• Thought to arrest growth and replication of bacteria at drug levels achieved
• Most of these agents are able to effectively kill pathogens, but they are unable to meet the arbitrary cut-off value in the bacterial definition
Bactericidal
• Able to effectively kill
>/=99% within 18-24° of incubation
Other Considerations
• It is possible for a drug to be bacteriostatic for one microbe and bactericidal for another
• Other factors have to be considered—host immune system, drug concentration at the site of infection, underlying severity of the illness
MIC—Minimal Inhibitory Concentration
Lowest antimicrobial concentration that prevents visible growth of a microbe after 24° of incubation
Quantitative measure of in vitro susceptibility
MIC is most common approach used by clinical labs
MBC—Minimum Bactericidal Concentration
Lowest concentration of antimicrobial agent that results in a 99.9% decline in colony count after overnight broth dilution incubations
MBC is rarely determined in clinical practice
Effect of the
Site of
Infection
Therapy—The
Blood-Brain
Barrier
Levels of an antibiotic must reach the site of infection for the bacteria to be eradicated
Natural barriers to drug delivery are created by some bodily structures—prostate,
testicles, placenta, vitreous, CNS
Particularly important—blood-brain
barrier—this barrier is a single layer of
endothelial cells fused by tight junctions
that prevent entry from the blood to the
brain of virtually all molecules, except those
that are small and lipophilic
Other
Considerations
Lipid Solubility
• Major determinant of drug’s ability to penetrate the blood-brain barrier
• Lipid soluble drugs [Chloramphenicol, Metronidazole] have significant penetration into the CNS
• Those with low lipid solubility [Penicillin] have limited penetration through the intact blood-brain barrier
• Infections in which the brain becomes inflamed, this barrier does not function as well—and local permeability is increased
Other
Considerations
Molecular Weight
Drugs with low molecular weight have an enhanced ability to cross the blood-brain barrier, while compounds with high
molecular weights [Vancomycin] penetrate
poorly—even in the presence of brain/meningeal inflammation
Other
Considerations
Protein Binding
High degree of protein binding of a drug restricts its entry into the CSF
Amount of free [unbound] drug in the serum, rather then the total amount of drug
present, is important for CSF penetration
Other
Considerations
Susceptibility to
Transporters
or Efflux Pumps
Antibiotics that have an affinity for
transporter mechanisms or do not have an affinity for efflux pumps have better CNS penetration
Patient Factors
Immune System
Eliminating the pathogen from the body depends on an intact immune system
Alcoholism, DM, HIV, malnutrition,
autoimmune disease, pregnancy, older age, immunosuppressants drugs can affect immune status
High dose of bactericidal drugs may be needed to resolve infection in these individuals
Renal Dysfunction
Renal disease can cause accumulation of certain antibiotics—dose adjustment prevents drug accumulation and ADEs
Direct monitoring of serum levels of some antibiotics [Vancomycin, aminoglycosides] is preferred to know the maximum and/or minimum values in order to prevent toxicity
Hepatic Dysfunction
Drugs that are concentrated or eliminated by the liver [Erythromycin, Doxycycline] must be used carefully in patients with liver disease
Poor Perfusion
Decreased circulation to a body area or decreased perfusion to the GI tract can result in decreased absorption, making
getting to a therapeutic concentration difficult with enteral routes of administration
Age
Renal and liver elimination processes are
poorly developed in newborns—making
them high risk to toxic effects
[Chloramphenicol, sulfonamides]
Young children should not receive
Tetracyclines or Quinolones which can
affect teeth, bones and joints
Older patients may have decreased renal
or liver function, which can alter
pharmacokinetics of certain antibiotics
Pregnancy and Lactation
Many drugs cross the placental barrier or
get into the nursing baby via the breast
milk—check the product information
before prescribing
The concentration of an antibiotic in fetal
circulation or in breast milk is usually low,
but the total dose to the infant may be
enough to cause detrimental effects—for
instance—congenital abnormalities have
been seen after pregnant women have
taken tetracyclines—so should not be
prescribed
Risk Factors for Multidrug-Resistant
Organisms
Multidrug-resistant pathogens need broader
antibiotic coverage, when empiric therapy is
being chosen
• Many risk factors
Prior use of antibiotics in last 90 days
Hospitalization for >2 days within last 90
days
Current hospitalization exceeding 5 days
Admission from a NH
High frequency of resistance in the
community or local hospital [using hospital antibiograms]
Immunosuppressive disease and/or
therapies
Safety of the
Agent
PCNs are among least toxic of ALL
antibiotics because they interfere
with a site or function unique to the
growth of the bacteria
Other agents have less specificity
and are reserved for life-threatening
infections because of potential for
serious toxicities
Cost of Therapy
Not uncommon for several drugs to
show similar efficacy in treating
infection, but vary in cost
Choice of therapy usually centers on site
of infection, severity, ability to take oral
meds—and then important to consider
cost
Route of Administration
Oral route is appropriate for infections that can be treated outpatient
Parenteral route is used when the med is poorly absorbed from the GI tract and for those with serious infections that need high serum concentrations of the antibiotic
In hospitalized patients that need IV drugs, switch to oral meds should occur as soon as possible
Switching patients from IV to oral, when the
patient is stable decreases cost, shortens length of stay and decreases complications from IV catheters
Antibiotics such as Vancomycin and
aminoglycosides are poorly absorbed from the gut and do not achieve high enough serum levels via oral ingestion
