Antibiotic Principles Flashcards
Describe differences between the ways we use ABX
Prophylactic Tx - the Pt has a condition that warrants the use of ABX to prevent an infection.
Empiric Therapy - We suspect and infection but do not know what the pathogen is
Definitive Tx - We know there is an infection and have a better idea of what the pathogen is
Standard approach for selecting an ABX therapy
Confirming the presence of an infection
determining the likeliest pathogen
Selecting an Empiric Tx
Monitoring the Response
Modifying or Deescalating the Tx
Confirming the Infection
Important to reduce the unnecessary use of ABX
Resistance, Altering Micro flora, Cost Burden, Nephro/hepatotoxic
Threshold for empiric use is cases by case, for example, a Pt who is immunocompromised.
What are some S/S of infection
Fever, Leukocytosis (>10000), Clinical local or systemic signs (UTI, confusion)
Fever is not always a Reliable Sign of infections
Drug induced - beta-lactams, convulsants, allopurinol, hydralazine, nitrofurantoin, sulfonamides, phenothiazines, and methyldopa
disease induced - collagen-vascular (autoimmune d/o) acute thrombosis, malignancies, fever of unknown origin.
Other drugs can mask a fever - NSAIDS, Tylenol, corticosteroids
WBCs
During infection
WBCs may be as high as 40,000cells/mL, with lots of immature band cells
may remain normal
May be increased due to underlying conditions - MI, Trauma, leukemia, coorticosteroids
S/S may help us to hone in on the source of the infection
Superficial or bone/joint infections - pain, inflammation, swellin, erythema, tenderness, purulent d/c
Deep seated infections -pneumonia, meningitis, endocarditis, UTI; May require examination of local tissue fluids
S/S may be referred to an organ -
Cough and sputum productions: Pneumonia
Flank Pain: Pyelonephritis
Fevers with no other Sx: may require a lengthy differential.
Determining the most likely of pathogens
Requires labs and diagnostics
Can include Gram stains, blood cultures, cultures from the infected site.
Try to get samples before ABX as these will alter the samples; but sometimes the Pt life is more important.
Gram Stains
Gram stains give first clues
Gram positive v negative
Shape of the organism - rods vs cocci
Growth Patterns - Clusters, chains, and pairs
Aerobic Gram Positives Examples
Cocci - Streptococci pnuemoniae, viridans, Strep A group; Enterococcus, Staphylococcus
Bacilli - Corynebacterium, Listeria
Anaerobic Gram Positive Examples
Cocci - Peptococcus, Peptostreptococcus
Bacilli - Clostridia, C. Acnes
Aerobic Gram Negative Examples
Cocci Neisseria, Moraxella
Bacilli - Enterobacteriaceae (E. colli, klebsiella, enterobacter, citrobacter, proteus, salmonella, shingella, etc), Campulobacter jejuni, P aeruginosa, H. pylori, H. influenzae
Anaerobic Gram Negative Examples
Bacilli- Baceroides (fragilis)
Atypical Bacteria
Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophilia
In an acutely ill and febrile patient
Always obtain blood samples, and try to coincide with fever spikes if possible.
Obtain two sets from two different peripheral sites; an aerobic bottle and an anaerobic bottle; obtain 1 hr apart.
Cultures and sensitivities
Provide identification and susceptibility to ABX
but can take 24 to 48 hours or more for sensitivities
Reported as susceptible S, Intermediate I, or Resistant R
Positive cultures dont always confirm the presence of an infection.
An infection refers to the bacteria that is present and causing the Sx
There are bacteria that colonize and are normal flora and not the cause of the Sx
Contamination of the sample due to improper technique.
The site of infection helps
Pneumonia can be indicative of SA, P. Aeruginosa, Klebsiella pneumoniae, Acinetobacter
Intr-abd infection may indicate B, fragilis, E. coli, Enterococcus faecalis/faecium.
UTI - E coli, klebsiella pneumoniae, proteus, SA, S. epidermis, enterococci, PA
IV site - SA, SE
When choosing an empiric ABX
Consider the type of infection
The Pt - MH, allergies, organ function
The ABX - Characteristics, relative toxicity, $$$, IV v Oral
Can consult
Infectious Disease Society of America
John Hopkins, ABX guideline
Sanford Guide to ABX therapy
General Considerations for selecting the empiric regimen
Is the infections Community acquired or is it nosocomial; nosocomial tend to be more resistant to ABX
Is the infections Mild v Severe; severe mean more aggressive.
Is this the first infection? Recurrent?
Infections from a removable source? - Is there a drain-able abscess? Remove a contaminated line.
Antibiotic Susceptibility
MIC - lowest concentration at which visible growth is prevented.
Susceptible - suggest high likelihood of clinical success at therapuetic concentrations
Intermediate - questionable likelihood of success; Would require aggressive dosing.
Resistant - high likelihood of therapeutic failure.
Antibiograms
Help ID and track local resistance patterns
Cultures from community on annual basis + susceptibility profile.
Pt factors
Age, Allergies and drug interactions, PMH, Pregnancy, Organ Function, metabolic and Genetics, costs and preferences, concomitant drugs(linezolid + ssris), Disease states
Pt Hx can be used to guide empiric ABX decisions
Sick contacts at home, work, social stiuation?
Pets like bird
Employment based exposures
recent travel to an area where the pathogen is endemic
Vaccination status?
Drug Factors
Pharmacokinetics and pharmacodynamics - does it get to the site of action; needs to touch the bacteria to work!
Tissue Penetration
Drug toxicity - may need to sacrifice efficacy to use
Pharmaco kinetic Considerations
Available routes of administration (A)
Tissue Penetration (Vd)
Drug-Drug interactions (metabolism)
Safety in renal/hepatic dysfunction (E)
Pharmacodynamic considerations
Bactericidal v bacteriostatic
Time-dependent vs concentration dependent
Will the drug get to the site of the infection
Adequate blood supply - is it an abscess, osteromyelitis, a deep Cellulitis
Is the infection in the CNS - can it cross the BBB
Volume of distribution - Tigecycline cannot Tx blood borne infections b/c it has a high Vd
Special Circumstance - daptomycin gets inactivated by pulmonary surfactant.
Dosing Strategies Based on how a medication will exert its effect - Time-Dependent Killers
Time-Dependent killers - Max Bactericidal activity is based on the medication being above the MIC for at least 40-50% of the dosing interval.
Therefore continuous or prolonged infusions can lead to therapeutic success, by maximizing T> MIC
*The duration of time @ [] leads to killing more dead
Ex are Beta-lactams, cephalosporins, carbapenems, and vanco
Dosing Strategies Based on how a medication will exert its effect - Concentrations-Dependent Killers
The higher the drug concentrations the greater the killing power.
Fluoroquinolones: Maximize the AUC/MIC ratio
Aminoglycosides: Maximize the Peak:MIC Ratio
Combination Therapy should be carefully considered, not universally applied
Can broaden the spectrum of coverage - increasing the chance of success; increases costs and risks, and resistance
May yield synergistic effects - B-Lactams + Aminoglycosides work well for endocarditis; But may increase the risk of superinfection with more resistant organisms
My prevent resistance - for example: Tb has multiple drugs as part of the course
Failure of antimicrobal Therapy
Need to consider the drug, host, and the pathogen
Selection and dosing of the ABX can influence Tx success
Empiric regimen may not cover the infecting organism- may have wrong Dx, empiric choice, or have a completely unexpected organism
*why monitoring the Pt is important
The concentration of the Antibiotic may be too low at the the infected site - b/c of poor absorption or distribution, drug-drug interactions, or drug-inactivation
*could have the correct ABX but it cant reach the site
Host Factors
May Render ABX less effective
Immunosuppression - such as from HIV, DM, COPD, Lack of natural defense from a burn or asplenia
Or from Chemo induced neurtopenia, chronic corticosteroid use, transplant anti rejection Tx, Drugs for autoimmune d/o
*May require a prolonged or increased dose.
Pathogens May be Resistant to the ABX Tx
Intrinsic Resistance - Naturally occuring; IE gram neg are unaffected by vancomycin which cannot penetrate their outer cell membrane
Acquired - a normally sensitive organism develops resistance through genetic mutation which can be shared in plasmids.
4 categories of acquired antimicrobial resistance
Alteration in the target site (binding site)
Reduced intracellular antimicrobial exposure - more difficult to penetrate or efflux pumps spit it back out.
Bypass of natural metabolic processes - pathogen finds a new metabolic pathway
Drug inactivation - Enzyme degrades antimicrobials.
Resistance Patterns
Staphylococcus - B-lactamases - affects all pcn
MRSA - Alter PBP - affects pcn cephalosporins, some fluoroquinolones
Streptococcus - Alter binding sites - pcn, macrolides
Enterococcus - alterations to target site - vancomycin
Pseudomonas - reduced permeability - pcn, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones
Pseudomonas - B-Lactamase production - pcn
Enterobacteriaceae - b-lactamase production - pcn
When Discussing with a Pt
Allergies?
Other Medications?
counsel on taking full course.
Women on OCP may need a back up for up to 7 D after the Course.
Come back if not getting better, or ADR
Probiotics
ABX stewardship
Slows resistance
Saves Money
Avoids Adverse events
