Bacteriology 14: Principles of treatment of bacterial infections

Question 1

What is the general principles of treatment of bacterial infections?

Answer 1

Correctly diagnose presence of a bacterial infections!

**Determine what is the underlying host **
(tissue) compromise and address this
“stressor” (= predisposing factor) in
your treatment plan, for example:
treat sarcoptic mange
treat urolithiasis

Determine the likely causative agent or agents
-If it is bacteria that are predictable susceptible to an antibiotic, or infection commonly responds to routine antibiotics
- may not need to positively identify bacteria or do a
susceptibility test (= empirical therapy)
-If it is bacteria that are not predictably sensitive, then need to collect a sample and submit for culture and susceptibility testing

Administer appropriate antibiotic
-Judicious use of antibiotics

Include appropriate ancillary treatments
-Debride/lavage any necrotic tissues*
-Drain any abscesses*
-Promote innate defense mechanisms
ex.: bronchodilators, nebulization, fluid therapy

Question 2

Antibiotic nomenclature?

Answer 2

Antimicrobials against little life
-bacteria, viruses, fungi, protozoa

Antibacterials LARGEST class
-“Natural” and synthetic/semisynthetic

Antibiotics
-substance made by a microorganism that acts upon another microorganism

Question 3

Antibiotics are always __________, but an _____________ is NOT always an Antibiotic!

Answer 3

ANTIBACTERIAL

ANTIBACTERIAL

Question 4

Are we making more or less antibiotics in comparison to history?

Answer 4

LESS

Question 5

Why is it stressful that we are not getting new antibiotics?

Answer 5

Due to there be an increase of antibiotic resistance

Question 6

What are the 4 basic mechanisms of resistance?

Answer 6

Prevent entry of drug

Pump drug out of the bacteria

Inactive drug (modification/degradation)

Change target site for the drug

Question 7

What kind of resistance do we have?

Answer 7

Intrinsic and Acquired resistance

Question 8

How does Intrinsic resistance work?

Answer 8

BActer’a natural ability to resist effects

All bacteria of a certain type posses this ability
-Aminoglycosides for anaerobes
-Metronidazole for aerobes
-Sulfonamides, trimethoprim, tetracyclines,
chloramphenicol for Pseudomonas aeuruginosa
- A normal *P. auruginosa will look “ multi- drug resistant”

Question 9

Acquired Resistance works by?

Answer 9

The bacteria gains the ability to resist a drug, where it was previously susceptible

Tends to be found in some strains/subtypes of a bacterial species

Multiple mechanisms by which bacteria can acquire resistance
-Mutation
-Acquisition of resistance genes

Question 10

What are the mechanisms of Acquired resistance?

Answer 10

Mutation of genes that code for physiological processes
-mycobacterium tuberculosis & rifamin - rpoB

Acquisition of foreign genes that encode resistance
-Horizontal gene exchage which are then passed on vertically
- MRSA- mecA

Question 11

Antimicrobial Susceptibility testing in small animals?

Answer 11

Antimicrobial accounted for 51% of prescriptions

52% of animals diagnosed with a new disease were prescribed antimicrobials

Culture and susceptibility testing in SA emergency & Critical Care patients
given too often ~many times they do NOT have infection

Question 12

Is susceptibility tests invivo or invitro test?

Answer 12

INVITRO

Question 13

When are susceptibility tests indicated?

Answer 13

Young or critical ill patients
-decreased immune defenses

Site of infection (should be) sterile
-specially when it is difficult to treat
-or have a significant impact on the health of a patient

Bacterial pathogens whose susceptibility canNOT be reliably predicted or if rapid development of resistance is anticipated
-ex. E.coli, S. aureus, Klebsiella spp., and enterobacter spp

Failure of presumptive or confirmed bacterial infection to respond to therapy

Question 14

Is there times we should NOT do susceptibility testing?

Answer 14

YES

Predictably susceptible
-beta-hemolytic streo.

High level of efficacy of empirical therapy
-treatment of uncomplicated cystitis in dogs

If have multiple bacteria isolated from abscesses or wounds

Testing of non-pathogenic normal flora is meaningless
-if isolated, it is because the was suboptimal sample collection

Testing the susceptibility of (many) strict anaerobes
-difficult and most anaerobes are predicatbly sensitive to a range of antimicrobials, penicillin, metro, and clindamycin

Question 15

How do we preform these tests preformed?

Answer 15

Agar Disk Diffusion
-kirby bauer modification

Broth Dilution tests
-broth microdilution most common

Gradient Dilution tests

ALL should be interpreted by clinical and laboratory standards

Question 16

Agar Disc diffusion commonly used?

Answer 16

YES

Question 17

Broth microdilution directly measure what?

Answer 17

MIC (Minimum inhibitory concentration)

Two-fold dilutions of antimicrobials are inoculated in a 96 well plate
-the concentrations represent serum concentrations of the antimicrobial in the patient when the drug is administered at recommended dosages

The MIC is the lowest concentration of the
antimicrobial agent that completely inhibits growth of the organism (determined visually)

Question 18

What are the advantages of dilution susceptibility systems?

Answer 18

MIC of the bacteria for the antimicrobial can be
determined

May be used to optimize antimicrobial therapy by
application of pharmacokinetic and pharmacodynamic
principles
- You usually need a pharmacologist to help you do
this

Question 19

What are the limitations of both systems?

Answer 19

Interpretive criteria to establish susceptibility breakpoints are available for only a small number of antimicrobial drugs IN ANIMALS!

Question 20

In vitro susceptibility testing can be used to reasonably predict in vivo _________ of a
particular antimicrobial BUT ONLY if the ____________ of these tests are understood & applied

Answer 20

Efficacy

Limitations

Question 21

Are the MIC values derived from susceptibility tests are ___________ _____________ _____, rather they are ____________ to “susceptible”, “resistant” or “intermediate” based on ____________ __________

Answer 21

Rarely directly used

Translated

Breakpoint values

Question 22

Breakpoints are established based on?

Answer 22

Obtainable SERUM concentrations of the drug & based on PK/PD data

Question 23

What does it mean when your organism IS susceptible to a drug?

Answer 23

Treatment with this drug using standard label or recommended doses has high probability of a cure

Question 24

What does it mean when your organism is resistant to a drug?

Answer 24

Treatment with this drug is associated with treatment failure regardless of the dose administered or location of the infection

Function of either:
-A specific resistance mechanisms of the bacterial
strain
-Low concentrations of drug in a host species

Question 25

What does it mean when an organism is intermediate to a drug?

Answer 25

Uncertain therapeutic effect of the drug
unless dosing modifications or site-specific
drug concentration occurs

~can be good in urinary tract

Question 26

Factors in Interpretation?

FIRST STEP

Answer 26

Breakpoints are based on the average blood
concentrations of antimicrobials that can be
achieved with *standard, fixed dose regimens *

Breakpoints used in veterinary medicine are
often extrapolated from human data

Relatively few breakpoints have been derived for
antibiotics given to animals

Breakpoints are based on the AVERAGE BLOOD CONCENTRATIONS of antimicrobials
that can be achieved with STANDARD, FIXED DOSE REGIMENS
Most tissues that have acute inflammation
mean that infection site concentrations of
abx = blood concentrations

Question 27

Factors in Interpretation?

SECOND STEP

Answer 27

The terms “susceptible” and “resistant” only
directly refer to concentrations of antimicrobials
used in vitro.

Microorganisms that are designated as
“susceptible” may be responsive in vivo in one
location, but “resistant” in another tissue
location
-This is the result of variable drug concentration
attainable across tissues.

Breakpoints don’t indicate the ability of the drug to penetrate to the site and act within the conditions found at the site
- ex. necrotic tissue, pus, tissue pH, bacterial
concentrations, or presence of bacterial biofilms

Similarly, the predicted susceptibility in vitro may NOT correspond to clinical efficacy
-Intracellular organisms
Body sites with limited antimicrobial penetration
- ex. Inside of macrophages, chronic infections in
prostate, CNS (blood-brain barrier), anterior and
posterior segments of the eye, and mammary tissues

Question 28

Factor in interpretation summary

Answer 28

Question 29

Surface infections do you recommend susceptibility?

Answer 29

NO

hard to predict what actually is going on

Question 30

Factor in Interpretations

THIRD STEP

Answer 30

In vitro susceptibility testing is generally only reliable when applied to common, rapidly growing microorganisms
ex. Staphylococcus spp, Enterobacterales (E. coli,
Klebsiella, Salmonella, Proteus) and Pseudomonas
aeruginosa

Infections caused by fastidious or slow growing
bacteria (e.g., strict anaerobes, Nocardia spp) are
usually treated more reliably on the basis of published guidelines

Question 31

Factor in Interpretations

FOURTH STEP

Answer 31

Susceptibility test results are a prediction of the
expected response to treatment, NOT a guarantee of therapeutic success!
-Extraneous factors frequently influence the outcome of antimicrobial therapy
So susceptibility testing would be better called “resistance testing”, since resistance will likely more reliably predict failure to respond to anantimicrobial than susceptibility will predict successful response