Infectious Diseases Exam 1 (Ernst) 2nd lecture

in the selection process, what relates to the patient and the bug?

-immune status

-site of infection

-age

in the selection process, what relates to the bug and the drug?

-susceptibility

-site of infection

-protein binding

-pH

in the selection process, what relates to the drug and the patient?

-immune status

-PK

-toxicity

-organ function

-PD

what are the steps of the selection process with antimicrobial drug therapy?

-establish need for antimicrobial therapy

-attempt to identify pathogen

-select empiric antimicrobial therapy

-monitor therapy for efficacy and toxicity

-refine antimicrobial therapy for definitive identification of pathogen and infection

when might an infection be suspected?

when there are signs of inflammation, such as fever, pain, swelling, or redness

if a person has a fever, does that mean they are infectious?

NO, there are many non-infectious things that can cause fevers

what are some clinical signs of infection?

-increased WBC

-ESR

-CRP

-LFTs

-PCT elevation

what is a gram stain?

test done to identify organisms based on cell wall structure and morphology

what can a gram stain be performed on?

-sputum

-urine

-CSF

-wound specimens

what color do gram positive organisms stain?

purple

what color do gram negative organisms stain?

red

list examples of gram positive organisms

-Staphylococci

-Pneumococci

-Streptococci

-Listeria

-Cutibacterium

-Corynebacterium

-Clostridium

-Bacillus

list examples of gram negative organisms

-Neisseria meningitidis

-Neisseria gonorrhoeae

-Escherichia coli

-Klebsiella spp.

-Enterobacter spp.

-Citrobacter spp.

-Pseudomonas spp.

-Salmonella spp.

-Shigella spp.

-Haemophilus influenzae

what are gram positive cocci in clusters?

Staphylococcus

what are coagulase negative Staphylococcus?

-Staphylococcus epidermidis

-Staphylococcus saprophyticus

what are coagulase positive Staphylococcus?

Staphylococcus aureus

what are gram positive cocci in pairs or chains?

Streptococcus or Enterococcus

list examples of gram-negative bacilli

-Escherichia coli

-Klebsiella spp

-Enterobacter spp

-Serratia marcescens

-Proteus spp

-Pseudomonas aeruginosa

-Haemophilus influenzae

list examples of gram negative cocci

-Moraxella catarrhalis

-Neisseria spp

what are examples of non gram staining bacteria?

-Chlamydia spp

-Mycoplasma pneumoniae

-Legionella spp

-Mycobacteria

-Rickettsiae

-Spirochetes

list examples of viral organisms that do not gram stain

-influenza A and B

-hepatitis viruses

-cytomegaloviruses

where do gram positive anaerobes generally reside?

mouth and upper GI tract

list examples of gram positive anaerobes

-Peptostreptococcus

-Peptococcus

-Propionibacterium acnes

-Clostridium spp

-Finegoldia magna

-Anaerococcus spp

where do gram negative anaerobes generally reside?

lower GI tract

list examples of gram negative anaerobes

-Bacteroides fragilis

-Prevotella

what are benefits of rapid diagnostic technologies?

-quickly identify pathogens

-streamline antimicrobial therapy

-improve infection control measures

-results available in 15 minutes to a few hours

what can rapid antigen tests be used to test for?

-group A strep

-influenza

what is a limitation of rapid antigen tests?

test may remain positive even if patient is recovered

what can immunofluorescence test for?

-CMV

-RSV

-syphilis

-Lyme disease

what can ELISA test for?

-HIV

-HSV

-Neisseria gonorrhoeae

what is an AFB test used for?

mycobacteria

what is india ink used to test for?

cryptococcus

what does potassium hydroxide test for?

fungal pathogens

what do serologic tests look for?

nonspecific or specific antibodies

what is a DNA probe hybridization test?

DNA FISH that looks for evidence of organisms

what is MALDI-TOF used for?

detection of bacteria and yeast

what is MIC?

lowest concentration of an agent that inhibits the visible growth of an organism in vitro

what is MBC?

lowest concentration of an agent which results in a 99.9% reduction in colony forming units

what are methods for determining the MIC?

-macro-broth dilution

-micro-broth dilution

-agar dilution

-Kirby-Bauer disk diffusion

-epsilometer strip

how is a zone of inhibition used to determine if an organism is susceptible?

diameter of zone of inhibition is compared to the list to see if the zone is big enough for the organism to be considered susceptible

on an E test, how is the MIC determined?

by the point at which the zone of inhibition intersects the test strip

what are breakpoint values?

system developed to evaluate MIC results

what are breakpoint values based on?

-drug pharmacokinetics

-distribution of MICs

-clinical efficacy

what does it mean if an organism has a low MIC?

they are more likely to be killed than isolates with high MICs

what does an MIC50 mean?

MIC that inhibits 50% of organisms

what are limitations of MICs?

-do not provide information regarding the rate or extent of killing

-conducted with standard inoculum

-lack of plasma proteins and complement

what are factors that influence potential pathogens?

-patient characteristics

-age

-immune status

-comorbid conditions

-site of infection

what commonly causes meningitis in neonates?

-E. coli

-Strep agalactiae

-Listeria monocytogenes

-Klebsiella

what commonly causes meningitis in adults?

-Strep pneumoniae

-N. meningitidis

what does empiric therapy usually target?

broad spectrum of potential pathogens

what is an antibiogram used for?

selection of empirical regimens before ID and susceptibility results are known

what needs to be done regarding allergies when choosing an antimicrobial regimen?

properly assess and distinguish them from adverse effects and watch for cross reactivity

what needs to be considered when choosing an antimicrobial regimen and avoiding toxicity?

monitor renal function and pre-existing organ impairment

what is the Cockroft and Gault equation?

CrCl = ((140-age) x LBW) / (SCr x 72) (all x 0.85 if female)

what is the equation for LBW in males?

50 + 2.3(inches over 5')

what is the equation for LBW in females?

45.5 + 2.3(inches over 5')

when should adjusted weight be used in Cockcroft Gault?

if actual body weight is >20% over LBW or BMI > 25

what is the equation for adjusted body weight?

LBW + 0.4(actual - LBW)

what drugs need to be dose adjusted for Childs Pugh classification?

-caspofungin

-voriconazole

-tigecycline

-eravacycline

what factors impact Childs Pugh classification?

-ascites

-bilirubin

-albumin

-INR

-encephalopathy

what do liver transaminases indicate?

acute liver toxicity/injury, NOT liver function

what does a Childs Pugh classification of 5-6 mean?

mild liver disease

what does a Childs Pugh classification of 7-9 mean?

moderate liver disease

what does a Childs Pugh classification of 10-15 mean?

severe liver disease

what can site of infection impact with antimicrobials?

antimicrobial selection

what are underlying conditions that may impact antimicrobial therapy?

chronic illness, pregnancy

why is dosing of antimicrobials in obesity difficult?

there is decreased reliability of renal function estimating equations and alterations in drug distribution

what is pharmacokinetics?

fate of an agent within a system characterized by absorption, distribution, metabolism, and elimination

what is pharmacodynamics?

characteristics of the interaction between a xenobiotic, its active site, and pharmacological action

what makes up pharmacodynamics of antimicrobials?

-concentration/activity relationships

-postantibiotic effect

describe concentration-dependent bactericidal activity

rate and/or extent of bactericidal activity increases with increasing antimicrobial concentrations

what is the goal of a concentration-dependent bactericidal activity?

to optimize the peak:MIC for higher bacteria killing

what are antimicrobials that exhibit concentration-dependent bactericidal activity?

-aminoglycosides

-fluoroquinolones

-metronidazole

-amphotericin B

-daptomycin

describe non-concentration-dependent bactericidal activity

rate and extent of killing do not increase with increasing antibiotic concentrations, but rather bactericidal activity is increased by increasing the length of exposure

what is the goal of a non-concentration-dependent bactericidal activity?

optimize the time concentrations to remain above the MIC

what is the efficacy of non-concentration-dependent agents dependent on?

trough concentrations

what can be used to optimize the activity of non-concentration-dependent bactericidal activity and keep t>MIC?

continuous infusion and extended infusion

what are antimicrobials that exhibit concentration-independent killing?

-beta-lactams

-glycopeptides

-clindamycin

-macrolides

-fluconazole

what is the post-antibiotic effect (PAE)?

persistent suppression of bacterial growth following a brief exposure to an antimicrobial

what can the post-antibiotic effect be a result of?

-non-lethal cell damage

-persistence of the antimicrobial at the binding site

what factors can affect the post-antibiotic effect?

-microorganism

-antimicrobial

-length of antimicrobial exposure

-antimicrobial concentration

how should agents that exhibit concentration-dependent killing and have long post-antibiotic effects be administered?

as large, infrequent doses to maximize their pharmacodynamic properties

what dosing regimen has been studied to optimize the antibacterial activity of aminoglycosides?

once-daily dosing

with traditional dosing of aminoglycosides, what is the desired peak concentration?

8-10

with traditional dosing of aminoglycosides, what is the desired trough concentration?

less than 2

with synergy of aminoglycosides for gram positive infections, what is the desired peak concentration?

3-4

if the CrCl is >60, what is the initial interval of dosing for aminoglycosides?

24 hours

if the CrCl is 40-59, what is the initial interval of dosing for aminoglycosides?

36 hours

if the CrCl is 30-39, what is the initial interval of dosing for aminoglycosides?

48 hours

if the CrCl is <30, what is the initial interval of dosing for aminoglycosides?

use traditional dosing

what are some good reminders when monitoring levels of a drug?

check drug admin time and time the level was obtained

what peak:MIC correlates best with outcome for fluoroquinolones?

10:1 to 20:1

what is the target AUC:MIC for gram negative organisms when treating with fluoroquinolones?

125:1

what is the target AUC:MIC for gram positive organisms when treating with fluoroquinolones?

30-40 or greater

how should agents that exhibit concentration-independent killing and have relatively short/no post-antibiotic effect be dosed?

frequent dosing, continuous infusions, or extended infusions

what could a continuous infusion of a beta-lactam do for its serum concentrations?

provide serum concentrations above the MIC of a pathogen for 100% of the dosing interval

if continuous infusion of beta lactams is used, what should the rate of infusion be targeted at?

to maintain serum concentrations at least 4 times the MIC

what is the continuous infusion regimen of penicillin?

24 MU over 24 hours by continuous infusion

what is the continuous infusion regimen of piperacillin/tazobactam?

3.375 g over 4 hours every 8 hours

what AUC:MIC is associated with better outcomes for Staph aureus when using vancomycin?

AUC:MIC >400