Lab Tests for Ab Tx

Normal Chem 7 Ranges

Na: 135-145

K: 3.5-5.0

Cl: 95-105

Co2: 22-28

BUN: 7-24

SCr: 0.7-1.4

Glu: 60-110

CBC normal ranges

WBC: 4-10k

Hgb: 10/12-14/16

Hct: 35-45

Plt: 145-450k

What is a differential diagnosis

An educated guess of what is causing the presenting condition. Can be used to help diagnose physical or mental health disorders

Criteria of diagnostic tests

Reliability: the extent to which the test yields the same results on repeated trials

Validity: the quality of correctness of a measure

Sensitivity: the ability of a test to correctly identify people who have a given disease or disorder. The more sensitive the fewer false negatives.

Specificity: the ability to test correctly. The more specific, the fewer false positive results

What are biomarkers

Defined characteristics that are indicators of normal biological processes, pathogenic processes, or response to an exposure or intervention, including therapeutic interventions. Not an assessment of how an individual feels.

Types of biomarkers

Molecular, histologic, radiographic or physiologic

Diagnostic biomarkers

Used to detect or confirm the presence of a disease or condition of interest or to identify individuals with a subtype of the disease

Monitoring biomarkers

Measured repeatedly for assessing the status of a disease or medical condition, or for evidence of exposure to a medical product or an environmental agent

Prognostic biomarker

Used to identify the likelihood of a clinical event, disease recurrence, or progression in patients who have the disease or medical condition of interest.

Steps of antimicrobial selection

Empiric therapy, targeted therapy, culture targeted therapy, stop antibiotics

What are antibiograms

Tools that provide information on the susceptibility of bacteria to various antibiotics. Assist in the selection of appropriate empiric therapy. They monitor resistance trends over time within an institution. They can also help with stewardship programs. If susceptibility is less than 80-85% an antibiotic is not appropriate for empiric therapy.

Gram stain

Used for organism identification. Determines gram negative (pink) or positive (purple)

Acid fast stain (AFB)

Identify mycobacteria that have no cell walls

KOH stain

Identify fungi

Staphylo prefix

Clusters

Strepto prefix

Chains

What is bacteria colonization

Presence of organisms without clinical or sub-clinical disease. Organisms that occur naturally in our tissue that provide benefits by competing for resources and suppressing growth of pathogenic bacteria or fungi

Bacterial contamination

Presence of organisms on a body surface without invasion or response.

Bacterial infection

Able to transmit infections to others

Bacterial carrier

Person who is infected with an organism but shows no evidence of disease

Staph. Aureus colonization

MSSA is carried by 16-35% of people. MRSA colonizes about 4-8% of people. They can infect once natural cutaneous barriers are damaged.

Purpose of biomarkers for infectious disease

Should facilitate early rapid diagnosis, predict the course and prognosis of the disease and guide therapeutic decisions.

Examples of ID biomarkers

WBC, ESR, CRP, and Serum procalcitonin (PCT)

White blood cell differential

Neutrophils

Lymphocytes

Monocytes

Eosinophils

Basophils

Elevation in WBCs

Can be due to non-disease factors like stress arthritis. Drugs like corticosteroids can increase WBCs.

Granulocytes

Neutrophils, Eosinophils, and Basophils

Agranulocytes

Lymphocytes: T + B cells associated with viral infections

Monocytes/macrophages

Erythrocyte Sedimentation Rate

Measures how many RBCs drift through a test tube of blood and settle at the bottom in one hour. Proteins generated in disease cause RBCs to stick together increasing the rate at which they drift down the tube. Slower to change. Nonspecific for infections. Can be caused by multiple disease. False positives occur in pregnancy or hormone replacement.

Normal ESR value

<15 mm/hr

CRP

CRP is a substance that the liver makes in response to inflammation. Increases/Decreases fast than ESR.

Normal CRP value

<10mg/L

>10 indicates infection, trauma, or chronic disease

Procalcitonin

Nonspecific can be used in several infections. Precursor to calcitonin that lowers blood calcium

Normal procalcitonin value

<0.15ng/mL

.15-2 could mean possible local infection

>2ng/mL indicates systemic infection

Blood Culture Sample Collection

Can be in aerobic or anaerobic tubes. 10mL in each tube. Send to lab to determine sensitivities to bacteria. Need to ensure proper collection and handling of specimen. Can remove antibiotic to allow organism to grow uninhibited.

Rapid testing (RDT)

Has improved the ability to diagnose infections and determine the antimicrobial susceptibilities for numerous pathogens including fastidious or slow growing mycobacteria and viruses.

Antigen test

Reveals if someone is currently infected with a pathogen. Once the infection is gone the antigens disappear. Very fast but at the cost of some sensitivity.

Nucleic Acid/PCR Test

Detect the presence of genetic material. Can take hours but are highly sensitive.

Antibody Testing

Serology. A negative test may occur if the test is taken too soon before any antibodies are being produced. False positive can also occur as a result of previous infection and cross-reactivity with other viruses.

Minimal Inhibitory Concentration

The lowest antimicrobial concentration that prevents visible growth of an organism after 24 hours of incubation in a specific growth medium. Measured in ug/mL

Minimum Bactericidal Concentration (MBC)

Lowest concentration of a given antimicrobial that will kill 99.99% of the patients’ organisms after 18-24 hours of incubation. Not routinely performed.

Bacterial tolerance

If the MBC/MIC ratio is >32 the organism is considered tolerant to the antibiotic. Clinical significance is unknown.

Kirby Bauer Disk Diffusion Test

Qualitative test applicable to organisms that grow rapidly on artificial media. Organisms are streaked across the surface of the agar followed by application of antibiotic disks. Results are measured in S (sensitive), I (intermediate), R (resistant). They are fast, low cost, and are minimally labor intensive.

Disadvantage of Disk Diffusion Test

Does not show MBC

Broth Dilution

Done in micro and macrotubes, only difference is volume. These tests can be automated and can determine MBC. Disadvantage is that macrotubes are labor intensive.

E-Test

Quantitative test expressed as mcg/mL. Antibiotics diffuse from plastic strips in a gradient. Strip is placed on an agar plate which is then incubated. Bacteria will grow in a tear shape and show a zone of inhabitation which the MIC is read from.

Advantages of E-test

Quantify MIC, easy to produce and reproduce. Multiple antibiotics can be tested on one plate

Disadvantages of E-test

E-strips are expensive. MBC can not be determined.

Clinical utility of MIC

Used to determine selection of definitive antibiotic therapy. If the concentration of antibiotic achievable in blood will be enough to inhibit bacterial growth. A bacteria is resistant if the MIC is above the achievable antibiotic concentration.

Clinical utility of MBC

Determines when bactericidal activity is required for successful outcome in disease like meningitis or endocarditis.

Pharmacokinetics

What the body does to the drug

Pharmacodynamics

What the drug does to the body

Antimicrobial PD

Relationship between the drug, the patient, and the organism. Considers toxicity to patient, susceptibility to organism, and immune response as a result of the pathogen.

Which drugs use Cmax/MIC PD parameters

Aminoglycosides and Fluoroquinolones

Concentration dependent killing antibiotics, maximize exposure

Which drugs use AUC/MIC PD parameters

Macrolides, Ketolides, Glycopeptides

Concentration dependent killing antibiotics, maximize exposure

Which drugs use Trough (T)/Cmin>MIC PD parameters

Beta lactams, tetracyclines, Oxazolidinones

Concentration independent killing antibiotics

Time dependent, optimize duration of exposure

SDD

Susceptible Dose dependent. Need higher drug exposure to achieve susceptibility breaking point.

Antimicrobial Absorption

IV administration rapid and complete - if the gut works use it. Absorption takes about 30 minutes

Antimicrobial Distribution

Dependent on class - penetrate the site of action/infection

Antimicrobial Metabolism

Many are hepatically metabolized - drug interaction

Antimicrobial Elimination

Most are renally eliminated therefore require dosage adjustments in renal dysfunction.

GFR

Calculated using age, sex, race, scr. A GFR <60 mL/min/1.73m² may indicate kidney disease. It is the rate at which plasma is filtered across the glomerulus. Normal range in 90-150

Half life

Is the time is takes for a drug to lose half its strength in the body. Dosing intervals are based upon the half life of a drug and the time/amount it takes to reach a steady state.

Steady state

Can be achieved in 3-5 half-lives. Defined as the amount of drug administer per until time equal drug eliminated per unit of time. Drug in = Drug out. Not all drugs need to achieve CSS to have a therapeutic effect.

Considerations in Adjusting Dose

CrCl, toxicities of antibiotics, clinical conditions, infection type, and targeted organism

Antibiotics that do not require renal dosage adjustments

Nafcillin/Dicloxacillin, doxycycline, azithromycin, tigecycline, linezolid

PK Consideration

Renal elimination changes with age, tissue penetration differs between drug classes, and the concentration/therapeutic index of a drug

Aminoglycoside penetration

Limited penetration into certain organs like the lungs and brain

Beta lactam penetration

Have very high penetration

Therapeutic Drug monitoring (TDM)

Routine monitoring of serum concentrations is currently used for a select few antimicrobials like aminoglycosides and vancomycin in an attempt to minimize toxicity and maximize efficacy.

Goal of antimicrobial therapy

Minimize toxicities and eradicate pathogen

Vancomycin

Has a lot of side effects including ototoxicity and nephrotoxicity. AUC/MIC target should be 400-600 for patients with MRSA. AUC/MIC ratio >400 achieves bactericidal activity

Vancomycin dosing

Weight based 15mg/kg x actual body weight rounded to nearest 250mg. Choose dosing interval based on CrCl.

CrCl:

• >100 q6-8hours

• 80-100 q8 hours

• 50-79 q12 hours

• <25 q36-48

Why use AUC for vancomycin

AUC/MIC ratio is the primary PK/PD predictor of vancomycin activity. Troughs are imprecise for AUC. Higher troughs >17 are associated with AUC>600 and increased risk of Acute kidney injury (AKI). AUC guided dosing and monitoring reduces rates of AKI.

When to use IV

Patients can not swallow or absorb antibiotics. Cases of sepsis or meningitis.

When is IV contraindicated

Phlebitis, extravasation injury, thrombosis, systemic infection.

Why are IVs not preferred by patients

Prolongs length of stay, inconvenient, higher cost

Which antibiotics can be used Oral and IV

TMP/SMX, quinolones, tetracyclines, clindamycin, linezolid, rifampin, metronidazole, fluconazole, voriconazole, valganciclovir