Infectious Diseases Introduction

Contact Information

• Current schedule is Monday, Tuesday, Thursday, Friday, from 12:15 PM to 4:15 PM.
• Current schedule is Wednesday, from 8:30 AM to 12:30 PM.
• Office number is 336.
• Email address is [email protected].

Introduction to Infectious Diseases

• The material is presented by Angelique Pereira, Pharm.D., BCPS

Objectives for Learning

• Differentiate bacteria based on Gram stain, morphology, and classification.
• Understand the differences between infection, colonization, and contamination.
• Identify likely organisms based on the infection site.
• Interpret an antibiogram.
• Understand drug and host factors for antimicrobial therapy selection.
• Determine if a patient can switch from IV to PO antibiotics.
• Identify key resources for infectious diseases.

Stepwise Approach to Infections

• Establish the presence of infection.
• Determine the source of infection.
• Identify the likely pathogen(s).
• Select appropriate empiric antimicrobial therapy.
• De-escalate to definitive antimicrobial therapy when appropriate.
• Monitor clinical response and adverse effects.

Establishing Infection and Determining Source

• The first two steps in addressing infectious diseases involves establishing the presence of infection and pinpointing its source.

History/Clinical Presentation

• Obtain the full patient history.
• The clinical presentation varies depending on the location of the infection.
• Skin infections often present with swelling, inflammation, pain, erythema, and purulence.
• Lower respiratory tract infections present with cough, rales, rhonchi, wheeze, and sputum production.
• Central nervous system infections may cause neck stiffness, photophobia, headache, altered mental status, and dizziness.
• Systemic manifestations include fever (>100.4ºF), tachypnea, tachycardia, hypotension, and altered mental status.

Laboratory Tests

• Leukocytosis is marked by an elevated white blood cell count (WBC).
• Normal WBC range is 5-10x10^3 cells/μL.
• Neutrophilia indicates elevated levels of neutrophils.
• Neutrophilia is commonly seen in bacterial infections.
• Bands or immature neutrophils indicate a "left shift".
• "Segs", segmented neutrophils, are mature neutrophils.
• Eosinophilia is an elevated eosinophil count.
• Eosinophilia is often seen in parasitic infections.

Inflammatory Markers

• Inflammatory markers are elevated when inflammation is present.
• These markers are often elevated during infections.
• Inflammatory markers are non-specific.
• Common inflammatory markers include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT).

Radiology Tests

• Utilize X-rays, CT scans, and MRIs for diagnosis.

Gram Stain/Culture

• Specimens are taken from the suspected source (e.g., blood, urine, sputum).
• Gram staining is a preliminary bacterial identification technique.
• Cultures detect bacteria or fungi and identify the type.
• Cultures take about 5 days to finalize.

Infection vs. Colonization vs. Contamination

• Isolation of an organism on Gram stain or culture can indicate one of three conditions.
• Infection involves an organism causing a pathogenic effect.
• Colonization involves the presence of an organism without causing infection.
• Normal flora colonize body structures and systems without causing disease.
• Contamination refers to accidental introduction of bacteria into a specimen.

Normal Flora Bacteria

• Normal flora are present in various parts of the body; examples of these are outlined in a table.

Infection Considerations

• Corticosteroids can increase WBC counts.
• Fever is common in many disease states, including autoimmune diseases, cancers, and pulmonary embolism.
• Fever can be drug-induced by antimicrobials, anticonvulsants, and antiarrhythmics.
• It's important to evaluate the whole clinical picture to determine if an infection is present.

Clinical Scenario 1

• TJ presents with pain, warmth, and redness in the right lower leg.
• Physical exam showed swelling, tenderness, warmth, and erythema (RLE).
• Vitals show BP 135/95, HR 112, RR 18, and T 103.1F.
• It's important to determine if this is consistent with an infection and know what else to test.

Clinical Scenario 1 Lab Results

• Significant labs include WBC 22x103 cells/μL and CRP 17 mg/dL.
• The normal reference range for CRP is <1 mg/dL.
• CT scan shows severe acute cellulitis from the right inner thigh/posterior groin and lateral thigh.
• No evidence of abscess.

Identifying Pathogens

• After establishing the presence and source of infection the likely pathogens are identified.

Factors Influencing Suspected Organisms

• Site of infection
• Setting (community vs. nosocomial)
• Geographic location/travel history
• Occupation
• Immune status (e.g., HIV, transplant patients)
• Animal exposure
• Medical history
• Comorbidities
• Social history
• Surgical history

Bacterial Classification

• Bacteria are classified by Gram stain/morphology, Gram-positive or Gram-negative, Cocci or bacilli, Pairs/chains/clusters/branching, Aerobic or anaerobic, Spore-forming or non-spore forming and Biochemical tests or Hemolysis (blood agar plate).

Empiric vs. Definitive Therapy

• After identifying the likely pathogen, empiric antimicrobial therapy & de-escalate to appropriate definitive antimicrobial therapy,

Empiric therapy

• Empiric therapy treats suspected infection without identifying the pathogen and using antimicrobials to cover most likely organisms.
• Empiric therapy is broad-spectrum" and starts as soon as possible, even before microbiological results are available.

Definitive therapy

• Definitive therapy changes to most narrow spectrum antimicrobial possible after identification of pathogen and susceptibility (de-escalation)

Empiric Therapy Local Patterns

• An antibiogram is annual summary of antibiotic susceptibility for the most common organisms isolated at that institution. Includes both the number of isolates (non-duplicate) and susceptibility to antibiotics important for empiric therapy choice.

Sample Antibiogram Tables

• Sample antibiogram tables for urine and non-urine sources

Interpreting an Antibiogram

• A patient is growing E. coli in the blood. What antibiotic has the bestcoverage of this organism? What other antibiotics have good coverage ofthis organism?
• A physician wants to know if ciprofloxacin would be a good option fortreating Proteus mirabilis based on our antibiogram. How do you respond? What is the chance that ciprofloxacin will cover this organism?

Host Factors Influencing Choice of Antimicrobial

• Factors to consider include site of infection, allergies, age, genetic abnormalities, pregnancy, renal/liver function, comorbidities, and severity of infection.

Drug Factors Influencing Antimicrobial Choice

• Clinical Evidence
• Pharmacokinetics and pharmacodynamics
• Toxicity
• Drug-drug interactions
• Route of administration
• Combination therapy:
• Synergy: drug combination exerts an effect great than the sum of their individual effects
  • E.g. Beta-lactam and aminoglycoside against enterococci

Pharmacokinetics/Pharmacodynamics

• ADME factors
• Absorption: oral medications
  • Feeding, changes in gastric PH, chelation
• Distribution: penetration to the site of infection
  • In general, most agents have poor penetration into the eye, prostate, bone,CNS
• Elimination: metabolism and excretion
  • Kidney dysfunction, dialysis, hepatic impairment, drug interactions

Bactericidal or Bacteriostatic

• Bacteriostatic: inhibits growth of bacteria and bacteriicidal kills bacteria

Time vs Concentration

• Time-dependent (T>MIC): Antibiotics that have maximal effect when serumdrug concentrations exceed the MIC > 50% of the dosing interval and concentration-dependent (Cmax:MIC) are Antibiotics that have maximal effect by optimizing concentration above the MIC

Definitive Therapy Details

• Once a culture has identified a pathogen, you want to be sure that empiric therapy is covering that organism, after susceptibilities change antimicrobial to the most narrow spectrum antimicrobial possible (i.e. de-escalation) Also must take into account both host and drug factors when choosing an agent ### Back to TJ
• Details of a second clinical scenario and questions to consider are presented.

IV to PO

• When a patient improves clinically, it may be appropriate to switch the patient from an IV agent to an oral agent, most hospitals have a pharmacy protocol and criteria.
• Switch criteria includes: IV therapy for at least 24 hours, Functioning Gl tract , Tolerating other feeds/diet and/or oral medications , Afebrile for 24 hours, Heart rate < 100 bpm, Respiratory rate < 24 breaths/min, SBP > 90 mmHG, O2 saturation > 90% on room air or at baseline, and WBC declining

Clinical Response Factors

• Clinical Response Monitoring parameters vary in each case and includes, resolution of signs/symptoms of infection, decreasing WBC, resolution of fever, Negative cultures, inflammatory markers, radiology, etc.
• Treatment failure can be due to inadequate source control, wrong drug/dose, undetected organism not be treated, drug resistance to selected antimicrobial, etc..

Switching IV to PO

• Do not change IV to PO in certain severe infections like Endocarditis/endovascular infections, Osteomyelitis and CNS infections, and Other severe infections where oral antibiotics may not achieve adequate antimicrobial levels

Resources You Can Use

• Key resources for managing infectious diseases include Infectious Diseases Society of America (IDSA), Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (DHHS), and The Sanford Guide to Antimicrobial Therapy.

Final Info on the Presentation

• The subject matter is Introduction to Infectious Diseases by Angelique Pereira, Pharm.D., BCPS