Infectious Diseases Introduction

• Introduction to Infectious Diseases presented by Angelique Pereira, Pharm.D., BCPS.
• Contact info: Email at [email protected], office 336, schedule MoTuThFr 12:15-4:15, We 8:30-12:30

Objectives

• Differentiate bacteria based on Gram stain, morphology, and classification characteristics
• Distinguish between infection, colonization, and contamination
• Identify likely organisms by infection site
• Interpret antibiograms
• Understand drug/host factors for optimal antimicrobial therapy
• Determine patient suitability for IV to PO antibiotic conversion
• Identify resources for infectious diseases

Stepwise Approach

• Establish infection presence
• Determine infection source
• Identify likely pathogens
• Select appropriate empiric antimicrobial therapy
• De-escalate antimicrobial therapy to appropriate
• Monitor for clinical response and adverse effects

History/Clinical Presentation

• Obtain patient history
• Clinical presentation varies by infection location
• Skin infections: swelling, inflammation, pain, erythema, and purulence
• Lower respiratory tract infections: cough, rales, rhonchi, wheeze, and sputum production
• CNS infections: neck stiffness, photophobia, headache, altered mental status, and dizziness
• Systemic manifestations: fever (> 100.4ºF), tachypnea, tachycardia, hypotension, and altered mental status

Clinical Presentation

• History and physical exam are performed
• Labs include CBC, metabolic panel etc
• Vital signs are taken

Laboratory Tests

• Leukocytosis indicates an elevated white blood cell count (WBC).
• Normal WBC: 5-10x103 cells/μL
• Neutrophilia indicates elevated neutrophils associated with bacterial infections
• Bands (immature neutrophils) indicate a "left shift"
• "Segs" indicate segmented neutrophils are mature neutrophils
• Eosinophilia indicates an elevated eosinophil count; seen in parasitic infections
• Inflammatory markers are elevated in the presence of infection, but are non-specific markers
• Commonly ordered inflammatory markers: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT)
• Radiology tests include X-rays, CT scans, and MRIs

Gram Stain/Culture

• Specimen is taken from the source ie blood, urine, sputum, stool, wound, or abscess
• Gram stain is a technique for preliminary bacteria identification
• Culture detects bacteria or fungi presence, identifies microbe type
• Cultures finalize in about 5 days

Infection vs. Colonization vs. Contamination

• Isolation of an organism can be one of three things
• Infection is an organism causing a pathogenic effect
• Colonization is presence of an organism without causing infection, like normal flora that colonize multiple body structures and systems
• Contamination is accidental introduction of bacteria into a sample

Examples of normal flora bacteria

• Gram-positive cocci include Staphylococcus spp. and Streptococcus spp.
• Gram-positive rods include Corynebacterium spp. and Propionibacterium spp.
• Gram-negative cocci include Neisseria
• Gram-negative rods include Enteric bacilli and Haemophilus spp.
• Other normal flora include Spirochetes and Mycoplasma

Infection or Not?

• Corticosteroids can increase WBC
• Fever is a common finding in many disease states, including autoimmune diseases, cancers, chronic liver disease, and pulmonary embolism
• Fever can be drug induced, from antimicrobials, anticonvulsants, and antiarrhythmics
• Always look at the whole clinical picture when determining infection

Factors Influencing Suspected Organisms

• Site of infection and setting (community vs. nosocomial)
• Geographic location/travel, occupation, and immune status
• Medical, social, and surgical history
• Comorbidities and animal exposure

Bacterial Classification

• Gram stain and morphology determine if bacteria are positive or negative, cocci or bacilli
• Bacteria are classified by pairs, chains, clusters, branching, aerobic or anaerobic
• Spore-forming bacteria are classified spore-forming versus nonspore-forming
• Classification via biochemical tests (e.g., coagulase positive or negative) and hemolysis on blood agar plates

Clinically Relevant Gram Positive Bacteria

• Cocci include Streptococci: Streptococcus pneumoniae, Viridians group Streptococcus, Streptococcus pyogenes group A
• Cocci include Enterococcus facecalis/faecium, Staphylococci: Staphylococcous aureus, Staphylococcus epidermis
• Cocci include Peptococcus and Peptostreptococcus
• Rods include Corynebacterium, Listeria, and Bacillus (Anthrax)
• Anaerobic include Clostridia: Clostridium difficile, Clostridium perfringens, Clostridium tetani and Propionibacterium acnes

Clinically Relevant Gram Negative Bacteria

• Cocci include Moraxella and Neisseria (N. meningitidis; N. gonorrhoeae)
• Rods include Pseudomonas aeruginosa as a respiratory organism: Haemophilus influenzae Bordetella pertussis, Legionella pneumophila, Stenotrophomonas maltophilia, Acinetobacter baumannii, Campylobacter jejuni, and Vibrio cholerae
• Rods include Enteric-related organism as respiratory: Proteus, E. Coli, Klebsiella (PEK), Enterobacter, Citrobacter, Serratia, Providencia, Morganella, Salmonella, Shigella, and Helicobacter pylori
• Anaerobic Rods include Bacteroides: Bacteroides fragilis and Prevotella

Atypical and Resistant Pathogens

• Atypical pathogens: Chlamydia spp., Mycoplasma spp., Legionella spp.
• Resistant pathogens include Staph. aureus, Methicillin-Susceptible S. aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA)
• Resistant pathogens also include Vancomycin-Resistant S. aureus (VRSA), Enterobacteriaceae: Extended-spectrum beta-lactamases (ESBL), carbapenem-resistant Enterobacteriaceae (CRE), E. coli, Klebsiella, Citrobacte, Enterobacter, Serratia, Proteus, Shigella, and Salmonella
• Resistant pathogens also include Enterococcus: Vancomycin-resistant enterococcus (VRE) and Multi-drug resistant (MDR) Pseudomonas aeruginosa

Identifying Bacteria

• Gram-positive cocci are identified based on catalase and coagulase tests
• Gram-negative rods are identified based on lactose fermentation

Cultures

• Sample is taken of presumed infectious material
• Collection done prior to antibiotics
• Method of multiplying microbial organisms by growing ("culturing")
• Culture media varies, some is general enriched, or specialized
• Culture media can be for aerobic or anaerobic conditions

Susceptibilities

• Microbiology labs quantify antimicrobial activity via minimum inhibitory concentration (MIC)
• MIC is the lowest antimicrobial concentration preventing visible organism growth
• MICs are unique to drugs and bacteria
• Quantitative MIC results are interpreted as a qualitative susceptibility to a specific antimicrobial
• Breakpoint: MIC at which an organism is deemed susceptible, intermediate, or resistant
• The Clinical and Laboratory Standards Institute (CLSI) establishes breakpoints, varying by bacteria and antimicrobial agent

Qualitative Susceptibility Test

• Antimicrobial-impregnated disks on culture media observe bacterial growth
• A zone of growth inhibition = antimicrobial is active
• The diameter of inhibition is reported as sensitive, intermediate, or resistant (CLSI guidelines)

Quantitative Susceptibility Tests

• Bacterial inoculum undergoes serial dilutions of antimicrobials in broth
• After incubation, wells are examined for bacterial growth
• Minimum inhibitory concentration (MIC) is antimicrobial concentration that inhibits bacterial growth

Rapid Diagnostic Tests (RDT)

• Results are available within 15 minutes to a few hours
• Major focus on pathogens with increased morbidity/mortality
• E.g., MRSA, VRE, ESBL, influenza, C.diff
• Current techniques involve genomic testing methodologies
• mecA gene: MRSA
• vanA & vanB gene: vancomycin-resistance VRE, VRSA

Empiric vs. Definitive Therapy

• Empiric therapy treats suspected infection without pathogen identification, and covers likely microbes ("broad-spectrum")
• Definitive therapy changes to narrow antimicrobials once pathogen/susceptibility are identified (de-escalation)

Empiric Therapy

• Local antibiograms give annual antibiotic susceptibility summaries
• Includes isolate numbers and % susceptibility to antibiotics
• Important when choosing therapy

Antibiogram Interpretation

• Determine the antibiotic with the best coverage for a specific organism
• Determine how likely is it that Ciprofloxacin will kill Proteus mirabilis based on the antibiogram

Host Factors Influencing Antimicrobial Choice

• Site of infection, allergies, history of ADRs, and age
• Genetic abnormalities and pregnancy
• Renal/liver function and comorbidities
• Severity of infection

Drug Factors Influencing Antimicrobial Selection

• Clinical evidence
• Pharmacokinetics and pharmacodynamics
• Toxicity and drug-drug interactions
• Route of administration
• Combination therapy has synergistic effects

Pharmacokinetics/Pharmacodynamics

• ADME: absorption, distribution, metabolism, and excretion
• Absorption of oral medications depends on feeding, gastric pH, and chelation
• Distribution: penetration to infection site
• Agents generally have poor penetration into the eye, prostate, bone, and CNS
• Elimination depends on kidney function, dialysis, hepatic impairment, and drug interactions

Pharmacokinetics/Pharmacodynamics

• Bacteriostatic inhibits growth of bacteria
• Bacteriocidal kills bacteria
• Static: Macrolides, Clindamycin, Linezolid/tedizolid, Tetracyclines Sulfonamides
• Cidal: Beta-lactams, Aztreonam, Fluoroquinolones, Aminoglycosides, Vancomycin, Daptomycin, Rifampin, Metronidazole, Polymyxins
• Concentration/Time Dependent Killing

Time-Dependent vs. Concentration-Dependent

• Time-dependent (T>MIC) antibiotics have full effect when serum drug concentrations exceed the MIC >50% of the dosing interval.
• Concentration-dependent (Cmax:MIC) antibiotics have full effect by optimizing concentration above the MIC.
• AUC:MIC relates to the amount of time above the MIC and the total exposure of antibiotic to the organism
• Time: Beta-lactams
• Concentration: Aminoglycosides, Fluoroquinolones, Daptomycin
• AUC: Vancomycin, Macrolides, Tetracyclines

Definitive Therapy

• Be sure empiric therapy covers causative organism(s)
• Change antimicrobial to narrowest possible spectrum
• Account for host/drug factors

Drug Monitoring

• Watch for toxicity from rash, allergic reaction, renal toxicity, ototoxicity, etc.
• Consider drug interactions and dose adjustments, such as in renal impairment
• Check serum drug levels for vancomycin and aminoglycosides

Patient's Clinical Response

• Monitor for resolution of infection signs/symptoms
• Monitor decreasing WBC
• Monitor fever resolution
• Monitor inflammatory markers and radiology
• Monitor for negative cultures
• Treatment failure can be due to inadequate source control, wrong drug/dose, undetected organism, or drug resistance

IV to PO

• Switch when a patient improves clinically
• Evaluate pharmacy protocol, which may vary among institutions
• Switch IV to PO if IV therapy has been going for at least 24 hours, there is a functioning GI tract, the patient can tolerate other feeds/diet and/or oral medications
• Switch to PO if the patient is afebrile for 24 hours, heart rate is < 100 bpm, respiratory rate is < 24 breaths/min, SBP is > 90 mmHG, 02 saturation > 90% on room air or at baseline, and WBC is declining

More on IV to PO

• Do not switch from IV to PO in severe infections such as endocarditis/endovascular infections, osteomyelitis and CNS infection
• Other severe infections where oral antibiotics may not reach antimicrobial levels need to stay on IV

Important Resources

• Infectious Diseases Society of America (IDSA)
• Centers for Disease Control and Prevention (CDC)
• U.S. Department of Health and Human Services (DHHS)
• AIDSinfo guidelines on HIV/AIDS
• Sanford Guide to Antimicrobial Therapy
• Pocket guide of antibiotic coverage/treatment