Study Notes for ID Exam 1

ID Exam 1 Material

Penicillin's

• General Effectiveness:

  • Effective against streptococci, enterococci, and anaerobes

• Natural Penicillins (Pen V, Pen G):

  • Effective against MSSA (Methicillin-Sensitive Staphylococcus Aureus) and streptococci

• Penicillinase Resistant Penicillins (e.g., oxacillin, nafcillin, dicloxacillin):

  • Effective against streptococci, enterococci, anaerobes
  • +/- effectiveness against enterobacterales

• Amino Penicillins (e.g., ampicillin and amoxicillin):

  • Effective against streptococci, enterococci, enterobacterales, pseudomonas, and anaerobes

• Extended Spectrum Penicillins (e.g., piperacillin and ticarcillin):

  • Effective against MSSA, streptococci, enterococci, enterobacterales
  • ++ effectiveness against anaerobes

• Combination Therapy:

  • Amoxicillin/Clavulanate and Ampicillin/Sulbactam:
  • Effective against MSSA, streptococci, enterococci, enterobacterales, and pseudomonas
  • ++ effectiveness against anaerobes
  • Ticarcillin/Clavulanate and Piperacillin/Tazobactam:
  • Combination noted for their enhanced effects
  • Sulbactam/Durlobactam:
  • Active against Acinetobacter baumannii ONLY

• Color Coding:

  • Purple = Gram Positive (G+)
  • Pink = Gram Negative (G-)
  • Orange = Anaerobes
  • Lime = Atypical

Cephalosporin's

• General Effectiveness:

  • Effective against MSSA and streptococci
  • +/- effectiveness against enterobacterales

• 1st Generation (e.g., cefazolin, cephalexin, cefadroxil):

  • Effective against MSSA, streptococci, and anaerobes
  • +/- effectiveness against enterobacterales

• 2nd Generation (e.g., cefuroxime, cefprozil, cefaclor):

  • ++ effectiveness against anaerobes
  • Effective against MSSA, streptococci, and enterobacterales

• 2nd Generation Cephamycins (e.g., cefotetan, cefoxitin):

  • Effective against MSSA, streptococci, enterobacterales, anaerobes
  • +/- effectiveness against pseudomonas (ceftazidime has activity)

• 3rd Generation (Various, e.g., ceftriaxone, cefotaxime, cefdinir, etc.):

  • Purple = G+
  • Pink = G-
  • Orange = Anaerobes
  • Lime = Atypical

• 4th Generation (e.g., cefepime):

  • Effective against MSSA, MRSA (Methicillin-Resistant Staphylococcus Aureus), streptococci, enterobacterales, and +/- pseudomonas

• 5th Generation (e.g., ceftaroline, ceftobiprole):

  • ++ effectiveness against enterobacterales

• Combination Therapies:

  • Cefepime/Enmetazobactam:
  • Effective against pseudomonas, MSSA, streptococci, ++ enterobacterales
  • Ceftazidime/Avibactam:
  • ++ effectiveness against pseudomonas and anaerobes
  • Ceftolozane/Tazobactam:
  • + effectiveness against streptococci, ++ effectiveness against enterobacterales and pseudomonas
  • Cefiderocol:
  • +/- effectiveness against streptococci

Carbapenems and Monobactam

• General Effectiveness:

  • ++ effectiveness against anaerobes, enterobacterales
  • + effectiveness against MSSA, streptococci, pseudomonas
  • +/- effectiveness against enterococci

• Specific Carbapenems and Monobactams:

  • Meropenem, Imipenem/Cilastatin, Doripenem:
  • ++ effectiveness against anaerobes
  • + effectiveness against MSSA, streptococci, enterobacterales
  • Ertapenem:
  • ++ effectiveness against enterobacterales
  • + effectiveness against MSSA, streptococci, anaerobes
  • Sulopenem:
  • + effectiveness against enterobacterales, pseudomonas
  • Aztreonam:
  • ++ effectiveness against enterobacterales
  • + effectiveness against pseudomonas

• Combination Therapy:

  • Aztreonam-Avibactam

• Color Coding:

  • Purple = G+
  • Pink = G-
  • Orange = Anaerobes
  • Lime = Atypical

Peptide Antibiotics

• General Effectiveness:

  • + effectiveness against MSSA, MRSA, streptococci, enterococci, anaerobes

• Vancomycin:

  • Ineffective against VRSA (Vancomycin-Resistant Staphylococcus Aureus) and VRE (Vancomycin-Resistant Enterococci)
  • Effective against:
  • ++ enterococci
  • + MSSA, MRSA, streptococci

• Additional Peptides:

  • Telavancin, Dalbavancin, Oritavancin:
  • ++ effectiveness against enterococci
  • + MSSA, MRSA, streptococci
  • Daptomycin:
  • ++ effectiveness against enterobacterales, pseudomonas

• Polymyxin B and E:

  • + effectiveness against enterobacterales, pseudomonas

• Aminoglycosides (e.g. Amikacin, Tobramycin, Gentamicin, Plazomicin):

• Color Coding:

  • Purple = G+
  • Pink = G-
  • Orange = Anaerobes
  • Lime = Atypical

Tetracyclines, Oxazolidinones, Macrolides, Lincosamides, Quinupristin-Dalfopristin

• General Effectiveness:

  • + effectiveness against MSSA, MRSA, atypical pathogens
  • +/- effectiveness against streptococci, enterococci, enterobacterales, anaerobes

• Tetracyclines:

  • ++ effectiveness against anaerobes
  • + effectiveness against MSSA, MRSA, streptococci, enterococci, enterobacterales, atypicals

• TCN Derivatives:

  • ++ effectiveness against enterococci
  • + effectiveness against MSSA, MRSA, streptococci, anaerobes

• Oxazolidinones:

  • + effectiveness against atypical pathogens, MSSA
  • +/- effectiveness against MRSA, streptococci, anaerobes

• Macrolides:

  • + effectiveness against MSSA, streptococci, anaerobes
  • +/- effectiveness against MRSA

• Lincosamides:

  • + effectiveness against MSSA, MRSA, streptococci, atypical pathogens
  • +/- effectiveness against enterococci

• Quinupristin-Dalfopristin:

  • + effectiveness against MSSA, MRSA, streptococci, enterococci, enterobacterales, anaerobes

• Gepotidacin:

• Color Coding:

  • Purple = G+
  • Pink = G-
  • Orange = Anaerobes
  • Lime = Atypical

Fluoroquinolones, Bactrim, Flagyl, and Fidaxomicin

• General Effectiveness:

  • + effectiveness against enterobacterales, pseudomonas, atypical pathogens
  • +/- effectiveness against MSSA, MRSA, streptococci, anaerobes

• Ciprofloxacin:

  • + effectiveness against MSSA, streptococci, enterobacterales, pseudomonas, atypical
  • +/- effectiveness against MRSA, enterococci, anaerobes

• Levofloxacin:

  • + effectiveness against MSSA, MRSA, streptococci, enterobacterales, anaerobes, atypical
  • +/- effectiveness against enterococci

• Moxifloxacin:

  • + effectiveness against MSSA, MRSA, streptococci, enterobacterales, pseudomonas, anaerobes, atypical
  • +/- effectiveness against enterococci

• Delafloxacin:

  • + effectiveness against MSSA, MRSA
  • +/- effectiveness against streptococci, enterobacterales

• Bactrim:

  • ++ effectiveness against anaerobes

• Metronidazole (Flagyl):

  • + effectiveness against anaerobes

• Fidaxomicin:

  • Specific coverage against C. difficile only

• Color Coding:

  • Purple = G+
  • Pink = G-
  • Orange = Anaerobes
  • Lime = Atypical

Tips

• Antibiotics with + Activity:

  • Include but are not limited to:
  • Ceftaroline, ceftobiprole, vancomycin, daptomycin, lipoglycopeptides, tetracyclines, TCN derivatives, linezolid, moxifloxacin, delafloxacin, Bactrim, quinupristin-dalfopristin

• Antibiotics with +/- Activity:

  • Include but are not limited to:
  • Levofloxacin, ciprofloxacin, clindamycin, macrolides

• MRSA Activity:

  • Antibiotics with + activity against MRSA include:
  • Piperacillin, ticarcillin, pip-tazo, tic-clav, ceftazidime, cefepime, cefepime-enmetazobactam, ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, meropenem, imipenem-cilastatin, doripenem, meropenem-vaborbactam, aztreonam, aztreonam-avibactam, polymyxins, aminoglycosides, ciprofloxacin, levofloxacin, delafloxacin

• Antibiotics with +/- Activity against MRSA:

  • Ceftaroline, ceftobiprole

• Pseudomonas Activity:

  • Note: No enterococcus or atypical coverage in cephalosporins

• Daptomycin, Linezolid, and Lipoglycopeptides:

  • Active against vancomycin-resistant bacteria

• Ertapenem and Sulopenem (Monkeycillin):

  • No Acinetobacter, pseudomonas, or enterococcus (APE) coverage

• Flagyl Coverage:

  • Covers all anaerobes

• Fidaxomicin Coverage:

  • Only covers C. difficile.

Antimicrobial Resistance

• Definition:

  • Resistance of bacteria, fungus, and parasites to antimicrobial medications previously effective in treating infections.

• Minimum Inhibitory Concentration (MIC):

  • Defined as the lowest concentration that will inhibit visible growth of a microorganism.

• Minimum Bactericidal Concentration (MBC):

  • Lowest concentration of an antibiotic that will kill 99.9% of the original inoculum.

• Breakpoint:

  • The MIC that defines susceptibility for each organism-antibiotic pair.

Susceptibility vs Resistance

• Susceptible:
  • MIC < breakpoint
• Intermediate:
  • MIC ~ breakpoint
• Resistant:
  • MIC > breakpoint

Impact of Antimicrobial Resistance

• Statistics:
  • Over 2.8 million resistant infections leading to approximately 35,000 deaths.
• Contributing Factors:
  • Over prescription, subtherapeutic dosing/incomplete treatment courses, self-medication.
• Consequences of Inappropriate Antibiotic Use:
  • Decreased effectiveness of antibiotics, increased need for combination therapy, and necessity for impact dosing.

Mechanisms of Genetic Transfer

• Acquired Resistance:
  • Resistance through genetic changes via mutations or the acquisition of new genetic material.
• Intrinsic Resistance:
  • Resistance is a natural feature of some organisms.
• Methods of Gene Transfer:
  • Conjugation:
  • Transfer of genetic material through direct cell-to-cell contact.
  • Transformation:
  • Uptake of free DNA from the environment by bacteria.
  • Transduction:
  • Transfer of DNA from one bacteria to another via bacteriophage, which can be generalized (accidental DNA transfer) or specialized (specific genes transferred).
  • Some bacteria exhibit natural resistance (e.g., atypicals lack a cell wall, making them unaffected by antibiotics targeting cell wall synthesis).

Mechanisms of Resistance

• Types of Resistance Mechanisms:
  • Enzyme Degradation:
  • Example: Beta-lactamases that break down beta-lactam antibiotics (penicillins, cephalosporins).
  • Target Modification:
  • Example: Altered penicillin-binding proteins in MRSA (MecA) and Vancomycin-resistant strains (VanA).
  • Efflux Pumps:
  • Mechanism to pump drugs out of the cell.
  • Bypass Pathways:
  • Bypass affected metabolic pathways to negate drug effect.
• Specific Enzymes Identified:
  • Carbapenemases:
  • Inactivate carbapenems.
  • Aminoglycoside-Modifying Enzymes:
  • Add chemical groups to aminoglycosides preventing binding to bacterial ribosomes.
  • Modified Ribosomal Subunits:
  • Impact macrolides, tetracyclines, aminoglycosides.
  • Mutations in DNA Gyrase/Topoisomerase:
  • Impact fluoroquinolone binding.

Inducible Resistance

• Weak Inducers:
  • Ceftazidime, Ceftriaxone, Piperacillin, Cefepime, Meropenem
• Strong Inducers:
  • Aminopenicillins, Cefazolin, Cephalexin, Cefoxitin, Imipenem
  • AmpC Beta-Lactamases:
  • AMPr suppresses its own production, but some beta-lactams induce production leading to degradation of AMPr, which causes a conformational change resulting in increased enzyme production.

Antimicrobial Stewardship (AMS)

• Purpose:
  • A coordinated program promoting the appropriate use of antimicrobials to reduce microbial resistance, decrease healthcare-associated infections, and improve patient outcomes.
• Choosing An Antibiotic (ABX):
  • Consider coverage, site of action, indication, and bioavailability.

Initiating Antibiotic Treatment

• Treatment Based On:
  • Covering the most likely organism(s).
• Types of Therapy:
  1. Empiric Therapy:
     • Treatment based on the understanding of organisms but lacking specific susceptibilities.
  • Use antibiograms to predict efficacy.
  1. Organism Identified Therapy:
     • Treatment guided by known organism and its susceptibilities.
  2. Definitive Therapy:
     • Treatment confirmed based on specific data.

MRSA Detection in Nares

• Procedure:
  • Validated test for detection of MRSA in pneumonia performed within 48 hours of admission and prior to anti-MRSA therapy.
• High Negative Predictive Value (>90%):
  • Effective rule-out for the following infections: BSI (Bloodstream Infection), IAI (Intra-Abdominal Infection), respiratory infections, wound cultures, UTIs.

Definitive Therapy (Streamlining)

• Choosing Antibiotics from Susceptibilities:
  • Avoid comparing MIC/breakpoints across different antibiotics.
  • Consider adverse effects, evidence level, and cost. Favor choosing narrow spectrum options when possible.
• IV to PO Step-down:
  • Can save money and facilitate patient discharge but may not always be suitable.
  • De-escalation and Treatment Duration:
  • Reduces the rate of bacterial resistance.

Acute Otitis Media (AOM)

• Symptoms:

  • Otalgia (ear pain), fever, irritability, fullness/pressure in the ear, balance problems, tinnitus.
  • In infants: Ear tugging, fussiness, difficulty sleeping, otorrhea (ear discharge).

• Signs & Symptoms (S&S):

  • Children ≥ 6 months with severe AOM (toxic appearance, persistent ear pain lasting >48 hours, fever).
  • Children with AOM with otorrhea (ear discharge).
  • Children 6-23 months with bilateral otitis media.
  • Adults with AOM, based on limited data regarding safety with withholding antibiotics.

• Indications:

  • Choose antibiotics based on spectrum required, allergies, tolerance, previous antibiotic exposure, cost, and resistance factors.

AOM Treatments

• First-Line Treatments:
  • Amoxicillin
  • Augmentin: Only if patient has received amoxicillin in the preceding 30 days, has concurrent conjunctivitis, or has a history of recurrent infections resistant to amoxicillin.
• First Line for:
  • Children: Augmentin straight away.
  • Adults: Non-severe cases treated with cefdinir, cefuroxime, cefpodoxime, ceftriaxone.
  • Cephalosporin Allergy in Adults: Clindamycin.
• Duration of Treatment:
  • Children <2 years: 10 days
  • Children 2-5 years: 7 days
  • Children ≥6 years: 5 days
  • Adults: 5-7 days for mild-moderate AOM, 10 days for severe/refractory cases.

AOM Treatment Failure

• Failure after Amoxicillin: Go to Augmentin.
• Failure after Augmentin or oral cephalosporin: Transition to ceftriaxone.
• Levofloxacin: If allergy present.

Acute Bacterial Rhinosinusitis

• Likely Bacterial Source:

  • Onset of persistent symptoms lasting >10 days without improvement.
  • Severe onset with high fever and purulent nasal discharge/facial pain lasting 3-4 consecutive days.
  • Onset with worsening symptoms following initial improvement from a viral infection.

• Signs & Symptoms (S&S):

  • Purulent nasal discharge, nasal congestion/fullness, cough, fatigue, facial pain, fever, headache, ear pain, halitosis, dental pain.

Acute Bacterial Rhinosinusitis Treatment

• First-Line in Children and Adults Without Penicillin Allergy:

  • Augmentin

• First-Line in Children With Penicillin Allergy:

  • Non-severe: Clindamycin PLUS cefixime or cefpodoxime.
  • Severe: Levofloxacin.

• First-Line in Adults With Penicillin Allergy:

  • Doxycycline, Levofloxacin, or Moxifloxacin.

• Duration of Treatment:

  • Children: 10-14 days
  • Adults: 5-7 days.

Acute Bacterial Rhinosinusitis Treatment Failure

• Failed Augmentin:
  • Transition to Clindamycin PLUS cefixime or Levofloxacin monotherapy.

Acute Pharyngitis

• Strep Throat (S. pyogenes):

  • Clinical diagnosis utilizing Centor score, rapid antigen detection tests (RADTs), throat swab (gold standard).

• Symptoms:

  • Sore throat, pain swallowing, fever, N/V, headache, abdominal pain, inflammation of tonsils/pharynx, enlarged tender cervical lymph nodes, red swollen uvula.

Acute Pharyngitis Treatment

• First-Line Treatments:

  • PenVK or Amoxicillin.
  • If patient unable to tolerate enteral therapy: Benzathine Penicillin G.

• First Line for Children and Adults Without Penicillin Allergy:

  • Non-severe: Cephalexin.
  • Severe: Azithromycin, Clarithromycin, or Clindamycin.

• First Line for Children and Adults With Penicillin Allergy:

  • Unasyn or Augmentin.
  • Clindamycin if allergic to penicillin.
  • If Acute Pharyngitis progresses to peritonsillar abscess or phlegmon, treat for 10 days, Azithromycin for 5 days, including IM injection.

• Duration of Treatment:

  • Peritonsillar abscess: 10-14 days.

Acute Bronchitis

• Symptoms:

  • Cough starting nonproductive, progressing to mucopurulent sputum.

• Signs & Symptoms (S&S):

  • Wheezing, dyspnea, cyanosis, signs of airway obstruction, and fever.
  • Recommend use of analgesics/antipyretics (Tylenol or Ibuprofen); avoid aspirin in children <19.
  • Inhaled beta-agonists, steroids, and antibiotics/antivirals generally NOT recommended.

• Treatment Approach:

  • Provide supportive care.

Pertussis (Whooping Cough)

• Diagnosis:

  • Culture of nasal secretions (gold standard), PCR of nasal secretions.

• Symptoms:

  • Cough worse at night, paroxysmal, may have whooping sound, affecting sleep and leading to fatigue, and episodes of sweating.

Pertussis Treatment

• Antimicrobial Choices:

  • Azithromycin.
  • Erythromycin (ER) as an alternative.

• First Line for Infants Less than 1 Month Old:

  • Azithromycin, erythromycin, clarithromycin.
  • Bactrim as an alternative, contraindicated in infants <2 months.

• Initiate Treatment:

  • Within 21 days of cough onset from sick contact regardless of vaccination status.
  • TDaP Vaccination: Consider for prophylaxis.

Signs & Symptoms of Each Infection

• AOM:

  • Otalgia, fever, irritability, fullness in ear, balance issues, tinnitus.
  • Infants exhibit ear tugging and irritability with trouble sleeping.

• Acute Bacterial Rhinosinusitis:

  • Purulent nasal discharge, nasal congestion, cough, fatigue, facial pain, fever, halitosis.

• Acute Pharyngitis (Strep throat):

  • Sore throat, pain with swallowing, fever, nausea/vomiting, headache, abdominal discomfort, inflammation of tonsils, enlarged/tender cervical lymph nodes, red/swollen uvula.

• Acute Bronchitis:

  • Nonproductive cough evolving into purulence, wheezing, cyanosis, indications of airway obstruction, fever.

• Pertussis (Whooping Cough):

  • Cough worse at night, may have paroxysms and whooping sound, fatigue, sweating episodes.