Patho: week 15 - Antimicrobial Therapy

common infections

• Acne: bacterial, viral

• Bronchitis: bacterial, viral

• Conjunctivitis: bacterial, viral

• Otitis media: bacterial, viral

• STD: viral, bacterial

• Skin/soft tissue infection: fungal, viral, bacterial

• Streptococcal pharyngitis: bacterial

• Traveler’s diarrhea: bacterial

• Upper respiratory tract infection: viral, bacterial

• UTI: bacterial

infections: top 10 causes of death in US

• Septicemia: infection in the bloodstream

• Pneumonia

• Influenza

  • airway compromise: compromises rest of body

site in infection

• Known or suspected sources:

  • Initial s/s 

  • Known exposure

  • Open wound 

  • Surgical site 

  • invasive devices

infection source: invasive device- CLABSI, CAUTI, PICC, VAC, PIV

• Invasive devices: microorganism moves into tissues, blood stream, or tracts - high infection risk → hospital pays for infections (considered 100% preventable)

  • CLABSI: central line associated blood infection 

  • CAUTI: catheter associated UTI

    • Non-invasive device: condom catheter, pure wick → not an infection risk, not invasive

  • PICC: IV potential for infection directly into blood 

  • VAP: ventilator associated pneumonia 

  • PIVs: peripherally inserted IV

    • Prevention is the best medicine: assess for line need, remove line if appropriate, provide care

organism identification: specimen - types & results

• Preliminary result: 24-48 hrs 

  • Essential to obtain specimen prior to initiating antimicrobial tx 

    • Difficult to differentiate whether a negative culture is due to the absence of organisms or is a result of administered antibiotic

• Specimen types: 

  • Blood

  • Sputum

  • Urine

  • Fluid/exudate

  • Tissue

  • CSF

specimen: organism sensitivity test

• Once identified, organism is tested for susceptibility to various antibiotics 

  • Treatment adjusted for optimal efficacy against specific infectious organism 

    • Narrow-spectrum if possible 

    • Final result: 72+ hrs 

• GOAL: definitive treatment 

  • Use narrowest-spectrum drug if possible

• Sensitivity test: start broad spectrum, wait for micro → narrow spectrum antibiotics 

infection v colonization

• Infection: organism dwelling on/in body tissue, immune activation, symptomatic

• Colonization: presence of microorganism without s/s disease 

  • Organism dwelling on/in bodily tissue or on surface of indwelling device 

  • Asymptomatic

antimicrobial therapy: terms - prophylactic, empiric, definition

• Prophylactic: prevent infection associated with high risk procedures/ conditions

  • Invasive procedures  

• Empiric: infection is strongly suspected but, source/specific pathogen unknown

  • Waiting on labs: window - broad spectrum antimicrobials  

• Definitive: when specific pathogen susceptibility is identified

  • Based on recommendation from sensitivity report

antimicrobial therapy: selection of agent - factors

• Selection of the most appropriate antimicrobial agent requires knowledge 

  • site of the infection 

  • organism’s identity 

  • organism’s susceptibility to a particular agent 

  • patient factors 

  • the safety of the agent

empiric therapy:

• Therapy ideally initiated after specimen laboratory analysis

  • Antimicrobial agent selected after the organism has been identified

    • drug susceptibility determines definitive treatment plan

• Delay: fatal in critically ill pts - infection of unknown origin/waiting sensitivity results 

  • Immediate empiric therapy is indicated:

    • Drug choice in the absence of susceptibility data is influenced by the site of infection and the patient’s history 

    • Typically broad-spectrum agents for both gram-negative, gram-positive, and anaerobic bacteria

anti-infectives

• A large class of drugs that treat a broad range of infections 

  • Bacterial 

  • Viral 

  • Fungal 

  • Protozoa

• Treatment of infections: selective toxicity 

  • Injure/kill an invading microorganism without harming host 

  • Careful control of drug concentration to attack the microorganism with minimum harm to the host

vaccination: immunization schedule, function

• Immunization schedules: vary - age, geographic location, and specific risk factors 

• How they work: normal response in healthy immune system triggers production of organism-specific antibodies for later use when same viral antigen reappears 

  • Live attenuated: weakened

  • Inactivated:

  • Toxoids: toxin from pathogen

antimicrobial classes: antifungal, antiviral, antibiotic

• Antifungals: toxic-environmental changes first

• Antivirals: immune can overcome with minimal assistance - not that common

• Antibiotics: most common, immune system needs help

antiviral agent: purpose, moa, effectiveness

• purpose: works synergistically w health immune system —> eliminate/supress viral activity

• moa: destroy virions/inhibiting the ability of viruses to replicate

  • Enter cells infected with virus 

  • Interfere with viral nucleic acid synthesis & regulation

  • Interfere with ability of virus to bind to cells

  • Stimulate body’s immune system

• Most effective if administered within 48-72h of onset of s/s: keep the colony small 

  • Wait too long: hard to treat 

antifungal agents: use, moa, choice, side effects

• Treat infections caused by: fungi, yeast 

• moa:

  • Interfere w DNA synthesis 

  • Inhibit cell division/cellular metabolism 

• Choice of drug depends on type/ location of infection 

  • Topical (powder, liquid, ointment)

  • Ophthalmic (gtts)

  • Systemic (PO, IV)

• SE: highly toxic

antibiotic: use

• Antibiotics specifically treat infections caused by bacteria

  • Staph

  • Strep

  • E. coli

antibiotic: viral infections

• do not work against viral infections

  • viral: sore throat, cough, cold, flu, acute sinusitis

    • viral infection: self limiting

  • health immune system fight virus off alone

• Using antibiotics for viral infections:

  • Increase the risk of antibiotic resistance

  • Lower options for future treatments if an antibiotic is needed

  • Side effects/ extra cost due to unnecessary drug treatment

antibiotics: mechanism of action - bacteriostatic & bacteriocidal

• Bactericidal: kill bacteria 

• Bacteriostatic: keep bacteria from reproducing and growing 

  • Broad spectrum: gram +/-, aerobic, anaerobic 

• MOA: 

  • Interfere with cell wall synthesis 

  • Interfere with protein synthesis 

  • Interfere with DNA replication 

  • Act as metabolite to disrupt critical metabolic reactions inside the bacterial cell 

gram + and gram -

• Broad spectrum: treat both gram + and gram - infections

• Gram +: non-pathogenic - do not cause disease, part of the human microbiome (mouth,skin, intestine, respiratory tract)

• Gram -: 90-9% pathogenic - more resistant to antibiotics/develop resistance quickly

• Prevention: hand/food/water/personal hygiene 

antibiotic categories:

• Penicillins

• Sulfonamides

• Cephalosporins

• Carbapenems

• Macrolides

• Tetracyclines

• Aminoglycosides

• Quinolones

• Glycopeptides

penicillin: bactericidal, beta-lactam

• Bactericidal: kill a wide variety of gram-positive & some gram-negative bacteria 

• Also known as beta-lactam antibiotics: 

  • Some bacteria produce enzyme (beta-lactamase) capable of destroying PCN 

  • To improve effectiveness, typically paired with beta-lactamase inhibitors

penicillin: common formulations - PO, IV, IM

• Oral: amoxicillin/clavulanic acid (Augmentin) 

• Intravenous: concoction - penicillin + beta lactamase to destroy enzyme 

  • Ampicillin/sulbactam (Unasyn)

  • Piperacillin/tazobactam (Zosyn): common for empiric therapy

  • Nafcillin 

• IM: 

  • Procaine

  • Benzathine

sulfonamides: bacteriostatic, allergy

• Bacteriostatic: some gram-positive & many gram negative bacteria

  • resistance is widespread

• sulfa allergy: true allergy - cannot take any

sulfomides: indications, formulations - PO, inject

• Indications 

  • UTIs 

  • treatment or prevention of pneumocystis pneumonia 

  • ear infections (otitis media)

•  Oral or Injectable: 

  • sulfamethoxazole-trimethoprim (Bactrim, Bactrim DS, Septra)

  • sulfisoxazole (combined with erythromycin)

cephalosporins: bactericidal

• Bactericidal: five generations with increasing expanded coverage to include gram-positive, gram-negative, and/or anaerobic infections 

cephalosporins: indications, injectables

• Common indications 

  • Strep throat

  • Ear infections 

  • UTIs

  • Skin infections

  • Meningitis 

• Injectable: 

  • cefazolin (Ancef, Kefzol)

  • ceftriaxone (Rocephin): strep throat IM

  • cefepime (Maxipime)

carbapenems: bactericidal, side effect

•  Bactericidal: broadest spectrum antibacterial action

  • Side effect: risk of seizure activity

    • May require dose adjustment in renal impairment

      • AMS, seizures, nephrotoxicity

carbapenems: use, injectable

• Used for moderate to life-threatening bacterial infections: 

  • Connective tissue

  • Complex intrabdominal infections

  • Osteomyelitis

  • Meningitis 

  • Multidrug-resistant hospital-acquired infections 

• Injectable only

  • meropenem (Merrem): level up, multi drug resistant organisms

  • ertapenem (Ivnanz)

  • imipenem/cilastatin (Primaxin)

macrolides: bacteriostatic, side effect

• Bacteriostatic: 

  • Contraindicated due to risk for cardiac dysrhythmia (prolonged QT interval)

    • EKG

macrolides: indications, PO

• Common indications

  • Community-acquired pneumonia

  • Pertussis (whooping cough) 

  • Uncomplicated skin infections 

  • Listeria 

  • Chlamydia

  • Legionella 

• Oral: 

  • clarithromycin (Biaxin)

  • Erythromycin

  • azithromycin (Zithromax) – also available for IV admin

tetracyclines: bacteriostatic

• Bacteriostatic: broad-spectrum against spirochetes and a variety of gram negative and gram-positive bacteria 

  • Side effect: photosensitivity - UV light

tetracycline: use, PO/inject

• Used to treat: 

  • Acne

  • Chlamydia

  • Syphilis

  • RMSF

  • Lyme disease

  • MRSA 

• Formulations: 

  • Oral: doxycycline (Vibramycin)

  • Injection: tigecycline (Glycylcycline)

aminoglycosides: bactericidal, side effects

• Bactericidal: highly potent Big Guns for virulent infections 

• Side effects:

  • Nephrotoxic

  • Ototoxic: administer too fast → tinnitus, permanent damage 

    • Administer IV: low and slow 

  • Require monitoring of serum levels for dosing adjustment

aminoglycosides: use, IV

• Typically used for systemic infection (septicemia)

  • Also prophylaxis in high risk GI or GU procedures 

• Intravenous only

  • Gentamicin

  • Tobramycin

  • streptomycin

quinolones: bactericidal, side effects

• Bactericidal: broad-spectrum of activity 

  • prolonged QT-interval = lethal cardiac dysrhythmias

  • hypoglycemia

  • spontaneous tendon rupture

  • Myasthenia gravis

quinolones: use, PO/inject

• Used for difficult-to-treat infections: 

  • UTIs when other options are aren’t effective

  • Bacterial prostatitis

  • Anthrax

  • Plague 

• Oral or Injection: 

  • ciprofloxacin (Cipro): UTI 

  • levofloxacin (Levaquin)

  • moxifloxacin (Avelox)

glycopeptides: bacteriostatic, side effects

• Bactericidal: highly potent “Big Guns” for virulent infections 

• Side effects:

  • Nephrotoxic

  • Ototoxic 

  • Red Man Syndrome: full body rash - not true allergy, adverse reaction → may still get it, pretreat with antihistamines 

    • Associated with vancomycin

  • Require monitoring of serum levels for dosing adjustment

glycopeptides: use, PO/inject

• Commonly used for treating: 

  • MRSA

  • Complicated skin infections

  • C. difficile-associated diarrhea

  • Endocarditis resistant to beta-lactams and other antibiotics 

• Oral or Injectable 

  • vancomycin (Vancocin)

    • Zosyn + vancomycin: empiric treatment 

  • daptomycin

therapeutic monitoring: peak & trough lvl

• Therapeutic monitoring: dose adjusted based on calculations using lab values 

  • EX: Serum Creatinine (renal function)

• Serum drug level drawn at specific times based on typical half-life: help nurse admin right dose at the right time

  • Trough: time of lowest expected drug level 

  • Peak: time of highest expected drug level

    • Timing very important: trough before next dose 

potential response to treatment: therapeutic, subtherapeutic, superinfection

• Therapeutic response: decrease in specific s/s of infection

  • fever, elevated white blood cell count, redness, inflammation, drainage, pain

• Subtherapeutic response: s/s of infection do not improve 

• Superinfection: 

  • Pseudomembranous colitis: Clostridium difficile

  • Secondary infection (thrush, vaginitis)

  • Resistance

antibiotic common side effects: GI, UV, fever, teeth

• GI: nausea, vomiting, diarrhea 

• Photosensitivity: sensitivity to light and/or being more prone to sunburn while on tx 

• Fever worsens

• Tooth discoloration: most prevalent in children whose teeth are still developing - tetracycline

antibiotic adverse reaction: allergic reaction

• Allergic reaction

  • Hives: can easily lead to an airway issue - stop infusion, supervise them, airway, notify provider 

  • Trouble breathing

  • Swelling of the face or tongue

antibiotic adverse reaction: Stevens johnson syndrome (SJS)

• Disorder of skin/ mucous membranes

  • Common: weakened immune system or family hx of SJS

    • Starts with flu-like symptoms (sore throat, fever)

    • painful rash that spreads/blisters

    • skin pain

    • cough: pain in mouth and throat

• Associated with vancomycin allergies

prescription considerations

• Age

• Pregnancy & lactation

• Immune system

• Renal dysfunction

• Hepatic dysfunction

• Poor perfusion

• Multidrug-resistant organism

MDRO: multidrug-resistant organisms

• Need broader coverage 

• Common risk factors:

  • prior antimicrobial therapy in the preceding 3 mos 

  • hospitalization for greater than 2 days within the preceding 3 mos 

  • current hospitalization exceeding 5d 

  • high frequency of resistance in the community or local hospital unit (assessed using hospital antibiograms) 

  • immunosuppressive diseases and/or therapies

candida auris: risk, protection

• Fungus: global healht threat

  • multi-drug resistant

  • difficult to identify without specific tech

  • causes outbreaks

• Risk of C. auris infection to healthy people/ healthcare personnel is very low

  • US: C. auris infection spreads mostly in long term healthcare facilities among patients with severe medical problems

  • Healthy people not at risk for C. auris infections

    • can be colonized on their skin

• Protection:

  • Hand hygiene: friction + water to-remove spores

  • Environmental surfaces: disinfected

antibiotic resistance: steps

• lots of germs, few drug resistant

• antibiotics kill bacteria causing illness & good bacteria that protect body from infection

• drug-resistant bacteria grow and take over

• bacteria share drug resistance

strategies for reducing antimicrobial use

• Vaccinations: prevent infection

• Practice/educate others in infection prevention:

  • hand hygiene, avoid touching eyes, cough ettiquetetiquette

• educate pts: antibiotics needed/not

  • risks: allergies, C diff, antibiotic resistance

  • discourage saving of left-over antibiotics

• avoid antibiotics viral infections

• avoid treating positive cultures in the absence of s/s

  • treat infection not contamination/colonization

nursing considerations: infection control

• Infection control measures

  • Prevention: removal of unnecessary indwelling devices

  • Hand hygiene & environmental disinfection

  • Utilize PPE correctly

  • Patient isolation when deemed necessary

• Identify infection source & organism

  • Cultures properly collected

  • Follow-up & communicate culture results

  • Antibiotics are not always indicated

• Advocate for appropriate treatment

  • Limit use of broad spectrum antimicrobials

  • Treatment is in line with microbiology results

  • Engage physicians & pharmacists regarding oral therapy options

• Monitor for S/S side effects & adverse reactions

  • Educate pt: side effects & treat PRN

  • Recognize s/s of anaphylaxis /adverse reaction

  • Assess for S/S consistent with C. difficile