Anti-Infectives Chapter 17 Comprehensive Notes

Overview of Anti-Infectives

  • Chapter focus: agents that treat infectious organisms (bacteria, viruses, fungi, protozoa)

  • FIRST clinical step ⇒ identify the causative organism & select a drug to which the organism is sensitive

  • Limited true antivirals exist; far larger catalogue for bacteria & fungi

Culture & Sensitivity (C&S) Testing

  • Ordered when precise pathogen/drug match is desired (e.g., persistent UTI)

  • Specimen examples: mid-stream clean-catch urine, throat swab, wound exudate

  • Procedure recap

    • Specimen streaked on agar ("red Jell-O" appearance)

    • Discs impregnated with candidate drugs (labelled A, M, X, etc.) placed on plate

    • Incubate 24\;\text{h} at 98.6\,^{\circ}\text{F} \;(37\,^{\circ}\text{C})

    • After growth (white hazy colonies) inspect inhibition zones:

    • Clear halo → organism sensitive (drug killed/stunted growth)

    • Over-growth on disc → resistant (drug ineffective)

    • Partial/blurred zones → "intermediate/questionable" efficacy

    • Report returns in 24{-}48\;\text{h}

Empiric Therapy

  • “Best-guess” drug chosen before C&S report based on:

    • Patient’s past infection history

    • Local resistance patterns

    • Site-specific common flora

  • Example: recurrent UTI pt usually clears with Drug C ➜ physician starts Drug C while waiting on C&S confirmation

Drug Resistance

  • Causes: sub-therapeutic dosing, premature discontinuation, over-prescribing, agricultural use

  • Clinically significant resistant organisms

    • MRSA (\text{Methicillin-Resistant Staphylococcus aureus}) – often only susceptible to vancomycin

    • Influenza A strains resistant to oseltamivir (Tamiflu)

    • Candida species resistant to fluconazole (Diflucan)

Factors in Drug Selection

  1. Infection site & penetration ability

  2. Hepatic/renal function – may mandate dose reduction

  3. Age – children & elderly accrue toxicity faster

  4. Pregnancy/Lactation – avoid teratogens (e.g., tetracycline, streptomycin)

  5. Resistance likelihood in community

  6. Documented allergies (penicillin, sulfa, etc.)

Adverse-Reaction Categories

  1. Allergic / Hypersensitivity

    • Rash, hives, mild fever

    • Severe form = anaphylaxis (laryngeal edema, hypotension)

  2. Direct Toxicity

    • Organ-specific: \text{oto} (ear), \text{nephro} (kidney), \text{hepato} (liver)

  3. Indirect Toxicity / Superinfection

    • Secondary infection after normal flora destroyed (diarrhea, vaginitis, stomatitis, glossitis)

    • Prevention/Tx: probiotic yogurt, buttermilk, OTC lactobacillus (“acidophilus”)

Vaccines & Immunizations

  • Always consult CDC schedules (\text{http://www.cdc.gov/vaccines}) (most current authority)

  • Influenza vaccine for ALL >6 months every year between Aug → Nov

  • MA role: educate on prophylaxis & debunk myths (no proven causal link between MMR & autism per IOM/ISRC)

Antibiotics – Foundational Principles

  • Effective only vs bacteria; do NOT treat viral/fungal illness

  • Over-use for viral colds historically drove resistance (e.g., routine amoxicillin for sniffles)

  • Duration compliance critical: finish entire course; never “save leftovers” or share

Specific Antibiotic Classes

Aminoglycosides

  • Agents: Gentamicin

  • Spectrum: serious gram-negative infections (E. coli septicemia), often in combination with other antibiotics

  • ROA: IM or IV (poor GI absorption)

  • Therapeutic drug monitoring (peak/trough serum levels) mandatory

  • Mnemonic “NHB” → major toxicities

    • N → Nephrotoxicity (monitor I&O, BUN/Cr)

    • H → Hearing loss (ototoxicity; avoid if baseline impairment)

    • B → Blurred vision (neuro-/vestibular)

  • Precautions: apply to those with history of hearing loss.

Cephalosporins

  • Beta-lactam class “cousin” to penicillins (cross-reactivity risk)

  • Generations ↑ = broader gram-negative coverage

  • Common agents to recall:

    • 1st Gen: cephalexin (Keflex)

    • 2nd Gen: cefaclor (Ceclor), cefuroxime (Ceftin)

    • 3rd Gen: ceftriaxone (Rocephin), cefpodoxime, Suprax

  • Adverse effects: Hypersensitivity, including rash, edema, or anaphylaxis (especially in those allergic to penicillin)

  • Assess for rash/hives in penicillin‐allergic pts

Macrolides

  • Agents: erythromycin (Ery-Tab), azithromycin (Zithromax, Z-Pak, TRI-PAK), clarithromycin

  • Uses: respiratory tract, skin, STIs; substitute when PCN allergy present

  • Azithromycin regimens: 5-day (2 tab Day 1, then 1/day ×4) or 3-day (500mg for three days)

  • Clarithromycin part of triple therapy vs H.\;pylori ulcers (e.g., in combination with amoxicillin and lansoprazole - Prevpac Kit)

  • Low global toxicity ("least toxic" class)

Penicillins

  • Agents: amoxicillin (Amoxil), amoxicillin-clavulanate (Augmentin), benzathine PCN G

  • Standard Uses: strep, staph, meningococcal, syphilis (benzathine PCN G)

  • Amoxicillin:

    • Prophylaxis for infective endocarditis prior to dental work

    • First-line for pediatric otitis media

    • Also used in combination with other drugs to treat H.\;pylori infection associated with duodenal ulcer disease

  • Amoxicillin + clavulanate = Augmentin (β-lactamase resistant, “extended spectrum”)

  • Vigilance: anaphylaxis, cross-reactivity with cephalosporins

  • Note: Potentiation of penicillin with probenecid exists.

Quinolones (Fluoroquinolones)

  • Key drugs: ciprofloxacin (Cipro), levofloxacin (Levaquin)

  • Broad utility: UTI, sinusitis, LRTI, GI, bones, joints, gonorrhea

  • Growing resistance → reserved for confirmed need

  • Adverse effects:

    • GI upset (nausea, pseudomembranous colitis)

    • \text{Tendon/cartilage damage} (boxed warning) esp. elderly, athletes, children

  • Avoid with theophylline (↑ toxicity)

  • Assess vascular pts (arteriosclerosis) carefully

  • Precautions: Older adults, especially with GI disease or arteriosclerosis; Children or adolescents (potential for cartilage damage).

Tetracyclines

  • Agents: doxycycline (Vibramycin)

  • Uses: some uncommon bacteria, Rocky Mountain spotted fever, atypical pneumonia, some STIs, and some severe cases of inflammatory acne.

  • Adverse effects:

    • Photosensitivity, with exaggerated sunburn

    • Discolored teeth in fetus or young children

  • Precautions/Contraindications: avoid in pregnancy/lactation due to teratogenic effects.

Antifungals

  1. Amphotericin B

    • ROA: IV for life-threatening systemic mycoses

    • Requires hospital & close monitoring (nephro-, hepato-, electrolyte issues)

  2. Fluconazole (Diflucan)

    • ROA: Oral/IV

    • Uses: 1-dose regimen for vaginal candidiasis; 3–7 day repeat prevents recurrence; also thrush, esophageal, disseminated candida

  3. Micafungin (Mycamine)

    • ROA: IV

    • Uses: prophylaxis during stem-cell transplant; esophageal candida

  4. Nystatin (Mycostatin)

    • ROA: Topical/oral suspension

    • Uses: diaper rash, oral thrush, vaginal yeast, topical treatment of skin fungus

  • Patient teaching: continue full course—even when symptoms clear—because fungi relapse easily.

Antituberculosis (Anti-TB) Agents

  • TB organism: Mycobacterium tuberculosis (lung-predominant)

  • Drug use goals:

    1. Treat latent/asymptomatic infection (positive PPD or exposure)

    2. Treat active disease & prevent relapse

  • Standard multi-drug regimens: isoniazid (INH), rifampin, ethambutol, pyrazinamide.

    • For asymptomatic TB, INH alone for 6–12 months. Alternatively, rifampin with pyrazinamide.

  • Side effects:

    • Nausea

    • Body fluids colored red-orange with rifampin

  • Note: Drug regimens are lengthy (6-24 months) and noncompliance is a common issue.

  • Other agents sometimes used: Streptomycin (administered by deep IM injection, alternating sites), Quinolones (ciprofloxacin, levofloxacin), Tetracyclines (doxycycline).

Antivirals

Neuraminidase Inhibitors

  • Agents: Oseltamivir (Tamiflu) PO, Zanamivir (Relenza) inhaled

  • Active vs influenza A & B

  • Must start ≤48\;\text{h} of symptom onset; ↓ illness ≈ 1 day (If >48 h since onset most pts receive only supportive care)

Other Antivirals

  • Ribavirin:

    • ROA: Aerosolized (nasal delivery systems/special administration tents/hoods)

    • Uses: treats RSV in infants/children, also hantavirus (rodent borne)

    • Caution: teratogenic—pregnant staff avoid exposure

  • Acyclovir (Zovirax): used for herpes zoster (shingles), herpes simplex (cold sores, genital herpes)

  • Valacyclovir (Valtrex): prodrug of acyclovir, also for herpes infections.

  • Zostavax: herpes zoster vaccine approved for prevention of shingles.

Antiretroviral Agents (ARVs) for HIV

  • Protease Inhibitors (PIs):

    • Action: block the activity of the HIV enzyme needed for viral replication

    • Adverse effects: Fat redistribution, hyperlipidemia, new-onset diabetes mellitus

  • Integrase Inhibitors: Raltegravir (Isentress)

    • Action: first ARV designed to slow the advancement of HIV infection by blocking the enzyme needed for viral replication

Miscellaneous Anti-Infectives

Metronidazole

  • Agent: Metronidazole (Flagyl)

  • Uses: Used to treat trichomonas vaginalis, also part of H.\;pylori treatment.

Vancomycin

  • Agent: Vancomycin

  • Uses: Drug of choice for MRSA

Agents for Vancomycin-Resistant Enterococci (VRE)

  • Agents: linezolid (Zyvox), clindamycin (Cleocin), metronidazole (Flagyl)

Sulfonamides

  • Agents: sulfamethoxazole–trimethoprim (Bactrim, Bactrim DS)

  • Among the oldest anti-infectives.

  • Uses: commonly used for treatment of UTIs and other infections.

Urinary Anti-Infectives

  • Agents: nitrofurantoin (Macrobid, Macrodantin)

  • Uses: most commonly used for initial or recurrent empiric treatment of uncomplicated lower UTI

  • Notes: Avoiding antacids is advised.

Patient & Family Education Highlights

  • Finish all antibiotic/antifungal doses even after feeling better

  • Recognize s/sx of allergic reaction; seek emergency help for wheeze, swelling, rash

  • Probiotics or fermented foods during/after antibiotics to restore flora

  • Avoid sharing “leftover” meds; ideally none should remain

  • Report tinnitus, reduced urine output, severe diarrhea, tendon pain during therapy

  • For Tamiflu: emphasize 48 h window; after that expect only symptomatic management

  • Vaccination counseling: separate myths from evidence, emphasize schedules

Ethical / Practical Connections

  • Over-prescribing fuels community resistance—providers & MAs bear stewardship responsibility

  • Waiting 72 h before pediatric antibiotic Rx (fever watch) balances benefit vs resistance risk

  • Public health: MRSA & drug-resistant candida highlight need for infection-control protocols

Mnemonics & Study Tricks

  • Aminoglycoside → “NHB” (Nephro, Hearing, Blurred sight)

  • PCN dental prophylaxis → "Amox before box" (Amoxicillin before the dentist’s box of tools)

  • Flu Tx 48 → “Fly before 2 days” (neuraminidase inhibitor must start within 48 h)

  • Macrolide use → "Macro lungs & love" (respiratory + STIs)

Real-World Anecdotes / Examples

  • Instructor’s ankle cartilage injury after Cipro while doing gym step class → illustrates quinolone tendon risk even in adults

  • Pediatric practice: physicians now delay antibiotics for simple viral URIs; parents instructed to monitor fever first 72 h

  • Home remedies gaining traction (honey-lemon tea, turmeric-cinnamon) but cannot replace antibiotics for proven bacterial disease — patient counseling required

Common Anti-Infective Agents: Generic and Brand Names with Key Effects

  1. Aminoglycosides

    • Gentamicin

      • Side Effects: Nephrotoxicity, Ototoxicity (hearing loss), Blurred vision.

      • Uses: Serious gram-negative infections (e.g., E. coli septicemia).

  2. Cephalosporins

    • cephalexin (Keflex)

    • cefaclor (Ceclor)

    • cefuroxime (Ceftin)

    • ceftriaxone (Rocephin)

    • cefpodoxime, Suprax

      • Side Effects: Hypersensitivity (rash, edema, anaphylaxis), especially with penicillin allergy.

      • Uses: Broad-spectrum, increasing gram-negative coverage with higher generations.

  3. Macrolides

    • erythromycin (Ery-Tab)

    • azithromycin (Zithromax, Z-Pak, TRI-PAK)

    • clarithromycin

      • Side Effects: Generally low global toxicity; Clarithromycin may cause GI upset as part of H.\;pylori triple therapy.

      • Uses: Respiratory tract infections, skin infections, STIs; substitute for penicillin allergy; H.\;pylori ulcers (clarithromycin).

  4. Penicillins

    • amoxicillin (Amoxil)

    • amoxicillin-clavulanate (Augmentin)

    • benzathine PCN G

      • Side Effects: Anaphylaxis, hypersensitivity reactions, cross-reactivity with cephalosporins.

      • Uses: Strep, staph, meningococcal, syphilis; endocarditis prophylaxis (amoxicillin); pediatric otitis media (amoxicillin).

  5. Quinolones (Fluoroquinolones)

    • ciprofloxacin (Cipro)

    • levofloxacin (Levaquin)

      • Side Effects: GI upset (nausea, pseudomembranous colitis), Tendon/cartilage damage (boxed warning, esp. elderly/children/athletes).

      • Interactions: Increased toxicity with theophylline.

      • Uses: UTIs, sinusitis, lower respiratory tract infections, GI, bones, joints, gonorrhea.

  6. Tetracyclines

    • doxycycline (Vibramycin)

      • Side Effects: Photosensitivity (exaggerated sunburn), discolored teeth (fetus/young children).

      • Uses: Rocky Mountain spotted fever, atypical pneumonia, certain STIs, inflammatory acne.

  7. Antifungals

    • Amphotericin B

      • Side Effects: Significant nephrotoxicity, hepatotoxicity, electrolyte disturbances; requires close monitoring.

      • Uses: Life-threatening systemic mycoses (IV).

    • Fluconazole (Diflucan)

      • Side Effects: Generally well-tolerated, may cause headache or GI upset.

      • Uses: Vaginal, oral (thrush), esophageal, and disseminated candidiasis.

    • Micafungin (Mycamine)

      • Side Effects: Generally well-tolerated, may require liver function monitoring.

      • Uses: Prophylaxis during stem-cell transplant, esophageal candida.

    • Nystatin (Mycostatin)

      • Side Effects: Generally minimal for topical/oral suspension (may cause GI upset with oral forms).

      • Uses: Diaper rash, oral thrush, vaginal yeast infections.

  8. Antituberculosis (Anti-TB) Agents

    • isoniazid (INH)

    • rifampin

    • ethambutol

    • pyrazinamide

      • Side Effects: Nausea; Rifampin causes orange/red discoloration of body fluids; INH can cause peripheral neuropathy.

      • Uses: Latent or active tuberculosis infection.

  9. Antivirals

    • Neuraminidase Inhibitors

      • oseltamivir (Tamiflu)

      • zanamivir (Relenza)

        • Side Effects: Nausea, vomiting (Tamiflu); bronchospasm (Relenza).

        • Uses: Influenza A & B (effective if started within 48\;\text{h} of symptom onset).

    • Ribavirin

      • Side Effects: Teratogenic (significant risk of birth defects), hemolytic anemia.

      • Uses: RSV in infants/children (aerosolized), Hantavirus.

    • acyclovir (Zovirax)

    • valacyclovir (Valtrex)

      • Side Effects: Nausea, vomiting, diarrhea, headache.

      • Uses: Herpes simplex (cold sores, genital herpes), herpes zoster (shingles).

  10. Antiretroviral Agents (ARVs) for HIV

    • Protease Inhibitors (PIs) (e.g., ritonavir, lopinavir/ritonavir)

      • Side Effects: Fat redistribution, hyperlipidemia, new-onset diabetes mellitus.

      • Uses: Block HIV enzyme activity to slow viral replication.

    • raltegravir (Isentress)

      • Side Effects: Headache, nausea, fatigue.

      • Uses: Integrase inhibitor, blocks enzyme for viral replication in HIV.

  11. Miscellaneous Anti-Infectives

    • metronidazole (Flagyl)

      • Side Effects: Nausea, metallic taste, disulfiram-like reaction with alcohol.

      • Uses: Trichomonas vaginalis, H.\;pylori (part of combination therapy), bacterial vaginosis, C. difficile.

    • vancomycin

      • Side Effects: Ototoxicity, nephrotoxicity, Red Man Syndrome (with rapid IV infusion).

      • Uses: Drug of choice for MRSA and other serious gram-positive infections, C. difficile colitis (oral).

    • linezolid (Zyvox)

      • Side Effects: Myelosuppression (thrombocytopenia), peripheral neuropathy.

      • Uses: Vancomycin-Resistant Enterococci (VRE), MRSA.

    • clindamycin (Cleocin)

      • Side Effects: Pseudomembranous colitis (\text{C. difficile} overgrowth - boxed warning).

      • Uses: Various bacterial infections, including some VRE strains.

    • Sulfamethoxazole–trimethoprim (Bactrim, Bactrim DS)

      • Side Effects: Nausea, vomiting, rash, Stevens-Johnson syndrome, photos