antimicrobial therapy

Penicillin

• MOA: Activate bacterial autolysins to digest peptidoglycan cell wall & inhibits transpeptidase (cross-links peptidoglycan molecules to form a rigid cell wall)

• Bactericidal against gram + organisms

• Beta lactam ring

• Penicillin G- given IM or IV, narrow spectrum, active against mostly  gram+ organisms, used for pneumonia and meningitis 

  • Least toxic of all antibx

  • Penicillin ALLERGY (cross-sensitivity to other beta lactam)

• Resistance: via beta-lactamase (cleaves beta lactam ring → inactivates drug)

Cephalosporins

• Bactericidal

• Beta lactam ring

• 1st gen→ 5th gen

  • 5th generation: covers wider range of bacteria (gram + and -), increased beta lactamase resistance (can function against antibx resistant bacteria)

• Adverse Effects:

  • Abdominal pain, nausea, vomiting, diarrhea– take with food 

  • Superinfections such as C diff

  • Allergic reactions- anaphylaxis or maculopapular rash (Cross allergy with penicillin)

  • Nephrotoxicity– monitor renal function

  • If given IM or IV, risk for thrombophlebitis and abscess formation

  • Alcohol intolerance

Carbapenems

• Beta lactam structure

• Resistant to beta lactamases (resistant to resistance)

• Very broad spectrum

• Administered IV or IM (never PO)

• Indicated in tx of serious CNS infections

• Adverse effects:

  • GI, Hypersensitivity, Superinfection, seizures (renal dysfunction)

• Excreted by kidneys – monitor renal function

Vancomycin

• No beta lactam ring

• Used for serious infections only with gram + bacteria such as C diff and MRSA

• Toxicity→ renal failure

• Ototoxic

• Vancomycin Infusion Syndrome– SLOW infusion and dilute solution

• Thrombophlebitis

• Immune-mediated thrombocytopenia

• Must be given IV unless for C diff

• Avoid extravasation – may cause necrosis 

Gentamicin

• Aminoglycosides

• IM/IV

• Adverse effects:

  • Nephrotoxic- monitor renal function & encourage fluids

  • Ototoxic

  • Vestibular effects (balance, headache)

  • Neuromuscular blockade (flaccid paralysis, respiratory depression)

  • GI

• Monitor for drug levels!! Peaks and Troughs

  • Elevated trough is associated with toxicity 

  • Check peak 30 mins after given and check trough prior to med administration

Doxycycline

• Tetracycline

• Adverse effects:

  • GI irritation

  • Effect on bone and teeth (do not give if pregnant, breastfeeding, children <8)

  • Superinfection

  • Hepatotoxicity

  • Nephrotoxic

  • Photosensitivity– wear sunscreen

• Take on empty stomach (1 hr before or 2 hours after meal) with full glass of water

• Do not take with vitamins or milk because of risk for chelation

• Can decrease effectiveness of oral contraceptives 

Macrolides

• Prototype: Azithromycin

• Broad spectrum 

• Common replacement for people with penicillin allergy

• Adverse effects:

  • GI

  • QT prolongation

  • Superinfection

  • Hepatotoxicity 

  • Hearing loss 

• Take orally 1 hr before or 2-3 hr after meals with full glass of water

• Monitor liver function

• Excreted in bile (not kidneys)

Trimethoprim sulfamethoxazole (Bactrim):

• Blocks folic acid synthesis (bacterial metabolite)

• Cross hypersensitivity with other sulfur-based drugs

• Adverse effects:

  • Kernicterus

  • Blood dyscrasias (hemolytic anemia)

  • Hepatotoxicity

  • Hyperkalemia

  • Hypoglycemia

  • Hyponatremia

Fluoroquinolones

• Blocks bacterial nucleic acid synthesis 

• Adverse effects:

  • Black Box–Tendon rupture (ex: Achilles)

  • Phototoxicity- sunscreen

• Absorption reduced by cations (antacids, dairy products)

• Increases levels of warfarin

Antifungals

Fluconazole:

• Broad spectrum

• Fungal and yeast infections

• Oral, IV, topical

• Inhibits synthesis of ergosterol → causes increased membrane permeability and leakage of cellular components 

• Adverse effects:

  • GI

  • Headache

  • Cardiac suppression (transient decrease in EF)

  • Liver injury

CYP450 inhibitor

Antivirals:Acyclovir:

• Only active against herpesvirus family

• First choice for HSV or VZV infection

• Inhibits viral replication

• Side effects:

  • N/A

  • GI, headache, vertigo

Antivirals:Oseltamivir (Tamiflu)

Treatment of Influenza A and B

• Start within 2 days of symptom onset

• Approved for influenza prophylaxis within 48 hours of exposure

• Do not use if patient <1 

• Inhibits enzyme responsible for viral replication

• *Vaccination remains primary strategy for prevention of flu