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Cellulitis

Definition

• Andrews' Diseases of the Skin, Ch. 14 - Rosen's Emergency Medicine, Ch. 126

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Clinical Features

• Erythema - diffuse, rapidly spreading, typically with poorly defined and irregular borders
• Warmth, swelling (edema), and tenderness at the affected site
• Systemic features - fever, chills, malaise (not always present)
• Lymphangitis - linear streaks of inflammation extending proximally along vascular tracts, especially with Streptococcal or Pasteurella infections (e.g., animal bites)
• Vesicles or bullae - can form when localized edema becomes severe, causing epidermal layer separation

• Gangrene
• Metastatic abscesses
• Severe sepsis
• Necrotizing fasciitis (a distinct, life-threatening entity requiring urgent surgical debridement)

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Causative Organisms

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Risk Factors

• Disruption of the skin barrier (wounds, tinea pedis, insect bites, ulcers)
• Venous insufficiency / lymphedema / peripheral edema
• Obesity
• Diabetes mellitus
• Immunodeficiency / immunosuppression
• Prior history of cellulitis (recurrence is common)
• Saphenous phlebectomy, lymphadenectomy, or prior irradiation

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Diagnosis

• Blood cultures: Not indicated in uncomplicated cases; reserved for immunocompromised patients or those with systemic sepsis
• Wound cultures: Only if an open wound is present; needle aspiration or biopsy are not recommended for typical nonpurulent cellulitis
• Imaging:
  • Ultrasound: Useful to differentiate cellulitis from abscess; can also identify foreign bodies
  • Plain X-ray / CT: Used when necrotizing infection is suspected (may reveal soft tissue gas along fascial planes) or to evaluate for osteomyelitis in diabetic foot

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Differential Diagnosis ("Pseudocellulitis")

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Management

Outpatient (mild, no systemic toxicity)

• Nonpurulent cellulitis: Dicloxacillin or cephalexin 500 mg every 6 hours for 5 days (covers streptococci and MSSA)
• If MRSA suspected (risk factors: prior MRSA infection, IV drug use, incarceration, competitive sports, recurrent furunculosis): trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline

Inpatient (systemic toxicity, immunocompromised, failure of oral therapy)

• IV penicillin or cephalosporins (e.g., cefazolin) for streptococcal infections
• IV vancomycin or linezolid if MRSA is a concern

Adjunctive measures

• Limb elevation
• Compression therapy for lymphedema (reduces recurrence)
• Marking the borders of erythema with a pen to monitor progression

Recurrent cellulitis

• Prophylactic penicillin (long-term low-dose) is used in patients with recurrent episodes due to lymphedema
• A 2026 systematic review (PMID 41275489) examines the evidence for secondary prevention strategies
• Treat any portal of entry (e.g., antifungal for tinea pedis)

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Key Takeaways

1. Cellulitis = diffuse, poorly-bordered skin infection; erysipelas = well-demarcated, raised borders
2. Most cases are streptococcal (nonpurulent); purulent cellulitis suggests S. aureus / CA-MRSA
3. The clinical mimicry rate is high (~30%) - always consider stasis dermatitis, DVT, and contact dermatitis
4. Bilateral "cellulitis" is almost never cellulitis
5. Necrotizing fasciitis is a surgical emergency; pain out of proportion to findings is a red flag
6. A recent network meta-analysis (PMID 39240378) confirms the efficacy of first-line antibiotics (cephalosporins, penicillins) for cellulitis and erysipelas

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Cellulitis with Hand Swelling in Type 2 Diabetes

Why Diabetes Makes This Dangerous

1. Immune dysfunction - Neutrophil and monocyte-macrophage function are directly impaired by hyperglycemia. Cellular immunity shows reduced proliferative response. These defects are worsened by poor glucose control and improve with tighter glycemic management.
2. Vascular insufficiency - Microangiopathy and atherosclerosis reduce tissue perfusion, impairing antibiotic delivery and healing.
3. Sensory neuropathy - Leads to wound neglect; patients may present late with advanced infection. They may have malaise without fever, or purulent discharge without pain - atypical presentations that delay diagnosis.

• Rosen's Emergency Medicine, Ch. 33 - diabetic immunocompromise

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Clinical Presentation

• Diffuse erythema with poorly defined borders
• Dorsal hand swelling (key anatomical point below)
• Warmth and tenderness
• Possible lymphangitis - red streaks tracking proximally up the forearm

Why the Dorsum Swells

"The veins and lymphatics course through the softer tissues on the dorsum of the hand. Therefore, the dorsum of the hand often swells whenever there is an inflammatory or infectious process. For this reason, a deep space infection initially may be misdiagnosed as cellulitis over the dorsum of the hand."

• Tintinalli's Emergency Medicine, Ch. 283

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Red Flag Features (Urgent / Admit)

"If deep structures of the hand are involved, emergently consult a hand specialist because treatment likely will involve inpatient care and operative drainage."

• Tintinalli's Emergency Medicine, Ch. 283

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Microbiology in Diabetic Patients

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Severity Classification (IDSA / IWGDF)

• Fischer's Mastery of Surgery, Table 246.1 / Sabiston Textbook of Surgery, Table 35.5

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Management

1. Glycemic Control

2. Antibiotic Therapy

• Nonpurulent: Cephalexin 500 mg every 6 hours OR TMP-SMX 160/800 mg twice daily
• If MRSA suspected: TMP-SMX 1-2 DS tabs q12h, doxycycline 100 mg q12h, or clindamycin 300-450 mg q8h
• Duration: 5-7 days (can extend if infection persists)

• Vancomycin IV (recommended given high CA-MRSA prevalence in most communities - up to 47-78% of hand infections)
• Add coverage for enteric gram-negatives (e.g., piperacillin-tazobactam) for immunocompromised patients or those with open trauma
• Broaden empirically for suspected polymicrobial infection in severe/chronic wounds

"Antibiotic therapy is needed for... comorbid diseases (diabetes mellitus); immunosuppression, location on face, hand, or genitalia." - Washington Manual of Medical Therapeutics

3. Immobilization and Elevation

• Apply a bulky hand dressing with splint in position of function: wrist 15-30° extension, MCP joints 50-90° flexion, IP joints 5-15° flexion
• Elevate above the level of the heart - on pillows or suspended in stockinette
• This reduces inflammation, prevents secondary injury, and limits fascial spread

4. Wound Care

• If purulent: incision and drainage (I&D) - superficial abscesses (≤5 cm) in ED; deep space infections require OR
• Avoid superficial wound swabs (unreliable, reflect colonization) - obtain deep tissue cultures at debridement
• Debride all necrotic tissue

5. Imaging

• Plain X-ray: first line - detects foreign bodies, bony involvement, soft tissue gas
• Ultrasound (point-of-care): differentiates cellulitis from abscess; assists foreign body localization
• CT: for suspected deep space infection, necrotizing fasciitis (tissue gas along fascial planes)
• MRI: most sensitive for osteomyelitis if bone involvement is suspected

6. Surgical Consultation

• Any deep space infection
• Flexor tenosynovitis
• Collar-button abscess
• Necrotizing fasciitis
• Failure to improve within 24-48 hours of parenteral antibiotics

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Key Takeaways

1. Dorsal swelling ≠ dorsal infection - the infection source is often volar; always examine the palmar surface carefully.
2. CA-MRSA dominates hand infections (up to 78% in ED studies) - empiric vancomycin IV is appropriate for moderate-severe infection.
3. Diabetics present atypically - absent fever or pain does not rule out serious infection; signs of hyperglycemia or metabolic instability indicate severity.
4. Hand infections in diabetics need early hand surgery involvement - delays cost fingers.
5. Tight glucose control is both treatment and prevention - hyperglycemia is the root cause of immune failure.
6. Superficial wound swabs are unreliable - always culture deep tissue at debridement.
7. The threshold for admission and parenteral antibiotics is lower in diabetic patients than in the general population.

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Propylthiouracil (PTU) 50 mg Tablet

Drug Overview

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Mechanism of Action

1. Inhibits thyroid peroxidase (TPO) - blocks oxidation and organification of iodide, preventing thyroid hormone (T3 and T4) synthesis. It also blocks coupling of iodotyrosines.
2. Inhibits peripheral deiodination of T4 → T3 (type 1 deiodinase inhibition) - this is unique to PTU (methimazole does NOT have this effect), making PTU especially useful in thyroid storm where rapid T3 lowering is needed.

Note: PTU does not block iodide uptake into the gland.

• Katzung's Basic and Clinical Pharmacology, 16e - Goldman-Cecil Medicine

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Pharmacokinetics

• Katzung's Basic and Clinical Pharmacology, 16e

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Indications (When PTU is Preferred Over Methimazole)

"Due to the hepatotoxicity of propylthiouracil, the FDA has limited indications for its use to the first trimester of pregnancy, the treatment of thyroid storm, and patients with minor adverse reactions to methimazole."

• Harrison's Principles of Internal Medicine, 22e

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Dosing

Hyperthyroidism (Graves' disease) - Titration Regimen

• Lower doses may suffice in areas of low dietary iodine intake.
• Thyroid function (free T4) is reviewed at 4-6 weeks; dose is titrated down as levels normalize.
• TSH remains suppressed for weeks after euthyroidism - do not use TSH alone to monitor early response.

Block-Replace Regimen (alternative)

• Full suppressive dose of PTU maintained + levothyroxine (LT4) supplementation added to avoid drug-induced hypothyroidism.

Thyroid Storm

• 500-1,000 mg loading dose, then 200-400 mg every 4-6 hours (much higher doses than routine hyperthyroidism)

Equivalence

• 400 mg PTU ≈ 30 mg methimazole (roughly 13:1 ratio)

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Adverse Effects

Common (3-12% of patients)

• Nausea, GI distress - most common early effects
• Maculopapular pruritic rash (4-6%) - most common cutaneous effect; may respond to antihistamine or switching to methimazole
• Urticaria, fever, arthralgia (1-5%)

Serious / Rare

"An increased risk of severe hepatitis, sometimes fatal, is reported with propylthiouracil (black box warning), so it should be avoided in children and adults unless no other options are available."

• Katzung's Basic and Clinical Pharmacology, 16e

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Special Populations

Pregnancy

• First trimester: PTU is preferred (methimazole carries teratogenic risk)
• Second/third trimester: Switch to methimazole (PTU hepatotoxicity risk outweighs teratogenic benefit at this stage)
• Both thionamides cross the placenta (FDA Pregnancy Category D); both can cause fetal hypothyroidism - use the lowest effective dose
• Both are considered safe during breastfeeding (low concentrations in breast milk)

Children

• PTU should be avoided due to high hepatotoxicity risk; methimazole is preferred

Elderly / Cardiac patients

• Lower threshold to use antithyroid drugs before radioiodine
• Adjunct propranolol (20-40 mg every 6 hours) or atenolol to control adrenergic symptoms (palpitations, tremor, heat intolerance) while waiting for PTU to take effect

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Drug Interactions

• Warfarin: Thyrotoxicosis increases warfarin metabolism; as PTU corrects hyperthyroidism, warfarin dose may need reduction (increased bleeding risk)
• Digoxin: Higher doses needed in thyrotoxic state; reduce as euthyroidism is restored
• Radioiodine (¹³¹I): PTU has a prolonged radioprotective effect - must be stopped for a longer period before radioiodine than methimazole, or a larger radioiodine dose will be needed

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Monitoring

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Remission and Long-Term Outcomes (Graves' Disease)

• Maximum remission rates: 30-60% after 12-18 months of treatment
• Higher remission rates when TRAb levels become undetectable
• Relapse is more likely in: younger patients, males, smokers, large goiters, severe hyperthyroidism at presentation, persistent TRAb
• If relapsed after antithyroid drugs: proceed to radioiodine (¹³¹I) or thyroidectomy
• Alternative: Continue low-dose antithyroid drug for up to 10 years

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Key Summary

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Potassium 5.2 mEq/L - What Does It Mean and What To Do?

Interpretation

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First - Rule Out Pseudohyperkalemia

• Hemolysis in the blood tube (most common) - blood left too long, tight tourniquet, difficult venepuncture
• Thrombocytosis (platelet count >1,000,000)
• Leukocytosis (WBC >100,000)
• Prolonged fist clenching during blood draw

If the sample was haemolysed or there are no clinical symptoms, repeat the test with a fresh sample before taking any action.

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What To Do at 5.2 mEq/L (Mild Hyperkalemia)

"Mild hyperkalemia (potassium level 5 to 5.5 mEq/L) generally requires no treatment other than education to avoid foods with large concentrations of potassium."

• Goldman-Cecil Medicine

Step 1 - Get an ECG

Step 2 - Find and Treat the Cause

• Tintinalli's Emergency Medicine, Table 17-17

Step 3 - Dietary Potassium Restriction

• Rice, white bread, pasta
• Apples, grapes, berries
• Cabbage, cauliflower, cucumber
• White chicken, egg white

Step 4 - Review and Adjust Medications

• Stop or reduce potassium supplements (including multivitamins with potassium)
• Stop salt substitutes (most are potassium chloride)
• If on an ACE inhibitor / ARB: discuss with the prescribing doctor - may need dose reduction or monitoring (do not stop independently without medical advice as these drugs protect the kidneys and heart)
• If on potassium-sparing diuretics (spironolactone, amiloride): review dose
• If on NSAIDs (ibuprofen, diclofenac): stop if possible (impair renal K+ excretion)

Step 5 - Repeat the Potassium Level

• Recheck potassium in 1-2 weeks after dietary changes and medication review
• Monitor more closely if there is CKD, diabetes, or ongoing use of ACE inhibitor/ARB

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When to Escalate (Medical Emergency)

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Summary - What to Do at K+ 5.2 mEq/L

1. Repeat the test to confirm (rule out haemolysis)
2. Get an ECG - to confirm no cardiac changes
3. Dietary education - avoid high-potassium foods
4. Review medications - stop K+ supplements, salt substitutes, unnecessary NSAIDs
5. Check for underlying cause - CKD? Diabetes? ACE inhibitor/ARB?
6. Recheck potassium in 1-2 weeks
7. No urgent drug treatment needed at this level unless ECG changes are present

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Heavy Infection & Severe Cellulitis - Antibiotic Guide

Severity Classification - Choose Your Tier First

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TIER 1 - MILD (Outpatient, Oral)

Nonpurulent Cellulitis (Strep-dominant)

Purulent Cellulitis / Abscess (MRSA-dominant)

Plus incision and drainage (I&D) for any abscess - this alone may be sufficient for small abscesses (<5 cm) without systemic signs.

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TIER 2 - MODERATE (Hospital Admission, IV Antibiotics)

Nonpurulent Cellulitis (IV)

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TIER 3 - SEVERE (ICU-Level, Broad-Spectrum IV)

Nonpurulent Severe Cellulitis / Sepsis from Cellulitis

• Ciprofloxacin 400 mg IV every 12 hours + Metronidazole 500 mg IV every 8 hours (+ vancomycin for MRSA)
• Ciprofloxacin + Clindamycin (anaerobic coverage)

Purulent Severe Cellulitis / Sepsis

• Fitzpatrick's Dermatology, Table 151-5 - Tintinalli's Emergency Medicine, Table 192-4 - Goldman-Cecil Medicine

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TIER 4 - NECROTIZING FASCIITIS (Surgical Emergency + IV)

• Vancomycin + Ciprofloxacin 400 mg IV q12h + Clindamycin 600 mg IV q8h

• Vancomycin + Meropenem 1 g IV q8h + Clindamycin

Mandatory surgical debridement - all necrotic tissue must be excised. Antibiotics alone cannot treat necrotizing fasciitis.

• Goldman-Cecil Medicine, Table 94-2 - Rosen's Emergency Medicine, Table 127.3

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Special Situations - Targeted Coverage

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Stepwise Management of Severe Cellulitis

1. ASSESS severity → SIRS criteria, ECG, blood cultures, CBC, CMP, CRP/ESR
2. RULE OUT necrotizing fasciitis → X-ray (gas?), CT, surgical review
3. START IV antibiotics IMMEDIATELY → Vancomycin + Pip-Tazo
4. MARK THE BORDERS → outline erythema with pen, photograph it
5. ELEVATE + IMMOBILIZE the limb
6. CULTURE → blood cultures x2, wound swab/deep tissue if purulent
7. DRAIN any abscess (I&D or surgical)
8. GLYCEMIC CONTROL → critical in diabetics
9. REASSESS at 24-48 hours → not improving? Broaden, check for abscess, rule out NF
10. NARROW antibiotics once culture sensitivities available

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Duration of Antibiotic Therapy

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Quick Reference Summary

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Cellulitis Leg - Imaging Guide

Key Principle

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1. ULTRASOUND (First-Line Imaging)

Classic Ultrasound Finding: "Cobblestoning"

What Ultrasound Shows

Ultrasound Key Uses

• Cellulitis vs. Abscess - the most common reason to scan; abscess appears as a walled-off fluid collection vs. the diffuse cobblestoning of cellulitis
• Locating foreign bodies - more sensitive than plain X-ray for radiolucent objects
• Guiding drainage - real-time abscess aspiration/I&D
• Point-of-care (POCUS) - can be done immediately at the bedside in the ED
• Rosen's Emergency Medicine, Ch. 126

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2. CT SCAN (Computed Tomography)

CT Findings in Cellulitis

When to Use CT

• Suspected necrotizing fasciitis (gas in tissue, crepitus, skin necrosis, severe systemic toxicity)
• Post-surgical wound infections (extension into deeper structures)
• Suspected deep abscess or undrained collection not seen on ultrasound
• Osteomyelitis (though MRI is more sensitive)
• Diabetic leg infections with concern for deep spread

"Plain radiographs or computed tomography (CT) may reveal soft tissue gas or inflammation along fascial planes, but cannot rule out necrotizing infection."

• Rosen's Emergency Medicine

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3. CT WITH IV CONTRAST - Necrotizing Fasciitis vs. Cellulitis

CT Differentiation: Cellulitis vs. Necrotizing Fasciitis

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4. MRI (Magnetic Resonance Imaging)

MRI Findings

When to Use MRI

• Suspected osteomyelitis (most sensitive modality - detects before plain films show changes)
• Deep infection extent assessment
• Uncertain diagnosis after ultrasound/CT
• Spinal / pelvic extension concern

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5. PLAIN X-RAY

Note: Plain X-ray cannot rule out NF or osteomyelitis (both may be normal in early stages).

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Imaging Pathway Summary

CLINICAL CELLULITIS - leg swelling, redness, warmth
         |
         ├── Typical, no systemic signs, no fluctuance
         │         → NO imaging needed (clinical diagnosis)
         │         → Treat empirically
         │
         ├── Fluctuance / Possible abscess?
         │         → ULTRASOUND (bedside POCUS)
         │         → Cobblestoning = cellulitis
         │         → Fluid collection = abscess → I&D
         │
         ├── Crepitus / Gas / Rapidly spreading / Bullae / Sepsis?
         │         → URGENT CT with IV contrast
         │         → Look for gas, fascial tracking
         │         → If positive → EMERGENCY SURGERY
         │
         ├── Post-surgical / Deep extension suspected?
         │         → CT with IV contrast
         │
         ├── Diabetic / Chronic ulcer / Exposed bone?
         │         → Plain X-ray FIRST
         │         → MRI if osteomyelitis suspected
         │
         └── Diagnostic uncertainty / NF staging?
                   → MRI (most sensitive for extent + osteomyelitis)

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Quick Scan Reference

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Cellulitis - Ointments and Topical Treatments

Important Principle First

• Small superficial entry-point wounds (impetigo-like lesions, minor abrasions)
• Wound care after drainage/debridement
• Preventing portal-of-entry infections (e.g., tinea pedis, minor cuts)
• Decolonizing MRSA carriers to prevent recurrence

"Topical antibiotics are typically reserved for superficial cutaneous infections such as impetigo."

• Dermatology 5e (Dermatology 2-Volume Set)

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Topical Antibiotic Ointments - Full Reference Table

• Dermatology 5e, Table 127.3

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Drug-by-Drug Guide

1. Mupirocin (Bactroban) 2% - THE KEY TOPICAL

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2. Fusidic Acid (Fucidin) 2% - Common in Asia, Europe, India

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3. Retapamulin (Altabax) 1% Ointment

• Novel pleuromutilin antibiotic - inhibits 50S ribosomal subunit
• Active against MSSA and Strep pyogenes (not MRSA)
• Used for impetigo; limited use for mild infected wounds
• Apply BID for 5 days

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4. Bacitracin Ointment - Over-the-Counter

• Inhibits gram-positive cell wall synthesis
• Useful for preventing infection in small wounds, cuts, abrasions
• Applied after minor procedures (e.g., biopsy, suturing) to keep wound moist and prevent superficial infection
• Not effective against gram-negatives or MRSA
• Allergic contact dermatitis is common with bacitracin - one of the most common contact allergens in North America

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5. Neosporin / Polysporin - Over-the-Counter Combinations

• Polysporin = Bacitracin + Polymyxin B (gram-positive + gram-negative cover)
• Neosporin = Bacitracin + Polymyxin B + Neomycin (broadest OTC cover)
• Useful for minor wound care but neomycin is a major allergen - avoid in sensitive patients
• Not suitable for treating established cellulitis

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6. Silver Sulfadiazine (SSD) 1% Cream

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Antimicrobial Wound Dressings (for Cellulitis + Open Wounds)

Silver dressings release antibacterial Ag+ ions for 3-7 days, require less frequent changes, and are active against MRSA and VRE with very low resistance risk.

• Dermatology 5e

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When to Use Each - Practical Guide

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Key Summary