What first‑line antibiotic should I prescribe for an otherwise healthy adult with uncomplicated urinary‑tract infection (UTI), community‑acquired pneumonia (CAP), non‑purulent cellulitis, or acute bacterial sinusitis, considering age, renal and hepatic function, allergy profile, and local resistance patterns?

First-Line Antibiotic Selection for Common Outpatient Infections in Healthy Adults

Uncomplicated Urinary Tract Infection (UTI)

For uncomplicated UTI in otherwise healthy adults, prescribe nitrofurantoin, trimethoprim-sulfamethoxazole (if local resistance <20%), or fosfomycin as first-line agents; reserve fluoroquinolones for complicated infections or when first-line agents cannot be used. 1

Recommended First-Line Agents:

• Nitrofurantoin 100 mg twice daily for 5 days (preferred for uncomplicated cystitis) 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (only if local resistance <20% and no recent use within 3 months) 1, 2
• Fosfomycin 3 g single dose (alternative option) 1

Critical Pitfalls to Avoid:

• Do not use fluoroquinolones (ciprofloxacin, levofloxacin) as first-line therapy for uncomplicated UTI due to serious adverse effects (tendinopathy, QT prolongation, CNS toxicity) that outweigh benefits when safer alternatives exist 1, 3
• Avoid ampicillin or amoxicillin alone due to worldwide resistance rates exceeding 30% 1
• Do not use oral cephalosporins as they have 15-30% higher failure rates compared to preferred agents 1

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Community-Acquired Pneumonia (CAP)

For outpatient CAP in healthy adults without comorbidities or recent antibiotic use, prescribe amoxicillin 1 g three times daily as first-line monotherapy; add a macrolide (azithromycin or clarithromycin) for hospitalized patients or when atypical pathogens are suspected. 4, 5

Outpatient Management (No Comorbidities):

• Amoxicillin 1 g three times daily for 5-7 days 4
• Alternative for penicillin allergy: Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for 4 days OR clarithromycin 500 mg twice daily for 5-7 days) 4
• Doxycycline 100 mg twice daily for 5-7 days is an acceptable alternative 4

Hospitalized Non-ICU Patients:

• Combination therapy: Amoxicillin (or ceftriaxone 1-2 g IV daily) PLUS azithromycin 500 mg daily 4, 5
• This combination provides coverage for both typical bacteria (S. pneumoniae) and atypical pathogens (Mycoplasma, Legionella) 4, 5

Critical Considerations:

• Respiratory fluoroquinolones (levofloxacin 750 mg daily for 5 days or moxifloxacin) are alternatives but should be reserved for penicillin-allergic patients or treatment failure 4
• Minimum treatment duration is 5 days with clinical stability (afebrile ≥48 hours, hemodynamically stable) 4, 6
• Do not use moxifloxacin for UTI but it is acceptable for CAP 1

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Non-Purulent Cellulitis

For non-purulent cellulitis in healthy adults, prescribe cephalexin 500 mg four times daily or dicloxacillin 500 mg four times daily for 5-7 days to cover Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus.

First-Line Agents:

• Cephalexin 500 mg four times daily for 5-7 days (preferred oral agent)
• Dicloxacillin 500 mg four times daily for 5-7 days (alternative)
• Penicillin allergy: Clindamycin 300-450 mg three times daily for 5-7 days

When to Suspect MRSA:

• Purulent drainage, abscess formation, or failure of β-lactam therapy suggests MRSA
• In these cases, switch to trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily OR doxycycline 100 mg twice daily

Critical Pitfalls:

• Non-purulent cellulitis does NOT require MRSA coverage in otherwise healthy adults without risk factors
• Avoid broad-spectrum agents (fluoroquinolones, amoxicillin-clavulanate) for simple cellulitis

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Acute Bacterial Sinusitis

For acute bacterial sinusitis in healthy adults without recent antibiotic use, prescribe amoxicillin-clavulanate 500/125 mg three times daily (or 875/125 mg twice daily) for 5-7 days as first-line therapy. 4

First-Line Therapy (Mild Disease, No Recent Antibiotics):

• Amoxicillin-clavulanate 500/125 mg three times daily OR 875/125 mg twice daily for 5-7 days 4
• Alternative: Amoxicillin 1.5-3 g/day (divided doses) if β-lactamase-producing H. influenzae is uncommon locally 4

Penicillin Allergy:

• Doxycycline 100 mg twice daily for 5-7 days 4
• Respiratory fluoroquinolone (levofloxacin 750 mg daily for 5 days or moxifloxacin 400 mg daily for 5-7 days) 4

High-Risk Patients (Recent Antibiotics, Moderate Disease):

• High-dose amoxicillin-clavulanate 2000/125 mg twice daily (Augmentin XR formulation) 4, 7
• Respiratory fluoroquinolone (levofloxacin, moxifloxacin) 4
• Ceftriaxone 1-2 g IM/IV once daily (for initial dose if severe) 4

Critical Decision Points:

• Recent antibiotic use within 4-6 weeks is a major risk factor for resistant organisms requiring broader coverage 4
• Failure to improve after 72 hours warrants switch to alternative agent or re-evaluation 4
• Macrolides (azithromycin, clarithromycin) have limited effectiveness (73% calculated efficacy) and should only be used for immediate Type I penicillin allergy 4

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Key Adjustments for Special Populations

Renal Impairment:

• CrCl 30-50 mL/min: Reduce fluoroquinolone doses (levofloxacin 750 mg loading, then 250 mg every 48h) 1
• CrCl <30 mL/min: Avoid nitrofurantoin; reduce TMP-SMX to once daily dosing 1
• Ceftriaxone requires no renal adjustment (biliary excretion) 1

Hepatic Impairment:

• Most first-line agents (amoxicillin, cephalosporins, fluoroquinolones) require no dose adjustment for mild-moderate hepatic dysfunction
• Avoid high-dose amoxicillin-clavulanate in severe hepatic impairment due to clavulanate hepatotoxicity risk 7

Allergy Considerations:

• True Type I penicillin allergy (anaphylaxis): Use fluoroquinolones, macrolides, or doxycycline 4
• Non-severe penicillin reactions: Cephalosporins (cefuroxime, cefpodoxime) are generally safe with <2% cross-reactivity 4
• Sulfa allergy: Avoid TMP-SMX; use nitrofurantoin or fluoroquinolones for UTI 1

Local Resistance Patterns:

• Fluoroquinolone resistance >10%: Give initial IV ceftriaxone 1 g before oral fluoroquinolone for UTI/pyelonephritis 1, 8
• TMP-SMX resistance >20%: Avoid empiric use for UTI 1, 2
• High penicillin-resistant S. pneumoniae prevalence: Use high-dose amoxicillin (4 g/day) or amoxicillin-clavulanate (2000/125 mg twice daily) for sinusitis and CAP 4