For an otherwise healthy adult with uncomplicated community‑acquired pneumonia, should I prescribe doxycycline or moxifloxacin?

Doxycycline vs Moxifloxacin for Uncomplicated Community-Acquired Pneumonia

For an otherwise healthy adult with uncomplicated community-acquired pneumonia, prescribe doxycycline 100 mg twice daily for 5–7 days as first-line therapy; reserve moxifloxacin for patients with comorbidities or when doxycycline cannot be used. 1, 2

Evidence-Based Treatment Algorithm

First-Line: Doxycycline for Healthy Adults Without Comorbidities

• Doxycycline 100 mg orally twice daily is the recommended alternative to amoxicillin for previously healthy outpatients, with an initial loading dose of 200 mg on day 1 to achieve therapeutic levels more rapidly. 1, 2

• The 2019 IDSA/ATS guidelines provide a conditional recommendation with low-quality evidence for doxycycline monotherapy in this population, acknowledging limited RCT data but recognizing its broad spectrum against typical and atypical pathogens. 1, 2

• A 2023 meta-analysis of 6 RCTs (834 patients) demonstrated comparable clinical cure rates between doxycycline and comparators (macrolides/fluoroquinolones), with subgroup analysis of high-quality studies showing significantly higher cure rates with doxycycline (87.1% vs 77.8%, OR 1.92). 3

• Doxycycline provides coverage against Streptococcus pneumoniae (90–95% of strains), Haemophilus influenzae, and all atypical organisms (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella species). 2

When to Use Moxifloxacin Instead

• Reserve moxifloxacin 400 mg once daily for patients with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; immunosuppression) who require broader coverage. 1

• Moxifloxacin is a respiratory fluoroquinolone with strong recommendation and moderate-quality evidence for patients with comorbidities, achieving >98% activity against S. pneumoniae including penicillin-resistant isolates. 1

• A Phase III trial of moxifloxacin 400 mg once daily for 10 days in 196 CAP patients demonstrated 93% overall clinical resolution and 91% bacteriological response, with particular efficacy against atypical pathogens (89% for C. pneumoniae, 93% for M. pneumoniae). 4

• Fluoroquinolones should be avoided as first-line therapy in healthy adults due to FDA warnings about serious adverse effects including tendinopathy, peripheral neuropathy, and CNS effects, and to preserve this class for patients who truly need it. 1

Treatment Duration and Monitoring

• Treat for a minimum of 5 days and continue until afebrile for 48–72 hours with no more than one sign of clinical instability; typical duration is 5–7 days for uncomplicated CAP. 1, 2

• Assess clinical response at 48–72 hours: fever should resolve within 2–3 days of appropriate therapy. 1

• Extend therapy to 14–21 days only if Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli are identified. 1

Critical Pitfalls to Avoid

• Do not use doxycycline if the patient received it within the past 90 days—select an agent from a different antibiotic class to reduce resistance risk. 1, 2

• Do not use doxycycline monotherapy for hospitalized patients—combination therapy with a β-lactam plus doxycycline is required to ensure adequate pneumococcal coverage. 2

• Do not use macrolide monotherapy in regions where pneumococcal macrolide resistance exceeds 25%, as breakthrough bacteremia occurs more frequently with resistant strains. 1

• Counsel patients about photosensitivity with doxycycline, a common side effect that may limit use in certain geographic areas. 2, 5

• Do not use fluoroquinolones routinely in healthy adults—a 2024 comparative safety study of 145,137 CAP patients showed broad-spectrum antibiotics (including fluoroquinolones) were associated with increased risk of adverse drug events compared to narrow-spectrum regimens like macrolides or doxycycline. 6

Cost and Length-of-Stay Considerations

• A 2010 double-blind trial comparing doxycycline to levofloxacin in hospitalized CAP patients demonstrated equivalent efficacy with shorter length of stay (4.0 vs 5.7 days, P<0.0012) and significantly lower antibiotic costs ($64.98 vs $122.07, P<0.0001). 7

• Retrospective studies suggest combination β-lactam/macrolide therapy or fluoroquinolone monotherapy may improve outcomes in hospitalized patients, but well-designed prospective randomized trials confirming superiority are lacking. 8

When to Escalate or Hospitalize

• Admit patients with CURB-65 score ≥2, respiratory rate ≥30 breaths/min, oxygen saturation <90% on room air, systolic blood pressure <90 mmHg, altered mental status, multilobar infiltrates, or inability to maintain oral intake. 1

• For hospitalized non-ICU patients, use ceftriaxone 1–2 g IV daily plus doxycycline 100 mg IV/PO twice daily as an alternative to β-lactam plus macrolide. 2

• For ICU patients with severe CAP, do not use doxycycline—use a potent β-lactam plus either azithromycin or a respiratory fluoroquinolone. 2