Treatment of Moderate‑Risk Community‑Acquired Pneumonia in Adults
For moderate‑risk community‑acquired pneumonia in adults (defined as age ≥ 65 or presence of comorbidities such as COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use), the combination of azithromycin plus cefixime is NOT appropriate; instead, use either amoxicillin‑clavulanate 875/125 mg orally twice daily PLUS azithromycin (500 mg day 1, then 250 mg daily for 5–7 days) OR a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) as monotherapy. 1
Why Azithromycin + Cefixime Is Inadequate
Cefixime is not listed as a recommended oral β‑lactam in the 2019 IDSA/ATS guidelines for community‑acquired pneumonia; the preferred oral β‑lactams are amoxicillin‑clavulanate, cefpodoxime, or cefuroxime, all of which have superior pneumococcal coverage compared with cefixime. 1
Oral cephalosporins (including cefixime) demonstrate inferior in‑vitro activity against Streptococcus pneumoniae compared with high‑dose amoxicillin or amoxicillin‑clavulanate, making them suboptimal for empiric therapy in moderate‑risk patients. 1
Cefixime lacks adequate coverage for penicillin‑resistant S. pneumoniae strains (MIC > 2 mg/L), which are common in patients with comorbidities or recent antibiotic exposure. 1
Recommended Outpatient Regimens for Moderate‑Risk CAP
Option 1: Combination β‑Lactam + Macrolide (Preferred)
Amoxicillin‑clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg on day 1, then 250 mg daily for days 2–5 achieves approximately 91.5 % favorable clinical outcomes by covering typical bacteria (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical pathogens (Mycoplasma, Chlamydophila, Legionella). 1, 2
High‑dose amoxicillin‑clavulanate targets ≥ 93 % of S. pneumoniae isolates, including drug‑resistant strains, making it superior to oral cephalosporins. 1
Alternative β‑lactams (cefpodoxime or cefuroxime) can be substituted for amoxicillin‑clavulanate, but they must be combined with azithromycin or doxycycline to ensure atypical coverage. 1
Doxycycline 100 mg orally twice daily can replace azithromycin when macrolides are contraindicated (e.g., QT prolongation, drug interactions). 1, 3
Option 2: Respiratory Fluoroquinolone Monotherapy (Alternative)
Levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily for 5–7 days is active against > 98 % of S. pneumoniae isolates, including penicillin‑resistant strains, and provides comprehensive coverage of atypical organisms. 1
Fluoroquinolones should be reserved for patients with β‑lactam allergy or when combination therapy is contraindicated, due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1
Treatment Duration and Transition Criteria
Minimum duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability (temperature ≤ 37.8 °C, heart rate ≤ 100 bpm, respiratory rate ≤ 24 breaths/min, systolic BP ≥ 90 mmHg, oxygen saturation ≥ 90 % on room air, ability to maintain oral intake, normal mental status). 1
Typical total course for uncomplicated CAP: 5–7 days. 1
Extended courses (14–21 days) are required only for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram‑negative enteric bacilli. 1
When to Hospitalize Instead of Outpatient Management
Hospitalization is mandatory when any of the following are present: respiratory rate > 24 breaths/min, oxygen saturation < 92 % on room air, systolic blood pressure < 90 mmHg, inability to maintain oral intake, altered mental status, multilobar infiltrates, or unstable comorbid conditions. 1
Use validated severity scores (Pneumonia Severity Index or CURB‑65) together with clinical judgment to determine the need for inpatient care; PSI class IV–V or CURB‑65 ≥ 2 mandates admission. 1
Monitoring and Follow‑Up
Clinical review at 48 hours (or sooner if symptoms worsen) to assess response, oral intake, and adherence. 1
Indicators of treatment failure that warrant hospital referral include: no clinical improvement by day 2–3, development of respiratory distress (respiratory rate > 30 /min, oxygen saturation < 92 %), inability to tolerate oral antibiotics, or new complications such as pleural effusion. 1
If amoxicillin‑clavulanate + azithromycin fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1
Routine follow‑up at 6 weeks for all patients; obtain a chest radiograph only if symptoms persist, physical signs remain abnormal, or the patient has high risk for underlying malignancy (e.g., smokers > 50 years). 1
Critical Pitfalls to Avoid
Never use macrolide monotherapy in patients with comorbidities or age ≥ 65, as it fails to cover typical pathogens such as S. pneumoniae and is associated with breakthrough bacteremia in infections caused by resistant strains. 1
Avoid oral cephalosporins (cefixime, cefuroxime, cefpodoxime) as first‑line agents for moderate‑risk CAP because of their inferior pneumococcal coverage compared with high‑dose amoxicillin‑clavulanate. 1
Do not use fluoroquinolones indiscriminately in uncomplicated outpatient CAP; reserve them for patients with β‑lactam allergy or documented treatment failure. 1
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1
Prevention and Vaccination
Offer pneumococcal polysaccharide vaccination to all adults ≥ 65 years and to those with high‑risk conditions (e.g., COPD, diabetes, chronic heart/liver/renal disease, malignancy, asplenia, immunosuppression). 1
Recommend annual influenza vaccination for all patients, especially those with chronic medical illnesses. 1
Provide smoking‑cessation counseling to every current smoker. 1