Is cefalexin effective for Community-Acquired Pneumonia (CAP)?

Cefalexin is NOT recommended for community-acquired pneumonia

Cefalexin should not be used as first-line therapy for CAP because it lacks adequate coverage against the primary bacterial pathogens, particularly Streptococcus pneumoniae, and has no activity against atypical organisms.

Why Cefalexin is Inadequate for CAP

Insufficient Spectrum of Activity

• Cefalexin is a first-generation cephalosporin with the narrowest antimicrobial spectrum and lowest potency among oral cephalosporins when tested against respiratory pathogens 1
• It demonstrates significantly inferior activity compared to amoxicillin, second-generation cephalosporins (cefuroxime), and third-generation cephalosporins (cefpodoxime, cefdinir) against S. pneumoniae, the most prominent invasive bacterial pathogen in CAP 1
• Cefalexin has no activity against atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella) that are common causes of CAP, particularly in school-aged children and adolescents 2

Guideline-Based Recommendations Exclude Cefalexin

For Pediatric CAP (Outpatient):

• Amoxicillin is the strongly recommended first-line therapy for previously healthy, appropriately immunized children with mild to moderate CAP (90 mg/kg/day in 2 doses) 2
• Alternative oral β-lactams listed in guidelines include second- or third-generation cephalosporins (cefpodoxime, cefuroxime, cefprozil)—notably, cefalexin is absent from these recommendations 2
• Macrolides should be added for school-aged children and adolescents when atypical pathogens are suspected 2

For Adult CAP (Outpatient):

• Guidelines recommend β-lactams such as ampicillin-sulbactam, ceftriaxone, or cefotaxime—not cefalexin 2
• Cefuroxime is specifically mentioned as an acceptable oral β-lactam option for outpatients with risk factors, but it must be combined with a macrolide or doxycycline 3
• Cefalexin is conspicuously absent from all major CAP treatment algorithms 2, 3

For Hospitalized Patients:

• Ampicillin or penicillin G are preferred for fully immunized children when local resistance patterns permit 2
• Third-generation cephalosporins (ceftriaxone, cefotaxime) are recommended for incompletely immunized children, areas with high penicillin resistance, or life-threatening infections 2
• For adults, β-lactam plus macrolide or respiratory fluoroquinolone monotherapy are standard 2

What to Use Instead

Outpatient CAP Treatment Algorithm

For children:

• First-line: Amoxicillin 90 mg/kg/day (strong recommendation) 2
• If atypical pathogens suspected: Add macrolide (azithromycin or clarithromycin) 2
• If β-lactam allergy: Macrolide monotherapy or levofloxacin (age-appropriate dosing) 2
• Alternative β-lactams: Cefpodoxime, cefuroxime, or cefprozil (NOT cefalexin) 2

For adults:

• Without comorbidities: Macrolide monotherapy (azithromycin, clarithromycin) or doxycycline 3
• With comorbidities or risk factors: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily) OR β-lactam (amoxicillin-clavulanate, cefuroxime) plus macrolide/doxycycline 2, 3

Inpatient CAP Treatment Algorithm

For children:

• Fully immunized, low resistance area: Ampicillin 150-200 mg/kg/day IV or penicillin G 2
• Incompletely immunized or high resistance: Ceftriaxone 50-100 mg/kg/day IV or cefotaxime 150 mg/kg/day IV 2
• Add macrolide if atypical pathogens (M. pneumoniae, C. pneumoniae) are considerations 2

For adults:

• Non-ICU: β-lactam (ampicillin-sulbactam, ceftriaxone, cefotaxime) plus macrolide OR respiratory fluoroquinolone monotherapy 2
• ICU: β-lactam plus macrolide OR β-lactam plus fluoroquinolone 2

Critical Pitfalls to Avoid

• Do not use cefalexin even though it is a cephalosporin—its first-generation status means inadequate pneumococcal coverage and zero atypical pathogen activity 1
• Avoid recent β-lactam exposure: If the patient received β-lactams within 3 months, switch to a respiratory fluoroquinolone to prevent resistance 3
• Do not use cefuroxime alone: It requires combination with a macrolide or doxycycline because it lacks atypical pathogen coverage 3, 4
• Recognize that older studies showing cefalexin "success" (such as the 1983 trial) 5 predate current resistance patterns and guideline development—these findings are not applicable to modern CAP management

Historical Context

While a 1983 study showed clinical cure in all 34 patients treated with cefalexin or cefadroxil for mild-to-moderate CAP 5, this research predates:

• The pneumococcal conjugate vaccine era
• Current pneumococcal resistance patterns
• Recognition of atypical pathogens as major CAP causes
• Modern guideline development emphasizing broader spectrum agents

Modern evidence demonstrates that cefalexin is among the least potent oral cephalosporins with the narrowest spectrum 1, explaining its exclusion from all contemporary CAP guidelines 2, 3.