What is Bordetella pertussis susceptible to?

Bordetella pertussis Antimicrobial Susceptibility

Bordetella pertussis is susceptible to macrolide antibiotics (azithromycin, clarithromycin, erythromycin) as first-line agents, with trimethoprim-sulfamethoxazole (TMP-SMZ) as an alternative for patients who cannot tolerate macrolides. 1

First-Line Antimicrobial Agents

Macrolide Antibiotics

Azithromycin is the preferred first-line agent due to superior tolerability, convenient dosing, and significantly lower risk of infantile hypertrophic pyloric stenosis (IHPS) compared to erythromycin, particularly in infants <1 month of age. 2

• Azithromycin dosing: Adults receive 500 mg on day 1, then 250 mg daily on days 2-5; children ≥6 months receive 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) on days 2-5. 1, 2

• Clarithromycin is equally effective as erythromycin and azithromycin for eradicating B. pertussis from the nasopharynx, but should not be administered to infants <1 month due to unknown association with IHPS. 1

• Erythromycin (40-50 mg/kg/day in children, 1-2 g/day in adults for 14 days) was historically the treatment of choice but has fallen out of favor due to gastrointestinal adverse effects, poor adherence with the 14-day regimen, and association with IHPS in infants <1 month. 1, 2

In Vitro Activity Confirmation

B. pertussis demonstrates in vitro susceptibility to all three macrolides (erythromycin, azithromycin, clarithromycin), with the organism exhibiting MIC values ≤4 mcg/mL for azithromycin. 3, 4

Alternative Antimicrobial Agent

Trimethoprim-sulfamethoxazole (TMP-SMZ) is effective in eradicating B. pertussis from the nasopharynx and serves as an alternative for patients aged >2 months who have contraindications to macrolides or are infected with macrolide-resistant strains. 1

• TMP-SMZ dosing: Children >2 months receive trimethoprim 8 mg/kg/day plus sulfamethoxazole 40 mg/kg/day in 2 divided doses for 14 days; adults receive trimethoprim 320 mg/day plus sulfamethoxazole 1,600 mg/day in 2 divided doses for 14 days. 1

• Contraindicated in infants <2 months, pregnant women, and nursing mothers due to kernicterus risk. 1

Macrolide Resistance Considerations

Macrolide-resistant B. pertussis is rare (<1%) but has been documented, primarily associated with the 23S rRNA A2047G mutation. 2, 5, 6

• When macrolide resistance is confirmed or suspected, TMP-SMZ becomes the treatment of choice for patients >2 months of age. 1

• Resistance patterns may correlate with specific genotypes, though clinical significance remains under investigation. 6

Agents with Inadequate Clinical Evidence

Despite in vitro activity, the following antimicrobials lack demonstrated clinical effectiveness for pertussis treatment and should not be used:

• Ampicillin and amoxicillin were ineffective in clearing B. pertussis from the nasopharynx despite in vitro activity, likely due to poor penetration into respiratory secretions. 1

• Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin), tetracyclines, chloramphenicol, and cephalosporins exhibit variable in vitro inhibitory activity but have no published data demonstrating clinical effectiveness. 1

• Other macrolides (roxithromycin) and ketolides (telithromycin) show in vitro activity but lack clinical effectiveness data. 1

Critical Treatment Timing

Early antibiotic administration during the catarrhal phase (first 2 weeks) rapidly clears B. pertussis from the nasopharynx, decreases coughing paroxysms, and reduces complications. 1, 2

• Treatment initiated after 3 weeks (paroxysmal phase) has limited clinical benefit for symptom modification but remains indicated to prevent transmission. 1, 2

• Approximately 80-90% of untreated patients spontaneously clear B. pertussis within 3-4 weeks from cough onset. 2

Important Clinical Caveats

• Isolation for 5 days after starting antibiotics is essential to prevent transmission, as B. pertussis is highly contagious with attack rates of 80-90% among susceptible household contacts. 1, 2

• Postexposure prophylaxis uses the same antimicrobial regimens and dosing as treatment, prioritizing close contacts, infants <12 months, and pregnant women in the third trimester. 2

• Drug interactions: Clarithromycin and erythromycin (but not azithromycin) inhibit cytochrome P450 (CYP3A), requiring caution with concomitant medications metabolized by this pathway. 1, 2