What are the resistance rates of Streptococcus pneumoniae?

Streptococcus pneumoniae Resistance Rates

Resistance rates for Streptococcus pneumoniae vary significantly by geographic location, antibiotic class, and patient population, but in the United States, approximately 40% of strains show penicillin nonsusceptibility, 28-29% demonstrate macrolide resistance, and resistance to trimethoprim-sulfamethoxazole approaches 35%. 1, 2

Geographic Variation in Resistance

United States:

• Penicillin nonsusceptibility: Nearly 40% of strains causing disease in adults, with 12% penicillin-intermediate and 25% penicillin-resistant 1, 2
• Macrolide resistance: Averages 28-29% nationally, but ranges from 23% in the northwest to 30% in the northeast 1, 2
• Trimethoprim-sulfamethoxazole resistance: Approximately 35% of isolates 2, 3
• Tetracycline resistance: Approximately 20-22% of isolates 2, 3
• Fluoroquinolone resistance: Remains low but increasing, with resistance affecting >98% susceptibility rates 4, 5

Europe:

• Rates vary substantially by country, with higher resistance in France and Israel historically, though both showed decreasing trends 6
• Belgium, Lithuania, and Norway demonstrated significant decreases in penicillin-nonsusceptible S. pneumoniae (PNSP) 6
• Croatia, Hungary, Ireland, and Turkey showed significant increases in fully resistant isolates 6
• Netherlands and Germany maintain lower resistance rates due to strict antibiotic usage limitations 6

Eastern and Southern Mediterranean:

• Overall 26% of invasive isolates were non-susceptible to penicillin 6
• Algeria reported 44% and Lebanon 40% penicillin nonsusceptibility 6

Resistance Mechanisms and Clinical Significance

Penicillin Resistance:

• Results from genetic structural modifications in penicillin-binding proteins, not beta-lactamase production 3, 7
• Critical caveat: Intermediate resistance (MIC 0.1-1.0 mg/mL) is not clinically important for pneumonia treatment when standard doses are used, though it matters for meningitis 6
• High-grade resistance (MIC ≥4 mg/mL) may be clinically significant even for pneumonia 6

Macrolide Resistance:

• 71% is efflux-mediated (modest resistance, MIC 1-32 mg/L) 1, 6
• 27% involves target site modification (high-level resistance, MIC ≥64 mg/L) 1, 6
• High-level resistance associated with the MLS_B phenotype is dominant in Europe and South Africa and cannot be overcome with dose escalation 6

Multidrug Resistance:

• Increasingly common, particularly with serotype 19A strains 6
• Penicillin-resistant strains frequently show resistance to multiple antibiotic classes 2, 3

Clinical Implications by Infection Site

For Pneumonia:

• Intermediate penicillin resistance does not predict treatment failure with appropriate beta-lactam dosing 6
• Ceftriaxone and cefotaxime maintain >99% coverage even against intermediately resistant strains 1, 8
• Macrolides should be avoided as monotherapy when local resistance exceeds 25% due to treatment failure risk 4

For Meningitis:

• All resistance levels are clinically significant due to lower CSF antibiotic concentrations 6
• Ceftriaxone or cefotaxime with vancomycin is recommended until susceptibility is known 7

Temporal Trends

• Penicillin nonsusceptibility increased markedly in the United States during the 1990s and continued rising through the early 2000s 6
• The pneumococcal conjugate vaccine has contributed to decreased resistance prevalence since 2000 1
• Serotype 19A with high-level penicillin resistance (amoxicillin MIC ≥4 mg/L, cefotaxime MIC ≥2 mg/L) increased from 6.7% to 35% between 1998 and 2005 in the United States 6
• Multidrug-resistant serotype 19A strains are increasing in Spain and France 6

Key Pitfall to Avoid

Do not equate in vitro resistance with clinical failure for non-meningeal infections. The CLSI revised penicillin breakpoints in 2008 specifically for non-meningitis infections treated with IV penicillin (susceptible ≤2 mg/mL, intermediate 4 mg/mL, resistant ≥8 mg/mL) because clinical response was preserved despite reduced in vitro susceptibility 6. The older breakpoints (susceptible ≤0.06 mg/mL) remain applicable only for oral penicillin or meningitis 6.