Which bacteria are most likely to be resistant to amoxicillin?

Bacteria Most Likely to be Resistant to Amoxicillin

The bacteria most likely to be resistant to amoxicillin include Escherichia coli (with approximately 75% resistance), Enterobacter species, Citrobacter species, Serratia species, Klebsiella species, and Moraxella catarrhalis (nearly 100% resistance). 1, 2

Major Resistant Bacteria and Mechanisms

Enterobacteriaceae with Intrinsic Resistance

• Enterobacter species, Citrobacter species, and Serratia species possess chromosomal inducible AmpC β-lactamases that confer intrinsic resistance to amoxicillin 1, 2
• These bacteria can easily express AmpC enzymes at high levels through mutation, leading to resistance to many β-lactam antibiotics 1, 3
• Klebsiella pneumoniae produces SHV-1 β-lactamases and K. oxytoca produces chromosomal K1 β-lactamase, causing resistance to amoxicillin 2

Common Respiratory Pathogens

• Moraxella catarrhalis is nearly 100% β-lactamase positive, making it highly resistant to amoxicillin 1
• Between 10% and 42% of Haemophilus influenzae strains are β-lactamase positive and resistant to amoxicillin 1
• Streptococcus pneumoniae has variable resistance rates (10-15% nationally, but up to 50-60% in some areas) due to altered penicillin-binding proteins 1

Escherichia coli

• Global data shows that approximately 75% (range 45-100%) of E. coli urinary isolates are resistant to amoxicillin 1
• This high resistance rate has led to the removal of amoxicillin from WHO recommendations for empiric treatment of urinary tract infections 1
• E. coli can acquire resistance through plasmid-mediated β-lactamases or occasionally through hyperexpression of chromosomal AmpC enzymes 1, 4

Resistance Mechanisms

β-lactamase Production

• The primary mechanism of amoxicillin resistance is through β-lactamases that cleave the β-lactam ring, rendering the antibiotic inactive 5, 6
• Common β-lactamases include:
  • TEM-1, TEM-2, SHV-1, OXA-1 (broad-spectrum β-lactamases) 2
  • Extended-spectrum β-lactamases (ESBLs) that hydrolyze many β-lactams 1
  • AmpC β-lactamases (both chromosomal and plasmid-mediated) 3, 7

Other Resistance Mechanisms

• Altered penicillin-binding proteins (PBPs) with reduced affinity for β-lactams (common in S. pneumoniae and MRSA) 1
• Reduced influx through porin loss or enhanced efflux pump activation 3
• Increased plasmid copy numbers or gene amplification 4

Clinical Implications

Treatment Considerations

• Amoxicillin-clavulanate remains effective against many amoxicillin-resistant strains that produce certain β-lactamases 1
• For suspected AmpC-producing Enterobacterales, carbapenems or cefepime may be more appropriate 7
• High-dose amoxicillin (80-90 mg/kg/day) may overcome intermediate resistance in S. pneumoniae 1
• Local resistance patterns should guide empiric therapy decisions 1

Risk Factors for Resistant Organisms

• Recent antibiotic use (within previous 30 days) 1
• Young age (less than 2 years in pediatric populations) 1
• Attendance at childcare facilities 1
• Healthcare-associated infections (particularly for AmpC producers) 7

Geographic Considerations

• Resistance patterns vary considerably by region and community 1
• In low and lower-middle-income countries, resistance to amoxicillin among Gram-negative bacteria causing neonatal sepsis is particularly high 1
• The emergence of ESBL-producing organisms is becoming a significant problem in outpatient settings worldwide 1