What bacteria are covered and not covered by penicillins (Penicillin)

Penicillin Coverage Spectrum

Penicillins are effective against most Gram-positive bacteria and some Gram-negative bacteria, but are ineffective against methicillin-resistant Staphylococcus aureus (MRSA), many Enterobacteriaceae, and most anaerobes that produce beta-lactamases.

Bacteria Covered by Penicillins

Gram-Positive Bacteria

• Streptococcus pneumoniae (penicillin-susceptible strains) 1
• Streptococcus pyogenes (Group A strep) 1
• Groups B, C, and G Streptococci 1
• Viridans group streptococci (penicillin-susceptible strains) 1
• Staphylococcus aureus (only penicillin-susceptible strains, which are increasingly rare) 2
• Enterococcus species (ampicillin/amoxicillin, not natural penicillin) 3
• Listeria monocytogenes (ampicillin/amoxicillin) 3

Gram-Negative Bacteria

• Neisseria meningitidis (penicillin-susceptible strains) 4
• Neisseria gonorrhoeae (increasingly resistant) 4
• Haemophilus influenzae (ampicillin/amoxicillin for non-beta-lactamase producing strains) 3
• Escherichia coli (ampicillin/amoxicillin for susceptible strains) 3
• Proteus mirabilis (ampicillin/amoxicillin) 3
• Salmonella species (ampicillin/amoxicillin) 3
• Shigella species (ampicillin/amoxicillin) 3

Other Organisms

• Treponema pallidum (syphilis) 4
• Actinomyces species 4

Bacteria Not Covered by Penicillins

Resistant Gram-Positive Bacteria

• Methicillin-resistant Staphylococcus aureus (MRSA) 2
• Penicillin-resistant Streptococcus pneumoniae (high-level resistance) 1
• Coagulase-negative staphylococci (most strains) 1

Resistant Gram-Negative Bacteria

• Beta-lactamase producing Haemophilus influenzae 3
• Most Enterobacteriaceae (Klebsiella, Enterobacter, Citrobacter, Serratia) 3
• Pseudomonas aeruginosa (except for specific antipseudomonal penicillins like piperacillin) 3
• Acinetobacter species 1
• Stenotrophomonas maltophilia 1
• Burkholderia cepacia 1

Other Resistant Organisms

• Mycoplasma species
• Chlamydia species
• Rickettsia species
• Mycobacteria species
• Most anaerobes that produce beta-lactamases

Penicillin Resistance Mechanisms

1. Beta-lactamase production: Enzymes that break down the beta-lactam ring, rendering penicillins ineffective 4

   • Common in Staphylococcus aureus
   • Increasing in Haemophilus influenzae and Neisseria gonorrhoeae

2. Altered penicillin-binding proteins (PBPs):

   • Primary mechanism in Streptococcus pneumoniae 5
   • Mechanism for MRSA (mecA gene) 1

3. Decreased permeability: Reduced ability of the antibiotic to penetrate the bacterial cell wall

Clinical Implications of Resistance

• Streptococcus pneumoniae: Despite intermediate resistance to penicillin, non-meningeal infections may still respond to high-dose penicillin therapy 1
• Staphylococcus aureus: Most strains (>90%) are now resistant to penicillin, requiring penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) for MSSA infections 2
• MRSA: Requires non-beta-lactam antibiotics like vancomycin, linezolid, or daptomycin 2

Penicillin Subtypes and Coverage

1. Natural Penicillins (Penicillin G, Penicillin V):

   • Primarily effective against susceptible Gram-positive cocci
   • Some spirochetes and Gram-negative cocci

2. Penicillinase-resistant Penicillins (Methicillin, Oxacillin, Nafcillin, Flucloxacillin):

   • Effective against penicillinase-producing Staphylococcus aureus
   • Not effective against MRSA

3. Aminopenicillins (Ampicillin, Amoxicillin):

   • Extended coverage to include some Gram-negative bacteria
   • Susceptible to beta-lactamases

4. Beta-lactamase Inhibitor Combinations (Amoxicillin-clavulanate, Ampicillin-sulbactam):

   • Restored activity against beta-lactamase producers
   • Broader spectrum than aminopenicillins alone

5. Antipseudomonal Penicillins (Piperacillin, Ticarcillin):

   • Extended Gram-negative coverage including Pseudomonas aeruginosa
   • Often combined with beta-lactamase inhibitors (e.g., piperacillin-tazobactam)

Important Clinical Considerations

• Penicillin resistance in pneumococci is increasing worldwide, with rates varying significantly by region 1
• For non-meningeal pneumococcal infections, high-dose penicillin may still be effective even for strains with intermediate resistance 5
• For meningitis caused by S. pneumoniae, third-generation cephalosporins are preferred due to concerns about penicillin resistance 1
• Always consider local resistance patterns when selecting empiric therapy

Understanding the spectrum of activity of penicillins is crucial for appropriate antibiotic selection and effective treatment of bacterial infections.