Non-Beta-Lactams that act on bacterial cell walls/plasma membranes
Vancomycin
– Gram-positive bacteria, including MRSA (methicillin-resistant Staphylococcus aureus),
Staphylococcus epidermidis,
Enterococci, and
Clostridium difficile.
– Gram-negative bacteria are generally resistant to vancomycin.
– Inhibits peptidoglycan synthesis by binding to D-ala-D-ala in Gram-positive bacteria
– Resistance arises when cell wall precursors are modified to D-ala-D-lac.
– This is an example of bacterial resistance due to modification of a target site.
– Histamine release that can cause widespread flushing sometimes referred to as “Red Man Syndrome.”
This can be avoided by giving antihistamines and administering vancomycin slowly.
– Nephrotoxicity, ototoxicity
– Thrombophlebitis (venous obstruction due to blood clot formation).
Be aware that these adverse effects are more likely when vancomycin is administered at high doses, for long duration, and/or in combination with other drugs.
Bacitracin
– Gram-positive infections, especially of the skin
– Inhibits bacterial cell wall synthesis.
– Nephrotoxicity
Because of this, bacitracin it is typically used as a topical drug.
Daptomycin
–
Staphylococcus aureus infections
Including
MRSA infections, bacteremia, and
endocarditis.
– Also used to treat infections caused by
Vancomycin-resistant Enterococci (VRE)
- Gram-negative bacteria are intrinsically resistant
- Not appropriate for pneumonia because the pulmonary surfactant binds and inactivates it
- Mechanism of Action
– Disrupts of the ionic gradients of Gram-positive cell membranes, leading to bacterial cell death.
– Reversible
myopathies
Creatine phosphokinase levels should be monitored to avoid serious complications, such as
rhabdomyolysis (destruction of skeletal muscle).
– Eosinophilic pneumonia
Polymyxins
– Gram-negative bacteria
Specifically, are are used to treat external infections of the ear and eye.
– Colistin, aka, polymyxin E, is also effective against
Acinetobacter and
Pseudomonas infections.
– Increase cytoplasmic membrane permeability, which leads to cell death.
– Can be very nephrotoxic, which is why they are typically used for external infections.
They are a last resort treatment in systemic infections.
Isoniazid
– Replicating
Mycobacterium tuberculosis
– Disrupts mycolic acid synthesis.
– Neurotoxicity
Can be avoided in high-risk patients by administering vitamin B6
– Hepatotoxicity
Ethambutol
– Mycobacterium tuberculosis and some other mycobacteria strains
– Inhibits the synthesis of cell wall arabinogalactan
– Optic neuropathies
Changes in acuity and red-green color blindness.
