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Microbiology, 2021

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14.3 • Mechanisms of Antibacterial Drugs 575<br />

pathogens has led to increased use of intravenous colistin in hospitals, often as a drug of last resort to treat<br />

serious infections. The antibacterial daptomycin is a cyclic lipopeptide produced by Streptomyces<br />

roseosporus that seems to work like the polymyxins, inserting in the bacterial cell membrane and disrupting<br />

it. However, in contrast to polymyxin B and colistin, which target only gram-negative bacteria, daptomycin<br />

specifically targets gram-positive bacteria. It is typically administered intravenously and seems to be well<br />

tolerated, showing reversible toxicity in skeletal muscles.<br />

Drugs That Inhibit Bacterial Membrane Function<br />

Mechanism of Action<br />

Drug Class<br />

Specific<br />

Drugs<br />

Spectrum of<br />

Activity<br />

Clinical Use<br />

Interacts with<br />

lipopolysaccharide in the outer<br />

membrane of gram-negative<br />

bacteria, killing the cell through<br />

the eventual disruption of the<br />

outer membrane and<br />

cytoplasmic membrane<br />

Polymyxins<br />

Polymyxin<br />

B<br />

Polymyxin<br />

E (colistin)<br />

Narrow<br />

spectrum<br />

against gramnegative<br />

bacteria,<br />

including<br />

multidrugresistant<br />

strains<br />

Narrow<br />

spectrum<br />

against gramnegative<br />

bacteria,<br />

including<br />

multidrugresistant<br />

strains<br />

Topical preparations to<br />

prevent infections in<br />

wounds<br />

Oral dosing to<br />

decontaminate bowels to<br />

prevent infections in<br />

immunocompromised<br />

patients or patients<br />

undergoing invasive<br />

surgery/procedures.<br />

Intravenous dosing to<br />

treat serious systemic<br />

infections caused by<br />

multidrug-resistant<br />

pathogens<br />

Inserts into the cytoplasmic<br />

membrane of gram-positive<br />

bacteria, disrupting the<br />

membrane and killing the cell<br />

Lipopeptide<br />

Daptomycin<br />

Narrow<br />

spectrum<br />

against grampositive<br />

bacteria,<br />

including<br />

multidrugresistant<br />

strains<br />

Complicated skin and<br />

skin-structure infections<br />

and bacteremia caused<br />

by gram-positive<br />

pathogens, including<br />

MRSA<br />

Table 14.4<br />

CHECK YOUR UNDERSTANDING<br />

• How do polymyxins inhibit membrane function?

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