Which antibiotic class is considered a last-resort option for multidrug-resistant gram-negative infections and is associated with nephrotoxicity and neurotoxicity?

Which antibiotic class is considered a last-resort option for multidrug-resistant gram-negative infections and is associated with nephrotoxicity and neurotoxicity?

• A. Polymyxins
• B. Aminoglycosides
• C. Carbapenems
• D. Fluoroquinolones

Answer: (A)

Polymyxins are kept in reserve for multidrug-resistant gram-negative infections because they are highly potent against these bacteria, but they carry significant toxicity. They work by binding to the lipopolysaccharide and phospholipid components of the outer membrane of gram-negative bacteria, acting as detergents that disrupt the membrane and cause bacterial cell death. This makes them one of the last-line options when other antibiotics fail due to resistance, including against organisms like Pseudomonas, Acinetobacter, and some carbapenem-resistant Enterobacteriaceae. The reason they’re the best answer here is their notorious toxicity profile: nephrotoxicity and neurotoxicity are well-recognized risks. Kidney injury is dose- and duration-dependent, so renal function must be closely monitored and dosing adjusted for kidney impairment. Neurotoxic effects can include paresthesias, dizziness, ataxia, and in severe cases neuromuscular blockade that can interfere with respiration. Because of these risks, polymyxins are used when safer, more effective options are not available, and they’re often paired with careful dosing and monitoring. Aminoglycosides can cause nephrotoxicity and have ototoxicity, but they’re not typically considered the ultimate last-resort for MDR gram-negatives. Carbapenems and fluoroquinolones are broad but do not carry the same defining last-resort toxicity profile, and they’re not the class most associated with this specific nephro- and neurotoxic risk.

Polymyxins are kept in reserve for multidrug-resistant gram-negative infections because they are highly potent against these bacteria, but they carry significant toxicity. They work by binding to the lipopolysaccharide and phospholipid components of the outer membrane of gram-negative bacteria, acting as detergents that disrupt the membrane and cause bacterial cell death. This makes them one of the last-line options when other antibiotics fail due to resistance, including against organisms like Pseudomonas, Acinetobacter, and some carbapenem-resistant Enterobacteriaceae.

The reason they’re the best answer here is their notorious toxicity profile: nephrotoxicity and neurotoxicity are well-recognized risks. Kidney injury is dose- and duration-dependent, so renal function must be closely monitored and dosing adjusted for kidney impairment. Neurotoxic effects can include paresthesias, dizziness, ataxia, and in severe cases neuromuscular blockade that can interfere with respiration. Because of these risks, polymyxins are used when safer, more effective options are not available, and they’re often paired with careful dosing and monitoring.

Aminoglycosides can cause nephrotoxicity and have ototoxicity, but they’re not typically considered the ultimate last-resort for MDR gram-negatives. Carbapenems and fluoroquinolones are broad but do not carry the same defining last-resort toxicity profile, and they’re not the class most associated with this specific nephro- and neurotoxic risk.