What antibiotic is too toxic for treating bacterial infections?

From the Guidelines

Doxorubicin is classified as an antibiotic but is too toxic to treat bacterial infections, and its use is limited to cancer treatment due to its significant toxicity to human cells, particularly heart tissue, as evidenced by its mechanism of intercalating DNA and inhibiting topoisomerase II 1.

Mechanism and Toxicity

The mechanism of doxorubicin, which involves interfering with DNA replication, is valuable for targeting rapidly dividing cancer cells but would cause unacceptable damage if used against bacterial infections. This is because doxorubicin belongs to the anthracycline class of antibiotics, which are known for their cytotoxic properties.

• Doxorubicin works by intercalating DNA and inhibiting topoisomerase II, which prevents DNA repair and leads to cell death.
• This mechanism is not suitable for treating bacterial infections due to its high toxicity to human cells.
• Other examples of antibiotics too toxic for systemic infection treatment include actinomycin D and mitomycin C, which are also repurposed as cancer treatments due to their cytotoxic properties.

Clinical Use and Alternatives

Doxorubicin is used as a chemotherapeutic agent to treat various cancers, including breast cancer, bladder cancer, lymphoma, and leukemia.

• The use of doxorubicin is limited to cancer treatment due to its significant toxicity to human cells, particularly heart tissue.
• Alternative antibiotics, such as those listed in the guidelines for community-acquired intra-abdominal infection, are preferred for treating bacterial infections due to their lower toxicity and effectiveness 1.
• The choice of antibiotic should be based on local microbiologic data, cost advantage, allergies, and formulary availability, as well as the severity of the infection and the patient's overall health status.

From the FDA Drug Label

PRECAUTIONS General Prescribing polymyxin B in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. If signs of respiratory paralysis appear, respiration should be assisted as required, and the drug discontinued.

The drug Polymyxin B (IV) is classified as an antibiotic and can be used to treat bacterial infections. However, it has potential toxic effects, such as respiratory paralysis, which requires careful monitoring and may necessitate discontinuation of the drug.

• The drug label does mention the risk of toxicity, but it does not state that it is too toxic to treat bacterial infections.
• The label emphasizes the importance of using the drug only when there is a proven or strongly suspected bacterial infection.
• Key points to consider when using Polymyxin B (IV) include:
  • Monitoring renal function and blood levels of the drug
  • Avoiding concurrent use of certain other drugs
  • Being aware of the risk of superinfection and resistance 2

From the Research

Antibiotic Toxicity

• The question of whether an antibiotic is too toxic to treat bacterial infections can be complex, as different antibiotics have varying levels of toxicity and efficacy against different types of bacteria.
• Polymyxins, a class of antibiotics, have been shown to be associated with a higher risk of nephrotoxicity compared to non-polymyxin-based regimens 3.
• A study on polymyxin B-associated nephrotoxicity found that the incident rate of nephrotoxicity in patients with normal renal function was 32.82% 4.
• In contrast, daptomycin, a cyclic lipopeptide antibiotic, has been shown to have a good safety profile and low nephrotoxicity 5, 6, 7.
• However, the use of high-dose daptomycin (>6 mg/kg/day) may be necessary for difficult-to-treat Gram-positive infections, and its safety and efficacy in these cases have been explored 5, 6.

Factors Influencing Toxicity

• Several factors can influence the risk of nephrotoxicity associated with antibiotic use, including the type and dose of the antibiotic, patient age, and the presence of underlying diseases or concomitant nephrotoxic agents 3, 4.
• For example, the use of furosemide (>20 mg/day) and high baseline serum creatinine have been identified as independent risk factors for polymyxin B-associated acute kidney injury 4.
• The maintenance dose of polymyxin B may also be related to the severity of nephrotoxicity 4.

Clinical Implications

• The choice of antibiotic and dosing regimen should be carefully considered in patients with renal insufficiency or other risk factors for nephrotoxicity 3, 4, 7.
• Close monitoring of serum creatinine levels is recommended when using antibiotics with potential nephrotoxicity, such as polymyxins 4.
• The use of daptomycin, with its low nephrotoxicity profile, may be a suitable option for patients with Gram-positive infections and renal insufficiency 6, 7.