What if two bacterial isolates are susceptible to completely different antibiotics, should two different antibiotics be used simultaneously?

From the Guidelines

When two bacterial isolates are susceptible to completely different antibiotics, using both antibiotics simultaneously (combination therapy) is often the most appropriate approach to ensure effective treatment of both bacterial strains. This is particularly relevant in cases where the infection is severe or the patient has a high risk of complications, as highlighted in the guidelines for the diagnosis and management of foot infections in persons with diabetes 1. The decision to use combination therapy should be based on factors such as the clinical severity of the infection, the presence of bone infection, and the likelihood of non-Gram-positive cocci (GPC) etiologic agents, among others.

Key considerations when implementing combination therapy include:

• Monitoring for potential drug interactions and increased risk of adverse effects
• Assessing the development of resistance to the antibiotics used
• Adjusting the duration of treatment according to the infection site and severity, typically ranging from 7-14 days
• Reevaluating the need for combination therapy once culture results and susceptibilities are fully known, and considering narrowing therapy to a single agent if possible

For example, if one isolate is susceptible only to vancomycin and another only to ciprofloxacin, both antibiotics would need to be administered according to their standard dosing regimens, such as vancomycin 15-20 mg/kg IV every 8-12 hours and ciprofloxacin 400 mg IV or 500-750 mg orally every 12 hours. This approach is supported by the principle that each antibiotic addresses a specific pathogen that would otherwise survive if only one antibiotic were used, as discussed in the context of diabetic foot infections 1.

From the Research

Antibiotic Susceptibility and Resistance

• When two bacterial isolates are susceptible to completely different antibiotics, the use of two different antibiotics simultaneously may be considered in certain cases.
• However, this approach is not always recommended, as it may lead to increased resistance and other complications 2.
• The decision to use multiple antibiotics should be based on the specific characteristics of the bacterial isolates and the patient's condition.

Combination Therapy

• Some studies have investigated the use of combination therapy, where two or more antibiotics are used together to treat bacterial infections 3, 4.
• These studies have shown that combination therapy can be effective in certain cases, but it is not always the best approach.
• The use of combination therapy should be carefully considered, taking into account the potential risks and benefits.

Sequential Therapy

• Another approach is sequential therapy, where antibiotics are used one after the other to treat bacterial infections 5.
• This approach has been shown to be effective in certain cases, particularly when the bacterial isolates have developed resistance to multiple antibiotics.
• Sequential therapy can help to reduce the development of resistance and improve treatment outcomes.

Considerations for Antibiotic Use

• When considering the use of antibiotics, it is essential to take into account the potential risks and benefits, including the development of resistance 6, 2.
• Antibiotics should be used judiciously, and the choice of antibiotic should be based on the specific characteristics of the bacterial isolates and the patient's condition.
• The use of antibiotics should be carefully monitored, and adjustments should be made as necessary to ensure effective treatment and minimize the risk of resistance.