Will an antibiotic with intermediate sensitivity on a susceptibility test clear an infection or should it be changed?

From the Guidelines

An antibiotic with intermediate sensitivity on a susceptibility test may not reliably clear an infection and should generally be changed if better options are available. When a pathogen shows intermediate sensitivity, it means the antibiotic might work but at a higher risk of treatment failure compared to antibiotics showing full sensitivity. In clinical practice, it's preferable to select an antibiotic to which the organism is fully susceptible whenever possible, as suggested by the British Thoracic Society guideline for bronchiectasis in adults 1. If no better options exist, an intermediately sensitive antibiotic might be used with dose optimization (such as higher doses, more frequent administration, or extended infusions for IV antibiotics) and close monitoring of clinical response.

Some key points to consider include:

• The site of infection, as some antibiotics achieve higher concentrations in certain tissues, potentially overcoming intermediate sensitivity.
• The need for close monitoring of clinical response, with reassessment of treatment if symptoms persist or worsen within 48-72 hours.
• The importance of antibiotic sensitivity testing in guiding treatment decisions, as emphasized by the Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults 1.
• The potential for treatment failure with intermediately sensitive antibiotics, highlighting the need for careful consideration of treatment options.

In general, the decision to change an antibiotic due to intermediate sensitivity should be based on the individual patient's clinical response and the availability of better treatment options. Antibiotics should only be changed if there is no clinical response, as stated in the British Thoracic Society guideline 1. By prioritizing the use of fully susceptible antibiotics and closely monitoring patient response, clinicians can optimize treatment outcomes and minimize the risk of treatment failure.

From the FDA Drug Label

A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation.

An antibiotic with intermediate sensitivity on a susceptibility test may not reliably clear an infection. The intermediate category implies that the result is equivocal, and the drug may not be effective in achieving adequate concentrations to inhibit the pathogen.

• The infection may not be fully cleared with the current antibiotic.
• Consider repeating the test or using alternative antibiotics to which the microorganism is fully susceptible.
• In some cases, high dosage of the current antibiotic or its concentration in specific body sites might still be effective, but this should be approached with caution and careful monitoring. 2

From the Research

Antibiotic Sensitivity and Infection Treatment

• The effectiveness of an antibiotic with intermediate sensitivity in clearing an infection is a complex issue, and the decision to change the antibiotic should be based on various factors, including the type of infection, the causative pathogen, and the patient's clinical response 3, 4.
• Studies have shown that intermediate sensitivity to an antibiotic can lead to treatment failure, and the risk of resistance emergence is higher when the antibiotic is used at suboptimal doses or for an extended period 5, 6.
• The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) are important parameters in determining the effectiveness of an antibiotic against a particular pathogen 5.
• In some cases, antibiotics with intermediate sensitivity may still be effective in clearing an infection, especially if the pathogen is susceptible to the antibiotic at higher concentrations 7.
• However, the risk of resistance emergence and treatment failure should be carefully considered, and alternative antibiotics with better susceptibility profiles may be preferred 4, 6.

Factors Influencing Treatment Outcome

• The type of infection, such as urinary tract infection or pneumonia, can influence the treatment outcome and the risk of resistance emergence 3, 4.
• The causative pathogen and its susceptibility profile are critical factors in determining the effectiveness of an antibiotic 3, 5.
• Patient-related factors, such as underlying medical conditions and previous antibiotic use, can also impact the treatment outcome and the risk of resistance emergence 6.
• The use of machine learning algorithms and whole-genome sequencing can help predict the risk of resistance emergence and guide personalized antibiotic therapy 6.

Clinical Implications

• Clinicians should carefully evaluate the antibiotic susceptibility profile and the patient's clinical response when deciding whether to continue or change an antibiotic with intermediate sensitivity 3, 4.
• Alternative antibiotics with better susceptibility profiles should be considered, especially in cases where the risk of resistance emergence is high 4, 6.
• The use of antibiotic stewardship programs and machine learning algorithms can help optimize antibiotic therapy and reduce the risk of resistance emergence 6.